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PREFACE A text that has gone into its 6th edition has been well received by the medical profession. This book is designed to be concise with a consistent format so that the clinician can focus on a specific area. In some instances the text can be photocopied and given to the patient as a reference. In this way, the time necessary to explain the problem to the patient may be significantly reduced. This edition has had major modifications and embraces evidence-based medicine. Perhaps the biggest change in this edition is the addition of pictures. This allows the clinician to read about and actually see a picture of select disease entities. The authors have been selected based on their expertise, their recent publications, and the methods of management based on the most recent clinical advances. The format includes the CPT codes for billing purposes, short description of the condition, etiology/incidence, course/ prognosis, laboratory fi ndings, differential diagnosis; prophylaxis, treatment (local and systemic, surgical or other), miscellaneous (names and addresses of support groups) and key references. Although drug dosages and methods of administration have been scrutinized, it is important that each physician exercise his or her own judgment in the choice and use of a drug. The physician is advised to check the product information included in the drug’s package insert before drug administration. New data and individual clinical situations can change the drug regimen. We have had contributions from more than 400 authors throughout the world. In sincere gratitude for their time and effort, we have acknowledged them in the front of this book. We wish to express our appreciation and pay special tribute to Renee Tindall and Bree Jensvold, who worked with diligence, devotion, and skill to create this book. F. Hampton Roy Frederick W. Fraunfelder Frederick T. Fraunfelder
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CONTRIBUTORS Richard L. Abbott MD Thomas W. Boyden, Endowed Chair in Ophthalmology Health Science Clinical Professor Research Associate, Francis I. Proctor Foundation University of California, San Francisco Beckman Vision Center San Francisco CA USA 14 Erysipelas Natalie A. Afshari MD Associate Professor of Ophthalmology Cornea and Refractive Surgery Duke University Eye Center Duke University Medical Center Durham NC USA 209 Reis–Bucklers Corneal Dystrophy Jaya Agrawal MS, DNB, MNAMS, FRCS Consultant Ophthalmologist T. P. Agrawal Institute of Ophthalmology Meerut Uttar Pradesh India 58 Cysticercosis Shishir Agrawal MS, DNB, FRCS, MRCOphth, FRF Consultant Ophthalmologist T. P. Agrawal Institute of Ophthalmology Meerut Uttar Pradesh India 58 Cysticercosis Trilok P. Agrawal MS Consultant Ophthalmologist T. P. Agrawal Institute of Ophthalmology Meerut Uttar Pradesh India 58 Cysticercosis Levent Akduman MD Associate Professor of Ophthalmology Department of Ophthalmology St Louis University School of Medicine St Louis MO USA 82 Thalassemia
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Esen K. Akpek MD Associate Professor of Ophthalmology Director, Ocular Surface Diseases and Dry Eye Clinic Wilmer Eye Institute Johns Hopkins Hospital Baltimore MD USA 347 Scleritis Amal Al-Sayyed MD Oculoplastics Fellow University of Toronto Ophthalmology Toronto East General Hospital Toronto ON Canada 41 Rabies Thomas A. Albini MD Fellow, Vitreoretinal Diseases and Surgery Department of Ophthalmology Baylor College of Medicine Houston TX USA 257 Fungal Endophthalmitis Deborah M. Alcorn MD Associate Professor of Ophthalmology and Pediatrics Department of Ophthalmology and Pediatrics Stanford University School of Medicine Stanford CA USA 67 Oculocerebrorenal Syndrome 70 Galactosemias Amar Alwitry MD, MRCS, MRCSEd, MRCOphth, FRCOphth Consultant Ophthalmologist Derbyshire Royal Infirmary Derby UK 331 Central or Branch Retinal Artery Occlusion Anouk Amzel MD, MPH Assistant Professor of Pediatrics Columbia University School of Medicine New York NY USA 17 Haemophilus influenzae
Nicole J. Anderson MD Ophthalmologist Mississippi Vision Correction Center, PLLC Flowood MS USA 208 Posterior Polymorphous Dystrophy Ejaz A. Ansari BSc(Hons), MBBCh, FRCOphth, MD Consultant Ophthalmic Surgeon Eye, Ear and Mouth Unit Maidstone Hospital Maidstone Kent UK 66 Hypovitaminosis Andrew Antoszyk MD Charlotte Eye Ear Nose and Throat Associates Charlotte NC USA 350 Persistent Hyperplastic Primary Vitreous James H. Antoszyk MD Charlotte Eye Ear Nose and Throat Associates Charlotte NC USA 350 Persistent Hyperplastic Primary Vitreous James V. Aquavella MD Professor of Ophthalmology University of Rochester Eye Institute Rochester NY USA 200 Keratoconjunctivitis Sicca and Sjögren’s Syndrome 296 Lacrimal Hyposecretion 348 Scleromalacia Perforans Sumaira A. Arain MD Research Fellow Department of Ophthalmology University of California Sacramento CA USA 236 Distichiasis
J. Fernando Arévalo MD Director Clínica Oftalmologica Centro Caracas Caracas Venezuela 57 Coenurosis
Carlos W. Arzabe MD Ophthalmic Surgeon Hospital del Ojo Santa Cruz Bolivia 61 Ocular Toxocariasis La-ongsri Atchaneeyasakul MD Associate Professor Department of Ophthalmology Division of Pediatric Ophthalmology and Strabismus Faculty of Medicine Siriraj Hospital Mahidol University Bangkok Thailand 76 Mucopolysaccharidosis IV 336 Gyrate Atrophy of the Choroid and Retina with Hyperornithinemia 338 Refsum’s Disease Huban Atilla MD Associate Professor of Ophthalmology Department of Ophthalmology Pediatric Ophthalmology and Strabismus Ankara University, Faculty of Medicine Ankara Turkey 113 Functional Amblyopia Ümit Aykan MD Assistant Professor Department of Ophthalmology GATA H. Pasa Training Hospital Istanbul Turkey 260 Exfoliation Syndrome Brandon D. Ayres MD Cornea Fellow Wills Eye Hospital Philadelphia PA USA 201 Keratoconus
Kristi Bailey MD Resident Department of Ophthalmology Oregon Health and Science University Casey Eye Institute Portland OR USA 325 Orbital Cellulitis and Abscess 326 Orbital Graves’ Disease Frank G. Baloh MD Lehigh Valley Eye Center Allentown PA USA 27 Molluscum Contagiosum Irina S. Barequet MD Lecturer in Ophthalmology Goldschleger Eye Institute Sheba Medical Center Tel Aviv University Sackler Faculty of Medicine Tel Hashomer Israel 186 Bacterial Corneal Ulcers André Barkhuizen MBBCh(Rand), MMed(UCT), FCP(SA), FACR Associate Professor of Medicine and Staff Physician Arthritis and Rheumatic Disease Oregon Health and Science University and Portland VA Medical Center Portland OR USA 97 Systemic Lupus Erythematosus Michael A. Bearn FRCOphth, BMedSci Consultant Ophthalmologist Dr Gray’s Hospital Elgin Scotland UK 295 Lacrimal Hypersecretion Rubens Belfort Jr MD Professor of Ophthalmology Department of Ophthalmology Federal University of São Paulo São Paulo Brazil 3 Acquired Immune Deficiency Syndrome
A. Robert Bellows MD Boston Eye Surgery and Laser Center Ophthalmic Consultants of Boston Boston MA USA 170 Choroidal Detachment Audina M. Berrocal MD Assistant Professor of Ophthalmology Department of Ophthalmology Bascom Palmer Eye Institute University of Miami School of Medicine Miami FL USA 28 Moraxella
Contributors
Guruswami Arunagiri MD, FRCSEd Attending Physician Department of Ophthalmology Geisinger Medical Center Danville PA USA 188 Corneal Abrasions, Contusions, Lacerations and Perforations
Juan J. Barbón MD Consultant Ophthalmologist Ophthalmology Department Hospital San Agustín Avilés-Asturias Spain 87 Psoriasis
Marijke Wefers Bettink-Remeijer MD Neuro-Ophthalmologist Neuro-Ophthalmology Department Rotterdam Eye Hospital Netherlands 110 Cluster Headache Anuja Bhandari MD, FRCOphth Assistant Professor Department of Ophthalmology University of Washington Seattle WA USA 253 Trichiasis M. Tariq Bhatti MD Associate Professor Departments of Ophthamology and Medicine (Division of Neurology) Duke University Eye Center Duke University Medical Center Durham, NC USA 80 Carotid Cavernous Fistula Mark S. Blumenkranz MD Professor and Chairman Department of Ophthalmology Stanford University School of Medicine Stanford CA USA 329 Acute Retinal Necrosis Kostas G. Boboridis MD, PhD Ophthalmic and Oculoplastic Surgeon Ophthalmology Department Aristotle University of Thessaloniki Thessaloniki Greece 237 Ectropion James P. Bolling MD Associate Professor and Chair Department of Ophthalmology Mayo Clinic Jacksonville FL USA 353 Vitreous Wick Syndrome
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Contributors
Vivien Boniuk MD, FRCS(C) Director of Ophthalmology, Queens Hospital Center Associate Professor of Ophthalmology Albert Einstein College of Medicine Long Island Jewish Medical Center New York NY USA 44 Rubella Paul Jorge Botelho MD Clinical Assistant Professor at Brown Medical School Department of Surgery Center for Sight Fall River MA USA 13 Epidemic Keratoconjunctivitis Paul W. Brazis MD Professor of Neurology Department of Ophthalmology Mayo Clinic, Jacksonville Jacksonville FL USA 106 Acquired Inflammatory Demyelinating Neuropathies Fion D. Bremner BSc, MBBS, PhD, FRCOphth Consultant Ophthalmic Surgeon and Consultant in Neuro-ophthalmology Department of Neuro-ophthalmology National Hospital for Neurology and Neurosurgery London UK 312 Congenital Pit of Optic Disc Edward G. Buckley MD Professor, Ophthalmology and Pediatrics Department of Pediatric Ophthalmology & Strabismus & Neuro-ophthalmology Duke University Eye Center Durham NC USA 220 Congenital Esotropia John D. Bullock MD, MPH, MSc Infectious Disease Epidemioligist Clinical Professor of Community Health Professor of Mathematics and Statistics Emeritus Professor and Chair of Ophthalmology Wright State University School of Medicine Dayton OH USA 32 Nocardiosis 171 Choroidal Folds
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David Matthew Bushley MD Cornea and Refractive Surgery Duke University Eye Center Duke University Medical Center Durham NC USA 209 Reis–Bucklers Corneal Dystrophy Jorge Alberto F. Caldeira MD Emeritus Professor of Ophthamology Division of Ophthalmology Faculdade de Medicina University of São Paulo Brazil 233 V-pattern Strabismus Anne Carricajo PhD Microbiologist Department of Microbiology Bellevue Hospital Saint-Etienne France 1 Acinetobacter Gian Maria Cavallini MD Associate Professor of Ophthalmology Department of Ophthalmology University of Modena and Reggio Emilia Medical School Modena Italy 313 Drug-induced Optic Atrophy Matilda Frances Chan MD, PhD Ophthalmology Resident Department of Ophthalmology University of Rochester Eye Institute Rochester NY USA 20 Infectious Mononucleosis Damon B. Chandler MD Fellow, Ophthalmic Plastic and Reconstructive Surgery Scheie Eye Institute University of Pennsylvania Philadelphia PA USA 29 Mucormycosis H. Channa MD Professor in Ophthalmology Service d’Ophtalmologie Hôpital Militaire d’Instruction Med V Rabat Morocco 131 Kaposi’s Sarcoma Devron H. Char MD Director, The Tumori Foundation San Francisco CA Clinical Professor of Ophthalmology Department of Ophthalmology Stanford University School of Medicine Palo Alto CA USA 139 Metastatic Tumors to the Eye and Its Adnexa 142 Neuroblastoma
Steve Charles MD Clinical Professor of Ophthalmology Department of Ophthalmology University of Tennessee College of Medicine Memphis TN USA 351 Proliferative Vitreoretinopathy Teresa C. Chen MD Assistant Professor of Ophthalmology Harvard Medical School Massachusetts Eye and Ear Infirmary Glaucoma Service Boston MA USA 101 Weill–Marchesani Syndrome 269 Normal-tension Glaucoma (Low-tension Glaucoma) Steven S. T. Ching MD Professor of Ophthalmology Department of Ophthalmology University of Rochester Rochester NY USA 20 Infectious Mononucleosis Christophe Chiquet MD, PhD Associate Professor of Ophthalmology Department of Ophthalmology University Hospital Grenoble Grenoble France 157 Intraocular Foreign Body: Steel or Iron Phillip Hyunchul Choo MD Associate Professor of Clinical Ophthalmology Department of Ophthalmology University of California Sacramento CA USA 236 Distichiasis Timothy Y. Chou MD Corneal Specialist Nassau University Medical Center, Cornea Division Ophthalmic Consultants of Long Island Rockville Center NY USA 211 Superior Limbic Keratoconjunctivitis Stephen P. Christiansen MD Professor of Ophthalmology and Pediatrics Director, Pediatric Ophththalmology and Adult Strabismus Department of Ophthalmology University of Minnesota Minneapolis MN USA 68 Tyrosinemia II 222 Convergence Insufficiency
Kelly D. Chung MD Assistant Professor, Ophthalmology Casey Eye Institute Portland OR USA 298 Adults Cataracts
Michael P. Clarke MBBChir, DO, FRCS, FRCOphth Reader in Ophthalmology University of Newcastle Claremont Wing Eye Department Royal Victoria Infirmary Newcastle Upon Tyne UK 218 Basic and Intermittent Exotropia David K. Coats MD Professor of Ophthalmology and Pediatrics Baylor College of Medicine Department of Pediatric Ophthalmology Houston TX USA 289 Congenital Anomalies of the Lacrimal System Elisabeth J. Cohen MD Director, Cornea Service Wills Eye Institute Professor of Ophthalmology Jefferson Medical College Philadelphia PA USA 281 Iridocorneal-endothelial Syndrome R. Max Conway MBBS, PhD, FRANZCO Director Sydney Ocular Oncology Center University of Sydney Sydney NSW Australia 284 Iris Melanoma Catherine Creuzot-Garcher MD, PhD Head, Department of Ophthalmology Professor University of Burgundy Dijon France 111 Creutzfeldt–Jakob disease
Theodore H. Curtis MD Fellow Oregon Health and Science University Casey Eye Institute Portland OR USA 52 Typhoid Fever 130 Juvenile Xanthogranuloma 229 Nystagmus Roger A. Dailey MD, FACS Professor of Ophthalmic Facial Plastic Surgery Lester T. Jones Endowed Chair Director, Oculofacial Plastic Surgery Division Oregon Health and Science University Casey Eye Institute Portland OR USA 148 Sebaceous Gland Carcinoma 238 Entropion 239 Epicanthus 244 Lagophthalmos 248 Marcus Gunn Syndrome 250 Orbital Fat Herniation 326 Orbital Graves’ Disease Richard M. Davis MD Professor and Chair Department of Ophthalmology University of South Carolina School of Medicine Columbia SC USA 190 Corneal Mucous Plaques Romain De Cock MBChB, FRCS, FRCOphth Consultant Ophthalmologist Ophthalmology Clinic Queen Elizabeth the Queen Mother Hospital Margate Kent UK 182 Ligneous Conjunctivitis Jan-Tjeerd H. N. de Faber MD Pediatric Ophthalmologist The Rotterdam Eye Hospital Rotterdam The Netherlands 109 Chronic Progressive External Ophthalmoplegia 110 Cluster Headache
Daniel de la Mano MD Consultant Dermatologist Dermatology Department Hospital San Agustín Avilés-Asturias Spain 87 Psoriasis Nick W. H. M. Dekkers MD, PhD Formerly, Ophthalmologist St Elizabeth Hospital Tilburg The Netherlands 45 Rubeola
Contributors
George A. Cioffi MD Chairman, Devers Eye Institute Clinical Vice President of Ophthalmology Legacy Health System and Professor of Ophthalmology Oregon Health and Science University Portland OR USA 268 Malignant Glaucoma 282 Iris Bombé
Emmett T. Cunningham Jr MD, PhD, MPH Director, The Uveitis Service California Pacific Medical Center San Francisco, CA and Adjunct Clinical Professor Department of Ophthalmology Stanford University School of Medicine Stanford CA USA 24 Leptospirosis
Monte Anthony Del Monte MD Skillman Professor of Pediatric Ophthalmology Professor of Pediatrics and Communicable Diseases Director of Pediatric Ophthalmology and Strabismus WK Kellogg Eye Center and Mott Children’s Hospital University of Michigan Ann Arbor MI USA 105 Sturge–Weber Syndrome David A. Della Rocca MD New York Eye and Ear Infirmary Department of Oculoplastics St Luke’s Roosevelt Hospital Center Department of Ophthalmology New York NY USA 240 Eyelid Contusions, Lacerations and Avulsions Robert C. Della Rocca MD, FACS Chairman of Ophthalmology St Luke’s Roosevelt Hospital Center Chief of Oculoplastic Surgery The New York Eye and Ear Infirmary New York NY USA 240 Eyelid Contusions, Lacerations and Avulsions Deepinder K. Dhaliwal MD Associate Professor, Ophthalmology Eye and Ear Institute Pittsburgh PA USA 39 Pseudomonas aeruginosa Diana V. Do MD Assistant Professor of Ophthalmology Wilmer Eye Institute Johns Hopkins University School of Medicine Baltimore MD USA 34 Ocular Histoplasmosis 99 Uveitis Associated with Juvenile Idiopathic Arthritis
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Peter J. Dolman MD, FRCSC Clinical Professor, Ophthalmology UBC Eye Care Centre Vancouver BC Canada 323 Orbital Inflammatory Syndromes
Contributors
Sean P. Donahue MD, PhD Professor of Pediatric Ophthalmology and Adult Strabismus Vanderbilt Eye Center Vanderbilt University Medical Center Nashville TN USA 6 Bacillus Species Infections 33 Ocular Candidiasis Eric D. Donnenfeld MD, FACS Founding Partner, Ophthalmic Consultants of Long Island Co-Director, Cornea Division Manhattan Eye, Ear and Throat Hospital New York NY USA 211 Superior Limbic Keratoconjunctivitis Graham Duguid MD, BMedBiol, FRCS Consultant Ophthalmic Surgeon Western Eye Hospital London UK 339 Retinal Detachment Jay S. Duker MD Director, New England Eye Center Chairman and Professor of Ophthalmology Tufts New England Medical Center Tufts University School of Medicine Boston MA USA 308 Macular Hole James P. Dunn Jr MD Associate Professor of Ophthalmology Director, Division of Ocular Immunology The Wilmer Ophthalmological Institute Baltimore MD USA 310 Ankylosing Spondylitis and Reiter’s Disease Steven P. Dunn MD Michigan Cornea Consultants Southfield MI USA 89 Amyloidosis Hon-Vu Q. Duong MD Attending Ophthamlogist Westfield Eye Centre Las Vegas NV USA 81 Sickle Cell Disease 122 Basal Cell Carcinoma
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Robert A. Egan MD Assistant Professor of Ophthalmology, Neurology and Neurosurgery Casey Eye Institute Portland OR USA 49 Tetanus 138 Meningioma Michael D. Eichler MD Staff Ophthalmologist Eye Surgeons and Physicians, PA St. Cloud Hospital St. Cloud MN USA 136 Lymphoid Tumors Mays El-Dairi MD Chief Resident Department of Ophthamology American University Beirut Beirut Lebanon 79 Hyperlipoproteinemia Forrest J. Ellis MD Assistant Professor of Pediatrics and Ophthalmology Director, Pediatric Ophthalmology Rainbow Babies and Children’s Hospital Case Western Reserve University School of Medicine Cleveland OH USA 221 Congenital Fibrosis of the Extraocular Muscles Geoffrey Emerson MD, PhD Resident Department of Ophthalmology The Wilmer Eye Institute Baltimore MD USA 334 Diffuse Unilateral Subacute Neuroretinitis
Teodoro Evans MD Vitreoretinal Fellow Institute of Ocular Surgery University of Costa Rica San Jose Costa Rica 57 Coenurosis Julie Falardeau MD, FRCSC Assistant Professor of Ophthalmology Casey Eye Institute Portland OR USA 127 Ewing’s Sarcoma 311 Compressive Optic Neuropathies Bishara M. Faris MD, FACS Lecturer on Ophthalmology, Harvard Faculty of Medicine Clinical Professor of Ophthalmology Department of Ophthalmology Boston University School of Medicine Westboro MA USA 346 Scleral Staphylomas and Dehiscences Marianne E. Feitl MD Associate Professor of Ophthalmology and Visual Science Department of Ophthalmology and Visual Science University of Chicago Hospitals Chicago USA 266 Juvenile Glaucoma Warren L. Felton III MD Professor and Associate Chair of Clinical Activities Department of Neurology Associate Professor of Ophthalmology Chair, Division of Neuro-Ophthalmology Virginia Commonwealth University Richmond VA USA 129 Hodgkin’s Disease
M. Vaughn Emerson MD Fellow Department of Ophthalmology Oregon Health and Science University Portland OR USA 328 Acquired Retinoschisis 343 Subretinal Neovascular Membranes
Stephen S. Feman MD, FACS Davisson Professor of Ophthalmology Department of Ophthalmology St Louis University School of Medicine St Louis MO USA 82 The Thalassemias
Laura B. Enyedi MD Assistant Professor of Ophthalmology and Pediatrics Department of Ophthalmology Duke University Eye Center Durham NC USA 220 Congenital Esotropia
Timothy J ffytche LVO, FRCS, FRCOphth Consultant Ophthalmologist Formerly, The London Clinic Harley Street London UK 23 Leprosy
Christina J. Flaxel MD Associate Professor of Ophthalmology Casey Eye Institute Portland OR USA 340 Retinal Venous Obstruction
Allen Foster OBE, FRCS Professor Clinical Research Unit London School of Hygiene and Tropical Medicine London UK 50 Trachoma Frederick T. Fraunfelder MD Professor Department of Ophthalmology Oregon Health and Science University Portland OR USA 153 Electrical Injury Frederick W. Fraunfelder MD Associate Professor Department of Ophthalmology Oregon Health and Science University Portland OR USA 124 Conjunctival or Corneal Intraepithelial Neoplasia and Squamous Cell Carcinoma 149 Squamous Cell Carcinoma 297 Uveoparotid Fever H. Mackenzie Freeman MD Associate Clinical Professor Harvard University Faculty of Medicine Retina Specialists of Boston Boston MA USA 346 Scleral Staphylomas and Dehiscences Mitchell H. Friedlaender MD Head, Division of Ophthalmology Director, Scripps Clinic Laser Vision Center La Jolla CA USA 88 Urticaria and Hereditary Angioedema
Wayne E. Fung MD Clinical Professor of Ophthalmology California Pacific Medical Center Pacific Eye Associates San Francisco CA USA 306 Cystoid Macular Edema Philippe Gain MD, PhD Professor of Ophthalmology Department of Ophthalmology University Hospital Saint-Etienne France 1 Acinetobacter 157 Intraocular Foreign Body: Steel or Iron Jaime R. Gaitan MD Department of Ophthalmology Bascom Palmer Eye Institute University of Miami School of Medicine Miami FL USA 28 Moraxella Stephen Gancher MD, FAAN Adjunct Associate Professor Department of Neurology Oregon Health and Science University and Staff Neurologist Kaiser Permanente Portland OR USA 118 Parkinson’s Disease Tim Gard MD Clinical Instructor, Ophthalmology Oregon Health and Science University Hillsboro Eye Clinic Hillsboro OR USA 309 Solar Retinopathy Devin M. Gattey MD Assistant Professor of Ophthalmology Casey Eye Institute Oregon Health and Science University Portland OR USA 301 Dislocation of the Lens
Peter L. Gehlbach MD, PhD Associate Professor of Ophthalmology Wilmer Eye Institute Johns Hopkins University School of Medicine Baltimore MD USA 156 Intraocular Foreign Body: Nonmagnetic, Chemically Inert Mehdi Ghajarnia MD Cornea Fellow John A Moran Eye Center Salt Lake City, UT USA 39 Pseudomonas aeruginosa
Contributors
Rod Foroozan MD Assistant Professor of Ophthalmology Department of Ophthalmology Baylor College of Medicine Houston TX USA 119 Tolosa–Hunt Syndrome
Larry P. Frohman MD Professor of Ophthalmology & Visual Sciences and Neurology & Neurosciences Department of Ophthalmology University of Medicine and Dentistry of New Jersey New Jersey Medical School Newark NJ USA 96 Scleroderma
Vinícius Coral Ghanem MD Ophthalmologist Sadalla Amin Ghanem Eye Hospital Santa Catarina Brazil 86 Ocular Rosacea Amit Kumar Ghosh MD, FACP Associate Professor of Medicine Mayo Clinic College of Medicine Rochester MN USA 116 Multiple Sclerosis Chandak Ghosh MD, MPH Medical Consultant for Federal Policy US Department of Health and Human Services Health Resources and Services Administration New York NY USA 17 Haemophilus influenzae Matthew Giegengack MD Fellow Casey Eye Institute Portland OR USA 273 Phacanaphylactic Endophthalmitis Geoffrey Gladstone MD, FAACS Clinical Professor of Ophthalmology Michigan State University School of Medicine Southfield, MI USA 254 Xanthelasma Daniel H. Gold MD, FRCOphth Clinical Professor of Ophthalmology University of Texas Medical Branch Galveston TX USA and Visiting Lecturer Tel Aviv University Sackler Medical School Tel Aviv Sourasky Medical Center Tel Aviv Israel 95 Sarcoidosis
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Richard L. Golub MD Pediatric Ophthalmology Fellow Storm Eye Institute / MUSC Charleston SC USA 227 Inferior Rectus Muscle Palsy
Contributors
Dan S. Gombos MD, FACS Associate Professor, Section of Ophthalmology Department of Head & Neck Surgery The University of Texas MD Anderson Cancer Center Houston TX USA 304 Traumatic Cataract George M. Gombos MD, FACS Professor Emeritus State University of New York Health Science Center at Brooklyn Chief, Section of Ophthalmology, Department of Surgery New York Harbor Health Science Center – Brooklyn Veterans Administration Hospital Brooklyn NY USA 304 Traumatic Cataract William V. Good MD Senior Scientist Smith-Kettlewell Eye Research Institute San Francisco CA USA 183 Ophthalmia Neonatorum Shawn Goodman MD Ophthalmologist Child Eye Care Associates Lake Oswego OR USA 224 Duane’s Retraction Syndrome John D. Gottsch MD Margaret C. Mosher Professor of Ophthalmology Wilmer Ophthalmological Institute The Johns Hopkins Hospital Baltimore MD USA 13 Epidemic Keratoconjunctivitis Srinivas Goverdhan MD, FRCS(Ed) Specialist Registrar in Ophthalmology Southampton Eye Unit Southampton University Hospitals Southampton UK 84 Contact Dermatitis Baird S. Grimson MD Professor of Ophthalmology Department of Ophthalmology University of North Carolina Chapel Hill NC USA 120 Trigeminal Neuralgia
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Adolfo Güemes MD Professor of Ophthalmology Consultores Oftalmológicos Montevideo Buenos Aires Argentina 303 Microspherophakia Roberto Guerra MD Professor of Ophthalmology Department of Ophthalmology University of Modena and Reggio Emilia School of Medicine Modena Italy 313 Drug-induced Optic Atrophy Julia A. Haller MD Robert Bond Welch Professor of Opthalmology Wilmer Ophthalmological Institute Johns Hopkins Medical Institutions Baltimore MD USA 166 Intraocular Epithelial Cysts Kristin M. Hammersmith MD Instructor, Jefferson Medical College Thomas Jefferson University and Assistant Surgeon, Cornea Service Wills Eye Hospital and Director, Cornea Fellowship Program Wills Eye Institute Philadelphia PA USA 210 Schnyder’s Crystalline Corneal Dystrophy Irvin L. Handelman MD Retina Northwest Portland OR USA 352 Vitreous Hemorrhage Roderick N. Hargrove MD Assistant Professor of Ophthalmology Department of Ophthalmology University of Tennesse Memphis TN USA 123 Capillary Hemangioma Michael S. Harney MD, MB, FRCSI(ORL) Specialist Registrar in Otolaryngology Department of Otolaryngology RCSI Education and Research Centre Beaumont Hospital Dublin Ireland 107 Bell’s Palsy
Richard A. Harper MD Associate Professor of Ophthalmology Department of Ophthalmology University of Arkansas for Medical Sciences Little Rock AR USA 158 Iris Lacerations, Iris Holes and Iridodialysis Sarah R. Hatt DBO Research Orthoptist Ophthalmology Research Mayo Clinic Rochester MN USA 218 Basic and Intermittent Exotropia Barbara S. Hawkins PhD Professor of Ophthalmology and Epidemiology Wilmer Eye Institute, Clinical Trials and Biometry Johns Hopkins University School of Medicine Baltimore MD USA 34 Ocular Histoplasmosis Sohan S. Hayreh MD, MS, PhD, DSc, FRCS(Edin), FRCS(Eng), FRCOphth Professor Emeritus of Ophthalmology and Director Ocular Vascular Department of Ophthalmology and Visual Sciences University of Iowa Hospitals and Clinics Iowa City IA USA 98 Giant Cell Arteritis Arnd Heiligenhaus MD Professor of Ophthalmology Department of Ophthalmology St. Franziskus Hospital Münster Germany 83 Atopic Dermatitis Carsten Heinz MD Department of Ophthalmology St Franziskus Hospital Münster Germany 83 Atopic Dermatitis Leon W. Herndon MD Associate Professor of Ophthalmology Duke University Eye Center Durham NC USA 261 Glaucoma Associated with Anterior Uveitis
Koji Hirano MD, PhD Professor Department of Ophthalmology Ban-Buntane Hotokukai Hospital Fujita Health University Nagoya Japan 78 Fabry Disease Edward J. Holland MD Director, Cornea Services Professor of Ophthalmology University of Cincinnati Cincinnati Eye Institute N.KY Edgewood KY USA 203 Macular Corneal Dystrophy Gary N. Holland MD Vernon O. Underwood Family Professor of Medicine Chief, Cornea and Uveitis Division Department of Ophthalmology David Geffen School of Medicine at UCLA Jules Stein Eye Institute Los Angeles CA USA 63 Toxoplasmosis
Richard B. Hornick MD, MACP Clinical Professor of Medicine University of Florida School of Medicine and Florida State University School of Medicine Orlando FL USA 40 Q Fever H. Dunbar Hoskins Jr MD Executive Vice President American Academy of Ophthalmology San Francisco CA USA 260 Exfoliation Syndrome James W. Hung MD Ophthalmic Consultants of Boston Boston MA USA 170 Choroidal Detachment Brian A. Hunter MD Ocular Pathology Fellow Morgan Eye Center University of Utah Salt Lake City UT USA 255 Anophthalmos Krista A. Hunter MD Pediatric Fellow Department of Ophthalmology Oregon Health and Science University Casey Eye Institute Portland OR USA 226 Extraocular Muscle Lacerations 300 Congenital and Infantile Cataracts
Eric R. Holz MD Assistant Professor of Ophthalmology Baylor College of Medicine Houston TX USA 256 Bacterial Endophthalmitis 257 Fungal Endophthalmitis
Alex P. Hunyor MBBS, FRANZCO, FRACS Vitreoretinal Surgeon Sydney Eye Hospital Sydney Australia 307 Epimacular Proliferation 349Familial Exudative Vitreoretinopathy
Sachiko Hommura MD, PhD Assistant Professor Department of Ophthalmology University Hospital of Tsukuba Ibaraki Japan 173 Expulsive Hemorrhage
Brian Hurwitz MD, FRCP, FRCGP General Practitioner and Professor of Medicine and the Arts King’s College London London UK 177 Bacterial Conjunctivitis
Jeffrey D. Horn MD Assistant Professor of Ophthalmology Department of Ophthalmology and Visual Sciences Vanderbilt Eye Institute Nashville TN USA 7 Blastomycosis
Thomas S. Hwang MD Assistant Professor of Ophthalmology Casey Eye Institute Portland OR USA 305 Age-related Macular Degeneration 330 Branch Retinal Vein Occlusion 335 Eales Disease
Robert A. Hyndiuk MD Professor Emeritus Department of Ophthalmology Medical College of Wisconsin Milwaukee WI USA 46 Sporotrichosis Ozge Ilhan-Sarac MD Fellow in Ophthalomolgy Ocular Surface Diseases and Dry Eye Clinic The Wilmer Eye Institute The John Hopkins School of Medicine Baltimore MD USA 347 Scleritis
Contributors
Simon J. Hickman MA, PhD, MBBChir, MRCP Consultant Neurologist and Neuro-Ophthalmologist Department of Neurology Royal Hallamshire Hospital Sheffield UK 314 Inflammatory Optic Neuropathies 316 Optic Neuritis
Edsel Ing MD, FRCSC Assistant Professor of Ophthalmology University of Toronto Ophthalmology Toronto East General Hospital Toronto ON Canada 41 Rabies Masanori Ino-ue MD, PhD Associate Director Chairman in Ophthalmology Kohnan Hospital Kobe Japan 287 Rubeosis Iridis Carlos M. Isada MD The Cleveland Clinic Cleveland OH USA 16 Gonococcal Ocular Disease Saylin Iturriaga MD Institute of Ocular Surgery San José Costa Rica 57 Coenurosis Joseph D. Iuorno MD Clinical Instructor Department of Ophthalmology University of Minnesota Minneapolis MN USA 198 Granular Corneal Dystrophy Andrew G. Iwach MD Associate Clinical Professor of Ophthalmology University of California, San Francisco Glaucoma Center of San Francisco San Francisco CA USA 260 Exfoliation Syndrome
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Mohan N. Iyer MD Fellow, Vitreoretinal Diseases and Surgery Ophthalmology Department Baylor College of Medicine Houston TX USA 256 Bacterial Endophthalmitis Contributors
Natalio J. Izquierdo MD Associate Professor of Ophthalmology Medical Sciences University of Puerto Rico San Juan Puerto Rico 102 Down Syndrome Lee M. Jampol MD Louis Feinberg Professor and Chairman Department of Ophthalmology Northwestern University Medical School Chicago IL USA 162 Hypertension Suzanne Johnston MD Chief Resident Eastern Virgina Medical School Norfolk VA USA 8 Brucellosis Sibel Kadayifçilar MD Professor of Ophthalmology Department of Ophthalmology Hacettepe University Ankara Turkey 94 Rheumatoid Arthritis Ian H. Kaden MD Morristown Memorial Hospital Randolph NJ USA 30 Mumps Dieudonne Kaimbo Wa Kaimbo MD, PhD Professor of Ophthalmology Department of Ophthalmology University of Kinshasa Kinshasa Democratic Republic of Congo 51 Tuberculosis Rashmis Kapur MD Resident in Ophthalmology Department of Ophthalmology and Visual Sciences University of Illinois at Chicago Chicago IL USA 189 Corneal Edema
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Peter R. Kastl MD, PhD Professor of Ophthalmology and Biochemistry Department of Ophthalmology Tulane University School of Medicine New Orleans LA USA 199 Juvenile Corneal Epithelial Dystrophy Garyfallia Katsavounidou MS Graduate Student Department of Architecture and Design Massachusetts Institute of Technology Boston MA USA 278 Aniridia Ayat Kazerouni BS, BA Back Office Supervisor Ophthalomogy Tayani Eye Institute San Clemente CA USA 46 Sporotrichosis Michael Kazim MD Clinical Professor of Ophthalmology and Surgery Department of Ophthalmology Columbia University New York NY USA 135 Lymphangioma
Sangeeta Khanna MD Fellow, Neuro-Ophthalmology Division of Ophthalmology Case Western Reserve University MetroHealth Medical Center Cleveland OH USA 47 Staphylococcus 73 Mucopolysaccharidosis II 74 Mucopolysacccharidosis III Peng Tee Khaw PhD, FRCP, FRCS, FRCOphth, FIBiol, FRCPath, FMedSci Professor of Glaucoma and Ocular Healing Paediatric Glaucoma Unit Moorfields Eye Hospital London UK 265 Primary Congenital Glaucoma James L. Kinyoun MD Professor of Ophthalmology Department of Ophthalmology University of Washington Seattle WA USA 100 Wegener Granulomatosis Caitriona Kirwan MB, MRCOphth Fellow, Department of Ophthalmology Mater Private Hospital Dublin Ireland 137 Medulloepithelioma
Sanjay R. Kedhar MD Clinical Instructor of Ophthalmology Division of Ocular Immunology The Wilmer Eye Institute Johns Hopkins School of Medicine Baltimore MD USA 310 Ankylosing Spondylitis and Reiter’s Disease
Tero Kivelä MD, FEBO Professor of Ophthalmology Department of Ophthalmology Helsinki University Central Hospital Helsinki Finland 146 Periocular Merkel Cell Carcinoma
Ronald V. Keech MD Clinical Professor of Ophthalmology Department of Ophthalmology University of Iowa Hospitals & Clinics Iowa City IA USA 223 Dissociated Vertical Deviation
Michael L. Klein MD Professor of Ophthalmology Director, Macular Degeneration Center Casey Eye Institute Portland OR USA 305 Age-related Macular Degeneration 330 Branch Retinal Vein Occlusion 335 Eales Disease
Robert C. Kersten MD Professor of Clinical Ophthalmology Department of Ophthalmology University of Cincinnati College of Medicine Cincinnati OH USA 140 Mucocele Marshall P. Keys MD, PA Ophthalmologist in Private Practice Rockville MD USA 112 Dyslexia
Stephen A. Klotz MD Professor of Medicine Section of Infectious Diseases University of Arizona Tuscon AZ USA 10 Coccidioidomycosis
Peter R. Laibson MD Professor of Ophthalmology Jefferson Medical College Thomas Jefferson University and Director Emeritus, Cornea Service Wills Eye Institute Philadelphia PA USA 193 Epithelial Basement Membrane Dystrophy 210 Schnyder’s Crystalline Corneal Dystrophy
Regis P. Kowalski MS, [M]ASCP Associate Research Professor of Ophthalmology Ophthalmic Microbiology The Eye and Ear Institute Pittsburgh PA USA 39 Pseudomonas aeruginosa
Rohit R. Lakhanpal MD Clinical Assistant Professor of Ophthalmology and Visual Sciences Vitreoretinal Surgery Service Department of Ophthalmology University of Maryland School of Medicine Practice Partner Eye Consultants of Maryland Owings Mills MD USA 257 Fungal Endophthalmitis
Jay H. Krachmer MD Professor; Head, Department of Ophthalmology Department of Ophthalmology University of Minnesota Minneapolis MN USA 89 Amyloidosis 198 Granular Corneal Dystrophy Theodore Krupin MD Professor of Ophthalmology Northwestern University Chicago IL USA 266 Juvenile Glaucoma Ferenc Kuhn MD, PhD Associate Professor of Ophthalmology Department of Ophthalmology University of Alabama at Birmingham School of Medicine and President , American Society of Ocular Trauma Birmingham AL USA 154 Management of Screral Ruptures and Lacerations Abhaya Vivek Kulkarni MD, PhD, FRCSC Consultant Neurosurgeon Division of Neurosurgery Hospital for Sick Children Toronto, Ontario Canada 125 Craniopharyngioma Robert C. Kwun MD Partner Retina Associates of Utah Salt Lake City UT USA 169 Angioid Streaks
Byron L. Lam MD Professor, Department of Ophthalmology Bascom Palmer Eye Institute Miami FL USA 43 Rocky Mountain Spotted Fever 245 Lid Myokymia Laurent Lamer MD, FRCS(c) Associate Professor Department of Ophthalmology University of Montreal Montreal, Quebec Canada 31 Newcastle Disease David P. Lawlor MD Ophthalmologist Private Practice Newport VT USA 302 Lenticonus and Lentiglobus Andrew W. Lawton MD Clinical Associate Professor of Ophthalmology University of Tennessee, Memphis Little Rock Eye Clinic Little Rock AR USA 317 Papilledema Alan B. Leahey MD Lehigh Valley Eye Center Allentown PA USA 27 Molluscum Contagiosum
Russell LeBoyer MD Department of Ophthalmology Baylor College of Medicine Houston TX USA 119 Tolosa–Hunt Syndrome Andrew G. Lee MD Professor of Ophthalmology, Neurology and Neurosurgery University of Iowa Hospitals Iowa City IA USA 106 Acquired Inflammatory Demyelinating Neuropathies
Contributors
John Ko MD, FACS Clinical Assistant Professor Department of Ophthalmology Michigan Wayne State University Hospital Detroit MI and Clinical Instructor William Beaumont Hospital Loyal Oak MI USA 240 Eyelid Contusions, Lacerations and Avulsions
Wen-Hsiang Lee MD, PhD Clinical Fellow, Retina Division Wilmer Ophthalmological Institute Johns Hopkins University School of Medicine, Baltimore MD and Assistant Professor of Clinical Ophthalmology Vitreoretinal Service Bascom Palmer Eye Institute University of Miami School of Medicine Miami, FL USA 166 Intraocular Epithelial Cysts William Barry Lee MD, FACS Consultant Eye Consultants of Atlanta Piedmont Hospital Atlanta GA USA 160 Shaken Baby Syndrome 216 Accommodative Esotropia Sharon S. Lehman MD Clinical Assistant Professor of Ophthalmology and Pediatrics Jefferson Medical College Division Chief, Ophthalmology A.I. duPont Hospital for Children Wilmington DE USA 85 Erythema Multiforme Major Howard M. Leibowitz MD Sherwood J. and H. Lorene Tarlow Professor of Ophthalmology Chairman of the Department, Emeritus Department of Ophthalmology Boston University School of Medicine Boston MA USA 38 Proteus James Leong MMed(OphthSc) MBBS(Hons) Ophthalmology Regsitrar Sydney Eye Hospital Sydney NSW Australia 37 Propionibacterium acnes
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Contributors
Alex V. Levin MD, MHSc, FAAP, FAAO, FRCSC Associate Professor Department of Pediatrics, Genetics & Ophthalmology & Vision Sciences Department University of Toronto Ontario, Toronto Canada 77 Mucopolysaccharidosis VII
Richard D. Lisman MD, FACS Clinical Professor of Ophthalmology New York University School of Medicine Surgeon Director, Manhattan Eye, Ear & Throat Hospital New York NY USA 321 External Orbital Fractures 322 Internal Orbital Fractures
Leonard A. Levin MD, PhD Canada Research Chair Department of Ophthalmology University of Montreal Montreal, Canada and Professor Department of Ophthalmology and Visual Sciences University of Wisconsin Madison WI USA 318 Traumatic Optic Neuropathy
David Litoff MD Chief of Ophthalmology Kaiser Permanente Colorado Assistant Clinical Professor of Ophthalmology University of Colorado Boulder CO USA 285 Iris Prolapse
Mark R. Levine MD, FACS Clinical Professor of Ophthalmology Case Western Reserve School of Medicine Cleveland OH USA 159 Orbital Implant Extrusion Norman S. Levy MD, PhD Director Florida Ophthalmic Institute Gainesville FL USA 141 Neurilemoma
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James C. Liu MD, MBA Chairman of Ophthalmology Department Good Samaritan Hospital San Jose CA USA 187 Conjunctival, Corneal or Scleral Cysts Evan Loft MD Resident Physician in Ophthalmology Emory Eye Center Emory University Atlanta GA USA 235 Blepharoconjunctivitis
Thomas J. Liesegang MD Professor of Ophthalmology Mayo Clinic College of Medicine Jacksonville FL USA 53 Varicella and Herpes Zoster 280 Fuchs’ Heterochromic Iridocyclitis
Ronald R. Lubritz MD, FACP Clinical Professor of Medicine (Dermatology) Tulane Medical Center New Orleans, LA Hattiesburg Clinic Hattiesburg MS USA 121 Actinic and Seborrheic Keratosis
Lyndell L. Lim MBBS, FRANZCO Mankiewicz-Zelkin Crock Fellow Centre for Eye Research Australia University of Melbourne East Melbourne, Victoria Australia 344 White Dot Syndromes
David C. W. Mabey DM, FRCP Professor, Clinical Research Unit London School of Hygiene & Tropical Medicine London UK 50 Trachoma
Linda H. Lin MD Ophthalmologist, Glaucoma Specialist Private Practice Houston TX USA 180 Filtering Blebs and Associated Problems
Ian A. Mackie MBChB, DO, FRCS, FCOphth Consulting Ophthalmologist Harley Street London UK 205 Neuroparalytic Keratitis
Srilakshmi Maguluri MD Clinical Instructor and Retina Fellow Department of Ophthalmology and Visual Sciences Vanderbilt University Medical Center Nashville TN USA 33 Ocular Candidiasis M. Maliki MD Specialist in Anatomy Pathology Department of Anatomy Pathology Ibn Sina Hospital Rabat Rabat Morocco 131 Kaposi’s Sarcoma Nick Mamalis MD Professor of Ophthalmology John A Moran Eye Center Department of Ophthalmology and Visual Sciences University of Utah Salt Lake City UT USA 255 Anophthalmos Mark J. Mannis MD, FACS Professor and Chairman Department of Ophthalmology University of California, Davis Sacramento CA USA 86 Ocular Rosacea Steven L. Mansberger MD, MPH Associate Scientist, Devers Eye Institute Legacy Health System Adjunct Assistant Professor Department of Ophthalmology Clinical Assistant Scientist Department of Public Health and Preventative Medicine Oregon Health and Science University Portland OR USA 271 Ocular Hypotony Ahmad M. Mansour MD Clinical Professor Department of Ophthalmology AUB American University of Beirut Beirut Lebanon 79 Hyperlipoproteinemia Alexandre S. Marcon MD Director, Cornea Service and Medical Director Santa Casa de Porto Alegre Eye Bank Porto Alegre RS Brazil 192 Detachment of Descemet’s Membrane 203 Macular Corneal Dystrophy
Peter B. Marsh MD Kaiser Permanente Clackamas Eye Care Portland OR USA 252 Seborrheic Blepharitis Rookaya Mather MD, MBBCh, FRCS(C), DABO Assistant Professor Department of Ophthalmology University of Western Ontario London, Ontario Canada 48 Streptococcus William D. Mathers MD Professor of Ophthalmology Department of Ophthalmology Oregon Health and Science University Casey Eye Institute Portland OR USA 59 Demodicosis 62 Pediculosis and Phthiriasis K. Matti Saari MD, MedScD, FEBO Professor and Chairman Department of Ophthalmology Institute of Clinical Sciences University of Turku Tampere Finland 54 Yersiniosis Louise A. Mawn MD, FACS Associate Professor of Ophthalmology and Neorological Surgery Director, Ophthalmic Plastic and Reconstructive Surgery Vanderbilt Eye Institute Vanderbilt University Medical Centre Nashville TN USA 293 Lacrimal System Contusions and Lacerations Penny J. McAllum FRANZCO Formerly at Department of Ophthalmology University of Auckland Auckland New Zealand 26 Microsporidial Infection
Rex M. McCallum MD Professor of Medicine Duke University School of Medicine Durham NC USA 91 Cogan Syndrome Peter McCluskey MD, FRANZCO,FRACS Professor of Ophthalmology Department of Ophthalmology Liverpool Hospital Liverpool NSW Australia 37 Propionibacterium acnes Gregory J. McCormick MD Fellow, Cornea and Refractive Surgery University of Rochester Eye Institute Rochester NY USA 348 Scleromalacia Perforans Steven A. McCormick MD Director Department of Pathology The New York Eye and Ear Infirmary New York NY USA 249 Melanocytic Lesions of the Eyelids James P. McCulley MD, FACS, FRCOphth Professor and Chairman of Ophthalmology Department of Ophthalmology UT Southwestern Medical Center Dallas TX USA 150 Acid Burns
Douglas L. Meier MD Ophthalmologist Department of Ophthalmology The Portland Clinic Portland OR USA 202 Lattice Corneal Dystrophy David M. Meisler MD, FACS Professor of Opthalmology Cleveland Clinic Lerner College of Medicine Cole Eye Institute Cleveland OH USA 16 Gonococcal Ocular Disease
Contributors
Italo M. Marcon MD Ophthalmologist in Chief Santa Casa de Porto Alegre University Hospital Professor of Ophthalmology Faculdade Federal de Ciências Médicas — FFFCMPA Porto Alegre RS Brazil 192 Detachment of Descemet’s Membrane 203 Macular Corneal Dystrophy
Saul C. Merin MD Professor of Ophthalmology Department of Ophthalmology Hadassah Hebrew University Medical Center Jerusalem Israel 341 Retinitis Pigmentosa Dale R. Meyer MD Director, Ophthalmic Plastic Surgery Professor of Ophthalmology Lions Eye Institute Albany Medical Center Albany NY USA 246 Lid Retraction Roger F. Meyer MD Professor Emeritus of Ophthalmology University of Michigan Ann Arbor MI USA 30 Mumps
John G. McHenry MD, MPH Associate Professor of Ophthalmology Department of Ophthalmology UT Southwestern Medical Center at Dallas Dallas TX USA 319 Vasculopathic Optic Neuropathies
Kevin S. Michels MD Ophthalmology Resident Department of Ophthalmology Oregon Health and Science University Portland OR USA 243 Hordeolum
Alan A. McNab MBBS, FRANZCO Director, Orbital Plastic and Lacrimal Clinic St Vincents Private Hospital Fitzroy Australia 134 Liposarcoma
Tatyana Milman, MD, FAAO Department of Pathology Wills Eye Hospital Thomas Jefferson University Philadelphia PA USA 249 Melanocytic Lesions of the Eyelids
Jared J. Mee MBBS Ophthalmologist Northern Hospital Epping, Melbourne Australia 117 Myasthenia Gravis
Roni Mintz MD Lecturer of Ophthalmology WK Kellogg Eye Center University of Michigan Ann Arbor MI USA 22 Koch–Weeks Bacillus
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Chantal F Morel MD, FRCP(C) Genetic Metabolic Fellow Division of Clinical and Metabolic Genetics The Hospital for Sick Children Toronto, Ontario Canada 77 Mucopolysaccharidosis VII Contributors
William R. Morris MD Associate Professor of Ophthalmology Department of Ophthalmology University of Tennessee Health Science Center Hamilton Eye Institute Memphis TN USA 194 Filamentary Keratitis Mark L. Moster MD Director, Neuro-Ophthalmology Albert Einstein Medical Center and Professor of Neurology, Thomas Jefferson University School of Medicine and Instructor, Neuro-Ophthalmology, Wills Eye Hospital Philadelphia PA USA 29 Mucormycosis John Mourani MD Fellow in Infectious Diseases Section of Infectious Diseases University of Arizona Tuscon AZ USA 10 Coccidioidomycosis Cristina Muccioli MD Professor of Ophthalmology Department of Ophthalmology Federal University of São Paulo São Paulo Brazil 3 Acquired Immune Deficiency Syndrome Raghu C. Mudumbai MD Associate Professor Residency Program Director Department of Ophthalmology University of Washington Medical Center Seattle WA USA 215 Abducens (Sixth Nerve) Paralysis 219 Brown’s Syndrome 258 Angle Recession Glaucoma
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Fernando H. Murillo-Lopez MD Instructor Department of Ophthalmology Bolivian Ophthalmology Society Bolivian National Institute of Ophthalmology La Paz Bolivia 71 Mucopolysaccharidosis IH 72 Mucopolysaccharidosis IH/S Shoib Myint DO, FAACS Departments of Ophthalmic and Facial Plastic Surgery William Beaumont Eye Institute Royal Oak MI USA 254 Xanthelasma Parveen K Nagra MD Instructor of Ophthalmology Cornea Service Wills Eye Institute Thomas Jefferson University Philadelphia PA USA 213 Thygeson’s Superficial Punctate Keratopathy A Naoumi MD Professor in Ophthalmology Service d’Ophtalmologie Hôpital Militaire d’Instruction Med V Rabat Morocco 131 Kaposi’s Sarcoma John Nassif MD Private Practice Clearwater FL USA 240 Eyelid Contusions, Lacerations and Avulsions Michelle T. Nee MD Clinical Fellow in Glaucoma Department of Ophthalmology University of California, San Francisco San Francisco CA USA 267 Lens-induced Glaucoma Marcelo V. Netto MD Cornea and Refractive Surgery Staff Department of Ophthalmology University of São Paulo São Paulo Brazil 204 Mooren’s Ulcer
John D. Ng MD, MS, FACS Associate Professor of Ophthalmology Casey Eye Institute Oregon Health and Science University Portland OR USA 148 Sebaceous Gland Carcinoma 239 Epicanthus 248 Marcus Gunn Syndrome 290 Dacryoadenitis 292 Epiphora Hau T. Nguyen MD Fellow Devers Eye Institute Portland OR USA 268 Malignant Glaucoma Quan Dong Nguyen MD, MSc Assistant Professor of Ophthalmology Diseases of the Retina and Vitreous, and Uveitis Wilmer Eye Institute Johns Hopkins Hospital Baltimore MD USA 99 Uveitis Associated with Juvenile Idiopathic Arthritis Denis M. O’Day MD, FACS Professor of Ophthalmology Vanderbilt Eye Institute Nashville TN USA 6 Bacillus Species Infections 33 Ocular Candidiasis 197 Fungal Keratitis A. Justin O’Day MBBS, FRANZCO Associate Professor Victoria Parade Eye Consultants St Vincents Medical Centre Fitzroy Melbourne Australia 117 Myasthenia Gravis Henry S. O’Halloran MD, DOphth, FRCSI Pediatric and Neuro-Ophthalmologist Children’s Hospital San Diego San Diego CA USA 160 Shaken Baby Syndrome 216 Accommodative Esotropia Michael O’Keefe MB, FRCS, FRCOphth Professor of Ophthalmology Department of Ophthalmology Mater Private Hospital Dublin Ireland 137 Medulloepithelioma
Fumiki Okamoto MD, PhD Assistant Professor University of Tsukuba Ibaraki-ken Japan 173 Expulsive Hemorrhage
James C. Orcutt MD, PhD Department of Ophthalmology University of Washington Medical Center Seattle WA USA 253 Trichiasis 324 Optic Foramen Fractures Sema Oruc Dundar MD Professor of Ophthalmology Department of Ophthalmology Adnan Menderes University School of Medicine Aydin Turkey 286 Pars Planitis Aaron Osbourne MD, MRCOphth Specialist Registrar in Ophthalmology Department of Ophthalmology Eye, Ear, Nose and Throat Centre Queens Medical Centre Nottingham UK 331 Central or Branch Retinal Artery Occlusion Maristela Amaral Palazzi MD, PhD Ophthalmologist Department of Ophthalmology Boldrini Children Center Campinas São Paulo Brazil 145 Papilloma Earl A. Palmer MD, FAAP Professor of Ophthalmology and Pediatrics Departments of Ophthalmology and Pediatrics Casey Eye Institute Portland OR USA 342 Retinopathy of Prematurity
Jeffrey R. Parnell MD Clinical Instructor of Ophthalmology Department of Ophthalmology Northwestern University Medical School Retina Services of Illinois, LLC Chicago IL USA 162 Hypertension Cameron F. Parsa MD Assistant Professor of Ophthalmology Johns Hopkins University School of Medicine Wilmer Ophthalmological Institute The Johns Hopkins Hospital Baltimore MD USA 104 Neurofibromatosis 143 Optic Gliomas 163 Papillorenal Syndrome 277 Accommodative Spasm Sanjay V. Patel MD Assistant Professor of Ophthalmology Mayo Clinic College of Medicine Rochester MN USA 11 Dermatophytosis Emily Patterson MD Devers Eye Institute Portland OR USA 272 Open-angle Glaucoma 276 Primary Angle-closure Glaucoma Scott D. Pendergast MD Vitreoretinal Surgeon Partner, Retina Associates of Cleveland Inc. Beachwood OH USA 172 Choroidal Ruptures Henry D. Perry MD, FACS Senior Founding Partner and Director, Cornea Division Ophthalmic Consultants of Long Island and Clinical Associate Professor of Ophthalmology Weill Cornell School of Medicine New York NY USA 211 Superior Limbic Keratoconjunctivitis
Keith Roberson Peters MD, ABR, CAQ VIR, CAQ NR Associate Professor Department of Radiology University of Florida College of Medicine Gainsville FL USA 80 Carotid Cavernous Fistula Stephanie M. Po MD Chief Department of Ophthalmology Kaiser Permanente Walnut Creek CA USA 267 Lens-induced Glaucoma
Contributors
Richard J. Olson MD Associate Clinical Professor of Ophthalmology Department of Ophthalmology University of Iowa, Hospitals and Clinics Iowa City IA USA 223 Dissociated Vertical Deviation
Maria Papadopoulos MBBS, FRACO Consultant Ophthalmic Surgeon Paediatric Glaucoma Unit Moorfields Eye Hospital London UK 265 Primary Congenital Glaucoma
Russell Pokroy MD Senior Ophthalmologist Department of Ophthalmology Kaplan Medical Center Rehovot Israel 176 Allergic Conjunctivitis 185 Vernal Keratoconjunctivitis Allen Michael Putterman MD Professor of Ophthalmology Chief, Oculoplastic Surgery University of Illinois College of Medicine Chairman, Department of Ophthalmology Michael Reese Hospital and Medical Center Chicago IL USA 247 Madarosis Rubén Queiro PhD Consultant Rheumatologist Rheumatology Division University Hospital Central de Asturias Oviedo Spain 87 Psoriasis Nastaran Rafiei MD Wilmer Ophthalmogical Institute Johns Hopkins University School of Medicine Baltimore MD USA 104 Neurofibromatosis Type 1 Bahram Rahmani MD, MPH Assistant Professor of Ophthalmology Department of Ophthalmology Northwestern University Division of Ophthalmology Children’s Memorial Hospital Chicago IL USA 168 Traumatic Hyphema
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Contributors
Christopher J Rapuano MD Co-Director and Attending Surgeon, Cornea Service Co-Director, Refractive Surgery Department Wills Eye Institute and Professor of Ophthalomology Jefferson Medical College of Thomas Jefferson University Philadelphia PA USA 192 Detachment of Descemet’s Membrane 201 Keratoconus Karim Rasheed MD, MSc, MRCOphth Medical Director Sani Eye Center Templeton CA USA 206 Pellucid Marginal Degeneration S. R. Rathinam MNAMS, PhD Professor of Ophthalmology and Head,Uveitis Service Aravind Eye Hospital and Post Graduate Institute of Ophthalmology Madurai India 24 Leptospirosis Lawrence A. Raymond MD Associate Professor of Clinical Ophthalmology Retinal-Vitreous Surgeon Cincinnati Eye Institute Cincinnati OH USA 56 Baylisascaris Russell W. Read MD Associate Professor Ophthalmology and Pathology University of Alabama at Birmingham Birmingham AL USA 164 Vogt–Koyanagi–Harada Disease August Lafayette Reader III MD, FACS Clinical Professor of Ophthalmology California Pacific Medical Center San Francisco CA USA 114 Hysteria, Malingering and Anxiety States Franco M. Recchia MD Assistant Professor of Ophthalmology, Vitreo-retinal Surgery Department of Ophthalmology and Visual Sciences Vanderbilt University Medical Center Nashville TN USA 6 Bacillus Species Infections 33 Ocular Candidiasis
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James J. Reidy MD, FACS Associate Professor of Ophthalmology State University of New York School of Medicine and Biomedical Sciences Buffalo NY USA 42 Rhinosporidiosis Adam C. Reynolds MD Assistant Clinical Professor Intermountain Eye Center Boise ID USA 180 Filtering Blebs and Associated Problems 270 Ocular Hypertension Larry F. Rich MS, MD Professor of Ophthalmology Casey Eye Institute Portland OR USA 152 Conjunctival Lacerations and Contusions 184 Pterygium and Pseudopterygium Robert Ritch MD Professor of Clinical Ophthalmology New York Medical College Valhalla NY USA 275 Plateau Iris Richard M. Robb MD Associated Professor of Harvard Medical School Emeritus Chief of Ophthalmology, Department of Ophthalmology Children’s Hospital Boston Boston MA USA 126 Dermoid Pierre-Yves Robert MD, PhD Ophthalmologist CHU Dupuytren Limoges France 1 Acinetobacter Joseph E. Robertson Jr MD Professor and Chairman Department of Ophthalmology Casey Eye Institute Portland OR USA 307 Epimacular Proliferation 349 Familial Exudative Vitreoretinopathy
Shiyoung Roh MD Assistant Clinical Professor pf Ophthalmology Department of Ophthalmology Tufts University School of Medicine Lahey Clinic Peabody MA USA 103 Angiomatosis Retinae Jean-Paul Romanet MD Professor of Ophthalmology Department of Ophthalmology Hôspital Michallon Grenoble France 157 Intraocular Foreign Body: Steel or Iron Jack Rootman MD, FRCSC Professor Department of Ophthalmology & Visual Sciences Faculty of Medicine Eye Care Center Vancouver BC Canada 323 Orbital Inflammatory Syndromes Barbara L. Roque MD Ophthalmologist EYE REPUBLIC Ophthalmology Clinic Asian Hospital and Medical Center Alabang Muntinlupa City Philippines 133 Leiomyoma 178 Conjunctival Melanotic Lesions Manolette R. Roque MD, MBA Ophthalmologist EYE REPUBLIC Ophthalmology Clinic Asian Hospital and Medical Center Alabang Muntinlupa City Philippines 133 Leiomyoma 178 Conjunctival Melanotic Lesions Arthur L. Rosenbaum MD Professor of Ophthalmology and Vice Chairman, Department of Ophthalmology Chief, Pediatric Ophthalmology and Strabismus Division Jules Stein Eye Institute Los Angeles CA USA 225 Esotropia-High Accommodative Convergence-to-Accommodation Ratio James Todd Rosenbaum MD Professor of Medicine, Ophthalmology and Cell Biology Oregon Health and Science University Casey Eye Institute Portland OR USA 97 Systemic Lupus Erythematosus
Paul A. Rundle MBBS, FRCOphth Consultant Ocular Oncologist Department of Ophthalmology Royal Hallamshire Hospital Sheffield UK 174 Malignant Melanoma of the Posterior Uvea Alfredo A. Sadun MD, PhD F Thornton Professor of Vision Research University of Southern California Department of Ophthalmology Doheney Eye Institute Los Angeles CA USA 315 Ischemic Optic Neuropathies Norman A. Saffra MD Professor of Ophthalmology Medical and Surgical Eyesite Brooklyn NY USA 128 Fibrosarcoma Sarwat Salim MD, FACS Assistant Professor Department of Ophthalmology Hamilton Eye Institute University of Tennessee Medical Center at Memphis Memphis TN USA 258 Angle Recession Glaucoma
John R. Samples MA, MD Glaucoma Consultant Glaucoma Consultants & The Eye Clinic Portland OR USA 241 Facial Movement Disorders 259 Corticosteroid Induced Glaucoma 262 Glaucoma Associated with Elevated Venous Pressure Alvina Pauline D Santiago MD Clinical Associate Professor University of the Philippines College of Medicine and Chief, Section of Pediatric Ophthalmology, The Medical City and Consultant in Pediatric Ophthalmology St Luke’s Medical Center Quezon City Philippines 225 Esotropia: High Accommodative Convergence-to-Accommodation Ratio David A. Saperstein MD Associate Professor of Ophthalmology University of Washington Seattle WA USA 332 Central Serous Chorioretinopathy Richard A. Saunders MD Professor of Ophthalmology and Pediatrics Department of Ophthalmology MUSC, Storm Eye Institute Charleston SC USA 227 Inferior Rectus Muscle Palsy James A. Savage MD Nevada Eye and Ear Henderson NV USA 274 Pigmentary Dispersion Syndrome and Pigmentary Glaucoma Tina A. Scheufele MD Fellow in Vitreoretinal Surgery, New England Eye Center Tufts University School of Medicine Boston MA USA 308 Macular Hole Vivian Schiedler MD Ophthalmic Plastic and Reconstructive Surgery Fellow Department of Ophthalmology University of Washington Seattle WA USA 324 Optic Foramen Fractures
Thomas K. Schlesinger MD, PhD Department of Ophthalmology Oregon Health and Science University Portland OR USA 340 Retinal Venous Obstruction Abraham Schlossman MD, FACS Formerly, Clinical Professor of Ophthalmology New York University College of Medicine New York NY USA 264 Glaucomatocyclitic Crisis
Contributors
F. Hampton Roy MD, FACS Medical Director Hampton Roy Eye Center Little Rock AR USA 12 Diphtheria 18 Herpes Simplex 19 Inclusion Conjunctivitis 36 Pneumococcus 60 Echinococcosis 65 Inflammatory Bowel Disease 69 Diabetes 75 Mucopolysaccharidosis IV 92 Pseudoxanthoma Elasticum 108 Cerebral Palsy 132 Keratoacanthoma 147 Retinoblastoma 151 Alkaline Injury 161 Thermal Burns 165 Epithelial Ingrowth 167 Postoperative Flat Anterior Chamber 175 Sympathetic Ophthalmia 179 Corneal and Conjunctival Calcifications 191 Corneal Neovascularization 196 Fuchs’ Dellen 217 Acquired Nonaccommodative Esotropia
Lee K. Schwartz MD Consulant, Corneal External Disease Department of Ophthalmology California Pacific Medical Center San Francisco CA USA 242 Floppy Eyelid Syndrome Ingrid U. Scott MD, MPH Professor of Ophthalmology and Health Evaluation Sciences Department of Ophthalmology Penn State College of Medicine Hershey PA USA 35 Pharyngoconjunctival Fever Jennifer Scruggs MD Clinical Instructor of Ophthalmology New York University School of Medicine New York NY USA 135 Lymphangioma 321 External Orbital Fractures 322 Internal Orbital Fractures Ernesto I. Segal MD Clinical Assistant Professor University of Texas Medical Branch in Galveston Boca Raton FL USA 95 Sarcoidosis Ismail A. Shalaby MD, PhD Instructor in Ophthalmology Jonas Friedenwald Eye Institute Baltimore MD USA 2 Acquired and Congenital Syphilis Aziz Sheikh MSc, DCH, DRCOG, MD, FRCP, FRCGP Professor of Primary Care Research and Development Division of Community Health Sciences, GP Section University of Edinburgh Edinburgh UK 177 Bacterial Conjunctivitis
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John D. Sheppard MD, MMSc Professor of Ophthalmology, Microbiology and Molecular Biology Eastern Virginia Medical School Virginia Eye Consultants Norfolk VA USA 8 Brucellosis Contributors
Mark D. Sherman MD Assistant Professor Department of Ophthalmology Loma Linda University School of Medicine San Luis Obispo CA USA 5 Aspergillosis Carol L. Shields MD Professor, Thomas Jefferson Medical College Attending Surgeon and Associate Director Wills Eye Hospital Philadelphia PA USA 144 Orbital Rhabdomyosarcoma 263 Glaucoma Associated with Intraocular Tumors Jerry A. Shields MD Director, Oncology Services Wills Eye Hospital Philadelphia PA USA 144 Orbital Rhabdomyosarcoma 263 Glaucoma Associated with Intraocular Tumors Amarpreet Singh MD Fellow in Oculoplastic Surgery Case Western Reserve University of School of Medicine Cleveland OH USA 159 Orbital Implant Extrusion Christopher N. Singh MD Resident Department of Ophthalmology University of Washington Seattle WA USA 219 Brown’s Syndrome 332 Central Serous Chorioretinopathy Eric L. Singman MD, PhD Director Neuro-Ophthalmology, Low Vision and Vision Rehabilitation Family Eye Group Lancaster PA USA 115 Idiopathic Intracranial Hypertension and Pseudotumor Cerebri 288 Uveitis
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Donna Siracuse-Lee MD Physician in Ophthalmology Medical and Surgical Eyesite Brooklyn NY USA 128 Fibrosarcoma Aaron D. Smalley MD Resident in Ophthalmology Department of Ophthalmology Penn State Milton S Hershey Medical Center Hershey PA USA 35 Pharyngoconjunctival Fever Patricia W. Smith MD Triangle Eye Physicians, PA Raleigh NC USA 166 Intraocular Epithelial Cysts Anthony W. Solomon MBBS, PhD Lecturer, Clinical Research Unit London School of Hygiene & Tropical Medicine London UK 50 Trachoma Hassane Souhail MD Resident in Ophthalmology Service d’Ophtalmologie Hôpital Militaire d’Instruction Med V Rabat Morocco 131 Kaposi’s Sarcoma Daniel H. Spitzberg MD, FACS Ophthalmologist, Uveitis Specialist Ophthalmology Whitson Eyecare Indianapolis IN USA 21 Influenza Thomas C. Spoor MD, MS, FACS Michigan Neuro-Ophthalmology Grosse Point Farms MI USA 319 Vasculopathic Optic Neuropathies Robert L. Stamper MD Professor of Ophthalmology Director of the Glaucoma Service Department of Ophthalmology University of California, San Francisco San Francisco CA USA 267 Lens-induced Glaucoma
Walter J. Stark MD Professor of Ophthalmology Director of the Stark-Mosher Center for Cataract and Corneal Disorders The Wilmer Eye Institute The John Hopkins Hospital Baltimore MD USA 166 Intraocular Epithelial Cysts Eric A. Steele MD Assistant Professor of Ophthalmology Casey Eye Institute Oregon Health and Science University Portland OR USA 244 Lagophthalmos 250 Orbital Fat Herniation 251 Ptosis 294 Lacrimal Gland Tumors Thomas L. Steinemann MD Associate Professor of Ophthalmology Division of Ophthalmology Case Western Reserve University MetroHealth Medical Center Cleveland OH USA 47 Staphylococcus 181 Giant Papillary Conjunctivitis 212 Terrien’s Marginal Degeneration Ann U. Stout MD Assistant Professor of Ophthalmology Casey Eye Institute Portland OR USA 214 A-pattern Strabismus 230 Oculomotor (Third Nerve) Paralysis 232 Superior Oblique (Fourth Nerve) Palsy J. Timothy Stout MD, PhD Director Retina Services Devers Eye Institute and Casey Eye Institute Legacy Health System and Department of Ophthalmology Oregon Health and Science University Portland OR USA 328 Acquired Retinoschisis R. Doyle Stulting MD, PhD Professor of Ophthalmology Emory Eye Center Emory University Atlanta GA USA 208 Posterior Polymorphous Dystrophy 235 Blepharoconjunctivitis
Joel Sugar MD Professor of Ophthalmology Department of Ophthalmology and Visual Sciences University of Illinois at Chicago Chicago IL USA 189 Corneal Edema Donny W. Suh MD Clinical Assistant Professor Department of Ophthalmology University of Nebraska West des Moines IA USA 15 Escherichia coli Eric B. Suhler MD, MPH Chief of Ophthalmology Portland VA Medical Center and Assistant Professor of Ophthalmology Co-Director, Uveitis Service Casey Eye Institute Oregon Health and Science University Portland OR USA 9 Cat-scratch disease 49 Tetanus 344 White Dot Syndromes John H. Sullivan MD Clinical Professor Department of Ophthalmology University of California San Francisco San Francisco CA USA 234 Blepharochalasis John Everett Sutphin MD Professor and Chair Department of Ophthalmology University of Kansas Medical Center Kansas City KS USA 55 Acanthamebiasis Kenneth C. Swan MD Formerly, Professor Department of Ophthalmology Oregon Health and Science University Portland OR USA 283 Iris Cysts
Khalid F. Tabbara MD, ABO, FRCOphth Adjunct Professor of Ophthalmology Johns Hopkins University School of Medicine Baltimore MD USA and Medical Director The Eye Center Riyadh Saudi Arabia 64 Trichinosis 207 Phlyctenulosis Mandeep S. Tamber MD Neurosurgery Fellow Division of Neurosurgery Hospital for Sick Children Toronto, Ontario Canada 125 Craniopharyngioma Angelo P. Tanna MD Director, Glaucoma Service Department of Ophthalmology Northwestern University Feinberg School of Medicine Chicago IL USA 266 Juvenile Glaucoma Sinan Tatlipinar MD Cinical Fellow Retina Service The Wilmer Eye Institute The Johns Hopkins Hospital Baltimore MD USA 347 Scleritis Ramin Tayani MD, MPH, FAAO Medical Director Tayani Eye Institute San Clemente CA USA 46 Sporotrichosis Klaus D. Teichmann MD, FRCSC, FRACO, DiplABO Senior Academic Consultant and Chief of Anterior Segment King Khaled Eye Specialist Hospital Riyadh Kingdom of Saudi Arabia 327 Orbital Hemorrhages Mark A. Terry MD Director, Corneal Services Devers Eye Institute Scientific Director Lions Vision Research Laboratory of Oregon Portland OR USA 195 Fuchs’ Corneal Dystrophy
Clement Chee Yung Tham FRCS, FCOphth(HK) Professor, Department of Ophthalmology and Visual Science The Chinese University of Hong Kong Queen Mary Hospital Hong Kong SAR China 275 Plateau Iris A. Therzaz MD Professor in Ophthalmology Service d’Ophtalmologie Hôpital Militaire d’Instruction Med V Rabat Morocco 131 Kaposi’s Sarcoma
Contributors
Alan Sugar MD Professor of Ophthalmology and Visual Sciences WK Kellogg Eye Center University of Michigan Ann Arbor MI USA 11 Dermatophytosis 22 Koch–Weeks Bacillus
Gilles Thuret MD, PhD Ophthalmologist University Hospital Saint-Etienne France 1 Acinetobacter 157 Intraocular Foreign Body: Steel or Iron Christopher Graham Tinley MBChB, MRCOphth Ophthalmology Specialist Registrar West of England Eye Unit Royal Devon and Exeter NHS Foundation Trust Exeter UK 299 After-Cataracts Andrea C. Tongue MD Ophthalmologist Child Eye Care Associates Lake Oswego OR USA 231 Superior Oblique Myokymia Rodrigo J. Torres MD Fellow Devers Eye Institute Portland OR USA 282 Iris Bombé Robert N. Tower MD Assistant Professor, Ophthalmic Facial Plastic and Orbital Surgery Department of Ophthalmology University of Washington School of Medicine Seattle WA USA 238 Entropion 291 Dacryocystitis and Dacryolith
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Contributors
Elias I Traboulsi MD Professor of Ophthalmology Cleveland Clinic Lerner College of Medicine Head, Department of Pediatric Ophthalmology and Strabismus Cole Eye Institute Cleveland OH USA 73 Mucopolysaccharidosis II 74 Mucopolysacccharidosis III Rupan Trikha MD Ophthalmology Resident Department of Ophthalmology Geisinger Medical Center Danville PA USA 188 Corneal Abrasions, Contusions, Lacerations and Perforations Brenda J. Tripathi PhD Distinguished Professor of Pathology, Microbiology and Immunology University of South Carolina School of Medicine Columbia SC USA 190 Corneal Mucous Plaques Ramesh C. Tripathi MD, MS(Ophth), PhD, FACS, FICS, FRCOphth, FRCPath, FNASc(I) Distinguished Professor of Ophthalmology Department of Ophthalmology University of South Carolina School of Medicine Columbia SC USA 190 Corneal Mucous Plaques Ilknur Tugal-Tutkun MD Professor of Ophthalmology Department of Ophthalmology Istanbul Faculty of Medicine Istanbul University Istanbul Turkey 90 Behçet’s Disease Irene Tung MD Resident Baylor College of Medicine Houston TX USA 183 Ophthalmia Neonatorum Judith A. M. Van Evendingen MD Neuro-ophthalmologist Rotterdam Eye Hospital Rotterdam The Netherlands 109 Chronic Progressive External Ophthalmoplegia
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Jean D. Vaudaux MD Department of Ophthalmology Jules Gonin Eye Hospital Lausanne Switzerland 63 Toxoplasmosis Niteen S Wairagkar MBBS, MD Deputy Director National Institute of Virology Pune India 4 Acute Hemorrhagic Conjunctivitis Joseph D. Walrath MD Resident Edward S. Harkness Eye Institute New York NY USA 135 Lymphangioma Rory McConn Walsh MD, MB, FRCSI(ORL) Consultant Otolaryngologist and Senior Lecturer Department of Otolaryngology RCSI Education and Research Center Beaumont Hospital Dublin Ireland 107 Bell’s Palsy David S. Walton MD Clinical Professor of Ophthalmology Harvard Medical School Boston MA USA 101 Weill–Marchesani Syndrome 278 Aniridia Ronald E. Warwar MD Clinical Assistant Professor Department of Surgery Wright State University School of Medicine Dayton OH USA 32 Nocardiosis 171 Choroidal Folds Peter G. Watson MA, MBBChir, FRCS, FRCOphth, DO Honorary Consultant Ophthalmic Surgeon Addenbrooke’s Hospital, Cambridge and Moorfields Eye Hospital London UK 93 Relapsing Polychondritis 345 Episcleritis
John J. Weiter MD, PhD Associate Clinical Professor of Ophthalmology Department of Ophthalmology Harvard Medical School Cambridge MA USA 103 Angiomatosis Retinae Richard G. Weleber MD Professor of Ophthalmology and Molecular & Medical Genetics Casey Eye Institute Oregon Health and Science University Portland OR USA 76 Mucopolysaccharidosis IV 336 Gyrate Atrophy of the Choroid and Retina with Hyperornithinemia 338 Refsum’s Disease Fleming D. Wertz III MD, FACS Consultant in Ophthalmology Department of Ophthalmology Lahey Clinic Northshore Peabody MA USA 155 Intraocular Foreign Body: Copper Igor Westra MD, MSc Assistant Clinical Professor University of North Carolina, Chapel Hill Retina of Coastal Carolina PLLC Wilmington NC USA 279 Ciliary Body Concussions and Lacerations David T. Wheeler MD Associate Professor of Ophthalmology and Pediatrics Oregon Health and Science University Casey Eye Institute Portland OR USA 52 Typhoid Fever 130 Juvenile Xanthogranuloma 229 Nystagmus 300 Congenital and Infantile Cataracts Charles P. Wilkinson MD Chairman, Department of Ophthalmology, Greater Baltimore Medical Center Professor, Department of Ophthalmology John Hopkins University Baltimore MD USA 337 Peripheral Retinal Breaks and Vitreoretinal Degenerative Disorders
David J. Wilson MD Thiele-Petti Chair, Ophthalmology Director, Eye Pathology Laboratory Oregon Health and Science University Casey Eye Institute Portland OR USA 271 Ocular Hypotony
Matthew W. Wilson MD, FACS Associate Professor Department of Opthalmology University of Tennessee Health Services Center Memphis TN USA 123 Capillary Hemangioma Steven E Wilson MD Professor of Ophthalmology and Director of Corneal Research Cole Eye Institute The Cleveland Clinic Cleveland OH USA 204 Mooren’s Ulcer
Terry D. Wood MD Neuro-Ophthalmology Fellow Casey Eye Institute Oregon Health and Science University Portland OR USA 9 Cat-scratch disease 49 Tetanus 127 Ewing’s Sarcoma 311 Compressive Optic Neuropathies Lihteh Wu MD Associate Surgeon Institute of Ocular Surgery San José Costa Rica 57 Coenurosis 333 Coats’ Disease Ozgur Yalcinbayir MD Visiting International Scholar Department of Ophthalmology St Louis University School of Medicine St Louis MO USA 82 Thalassemia
Howard Shann-Cherng Ying MD, PhD Assistant Professor of Ophthalmology Department of Ophthalmology The John Hopkins University Wilmer Eye Institute Baltimore MD USA 156 Intraocular Foreign Body: Nonmagnetic, Chemically Inert Peter N. Youssef MD Resident Department of Ophthalmology University of Washington Medical Center Seattle WA USA 219 Brown’s Syndrome 332 Central Serous Chorioretinopathy
Contributors
M. Edward Wilson MD Pierre G. Jenkins Professor and Chairman Department of Ophthalmology and Director, Storm Eye Institute Medical University of South Carolina Charleston SC USA 228 Monofixation Syndrome
John L. Wobig MD Formerly, Professor of Ophthalmology Casey Eye Institute Oregon Health and Science University Portland OR USA 292 Epiphoria
Gerald W. Zaidman MD Professor of Ophthalmology Department of Ophthalmology Westchester Medical Center Valhalla NY USA 25 Lyme Disease
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DEDICATION To Michelle, Charles, Frederick, Kimberly, Robert, Nichols and Helena _____________ Wendee, Mikayla, Jacob, Gracie-Anne and Sara-Jane _____________ Yvonne, Yvette, Helene Jean, Nina, Rick and Nick ______________ Neeli, Blake, Tyler, Trey, Cooper and Keetin
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S ECT I O N
1
Infectious Diseases
In ophthalmology
1 ACINETOBACTER 041.9 Gilles Thuret, MD, PhD Saint-Etienne, France Pierre-Yves Robert, MD, PhD Limoges, France Anne Carricajo, PhD Saint-Etienne, France Philippe Gain, MD, PhD Saint-Etienne, France
Acinetobacter species can colonize normal conjunctiva. They have been described in post mortem conjunctival flora and detected during corneal storage before graft. Conjunctival colonization seems not to be modified by frequent-replacement contact lenses. They have been described in various ocular infections but remain scarce.
Endophthalmitis This most severe ocular infection due to Acinetobacter spp. has a rather chronic presentation. It can be postoperative, posttraumatic, endogenous or bleb-related.
Orbital abscess Bacteria of the Acinetobacter genus are ubiquitous and may live in soil, water, plants and on the healthy skin of human beings and animals. Acinetobacter spp. are frequently isolated in wastewater and activated sludge from wastewater treatment. Some have emerged as important healthcare-associated pathogens in hospitals, but they are rarely involved in eye and annex infections. There is no pathognomonic clinical presentation of Acinetobacter ocular infection, therefore laboratory diagnosis is necessary for the choice of antibiotic treatment.
Keratitis Acinetobacter is the third most frequent bacteria involved in corneal ulcers and abscesses, after Pseudomonas aeruginosa, and staphylococci. Main risk factors are lagophthalmos, burns, and stay in an intensive care unit. Acinetobacter keratitis may present as crystalline keratopathy (although not pathognomonic), contact lens adverse effect. It results, very occasionally, in corneal perforation.
Purulent conjunctivitis (mono or polymicrobial)
CLINICAL DIAGNOSIS
Chronic blepharitis Not categorically involved.
General considerations Acinetobacter spp. belong to the usual cutaneous flora, especially in wet zones (groin, axilla, interdigital spaces) and are also isolated from the mouth, throat, trachea, nose, conjunctiva, bladder and rectum. Colonization and type of species differ between healthy and hospitalized patients. They can survive on inert surfaces or in dust for more than 8 days. The most frequently isolated are Acinetobacter baumannii, A. lwoffi i, A. haemolyticus, A. johnsonii, A. radioresistens, A. genomospecies 3 and A. genomospecies 13 (Tjernberg and Ursing). A. baumannii is linked to many hospital acquired infections (up to 90% of all Acinetobacter hospital infection in some countries) including skin and wound infections, pneumonia, septicemia, urinary tract infection and meningitis. A. lwoffi, especially, is responsible for most cases of Acinetobacter-related meningitis. Acinetobacter spp. are responsible for nearly 10% of all nosocomial infections. Community-acquired infections, mainly pneumonia, generally happen in immunocompromised patients. Mortality and morbidity resulting from A. baumannii infection relate to the underlying cardiopulmonary and immune status of the host rather than the inherent virulence of the organism.
TAXONOMY AND LABORATORY DIAGNOSIS Acinetobacter spp. are included in the Moraxellaceae family. The classification has been completely reorganized since 1986 and constantly enriched. Previously, names included Achromobacter, Alcaligenes, Cytophaga, ‘Diplococcus,’ ‘Bacterium,’ ‘Herellea,’ ‘Lingelsheimia,’ ‘Mima,’ Micrococcus, Moraxella, Neisseria. Thirty-two species have been isolated among which 17 received a published validated name. Only 10 of them have been held responsible for human infections. Species belonging to the Acinetobacter genus are Gramnegative cocobacillary rods, not sporulated, sometimes encapsulated, non motile, non fermentative, strictly aerobic, catalase positive and oxidase-negative. Bacterial growth is easily obtained on the usual broth — both rich and minimal salts media (trypticase soy broth, brain heart infusion). Incubation temperature must be between 30 to 35ºC since some species do not grow at 37ºC. Diagnosis can also be achieved using universal polymerase chain reaction (PCR) amplifying a portion of the 16S rRNA gene
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followed by direct sequencing of the resulting amplicon. This technique is particularly relevant for small ocular samples, including aqueous and vitreous taps.
TREATMENT SECTION 1 • Infectious Diseases
While colonization should not be treated, infection should. Acinetobacter spp. has a chromosomic beta-lactamase not inhibited by clavulanate, active against first generation cephalosporine but not against ticarcillin. Nevertheless, due to the importance of resistant strains, susceptibility testing is required for each clinically significant strain. Throughout the years multiresistant strains have emerged in hospitals. Some strains of A. baumannii are considered as the most resistant of all Gramnegative bacteria. Mechanisms of resistance are numerous: ● secretion of β-lactamases encoded either by the chromosome or by plasmids, ● acquisition of plasmids encoding resistance to aminosides, ● mutation of the DNA gyrase causing resistance to quinolones, ● transposon encoding resistance to chloramphenicol, etc.
Antibiotics Aminoglycosides (with amikacin the most active one > tobramycin > gentamicin), carbapenems (meropenem, imipenem — but associated with the rapid and worrying development of resistance), and fluoroquinolones remain the mainstay of therapy. Among b-lactams, although the carbapenems are still the most active antimicrobials against Acinetobacter species, carbapenems resistant strains have been reported in nosocomial outbreaks. Acinetobacter remains highly sensitive to other β-lactams: piperacillin/tazobactam, ticarcillin/clavulanate, ceftazidime, cefepime. Reappraisal of older compounds (e.g. polymyxin B, ampicillin/sulbactam) is necessary. Regarding fluoroquinolones, novel third and fourthgeneration fluoroquinolones demonstrate superior activity (×4 to ×16) when compared to ciprofloxacin: clinafloxacin > gatifloxacin > levofloxacin > trovafloxacin > gemifloxacin = moxifloxacin. They should be the first line drugs in the treatment of acinetobacter endophthalmitis (before ciprofloxacin) because of their good biodisponibility and intra ocular penetration. Other antibiotics: trimethoprim-sulfamethoxazole are effective against most strains whereas chloramphenicol, tetracycline, macrolides have little and/or no activity against Acinetobacter. Acinetobacter baumannii remains susceptible to antiseptics or disinfectants.
REFERENCES Gopal L, Ramaswamy AA, Madhavan HN, et al: Endophthalmitis caused by Acinetobacter calcoaceticus. A profi le. Indian J Ophthalmol 51:335– 340, 2003. Heinemann B, Wisplinghoff H, Edmond M, et al: Comparative activities of ciprofloxacin, clinafloxacin, gatifloxacin, gemifloxacin, levofloxacin, moxifloxacin, and trovafloxacin against epidemiologically defi ned Acinetobacter baumannii strains. Antimicrob Agents Chemother 44:2211– 2213, 2000. Jain R, Danziger LH: Multidrug-resistant Acinetobacter infections: an emerging challenge to clinicians. Ann Pharmacother 38:1449–1459, 2004. Kämpfer P, Tjernberg I, Ursing J: Numerical classification and identification of Acinetobacter genomic species. J Appl Bacteriol 75:259–268, 1993. Kau HC, Tsai CC, Kao SC, et al: Corneal ulcer of the side port after phacoemulsification induced by Acinetobacter baumannii. J Cataract Refract Surg 28:895–897, 2002. Kirwan JF, Potamitis T, el-Kasaby H, et al: Microbial keratitis in intensive care. BMJ 314:433–434, 1997. Rudolph T, Welinder-Olsson C, Lind-Brandberg L, et al: 16S rDNA PCR analysis of infectious keratitis: a case series. Acta Ophthalmol Scand 82:463–467, 2004. Van Gelder RN: Applications of the polymerase chain reaction to diagnosis of ophthalmic disease. Surv Ophthalmol 46:248–258, 2001. Van Looveren M, Goossens H: Antimicrobial resistance of Acinetobacter spp. in Europe. Clin Microbiol Infect 10:684–704, 2004.
2 ACQUIRED AND CONGENITAL SYPHILIS 095.8 Ismail A. Shalaby, MD, PhD Baltimore, Maryland Syphilis is a chronic systemic infection caused by the spirochete Treponema pallidum, for which humans are the only natural host. It has been known as a cause of ophthalmic disease for more than 100 years. Infections occurring through passage of the organism from an infected mother across the placenta to her fetus defi ne congenital syphilis. Acquired syphilis is usually transmitted sexually. Although congenital and acquired syphilis are caused by the same organism and are treated in a qualitatively similar fashion, their clinical course and physical fi ndings are sufficiently different to warrant separate discussions.
Acquired syphilis
ETIOLOGY/INCIDENCE Specificity in ophthalmology ●
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Active antibiotics commercially available topically: polymyxin B, tobramycin, ciprofloxacin, levofloxacin*, moxifloxacin* (* in certain countries). Active antibiotic that can be prepared for topical use (fortified antibiotic): ceftazidime. Active antibiotic for intravitreous injection (endophthalmitis): ceftazidime. Severe corneal abscess may require fortified antibiotics (ceftazidime), surgical scraping (see Chapter 186). Endophthalmitis is an actual emergency and often require repeated intra vitreous injections, and often a vitrectomy (see Chapter 257 and Chapter 258).
Acquired syphilis is a systemic disease that is caused by T. pallidum and that is usually transmitted through sexual contact, including vaginal, orogenital and anorectal intercourse. There have been rare cases of acquired syphilis occurring through nonsexual personal contact or from blood transfusion. Patients are most contagious during untreated primary and secondary syphilis, although patients with early latent syphilis can sometimes transmit disease. Infection does not confer immunity. The number of new cases in syphilis in the United States declined after the introduction of penicillin. A dramatic rise in the number of new cases of syphilis among homosexual men
COURSE/PROGNOSIS Primary syphilis T. pallidum penetrates intact mucous membranes at the site of sexual contact and causes an ulcerated papular lesion known as a chancre in 10 to 90 days (mean, 21 days), depending on the size of the inoculation. Multiple chancres are common, particularly in HIV-infected patients. Regional nontender lymphadenopathy appears within 1 week of onset of the chancre but is absent in chancres involving the anus, lower vulva and cervix, which drain to deep lymph nodes. Most chancres heal without scarring in 4 to 6 weeks, but lymphadenopathy may persist for months.
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inflammatory lesions of the cardiovascular system (aortitis, aortic regurgitation, and saccular aneurysms) in about 10% of patients, and gummas (gummata), which are rubbery, granulomatous, nodular lesions that can involve the skin, skeletal system, mouth, respiratory tract, liver, stomach and CNS. Gummas of the skin are often painless and indolent and may heal spontaneously with scarring. Gummas of the skeletal system frequently involve the long bones of the legs and often present with focal pain and tenderness.
Neurosyphilis Five patterns of syphilitic infection of the CNS are as follows: 1. Asymptomatic neurosyphilis: abnormal CSF fi ndings only; frequently progresses to clinical neurosyphilis. 2. Acute meningitis: cranial nerves 7 and 8 most commonly involved. 3. Meningovasculitis: classic picture of meningovascular syphilis is a relatively young adult who presents with a stroke syndrome that was preceded by subacute symptoms of meningitis and encephalitis. 4. Parenchymatous neurosyphilis: tabes dorsalis and generalized paresis. Tabes dorsalis symptoms include ataxia, paresthesia, wide-based gait and foot drop, deep pain, impotence, bladder disturbance, Charcot’s joints, and optic nerve atrophy. General paresis presents with widespread symptoms according to the mnemonic paresis (personality, affect, reflexes [hyperactive], eye [Argyll Robertson pupils], sensorium [illusions and delusions], intellect [dementia, orientation, and so on] and speech). 5. Gummatous neurosyphilis.
CHAPTER 2 • Acquired and Congenital Syphilis
occurred in the 1970s. Between 1981 and 1990, the incidence of primary and secondary syphilis increased from 13.7 to 20.3 per 100,000 persons. This increase, which primarily involved urban minorities, was attributed to various factors, including illegal drug use, trading sex for drugs, concurrent human immunodeficiency virus (HIV) infection, and decreased access to healthcare. Although by 2001 the national rate had fallen to 2.2 cases per 100,000, there was yet another rate increase in 2002 reaching 2.4 cases per 100,000. This increase occurred only in men, and in particularly among men who have sex with men (MSM). It is reported that a substantial number of MSM with syphilis report meeting anonymous partners in venues such as bathhouses and Internet chat rooms. Syphilitic uveitis, the most common ocular manifestation of syphilis, occurs in about 5% of patients with syphilis and accounts for about 1% to 2% of all cases of uveitis.
Secondary syphilis This stage of infection is characterized by localized or diffuse mucocutaneous lesions and generalized nontender lymphadenopathy. A primary chancre may persist in 15% to 25% of patients. The frequently pruritic skin rash consists of macular, papular, papulosquamous, and occasionally pustular lesions or a combination of all patterns. Condylomata lata (broad, moist, pink or gray-white vegetations resulting from enlargement and erosion of papular lesions in moist intertriginous areas) are seen in 10% of patients and are highly infectious. Superficial painless mucosal erosions called mucous patches occur in as many as 15% of patients and involve the lips, oral mucosa, tongue, palate, vulva, vagina, and glans penis. Flu-like symptoms such as malaise, weight loss, anorexia, sore throat, headache, and fever occur in 50% of patients. Patchy, nonscarring alopecia may be present. Uveitis and the many other ocular manifestations usually occur in this stage (see later).
Latent syphilis Latent syphilis is marked by immunity, the absence of clinical signs of infection, and an increased incidence of false-negative nontreponemal tests. One third of patients with untreated latent disease develop tertiary syphilis, usually 2 to 20 years after primary infection but much sooner in HIV-infected patients.
Tertiary (late) syphilis Tertiary syphilis is the end result of a slowly progressive inflammatory disease that begins early after the T. pallidum infection. Manifestations include: ● central nervous system (CNS) infection in about 8% of patients (see Neurosyphilis),
DIAGNOSIS Ocular manifestations Ophthalmic signs and symptoms can be present at any stage of syphilis and can involve any ocular structure. Eye disease is most frequently found in secondary syphilis and with CNS infection.
Primary syphilis Chancres can present, albeit rarely, on the conjunctiva or eyelid.
Secondary syphilis Iridocyclitis (usually granulomatous) is the most common finding. Other manifestations include papulosquamous eyelid rash, alopecia of the eyebrows and eyelashes, dacryocystitis, dacryoadenitis, conjunctivitis, episcleritis, scleritis, iris papules, lens dislocation, interstitial keratitis, intermediate uveitis, posterior uveitis, panuveitis, cystoid macular edema, retinitis (including retinal necrosis), pseudoretinitis pigmentosa, retinal periphlebitis, placoid posterior chorioretinitis, neuroretinitis, choroiditis and choroidal neovascular membrane. Optic nerve involvement includes optic neuritis, optic perineuritis, papilledema and papillitis. HIV-infected patients have more severe and more bilateral disease. In one study, more than half of the patients had ocular complaints as the initial manifestation of syphilis, usually with concurrent maculopapular rash.
Late syphilis Manifestations include the presence of gummas on the optic nerve, retina, extraocular muscles, sclera and iris. Ptosis,
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extraocular muscle weakness or palsy, pupillary abnormalities (Argyll Robertson pupils), optic nerve atrophy, retinal pigment hypertrophy and posterior pole/macular scars are other signs of late syphilis. Unexplained visual field defects may also be due to a late-stage syphilitic infection.
Neurosyphilis SECTION 1 • Infectious Diseases
Early CNS infections can present with iritis, iridocyclitis and other forms of uveitis. Late CNS disease causes pupillary abnormalities or optic atrophy. Ocular syphilis is more closely associated with cerebrospinal fluid (CSF) and neurologic abnormalities in HIV-positive than in HIV-negative patients. Acute syphilitic meningitis has occurred as early as 4 months after initial infection in HIV-infected patients.
Neurosyphilis Laboratory diagnosis and confirmation include a reactive serologic test plus a reactive VDRL in the CSF. However, neurosyphilis can be diagnosed if there is a positive serologic test with a negative VDRL, as long as there is elevated CSF protein or leukocyte count plus clinical signs or symptoms consistent with neurosyphilis in the absence of any other known cause for these abnormalities. Positive CSF serology and pleocytosis are found much more commonly in HIV-infected patients who have ocular syphilis than in HIV-negative patients who do not have ocular syphilis.
Differential diagnosis ● ●
Latent syphilis This is defined as seroreactivity without other evidence of disease. Early latent syphilis is diagnosed in patients infected within the previous year by either a documented seroconversion, unequivacol symptoms of primary or secondary syphilis, or having had a sex partner documented to have primary, secondary or early latent syphilis.
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Uveitis: sarcoidosis. Necrotizing retinitis: herpetic retinitis, cytomegalovirus retinitis. False-positive serologic tests for syphilis: other spirochetal infections (e.g. Lyme disease), malaria, leptospirosis, leprosy, measles, tuberculosis, chronic liver disease, connective tissue disease and blood transfusions.
TREATMENT Laboratory findings Nontreponemal tests (Venereal Disease Research Laboratory [VDRL] and rapid plasma reagin [RPR]) are used to quantify antibodies against cardiolipin, and the titer may be used to assess the response to treatment. The titer is not proportional to the severity of disease; extremely high titers in HIV-infected patients may result from polyclonal B cell stimulation. Treponemal tests (fluorescent treponemal antibody absorption [FTA-ABS] and microhemagglutination-Treponema pallidum [MHA-TP]) are more specific but less quantifiable and the test remains positive after treatment. False-positive results can occur with either test; a weakly positive FTA-ABS often is a false positive. Because all positive nontreponemal tests require confirmation with a treponemal test and because 38% of patients with ocular syphilis had a negative VDRL in one study, it is recommended by many clinicians that both tests be ordered. All patients with syphilis should be tested for HIV infection.
Parenteral penicillin is the preferred treatment for all stages of syphilis. The route, dosage, and length of treatment depend on the stage of the infection. Treatment of HIV-infected patients is discussed separately. Below are the United States Center for Disease Control recommendations. For pregnant women and neonates, see Congenital syphilis.
Primary and secondary syphilis ●
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Late latent syphilis, tertiary syphilis and syphilis of unknown duration ●
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Primary syphilis Laboratory tests are negative for 1 to 2 weeks after infection, so diagnosis requires confirmation of treponemes in lesions by dark-field microscopy. Treponemal tests become positive earlier than nontreponemal tests.
Penicillin G benzathine at 2.4 million units IM in a single dose. For penicillin-allergic (non pregnant) patients, doxycycline 100 mg PO b.i.d. or tetracycline 500 mg PO q.i.d. for 14 days.
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Penicillin G benzathine at 2.4 million units IM weekly for 3 weeks. For Penicillin-allergic (non pregnant) patients are treated with doxycycline 100 mg PO b.i.d. or tetracycline 500 mg PO q.i.d. for 14 days for early latent and 28 days for late latent infection; data regarding the efficacy of non penicillin regimens are scarce. Treatment of latent syphilis is intended to prevent occurrence or progression of late complications.
Secondary syphilis Both treponemal and nontreponemal tests are positive in nearly all cases.
Neurosyphilis and syphilitic eye disease ●
Latent syphilis Nontreponemal tests become negative in 99% of treated patients and 30% of untreated patients. Treponemal tests remain positive in 98% of treated and untreated patients. All patients who may have had syphilis for longer than 1 year should undergo lumbar puncture to look for evidence of neurosyphilis.
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Aqueous crystalline penicillin G 3.0 to 4.0 million units IV every 4 hours is administered for 10–14 days (total of 18–24 million units per day) (penicillin G benzathine does not achieve treponemicidal levels in the CSF). Penicillin-allergic (nonpregnant) patients are treated with doxycycline 100 mg PO b.i.d. or tetracycline 500 mg PO q.i.d. for 2 weeks for early latent and 4 weeks for late latent infection; data regarding the efficacy of nonpenicillin regimens are scarce.
Tertiary syphilis
Ocular disease
Laboratory tests are similar to those in latent syphilis. Organisms are rarely identified in gummas.
The ideal systemic regimen for ocular syphilis is not known. Many investigators recommend that all intraocular disease be
treated as neurosyphilis, even if the CSF examination is normal. Topical corticosteroids (e.g. prednisolone acetate 1%) and cycloplegic agents should be used to relieve the symptoms of anterior uveitis and other anterior segment inflammations. The dose and frequency of corticosteroid drops should be titrated according to the extent of the inflammation and then tapered carefully to avoid recurrence.
in 2002. This parallels the decline in incidence of acquired infection in women.
COURSE/PROGNOSIS Systemic findings ●
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Early syphilis can be treated as in HIV-negative patients. Because of reports of treatment failure in HIV-infected patients, some investigators recommend that all HIVinfected patients be treated with a regimen appropriate for neurosyphilis, regardless of the clinical stage of syphilis (aqueous penicillin G 4.0 million units IV every 4 hours for 10 days, followed by penicillin G benzathine 2.4 million units IM weekly for 3 weeks). Quantitative nontreponemal tests should be repeated at 1, 2, and 3 months after treatment and then every 3 months thereafter, until a satisfactory serologic response occurs.
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Ophthalmic findings ●
Complications The Jarisch–Herxheimer reaction is an acute self-limited systemic febrile reaction accompanied by headache, myalgia, tachycardia, hyperventilation, and mild hypotension that occurs within 1 to 2 hours and lasts 12 to 24 hours after any effective therapy for syphilis. It can occur in any stage of syphilis (10% to 25%) but is particularly common in secondary syphilis (70% to 90%). It may also induce early labor or cause fetal distress in pregnant women. This should not prevent or delay therapy; patients should be warned of this reaction before treatment. The Jarisch–Herxheimer reaction is self-limited and can be symptomatically treated with aspirin every 4 hours for 24 to 48 hours. Treatment with prednisone is warranted in cardiovascular syphilis and neurosyphilis because the reaction may be catastrophic in these patients.
Other antibiotic therapy There have been reports about the possible efficacy of ceftriaxone, and azithromycin in infectious syphilis. The human clinical studies on ceftriaxone have been limited, and the initial positive reports with azithromycin have been followed by several reports on treatment failures. Therefore, neither therapy is generally recommended at this time.
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DIAGNOSIS Laboratory findings ●
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Congenital syphilis
ETIOLOGY/INCIDENCE The transmission of T. pallidum from an untreated or inadequately treated mother to her fetus may occur at any stage of pregnancy and is especially common in untreated primary or secondary syphilis. The lesions of congenital syphilis may become apparent anytime after the first trimester up to early adolescence. Congenital syphilis causes fetal or perinatal death in 10% to 40% of the infants affected. The number of reported cases of congenital syphilis in the US rose between 1984 to 1991, reaching a peak of 100 cases per 100,000 live born infants. This increase paralleled the rise of primary and secondary syphilis, which were usually associated with the practice of trading sex for drugs. Fortunately, there has been a steady overall decline of incidence since then reaching a nadir of 11.2 cases per 100,000 live born infants
Bilateral interstitial keratitis is the classic and most common finding (10% of patients), occurring in persons 5 to 20 years of age. There is associated anterior uveitis, which is followed by endothelial edema leading to a generalized corneal edema. The cornea is then invaded by superficial and deep blood vessels from the periphery that appear to push a faint opacity in front of them. The blood vessels can form to meet a ‘salmon patch’ and the inflammation then subsides, leaving clear branching ‘ghost vessels’ around a translucent scar anterior to Descemet’s membrane. Chorioretinitis appearing as a bilateral salt-and-pepper granularity of the fundus. Pseudoretinitis pigmentosa. Secondary glaucoma may develop due to chamber angle damage from the initial anterior segment inflammation.
CHAPTER 2 • Acquired and Congenital Syphilis
HIV-infected patients
Infants: hepatosplenomegaly, generalized vesicular or bullous skin rash, condylomata lata, rhinitis (snuffles), jaundice (syphilitic hepatitis), osteochondritis and bone fractures, pseudoparalysis and edema secondary to nephrotic syndrome. Older children: anterior bowing of the shins, frontal bossing, Clutton’s joints, mulberry molars, saddle nose, rhagades and cardiovascular disease; widely spaced, peg-shaped teeth, eighth cranial nerve deafness and interstitial keratitis constitute Hutchinson’s triad. Meningovascular syphilis with nerve deafness (secondary to eighth cranial nerve involvement) is more common than other forms of neurosyphilis.
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Confi rmed congenital syphilis is defined by the Centers for Disease Control and Prevention as that occurring in an infant in whom T. pallidum is identified by dark-field microscopy. Presumptive congenital syphilis is defined as that occurring in an infant whose infected mother went untreated or was inadequately treated during pregnancy or an infant or a child who has a reactive treponemal test for syphilis plus (1) any evidence of congenital syphilis on physical examination, (2) evidence of congenital syphilis on long-bone radiographs, (3) a reactive CSF VDRL, (4) elevated CSF cell or protein count without other cause, (5) quantitative nontreponemal serologic titer 4-fold higher than the mother’s titer (with both drawn at birth), or (6) reactive test for FTAABS-19S-IgM antibody. Serologic tests in both infants and mothers may be negative if the syphilis was acquired near the end of the pregnancy. Maternally acquired antibodies will decrease during the first year of life.
Differential diagnosis ●
Other congenital infections (cytomegalovirus, rubella, toxoplasmosis), acquired syphilis (in cases of sexual abuse).
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TREATMENT Pregnant mothers
SECTION 1 • Infectious Diseases
Regardless of the state of pregnancy, women should be treated with penicillin according to the dosage and schedules appropriate for the stage of acquired syphilis recommended for nonpregnant individuals. Penicillin-allergic patients (positive for skin reaction tests) should undergo desensitization. Tetracycline is not recommended for pregnant women because of the potential for adverse effects to the fetus. Erythromycin is discouraged except for individuals who have been proved to be allergic to penicillin who are not candidates for desensitization.
Neonates (younger than 4 weeks) Aqueous crystalline penicillin G is preferred with the dosage based on chronologic rather than gestational age. The recommended dosage is 50,000 units/kg IV every 12 hours for the first week and then every 8 hours to complete a 10- to 14-day course. Some recommend procaine penicillin G at 50,000 units/kg IM daily for 10 days, but adequate CSF concentrations may not be achieved with this regimen. If more than 1 day of therapy is missed, the entire course should be restarted.
Infants Because of the difficulty of establishing a diagnosis of neurosyphilis in infants older than 4 weeks, it is recommended that aqueous crystalline penicillin G be given at a dose of 50,000 units/kg IV every 6 hours over a 10- to 14-day period. This is the same treatment as for neurosyphilis. For asymptomatic infants whose mothers were adequately treated during pregnancy, treatment is not necessary if follow-up can be ensured. For asymptomatic neonates with adequately treated mothers whose follow-up cannot be ensured, many recommend treatment with benzathine penicillin G 50,000 units/kg IM in a single dose (although efficacy data are lacking).
Older children Lumbar puncture should be performed to rule out neurosyphilis. If the CSF is abnormal, then the recommendation is to treat like neurosyphilis (i.e. aqueous crystalline penicillin G 50,000 units/kg IV every 6 hours for 10 to 14 days). The same treatment is given for children older than 1 year who have late or previously untreated congenital syphilis. If the CSF is normal, the CSF VDRL is negative, and there is minimal clinical manifestation of disease, some treat with only three doses of benzathine penicillin G 50,000 units/kg IM.
Ocular Topical corticosteroids and cycloplegics can relieve the symptoms of anterior uveitis and interstitial keratitis. Subconjunctival corticosteroids have been administered to relieve recalcitrant anterior segment inflammation. Severe corneal opacification may require keratoplasty. Greater postoperative inflammation and graft rejection may result after such surgery even in an old interstitial keratitis, requiring a more frequent or stronger antiinflammatory corticosteroid regimen.
Follow-up The American Academy of Pediatrics recommends that followup for all infants be incorporated into routine newborn care at 1, 2, 4, 6, and 12 months. Serologic tests should be performed until the patients become nonreactive. Patients with persistent, stable, low titers should be considered for retreatment. Treated
6
infants should be similarly followed, with a CSF examination at 6-month intervals until the patient becomes nonreactive. A reactive CSF VDRL test at 6 months is an indication for retreatment. All patients with neurosyphilis must be carefully monitored with periodic serologic testing, clinical evaluation at 6-month intervals, and repeat CSF examinations for at least 3 years. A thorough developmental evaluation should be done at age 2 on all children treated in infancy who are symptomatic at birth or had active congenital infection.
PREVENTION The ultimate cure for congenital syphilis is its prevention. Comprehensive prenatal care starting early in pregnancy is essential to detect any infection in the pregnant mother and institute adequate treatment. Sexually transmitted disease programs and drug addiction programs institute prenatal outreach programs to identify and reach the at-risk individuals. Partners of infected women (or men) should be identified and contacted to reach an even greater at-risk population.
REFERENCES Aldave AJ, King JA, Cunningham ET, Jr: Ocular syphilis. Curr Opin Ophthalmol 12:433–441, 2001. Centers for Disease Control and Prevention: Congenital syphilis–United States, 2002. MMWR 53:716–719, 2004. Centers for Disease Control and Prevention: Guidelines for the treatment of sexually transmitted diseases 2002. MMWR 51:1–78, 2002. Centers for Disease Control and Prevention: Primary and secondary syphilis–United States, 2002: MMWR 52:1117–1120–1497, 2003. Chen JC: Brief report: azithromycin treatment failures in syphilis infections–San Francisco, California, 2002–2003. Ann Emerg Med 44:232– 233, 2004. Golden MR, Marra CM, Holmes KK: Update on syphilis. Resurgence of an old problem. JAMA 290:1510–1514, 2003. Lynn WA, Lightman S: Syphilis and HIV: a dangerous combination. Lancet Infectious Diseases 4:456–466, 2004. Shalaby IA, Dunn JP, Semba RD, Jabs DA: Syphilitic uveitis in human immunodeficiency virus-infected patients. Arch Ophthalmol 115:469– 473, 1997. Sung L, MacDonald NE: Syphilis: a pediatric perspective. Pediatr Rev 19:17–22, 1997. Zeltser R, Kurban AK: Syphilis. Clin Dermatol 22:461–468, 2004.
3 ACQUIRED IMMUNE DEFICIENCY SYNDROME (AIDS) 090.9 Cristina Muccioli, MD, MBA São Paulo, Brazil Rubens Belfort, Jr., MD, PhD, MBA São Paulo, Brazil
DEFINITION/ETIOLOGY The acquired immune deficiency syndrome (AIDS) was first recognized in USA in 1981 as a newly infectious disease that became a global pandemic with the most devastating morbidity rate. The causative agent, known as human immunodeficiency virus (HIV) was fi rst identified in 1983 and serologic tests for HIV antibodies were available in 1985.
HIV is a member of the lentivirus family. There are two types of HIV: Type 1 (worldwide) and Type 2 (west Africa). HIV is a human retrovirus with RNA genome with reverse transcriptase enzyme. Three routes of human transmission of HIV have been described: sexual, blood-borne and mother-infant.
HIV has the ability to cause an insidious and progressive deterioration of the host’s immune function, leading to profound immunossupression. Central to the immunopathogenesis of the HIV is its interaction with the CD4 molecule in the helper/ inducer subset of T-lymphocytes. As CD4 T-lymphocytes play a key role in the induction of most immunologic responses, HIV-induced damage of the CD4 T lymphocyte population results in the abolition of a wide range of immune functions, ultimately leading to extreme immunosupression manifested by opportunistic infections and neoplasms pathognomonic for AIDS.
EPIDEMIOLOGY The AIDS pandemic enters its 24th year and the total number of people living with the human immunodeficiency virus (HIV) rose in 2004 to reach its highest level ever: an estimated 39.4 million (35.9 million–44.3 million) people are living with the virus. From this total, 4.9 million (4.3 million–6.4 million) people acquired HIV in 2004. The global AIDS epidemic killed 3.1 million (2.8 million–3.5 million) people in the past year. The number of people living with HIV has been rising in every region, compared with two years ago, with the steepest increases occurring in East Asia, and in Eastern Europe and Central Asia. The number of people living with HIV in East Asia rose by almost 50% between 2002 and 2004, an increase that is attributable largely to China’s swiftly growing epidemic. In Eastern Europe and Central Asia, there were 40% more people living with HIV in 2004 than in 2002. Accounting for much of that trend is Ukraine’s resurgent epidemic and the ever-growing number of people living with HIV in the Russian Federation. Sub-Saharan Africa remains by far the worst-affected region, with 25.4 million (23.4 million–28.4 million) people living with HIV at the end of 2004, compared to 24.4 million (22.5 million–27.3 million) in 2002. Just under two thirds (64%) of all people living with HIV are in sub-Saharan Africa, as are more than three quarters (76%) of all women living with HIV. The epidemics in sub-Saharan Africa appear to be stabilizing generally, with HIV prevalence at around 7.4% for the entire region. But such a summary perspective hides important aspects. First, roughly stable HIV prevalence means more or less equal numbers of people are being newly infected with HIV and are dying of AIDS. Beneath the apparent constancy of steady prevalence levels lie devastating realities-especially in southern Africa, which accounts for one third of all AIDS deaths globally. Second, the epidemics in Africa are diverse, both in terms of their scale and the pace at which they are evolving. There is no single ‘African’ epidemic. Some urban parts of East Africa display modest declines in HIV prevalence among pregnant women, while in West and Central Africa prevalence levels have stayed roughly steady at lower levels
DIAGNOSIS HIV-infected individuals whose CD4 T lymphocyte count is less than 200 cells/mL is classified as having AIDS. The presence of one of the specified indicator diseases (e.g. cytomegalovirus diseases, encephalopathy, candidiasis, etc.) is also diagnostic of AIDS, regardless of the CD4 T-lymphocyte count.
Clinical signs and symptoms An infectious mononucleosis-like syndrome (recognized as acute retroviral syndrome), develop in more than 50% of HIVinfected persons. This is observed 3 to 6 weeks after exposure and resolves spontaneously.
Laboratory findings Detectable antibody to HIV develops in the overwhelming majority of infected individuals within 6 months of exposure. The enzyme-linked immunosorbent assay (ELISA) is used for screening. Western blot, immunofluorescent antibody studies, p24 antigens determinations, qualitative DNA PCR studies, viral cultures and other techniques are used to evaluate suspected false-positive and false-negative test results.
CHAPTER 3 • Acquired Immune Deficiency Syndrome (AIDS)
COURSE/PROGNOSIS
than in the rest of sub-Saharan Africa. National HIV data, though, hide much higher levels of infection in parts of countries, as Nigeria illustrates. Southern Africa, unfortunately, offers only slight hints of possible future declines in HIV prevalence. The AIDS epidemic is affecting women and girls in increasing numbers. Globally, just under half of all people living with HIV are female. Women and girls make up almost 57% of all people infected with HIV in sub-Saharan Africa, where a striking 76% of young people (aged 15–24 years) living with HIV are female. In most other regions, women and girls represent an increasing proportion of people living with HIV, compared with five years ago.
Ophthalmologic disorders Until potent antiretroviral therapy (ART) became available, the most common retinal manifestation of immunodeficiency in advanced AIDS was CMV retinitis. Retinitis is the most common manifestation of CMV disease in adult individuals with AIDS. Before the era of potent antiretroviral therapy (ART), 16.5% to 34% of HIV-infected individuals eventually had reactivation of latent infection and development of clinically apparent CMV end-organ disease. Epidemiologic data regarding AIDS and CMV retinitis changed dramatically following the introduction of potent antiretroviral drugs (ARV) in the late 1990s. Several classes of antiretroviral drugs are currently available, including nucleoside reverse-transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, and protease inhibitors; the latter target viral proteases involved in the assembly of new viral particles rather than the viral genome. Any combination of three or more antiretroviral drugs, or a combination containing one protease inhibitor and one non-nucleoside reverse transcriptase inhibitor, are considered ART. The use of ART has been associated with reduced HIV replication and an increase in CD4+ T-lymphocyte counts, as well as a marked increase in survival. A reduced incidence of opportunistic infections, and a drop in newly diagnosed cases of CMV retinitis by 55% to more than 90%, were also observed.
7
SECTION 1 • Infectious Diseases
Most improvements in immune function seem to occur during the first year following initiation of ART and long-term immune reconstitution may not be complete. Moreover, community-based studies reveal that only a low proportion of patients actually end up with undetectable HIV blood levels after 14 months of HAART and that virological failure (manifested as recurrence of elevated HIV blood levels) may occur in up to 44% of patients treated with protease inhibitor within the first 6 months following initiation of therapy. Despite advances in immune reconstitution from ART, CMV retinitis remains the leading cause of blindness among patients with AIDS. Vision loss is common in patients with AIDS and CMV retinitis and may result from the agressiveness of the retinitis itself or from the retinal detachment. The rate of retinal detachment in patients with CMV retinitis may vary from 15 to 29%, according to the literature. The diagnosis of CMV retinitis is based on the clinical appearence of the retinal lesions. Typically, in the AIDS patients not receiving ART, the disease appears as a yellow to white area of retinal necrosis with hemorrhage and edema that follows a vascular distribution. The retinitis is necrotizing, with white-yellowish areas, hemorrhage to variable degrees and vasculitis. Anterior chamber and vitreous inflammation is usually mild without formation of posterior synechiae. Retinitis may be unilateral or bilateral, but cases presenting with unilateral disease have a high risk of second eye involvement, probably due to hematogenic dissemination. Spontaneous remission was extremely rare before ART. Three patterns of CMV retinitis are described: classical or hemorrhagic, granular and frosted branch angiitis. The first, classical, pattern of CMV retinitis, called hemorrhagic, is characterized by retinal areas with a granular, whitish and hemorrhagic aspect, usually with lesions close to the vascular arcades or to the optic nerve, and subretinal exudation. The retinal vessels in the necrotic area may be sheathed by vasculitis and consequently present retinal vascular, specially venous, occlusions. Central healing of the lesions occurs after necrosis, leading to atrophy of the retina and choroid. The second pattern of retinitis is the granular or atypical. The retina shows granular focal infi ltrates which increases linearly and slowly, leaving areas of retinal destruction with an atrophic retinal pigmentary epithelium allowing observation of details of the choroid. Retinal hemorrhages and vitreous cells usually are absent in this retinitis pattern. The third pattern, more rarely observed, associated or not with the classical, hemorrhagic form is characterized by severe vasculitis, with intense sheathing shown by arteries and veins, resembling frosted branch angiitis. Symptoms of CMV retinitis are often poor and may include floaters, light flashes, loss of central or peripheral visual field, and blurred vision. Asymptomatic retinitis can be detected by ophthalmologic screening of HIV-infected persons at high risk. Because of the unspecific and poor visual symptoms, patients with HIV infection should be educated about the symptoms of CMV retinitis and advised to seek care in a timely manner after the onset of visual symptoms. Many experts recommend that patients at high risk should have ophthalmologic screening every 3 to 6 months depending on the CD4 count levels. In general, ophthalmologic examinations should be performed immediately before therapy is initiated, at the end of the induction (or reinduction) therapy, and monthly thereafter.
8
The recent availability of several new modalities of therapy for CMV retinitis provides a number of appropriate treatment options. Since 1989, with the release of ganciclovir for endovenous use, the natural history of the disease changed. Foscarnet, in 1991, was approved for endovenous use and more recently, in 1996, another antiviral, cidofovir, was approved. All are virostatic and, when applied endovenously, cause important side effects: neutropenia for ganciclovir and renal toxicity for foscarnet and cidofovir. Before the ART era, treatment with any of the drugs had to be given initially as an induction (twice a day) dose for 2 to 3 weeks and then, a maintenance (once a day) dose for the rest of the life of the patient, leading to a significant worsening in the quality of life. Ganciclovir has poor oral bioavailability and oral ganciclovir, 3000 mg/day, is less effective than the IV form as a maintenance regimen but higher doses (4500 or 6000 mg/day) are approximately as effective as IV therapy. A new drug named Valcyte (valganciclovir) that is a prodrug of ganciclovir was developed for the treatment of cytomegalovirus (CMV) retinitis in patients with AIDS. Oral valganciclovir 900 mg provides a daily exposure of ganciclovir comparable to that of intravenous ganciclovir 5 mg/kg. The most common adverse events related to valgancyclovir is neutropenia. Local therapies (intraocular injections and intraocular implants) are efficient in CMV retinitis treatment. Indications include patients which are not able to receive intravenous therapy and as supplement in patients whose retinal disease is not completely controlled using maximum tolerated systemic medication. Maybe the best use for local therapy is in association with oral antivirals forms. Intraocular injections of ganciclovir or foscarnet, weekly or twice-weekly through a small-gauge needle have appeared to slow the progression of retinitis in uncontrolled case series conducted primarily in patients who cannot tolerate systemic therapy or in whom retinitis had progressed despite attempts at systemic therapy. The intravitreal ganciclovir implant is a pellet of ganciclovir to be implanted into the vitreous cavity without systemic absorption, drug interactions or side effects. This way for delivering drug into the eye could be more effective to better control of the retinitis. The majority of adverse events are retinal detachments; major intravitreous bleeding and rarely endophthalmitis. The recent availability of ART are changing the incidence, clinical presentation, and course of CMV disease, at least temporarily. The effectiveness of ART should not lull the medical community into the perception that CMV end-organ disease will disappear. Although the incidence of CMV retinitis are decreasing, patients may develop CMV disease prior to initiating antiretroviral therapy or before its full benefit is achieved (Figure 3.1.).
Differential diagnosis Acute retinal necrosis Acute retinal necrosis (ARN) syndrome represents a specific pattern of clinical presentations for certain herpes virus infections in the posterior segment of the eye. These include varicella zoster virus and herpes simplex virus 2. Patients with ARN usually complain of mild to moderate ocular or periorbital pain, foreign body sensation and red eye. Visual symptoms usually include hazy vision, floaters, and, rarely, decreased peripheral vision. Granulomatous keratic precipitates, cells, and
FIGURE 3.3 Progressive outer retinal necrosis.
CHAPTER 3 • Acquired Immune Deficiency Syndrome (AIDS)
FIGURE 3.1 CMV retinitis (hemorrhagic pattern).
FIGURE 3.4 Toxoplasmic lesion in AIDS. FIGURE 3.2 Acute retinal necrosis in AIDS.
flare in the anterior chamber as well as elevated intraocular pressure and an increasing number of vitreous cells are observed. The initial retinitis consists of the round or oval deep, yellowwhite lesions at the level of the retinal pigment epithelium or deep retina in the postequitorial fundus, typically sparing the macula area. The retinitis may remain limited to less than one quadrant of involvement, may involve multiple peripheral quadrants of the retina, or may become confluent in the periphery. Vitritis increases, sometimes limiting visualization of the fundus in severe cases. An exsudative retinal detachment occasionally develops in the inferior periphery. Medical treatment of choice is IV aciclovir. Retinal detachment is the most common cause of vision loss in patients with ARN, occurring in 24 to 80% of the cases. If retinal detachment is present, vitrectomy with endolaser, internal drainage of subretinal fluid, air-fluid exchange and silicone oil tamponade are recommended (Figure 3.2.).
Progressive outer retinal necrosis (PORN) syndrome Progressive outer retinal necrosis (PORN) syndrome is a form of the varicella zoster virus (VZV) chorioretinitis found almost exclusively in people with the acquired immunodeficiency syndrome (AIDS). This destructive infection has an extremely
rapid course that may lead to no light perception in affected eyes within days or weeks. Attempts at its treatment have had limited success. Rhegmatogenous retinal detachments often occur after the development of atrophic retinal holes, and silicone oil temponade has been found to be the most successful reattachment procedure (Figure 3.3.).
Ocular toxoplasmosis In HIV-infected patients, toxoplasmosis is the most common cause of non-viral central nervous system infection leading to toxoplasmic encephalitis. Ocular toxoplasmic lesions can be more severe and aggressive than the ones observed in immunocompetent individuals. Ocular toxoplasmosis occurs in 1–2% of patients with AIDS in the US and in 8–10% of AIDS patients in Brazil. Toxoplasmic retinochoroiditis is a serious disorder in HIVinfected patients and in other immunosuppressed individuals such as cancer patients or organ transplant recipients. It is generally more severe than in immunocompetent patients, with a broader range of clinical features. Ocular toxoplasmosis in immunosuppressed patients can be single lesions, multifocal lesions in one or both eyes, and broad areas of retinal necrosis. Although the majority of reported cases in HIV-infected patients have been unilateral, it is not uncommon to see bilateral cases.
9
SECTION 1 • Infectious Diseases
In cases with full-thickness necrosis, the retina appears to have a hard, ‘indurated’ appearance, with sharply demarcated borders. There is usually little retinal hemorrhage within the lesion itself. A prominent inflammatory reaction in the vitreous body and anterior chamber has been described in several reports of HIVassociated ocular toxoplasmosis. Lesions will continue to enlarge without treatment, which probably explains the fact that most reported patients have had extensive areas of retinal necrosis by the time diagnosis is made. In most reported cases of ocular toxoplasmosis in immunosuppressed patients, there have not been pre-existing scars. Infection of the iris with T. gondii has been reported in a patient with AIDS. (Figure 3.4.)
REFERENCES Arruda RF, Muccioli C, Belfort R, Jr: Ophthalmological fi ndings in HIV infected patients in the post-HAART (Highly Active Anti-retroviral Therapy) era, compared to the pre-HAART era. Rev Assoc Med Bras 50(2):148–152, 2004. Epub 2004 Jul 21. Belfort R, Jr: The ophthalmologist and the global impact of the AIDS epidemic. LV Edward Jackson Memorial Lecture. Am J Ophthalmol 129(1):1–8, 2000. Campo RE, Lalanne R, Tanner TJ, et al: Lopinavir/ritonavir maintenance monotherapy after successful viral suppression with standard highly active antiretroviral therapy in HIV-1-infected patients. d’Arminio Monforte A, Sabin CA, Phillips A, et al: The Antiretroviral Therapy Cohort Collaboration. The changing incidence of AIDS events in patients receiving highly active antiretroviral therapy. Arch Intern Med 165(4):416–423, 2005. Jabs DA, Van Natta ML, Thorne JE, et al: Studies of Ocular Complications of AIDS Research Group. Course of cytomegalovirus retinitis in the era of highly active antiretroviral therapy: 2. Second eye involvement and retinal detachment. Ophthalmology 111(12):2232–2239, 2004. Jabs DA, Van Natta ML, Thorne JE, et al: Studies of Ocular Complications of AIDS Research Group. Course of cytomegalovirus retinitis in the era of highly active antiretroviral therapy: 1. Retinitis progression. Ophthalmology 111(12):2224–2231, 2004.
EPIDEMIOLOGY First reported in 1969 in Ghana, AHC, spreading very fast across the continents, became pandemic in Africa, Southeast Asia, and Japan by the 1970s. Since then pandemics of AHC have been reported in 1981, 1986–1988, 1994–1996, and 2002– 2003 from various countries. Though the magnitude of each outbreak could not be assessed properly, the 2003 outbreak in Puerto Rico reported 490,000 persons with conjunctivitis. A few infections (4–20%) may be asymptomatic. AHC, affecting all age groups, causes economic loss due to absenteeism. Outbreaks are reported with mass movement of populations (e.g. refugees, pilgrims, etc.). Overcrowding, low socioeconomic status and poor sanitation, favors the transmission of the disease.
ETIOLOGY AHC is mainly caused by enterovirus-70 and coxsackie A 24 virus, though adenoviruses are also reported to be associated. Evolutionary analysis of EV-70 and CA24v, using the nucleotide sequence, indicates that the two viruses branched off from the prototype strain in 1984 in Taiwan. In 2002–2003 outbreaks of AHC, the virus strains were isolated from China, which on sequencing were identified as novel, unclassified human enteroviruses. Viruses responsible for AHC have been isolated from infected humans only with no animal reservoir being implicated. However, animals may play a role in maintaining the natural cycle during an interepidemic period.
Jabs DA: AIDS and ophthalmology in 2004. Arch Ophthalmol 122(7):1040– 1042, 2004.
DIAGNOSIS
Muccioli C, Belfort R, Jr: Treatment of cytomegalovirus retinitis with an intraocular sustained-release ganciclovir implant. Braz J Med Biol Res 33(7):779–789, 2000.
Clinical signs and symptoms
Nguyen QD, Kempen JH, Bolton SG, et al: Immune recovery uveitis in patients with AIDS and cytomegalovirus retinitis after highly active antiretroviral therapy. Am J Ophthalmol 129(5):634–639, 2000. UNAIDS: 2004 Report on the global AIDS epidemic. Geneva, UNAIDS, 2004. Vrabec TR: Posterior segment manifestations of HIV/AIDS. Surv Ophthalmol 49(2):131–157, 2004.
4 ACUTE HEMORRHAGIC CONJUNCTIVITIS 077.4 (Epidemic Hemorrhagic Conjunctivitis, Apollo 11 Disease) Niteen S. Wairagkar, MD Pune, India Acute hemorrhagic conjunctivitis (AHC), also known as epidemic hemorrhagic conjunctivitis and Apollo 11 disease, is a
10
relatively new disease entity. However, a similar eye disease occurring on ships was reported in 1819.
After a short incubation period of 24 to 48 hours, patients experience an explosive onset of symptoms, like ocular irritation, foreign body sensation, and periorbital pain. Full-blown conjunctivitis involving both eyes develops within hours with lid edema, chemosis, seromucous discharge, photophobia, excessive lacrimation, and subconjunctival hemorrhages in bulbar and palpebral conjunctiva. Pre-auricular lymphadenopathy with variable tenderness is present. Moderate follicular hypertrophy, diffuse epithelial keratitis, a transient low-grade iritis may also be present. Mild corneal ulceration after an episode of AHC has also been reported. Systemic symptoms are rare. In some cases respiratory disturbances accompanied the eye signs. Neurological complications like facial palsy, cranial nerve involvement, lumbosacral radiculomyelitis, and poliolike motor paralysis have been reported after episodes of AHC. In a series of patients (21–55 years) in Taiwan, radicular pains and acute flaccid paralysis developed within 5–37 days after the onset of AHC. Permanent incapacitation due to paralysis and muscular atrophy in the affected proximal muscles of the lower limbs was the main sequela in severe cases. Involvement of the meninges, cranial nerves and the white matter of the cord were observed in a few patients. Mortality due to AHC has not been reported.
TREATMENT Ocular
Wadia NH, Irani PF, Katrak SM: Neurological complications of a new type of conjunctivitis. Lancet 1:350–352, 1973. Wairagkar NS, Gogate SS, Labhsetwar AS: Investigation of an epidemic of acute haemorrhagic conjunctivitis in Pune, India. J Commun Dis 31(1):41–43, 1999.
PREVENTIVE MEASURES AHC is transmitted mainly by infected eye-to-hand-to-eye contact. Fomites, contaminated instruments, public washing facilities and swimming pools may be implicated in transmission. Careful hand washing, sterilization of ophthalmic instruments, avoiding contact with infected patients may prevent the transmission.
COMMENTS AHC is an extremely contagious, symptomatic and highly visible ocular disease that occurs in epidemics. Prolonged visual disability does not occur and patients recover with remarkably few sequelae. Because of the relatively benign course of the disease, over treatment with topical antibiotics and corticosteroids should be avoided.
REFERENCES Asbell PA, de la Pena W, Harms D, et al: Acute hemorrhagic conjunctivitis in central America: fi rst enterovirus epidemic in the western hemisphere. Ann Ophthalmol 17:205–209, 1985. Centers for Disease Control and Prevention (CDC): Acute hemorrhagic conjunctivitis outbreak caused by coxsackievirus A24–Puerto Rico, 2003. Morb Mortal Wkly Rep 53(28):632–634, 2004. Dalapathy S, Lily TK, Madhavan HN: Development and use of nested polymerase chain reaction for identification of adenovirus from conjunctivitis. J Clin Virol 11:77–84, 1998. Dussart P, Cartet G, Huguet P, et al: Outbreak of acute hemorrhagic conjunctivitis in French Guiana and West Indies caused by coxsackievirus A24 variant: phylogenetic analysis reveals Asian import. J Med Virol 75(4):559–565, 2005. Hung TP, Sung SM, Liang HC, et al: Radiculomyelitis following acute haemorrhagic conjunctivitis. Brain 99(4):771–790, 1976. Kew OM, Nottay BK, Hatch MH, et al: Oligonucleotide fi ngerprint analysis of enterovirus 70 isolates from the 1980 to 1981 pandemic of acute hemorrhagic conjunctivitis: evidence for a close genetic relationship among Asian and American strains. Infect Immun 41(2):631–635, 1983. Kono R: Apollo 11 disease or acute hemorrhagic conjunctivitis: a pandemic of a new enterovirus infection of the eyes. Am J Epidem 101(5):383– 390, 1975. Kono R, Miyamura K, Tajiri E, et al: Neurologic complications associated with acute hemorrhagic conjunctivitis virus infection and its serologic confi rmation. J Infect Dis 129(5):590–593, 1974.
5 ASPERGILLOSIS 117.3 Mark D. Sherman, MD Anaheim Hills, California
CHAPTER 5 • Aspergillosis
Topical broad-spectrum antibiotics, such as 10% sulfacetamide eye drops, four times daily, may be used to prevent secondary bacterial infection. Use of topical corticosteroids may predispose an already compromised cornea to develop microbial keratitis and such practice should be discouraged. In the majority of patients, infection is short in duration, self-limiting, and free of significant ocular sequelae.
Park SW, Lee CS, Jang HC, et al: Rapid identification of the coxsackievirus A24 variant by molecular serotyping in an outbreak of acute hemorrhagic conjunctivitis. J Clin Microbiol 43(3):1069–1071, 2005.
Aspergillosis is a generic term indicating infection by a member of the saprophytic fungus Aspergillus. Approximately 21 of the 900 species and subspecies of Aspergillus have been associated with human disease. Aspergillus spp. are commonly isolated from soil, vegetation, grains, airway systems and decaying organic matter. The spectrum of human disease caused by Aspergillus spp. includes allergic reactions, colonization of debilitated tissue without invasion, invasive destruction of specific organs and disseminated disease. Infection most commonly results from inhalation of spores. The respiratory system is the most common site of infection. Disseminated aspergillosis may involve the skin, central nervous system, brain, kidney and bone. Less common manifestations of aspergillosis include otomycosis, corneal ulcers, endophthalmitis and nasoorbital disease.
ETIOLOGY/INCIDENCE Aspergillus fungi can be found in most parts of the world. Aspergillosis is a major cause of fungal infection in both tropical and temperate climates. Infection is more common in individuals where contamination is more likely, such as with grain farmers and breeders of poultry. Orbital involvement is most commonly a result of spread from the paranasal sinuses. Corneal involvement requires direct inoculation such as occurs during ophthalmic surgery or occurs as a complication of contact lens wear or other local insult. Corneal involvement is more likely in individuals with compromised ocular defenses or pre-existing corneal disease. Keratomycosis caused by Aspergillus spp. accounts for almost 50% of all reported cases of oculomycosis. Endogenous Aspergillus endophthalmitis is associated with disseminated Aspergillus. Individuals at greatest risk are those who are intravenous drug abusers, immunosuppressed, or recipients of organ transplants. Aspergillus causes an occlusive vasculitis in the retina and choroid. Hyphae can penetrate the walls of the blood vessels to infect contiguous structures such as the vitreous and sclera.
Lin KH, Takeda N, Miyamura K, et al: The nucleotide sequence of 3c proteinase region of the coxsackievirus A24 variant: comparison of the isolates in Taiwan in 1985–1988. Virus Genes 5:121–131, 1991.
COURSE/PROGNOSIS
Lu YY, Yan JY, Feng Q, et al: A novel enterovirus associated with acute hemorrhagic conjunctivitis. Complete genome data. NCBI-GenBank Accession numbers: AY876913, AY876912. Online. Available at: http:// www.ncbi.nlm.nih.gov, 29 Apr 2005.
The therapy of Aspergillus infections is often complicated by a delay in diagnosis, the previous use of corticosteroids and the long-term use of antifungal medications. Aspergillosis
11
SECTION 1 • Infectious Diseases
requires intensive and aggressive treatment. Orbital aspergillosis has a poor prognosis for maintaining useful vision and a poor prognosis for life. Despite extensive debridement and antifungal treatment, Aspergillus spp. can reappear in previously involved tissues, especially when vascular invasion has occurred. The prognosis for Aspergillus endophthalmitis is similarly poor. Successfully treated Aspergillus keratomycosis may require later penetrating keratoplasty for visual rehabilitation.
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●
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false-positive results could occur if the specimen remains unnecessarily exposed. Gram’s, Giemsa, and GMS stains are better than KOH stains for detecting the branching septated hyphae that are typical of Aspergillus spp. Either Sabouraud’s media (Emmon’s modification) or blood agar will usually be positive within 48 hours. Blood cultures are routinely negative, even in fulminant cases.
Differential diagnosis
DIAGNOSIS
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Clinical signs and symptoms (ocular and periocular)
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Eyelid Lid edema may occur in association with deeper orbital involvement. A local chronic ulcerative granuloma may occur with direct inoculation.
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Conjunctive
●
Chemosis occurs with orbital involvement. Conjunctivitis may occur with Aspergillus canaliculitis.
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Fungal infection: Candida, Fusarium, Mucor, Coccidioides, Blastomyces and others depending on geographic location and risk factors. Bacterial infection: orbital cellulitis, subperiosteal abscess, syphilis, M. tuberculosis, or atypical mycobacteria. Orbital inflammatory disease: orbital pseudotumor, Graves’ ophthalmopathy, sarcoidosis, Wegener’s granulomatosis, idiopathic sclerosing orbititis, polyarteritis nodosa, other collagen-vascular disorders. Neoplasm: metastases, lacrimal gland tumor, lymphoma, leukemia. Vascular disease: carotid-cavernous fistula, cavernous sinus thrombosis, varix.
Cornea Aspergillus keratomycosis may present with a foreign body sensation, pain, redness and decreased vision. The eye is usually severely inflamed. There may be a central or paracentral corneal abscess, diffuse keratitis and satellite lesions. There commonly is an intense anterior chamber reaction with hypopyon.
Lacrimal system
TREATMENT Systemic ●
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Canaliculitis, dacryocystitis and dacryoadenitis can occur.
Sclera Scleritis is rare but may progress to perforation. ●
Orbit Patients may present with slowly progressive, unilateral proptosis with or without pain. Later signs include decreased vision and changes in ocular motility. An orbital granuloma or abscess may form. Optic atrophy due to vascular compromise in the orbital apex has been reported.
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Uveal tract Multifocal choroiditis associated with vitreous cells and retinal vasculitis can occur.
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Endophthalmitis Patients may present with decreased vision, pain, and photophobia. Clinical signs include anterior chamber cells, hypopyon, vitreous cells or snowball opacities, serous or exudative retinal detachment, posterior ischemic optic neuropathy and central retinal artery occlusion.
Local ●
Laboratory findings ●
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Aspergillus keratitis: six to eight scrapings with a Kimura spatula from the bed of the infection are needed for culture. In cases of suspected intraocular Aspergillus, intravitreal and anterior chamber aspirates should be concentrated by the use of a filter or by centrifugation before plating. Orbital biopsy material should be plated soon after collection because Aspergillus is a ubiquitous organism and
Systemic treatment should be prescribed in coordination with consultation from an infectious disease subspecialist. Amphotericin B (0.5 to 1.5 mg/kg/day) has been the mainstay of systemic therapy for disseminated aspergillosis. Amphotericin B has substantial and varied toxicity, which can limit its use. Newer therapies are now becoming available. Itraconazole (200 to 600 mg/day) has been reported to show effectiveness in some cases in which amphotericin B failed. The combination of amphotericin B with flucytosine (100 to 200 mg/kg/day) or rifampin (600 mg b.i.d.) has been reported to improve the clinical response. Other azole antifungal agents (fluconazole, miconazole, ketoconazole) have shown less effectiveness in the treatment of aspergillosis. The use of systemic steroids is controversial. They may be necessary in cases of visual loss and proptosis but should not be used until effective antifungal therapy has been started.
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Natamycin (5% suspension) is the only commercially available topical formulation for the treatment of ocular aspergillosis (keratomycosis). It is effective for superficial corneal infections but less effective for deep stromal infection. Topical amphotericin B (0.05% to 0.15% eyedrops prepared from the intravenous formulation) can be used for cases of deeper keratomycosis or cases refractory to natamycin. Subconjunctival injection of amphotericin B (1 mg) has been described but may be associated with significant local toxicity. Successful therapy requires frequent and prolonged administration of medication. Hourly eyedrops may be necessary
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Surgical ●
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Mechanical debridement of the fungal growth allows better penetration of antifungal medications. A penetrating keratoplasty may be required in cases of keratomycosis refractory to medical therapy. A lamellar keratoplasty is contraindicated. A vitrectomy may be necessary for treatment of intraocular Aspergillus infection. Orbital aspergillosis is a life-threatening condition. Prompt orbital debridement combined with systemic medical therapy is necessary.
most common cause of posttraumatic endophthalmitis occurring in the rural setting. It usually enters the eye as a result of penetrating trauma with a contaminated foreign body, although it can also occur following intraocular surgery or as a metastatic infection related to intravenous drug use. Most cases of Bacillus endophthalmitis result in extremely poor visual outcomes. Many patients require enucleation or evisceration. Bacillus species are usually resistant to penicillins and cephalosporins but are sensitive to vancomycin, clindamycin, and fourth-generation fluoroquinolones (e.g. levofloxacin and gatifloxacin). Infection with B. cereus typically causes a rapid and fulminant endophthalmitis, which may progress to panophthalmitis, often accompanied by fever and leukocytosis. Characteristically, a ring abscess of the cornea develops in 24 to 48 hours after infection. At this point, however, the infection is usually well established and portends an extremely poor prognosis for the return of vision. The severe ocular damage caused by B. cereus seems to be due to endotoxins.
ETIOLOGY/INCIDENCE ●
REFERENCES Bennett JE: Aspergillus species. In: Mandell GL, Bennett JE, Dolin R, eds: Mandell, Douglas, and Bennett’s principles and practice of infectious diseases. 4th edn. New York, Churchill Livingstone, 1995, vol 2. Foster CS: Fungal keratitis. Infect Dis Clin North Am 6:851–857, 1992. Gassry GG, Hornblass A, Harrison W: Itraconazole in the treatment of orbital aspergillosis. Ophthalmology 103:1467–1470, 1996. Hunt KE, Glasgow BJ: Aspergillus endophthalmitis: an unrecognized endemic disease in orthotopic liver transplantation. Ophthalmology 103:757–767, 1996. Levin LA, Avery R, Shore JW, et al: The spectrum of orbital aspergillosis: a clinicopathological review. Surv Ophthalmol 41:142–154, 1996. Rao NA, Hidayat AA: Endogenous mycotic endophthalmitis: variations in clinical and histopathologic changes in candidiasis compared with aspergillosis. Am J Ophthalmol 132:244–251, 2001. Weishaar PD, Flynn HW, Murray TG, et al: Endogenous aspergillus endophthalmitis: clinical features and treatment outcomes. Ophthalmology 105:57–65, 1998.
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COURSE/PROGNOSIS ● ● ● ●
Fulminant panophthalmitis. Acute onset in 12 to 48 hours. Postoperative retinal detachments. Phthisis, no light perception vision, and enucleation are extremely common.
DIAGNOSIS Clinical signs and symptoms ● ● ● ●
6 BACILLUS SPECIES INFECTIONS 041.8
Penetrating ocular trauma, usually in a rural setting. Contamination of contact lenses or solutions. Low-grade chronic endophthalmitis following cataract surgery (B. circulans). Intravenous drug use or immune compromise.
CHAPTER 6 • Bacillus Species Infections
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for the fi rst 2 to 7 days and then tapered over the course of several weeks. Topical steroids have been associated with the progression of keratomycosis. Intravitreal amphotericin B (5 to 10 μg) has been used for the treatment of Aspergillus endophthalmitis. A repeat injection may be necessary if persistence of organisms is suspected 2 to 7 days after initial injection. The use of intravitreal steroids is controversial. Intravitreal dexamethasone (400 μg) as an adjunct to intravitreal amphotericin B has been described.
Corneal ring infi ltrate, diffuse sub-epithelial infi ltrates. Hypopyon. Vitritis. Systemic infection (fever, leukocytosis).
Laboratory findings ●
Gram-positive rod on Gram stain.
Differential diagnosis Franco M. Recchia, MD Nashville, Tennessee Sean P. Donahue, MD, PhD Nashville, Tennessee Denis M. O’Day, MD Nashville, Tennessee Bacillus is a genus of nearly ubiquitous, aerobic, gram-positive, spore-forming rods increasingly recognized as a cause of ocular infection. The species B. cereus, B. anthracis, B. subtilis, B. lichenformis, B. thurigiensis and B. circulans have all been reported to cause ocular infection, most importantly a rapidly progressive and devastating endophthalmitis. Bacillus is the
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Endophthalmitis caused by other organisms. Other leading causes of postoperative and traumatic endophthalmitis include coagulase-negative staphylococcal and streptococcal species. Chronic, low-grade post-surgical endophthalmitis is commonly caused by Propionobacterium acnes. Ring abscess secondary to Pseudomonas aeruginosa or Proteus species.
PROPHYLAXIS ●
The only prophylaxis is prevention of the injury; thus, the use of protective eyewear cannot be overemphasized.
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TREATMENT
SECTION 1 • Infectious Diseases
A high index of suspicion and prompt institution of appropriate treatment are crucial to any chance of salvaging vision in cases of Bacillus endophthalmitis. Treatment consists of antibiotics (intravitreal, topical, possibly systemic) and vitrectomy surgery. Due to the accelerated and aggressive course of B. cereus endophthalmitis, vitreous tap with antibiotic injection alone is not recommended. ● Local therapy: fortified topical antibiotics (vancomycin HCl 50 mg/mL alternating hourly with fortified gentamicin 13 mg/mL); consider topical or subconjunctival corticosteroids. ● Intravitreal: vancomycin (1.0 mg in 0.1 cc injection). ● Systemic: Vancomycin, 1 g/day IV every 12 hours; clindamycin 40 mg/kg/day IV in divided doses; gentamicin 3– 5 mg/kg/day IV in divided doses. (The fourth-generation fluoroquinolones levofloxacin and gatifloxacin achieve vitreous concentrations above the minimum inhibitory concentration (MIC90) for Bacillus cereus. However, their use as monotherapy for intraocular infection is not recommended.) ● Surgical: pars plana vitrectomy with intravitreal injection of vancomycin.
Chen JC, Roy M: Epidemic Bacillus endophthalmitis after cataract surgery II: chronic and recurrent presentation and outcome. Ophthalmology 107(6):1038–1041, 2000. Donzis PB, Mondino BJ, Weissman BA: Bacillus keratitis associated with contaminated contact lens care systems. Am J Ophthlmol 105(2):195– 197, 1988. Drobniewski FA: Bacillus cereus and related species. Clin Microbiol Rev 6:324–338, 1993. Essex RW, Yi Q, Charles PG, Allen PJ: Post-traumatic endophthalmitis. Ophthalmology 111(11):2015–2022, 2004. Foster RE, Martinez JA, Murray TG, et al: Useful visual outcomes after treatment of Bacillus cereus endophthalmitis. Ophthalmol 103:390– 397, 1996. Shamsuddin D, Tuazon CU, Levy C, Curtin J: Bacillus cereus panophthalmitis: source of the organism. Rev Infect Dis 4:97–103, 1982. Vahey JB, Flynn Jr HW: Results in the management of Bacillus endophthalmitis. Ophthalmic Surgery 22(11):681–686, 1991.
7 BLASTOMYCOSIS 116.0 Jeffrey D. Horn, MD Nashville, Tennessee
COMPLICATIONS Ocular complications consist of the typical devastating visual outcome. Of 83 eyes reported on before 1996 with posttraumatic Bacillus endophthalmitis, 62 (75%) became phthisical, were enucleated, or had no light perception vision. The vast majority of the remaining cases had light perception vision. Foster and colleagues recently reported on five patients with Bacillus endophthalmitis who maintained acuities ranging from 20/25 to 20/200. All presented within 32 hours of injury and had vitrectomy within 48 hours of injury; all except one received intravitreal vancomycin. Retinal detachment, caused either by the acute injury or by associated intraocular inflammation, is common.
Blastomycosis is an acute or a chronic systemic, potentially life-threatening fungal disease characterized by granulomatous lesions that may involve any part of the body, with a predilection for the lungs, skin and bones. With the exception of eyelid involvement, ocular disease is exceedingly rare. There are reported cases, however, of keratitis, endophthalmitis, choroiditis and orbital disease.
ETIOLOGY/INCIDENCE ●
COMMENTS ●
The best hope of salvaging eyes infected with Bacillus lies with early diagnosis and prompt treatment; thus, penetrating trauma with a metallic foreign body or that occurring in a rural setting should always suggest the possibility of infection by this organism. Intravenous drug abuse is also an important risk factor for metastatic endophthalmitis caused by this organism. Fever and leukocytosis occurring with a fulminant endophthalmitis are especially suggestive of Bacillus spp. because most other organisms causing endophthalmitis do not typically produce systemic signs. When Bacillus spp. are suspected, an immediate diagnostic and therapeutic vitrectomy is indicated, with antibiotic therapy being initiated before surgery if an undue delay is anticipated. Intravitreal, intravenous, and topical antibiotics are important if vision is to be salvaged. Although the prognosis is extremely poor, retention of useful vision is possible.
REFERENCES Boldt HC, Pulido JS, Blodi CF, et al: Rural endophthalmitis. Ophthalmology 96:1722–1726, 1989.
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The causative organism is Blastomyces dermatitidis, a thermally dimorphic fungus that exists in the mycelial phase at 25ºC and in the yeast phase at 37ºC. Most cases are endemic and occur in the Ohio and Mississippi River Valleys, where the organism has been found in soil. Annual incidence is about 4 per 100,000 population in endemic areas with a male predominance. Initial infection is usually from inhalation of spores resulting in pulmonary disease, although percutaneous inoculation has rarely been reported.
COURSE/PROGNOSIS ●
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Pulmonary disease ranges from asymptomatic (up to 50%) to severe pneumonia and may resolve spontaneously. Acute disease resembles influenza or pneumonia symptomatically. Most diagnosed with blastomycosis have chronic pneumonia. Extrapulmonary disease results from hematogenous dissemination. It may occur during or after the pulmonary phase.
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Topical amphotericin B can be prepared by diluting an intravenous solution to a concentration of 0.15%. Optimal dosing frequency is not known. Miconazole is tolerated by subconjunctival injection at a daily dose of 5 mg of the undiluted intravenous preparation. It may be administered topically as a 1% solution and given every hour.
Surgical ●
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Surgical drainage of lid or orbit abscesses may be needed in addition to antifungal treatment. Penetrating or lamellar keratoplasty is indicated in cases of corneal perforation or scarring.
COMPLICATIONS DIAGNOSIS ● ●
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Skin lesion is usually papular with a verrucous border and an atrophic center. Extravasation of erythrocytes between the dermis and epidermis gives rise to multiple black dots that are characteristic of the disease. Culture is the defi nitive method of diagnosis, but can take up to 30 days. Broad-based budding yeast forms (8 to 15 μm) with doublecontoured walls are seen best with periodic acid-Schiff and Gomori methenamine silver stains. Chemiluminescent DNA probes are available.
Differential diagnosis ● ● ● ● ●
Tuberculosis. Staphylococcal infection. Squamous cell carcinoma. Leprosy. Cryptococcosis, and other deep mycoses.
TREATMENT
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Systemic amphotericin B toxicity can cause fever, chills, hypokalemia, renal failure, and anemia. Itraconazole toxicity is relatively uncommon but can cause nausea, vomiting, impotence and elevated plasma aminotransferase levels. Itraconazole requires an acid pH for absorption; therefore, patients on antacids or H2 receptor blockers may have reduced plasma levels. Ketoconazole toxicity can cause nausea, vomiting, and testicular and adrenal dysfunction; fatal hepatocellular damage is rare.
CHAPTER 7 • Blastomycosis
The skin is the most common extrapulmonary site affected (80%), followed by bone (25% to 50%), genitourinary system (about 10% in men), and central nervous system (5% to 10%). The eyelid has been reported to be affected in 25% of cases, although the recent literature suggests a much lower incidence. Ophthalmic manifestations: ● Eyelid: granulomas, cicatricial ectropion; ● Conjunctiva: rare granulomas either contiguous or noncontiguous with corneal involvement; ● Cornea: ulcer, perforation; ● Choroiditis; ● Orbit: cellulites; ● Endophthalmitis/panophthalmitis.
SUMMARY Blastomycosis requires systemic therapy, but for less severe or non-life-threatening disease, newer, safer, more convenient, and equally effective treatment modalities are available. Ocular infection is so rare that the most appropriate therapy remains an unanswered question. Experience with infection in other tissues indicates that treatment should be given for a prolonged period. When there is corneal involvement, consideration should be given to the topical administration of miconazole in combination with systemic therapy.
Systemic ●
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Amphotericin B is the treatment of choice for life-threatening disease. The initial intravenous dose is 5 mg, increasing slowly to 50 mg three times per week until a total dose of 2 to 2.5 g is reached. Itraconazole, an oral triazole antifungal agent, has been shown to be as effective as amphotericin B for non-lifethreatening disease, excluding CNS involvement, without the severe toxic reactions associated with amphotericin B. The dose is 200 to 400 mg/day for 6 months. Ketoconazole, an imidazole that also is administered orally, is slightly less efficacious and less well tolerated than itraconazole. It also is much less expensive. The dose is 200 to 800 mg/day for 6 months. Fluconazole, another oral triazole antifungal agent, appears to be as efficacious at 400 to 800 mg/day for 6 months as ketoconazole and may be an alternative for patients who are intolerant of itraconazole. More studies are necessary.
Topical ●
REFERENCES Barr CC, Gamel JW: Blastomycosis of the eyelid. Arch Ophthalmol 104:96– 97, 1986. Bartley GB: Blastomycosis of the eyelid. Ophthalmology 102:2020–2023, 1995. Dismukes WE, Bradsher RW, Cloud GC, et al: Itraconazole therapy for blastomycosis and histoplasmosis. Am J Med 93:489–497, 1992. Johns KJ, O’Day DM: Pharmacologic management of keratomycoses. Surv Ophthalmol 33:178–188, 1988. Pappas PG, Bradsher RW, Kauffman CA, et al: Treatment of blastomycosis with higher doses of fluconazole. Clin Infect Dis 25:200–205, 1997. Powers TP, Carlson AN, O’Day DM: Deep mycoses. In: Mannis MJ, Macsai MS, Huntley AC, eds: Eye and skin disease. Philadelphia, LippincottRaven, 1996:583–590. Safneck JR, Hogg GR, Napier LB: Endophthalmitis due to Blastomyces dermatitidis: case report and review of the literature. Ophthalmology 97:212–216, 1990.
Topical therapy may be indicated in conjunction with systemic therapy for corneal involvement.
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8 BRUCELLOSIS 01.8 (Mediterranean Fever, Malta Fever, Gibralter Fever, Undulant Fever, Rock Fever, Cyprus Fever) SECTION 1 • Infectious Diseases
John D. Sheppard, Jr., MD, MMSc Norfolk, Virginia Suzanne C. Johnston, MD Norfolk, Virginia
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Abdominal pain; Arthralgia; Chills, excessive sweating; Anorexia, weight loss; Splenomegaly, hepatomegaly; Diffuse lymphadenopathy; Nervousness, depression.
In a recent prospective study Gungor et al found that 26% of participants with systemic brucellosis had some form of ocular involvement.
Ocular Brucellosis is a zoonotic disease caused by intracellular bacteria in the genus Brucella. This gram negative, aerobic, nonmotile coccobacillus causes a chronic, granulomatous infection. The organism responsible for brucellosis was discovered by David Bruce in 1886. Six species of Brucella have since been identified, four of which are known to be transmitted to humans: 1. B. abortus, carried mainly by cattle but also by sheep, goats, camels, yaks, horses and dogs. 2. B. melitensis, most common and most virulent species, carried by sheep and goats and less commonly by cattle. 3. B. suis, carried by swine. 4. B. canis, carried by beagle dogs.
ETIOLOGY/INCIDENCE Brucellosis is most commonly transmitted to humans by the consumption of infected meat or unpasteurized dairy products. Less commonly, it is spread through inhalation of infected aerosolized particles and contact with skin creams prepared from animal products. Brucellosis can enter through mucous membranes or broken skin. Brucellosis is rare in developed countries, with an incidence of about 1 per 1 million; 100 cases are reported annually in the United States. However, it is a relatively common health problem in developing countries, with 850 cases per 1 million reported annually in the Arabian Gulf countries, for example. These estimates are most likely low since brucellosis remains largely underreported.
Brucellosis can affect any ocular structure, with the most common being: ● Optic nerve involvement: ● optic nerve edema, ● retrobulbar neuritis, ● optic nerve atrophy. ● Papilledema; ● Chiasmal arachnoiditis; ● Uveitis (may be acute or chronic with recurrent attacks, inflammation may be severe with hypopyon); ● Iritis (granulomatous or nongranulomatous); ● Choroiditis (multifocal and nodular or geographic); ● Panuveitis; ● Eyelid edema; ● Dacryoadenitis; ● Conjunctivitis; ● Episcleritis, scleritis; ● Extraocular muscle palsies (most commonly IV, VI, and VII); ● Keratitis, with coin-shaped subepithelial infi ltrates; ● Corneal ulcers; ● Endophthalmitis (rare, occurs during bacteremic stage); ● Retinal edema, hemorrhages, or detachment.
Laboratory findings The diagnosis of systemic brucellosis depends on: ● Clinical manifestations; ● Blood and tissue cultures. Ocular brucellosis may be diagnosed via: Culture of tears and other ocular fluids; ● Detection of ocular (and systemic) Brucella antibodies (Witmer’s coefficient); ● Increasing serum antibody titers (presumptive diagnosis). ●
COURSE/PROGNOSIS Brucellosis has a variable presentation and course in humans. Length of incubation varies from a few days to several months with an average of three weeks. Humans and animals may initially be asymptomatic or may present with mild flu-like symptoms. If not treated appropriately, the acute phase can become chronic or relapsing.
DIAGNOSIS Clinical signs and symptoms Systemic Acute systemic infection is characterized by: ● Fever (classically intermittent with diurnal variation); ● Headache;
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Isolation of the organism decreases with chronic brucellosis making serologic assays more important: ● Serum agglutination test: most reliable. Titers greater than 1:160 diagnostic when associated with characteristic clinical presentation. Titers greater than 1:640 indicate chronic infection. ● Complement fi xation test; ● Radioimmunoassay (RIA): IgM predominates in acute cases, IgG predominates in chronic disease; ● Enzyme-linked immunosorbent assay (ELISA): IgG and IgM titers (useful in neurobrucellosis); ● Polymerase chain reaction assay (PCR).
TREATMENT
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Systemic
Various combinations of these medications have been used. The World Heath Organization issued guidelines in 1986 recommending doxycycline for six weeks in combination with either streptomycin for 2–3 weeks or rifampin for 6 weeks. Doxycycline/streptomycin has been associated with lower recurrence rates and may be preferable in areas where tuberculosis is also endemic given concern for community resistance to rifampin. Protracted administration of triple regimens may be necessary for neurobrucellosis. Treatment should continue for one or two months if infection is localized in the heart bone or eye. Doxycycline should be avoided in children and pregnant women.
Ocular Topical medications used during attacks of uveitis associated with brucellosis infection: ● Atropine; ● Corticosteroids. Topical and systemic steroids have been used to minimize damage to the eye during the ocular phase of the disease. Relapses are common after tapering corticosteroid therapy. Steroids should be used cautiously and for brief periods if possible for ocular inflammation.
COMPLICATIONS Systemic Complications associated with brucellosis infection: ● Pneumonia; ● Hepatitis; ● Splenic abscess; ● Epididymitis/orchitis; ● Prostatitis; ● Endocarditis; ● Arthritis; ● Osteomyelitis; ● Meningoencephalitis.
Ocular Ocular complications: ● Glaucoma; ● Cataract; ● Ocular hypotony; ● Cystoid macular edema;
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REFERENCES Al-Kaff AS: Brucellosis. In: Fraunfelder FT, Roy FH, eds: Current ocular therapy. 5th edn. Philadelphia, WB Saunders, 2000:15–16. Al-Kaff AS: Ocular brucellosis. Int Ophthalmol Clin 35:139–145, 1995. Elrazak MA: Brucella optic neuritis. Arch Intern Med 151:776–778, 1991. Gungor K, Bekir NA, Namiduru M: Ocular complications associated with brucellosis in an endemic area. Eur J Ophthalmol 12(3):232–237, 2002. Lyall M: Ocular brucellosis. Trans Ophthalmol Soc UK 93:689–697, 1973. Pappas G, Akritidis N, Bosilkovski M, Tsianos E: Medical progress: brucellosis. N Engl J Med 352(22):2325–2336, 2005. Rabinowitz et al: Bilateral mutifocal choroiditis with serous retinal detachment in a patient with Brucella infection: case report and review of literature. Arch Ophthalmol 123:116–118, 2005. Walker J, Sharma OP, Rao NA: Brucellosis and uveitis. Am J Ophthalmol 114(3):374–375, 1992.
CHAPTER 9 • Cat-scratch Disease
The treatment of brucellosis requires four to eight weeks of therapy. More than one therapeutic agent is generally required to prevent relapses. Effective medications are listed: ● Doxycycline 100 mg twice daily for six weeks; ● Cefi xime 400 mg daily in one to two doses; ● Rifampin 600–1200 mg/day for six weeks; ● Trimethoprim-sulfamethoxazole 960 mg twice daily for six weeks; ● Streptomycin 15 mg/kg/day IM for 2–3 weeks; ● Netilmicin 150 mg twice daily IM or (1.5–2 mg/kg/dose); ● Ofloxacin 400 mg b.i.d. for six weeks; ● Ciprofloxacin 500 mg twice daily for six weeks; ● Gentamicin 5 mg/kg/day in three divided IV doses for 5–7 days.
Retinal detachment; Phthisis bulbi; Optic neuropathy.
Woods AC: Nummular keratitis and ocular brucellosis. Arch Ophthalmol 35:490, 1946. Young E: Human brucellosis. Rev Infect Dis 5(5):821–842, 1984.
9 CAT-SCRATCH DISEASE 078.3 (Bartonella henselae Infection) Terry D. Wood, MD Portland, Oregon Eric B. Suhler, MD Portland, Oregon Cat-scratch disease (CSD) is usually a benign, self-limited illness characterized by regional lymphadenopathy lasting weeks to months after local inoculation with the gram-negative bacillus Bartonella henselae. The majority of cases (60–80%) occur in persons under 21 years old. A ‘typical’ CSD infection is manifest by the appearance of a localized skin papule at the inoculation site 3–10 days after exposure. This progresses to a pustule, which may or may not be recalled by the patient. Regional lymphadenopathy follows 1 to 7 weeks later and may be the only sign or symptom detected. The lymph node is tender 80% of the time and suppurates in 15%. ‘Typical’ CSD encompasses 89% of all cases. Of the remaining 11% ‘atypical’ CSD cases, approximately half involve the ocular structures. The most common of these is Parinaud’s oculoglandular syndrome, which encompasses 6% of all cases and presents as a unilateral granulomatous conjunctivitis. One to two percent develop neurologic findings; encephalopathy is the most common manifestation in this sub-category, and focal fi ndings may involve the cerebral cortex, thalamus, or the basal ganglia. Neuroretinitis, a clinical syndrome comprised of papillopathy and an exudative maculopathy typically manifesting as a ‘macular star,’ is a relatively common neurologic sequelae, although it is often initially misdiagnosed as optic neuritis. It is however, important to note that neuroretinitis is not associated with multiple sclerosis, making the appearance of a macular star a welcome finding in a young patient presenting
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with optic nerve edema. Less commonly reported intraocular manifestations of B. henselae infection include central retinal artery occlusion, central retinal vein occlusion, peripapillary angiomatosis and neovascular glaucoma.
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ETIOLOGY/INCIDENCE SECTION 1 • Infectious Diseases
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Causative agent, Bartonella (formerly Rochalimea) henselae. Removed from Rochalimea sp./order Rickettsiales when it was discovered not to be an obligate intracellular parasite. Fastidious, pleiomorphic, gram-negative bacillus. Most infections are caused by a scratch from a young, fleainfested bacteremic kitten, although transmission may also occur from a cat bite or lick (role of fleas in the transmission of human disease is unclear, although B. henselae DNA has been isolated from the fleas of bacteremic cats). Fleas appear to serve as the vector of transmission between cats. Bacteremic cats are usually less than 1 year old, are asymptomatic, and do not require treatment. Inoculation has also been reported from other animals (monkey, rabbit, squirrel). Infections are more common in the autumn and early winter months (60%). Mean age of onset is 12 years; predominance of patients are 7–30 years of age. Incidence of disease 1/10,000. May occur in intrafamilial epidemics in families with kittens. No evidence to support person-to-person transmission.
PARINAUD’S OCULOGLANDULAR SYNDROME (POGS) ●
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Most common form of ‘atypical’ CSD: accounts for 6% all cases of CSD. Theorized alternative route of inoculum is from wiping eye after touching cat fur harboring cat saliva with organism (residual from cat self-cleaning).
Clinical presentation characterized by: ● Unilateral granulomatous conjunctivitis; ● Single or multiple soft granulomas, 0.5–2.0 mm (may enlarge and ulcerate); ● Redness, irritation, chemosis and watery discharge; ● No serious corneal complications reported; ● Ipsilateral preauricular/submandibular lymphadenopathy, occasionally cervical. May be accompanied by fever, malaise, anorexia, weight loss.
DIAGNOSIS/LABORATORY FINDINGS ●
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Histopathologic (best diagnostic indicator): ● Warthin–Starry silver impregnation stain of biopsied lymph node or other involved tissue reveals clumps of tiny pleiomorphic bacilli; ● Lymph nodes usually show evidence of granulomatous inflammation and stellate microabscesses which may coalesce.
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Skin test (Hanger–Rose): ● Former hallmark of diagnosis, now largely abandoned due to concerns regarding transmission of viral/prion infections. Serum immunofluorescent assay (IFA): ● Routinely available; ● Sensitivity of 84%, specificity of 96%; positive predictive value of 91%; ● Significant positive titers found in 3% of healthy controls; PCR gaining increasing use in diagnosis when serology is equivocal or inconclusive: ● Culture: difficult; ● Slow growing organism; requires 1–4 weeks.
Differential diagnosis ● ● ● ● ●
Tularemia. Sporotrichosis. Tuberculosis. Lymphoma. Syphilis.
Less common: sarcoid, coccidiomycosis, actinomycosis, blastomycosis, infectious mononucleosis, mumps, pasteurellosis, yersiniosis, glanders, chancroid, lymphogranuloma venereum, rickettsiosis, listerelliosis, ophthalmia nodosa. ● Work up: ● History and physical exam directed toward likely differential diagnoses, CBC, CXR, PPD with controls, RPR, FTA-ABS, B. henselae IFA; ● If clinically indicated conjunctival or lymph node biopsies, blood cultures.
TREATMENT ● ●
Symptomatic: warm compresses, analgesics, antipyretics. Aspiration of the lymph node only if distention causes pain: ● Needle drainage from site 1–2 cm away in unaffected skin.
Direct incision and drainage may lead to persistent sinus formation and is contraindicated. ● Consider antibiotics in moderate to severe cases or if the patient is systemically ill. Treatment, if effective, will usually improve clinical course within 48 hours: ● Rifampin, 10–20 mg/kg/d, PO q 12 or 24 hourly: dosing (87% effective). Often used as adjuvant to other antibiotics as listed below. ● Ciprofloxacin, 20–30 mg/kg/d given PO q 12 hourly: dosing (84% effective); ● Gentamicin sulfate, 5–7 mg/kg/d IV given q 8 hourly for 7 days: dosing (73% effective); ● Trimethoprim/sulfamethoxazole (Bactrim/Septra); 6– 12 mg/kg/day TMP and 30–60 mg/kg/day SMX given PO, q 12 hourly: dosing (58% effective); ● Macrolide and tetracycline antibiotics also deemed effective in many case reports — course of treatment: 4–6 weeks. Should be afebrile by 1 week, decreasing lymphadenopathy, no constitutional symptoms by 5–10 days.
BACILLARY ANGIOMATOSIS (EPITHELIAL ANGIOMATOSIS)
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Clinical features ●
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DIAGNOSIS Primarily clinical ● ●
Serologic: acute and convalescent titers useful. PCR useful in cases where serology is equivocal.
Differential diagnosis ●
DIAGNOSIS ●
Based on histopathologic finding on Warthin–Starry and H & E staining. ●
Differential diagnosis
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Kaposi’s sarcoma (must be ruled out histologically in HIV patients), pyogenic granuloma, angiosarcoma, hemangioma.
Syphilis, Lyme, TB should be ruled out if clinically indicated. Also tularemia, toxoplasmosis, HSV, HZV, EBV, psittacosis, parasitic disease/DUSN, salmonella, leptospira, histoplasmosis, toxocara. Influenza, mumps, coxsackie viruses, sarcoid. Hypertensive retinopathy/increased intracranial pressure especially with bilateral disease.
CHAPTER 9 • Cat-scratch Disease
●
Single or multiple cutaneous, subcutaneous, mucosal, visceral, or retinal lesions. Reddish vascular papules, nodules, or tumors, rarely plaque-like. Often similar in appearance to Kaposi’s sarcoma; range in size from small papules to large, ulcerating, exophytic growths which may erode underlying bone. Ophthalmic structures reported involved have included the conjunctiva and optic nerve head/peripapillary retina. Systemic manifestations may include fever, chills, malaise, anorexia, headache. Occurs more commonly and is more severe in AIDS/immunocompromised patients.
Primary site of pathology appears to be the optic nerve; Fluoroscein angiography shows leakage and/or staining of the disc but no leakage from the perifoveal capillaries; More often unilateral, however both sides may be involved clinically and/or angiographically; May present with sudden loss of visual acuity and/or field, transient visual obscurations, floaters, dyschromatopsia, or be completely asymptomatic; Visual acuity at presentation may vary from 20/20 to light perception; usually between 20/40 and 20/200.
TREATMENT TREATMENT Resolves rapidly with antibiotic regimens listed above. Standard course of 3–4 weeks.
NEURORETINITIS (LEBER’S IDIOPATHIC STELLATE NEURORETINITIS) ● ● ●
●
First hypothesized association with CSD in 1984. Generally reported to occur in 1–2% cases of CSD. Twenty-six percent of confirmed cases B. henselae infection in one series. CSD is implicated 2/3 of patients with the clinical presentation of neuroretinitis.
Clinical features ●
●
●
Optic disk edema, usually diffuse, varies in severity, may see disk hemorrhage. Resolves over 2 weeks to 2 months. Optic atrophy may follow uncommonly. ‘Macular star’ lipid exudates. Protein/lipid rich exudation from the nerve spreads to Henle’s layer in parafoveal region. Resolves over 6–12 months. May see residual RPE deficits.
Atypical CSD with neurologic manifestations (i.e. neuroretinitis, others as below) are usually treated with antibiotic regimens as listed above. There is no consensus on the duration of treatment; most reports 4–8 weeks, and there is no documented proof of efficacy of treatment versus nontreatment; anecdotal reports describe hastened visual recovery. Systemic steroids are controversial; they have been used in some series, but have not been shown to be beneficial or harmful.
PROGNOSIS Most patients (>90%) have very good recovery of Snellen acuity (20/40 or better); a small subset will have profound, persistent visual loss. In patients with excellent Snellen acuity, subtle subjective disturbance often remain (i.e. metamorphopsia, dyschromatopsia).
Other posterior pole manifestations of CSD (uncommon) ● ●
May also see: Peripapillary or macular serous retinal detachments; ● Focal or multifocal retinal infi ltrates/retinitis; ● Vitritis and/or anterior uveitis; ● Retinal vasculitis; ● Often an afferent pupillary defect, unless affected bilaterally; ● Variety of visual field deficits; often central, cecocentral ‘disk fields’; also arcuate, altitudinal, general constriction; ●
● ● ● ●
Optic neuritis. Branch retinal arterial occlusions. Serous retinal detachments. Peripapillary angiomatosis. Inflammatory mass of the optic nerve head. Panuveitis (has been reported to mimic VKH).
Other systemic manifestations May occur in either immunocompetent or immunosuppressed hosts, although tend to be more severe in the immunocompromised.
19
Infectious Fever/bacteremia, culture negative endocarditis, tonsillitis, osteomyelitis, brain abscess.
10 COCCIDIOIDOMYCOSIS 114.9 (Valley Fever, San Joaquin Fever)
Neurologic Seizures, coma, aseptic meningitis, encephalitis, cerebral arteritis, transverse myelitis, polyneuritis, radiculitis, peripheral neuropathy, Bell’s palsy. SECTION 1 • Infectious Diseases
John Mourani, MD Tucson, Arizona Stephen A. Klotz, MD Tucson, Arizona
Pulmonary Hilar adenopathy, pleural effusion.
ETIOLOGY/INCIDENCE GI Bacillary peliosis hepatitis and/or splenitis.
Other Hemolytic anemia, erythema nodosum or annulare, arthralgias, generalized lymphadenopathy.
REFERENCES Anbu AT, Foulerton M, McMaster P, Bakalinova D: Basal ganglia involvement in a child with cat-scratch disease. Pediat Infect Disease J 10:931– 932, 2003. Bafna S, Lee AG: Bilateral optic disk edema and multifocal retinal lesions without loss of vision in cat scratch disease. Arch Ophthalmol 114: 1016–1017, 1996. Cunningham ET, Koehler JE: Ocular bartonellosis. Am J Ophthalmol 130(3):340–349, 2000. Dreyer RF, et al: Leber’s idiopathic stellate neuroretinitis. Arch Ophthalmol 102(8):1140–1145, 1984. Gray AV, Michels KS, Lauer AK, Samples JR: Bartonella henselae infection associated with neuroretinitis, central retinal artery and vein occlusion, neovascular glaucoma, and severe vision loss. Am J Ophthalmol 137(1):187–189, 2004. Huang MC, Dreyer E: Parinaud’s oculoglandular conjunctivitis and catscratch disease. Int Ophthalmol Clinics 36(3):29–36, 1996. Khurana RN, Albini T, Green RL, et al: Bartonella henselae infection presenting as a unilateral panuveitis simulating Vogt-Koyanagi-Harada syndrome. Am J Ophthalmol 138(6):1063–1065, 2004. Labalette P, Bermond D, Dedes V, Savage C: Cat-scratch disease neuroretinitis diagnosed by a polymerase chain reaction approach. Am J Ophthalmol 132(4):575–576, 2001. Lee WR, Chawla JC, Reid R: Bacillary angiomatosis of the conjunctiva. Am J Ophthalmol 118(8):152–157, 1994. Margileth AM: Antibiotic therapy for cat-scratch disease: clinical study of therapeutic outcome in 268 patients and a review of the literature. Pediatr Infect Dis J 11:474–478, 1992. Newsom RW, Martin TJ, Wasilauskas B: Cat-scratch disease diagnosed serologically using an enzyme immunoassay in a patient with neuroretinitis. Arch Ophthalmol 114(4):493–494, 1996. Reed JB, et al: Bartonella henselae neuroretinitis in cat-scratch disease: diagnosis, management and sequelae. Ophthalmol 105(3):459–466, 1998.
Coccidioidomycosis is an infectious disease caused by Coccidioides immitis or C. posadasii. It is a dimorphic fungus endemic in southwestern United States, Mexico, and parts of Central and South America. The life cycle of Coccidioides species has a saprophytic phase wherein the fungus grows as a mold in the soil giving rise to arthroconidia. Primary infection occurs following inhalation of airborne arthroconidia that transform into spherules, thus beginning the parasitic phase. Patients with altered immune function, diabetes mellitus, acquired immune deficiency syndrome (AIDS), recipients of corticosteroids, pregnant patients, or transplant patients, are at particular risk for relapsing infection and/or extrapulmonary dissemination. African-American and Filipinos are at high risk for dissemination as well.
COURSE/PROGNOSIS During primary infection approximately 40% of patients will have a symptomatic illness consisting of influenza-like symptoms with fever, cough, myalgia and arthralgia. Nearly 5% will be left with pulmonary nodules or cavitary lesions. Less than 1% of patients develop disseminated disease. Symptomatic ocular involvement is rare and initial ocular symptoms are non-specific. Asymptomatic chorioretinal scars were seen in as many as 9% of patients seeking medical attention. The majority of lesions resolve spontaneously without therapy. Ocular involvement can be categorized as external or internal disease.
External involvement ●
●
Starck T, Madsen BW: Positive polymerase chain reaction and histology with borderline serology in Parinaud’s oculoglandular syndrome. Cornea 21(6):625–627, 2002. Suhler EB, Lauer AK, Rosenbaum JT: Prevalence of serologic evidence of cat scratch disease in patients with neuroretinitis. Ophthalmol 107(5): 871–876, 2000. Wong MT, et al: Neuroretinitis, aseptic meningitis, and lymphadenitis associated with Bartonella (Rochalimea) henselae infection in immunocompetent patients and patients infected with human immmunodeficiency virus type 1. Clin Infect Dis 21(2):352–360, 1995.
●
Phlyctenular conjunctivitis, scleritis, or episcleritis during primary pulmonary infection are hypersensitivity responses to coccidioidal antigen and usually subside without treatment. Corneal manifestations include a spectrum from superficial infi ltrate to necrotic inflammatory foci and perforation. Corneal opacities, staphyloma and perforation have been described. Granulomatous lesions of the eyebrow, lids, lacrimal gland, and palpebral conjunctiva may be a manifestation of disseminated disease or the only presentation. Direct inoculation has been reported. Orbital, optic nerve and extraocular muscle disturbance is due to direct granulomatous involvement or secondary to central nervous system disease.
Internal involvement ●
20
Anterior uvea (iris and ciliary body), iridocyclitis. With anterior chamber involvement, a white fluffy exudate can
●
With resolution of the acute inflammation chorioretinal lesions shrink and appear as sharply demarcated, punched-out, scars evolving with varying degrees of hyperpigmentation and depigmentation.
Diagnosis A high index of suspicion on the part of physicians is important in establishing this diagnosis. A history of living in endemic areas, travel to or temporary residence in such areas should alert the physician to the possibility of coccidioidomycosis.
Laboratory findings Direct examination of tissue from biopsy or cytologic specimens, and anterior chamber fluid, may demonstrate endosporulating spherules and/or granulomas. ● Coccidioides species grow in most routine culture media as early as 3 to 4 days. ● Laboratory personnel need to be notified about the possibility of isolation of this fungus due to potential for infection.
Serologic testing Serologic testing can detect IgM antibody demonstrating acute infection and IgG antibody, demonstrating present or past infection.
Differential diagnosis Includes other fungal infections, and granulomatous lesions.
TREATMENT Serious ocular infections need to be treated with systemic antifungal medications. The value and safety of intraocular injection is unproven, but amphotericin B has been administered topically and by intraocular injection. For systemic treatment, consultation with an infectious disease specialist is strongly recommended. Oral azoles are the mainstay of current therapy with fluconazole having the greatest documented efficacy.
Local ●
●
Conjuncitivitis, scleritis, episcleritis during acute primary infection: inflammation resolves with resolution of primary infection, topical corticosteroid might help. Granulomatous inflammation of conjunctiva and/or cornea: topical amphotericin B (AmB) or conjunctival/subconjunctival administration, which is painful with poor penetration.
●
Topical steroids should be used judiciously and sparingly to control inflammation once diagnosis of intraocular infection is confirmed and appropriate antifungal therapy is initiated.
Systemic ●
●
●
●
Fluconazole 400 to 800 mg/day has been used with success in patients with systemic infection even with meningeal involvement and is the most commonly used medication. The drug achieves good ocular levels. Amphotericin B, (AmB) IV indicated in severe systemic disease (0.3 mg/kg to 1.0 mg/kg/day in life-threatening illness). Amphotericin B lipid complex and liposomal amphotericin B are available for patients who do not tolerate AmB due to nephrotoxicity; efficacy in treatment of ocular coccidioidomycosis is unknown (5 mg/kg/day). Itraconazole has been used for non-meningeal involvement.
The newer azoles (voriconazole and posaconazole) and echinocandin (caspofungin) have in vitro activity but their efficacy in treatment of ocular disease is unknown.
CHAPTER 11 • Dermatophytosis
be observed adherent to the iris surface. Other anterior chamber findings may include mutton-fat precipitates, flare, cells, and hypopyon, along with anterior or posterior synechiae, or both. Posterior uvea (choroid), retinitis, choroiditis and chorioretinitis. Acute lesions vary from a large three disk diameter perimacular chorioretinal exudates to whitish-yellow, metallic, small (0.1–0.25 disc diameter) oval, depigmented slightly elevated, edematous appearing choroidal or chroioretinal patches scattered randomly throughout the fundus. Vascular sheathing and striate retinal hemorrhages occur. Retinal edema with detachment is associated with active choroiditis. The vitreous reaction can vary from a mild cyclitis to a dense turbid inflammatory exudate containing spherules.
COMPLICATIONS Local destruction, extraocular muscle palsies, corneal scarring and/or perforation, scleral necrosis and staphyloma, anterior and posterior synechiae, panophthalmitis, optic atrophy, and blindness. An excellent source of information for physicians and patients alike is the Valley Fever Center for Excellence: http://www.vfce. arizona.edu/.
REFERENCES Deresinski SC, Mirels LF, Kemper CA: Coccidioides immitis. In: Gorbach SL, Bartlett JG, Blacklow NR, eds: Infectious diseases. 3rd edn. Philadelphia, Lippincott Williams & Wilkins, 2004:2227–2245. Luttrull JK, Wan WL, Kubak BM, et al: Treatment of ocular fungal infections with oral fluconazole. Am J Ophthalmol 119(4):477–481, 1995. Moorthy RS, Rao NA, Sidikaro Y, Foos RY: Coccidioiomycosis iridocyclitis. Ophthalomol 101(12):1923–1928, 1994. Rodenbiker HT, Ganley JP, Galgiani JN, Axline SG: Prevalence of chorioretinal scars associated with coccidioidomycosis. Arch Ophthalmol 99(1):71–75, 1981. Rodenbiker HT, Ganley JP: Ocular coccidioidomycosis. Surv Ophthalmol 24(5):263–290, 1980. Review.
11 DERMATOPHYTOSIS 110.9 Sanjay V. Patel, MD Rochester, Minnesota Alan Sugar, MD Ann Arbor, Michigan Dermatophytosis is an infection by any of the keratinophylic fungi known as the ringworm fungi, most commonly Trichophyton, Epidermophyton and Microsporum spp., involving super-
21
SECTION 1 • Infectious Diseases
ficial skin, hair and nails. Dermatophytes are ubiquitous and have very low infectivity. Clinically, they are classified according to the area of skin involved, such as tinea capitis (ringworm of the scalp), tinea faciei (face), tinea corporis (body), tinea pedis (athlete’s foot) and onychomycosis (nails). Skin lesions are superficial and begin as red scaly papules that expand to become circular patches. As the lesion expands and the center clears, an annular pattern develops that is typical of ringworm. The lesions may be vesicular and single or multiple and often are intensely pruritic. Facial lesions may take a butterfly configuration. The rings may be multiple or biconcentric ‘bull’s eyes.’
ETIOLOGY ● ●
Trichophyton, Epidermophyton, Microsporum spp. Specific species may be acquired from soil, farm animals, household pets, or by direct or indirect human contact.
● ● ● ● ●
Miconazole 2%; Oxiconazole nitrate 1%; Sertaconazole nitrate 2%; Sulconazole 1%; Terbinafine 1%; Tolnaftate 1%.
Systemic The trend is toward early systemic use, especially for extensive lesions and those unresponsive to topical agents. Tinea capitis requires systemic treatment. In the past, the standard for systemic use was oral griseofulvin 125 to 250 mg (for children) and 500 mg (for adults) of microsize crystalline form once daily for at least 4 to 6 weeks. Newer agents offer greater effectiveness with a shorter treatment course, usually 2 to 4 weeks; these include: ● Ketoconazole 200 mg/day; ● Fluconazole 100 mg/day; ● Itraconazole 100 mg/day; ● Terbinafine 250 mg/day.
DIAGNOSIS Clinical signs and symptoms ●
●
● ●
●
●
●
The enlarging lesion typically leaves a ringworm pattern with little inflammation. Occasionally, a severe inflammatory reaction called kerion occurs. Untreated lesions may become chronic. Allergic reactions to fungi, known as dermatophytid, or ‘tid,’ reactions, cause noninfected vesicles, usually on the hands, and, rarely, an allergic conjunctivitis. Clinical findings may be more severe and atypical in immunosuppressed and human immunodeficiency virus-infected patients. Animal-derived infections are more acute than human — or soil-derived infections. Ocular findings: ● Eyelids: blepharitis, dermatitis, edema, madarosis, ulceration, preseptal cellulitis; ● Eyebrows: folliculitis, madarosis, scaly rash; ● Conjunctiva: infectious or allergic conjunctivitis; ● Cornea: fungal corneal ulcer (rare).
Laboratory findings ● ●
●
●
Keratinized tissue can be scraped from the lesion border. Septate hyphae branches on 20% potassium hydroxide stain. Culture on selective media requires 2 to 3 weeks to grow at room temperature. Rapid identification by polymerase chain reaction is possible.
TREATMENT Local Antifungal creams are useful for milder lesions. Creams should be applied twice daily to affected skin after cleansing; continue for 1 week after lesion clears. Available topical agents are: ● Butenafine 1%; ● Ciclopirox olamine 1%; ● Clotrimazole 1%; ● Econazole 1%; ● Haloprogin 1%;
22
●
The azole antifungals can cause hepatotoxicity, can increase the anticoagulant effect of coumadin and raise blood levels of several drugs, including cyclosporin A, digoxin, antiepileptic agents and oral hypoglycemic agents. Terbinafine and itraconazole have been shown to be safe and efficacious in children.
PRECAUTIONS ●
●
Corticosteroids topically or systemically may mask the appearance of dermatophytoses and increase their severity and duration. Lesions may relapse if antifungal agents are discontinued prematurely.
COMMENTS Ocular and periocular involvement by these fungi are rare. They usually result from extension from involved facial or scalp skin. Scalp ringworm occurs most frequently in children in hot, humid weather. Scalp ringworm is rare in adults and may be a sign of altered immunological status.
REFERENCES Fedukowicz HB, Stenson S: External infections of the eye: bacterial, viral and mycotic. 3rd edn. East Norwalk, CT, Appleton-Century-Crofts, 1985:194–196. Meis JF, Verweij PE: Current management of fungal infections. Drugs 61(Suppl 1):13–25, 2001. Velazquez AJ, Goldstein MH, Driebe WT: Preseptal cellulitis caused by Trichophyton (ringworm). Cornea 21:312–314, 2002. Warnock DW: Superficial fungal infections. In: Cohen J, Powderly WG, eds: Infectious diseases. 2nd edn. St Louis, Mosby, 2004:173–180. Weitzman I, Summerbell RC: The dermatophytes. Clin Microbiol Rev 8:240–259, 1995. Zaias N, Glick BP, Rebell G: Superficial mycoses. In: Mannis MJ, Macsai MS, Huntley AC, eds: Eye and skin disease. Philadelphia, LippincottRaven, 1996:573–582.
DIAGNOSIS
12 DIPHTHERIA 032.9 F. Hampton Roy, MD, FACS Little Rock, Arkansas
ETIOLOGY/INCIDENCE Diphtheria is an acute infectious disease caused by C. diphtheriae, a gram-positive, club-shaped organism. Only strains that are latently infected by a bacterial virus, diphtheria phage B, produce exotoxin and are capable of producing diphtheria. The toxin is responsible for the most common systemic complications of diphtheria, affecting the heart and nervous system; cranial nerve involvement can include the third, fourth and sixth nerves. C. diphtheriae is essentially a surface saprophyte, most commonly affecting the nasopharyngeal area; cutaneous diphtheria seems to be more frequently associated with external ocular involvement. The incubation period is 2 to 5 days after exposure. About 200 cases of nonocular diphtheria are reported annually in the United States, usually among individuals without adequate immunization histories. Widespread immunization of infants and children against diphtheria has limited the incidence recently to scattered outbreaks. However, a single inoculation does not confer lifetime immunity and booster injections of the protective toxoid are necessary every 3 to 5 years, particularly for children, who appear more susceptible to overt disease. Newborns usually are protected by transplacental globulin from the mother, although a few severe, nonocular infections in neonates have been reported. Healthy carriers of the C. diphtheriae organism, although not susceptible themselves, are a source of infection to others, but this means of transmission has become less important in populations with widespread immunization. The disease may occasionally be seen in fully immunized persons, but the infection is usually mild and rarely fatal; death is most frequent in the very young and the elderly. As a rule, the longer the delay in administration of antitoxin, the greater the incidence of complications and death.
The external ocular manifestations of diphtheria may include: ● Tender, red, swollen eyelids; ● Entropion; ● Meibomianitis; ● Trichiasis; ● Xerophthalmia, symblepharon; ● Ptosis; ● Accommodative spasm or paralysis of extraocular muscles; ● Convergence paralysis, divergence paralysis; ● Paralysis of third, fourth, or sixth nerve; ● Dacryoadenitis, dacryocystitis; ● Conjunctival hyperemia, petechiae; ● Catarrhal, membranous, pseudomembranous, or purulent conjunctivitis; ● Keratitis; ● Corneal ulcer, perforation.
CHAPTER 12 • Diphtheria
Diphtheria is an acute infectious disease caused by the grampositive bacillus Corynebacterium diphtheriae. It is characterized by a primary lesion, usually within the respiratory tract and more generalized symptoms caused by release and spread of bacterial exotoxins throughout the body. It most commonly affects children younger than 10 years. Conjunctivitis diphtheria has the property of exciting profuse exudation in the tissue of the conjunctivae, which has great tendency to coagulate, leading to necrosis of the infi ltrated tissue. Diphtheria can be life threatening because the exotoxins produced by the bacteria cause tissue necrosis and accumulation of the host’s leukocytes and erythrocytes in respiratory exudates, which can occlude the trachea and other air passages. In addition, the toxins circulating in the patient’s bloodstream can be deposited throughout the body; lesions may occur in the kidneys, heart and nerves, resulting in acute nephritis and serious cardiac debility.
Clinical signs and symptoms
Diphtheria also may result in serious intraocular complications, including: ● Cataract; ● Central retinal artery occlusion; ● Optic neuritis.
Laboratory findings Because diphtheria is an acute, serious illness, suspect cases should be promptly treated, even before a positive diagnosis is confirmed. Swabs of the throat of a suspected case, plated onto slides and stained with methylene blue or toluidine blue (in addition to samples for Gram’s stain), will demonstrate nonmotile rods that are roughly club shaped but pleomorphic, with granular and uneven staining. The intracellular granules take on a reddish, refractive appearance and are characteristic of the bacterium. Specimens also may be inoculated onto Loeffler coagulated serum slant tubes, blood agar plates and tellurite plates for diagnostic confi rmation.
TREATMENT Systemic A combination of antibiotics and antitoxin is necessary to effectively combat diphtheria; the patient should be treated promptly, if necessary even before a positive diagnosis is available, because the diphtheria toxins bind irreversibly to cells and the antitoxin then is ineffective except on circulating toxins. The severity of the disease depends on the amount of exotoxin absorbed before treatment is initiated; once clinical manifestations of the toxins appear, they cannot be neutralized by antitoxin administration. Treatment is begun by administering a small test dose of antitoxin subcutaneously and observing the patient for 1 to 2 hours for a localized reaction to the antitoxin or the horse serum in which it is prepared, or both. After ruling out anaphylactic reactions, a therapeutic dose of: ● Diphtheria antitoxin 10,000 to 100,000 units in 100 or 200 mL of isotonic saline may be administered intravenously over 30 minutes.
23
SECTION 1 • Infectious Diseases
Although antibiotics are thought to have little effect on the clinical course of the respiratory diphtheria infection, they may be of benefit in terminating toxin production. Antibiotic therapy is also of value because diphtheria infection typically is mixed with other bacteria, including staphylococci and pneumococci and many other organisms; in severe cases, streptococci are often present and there is evidence that tissue damage is due to the mixed infection rather than to the diphtheria toxin alone. Additional benefits of antibiotics are hastened clearance of the carrier state and prevention of spread of the organism to others: ● Penicillin is the drug of choice (procaine penicillin G 600,000 units IM twice daily for 7 to 16 days); ● Penicillin V PO may be substituted after the third day in patients with uncomplicated infections; ● Penicillin G (4 to 6 million units IV daily divided in four equal doses) may be used with IV solutions.
Frequent instillations of penicillin G sodium ointment 1000 units/g or erythromycin (0.5%) ointment are administered in addition to systemic antibiotics. If the infection involves the eyelid skin, cutaneous diphtheria responds well to local application of compresses soaked in penicillin solution 250 to 500 units/mL and diphtheria antitoxin 20,000 units IM. A canthotomy should not be done in an effort to separate the lids because the incision invariably becomes infected and actually increases the area of toxin absorption. Diphtheria membranes usually slough away spontaneously during convalescence; membranes should not be peeled off because this leaves a raw, suppurating surface and facilitates absorption of toxin. With this caveat, however, a glass rod or cotton-tipped applicator moistened with sterile saline may be used at intervals to break early symblepharon formation in the fornices.
In patients allergic to penicillin: ● Erythromycin (25 to 50 mg/kg/day IV for 10 to 14 days) may be substituted. However, erythromycin resistance has occurred in some recent diphtheria outbreaks; C. diphtheriae also is frequently resistant to cephalexin, colistin, lincomycin and oxacillin. The organism is usually sensitive to ampicillin, clindamycin, tetracycline and rifampin. Regardless of the antibiotic, therapy should be continued for at least 7 days.
Supportive
Steroids have been used to prevent or ameliorate myocarditis associated with diphtheria, but recent opinion holds that corticosteroids or corticotrophins are not of value in the treatment of diphtheria or any of its complications.
Ocular Treatment of external ocular diphtheria has two goals: neutralization of toxin and eradication of live organisms. There are several regimens for the topical and systemic administration of antitoxin and the amount given is often based on empiric decision. In general, the more severe the disease or the more extensive the membrane formation, the greater the amount of antitoxin required. After giving a test dose to rule out anaphylaxis: ● Diphtheria antitoxin 10,000 to 100,000 units is applied topically to the affected eye every 4 to 6 hours for 24 to 48 hours; ● A subconjunctival injection of diphtheria antitoxin also may be considered as an alternative to topical application. Commercially available immune and hyperimmune globulin preparations have low diphtheria antitoxin titers and thus are not particularly useful; however: ● A high-titer γ-globulin preparation made from the blood of persons with high titers of antitoxin is available as an investigational preparation that may be useful in special circumstances, such as for a patient who is highly allergic to the horse serum used to prepare commercial antitoxin. Intended for use in prophylaxis, it is obtainable from the Communicable Disease Division, State Department of Public Health, Lansing, Michigan. The treatment dose has not been established; this preparation should never be given intravenously. Antibiotics are not effective against diphtheria toxin but are indicated for the eradication of the bacilli and superinfections.
24
Patients with diphtheria should be isolated and hospitalized; bedrest is important for 3 weeks because of the frequency of myocardial involvement. Aspirin and codeine may be indicated for relief of pain.
Precautions Before antitoxin administration, tests for hypersensitivity to horse serum are mandatory. If the patient is allergic to horse serum, antitoxin may be administered after desensitization, or, if available, human diphtheria immune globulin may be substituted. Rarely, a patient may exhibit such marked hypersensitivity that antiserum cannot be administered without the risk of death. The heart rate of all patients should be monitored carefully during the administration of diphtheria antitoxin because anaphylaxis may occur. In addition, all patients with diphtheria should receive careful cardiac monitoring for developing myocarditis. Drugs with depressant effects on the heart must be used with extreme caution in patients with diphtheria. Patients with diphtheria should be quarantined until two successive cultures of the eye, skin, or other infected areas, taken at 24-hour intervals, are negative. If antibiotics have been given, cultures should not be taken until at least 24 hours after cessation of therapy.
REFERENCES Burkhard C, Choi M, Wilhelm H: Optic neuritis as a complication in preventive tetanus-diphtheria-poliomyelitis vaccination: a case report. Klin Monatsbl Augenheilkd 218(1):51–54, 2001. Chandler JW, Milam DF: Diphtheria corneal ulcers. Arch Ophthalmol 96:53–56, 1978. Dittmann S, Wharton M, Vitek C, et al: Successful control of epidemic diphtheria in the states of the Former Union of Soviet Socialist Republics: lessons learned. J Infect Dis 181(Suppl 1):S10–S22, 2000. Duke-Elder S, ed: System of ophthalmology. St Louis, CV Mosby, 1976: 46. Eller JJ: Diphtheria. In: Conn HF, ed: Current therapy. 6th edn. Philadelphia, WB Saunders, 1982:15–19. Harnisch JP: Diphtheria. In: Isselbacher KJ, et al, eds: Harrison’s principles of internal medicine. 9th edn. New York, McGraw-Hill, 1980:671–675. Rogell G: Infectious and inflammatory diseases. In: Duane TD, ed: Clinical ophthalmology. Hagerstown, MD, Harper & Row, 1982:33:9–10. Top FH, Wehrle PF: Diphtheria. In: Wehrle PF, Top FH, Sr, eds: Communicable and infectious diseases. 9th edn. St Louis, CV Mosby, 1981: 197–210.
13 EPIDEMIC KERATOCONJUNCTIVITIS 077.1 Paul Jorge Botelho, MD Baltimore, Maryland John D. Gottsch, MD Baltimore, Maryland
DIAGNOSIS Clinical signs and symptoms Following a 5- to 14-day incubation period, EKC presents as acute unilateral and then bilateral (75% of cases bilateral) papillary, follicular or mixed conjunctivitis. Other signs include hyperemia, chemosis, serous discharge, subconjunctival hemorrhages and fibrin conjunctival pseudomembranes. Often patients present with foreign body sensation associated with diffuse, punctuate superficial keratitis during the fi rst week. The lesions become raised and stain with fluorescein during the second week. After 14 days, subepithelial opacities may develop in up to 50% of patients. These opacities may be associated with pain, photophobia and decreased vision. The lesions usually spontaneously resolve over several months to years and are not associated with scarring or vascularization. The conjunctivitis and viral shedding can persist for up to two weeks. The patient and the clinician must take precautions to avoid transmitting the pathogen.
Ocular and periocular manifestations ●
●
●
Preauricular adenopathy, eyelid edema and serous discharge with lid matting. Diffuse papillary or follicular conjunctivitis with hyperemia, chemosis, subconjunctival hemorrhages and membrane or pseudomembrane formation (33% of cases) (Figure 13.1). Cornea diffuse superficial punctuate keratitis within the first week, followed by focal elevated punctuate epithelial lesions that stain with fluorescein during week two and in up to 50% of patients subepithelial opacities develop after 2 weeks associated with photophobia and blurred vision.
Laboratory findings Laboratory testing for the presence of adenovirus serotypes linked to eye infections in suspected cases of EKC may assist the clinician in confirming the diagnosis and implementing measures to control nosocomial outbreaks. Cases of follicular conjunctivitis with superficial keratitis, especially when unilateral, may pose a diagnostic challenge. In the differential diag-
FIGURE 13.1 hemorrhages.
Epidemic
keratoconjunctivitis
with
conjunctival
nosis are herpes simplex virus and adult inclusion conjunctivitis from Chlamydia trachomatis serotypes D–K. ● The gold standard for confirmatory diagnosis is viral isolation on cell culture from conjunctival scrapings. Viral isolation can take 1–2 weeks for completion. Recently, a shell-vial technique employing accelerated virus isolation and identification can reduce viral isolation time to three days. Because viable viral sample from conjunctival scrapings is needed, the sensitivity of this method is reduced compared to other techniques. It remains the definitive test of serotype identification in cases associated with epidemic outbreaks. ● Direct fluorescent anibody assay (DFA) is a rapid screening technique for adenoviral detection. Vigorous swabbing of the conjunctiva is performed to obtain an adequate sample size to avoid false negatives. Expertise is required to interpret the immunofluorescent results. Other methods of adenovirus antigen include enzyme immunoassay and immunochromatography. ● Polymerase chain reaction (PCR) assay for adenoviral detection is more sensitive than antigen detection and viral isolation methods. A comparison of PCR to a commercial immunoassay (adenoclone) found the PCR assay was positive in 46 of 58 adenoclone negative cases and positive in 11 of 11 adenoclone positive, culture positive swabs. It also maintains high specificity to common adenoviral pathogens. Newly designed primers in PCR assays have improved the sensitivity for adenoviral DNA recognition allowing for detection of most adenoviral subgroups associated with eye infections. Currently, PCR assays can be performed in several hours. ● Multiplex PCR assay can simultaneous screen for the presence of known viral and chlamydial pathogens associated with follicular keratoconjunctivitis. Using a series of primers in one reaction, the sensitivity of detecting adenovirus, herpes simplex virus and Chlamydia trachomatis using the multiplex PCR assay was equal to or greater than with conventional means for each pathogen individually. The test, which can be performed in seven hours, may reduce diagnostic confusion and allow the clinician to initiate the proper treatment plan and isolation precautions promptly.
CHAPTER 13 • Epidemic Keratoconjunctivitis
Epidemic keratoconjunctivitis (EKC) is an acute, highly contagious, follicular or papillary viral conjunctivitis associated with preauricular adenopathy, conjunctival pseudomembranes and diffuse superficial keratitis. Adenovirus, the causative agent in EKC, is a double-stranded DNA viruses classified according to serotype (1 to 49) and subgenus (A to F). Certain members of adenovirus subgroup D have been reported to cause significant outbreaks of EKC (primarily serotypes 8, 19 and 37). Others adenoviral serotypes associated with keratoconjunctivitis include 2–5,7–11,14,16,21–23 and 29. Adenoviruses have also been identified in cases of pharyngoconjunctival fever and hemorrhagic conjunctivitis.
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TREATMENT ●
SECTION 1 • Infectious Diseases
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Currently there are no effective topical or systemic antivirals agents in the management of EKC. No clinical trials have documented efficacy of antivirals with regards to duration of symptoms, severity of disease, reduction of viral shedding or decreased incidence of persistent subepithelial infi ltrates. Supportive treatment including topical artificial tears four times daily, topical decongestants, topical antihistamines and cold packs can be offered. Patients with pain, photophobia and decreased vision associated with epithelial keratitis or subepithelial infi ltrates may benefit from topical corticosteroids. In chronic cases of subepithelial infi ltrates, judicious use of a mild topical corticosteroid such as fluorometholone 0.1% can improve comfort and vision. Phototherapeutic keratectomy (PTK) has been described as an alternative to topical corticosteroid use in the management of persistent nummular superficial subepithelial infi ltrates following EKC. A reduced rate of recurrent nummuli following PTK was reported in several studies. Cidofovir [(S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)ade nosine] or S-HPMPA, a broadspectrum, long-acting nucleoside analogue which inhibits viral DNA polymerase, was evaluated in vivo by Gordon et al. The authors found that pretreatment with topical 0.1% cidofovir reduced the peak viral titer when given 1 day before inoculation into New Zealand white rabbits infected with adenovirus type 5. The topical cidofovir was administered six times a day for five days. However, a rebound increase in viral titers were noted in 25% of cases. A subsequent in vivo study (same pathogen and animal model) using cidofovir 0.2% topically 6 times a day for 10 days demonstrated a decrease in viral titers and reduction in the number of days of viral shedding. Delayed onset nasolacrimal blockage was reported in this study. Clinical trials comparing topical cidofovir to placebo in cases of EKC have not been reported to date.
PREVENTION OF TRANSMISSION INCLUDING NOSOCOMIAL INFECTIONS ●
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Modes, duration and ease of transmission of adenovirus in acute cases of EKC are discussed with the patient in detail. Patients with acute EKC are excused from work or school for up to two weeks while convalescing. Of paramount importance when managing a suspected case of EKC is the implementation of a procedure policy to prevent transmission to other patients. Numerous reports of nosocomial EKC epidemics have been described, including transmission of EKC via an ophthalmologist’s hands or instruments after managing an in-office case to a neonatal intensive care unit. Patients suspected to have acute conjunctivitis should be relatively isolated from other patients. Sources of transmission during an office visit include magazines, chair rests, slit lamp patient handles and multidose bottles of topical fluorescein. Following examination of any patient with communicable conjunctivitis, thorough cleaning of all examination equipment with chloramine-T should be performed immediately. Published guidelines regarding prevention and control of EKC at teaching eye institutes concluded that the following steps may decrease cases of rate of nosocomial infections;
patient screening and isolation, handwashing, instrument disinfectants, furlough of infected employees, wearing disposable gloves for every patient, cleaning all therapeutic or diagnostic contact lenses for 30 minutes in chloramine-T, use of disposable occluders and soaking tonometers for 30 minutes in chloramine-T solution following each use.
COMMENTS Outbreaks of EKC can present a significant health risk with ocular morbitity and loss of revenue. With the aid of several new PCR based adenoviral detection assays, prompt diagnosis and management of cases of EKC may limit the transmission of this highly contagious viral pathogen.
REFERENCES Chaberny IE, Schnitzler P, Geiss HK, Wendt C: An outbreak of epidemic keratoconjunctivitis in a pediatric unit due to adenovirus type 8. Infect Control Hosp Epidemiol 24(7):514–519, 2003. Cheung D, Bremner J, Chan JTK: Epidemic keratoconjunctivitis-do outbreaks have to be an epidemic? Eye 17:356–363, 2003. Cooper RJ, Yeo AC, Bailey AS, Tullo AB: Adenovirus polymerase chain reaction assay for rapid diagnosis of conjunctivitis 40(1):90–95, 1999. Elnifro EM, Cooper RJ, Klapper PE, et al: Diagnosis of viral and chlamydial keratoconjunctivitis: which laboratory test? Br J Ophthalmol 83:622– 627, 1999. Elnifro EM, Cooper RJ, Klapper PE, et al: Multiplex polymerase chain reaction for diagnosis of viral and chlamydial keratoconjunctivitis. Invest Ophthalmol Vis Sci 41(7):1818–1822, 2000. Gordon YJ, Romanowski EG, Araullo-Cruz T: Topical HPMPC inhibits adenovirus type 5 in the New Zealand rabbit ocular replication model. Invest Ophthalmol Vis Sci 35(12):4135–4143, 1994. Gottsch JD, Froggatt JW, III, Smith DM, et al: Prevention and control of epidemic keratoconjunctivitis in a teaching hospital. Ophthalmic Epidemiol 6(1):29–39, 1999. Kaufman HE: Treatment of viral diseases of the cornea and external eye. Progress in Retinal and Eye Research 19(1):69–85, 2000. Percivalle E, Sarasini A, Torsellini M, et al: A comparison of methods for detecting adenovirus type 8 keratoconjuctivitis during a nosocomial outbreak in a neonatal intensive care unit. J Clin Virol 28:257–264, 2003. Quentin CD, Tondrow M, Vogel M: Phototherapeutic keratectomy (PTK) after epidemic keratoconjunctivitis 96(2):92–96, 1999.
14 ERYSIPELAS 035 (St. Anthony’s Fire) Richard L. Abbott, MD San Francisco, California Erysipelas is an acute, localized inflammation of the skin and subcutaneous tissue that is characterized by redness, edema and induration.
ETIOLOGY/INCIDENCE The pathogenic organisms are usually group A β-hemolytic streptococcus, although occasional group B, C and G strains
have been identified. It is a disease affecting primarily adults between 60 and 80 years old, but its incidence is increasing in younger age groups.
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Trichinosis. Angioneurotic edema.
TREATMENT COURSE/PROGNOSIS
Systemic ● ●
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Ocular ●
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DIAGNOSIS ●
Clinical signs and symptoms Ocular or periocular manifestations ●
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Conjunctiva: chemosis, exudative or membranous conjunctivitis. Cornea: superficial punctate keratitis secondary to bacterial toxins or exposure with lid ectropion (late), ulcerative keratitis. Eyelids: abscess, blepharitis, ectropion, elephantiasis, erythema, gangrene, madarosis, marked edema necrosis, trichiasis. Iris: iridocyclitis. Lacrimal system: dacryoadenitis, dacryocystitis. Orbit: abscess, cellulitis, thrombophlebitis. Vitreous or retina: chorioretinitis, metastatic vitreous abscess.
Penicillin G is the drug of choice in treating erysipelas. Treatment should be instituted promptly and continued for 10 to 14 days to prevent the possibility of systemic spread. Intravenous penicillin G should be given in a minimum divided daily dosage of 6 million units. Once there is evidence of clinical improvement, the route of administration can be changed to oral medication. Penicillin V potassium should be given daily in four divided doses of 250 mg for the duration of the 10- to 14-day therapy period. In patients sensitive to penicillin, erythromycin may be substituted. Erythromycin may be given orally at an initial dosage of 500 mg four times daily for several days and then reduced to 250 mg four times daily for 10 days. In severely ill patients, erythromycin 500 mg IV should be given twice a day for the first 2 or 3 days before oral therapy is begun.
CHAPTER 14 • Erysipelas
The site of infection is the extremities or face. The primary facial infection often is a nasopharyngitis, from which the organism is transferred to the skin through an abrasion or a minute wound. Erysipelas may begin with an abrupt onset of fever, chills, malaise and nausea. A defi nite zone of redness soon appears, with edema, tenderness and a well-defined, advancing border. In more severe cases, vesicles may form on the surface. Typically, the infection involves the lymphatic spaces and is spread through these channels to neighboring areas. Constitutional symptoms include high temperature, headache, vomiting and localized pain. Without treatment, the disease is usually selflimited and runs its course within 4 days to several weeks. As the facial lesions spread, ocular involvement often occurs, consisting of marked edema and erythema of the lids. The edema is frequently extensive enough to prevent opening of the eyes. The disease may also progress to gangrene of the eyelids. Although less common, inflammation spreads from the lids to the conjunctiva, producing chemosis and external ophthalmoplegia. Other complications include dacryoadenitis, orbital thrombophlebitis, cellulitis, abscess and cavernous sinus thrombosis. A late result in chronic infections may be a solid edema or elephantiasis of the eyelids.
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In severe cases resulting in tissue destruction and lid necrosis, meticulous cleaning and debridement of the wounds on a daily basis should be the mainstay of local therapy. The wounds are surgically debrided and cleansed with a 1:1 solution of hydrogen peroxide and sterile saline and repacked daily with iodoform gauze. The use of warm saline compresses and topical broadspectrum antibiotic ointments helps accelerate the healing process and may prevent secondary bacterial contamination. The application of topical erythromycin ointment within the cul-de-sac helps prevent the occurrence of a secondary bacterial conjunctivitis. If there is a significant degree of lid contracture in the healing process, exposure keratitis may develop. This condition is best treated initially with tear substitute and lubricating ointments. Surgical repair of a cicatricial ectropion or other lid deformities may be required. It is prudent, however, to wait a minimum of 3 to 6 months before considering surgical intervention to allow the healing process to stabilize and reduce the likelihood of an undercorrection or overcorrection.
Laboratory findings ●
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Most often, it is difficult to defi nitively identify the inciting organism. The use of blood cultures, needle aspirates, or biopsy specimens has yielded fewer than 10% positive cultures. Detection of Streptococcus spp. in skin specimens with direct immunofluorescence is helpful.
Supportive ●
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Differential diagnosis ● ● ●
Ophthalmic herpes zoster. Allergic contact dermatitis. Myosis of collagen disease.
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Attention should be given to the patient’s physical, nutritional, emotional and recreational activity needs. Hospitalization is usually indicated, with the patient on bedrest. The patient should be isolated until the fever subsides and strict hygienic measures should be used by all hospital personnel who have contact with an infected patient. Alcohol and tepid sponge baths may be used to reduce high temperature. Vital signs should be monitored regularly.
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PRECAUTIONS ●
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SECTION 1 • Infectious Diseases
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Because erysipelas usually begins abruptly and may progress rapidly, appropriate antimicrobial therapy must be instituted as soon as possible. The diagnosis may be made on the basis of the clinical presentation of the illness and intravenous penicillin G or its substitute should be started immediately. Regardless of which drug is used, it is essential that treatment in full doses be given over a period of at least 10 days because relapses are relatively common. Continuous antibiotic prophylaxis is indicated only in patients with a high recurrence rate. Cultures and sensitivities should be obtained for confi rmation of the diagnosis only if there is exudate readily available for these studies. Needle aspiration from the lids or orbit is contraindicated in patients with erysipelas because of the possibility of spread of infection and injury to other structures.
COMMENTS Although lower extremity involvement is most common, when affecting the face, the erysipelas exanthem most frequently appears in the region of the eye, with the sites of predilection being the eyelid and the inner canthus. The pathophysiology of lid necrosis seems to be related to the release of proteolytic enzymes by the streptococcal organisms, which dissolve connective tissue bridges and allow rapid spread of the bacteria. Because the skin of the lid is so thin, large amounts of fluid can accumulate, thereby raising the tissue pressure and shutting off capillary circulation. The combination of diffuse bacterial spread and diminished blood supply leads to destruction and necrosis of the lid tissue. For treatment to be effective, one must make an early diagnosis and institute maximum parenteral antibiotic therapy combined with local debridement and topical antibiotic application. It is recommended that this therapy be continued for a minimum of 10 to 14 days until all evidence of the infection has resolved. Long-term therapy consists of lid plastic surgery after all healing processes have stabilized.
REFERENCES Abbott RL, Shekter WB: Necrotizing erysipelas of eyelids. Ann Ophthalmol 11:381–384, 1979. Bratton RL, Nesse RE: St Anthony’s fi re: diagnosis and management of erysipelas. Am Fam Phys 51:401–404, 1995.
15 ESCHERICHIA COLI 008.0 Donny W. Suh, MD, FAAP West Des Moines, Iowa The genus Escherichia is named after Theodor Escherich who isolated the type species of the genus in 1885. Escherichia coli is a facultatively anaerobic gram-negative rod that is found as a normal commensal in the gastrointestinal tract, from which it may spread to infect contiguous structures when normal anatomic barriers are interrupted. This bacillus can also be found in association with other pathogenic organisms in perforated or inflamed conditions. Escherichia coli has both a fermentative and respiratory type of metabolism.
ETIOLOGY/INCIDENCE Recent estimates suggest that more than 100,000 illnesses annually are attributable to shiga-toxin-producing E. coli, up to 50% of which are strains other than O157:H7. The urinary and gastrointestinal tracts are the usual portals of entry; however, once infection has occurred in a primary focus, further spread to distant organs may occur by means of the bloodstream. Septicemia is the most serious complication of E. coli infections. It occurs frequently in immunodeficient patients, in debilitated elderly patients with diabetes mellitus, in patients with urinary tract infection or biliary or intraperitoneal sepsis and after abortions or pelvic surgery. The most important are enterotoxigenic E. coli (ETEC), a cause of travelers’ diarrhea; enteropathogenic E. coli (EPEC), a cause of childhood diarrhea; enteroinvasive E. coli (EICE), a cause of dysentery-like disease; and enterohemorrhagic E. coli (EHEC), a cause of hemorrhagic colitis and the hemolytic-uremic syndrome in children. Ocular involvement is rare and may result in a mucopurulent conjunctivitis, most often in the elderly. Metastatic endophthalmitis may occur from E. coli septicemia and the usual portal of entry is the central retinal artery. The course of the endophthalmitis is acute; necrosis of the intraocular tissues and loss of vision can occur in less than 24 hours.
DIAGNOSIS Clinical signs and symptoms Ocular or periocular manifestations ●
Chartier C, Grosshans E: Erysipelas. Intl J Dermatol 35:779–781, 1996.
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Feingold DS, Weinberg AN: Group A streptococcal infections: an old adversary reemerging with new tricks? Arch Dermatol 132:67–70, 1996.
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McHugh D, Fison PN: Ocular erysipelas. Arch Ophthalmol 110:1315, 1992.
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Ochs MW, Dolwick MF: Facial erysipelas: report of a case and review of the literature. J Oral Maxillofac Surg 49:1116–1120, 1991.
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Anterior chamber: iritis, gas bubbles, hyphema, hypopyon. Conjunctiva: chemosis, hyperemia, pseudomembranous or purulent conjunctivitis, subconjunctival hemorrhage. Cornea: edema, keratitis, corneal ulcers, corneal infi ltrates. Globe: panophthalmitis, purulent endophthalmitis. Other: increased intraocular pressure, ocular pain, anterior and/or posterior uveitis, chorioretinitis.
Ronnen M, Suster S, Satewach-Millet M, et al: Erysipelas. Changing faces. Intl J Dermatol 24:169, 1986. Scott PM, Bloome MA: Lid necrosis secondary to streptococcal periorbital cellulitis. Ann Ophthalmol 13:461–465, 1981.
TREATMENT Systemic The choice of an appropriate antimicrobial agent in E. coli infections depends on the site and type of infection, as well as its severity. A number of antibiotics are effective against the
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Ocular In E. coli conjunctivitis, topical ciprofloxacin, ofloxacin, gatifloxacin, levofloxacin, moxifloxacin, or 0.3% tobramycin ophthalmic solutions are applied topically approximately six to eight times daily until the infection appears to be resolved. For a severe case, a more aggressive dose should be given during the first 24 to 48 hours in about 12 to 24 doses daily. For example, loads of three every 2 hours (drop at 8:00 a.m., 8:05 a.m. and 8:10 a.m.; then 10:00 a.m., 10:05 a.m. and 10:10 a.m.; and so on) for a total of 24 installations daily. Use of the concept of loading with well-tolerated topical antibiotics enhances compliance and optimizes effective microbial killing. Early systemic and local antibiotic therapy is essential for E. coli endophthalmitis. Blanket local antibiotic therapy should consist of 20 mg of subconjunctival gentamicin or tobramycin. Also, for topical treatment 0.3% tobramycin ophthalmic solution or 3rd and 4th generation quinolones, such as gatifloxacin, levofloxacin and moxifloxacin, 12 to 24 doses daily, may be added. In most cases of E. coli endophthalmitis, intravitreal injection of gentamicin or tobramycin 100 to 300 μg can be used. Amikacin can also be used at 400 μg. Intravitreal injection consists of a total of 0.1 mL. Systemic or local corticosteroids administered in combination with antibiotics may reduce the massive inflammatory response of the eye, which often is as destructive as the infection. Their use should be considered when highly effective
antibiotics are being used at optimal dosing and there is a need to control the retinitis occurring. Secondary involvement of the uveal tract may necessitate the use of a cycloplegic/mydriatic. Scopolamine 0.25% drops may be applied topically twice daily to aid in the relief of uveitis.
Supportive Hospitalization is necessary for E. coli endophthalmitis infection.
PRECAUTIONS The serum levels of aminoglycosides should be monitored to gauge therapeutic levels and to avoid toxicity because the ratio of therapeutic dose to toxic dose is very narrow. Ototoxicity and nephrotoxicity may occur even when serum levels have been appropriately monitored, so the risks should be weighed. The concurrent and/or sequential systemic use of potentially neurotoxic or nephrotoxic drugs should be avoided. Isolation and antimicrobial therapy of contacts are essential to abort epidemic infantile diarrhea. Many E. coli infections are hospital acquired, so strict hygienic measures are essential.
CHAPTER 15 • Escherichia Coli
bacillus, but no particular drug is uniformly active against all strains of E. coli, so sensitivity testing should guide the choice of antibiotics. Antimicrobial resistance occurs through plasmidmediated determinants, several of which can be found in the same plasmid. These multiresistent plasmids can be transferred by conjugation. For less severe E. coli infections, the initial treatment of choice may be ampicillin 2 to 4 g/day IM or IV. One may also consider other penicillins with β-lactamase inhibitor, cephalosporins, nitrofurantoin and trimethoprim-sulfamethoxazole. For more severe infections, the dose of ampicillin/sulbactam could be 3 g every 6 hours IV. One may also consider imipenem cilastatin, ciprofloxacin IV or cefotaxime. Aminoglycoside antibiotics are most commonly used against coliform bacillary infections, including E. coli; they include kanamycin, gentamicin, amikacin and tobramycin. Kanamycin is generally indicated for the initial treatment of serious E. coli infections. Severe urinary tract infections that seem to be resistant to other antimicrobial agents have responded to daily doses of kanamycin 15 mg/kg IM in divided doses every 6 to 8 hours. Alternative treatment may be a total daily dose of parenteral gentamycin 3 to 5 mg/kg administered in divided doses every 8 hours. In severe infections that appear to be resistant to kanamycin and gentamicin, amikacin is indicated. Amikacin is given in daily doses of 15 mg/kg in two or three equally divided doses. In severe cases of sepsis, a combination of antibiotics is given, which includes ampicillin and an aminoglycoside, the choice of which is based on knowledge of local susceptibility patterns. Ampicillin-sulbactam or cefatazime (a potent third-generation cephalosporin) is a suitable alternative, especially if an aminoglycoside-resistant nosocomial organism is suspected. Neomycin appears to be most effective against E. coli gastroenteritis. An oral daily dose of 25 mg/kg is usually indicated for 1 or 2 days.
COMMENTS E. coli is rarely found in the normal flora of the conjunctiva. It is most commonly seen as a source of infection in ophthalmia neonatorum. E. coli endophthalmitis is a rare complication of E. coli septicemia. It has a poor prognosis and early diagnosis and treatment are essential if useful vision is to be retained.
REFERENCES Aronson SB, Elliott JH: Ocular infl ammations. St Louis, CV Mosby, 1972: 103–105, 112–114, 228–230. Balestrazzi A, Blasi MA, Primitivo S, Balestrazzi: Escherichia coli endophthalmitis after trans-scleral resection of uveal melanoma. Eur J Ophthalmol 12(5):437–439, 2002. Barnett BJ, Stephens DS: Urinary tract infection: an overview. Am J Med Sci 314(4):245–249, 1997. Bonadio WA, Smith DS, Madagame E, et al: Escherichia coli bacteremia in children: A review of 91 cases in 10 years. Am J Dis Child 145:671–674, 1991. D’Amico DJ, Caspers-Velu L, Libert J, et al: Comparative toxicity of intravitreal aminoglycoside antibiotics. Am J Ophthalmol 100:264, 1985. Eisenstein BI: Escherichia coli infections. In: Isselbacher KJ, Braunwald E, Wilson JD, et al, eds: Harrison’s principles of internal medicine. 13th edn. New York, McGraw-Hill, 1994:661–663. Endophthalmitis Vitrectomy Study Group: Results of the endophthalmitis vitrectomy study: a randomized trial of immediate vitrectomy and of intravenous antibiotics for the treatment of postoperative bacterial endophthalmitis. Arch Ophthalmol 113:1479, 1995. Glasser DB, Baum J: Antibacterial agents. In: Tabbara K, Hyndiuk RA, eds: Infections of the eye. Little, Brown, Boston, 1996:207–230. Hyndiuk RA, Cokington CD: Bacterial keratitis. In: Tabbara K, Hyndiuk R, eds: Infections of the eye: diagnosis and management. Little, Brown, Boston, 1996:323–347. Shammas HF: Endogenous E. coli endophthalmitis. Surv Ophthalmol 21:429–435, 1977. Turck M, Schaberg D: Infections due to enterobacteriaceae. In: Isselbacher KJ, Adams RD, Braunwald E, eds: Harrison’s principles of internal medicine. 9th edn. New York, McGraw-Hill, 1980:629–634.
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16 GONOCOCCAL OCULAR DISEASE 098.4 Carlos M. Isada, MD Cleveland, Ohio David M. Meisler, MD, FACS Cleveland, Ohio SECTION 1 • Infectious Diseases
Gonorrhea is one of the oldest described diseases of humans and it remains one of the most common sexually transmitted diseases, with an estimated 800,000 new cases occurring in the United States annually. It is an infection that primarily involves mucosal surfaces, particularly columnar or cuboidal epithelium. Gonorrhea presents most commonly with involvement of the genital tract (urethra, cervix), anorectal region and pharynx. Disseminated gonococcal infection can also occur in both the neonate and the adult; this condition is characterized by a petechial rash, arthralgias, fever, or septic arthritis. This is caused by bacteremia from strains of Neisseria gonorrhoeae that produce minimal or no genital inflammation. Gonococcal ocular infection is a condition described since antiquity. It can affect newborns who are infected at the time of delivery, children and adolescents who are the victims of sexual abuse and sexually active adults who become infected through hand-eye inoculation. Gonococcal conjunctivitis is considered a medically urgent condition because of the potential of the organism to penetrate the intact cornea and progress rapidly to cause corneal ulceration and permanent vision loss.
ETIOLOGY/INCIDENCE The causative organism is N. gonorrhoeae, an oxidase- and catalase-postive, gram-negative diplococcus. In clinical specimens containing purulent secretions, the organism may be seen as intracellular bean-shaped bacteria within polymorphonuclear leukocytes or closely associated with leukocytes. Several other organisms can appear identical to N. gonorrhoeae on Gram’s stain, such as N. meningitidis and other nonpathogenic Neisseria spp. Structurally, the organism has an envelope (similar to other gram-negative bacteria) and pili, which mediate attachment to mucosal surfaces. Many strains carry plasmids that produce a β-lactamase enzyme that confers resistance to penicillin, termed a TEM-1 penicillinase. Tetracycline resistance is also plasmid mediated and these resistanceconferring plasmids are easily transferred to other gonococci. Antibiotic resistance can also occur via several chromosomal mutations, which tend to decrease the permeability of the outer membrane to β-lactam antibiotics and alter penicillin-binding proteins. Humans are the only natural reservoir for N. gonorrhoeae and transmission occurs primarily via sexual contact with the reservoir in asymptomatically infected persons. The disease is most common in individuals 20 to 24 years old.
ADULT GONOCOCCAL CONJUNCTIVITIS Although gonorrhea remains a common sexually transmitted disease, ocular involvement remains relatively infrequent. Nationwide statistics for the incidence of adult gonococcal conjunctivitis (AGC) are not kept specifically, but in some large series of patients with adult conjunctivitis, AGC occurs
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in fewer than 1% of cases. In the adult, gonococcal conjunctivitis is most commonly acquired after direct or manual contact with infected genital secretions or urine. The incubation period is usually less than one week from a potential exposure, but may be up to 3 weeks. Urethral symptoms (when present) usually precede ocular symptoms by 1 or more weeks, but notably, patients may never develop urethral symptoms. The prevalence of asymptomatic ocular colonization with N. gonorrhoeae in adults who have urogenital gonorrhea is unknown. Rare cases have been reported after the instillation of urine eyedrops as part of a folk remedy and after accidental laboratory inoculation. Because N. gonorrhoeae is capable of surviving outside the body for limited periods of time, the possibility of fomite transmission has been raised but likely is insignificant compared with hand-eye transmission.
PEDIATRIC AND ADOLESCENT GONOCOCCAL OCULAR DISEASE Although uncommon, the finding of gonococcal conjunctivitis in children after the neonatal period is strongly associated with sexual abuse or assault. AGC may be due to either sexual abuse or early sexual activity, with the same considerations as for the adult. In the limited number of cases described, the clinical course in this age group appears to be similar to that of adults.
GONOCOCCAL OPHTHALMIA NEONATORUM Gonococcal ophthalmia neonatorum (GON) has been described in the medical literature since antiquity. Neonatal conjunctivitis is the most common ocular disease of newborns, occurring in 1.6% to 12% of births. The epidemiology of this syndrome has changed dramatically after the introduction of the use of a 2% silver nitrate solution for the prophylaxis of ophthalmia neonatorum. In later years, the widespread use of prenatal screening helped decrease the incidence of GON from 10% to less than 1% in industrial countries. This has led some countries, such as the United Kingdom, to discontinue prophylaxis for ophthalmia neonatorum. Sweden likewise discontinued prophylaxis but still requires its use in neonates born to mothers who do not receive comprehensive prenatal care. In the United States, C. trachomatis is the most common cause of ophthalmia neonatorum, mirroring the increase in this organism as the leading sexually transmitted disease worldwide. The incidence of ophthalmia neonatorum in the United States secondary to C. trachomatis is about 8.2 in 1000 live births compared with 0.3 in 1000 live births secondary to N. gonorrhoeae. In other parts of the world, such as Africa, GON remains a serious concern due to the frequency of maternal gonococcal infection and the lack of systematic ocular prophylaxis. In some areas of Africa, the prevalence has been as high as 30 to 40 in 1000 live births. GON is almost always acquired via direct inoculation of the eyes during passage through an infected birth canal. The incubation period in neonates is generally 1 to 3 days. Occasional cases of delayed GON have been reported up to 19 days after delivery.
COURSE/PROGNOSIS
DIAGNOSIS Clinical signs and symptoms Adult gonococcal conjunctivitis AGC is characterized by profuse purulent discharge, severe conjunctival injection and marked edema and hyperemia of the eyelids. Early in the course, AGC is limited to the mucosal surfaces. Rare cases of asymptomatic AGC have been described, but the prevalence of asymptomatic or minimally symptomatic gonococcal conjunctival infection is unknown. Some cases may be complicated by extension to the corneal epithelium, leading to varying degrees of chemosis and stromal or epithelial keratitis. The degree of corneal involvement varies considerably, but when it does occur fi ndings commonly include subepithelial or stromal infi ltrates and marginal corneal melt. N. gonorrhoeae is one of the few organisms that can penetrate intact corneal epithelium. If treatment is delayed, there may be rapid progression to ulcerative keratitis and perforation. This observation of a potentially fulminant course led the Centers for Disease Control and Prevention (CDC) in 1986 to recommend immediate hospitalization and intravenous antibiotics for 5 days. This approach has since been liberalized, but the potential for fulminant disease remains well recognized and is an important aspect of management.
Gonoccocal ophthalmia neonatorum The clinical presentation of GON is similar to that of the AGC, as described, with copious purulent conjunctival discharge, hyperemia and edema. GON is considered a medical emergency because untreated cases commonly progress rapidly to corneal penetration and perforation of the globe, at times within 24 hours. Other localized manifestations of N. gonorrhoeae infection also may occur, including anorectal disease and rhinitis. Disseminated gonococcal infection can occur with neonatal infectious arthritis and meningitis. Neonates may acquire N. gonorrhoeae in utero if an infected mother develops premature rupture of membranes. This may result in a syndrome characterized by chorioamnionitis, meningitis, septicemia and pneumonia; N. gonorrhoeae can be recovered from orogastric aspirates of the neonate. Infants delivered by cesarean section
Differential diagnosis The differential diagnosis of ophthalmia neonatorum is wide and includes chemical conjunctivitis, bacterial infection (Moraxella catarrhalis, Staphylococcus aureus, Haemophilus spp., Streptococcus pneumoniae, Pseudomonas aeruginosa, enterococci and N. gonorrhoeae), Chlamydia trachomatis and herpes simplex virus. In the late 1800s, N. gonorrhoeae was the major cause of ophthalmia neonatorum, occurring in 10% of children in Europe with GON.
Laboratory findings The diagnosis of gonococcal ocular disease should be suspected in all newborns who present several days after delivery with conjunctivitis, particularly if any of the following risk factors are present: ● The mother lacked routine prenatal care. ● The mother has a history of sexually transmitted disease or substance abuse. ● The infant did not receive ophthalmia prophylaxis. Definitive diagnosis of GON cannot be made on clinical grounds alone and requires laboratory confi rmation. Evaluation for other causes of ophthalmia neonatorum is imperative, particularly detection of C. trachomatis. Chlamydia ophthalmia can be diagnosed by both specific tissue culture tests and nonculture tests such as immunoassays, nucleic acid amplification tests and direct fluorescent antibody tests. Gonococcal ocular disease in the adult is much more difficult to recognize because of its rare occurrence. The findings of copious purulent conjunctivitis with or without corneal involvement should suggest the diagnosis; a positive history of current urethral or urinary symptoms in the patient (or partner) is very helpful, but its absence does not exclude N. gonorrhoeae infection. A Gram’s stain smear is essential for the rapid diagnosis of N. gonorrhoeae. A ‘positive’ Gram’s stain is defi ned by the finding of typical gram-negative diplococci within polymorphonuclear leukocytes in conjunctival exudates. Many clinicians consider a positive Gram’s stain in the appropriate clinical setting to be compelling evidence for the presence of N. gonorrhoeae, even if a subsequent culture is negative. A Gram’s stain is considered ‘negative’ if no organisms are seen on oil immersion field, even in the presence of many neutrophils. An ‘equivocal’ Gram’s stain is characterized by (1) typical gram-negative diplococci that are found on the smear but are not cell associated or (2) atypical organisms that are neutrophil associated. The sensitivity of the Gram’s stain for detecting N. gonorrhoeae varies depending on the anatomic site, with a sensitivity of 95% to 100% from the male urethra (symptomatic) to 40% to 50% from the rectum. Limited data are available concerning the sensitivity of the Gram’s stain in gonococcal ocular disease, but it probably is high (more than 90% in one study). The specificity also is likely to be high, but occasionally Neisseria spp. other than N. gonorrhoeae can be detected. A positive or equivocal Gram’s stain of conjunctival exudate from a newborn is sufficient laboratory evidence to begin appropriate therapy. Treatment may be initiated in the newborn with conjunctivitis and a negative Gram’s stain if there is a high index of suspicion for gonococcal ocular disease based on the risk factors cited. The definitive diagnosis of N. gonorrhoeae infection rests on laboratory confirmation of the organism. Isolation of the gonococcus in culture remains the gold standard and specimens
CHAPTER 16 • Gonococcal Ocular Disease
In the largest reported series of AGC, 21 cases of cultureconfirmed N. gonorrhoeae conjunctivitis were retrospectively analyzed. Most patients were between 20 and 26 years old, a distribution similar to that of other gonococcal infections. The median time between the onset of conjunctivitis and presentation to the physician was 4 days. The majority of patients denied exposure to N. gonorrhoeae from their partners or active genital infection themselves. However, 57% of patients were found to have concurrent urethritis on testing. Bilateral eye involvement was noted in 38%, with visual acuity of 20/40 in more than 50% at initial presentation. In nearly all patients, the degree of conjunctivitis on presentation was severe, with copious purulent drainage; only one patient presented with a mild conjunctivitis. Three patients also had superficial ulceration and two had perforating ulcerative keratitis on presentation. After antibiotic therapy, more than 90% of the involved eyes had a visual acuity of 20/50 or better. No patients progressed to ulcerative keratitis after therapy was initiated. The two individuals who presented with perforating ulcerative keratitis did poorly and remained with only light perception acuity after antibiotics and keratoplasty.
also have been reported to have GON from in utero infection.
31
SECTION 1 • Infectious Diseases
should routinely be submitted for culture and antimicrobial susceptibility testing. Newer methods for the diagnosis of N. gonorrhoeae are increasingly popular and include nucleic acid probe technology and nucleic acid amplification techniques such as polymerase chain reaction (PCR). N. gonorrhoeae is a fastidious organism and requires specific culture techniques. Optimal isolation in culture requires a selective medium such as a chocolate agar, which contains antibiotics and incubation in 5% CO2. Several such media are effective, including Thayer–Martin medium (chocolate agar with vancomycin, colistin and nystatin), modified Thayer–Martin medium (trimethoprim, vancomycin, colistin and nystatin) and Martin– Lewis medium. Ideally, specimens should be inoculated onto appropriate chocolate agar as soon as possible because the organisms do not survive drying. Plates can be held at room temperature in candle extinction jars for several hours before incubation in CO2 at 35º to 37ºC. With proper collection and handling, growth of the organism can be seen within 24 to 48 hours. Alternatively, several commercially available transport systems can be used in settings in which immediate inoculation of media is not feasible. These systems preserve the viability of most of the organisms for a short period of time before plating onto selective media; if such a system is used, the specimen should be transported promptly to the laboratory. In some laboratories, nonculture techniques such as PCR, probes and enzyme immunoassays are being used routinely for the detection of N. gonorrhoeae from genital sites. The relative merits of these newer assays compared with traditional culture techniques are matters of some debate, particularly for nongenital specimens. These assays have not been formally studied (or approved) for the detection of N. gonorrhoeae from conjunctival exudates or scrapings and are not legally acceptable in suspected cases of child abuse. The optimal management of gonococcal eye infections requires isolation of the organism in traditional culture.
patients responded clinically with a significant decrease in the ocular discharge within 12 hours. There also was evidence of rapid microbiologic resolution, with all conjunctival scrapings taken at 6 hours negative in culture for N. gonorrhoeae. Based on this and other studies, the CDC in 2002 recommended that uncomplicated AGC should be treated with 1 g ceftriaxone IM in a single dose, with a single lavage of the infected eye with a saline solution. There are no consensus recommendations for individuals with more serious corneal ulcerations; such patients should be hospitalized immediately and treated with extended courses of ceftriaxone on an individual basis. Limited data are available regarding the use of fluoroquinolones in the treatment of AGC. In one study, oral norfloxacin was administered to 15 patients with culture-proved gonococcal conjunctivitis. Seven patients received 1200 mg norfloxacin PO for 3 days and eight patients received a single dose of 1200 mg. There was no progression of the corneal lesions during treatment and no significant toxicity was reported. Although quinolones are fi rst-line agents for uncomplicated gonococcal infections of the urethra, cervix, rectum and pharynx, the CDC has not recommended the use of fluoroquinolones in AGC (as of 2005). In addition, there has been an increase of fluoroquinolones-resistant N. gonorrhoeae in Southeast Asia, areas in the Pacific, Hawaii, California; this has led the CDC in 2002 to advise against empiric quinolone use for the empiric treatment of genital N. gonorrhoeae in these areas. In 2004 a similar recommendation was made by the CDC to avoid the empiric treatment of genital gonorrhea infection with quinolones in men who have sex with men because of an increase in quinolone-resistant N. gonorrhoeae in this group in the US. In 2003, the World Health Organization (WHO) recommended the following as first-line regimens for AGC: ● Ceftriaxone, 125 mg IM, as a single dose; or ● Spectinomycin, 2 g IM, as a single dose; or ● Ciprofloxacin, 500 mg PO, as a single dose.
TREATMENT The treatment of AGC has evolved due to the emergence of strains that are resistant to penicillin by plasmid-mediated βlactamase production, along with strains resistant to tetracyclines and some cephalosporins. Penicillinase-producing and non-penicillinase-producing strains of N. gonorrhoeae can cause AGC. Ceftriaxone is a parenteral third-generation cephaloporin recommended for the first-line treatment of more common manifestations of gonococcal infection, such as genital infection, pharyngitis and anorectal infection. This agent has the longest half-life of all of the available cephalosporins and is chemically stable in the presence of the β-lactamases produced by N. gonorrhoeae. The prolonged half-life results in sustained bactericidal levels of drug in the conjunctival sac.
ADULT GONOCOCCAL CONJUNCTIVITIS Only a limited number of studies have examined the efficacy of ceftriaxone in AGC. In the largest series reported, 12 adults with culture-proved gonococcal conjunctivitis were treated in an unblinded fashion with 1 g of ceftriaxone IM along with a single ocular saline lavage. The mean patient age was 26 years old. Symptoms consistent with urethritis were present in 69%. Corneal epithelial erosions were present on initial examination in 31%, but none had infi ltration of the corneal stroma. All
32
In areas of the world where these antimicrobials are not available, an alternative regimen is kanamycin 2 g IM, as a single dose. The WHO also noted that these regimens were likely to be effective, although there was no specific published data to support their use in AGC. Adults with gonococcal conjunctivitis require examination and testing for other sexually transmitted diseases, particularly Chlamydia trachomatis. Available studies suggest a significant coinfection rate with syphilis and a nontreponemal serologic test for syphilis should be considered, such as the rapid plasma reagin (RPR). Patients with AGC should also be told to refer their sex partner or partners for evaluation and treatment. There are no published series of gonococcal conjunctivitis in persons infected with human immunodeficiency virus (HIV). The CDC has recommended that HIV-infected persons with gonococcal infections of the cervix, urethra, rectum and pharynx be treated with the same regimens used for those who are negative for HIV. Individuals with AGC of unknown HIV status should be offered HIV testing.
PEDIATRIC AND ADOLESCENT GONOCOCCAL OCULAR DISEASE There are no published studies regarding the optimal treatment regimen in this age group. Gonococcal infections in children
GONOCOCCAL OPHTHALMIA NEONATORUM Optimal therapy for GON has similarly changed due to the increasing incidence of β-lactamase-producing gonococci. Previous recommendations by the CDC supported the use of aqueous crystalline penicillin G parenterally for non-β-lactamase-producing strains. However, penicillin has since been abandoned as first-line therapy for GON, given the prevalence of penicillinase-producing N. gonorrhoeae of more than 60% in some areas and the widespread development of chromosomally mediated resistance to penicillin in many strains of N. gonorrhoeae that do not produce β-lactamase. In a randomized clinical trial, 105 newborns in Kenya with GON were randomized to one of three regimens: ● A single dose of 125 mg ceftriaxone IM; ● A single dose of 75 mg kanamycin IM and 1% gentamicin ointment instilled in the eye q.i.d. for 7 days; ● A single dose of 75 mg kanamycin IM plus 1% tetracycline ointment in the eyes q.i.d. for 7 days. All newborns who received ceftriaxone were clinically and microbiologically cured. One of 26 neonates receiving the kanamycin plus tetracycline ointment had persistent conjunctivitis and 2 of 24 neonates receiving kanamycin and gentamicin ointment were treatment failures. Ceftriaxone also was effective in eradicating extraocular N. gonorrhoeae. In 2002, the CDC recommended GON treatment of 25 to 50 mg/kg ceftriaxone IV or IM in a single dose, not to exceed 125 mg. Topical therapy alone is not recommended and is considered unnecessary if systemic therapy is used. The World Health Organization also recommends ceftriaxone as the agent of choice; in areas of the world where ceftriaxone is not available alternatives include kanamycin 25 mg/kg IM as a single dose, to a maximum of 75 mg, or spectinomycin 25 mg/kgy IM as a single dose to a maximum of 75 mg. Ceftriaxone should be used with caution in infants with hyperbilirubinemia, especially those born prematurely, due to the liver metabolism of ceftriaxone. The CDC recommends hospitalization for infants with GON and careful observation for signs of disseminated infection such as meningitis and pneumonia. A single dose of ceftriaxone is likely curative for GON, although some clinicians prefer to continue daily dosing until cultures are negative at 2 to 3 days. Treatment failures with ceftriaxone may be due to simultaneous infection with C. trachomatis, which is intrinsically resistant to cephalosporins. It is important to test initially for
C. trachomatis at the same time as for N. gonorrhoeae because the former is more common and the clinical presentations may be indistinguishable. Both culture and nonculture tests are available for the diagnosis of C. trachomatis; nonculture tests include direct fluorescent antibodies, enzyme immunoassays and nucleic acid amplification tests. For testing of C. trachomatis, the specimen should contain conjunctival cells and not only exudates. Ophthalmia neonatorum caused by C. trachomatis should be treated with 50 mg/kg/day erythromycin base or ethylsuccinate orally divided into four doses daily for 14 days. The mothers of infants with GON should be tested for other sexually transmitted diseases and treated with standard regimens for gonococcal infections in the adult; current recommendations for uncomplicated infections of the cervix, urethra and rectum include one of the following: ● Cefi xime 400 mg PO in a single dose (limited availability); ● Ceftriaxone 125 mg IM in a single dose; ● Ciprofloxacin 500 mg PO in a single dose; ● Ofloxacin 400 mg PO in a single dose. Each of the regimens should include simultaneous treatment for C. trachomatis such as 1 g azithromycin PO in a single dose or 100 mg doxycycline PO b.i.d. for 7 days. The sex partners of mothers of infants with GON should be referred for evaluation.
CHAPTER 16 • Gonococcal Ocular Disease
involving more common sites such as the urethra, pharynx and rectum are treated with the same regimen recommended for adults (1 g ceftriaxone IM as a single dose) if the child weighs more than 45 kg or 125 mg ceftriaxone IM as a single dose if the child weighs less than 45 kg. This regimen should be adequate for uncomplicated ocular disease as well. Quinolones (ciprofloxacin, ofloxacin, levofloxacin and others) have previously been avoided in children based on toxicity data to articular damage in animal studies. In 2002, the CDC noted that there was no data showing this articular damage occurred in children; treatment of gonococcal infections in children 100) punctate gray-white cortical opacities. Located outside the nucleus. Wedge-shaped aggregates. Seen in increasing numbers with increasing age. Also seen in the general population, but with less numerous opacities.
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●
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Cataract extraction if indicated and as early as possible. Appropriate aphakic prescription (glasses, contact lenses or intraocular lenses). Monitor and appropriate treatment of glaucoma as indicated, medical or surgical. Appropriate amblyopia treatment. Monitor for potential strabismus. Minimize corneal epithelial trauma.
Subcapsular cataract, usually posterior ●
Increases in size and density with age.
Renal ●
Laboratory findings
●
Urinalysis
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● ●
● ●
Aminoaciduria, proteinuria, calciuria and phosphaturia. Urine ph is usually between 6.0 and 7.5 with bicarbonate loss evident in the urine with proximal renal tubular acidosis. Low urine osmolality and elevated 24 hour volumes. Elevated retinal binding protein (RBP) and n-acetylglucosaminidase (NAG) (both are sensitive markers of proximal tubular integrity).
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General ● ●
Serum ● ●
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●
Elevated acid phosphatase. Elevation of aspartate aminotransferase (AST), lactate dehydrogenase (LDH), creatine phosphokinase (CPK) and glutamic oxaloacetic transaminase (SGOT). Elevated total cholesterol (increased HDL) with normal serum triglycerides. Elevated a-2 band on serum protein electrophoresis.
Consistent periodic monitoring for renal complications. Alkalizing agents to manage metabolic acidosis. Citrates (sodium and/or potassium citrate). Oral phosphate and vitamin D (for rickets). Replacement of fluids, if polyuria. Calcium supplementation, as indicated. Carnitine may be indicated if abnormally low blood levels.
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Anticonvulsants in patients with seizures. Speech or physical therapy or both, as indicated by developmental delay. Behavioral modification as needed, especially for maladaptive behaviors. Feeding therapy, particularly with severe hypotonia.
Genetic counseling ●
Thirty percent of affected males have de novo mutations.
X-linked recessive.
Imaging studies ●
● ●
124
Brain MRI: Mild ventriculomegaly is evident in about one third of cases. White matter changes in the periventricular region. The increased signal intense areas may correspond to cysts with as yet no known clinical significance. Ocular ultrasound. If no view posteriorly, secondary to cataract, need to assess status of posterior segment R/O mass or RD.
COMMENTS Appropriate and prompt diagnosis is imperative in conjunction with the initiation of proper treatment. OCRL heterozygotes must be identified. Lenticular changes may be identified by means of dilatation and slit-lamp examination.
Support group Lowe Syndrome Association 222 Lincoln Street West Lafayette, IN 47906 (317) 743–3634
REFERENCES
Lavin CW, McKeown CA: The oculocerebrorenal syndrome of Lowe. Int Ophthalmol Clin 33:179–191, 1993. Lin T, Lewis RA, Nussbaum RL: Molecular confi rmation of carriers for Lowe Syndrome. Ophthalmol 106(1):119–122, 1999. Lowe CU, Terrey M, MacLachan EA: Organic aciduria, decreased renal ammonia production, hydrophthalmos, and mental retardation: a clinical entity. Am J Dis Child 83:164–184, 1952. Lowe M: Structure and function of the Lowe syndrome protein OCRL1. Traffic 6:711–719, 2005. Nussbaum RL, Orrison BM, Janne PA, et al: Physical mapping and genomic structure of the Lowe syndrome gene OCRL 1. Hum Genet 99:145–150, 1997. Tripathi RC, Cibis GW, Tripathi BJ: Pathogenesis of cataracts in patients with Lowe’s syndrome. Ophthalmol 93:1046–1051, 1986.
DIAGNOSIS
Walton DS, Katsavounidou G, Lowe CU: Glaucoma with the oculocerebrorenal syndrome of Lowe J Glaucoma 14(3):181–185, 2005.
Laboratory findings
CHAPTER 68 • Tyrosinemia II
Kruger SJ, Wilson ME, Jr, Hutchinson AK, et al: Cataracts and glaucoma in patients with oculocerebrorenal syndrome. Arch Ophthalmol 121(9):1234–1237, 2003.
the disease progresses, corneal ulceration, subepithelial and stromal scarring and corneal neovascularization may occur with resultant visual loss. Cataracts and glaucoma have also been described in untreated patients. Nystagmus and exotropia have been noted in some patients with tyrosinemia II; these may be a consequence of visual loss rather than a primary effect of the disease. Cutaneous lesions typically occur with or after the eye lesions. They begin as blisters or erosions on the palms and soles, particularly on the tips of the digits and the thenar and hypothenar eminences. The blisters crust and eventually become hyperkeratotic. The lesions are painful but not pruritic and often present in a linear distribution. The severity of cutaneous involvement may wax and wane independently of systemic or topical therapy. Some authors have described symptomatic improvement in ocular and cutaneous symptoms during the summer months. Mental retardation, learning disability, behavioral anomalies, microcephaly, growth retardation, and seizures have been noted in some patients with tyrosinemia II, but are, at best, inconsistent findings.
Serum ●
Tyrosinemia is diagnostic. Plasma tyrosine ranges from 16 to 62 mg/dL (normal, 0.6 to 2.1 mg/dL).
Urine
68 TYROSINEMIA II 270.2 (Pseudodendritic Keratitis, Recessive Keratosis Palmoplantaris, Richner– Hanhart Syndrome)
● ● ●
Liver biopsy ●
Stephen P. Christiansen, MD Minneapolis, Minnesota
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Herpes simplex keratitis: bilateral presentation, minimal staining with fluorescein or rose bengal, negative viral studies, normal corneal sensation and lack of response to topical antiviral therapy allow one to rule out a herpetic etiology.
TREATMENT Systemic ●
COURSE/PROGNOSIS Tyrosine crystallizes within cells, initiating an inflammatory cascade. Ocular involvement is usually heralded by pain, photophobia, tearing and conjunctival injection. The keratitis has been described as stellate or branching and is initially restricted to the epithelium. Most patients develop bilateral pseudodendritic keratitis early within the fi rst year of life. Onset is variable, however, and ranges from 2 weeks of age to late in the second decade. Some patients never develop ocular fi ndings. As
Decreased cTAT activity.
Differential diagnosis
ETIOLOGY/INCIDENCE Tyrosinemia II is a rare autosomal recessive metabolic disorder characterized by herpetiform corneal ulcers and painful keratoses of the hands and feet. It is caused by deficiency of hepatic cytoplasmic tyrosine aminotransferase (cTAT). The gene for this enzyme has been mapped to chromosome 16q 22.1–q22.3. Hepatic mitochondrial TAT levels are normal. Cytoplasmic TAT catalyzes the conversion of tyrosine to p-hydroxyphenylpyruvic acid. Deficiency of c-TAT results in elevated plasma tyrosine concentration, tyrosinuria, and tyrosyluria.
Tyrosinuria and tyrosyluria. Elevated tyrosine metabolites. No other amino acids elevated.
Dietary restriction of tyrosine and phenylalanine intake. This diet may be initiated with a prepared formula, such as the Mead Johnson 3200 AB diet. As plasma tyrosine levels decrease, the diet may be liberalized, with the goal of therapy being to maintain plasma tyrosine in the range of 10 mg/dL. Reduction of plasma tyrosine results in fairly rapid resolution of both ocular and cutaneous lesions, both of which will recur if an unrestricted diet is resumed. The effect of dietary control on the occurrence of mental retardation in tyrosinemia II is unknown.
Ocular ●
Symptomatic: the early ocular manifestations of tyrosinemia II respond rapidly to dietary therapy. Therefore, initial ocular therapy is usually symptomatic. Topical cortisteroid, antiviral, and antibiotic therapy have all been shown to be ineffective.
125
Medical ●
Oral retinoids have been used to control cutaneous lesions even when dietary compliance is poor. No other systemic or topical treatments have proven effective to date, including steroids.
Surgical ●
SECTION 4 • Diorders of Protein Metabolism
126
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Lamellar or penetrating keratoplasty may be necessary if corneal scarring or neovascularization has affected the visual axis. However, failure to address the underlying metabolic defect will promote recurrence of keratitis in the graft. Excimer laser photokeratectomy may be useful in this disorder if corneal scarring and neovascularization are superficial.
COMMENTS Patients with tyrosinemia II may fi rst present with ocular symptoms and signs. Thus, it is imperative that the ophthalmologist consider this metabolic cause of keratitis during this initial evaluation. Clinical suspicion of this disorder can be easily confirmed with amino acid studies. Early diagnosis and dietary intervention may ultimately prevent visual loss. Tyrosinemia II is distinct from tyrosinemia I, another recessive disorder caused by a deficiency of fumarylacetoacetate hydrolase. Patients with tyrosinemia I also have elevated levels
of tyrosine and its metabolites. However, these patients do not have the cutaneous or ocular findings of patients with tyrosinemia II. Rather, they characteristically have hepatic and renal dysfunction and failure.
SUPPORT GROUPS National Coalition for PKU & Allied Disorders, P.O. Box 1244, Mansfield, MA 02048 www.pku-allieddisorders.org Contact Person: Trish Mullaley, Phone: (877) 996-2723, E-mail:
[email protected] REFERENCES Scott CR: The genetic tyrosinemias. Am J Med Genet, Part C, Semin Med Genet 142C:121–126, 2006. Heidemann DG, Dunn SP, Bawle EV, et al: Early diagnosis of tyrosinemia type II. Am J Ophthalmol 107:559–560, 1989. Macsai MS, Schwartz TL, Hinkle D, et al: Tyrosinemia type II: nine cases of ocular signs and symptoms. Am J Ophthalmol 132:522–527, 2001. Natt E, Kida K, Odievre M, et al: Point mutations in the tyrosine aminotransferase gene in tyrosinemia type II. Proc Nat Acad Sci 89:9297– 9301, 1992. Shear CS, Nyhan WL: Tyrosinemia II, Oregon type. In: Buyse ML, ed: Birth defects encyclopedia. Dover, MA, Center for Birth Defects Information Services, 1990.
S ECT I O N
5
Disorders of Carbohydrate Metabolism
69 DIABETES MELLITUS 250.0 F. Hampton Roy, MD, FACS Little Rock, Arkansas
damage. Specific changes that have been noted are the loss of intramural pericytes and basement membrane thickening, which results in obstruction of the capillary lumen and a breakdown of the blood-retina barrier.
Ocular or periocular ●
ETIOLOGY/INCIDENCE Diabetes mellitus is a complex disorder of carbohydrate, lipid, and protein metabolism characterized clinically by hyperglycemia and a relative or total lack of insulin. It is a common disorder that is prevalent worldwide. The development of diabetes is influenced by multiple factors, both genetic and environmental. The disease may develop in the first or second decade of life (type I) or in middle or late life (type II); more than half of diabetic individuals older than 40 years are overweight. A family history of diabetes is positive in 25% of patients. The disease is generally transmitted as a recessive trait without sex linkage. The increased life span of diabetics due to the use of insulin and other hypoglycemic agents has also resulted in a longer duration of the disease. This is associated with an increased incidence of accelerated atherosclerosis and a triad of retinopathy, nephropathy and neuropathy. The degree of hyperglycemia is also thought to influence the incidence and severity of complications. Diabetic retinopathy is the most serious ocular manifestation of diabetes mellitus and it causes more blindness among working-age Americans than any other disease. More than 20 million people worldwide are estimated to be blind due to complications from diabetes. Having diabetes increases the risk of blindness by 25%. The etiology is multifactorial and is still not fully understood, but there is evidence to suggest strong relationships between retinopathy and the duration of diabetic disease and high levels of blood glucose. There is an increasing incidence of diabetes in the United States; an estimated 6% of the population is affected. Of the estimated 16 million diabetics in the United States, about half have retinopathy. Type II diabetes and its complications affect minority populations more than the white population. Native Americans, blacks, and Hispanics have twofold to sixfold higher incidence rates. The rate of clinically detectable retinopathy is less than 25% in patients with a known diabetes of less than 5 years, about 50% with a history of 5 to 15 years, and more than 75% with a history of more than 15 years. The exact cause of diabetic microvascular disease is not known; possibly, prolonged exposure to hyperglycemia results in glycosylation of tissue proteins with ultimate endothelial
●
●
●
●
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●
Ciliary body: glycogen deposits in pigment epithelium, thickening of basement membrane. Cornea: endothelial pigment deposits, hypesthesia, poor epithelial healing. Extraocular muscles: paralysis of third or sixth cranial nerve. Iris: ectropion uveae, glycogen deposits in pigment epithelium, pupillary abnormality, rubeosis iridis. Lens: cataracts, pigment deposits on epithelium, premature presbyopia. Macula: edema, ischemia, exudates, hemorrhage. Optic nerve: atrophy, papillopathy. Retina: microaneurysms, hard exudates, hemorrhages, cotton-wool spots, venous abnormalities, intraretinal microvascular abnormalities (IRMAs), neovascularization, detachment, arteriolar sclerosis. Vitreous: asteroid hyalosis, detachment, hemorrhage.
Diabetic retinopathy Diabetic retinopathy is the most common and one of the most serious ocular manifestations of diabetes mellitus. Visual loss, often severe, can result through one or more of the following mechanisms: macular edema due to breakdown of the blood– retina barrier, macular ischemia due to occluded perifoveal capillaries, fibrovascular proliferation with associated complications of vitreous hemorrhage, traction detachment of macula, and neovascular glaucoma.
Classification and clinical features of diabetic retinopathy Two stages are recognized: the early, or nonproliferative (NPDR), stage and the more advanced, or proliferative (PDR), stage. Macular edema can develop during either stage. NPDR is further described as mild, moderate, severe and very severe. Mild NPDR is characterized by the presence of microaneurysms; retinal edema, or ‘thickening’; and hard exudates. The Early Treatment Diabetic Retinopathy Study (ETDRS) coined the term clinically significant macular edema (CSME) to indicate situations in which edema or hard exudates involved or threatened to involve the center of the fovea. Moderate NPDR additionally presents with cotton-wool spots, IRMAs and venous beading. Severe NPDR is characterized by the presence of four quadrants of significant retinal hemorrhages, two quadrants of significant venous beading, or one quadrant of
127
SECTION 5 • Disorders of Carbohydrate Metabolism
significant IRMA. This is known as the ETDRS 4, 2, 1 rule. Very severe NPDR is defined as the presence of two or more of these criteria. Severe NPDR can progress to high-risk PDR in 15%, and very severe NPDR can progress to PDR in 45% of patients within 1 year. Venous beading, IRMAs, and extensive capillary nonperfusion on fluorescein angiography are important indicators of significant retinal ischemia. PDR is further described as early, high risk, or advanced. It is said to occur with the formation of new vessels on the disk (NVD) or elsewhere on the retina (NVE) and with associated proliferation of fibrous tissue. High-risk PDR, as defined by the Diabetic Retinopathy Study (DRS), presents with three or more of the following high-risk characteristics: ● Vitreous or preretinal hemorrhage. ● New vessels. ● New vessels at or within one disk area of the disk. ● Moderate to severe new vessels (NVD equal to or more than one third of the disk area or NVE equal to or more than one half of the disk area). Advanced PDR is associated with recurrent vitreous hemorrhage, retinal detachment, and neovascular glaucoma. Vision is seriously compromised, and a serious threat of blindness exists. Fluorescein angiography is of value in the early detection of microangiopathy and in the assessment of macular edema and retinal ischemia. It also aids in photocoagulation.
PROPHYLAXIS The best way to prevent the major complications of diabetes is probably to keep blood glucose levels as close to normal as possible. The Diabetes Control and Complications Trial (DCCT) has demonstrated that tight blood glucose control through intensive insulin therapy can delay the onset and slow the progression of retinopathy, nephropathy, and neuropathy in type I diabetics. Tightening of blood glucose control is seen to cause a deterioration in retinopathy in some patients with mild or moderate NPDR. This generally stabilizes with time.
TREATMENT The use of desperate measures such as pituitary ablation has been abandoned because of the associated morbidity and mortality rates. Various pharmacologic agents have been used to treat diabetic retinopathy; the past use of drugs like clofibrate, calcium dobesilate, aspirin, and aldose reductase inhibitors largely reflected the prevalent thinking regarding the possible causes of retinopathy. The ETDRS evaluated the role of aspirin in dosages of 650 mg/day for a possible role in treatment because of its antiplatelet aggregation and fibrinolytic actions. The Sorbinil Retinopathy Trial likewise evaluated the role of an aldose reductase inhibitor (sorbinil) aimed at blocking the effect of the enzyme aldose reductase and thus preventing the formation of toxic levels of sorbitol through the polyol metabolic pathway. None of these drugs have been found to be of value. Contemporary management of diabetic retinopathy consists of good medical control of diabetes, retinal photocoagulation, and additional vitreous surgery when needed.
Medical The DCCT has clearly established the value of tight control of blood glucose levels in type I diabetics. Good metabolic control
128
not only helps to prevent retinopathy but also helps to slow down its progression. Type II diabetes in persons whose diabetes cannot be controlled by diet alone or those who are unwilling or unable to adhere to a restrictive diet can be controlled with oral hypoglycemic agents, insulin, or both. Most type I diabetics require insulin.
Photocoagulation Retinal photocoagulation is the most successful tool in the treatment of diabetic retinopathy; the landmark studies of DRS and ETDRS have clearly established its value. The DRS proved the value of panretinal photocoagulation (PRP) in high-risk PDR and severe NPDR. The ETDRS, on the other hand, demonstrated the usefulness of macular photocoagulation (grid or focal) in CSME. Photocoagulation is commonly performed with lasers emitting in the green wave band such as argon or frequency-doubled YAG lasers. Lasers emitting in the red or yellow ranges are useful when there is blood in the vitreous or when treatment is needed very close to the fovea. The treatment technique used for PDR is called ‘panretinal’ or ‘scatter.’ It consists of the application of several hundred 500-μm-diameter burns to the midperipheral and peripheral portions of the retina. Treatment extends posteriorly to two disk diameters from the center of the macula in the temporal quadrants and to one-half disk diameter nasal to the optic disk. In addition, focal treatment using moderate-intensity confluent burns may be applied to new vessels on the surface of the retina. The total number of burns is usually 1200 to 1600, depending on the severity of the retinopathy. Each burn is of a duration of 0.1 to 0.2 second. Power is adjusted to achieve a moderately white burn. The treatment is applied on an outpatient basis with the patient under topical or retrobulbar anesthesia. Focal treatment to new vessels on the optic disk is not necessary. The regression of neovascularization is usually apparent soon (weeks to months) after treatment, but it is not always complete or permanent. When substantial regression of neovascularization is not obtained or not maintained, one or more additional scatter treatments over previously untreated retina are often followed by satisfactory regression. The ETDRS recommended treatment of CSME and formulated guidelines that consist of the identification and treatment of all leaking microvascular abnormalities located in an area 500 to 3000 μm from the center of the fovea. The treatment would be focal or in the form of a grid pattern, depending on the nature of the leakage. The burns used to treat the macula are smaller and mild. The complications of photocoagulation are generally mild and often transient; they include a decrease in light sensitivity, contraction of peripheral visual field, loss of accommodation, and nyctalopia. Intense treatments in a single session have been associated with more serious complications of detachment or hemorrhage of the choroid, macular pucker and subretinal neovascularization.
Surgical The aims of pars plana vitreous surgery are to remove vitreous hemorrhage, to relieve all traction threatening the macula, and to remove the scaffolding on which fibrovascular proliferation grows. It is required in eyes with severe retinopathy in which there is either nonresolving or recurrent vitreous hemorrhage that prevents vision or the delivery of photocoagulation, increasing vitreoretinal traction posing a threat to the macula from traction detachment, combined traction and rhegmatogenous
detachment, and progressive proliferation uncontrolled with photocoagulation, or, in some cases, with preretinal membrane. The Diabetic Retinopathy Vitrectomy Study emphasized the value of vitrectomy in severe proliferative disease and the usefulness of early vitrectomy (1 to 6 months) in eyes with vitreous hemorrhage in type I diabetics.
70 GALACTOSEMIAS 271.1 (Galactose-1-Phosphate Uridyl Transferase Deficiency, Galactokinase Deficiency, Galactose-6-Phosphate Epimerase Deficiency)
Diabetic retinopathy poses a major threat of blindness to patients with diabetes mellitus. This blindness is preventable in most cases. Early detection and proper diabetic control through diet, exercise, medication, or a combination probably are still the best tools for controlling the disease. Equally important are regular examinations that include ophthalmoscopic examinations through dilated pupils. Should retinopathy be seen, progression should be monitored by an ophthalmologist who can seek specialized care, such as photocoagulation or vitrectomy, at the appropriate time. It must be recognized that pregnancy and concurrent cardiovascular disease are higherrisk situations that require greater care. Photocoagulation with or without vitrectomy is largely an effective tool to retard the progression of retinopathy; however, it is an invasive procedure that involves some destruction of the retina. Some patients will complain of a decrease in visual acuity or a constriction of the visual fields after the procedure. Current emphasis therefore is on prevention and on the development of new drugs that are safe and have the potential of preventing or arresting the progress of retinopathy. Retinal ischemia is believed to result in the formation of a vascular endothelial growth factor, a molecule suspected to stimulate endothelial cells to multiply and cause neovascularization. Drugs that inhibit the formation of this molecule or block its vasoproliferative effect could play an important role in the management of PDR. Certain protein kinases could block the chemical trigger for angiogenesis. Antihistamines could be of value in preventing breakdown of the blood-retina barrier due to the liberation of bradykinin or serotonin. These agents are being investigated for their therapeutic potential.
REFERENCES Aiello LP, Avery RL, Arrigg PG, et al: Vascular endothelial growth factor in ocular fluid of patients with diabetic retinopathy and other retinal disorders. New Engl J Med 331:1480–1487, 1994. American Diabetes Association: Diabetes 1996: vital statistics. Alexandria, American Diabetes Association, 1996:32–33, 51–59. Carter JS, Monterrosa A, Pugh JA: Non-insulin-dependent diabetes mellitus in minorities in the United States. Ann Intern Med 125:221–232, 1996. Deb-Joardar N, Germain N, Thuret G, Manoli P, et al: Screening for diabetic retinopathy by ophthalmologists and endocrinologists with pupillary dilation and a nonmydriatic digital camera. Am J Ophthalmol 140(5):814–821, 2005. Early Treatment Diabetic Retinopathy Study Research Group: Focal photocoagulation treatment of diabetic macular edema. ETDRS Report 19. Arch Ophthalmol 113:1144–1155, 1995. El-Bradey M, Plummer DJ, Uwe-Bartsch D, Freeman WR: Scanning laser entoptic perimetry for the detection of visual defects associated with diabetic retinopathy. Br J Ophthalmol 90(1):17–19, 2006.
Deborah M. Alcorn, MD Stanford, California
ETIOLOGY/INCIDENCE Galactosemias are autosomal recessive disorders resulting from an error of galactose metabolism caused by a deficiency of any one of three enzymes: transferase, galactokinase, or epimerase. These enzymes catalyze the reactions in the Leloir pathway by which galactose is converted to glucose-1-phosphate. The main dietary source of galactose is mammalian milk, in which it is found in the form of disaccharide lactose. Lactose is then hydrolyzed with the release of the monosaccharides glucose and galactose. Worldwide estimates of incidence vary from 1 in 18,000 to 1 in 187,000 persons. In the United States, the incidence is approximately 1 in 50,000; it is rare in Asia; and it is more frequent in Europe, with an incidence of 1 in 40,000 persons. Classic galactosemia, which is the most common and the most severe form, is caused by the impairment of galactose1-phosphate-uridyl-transferase (GALT). The gene has been mapped to chromosome 9p13 and cloned. Within days of consuming milk, these infants develop a toxicity syndrome characterized by vomiting, diarrhea, failure to thrive, lethargy, jaundice and hepatomegaly. If left untreated, sepsis (usually E. Coli) and shock are likely. Approximately 30% develop cataracts. Galactokinase deficiency catalyzes the first step in galactose metabolism (phosphorylation of galactose). The deficiency results from mutation in the GALK1 gene on 17q24. Toxicity in galactokinase deficiency is milder, resulting primarily only in cataracts, usually occurring in the fi rst year of life. The exact prevalence of GALK deficiency is unknown, but felt to be 5000 mg/dL), there is whitening of all retinal vessels with inability to differentiate arteries from veins. Conjunctival and iris vessels might be creamy providing an easy slit-lamp follow-up for triglyceride level. Complications associated with lipemia retinalis include eruptive xanthoma, hepatosplenomegaly, acute pancreatitis, and atheroma.
Weight reduction and diet low in saturated fat and cholesterol are advocated. Extreme fat and cholesterol restriction has been achieved with vegetarian diets. Alcohol and estrogen should be avoided in certain types of hyperlipoproteinemias. Aerobic exercise improves insulin sensitivity, HDL-C concentrations and reduces coronary artery disease risk. Lipid lowering drugs include fibric acid derivatives (clofibrate, gemfibrozil, fenofibrate), niacin, omega-3 fatty acids, and statins (atorvastatin, simvastatin, rosuvastatin, cerivastatin, pravastatin, lovastatin, fluvastatin).
CHAPTER 79 • Hyperlipoproteinemia
Clinical manifestations are caused by deposition of lipids at various tendons, the vascular system, and the eye.
Surgical Ileal bypass or plasmapheresis are performed in selected cases of familial hypercholesterolemia. Liver transplanstation is rarely done in familial hypercholesterolemia.
COMMENTS Patients with lipid disorder have a higher risk for occlusive vascular disease which is decreased by healthy diet, desirable weight, and regular exercise.
REFERENCES Barchiesi BJ, Eckel RH, Ellis PP: The cornea and disorders of lipid metabolism. Surv Ophthalmol 36:1–22, 1991. Crispin S: Ocular lipid deposition and hyperlipoproteinaemia. Prog Retin Eye Res 21:169–224, 2002. Mansour AM, Raimer SS: Cerebrotendinous xanthomatosis and other xanthomas. In: Gold D, Weingeist TA, eds: The eye in systemic disease. Philadelphia: Lippincott, 1990:337–340. Uwaydat S, Mansour AM: Infantile lipemia retinalis et conjunctivalis. J Ped Ophthalmol Strab 7:47–49, 2000.
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Hematologic and Cardiovascular Disorders
80 CAROTID CAVERNOUS FISTULA 853.0 (Dural Shunt Syndrome, Carotid ArteryCavernous Sinus Fistula, Arteriovenous Communication or Arteriovenous Fistula) M. Tariq Bhatti, MD Durham, North Carolina Keith Robertson Peters, MD, ABR, CAQ VIR, CAQ NR Gainesville, Florida
INTRODUCTION Carotid cavernous fistulas represent an abnormal arteriovenous communication between the cavernous sinus (a venous structure) and the carotid arterial system (internal and/or external carotid arteries). Carotid cavernous fistulas can be classified as: high flow vs. low flow, direct vs. indirect (dural) or traumatic vs. spontaneous. The Barrow classification categorizes the fistulas depending on the angiographic pattern of the arterial flow. Depending on the type of carotid cavernous fistula and the pattern of venous drainage (anterior or posterior) the clinical manifestations can be variable and diverse.
through the fistula or spontaneous thrombosis of the superior ophthalmic vein.
DIAGNOSIS Clinical signs and symptoms (Figure 80.1) ● Red eye due to episcleral venous congestion (corkscrew episcleral vessels). ● Conjunctival chemosis. ● Eyelid or facial edema. ● Elevated intraocular pressure (asymmetric ocular pulse). ● Pulsating exophthalmos. ● Diplopia due to ocular motor cranial neuropathy or extraocular muscle congestion. ● Orbital (ocular) pain or headache. ● Orbital bruit (approximately 50% of dural fistulas). ● Retinal vascular congestion and hemorrhages. ● Visual loss due severe corneal exposure, glaucoma, retinopathy or optic neuropathy.
Laboratory findings ●
●
●
ETIOLOGY/INCIDENCE ●
Most carotid cavernous fistulas are of the direct type and caused by head trauma (70%–90%). Dural carotid cavernous fistulas are thought to be congenital in etiology and are more commonly seen in middle-aged or elderly women often associated with systemic arterial hypertension, atherosclerotic vascular disease and connective tissue disorders.
●
Differential diagnosis ● ●
COURSE/PROGNOSIS
● ●
Direct carotid cavernous fistulas can be life threatening due to severe epistaxis or intracranial (intracerebral or subarachnoid) hemorrhage therefore nearly all require intervention. In comparison, if left untreated dural carotid cavernous fistulas rarely result in neurological sequela but can be associated with significant ocular morbidity. Up to 50% of dural carotid cavernous fistula will close without treatment. Acute worsening of the ocular manifestations may occur from increased blood flow
Orbital ultrasonography: dilated superior ophthalmic vein and enlarged extraocular muscles. Computed tomography: dilated superior ophthalmic veins, dilated cerebral veins, and enlarged extraocular muscles. Magnetic resonance imaging: abnormal flow voids, dilated superior ophthalmic vein, enlarged extraocular muscles, and orbital congestion. Magnetic resonance angiography (maximum intensity projection and source images): flow signal abnormalities. Six-vessel cranial digital subtraction angiography (diagnostic procedure of choice): characterization of the arterial supply and venous drainage of fistula.
Chronic conjunctivitis. Orbital cellulites. Thyroid eye disease. Orbital arteriovenous malformation.
TREATMENT Ocular ● ●
Topical lubrication. Intraocular pressure lowering agents.
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SECTION 7 • Hematologic and Cardiovascular Disorders
b
a
FIGURE 80.1. External photograph demonstrating arterialization (corkscrew appearance) of conjunctival vessels. The lateral digital subtraction angiogram of the right common carotid artery in early arterial phase demonstrates immediate dense contrast filling of the cavernous sinus (arrowhead) with drainage anteriorally through the superior ophthalmic vein (straight arrow) and posteriorally through the inferior petrosal sinus (curved arrow).
Medical ●
Intermittent self-manual carotid artery compression.
Stereotactic radiosurgery Direct cavernous sinus surgery Endovascular embolization (recommended therapy of choice) ● ● ●
Transarterial route. Transvenous route. Superior ophthalmic vein route.
Miller NR: Carotid-cavernous sinus fistulas. In: Miller NR, Newman NJ, Biousse V, Kerrison JB, eds: Walsh and Hoyt’s clinical neuroophthalmology. 6th edn. Baltimore, Williams & Wilkins, 2005:2263–2296. Sergott RC, Grossman RI, Savino PJ, et al: The syndrome of paradoxical worsening of dural-cavernous sinus arteriovenous malformations. Ophthalmology 94(3):205–212, 1987. Tsai Y-F, Chen L-K, Su C-T, et al: Utility of source images of three dimensional time-of-fl ight magnetic resonance angiograpy in the diagnosis of indirect carotid-cavernous sinus fistulas. J Neuro-Ophthalmol 24:285–289, 2004.
Complications of endovascular embolization therapy ●
● ●
Carotid artery occlusion resulting in ipsilateral cerebral hemisphere ischemia. Transient worsening of ocular and orbital manifestations. Partial closure of fistula with persistent posterior venous drainage and cortical venous arterialization.
81 SICKLE CELL RETINOPATHY 282.60 Hon-Vu Q. Duong, MD Las Vegas, Nevada
COMMENTS ETIOLOGY/INCIDENCE The clinical manifestations of direct and dural carotid cavernous fistulas may overlap with the signs and symptoms being more dramatic in direct fistulas. All direct carotid cavernous sinus fistulas should be treated. In contrast dural fistulas can often be observed expectantly and in many cases may close spontaneously or after a diagnostic angiogram.
REFERENCES Barrow DL, Spector RH, Braun IF, et al: Classification and treatment of spontaneous carotid-cavernous sinus fistulas. J Neurosurg 62(2):248– 256, 1985. Goldberg RA, Goldey SH, Duckwiler G, Vinuela F: Management of cavernous sinus-dural fistulas. Indications and techniques for primary embolization via the superior ophthalmic vein. Arch Ophthalmol 114(6):707–714, 1996. Grove AS, Jr: The dural shunt syndrome. Pathophysiology and clinical course. Ophthalmology 91(1):31–44, 1984.
148
Sickle cell hemoglobinopathy encompasses a group of inherited genetic disorders, which cause erythrocytes to become sickled and affect multiple organ systems. The rigid sickled erythrocytes lead to vascular occlusion, which results in retinal hypoxia, ischemia, infarction, detachment, and neovascularization. In sickle cell anemia (SS disease), the amino acid substitution valine for glutamate occurs on the β-chain at the sixth position. This substitution, combined with conditions that may promote sickling triggers the deoxygenated Hb S to polymerize, making the erythrocyte rigid. This rigidity is partially responsible for the vasoocclusion. Vasoocclusion is also in part due to the interaction between sickled cells and the vascular endothelium with the end result of vascular stasis, hemolysis, and vasoocclusion. In the United States, sickle cell anemia primarily occurs in the black population, with approximately 0.2% of African-
American children afflicted by this disease. The prevalence in adults is lower because of the decrease in life expectancy. Sickle cell anemia is a homozygous-recessive disorder. Sickle cell C disease is the second most common form, resulting from amino acid substitution of lysine for glutamic acid, and commonly seen in West African populations. Sickle cell thalassemia is the third most common form of sickle cell disease.
Systemic disease associated with sickle cell anemia is more common and more severe than ocular disease. Sickle cell C disease and sickle cell thalassemia tend to have mild systemic manifestations however, ocular manifestations can be severe. Prognosis is fair to good if consistent follow-up care is maintained with both an internist/hematologist and an ophthalmologist.
DIAGNOSIS Clinical signs and symptoms Patients with a history of sickle cell anemia should undergo a dilated fundus exam based on retinal findings. Changes in the posterior segment are divided into 4 major categories: optic disc changes, macular changes, nonproliferative retinal changes, and proliferative retinal changes.
FIGURE 81.1. Sickle cell retinopathy.
Stage II — Arterioilar-venular anastomoses: shunting of blood from the occluded arterioles to the nearest venules. Often difficult to view by ophthalmoscopy an FA can demonstrate arteriovenous anastomoses that do not leak dye. Stage III — Neovascular proliferation: classic finding for stage IIII is the ‘sea fan –neovascularization’ lesion. On FA, sea fan lesions leak profusely (Figure 81.1). Stage IV — Vitreous hemorrhage: it may be spontaneous secondary to vitreous collapse and/or traction of the adherent neovascular tissue. Stage V — Retinal Detachment: detachments may be rhegmatogenous and/or tractional.
CHAPTER 81 • Sickle Cell Disease
COURSE/PROGNOSIS
Optic disc Intravascular occlusions primarily affect the small vessels on the surface of the optic disc and appear as dark red spots or clumps. They are often called the disc sign of sickling. They are self-limiting and do not produce any appreciable visual symptoms.
Differential diagnosis ● ● ● ● ●
Macula Vascular occlusion can lead to complete loss of vision or can lead to central or paracentral scotoma. A macular depression may be seen. Proliferative findings in the macular include macula hole, macula traction, enlarged segments of terminal arterioles, hairpin-shaped vascular loops, and abnormal foveal avascular zone.
●
BRVO CRVO. Eales disease. Hypertension. Retinopathy of prematurity. Proliferative diabetic retinopathy. Sarcoidosis.
TREATMENT Medical This condition is treated by an internist or hematologist.
Nonproliferative sickle cell retinopathy
Surgical/Ocular
While abnormal, nonproliferative changes are generally asymptomatic and do not require treatment. The nonproliferative changes include: ● venous tortuosity — common but not pathognomonic for sickle cell disease, ● salmon patch hemorrhage — intraretinal hematoma, found in the periphery, and confined to the neural retina, ● black sunburst — a pigmented chorioretinal scar, usually found in the periphery. These scars appear round or ovoid with stellate or speculate borders and often associated with iridescent spots, ● angiod streaks — breaks in Bruch membrane and appeared as pigmented striae that lie under the retinal vessels.
The primary goal in treating proliferative sickle cell retinopathy is to minimize or eliminate neovascularization. Although treatments are not indicated for stages I and II, most advocate treatment with stage III.
Laser photocoagulation It is relatively safe and one of the more commonly used therapeutic modality. Different techniques have been advocated and include scatter or feeder vessel photocoagulation.
Retinal cryotherapy Cryotherapy often is limited to cases with cloudy ocular media. Single freeze-thaw and triple freeze-thaw have been advocated in treating PSR.
Proliferative retinopathy Stage I — Peripheral arteriolar occlusion: areas of retinal ischemia secondary to nonperfusion become an abnormal grayish brown color.
Vitrectomy Vitrectomy is indicated in cases of nonresolving vitreous hemorrhage and retinal detachment.
149
COMPLICATIONS Anterior segment ischemia ● ● ● ● ●
SECTION 7 • Hematologic and Cardiovascular Disorders
●
The following measures can decrease complications. Preoperative partial exchange transfusion. Administer local anesthesia, stellate ganglion block. Cycloplegic (parasympathomimetics). Decrease IOP and should be kept less than 25 mmHg, preoperatively, intraoperatively, and postoperatively. Supplemental oxygen.
Recurrent retinal detachment Hyphema Neovascular glaucoma
COMMENTS Early detection and treatment may help decrease the retinal complications. Special concern should include repeated blood transfusion, hyphema, and scleral buckling. Ophthalmic care is determined by the proliferative stage. Patients should be well informed of their current and potential long-term complications. These patients are strongly encouraged to enroll at a local or regional sickle cell clinic along with providing these patients with local support group. Patients with diagnosed sickle cell disease should seek genetic counseling prior to starting a family.
REFERENCES Andreoli TE, et al: Disorder of red cells. In: Cecil’s essentials of medicine. 4th edn. 1997:383–387. Asdourian GK: Sickle cell retinopathy. In: Albert DM, Jakobiec FA, eds. Principles and practice of ophthalmology. 1994:II:1006–1018. Beutler E: Disorders of hemoglobin. In: Fauci AS, et al, eds: Harrison’s principle of internal medicine. 14th edn. 1998:645–652. Bunn HF: Pathogenesis and treatment of sickle cell disease. New Engl J Med 337(11):762–769, 1997. Fekrat S, Lutty G, Goldberg M: Hemoglobinopathies. In: Guyer D, et al: Retina-vitreous macula. 1999:I:438–458. Ho AC: Hemoglobinopathies. In: Yanoff, M, Duker, JS, eds. Ophthalmology. 2nd edn. Mosby, 2004:Ch119:891–895. Yanoff M, Fine BS: Sickle cell disease. In: Ocular pathology. 4th edn. 1996:377–378.
82 THE THALASSEMIAS 282.4 Stephen S. Feman, MD, FACS St. Louis, Missouri Levent Akduman, MD St. Louis, Missouri Ozgur Yalcinbayir, MD St. Louis, Missouri The thalassemias are a group of hereditary disorders characterized by decreased rates of hemoglobin polypeptide chain synthesis. They represent the clinical features of a series of pathologic alleles on chromosome 11 and 16. As a group, the
150
thalassemias are the most common single-gene problem in humans. The chromosomal abnormalities can result in total gene deletion, rearrangements of genetic loci, mutations that impair transcription, defects in the processing of genetic information, and errors in the translation of RNA. In the past, these disorders had a variety of historic names (Cooley’s anemia, thalassemia major, thalassemia minor, etc.). In an attempt to include all the manifestations of this disorder, a nomenclature related to the involved polypeptide chain has become popular (alpha-thalassemia for alpha polypeptide chain abnormalities, beta-thalassemia for beta polypeptide chain abnormalities, etc.). The clinical manifestations of this disorder are the results of inadequate globin production and the accumulation of blood products. The clinical features are diverse and can range from asymptomatic states to death from anemia. The most common clinical characteristic of the thalassemias is the development of a hypochromic microcystic anemia. However, in some patients, the pathologic changes represent such a small fraction of total globin synthesis that this abnormality is difficult to measure. In general, when a patient has one thalassemia gene and one normal gene, the disorder is called thalassemia trait (thalassemia minor in the older literature) and a relatively mild anemia is present. When two similar genes are present, there is a more severe impairment of hemoglobin synthesis and a more severe anemia (thalassemia major in the older literature). In addition, it is possible to describe the thalassemias in regard to the rate of hemoglobin polypeptide chain synthesis. Some recent publications use this to specify the relative amount of hemoglobin synthesis impairment and imply this information (i.e. severe, mild and silent form of thalassemia) is of greater clinical value than the other nomenclatures. The most common variety of thalassemia was described by Cooley and Lee in 1925. It is caused by a defect in the rate of synthesis of the beta-polypeptide chain of hemoglobin A. This abnormality results in a relative increase in the levels of hemoglobin A2 and hemoglobin F, along with the development of a microcystic hypochromic anemia. As the years progress, splenomegaly, hepatomegaly and discoloration of the skin and sclera occur. At one time, this particular disorder was thought to have a specific geographic distribution that extended from the Mediterranean through the Middle East, India and Southeast Asia. Although there is a relatively high gene frequency in those areas (it can range from 2.5% to 15% in those regions), it has been found that the thalassemias have a worldwide distribution.
COURSE/PROGNOSIS Infants are born free of anemia because of prenatal hemoglobin F production. In most patients, the clinical manifestations are first identified at about the 6th month of life. Without treatment, 80% of the patients with the classic form of this disorder will die within 5 years. In these young infants, the most common associated clinical features consist of pallor, irritability, growth retardation, abdominal swelling and jaundice. Transfusions to prevent the associated anemias have become a treatment standard.
Ocular or periocular manifestations Conjunctiva Focal regions of dilated and turtuous vessels.
Retina Vascular tortuosity; pigmented chorioretinal scars (black sunburst pattern); iridescent intraretinal deposits; focal arterial occlusions; central retinal vein occlusion; neovascularizations; hemorrhages; angioid streaks which may be associated with subretinal neovascularization; macular pucker; and macular ischemia.
Hemorrhages.
Whenever an intraocular hemorrhage, visual field defect, or retinal neovascular change is identified, one must search for an additional hemoglobin abnormality. If found, the treatment should be directed to the ocular and systemic manifestations of the other co-existing hemoglobinopathy to prevent additional visual loss. Regular, or yearly, ophthalmic examinations are recommended for patients with the thalassemias in order to detect and treat possible ocular complications and to monitor the potential iron toxicity.
THERAPY Systemic Transfusions to prevent the symptoms of anemia have been the standard of treatment for many years. In time, such therapy will result in an iron overload and hemosiderosis; this complication had been a common cause of death for these patients. However, with the use of iron chelators, such as deferoxamine and desferrioxamine, this danger is lessened. Nevertheless, splenomegaly can be a major problem for such patients and may need to be resolved with a splenectomy.
Ocular The most serious threats to vision occur in patients with thalassemia and sickle cell trait. Such patients develop multifocal areas of peripheral retinal neovascularization that result in vitreous hemorrhages. The vessels feeding and draining the neovascular growth can be identified by fluorescein angiography, and photocoagulation to occlude these vessels can prevent such hemorrhages. Then, the surrounding area of ischemic retina can be treated with a scatter photocoagulation pattern to reduce the stimulus for recurrent neovascularization and to prevent future problems in that retinal region.
Precautions Ocular complications indicate, in most cases, that the patient has a combination of thalassemia and some other hemoglobin abnormality. The treatment of the ocular manifestations associated with the other hemoglobin abnormality offers the greatest visual benefit to most patients. In addition, patients requiring frequent blood transfusions may show signs of retinal toxicity from the iron accumulation or from the desferrioxamine use. The clinical features of this type of retinal toxicity include night blindness, visual field defects and ERG changes.
REFERENCES Aessopos A, Farmakis D, Karagiorga M, et al: Pseudoxanthoma elasticum lesions and cardiac complications as contributing factors for strokes in beta-thalassemia patients. Stroke 28(12):2421–2424, 1997. Aessopos A, Voskaridou E, Kavouklis E, et al: Angioid streaks in sicklethalassemia. Am J Ophthalmol 117(5):589–592, 1994. Al-Hazzaa S, Bird AC, Kulozik A, et al: Ocular fi ndings in Saudi Arabian patients with sickle cell disease. Br J Ophthalmol 79(5):457–461, 1995.
CHAPTER 82 • The Thalassemias
Vitreous
COMMENTS
Carney MD, Jampol LM: Epiretinal membranes in sickle cell retinopathy. Arch Ophthalmol 105(2):214–217, 1987. Comings DE: Thalassemia. In: Williams WJ, Beutler E, Lichtman MA, et al, eds: Hematology. New York, Mc Graw-Hill, 328–345, 1972. Condon PI, Serjeant GR: Ocular fi ndings in sickle cell thalassemia in Jamaica. Am J Ophthalmol 74:1105–1109, 1972. Cooley TB, Lee P: A series of cases of splenomegaly in children with anemia and peculiar bone changes. Trans Am Pediatr Soc 37:29–35, 1925. Davies SC, Marcus RE, Hungerford JL, et al: Ocular toxicity of high-dose intravenous desferrioxamine. Lancet 2(8343):181–184, 1983. Dennerlein JA, Lang GE, Stahnke K, et al: Ocular fi ndings in Desferal therapy. Ophthalmologe 92(1):38–42, 1995. Feman SS, Westrich DJ: Macular arteriolar occlusions in sickle cell betathalassemia. Am J Ophthalmol 101:739–740, 1986. Goldberg MF, Charache S, Acacio I: Ophthalmologic manifestations of sickle cell thalassemia. Arch Intern Med 128:33–39, 1971. Gupta A, Agarwal A, Bansal RK, et al: Ischaemic central retinal vein occlusion in the young. Eye 7(Pt 1):138–142, 1993. Kinsella FP, Mooney DJ: Angioid streaks in beta thalassaemia minor. Br J Ophthalmol 72(4):303–304, 1988. Magli A, Fusco R, Mettivier V, Pisapia R: Ocular manifestations in thalassemia minor. Ophthalmologica 184:139–146, 1982. Theodossiadis G, Ladas I, Koutsandrea C, et al: Thalassemia and macular subretinal neovascularization. J Fr Ophtalmol 7(2):115–118, 1984.
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S ECT I O N
8
Dermatologic Disorders
Conjunctiva
83 ATOPIC DERMATITIS 691.8 (Atopic Eczema, Disseminated Neurodermatitis)
●
Cornea ●
Carsten Heinz, MD Muenster, Germany Arnd Heiligenhaus, MD Muenster, Germany
Conjunctival injection, chemosis, mucus discharge, papillary reaction, Trantas dots, squamous cell carcinoma.
Superficial punctate keratopathy (SPK), shield ulcer, scars, keratoconus, vascularization.
Lens ●
Cataract formation.
Retina ●
INCIDENCE/ETIOLOGY Atopic dermatitis (AD) is a chronic disease with a prevalence of 10–20% in children and 1–3% in adults. In acute AD a Th2 dominated immune process with production of cytokines as IL-4, IL-5 and IL-13 is found, while in chronic AD the mircomilieu comprises of both Th1 and Th2 cytokines. AD may also be complicated by rhinitis or asthma. The etiology seems to be multivariant. Familial disease increases the risk 2 to 3 fold. The hygiene hypothesis proposes that an in utero and postnatal immune stimulation with infectious agents with a subsequent predominantly Th1 immune response results in a lower risk of atopic manifestation. Food allergens, aeroallergens, bacteria and also emotional stress have been implicated to stimulate AD. Serum IgE is often elevated in patients with AD and sensitization against a variety of environmental allergens is frequent. However, manifestation or exacerbation of AD also occurs in the absence of exposure to environmental allergens. The high level of IgE autoantibodies against a broad variety of human proteins often correlates with disease severity and may contribute to pathogenesis.
Detachment due to rubbing of the eyelids or traumatic slapping.
TREATMENT Systemic ● ● ● ●
Avoidance of identified allergens. Oral corticosteroids. Systemic tetracycline as blepharitis treatment. Immunosuppression in severe cases, e.g. with cyclosporin A.
Topical Skin Lid hygiene, topical corticosteroids, calcineurin inhibitors (e.g. tacrolimus or pimecrolimus), antibiotics.
Ocular Unpreserved lubricants, mast cell stabilisators, antihistamines, cyclosporin A, topical corticosteroid, antibiotics, therapeutic contact lenses
Surgical ●
DIAGNOSIS Atopic dermatitis is a chronic relapsing, inflammatory skin disease that is characterized by pruritic eczematous skin lesion. Predominant localization varies with the patient’s age, with predilection on the extensor surfaces in young children and on the flexor surfaces in adults. Ocular involvement is reported in about 32%.
●
● ● ●
Tarsorhaphie or punctual occlusion in SPK. Amniotic membrane transplantation in corneal epithelial defects or shield ulcers. Cataract extraction with IOL implantation. Keratoplasty for keratoconus. Retinal detachment surgery.
COMMENTS OCULAR Eyelid ●
Erythema, exudates, crusting, scaling, blepharitis, secondary infection.
Atopic dermatitis is a chronic skin disease that also affects the eyelid leading to severe discomfort. Treatment of the skin disease is often satisfactory and should be managed cooperatively with dermatologists. The severity of eye affections varies extremely and may lead to visual loss. Treatment strategies
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include lubricants, topical mast cell stabilizers antihistamines or topical ciclosporin, and systemic immunosuppression or surgical interventions may be required to preserve vision.
REFERENCES Heinz C, Fanihagh F, Steuhl KP: Squamous cell carcinoma of the conjunctiva in patients with atopic eczema. Cornea 22(2):135–137, 2003.
SECTION 8 • Dermatologic Disorders
Hida T, Tano Y, Okinami S, et al: Multicenter retrospective study of retinal detachment associated with atopic dermatitis. Jpn J Ophthalmol 44(4):407–418, 2000. Hingorani M, Moodaley L, Calder VL, et al: A randomized, placebo-controlled trial of topical cyclosporin A in steroid-dependent atopic keratoconjunctivitis. Ophthalmology 105(9):1715–1720, 1998. Leung DY, Bieber T: Atopic dermatitis. Lancet 361(9352):151–160, 2003. Leung DY, Jain N, Leo HL: New concepts in the pathogenesis of atopic dermatitis. Curr Opin Immunol 15(6):634–638, 2003. Novak N, Bieber T, Leung DY: Immune mechanisms leading to atopic dermatitis. J Allergy Clin Immunol 112(6 Suppl):S128–S139, 2003. Schultz Larsen F, Diepgen T, Svensson A: The occurrence of atopic dermatitis in north Europe: an international questionnaire study. J Am Acad Dermatol 34(5 Pt 1):760–764, 1996. Sturgill S, Bernard LA: Atopic dermatitis update. Curr Opin Pediatr 16(4):396–401, 2004. Uchio E, Miyakawa K, Ikezawa Z, et al: Systemic and local immunological features of atopic dermatitis patients with ocular complications. Br J Ophthalmol 82(1):82–87, 1998.
reactivity may occur as this is caused by a common aldehyde metabolite. Atopic dermatitis (AD) is a common cause of chronic recurring eyelid dermatitis often developing as an atopic itchy red eye in childhood, but can also present in adulthood. Cell mediated immune defects within the skin and abnormal IgE levels have been described as possible mechanisms. Irritant contact dermatitis (ICD) is caused by excessive moisture or by acids, alkalis, resins, or chemicals capable of injuring any person’s skin if persistent contact is allowed. Allergy or hypersensitivity plays no role in irritant contact dermatitis.
DIAGNOSIS History is essential in making the diagnosis of contact dermatitis; a personal and family history of hay fever, asthma, eczema or childhood atopy supports the diagnosis of ACD. History may be positive for exposure to irritative or sensitizing substances including topical ocular medications like neomycin, atropine derivatives, preservatives (benzalkonium chloride, benzyl alcohol, thimerosal, etc.) and anti-glaucoma medications (betablockers). Patch testing is often required for an adequate diagnosis of ACD or ICD. Withdrawal of the offending substance often alleviates signs and symptoms.
Clinical signs and symptoms
84 CONTACT DERMATITIS 692.9 (Contact Allergy, Dermatitis Venenata)
Signs and symptoms include erythematous, edematous, exudative, and pruritic skin lesions; scaling, ulceration, and edema of the eyelids; conjunctivitis and keratitis, especially inferiorly; and punctate corneal staining or infi ltrates, especially inferiorly; itching of the skin and of the eye itself. With chronicity, the periorbital skin, particularly the upper eyelid becomes eczematous and lichenified.
Srini V. Goverdhan, MD, FRCSOphth Southampton, England
TREATMENT ETIOLOGY/INCIDENCE
Systemic ●
Contact dermatitis is a common immunologic skin condition which often presents to ophthalmologists as an eyelid or periorbital dermatitis. It results from exposure of the skin to a wide variety of substances with primary irritant properties commonly found in the environment, including drugs, dyes, plant resins, preservatives, cosmetics, resins, rubber derivatives and metals. Small incomplete hapten molecules bind to dermal protein, forming complete antigens. Initial exposure to haptens results in sensitization of CD8 + T lymphocytes, a second application triggers release of cytokines, which amplify the inflammatory response in the skin. There are three varieties of contact dermatitis: 1. Allergic, which is the common form; 2. Atopic; and 3. Irritant. Allergic contact dermatitis (ACD), unlike the irritant variety, occurs only in sensitized individuals and involves the mechanism of cell-mediated immunity. In ACD, an individual becomes sensitized to a given chemical or other sensitizing substance, and with re-exposure to the same chemical, an erythematous delayed hypersensitivity skin reaction is elicited. In Glaucoma, ACD has been seen with use of brimonidine or beta- blockers (timolol, befunolol, and carteolol) where cross-
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Poison ivy or poison oak dermatitis may require a course of oral corticosteroids. Desensitization may also be helpful. Antihistamines and mast-cell stabilizers can help control atopic symptoms in AD. Local reactions rarely require systemic therapy.
Local ●
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The allergen or irritant (determined by patch testing) should be removed from the patient’s environment. Topical corticosteroids may lead to the rapid relief of symptoms. Saline compresses and steroid lotions are helpful for skin lesions.
SUMMARY Contact sensitivity is a common ophthalmologic problem because of exposure to chemicals in eye drops. The best form of treatment is discontinuation or avoiding the offending substance. Steroid therapy can reduce symptoms, but it is not recommended on a long-term basis. Patch testing can be very helpful in determining the cause of contact dermatitis and in selecting alternative drugs to which the patient is not sensitive.
REFERENCES
DIAGNOSIS
Friedlaender MH: Allergy and immunology of the eye. New York, Raven, 1993:79–82.
Clinical signs and symptoms
Guin JD: Eyelid dermatitis: a report of 215 patients. Contact Dermatitis 50:87–90, 2004. Holdiness MR: Contact dermatitis to topical drugs for glaucoma. Am J Contact Dermatitis 12:217–219, 2001.
Zug KA, Palay DA, Rock B, et al: Dermatologic diagnosis and treatment of itchy red eyelids. Surv Ophthalmol 40:293–306, 996.
TREATMENT Systemic ●
85 ERYTHEMA MULTIFORME MAJOR 695.1 (Erythema Multiforme Exudativum, Stevens–Johnson Syndrome, Toxic Epidermal Necrolysis)
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Ocular ● ●
Sharon S. Lehman, MD Wilmington, Delaware
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ETIOLOGY/INCIDENCE ●
Erythema multiforme, Stevens–Johnson (SJS) and toxic epidermal necrolysis (TEN) represent a spectrum of disease characterized by an acute mucocutaneous reaction caused by hypersensitivity reaction to infection or drugs with activated T-lymphocytes acting destructively at the dermo-epidermal junction. Erythema multiforme is a disease ranging in severity from mild (erythema multiforme minor), which is a benign condition without mucosal involvement, to severe (erythema multiforme major), which is characterized by bullous-erosive mucocutaneous reactions. SJS, a form of erythema multiforme major, has limited full thickness epidermal necrosis, marked constitutional symptoms and low mortality rate. TEN is characterized by epidermal necrosis involving greater than 30% of the body surface with marked long term complications and mortality.
Multispecialty care, often in an ICU or burn unit, is required. Use of steroids is controversial. Use of antibiotics is based on clinical course and cultures. Immunosuppresive agents continue to be studied.
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Gentle eyelid hygiene should be performed as necessary. Preservative free artificial tear ointment should be frequently and liberally applied. Use of antibiotics is based on clinical course and cultures. Use of steroids is controversial. Use of topical anesthetics should be limited because of ocular surface toxicity. Daily examination and disruption of symblepharon is required. Chronic dry eye requires continued use of preservative free artificial tear products and consideration may be given to the use of topical cyclosporin A.
CHAPTER 85 • Erythema Multiforme Major
Manni G, Centofanti M, Sacchetti M, et al: Demographic and clinical factors associated with development of brimonidine tartrate 0.2%induced ocular allergy. J Glaucoma 13:163–167, 2004.
The target, or bull’s eye, lesions of erythema multiforme are diagnostic and are recognized by the central, dark-purple area or a blister surrounded by a pale, edematous, circular zone, which in turn is surrounded by a peripheral rim of erythema. The characteristic involvement of the oral and conjunctival mucosa can also aid in the diagnosis of Stevens–Johnson syndrome.
Surgical ●
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Consider symblepharon ring for prevention of adhesions if tolerated by patient. Consider amniotic membrane transplantation (AMT) in acute phase in order to promote healing and inhibit inflammation, vascularization and scar. Treatment for chronic dry eye may require punctual occlusion and tarsarrhaphy. Treatment for trichiasis and entropion may require epilation, cryoablation, electolysis and eyelid reconstruction. Treatment of severely affected eyes requires consideration of AMT, limbal stem cell transplantation and corneal transplantation with possible immunosuppression.
COURSE/PROGNOSIS ●
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The prodromal period before skin lesion usually includes fever, malaise, sore throat and arthralgias. Erythematous macules, papules, and the characteristic bull’s eye target skin lesions occur on the skin and ocular involvement includes: ● Eyelid: edema, erythema, and crusting occur initially with later entropion, scarring and trichiasis; ● Conjunctiva: initial chemosis and inflammatory pseudomembrane occur with later keratinization, scarring, symblepharon, ankyloblepharon, and a dry eye; ● Cornea: epithelial defects, limbal stem cell deficiency, corneal ulcers, vascularization, scarring and perforation occur.
COMMENTS The treatment of erythema multiforme major, SJS and TEN remains challenging. New treatments such as immunomodulatory therapy offer new hope but require further testing for proof of therapeutic efficacy.
REFERENCES Foulks GN: The evolving treatment of dry eye. Ophthalmol Clin N Am 16:29–35, 2003. John T, Foulks GN, John ME, et al: Amniotic membrane in the surgical management of acute toxic epidermal necrolysis. Ophthalmology 109:351–360, 2002.
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Lehman SL: Long-term ocular complication of Stevens-Johnson syndrome. Clin Pediatr 38:425–427, 1999.
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McKenna JK, Leiferman KM: Dermatologic drug reactions. Immunol Allergy Clin North Am 24:399–423, 2004.
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Metry DW, Jung P, Levy ML: Use of intravenous immunoglobulin in children with Stevens-Johnson syndrome and toxic epidermal necrolysis: seven cases and review of the literature. Pediatrics 112:1430–1436, 2003.
SECTION 8 • Dermatologic Disorders
Samson CM, Nduaguba C, Baltatzis S, et al: Limbal stem cell transplantation in chronic inflammatory eye disease. Ophthalmology 109:862– 868, 2002.
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Conjunctiva: interpalpebral or diffuse hyperemia, papillary and/or follicular reaction, pinguecula, scarring; Cornea: punctate erosions, pannus, neovascularization, lipid deposition, spade-shaped infi ltrates, scarring, thinning, ulceration, perforation, phlyctenule; Sclera: episcleritis, scleritis.
The prevalence of ocular complaints in patients with acne rosacea is estimated at between 45% and 85%. The primary symptoms include burning, itching, tearing, foreign body sensation, redness and pain; however, the symptoms may be out of proportion to the clinical signs of the disease.
Laboratory findings
86 OCULAR ROSACEA 695.3
None.
Differential diagnosis Vinicius Coral Ghanem, MD Joinville, Santa Catarina, Brazil Mark J. Mannis, MD, FACS Sacramento, California
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ETIOLOGY/INCIDENCE Acne rosacea is a chronic cutaneous disease of unknown etiology. It affects up to 10% of the population, most notably fairskinned women from 30 to 60 years of age. Theories of its pathogenesis have included gastrointestinal, psychological, infectious, climatic, pharmacological and immunological causes.
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Blepharitis, meibomitis, recurrent chalazion, sebaceous gland carcinoma. Staphylococcal and seborrheic blepharokeratoconjunctivitis. Dry eye syndrome. Medication toxicity. Interstitial keratitis. Skin disease: ● Acne vulgaris; ● Seborrheic dermatitis; ● Chronic topical corticosteroid therapy; ● Alcohol abuse; ● Phototherapy; ● Lupus erythematosus, perioral dermatitis, essential telangiectasia, tuberculosis, syphilis, dermatomyositis, etc.
COURSE/PROGNOSIS Rosacea is most commonly seen in adults although it has been reported in young children. The course may be characterized by recurrent inflammatory attacks of decreasing severity and frequency, or more commonly by chronic disease that lasts for more than 10 years, presenting chronic complications such as persistent facial edema, keratitis and rhinophyma. The prognosis of ocular rosacea is generally good. Nevertheless, corneal involvement may be as high as 30% in cutaneous rosacea and up to 85% in frank ocular rosacea.
DIAGNOSIS Clinical signs and symptoms Primary features include flushing (transient erythema), nontransient (persistent) erythema, papules, pustules and telangiectasias. The presence of one or more of these features with a central facial distribution is suggestive of rosacea. Secondary features include burning or stinging, plaques, dry appearance, edema, phymatous changes and involvement of more peripheral locations (neck, chest, scalp, ears and back). Persistent erythema and telangiectasia between acute episodes of inflammation are typical signs. Ocular involvement, commonly referred to as ocular rosacea, occurs in more than 50% of patients, usually affecting both eyes simultaneously. Clinical fi ndings may be confined to the eyes and may include: ● Eyelid: telangiectasias and erythema of the lid margin, meibomian gland dysfunction, anterior blepharitis, recurrent chalazion/hordeolum, madarosis, trichiasis;
156
TREATMENT Systemic The use of systemic antibiotics is the mainstay of treatment in most cases. We would stress that the treatment goal is to reduce the signs and symptoms rather than effecting a cure. Tetracycline is the most common initial regimen, 250 mg orally every 6 hours for a time period of 3 to 4 weeks, tapering to a maintenance dosage with improvement of the clinical condition. Alternatively, one can use 100 mg of doxycycline taken orally two times daily for 3–4 weeks with a subsequent taper. Symptomatic improvement commonly occurs before the clinical signs ameliorate and generally occurs 2 to 4 weeks after initiation of treatment. Patients who have recurrent disease or potentially sight-threatening complications may require a maintenance dose of up to 250 mg of tetracycline or 50 mg of doxycycline daily or every other day indefi nitely. Abrupt withdrawal of treatment may cause an exacerbation of the disease. Recently, a sub-antimicrobial-dose doxycycline (doxycycline hyclate, 20mg twice daily) has demonstrated results comparable to conventional doses of tetracyclines, but with significant fewer side effects. The effectiveness of this therapy has yet to be evaluated for ocular rosacea. Supplements rich in Omega 3 (flaxseed oil — 500 to 1000 mg 3 times per day) may also be helpful in reducing ocular symptoms. For dermatologic disease, oral metronidazole or erythromycin can also be employed. These treatment methods are less effective for cases of persistent lymphedema and rhinophyma, while oral isotretinoin has been used successfully in resistant cases and in rhinophyma.
Ocular
Topical Topical medications are usually combined with systemic treatment for successful control of symptoms and signs, especially in the case of ocular disease. The use of metronidazole 0.75% or 1% gel, sodium sulfacetamide 10%/sulfa 5% as a topical formulation or azelaic acid have shown good results. Topical corticosteroids must be used cautiously and for short periods, since their chronic usage can cause worsening of vasodilatation and telangiectasias.
Surgical Surgical treatment is reserved for the most severe cases of ocular rosacea that develop significant corneal thinning or impending or actual perforation. Surgical options may include: conjunctival flap, cyanoacrylate adhesive application, or lamellar or penetrating keratoplasty. Before considering a transplant for optical purposes, it is essential that any inflammatory signs be controlled. Even so, these corneas are usually vascularized and transplant surgery is high-risk. Maintenance of systemic and ocular treatment is vital. Dermatological surgical treatment is reserved for selected cases of telangiectasias and rhinophyma.
COMPLICATIONS The absorption of tetracycline may be hindered by food intake. Therefore, tetracycline should not be taken during meals or along with dairy products, antacids, or iron preparations. Doxycycline absorption, on the other hand, is not affected by food intake. Neither tetracycline nor doxycycline should be used in children under 12 years of age or in pregnant or nursing women. Patients using these drugs should be advised of gastrointestinal side-effects and photosensitivity.
COMMENTS Rosacea is a relatively common and frequently under-diagnosed disease by ophthalmologists, who may not carefully examine the patient’s face. Considering that there are no objective diagnostic tests currently available, both the ophthalmologist as well as the dermatologist must rely on clinical fi ndings, which
may be subtle. A careful facial examination with adequate illumination is essential. In 20% of the cases, ocular symptoms appear before skin disease, and since the ocular signs may be non-specific, the clinical diagnosis may be difficult. Nevertheless, if the ocular signs are diagnostic, empirical treatment should be initiated. Patient follow-up and management must be multidisciplinary, including not only the dermatologist but also the ophthalmologist.
REFERENCES Akpek EK, Merchant A, Pinar V, et al: Ocular rosacea: patient characteristics and follow-up. Ophthalmology 104:1863–1867, 1997. Alvarenga LS, Mannis MJ: Ocular rosacea. Ocul Surf 3(1):41–58, 2005. Brown SI, Shahinian J, Jr: Diagnosis and treatment of ocular rosacea. Ophthalmology 85:779–786, 1978. Browning DJ, Proia AD: Ocular rosacea. Surv Ophthalmol 31:145–158, 1986.
CHAPTER 87 • Psoriasis
Proper lid hygiene is fundamental in the successful treatment of ocular rosacea. Warm compresses, lid margin massage (meibomian gland expression), and careful cleaning of the cilia and lid margin with dilute baby shampoo or commercially available lid scrubs are very helpful. The frequency of lid hygiene depends on the severity of the disease and is generally performed 2–4 times per day. Approximately 40% of rosacea patients have signs of keratoconjunctivitis sicca. For this reason, artificial tears, preferentially without preservatives, should be used frequently. Punctal plugs may be helpful. Systemic antibiotics, lid hygiene and artificial tears in combination, may aid in restoration of the ocular surface by reduction of Staphylococcus aureus toxins and toxic free fatty acids present on the tear fi lm. In cases of severe lid margin disease, topical antibiotic and corticosteroid ointment may be used cautiously for short periods of time to control the acute exacerbations. Corticosteroid eye drops may be used, but with caution and preferably only for severe ocular inflammatory signs and symptoms.
Frucht-Pery J, Chayet AS, Feldman ST, et al: The effect of doxycycline on ocular rosacea. Am J Ophthalmol 107:434–436, 1989. Frucht-Pery J, Sagi E, Hemo I, et al: Efficacy of doxycycline and tetracycline in ocular rosacea. Am J Ophthalmol 116:88–92, 1993. Ghanem VC, Mehra N, Wong S, et al: The prevalence of ocular signs in acne rosacea: comparing patients from ophthalmology and dermatology clinics. Cornea 22(3):230–233, 2003. Macsai MS, Mannis MJ, Huntley AC: Acne rosacea. In: Mannis MJ, Macsai MS, Huntley AC, eds. Eye and skin disease. Philadelphia, LippincottRaven, 1996:335–341. Quaterman MJ, Johnson DW, Abele DC, et al: Ocular rosacea: signs, symptoms, and tear studies before and after treatment with doxycyline. Arch Dermatol 133:49–54, 1997. Sneddon IB: A clinical trial of tetracycline in acne rosacea. Br J Dermatol 78:649–652, 1966. Wilkin J, Dahl M, Detmar M, et al: Standard grading system for rosacea: report of the national rosacea society expert committee on the classification and staging of rosacea. J Am Acad Dermatol 50(6):907–912, 2004.
87 PSORIASIS 696.1 Rubén Queiro, MD Oviedo-Asturias, Spain Juan J Barbón, MD Avilés-Asturias, Spain Daniel de la Mano, MD Avilés-Asturias, Spain
ETIOLOGY/INCIDENCE Psoriasis is a chronic skin disorder characterized by excessive proliferation of the epidermis. Epidermal cells in psoriatic patches have lost regulatory control and exhibit accelerated growth. It can begin at any age but most commonly arises in the third decade. It is more common in white people and its prevalence is similar in both sexes. Psoriasis affects 1% to 2% of general population, and 7% to 40% of these patients develop arthritis as the main systemic complication. Most patients have minimal disease, but 15% have severe generalized disease. Psoriasis typically lasts for life, and infections, psychological distress, trauma, and some therapies are common causes of exacerbation. The etiology is unknown, but genetical and immunological factors are relevant in the etiopathogenesis.
157
DIAGNOSIS
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Clinical signs and symptoms Systemic
Ocular
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SECTION 8 • Dermatologic Disorders
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Characterized by sharply demarcated , geographically shaped, erythematous patches of skin covered with coarse, dry, silvery scales. When hyperkeratotic scales are removed, small blood droplets develop within seconds (Auspitz’s sign). Scalp, nails, elbows, knees, extensor surfaces of the extremities, and sacral region most commonly affected.
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Ocular ● ●
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Affects about 10% of patients with psoriasis. Lids: ● May develop plaques. ● Lid margins can be affected by scaling, with trichiasis and madarosis in severe cases. ● An obstructive type of meibomian gland dysfunction has been described in psoriatic patients. Conjunctiva: ● Nonspecific conjunctivitis. ● Yellow plaque-like lesions. ● Limbal phlyctenule-like lesions. Cornea: ● Superficial and deep opacities. ● Vascularization, infi ltration, and melting can occur, especially peripherally. ● Usually corneal involvement when there is active lid disease. Uveitis: The risk of uveitis is about 7% to 18%, especially in those affected by advanced spondylitis. Uveal inflammation may be anterior, posterior, and sometimes bilateral.
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Oral retinoids, particularly in association with UV therapy.
Topical corticosteroids for lid lesions, conjunctivitis, and uveitis. Adhesive dressings and detergent scrubs may be also used for skin lesions. Topical tar, anthralin derivates, and UV therapy probably not appropriate for lid lesions. Corneal melting: lubrication, bandage contact lenses, tarsorrhaphy, and treatment of systemic disease; high doses of oral corticosteroids (1 to 2 mg/kg of prednisone or equivalent) and oral CsA appear to provide systemic relief most rapidly, but corticosteroids are not recommended because of the high doses necessary and the severe exacerbations that often occur after esteroids are stopped. Corneal involvement can be slow to respond and can result in vascularization and scarring. Severe cases of uveitis may need systemic corticosteroids and immunosupresants such as CsA, azathioprine, alfainterferon or anti-TNF therapies.
COMPLICATIONS Retinoids have been reported to cause dry eyes, blepharitis, corneal opacities, cataracts, and decreased night vision. Conjunctival hyperemia, decreased lacrimation, and cataract have been described with psoralens and UVA, but the relationship is unclear. The use of adequate UV-blocking sunglasses after treatment is recommended. Methotrexate-treated patients may show reduced full-field electroretinogram and decreased vision.
REFERENCES TREATMENT Systemic Systemic treatment is undertaken in coordination with a dermatologist, and in cases of psoriatic arthritis with a rheumatologist.
Local Topical treatment ●
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Corticosteroids (most commonly fluorinated preparations such as halcinonide, fluocinonide, betamethasone, and triamcinolone) twice daily. Coal tar (2% to 5%) or tar derivate, with subsequent exposure to ultraviolet (UV) B light (Goeckerman regimen). Anthralin derivates (0.1% to 0.8%) with salicylic acid in a paste or ointment form and used in combination with tar and UV therapy (Ingram regimen). Waterproof adhesive dressings left in place for at least 1 week. Phototherapy through presensitization with psoralens and exposure to UVA light (320 to 400 nm). Intralesional injections of corticosteroids, such as 5 mg/mL triamcinolone. In severe cases, methotrexate 7.5 to 25 mg/week or cyclosporin A (CsA) 2.5 to 5 mg/kg/day.
Catsarou-Catsari A, Katambus A, Tkheodorpoulos P, et al: Ophthalmological manifestations in patients with psoriasis. Acta Derm Venereol (Stock) 64:557–559, 1984. Cram DL: Corneal melting in psoriasis. J Am Acad Dermatol 5:617, 1981. Eustace P, Pierse D: Ocular psoriasis. Br J Ophthalmol 54:810–813, 1970. McClure SL, Valentine J, Gordon KB: Comparative tolerability of systemic treatments for plaque-type psoriasis. Drug Saf 25:913–927, 2002. Ponjavic V, Granse L, Stigmar EB, et al: Reduced full-field electroretinogram (ERG) in a patient treated with methotrexate. Acta Ophthalmol Scand 82:96–99, 2004. Queiro R, Torre JC, Belzunegui J, et al: Clinical features and predictive factors in psoriatic arthritis-related uveitis. Semin Arthritis Rheum 31:264–270, 2002. See JA, Weller P: Ocular complications of PUVA therapy. Aust J Dermatol 34:1–4, 1993. Zengin N, Tol H, Balevi S, et al: Tear fi lm and meibomian gland functions in psoriasis. Acta Ophthalmol Scand 74:358–360, 1996.
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88 URTICARIA AND HEREDITARY ANGIOEDEMA 708.9 (Angioneurotic Edema, Giant Edema, Giant Urticaria, Hives, Nettle Rash, Quincke’s Disease)
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Local Subcutaneous injection or application of cotton pads soaked in 1 : 1000 epinephrine may be useful to treat severe conjunctival edema.
Surgical
ETIOLOGY/INCIDENCE Urticaria is a cutaneous eruption with multiple pathogenic mechanisms that may be immunologic or nonimmunologic. Its prevalence in the general population is estimated to be between 10% and 25%. No specific cause can be found in 50% of patients with chronic urticaria; in others, psychogenic, allergic and physical factors may play a role. The pathogenesis of urticaria is poorly understood. It is associated with uncontrolled mast cell degranulation and the release of mediators. Hereditary angioedema is an inherited deficiency of C1-esterase inhibitor. Hereditary angioedema (HAE) is an autosomal dominant disease, and characterized by repeated attacks of epithelial edema involving the skin, respiratory tract, and gastrointestinal tract. Repeated episodes of angioedema involving the skin and respiratory tract may lead to death from pharyngeal edema and asphyxiation.
If orbital edema develops to such an extent that the globe or optic nerve is threatened, relief from pressure should be provided. This may involve decompression of the lateral orbital wall. Surgery is rarely necessary.
SUMMARY Urticaria has numerous causes, and its pathogenesis is poorly understood. Basically, it is associated with uncontrolled mast cell degranulation and release of mediators. Therapy is designed to prevent mast cell release or inhibit the mediators of inflammation. Hereditary angioedema is an inherited deficiency of C1-esterase inhibitor and represents a chronic condition that is life threatening. Patients must be counseled intensively and emergency therapy must be available to them.
CHAPTER 88 • Urticaria and Hereditary Angioedema
Mitchell H. Friedlaender, MD La Jolla, California
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Antifibrinolytic agents for hereditary angioedema (aminocaproic acid or tranexamic acid). Anabolic steroids and impeded androgens and fresh frozen plasma. C1 esterase inhibitor concentrate (for HAE).
REFERENCES Bielory L, Noble KG, Frohman LP: Urticarial vasculitis and visual loss. J Allergy Clin Immunol 88:819–821, 1991.
DIAGNOSIS Clinical signs and symptoms Erythematous, elevated, multiple, pruritic skin lesions may be localized or widespread. Hereditary angioedema is characterized by repeated attacks of epithelial edema involving the skin, respiratory tract and gastrointestinal tract. Pharyngeal edema may be life threatening. Abdominal attacks may mimic intraabdominal crises.
Bowen T, Cicardi M: Canadian 2003 international consensus algorithm for the diagnosis, therapy, and management of hereditary angioedema. J Allergy Clin Immunol 114:629–637, 2004. Fay A, Abinun M: Current management of hereditary antio-oedema (C′1 esterase inhibitor deficiency). J Clin Pathol 55:266–270, 2002. Friedlaender MH: Allergy and immunology of the eye. New York, Raven, 1993:85–86. Kaplan AP: Chronic urticaria and angioedema. N Engl J Med 346:175–179, 2002. Kaplan AP: Chronic urticaria: pathogenesis and treatment. J Allergy Clin Immunol 114:465–474, 2004.
TREATMENT Systemic ● ● ● ●
Antihistamines for urticaria or angioedema. β-Adrenergic drugs. Systemic corticosteroids. Cyclosporin A.
Kozel MMA, Bossuyt PMM, Mekkes JR, Bos JD: Laboratory tests and identified diagnoses in patients with physical and chronic urticaria and angioedema: a systematic review. J Am Acad Dermatol 48:409–416, 2003. Mathews KP: Urticaria and allergic conjunctivitis. Curr Opin Immunol 2:535–541, 1990. Nzeako UC, Frigas E, Tremaine WJ: Hereditary angioedema: a broad review for clinicians. Arch Intern Med 161:2417–2429, 2001.
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Connective Tissue Disorders
DIAGNOSIS
89 AMYLOIDOSIS 277.3 Steven P. Dunn, MD Southfield, Michigan Jay H. Krachmer, MD Minneapolis, Minnesota
ETIOLOGY/INCIDENCE Amyloidosis is a disease complex that results in the accumulation of an amorphous, insoluble, fibrillar protein or aberrantly folded and assembled protein fragments in a variety of tissues. It is readily identified pathologically with polarizing light microscopy by it’s characteristic apple-green birefringence after Congo red staining. In recent years, the study of amyloid fibrils has led to the classification of amyloid on the basis of the biochemical composition of its subunit proteins. More than 25 fibrillar proteins have now been identified as precursor proteins in amyloidosis. The Nomenclature Committee of Amyloidosis has revised the classification scheme such that all forms are designated by ‘A’ + a suffi x that denotes the precursor protein. Most forms of amyloidosis can be categorized as localized or systemic forms. The two major types of systemic amyloidosis are AL (primary amyloidosis or myeloma-associated amyloidosis) and AA (secondary or reactive amyloid). AL results from deposition of terminal fragments of immunoglobulin kappa or lambda light chains: AA is associated with the acute phase reactant serum amyloid A (SAA) as the precursor protein. The reported incidence of systemic AL amyloidosis is 1/100,000 persons in Western countries. AA amyloidosis, related to familial Mediterranean fever has a defi nite ethnic predilection among Sephardic Jews, Armenians, Turks and Arabs having a higher incidence. An increased incidence is seen in patients with tuberculosis, leprosy, anklylosing spondylitis, rheumatoid arthritis and Crohn’s disease. Senile amyloidosis is thought to occur in almost all individuals over the age of 85. Six types of primary familial amyloidosis have now been described, and they appear to be related most frequently to an abnormality in transthyretin (prealbumin); however, mutations of apolipoprotein A-I, gelsolin, fibrinogen A and lysozyme are also seen. Amyloid deposits resulting from these conditions are usually associated with an autosomal dominant form of inheritance. These forms of amyloidosis are seen in greater frequency among patients originating from Portugal, northern Sweden, Japan, Iceland and Finland.
Clinical signs and symptoms Multisystem involvement is characteristic of primary systemic amyloidosis. Progressive peripheral polyneuropathy, cardiomyopathy, and gastrointestinal and skin involvement are seen most frequently. The eye may be involved in a number of ways; linear and veil-like vitreous opacities associated with slowly progressive visual loss, however, are virtually diagnostic of this disease. Discrete, bilateral, yellow-white, xanthoma-like subconjunctival nodules, occasionally with petechiae and hemorrhage, may be the initial findings. Involvement of the lacrimal and parotid glands may produce dryness of the eyes and mouth. Proptosis and external ophthalmoplegia have been attributed to amyloid deposits in the extraocular muscles. Pupillary abnormalities are thought to be due to amyloid neuropathy, or possibly secondary to deposits in the iris sphincter and dilator muscles. Neurotrophic keratitis and glaucoma may also be seen. Localized, primary amyloidosis may also affect the eye in the form of small pink-red nodules in the lids or conjunctiva. This form of the disease is usually bilateral and affects young adults in their 20s and 30s. A number of forms of primary corneal amyloidosis exist. The most commonly recognized is lattice corneal dystrophy, which has now been broken down into three subtypes based on inheritance pattern and clinical findings. Type I lattice corneal dystrophy is the classic form; it is autosomal dominant and presents with central, anterior, and midstromal lattice lines and dots and stromal haze. It is not associated with any systemic disorders and typically presents in patients between the ages of 10 and 40. A variant, Avellino dystrophy, has clinical and histologic features of both lattice and granular dystrophies. A mutation in the transforming growth factor beta-induced (TGFBI) gene on chromosome 5q31 is responsible for these conditions. Type II lattice corneal dystrophy, also known as Meretoja syndrome, is also autosomal dominant. It is actually a manifestation of a form of primary systemic amyloidosis known as Finnish hereditary amyloidosis. It is generally associated with blepharochalasis, bilateral facial nerve palsies, and peripheral neuropathy. Clinically, both peripheral and central lattice lines are found in the anterior stroma. Occasionally, conjunctival and adnexal deposits of amyloid may be seen. Recently, molecular genetics research has isolated a point mutation on the gelsolin gene in patients with clinical findings quite similar to those seen in Finnish hereditary amyloidosis. Type III lattice corneal dystrophy typically presents in an older age group and is thought to be a recessive disorder characterized by markedly thickened lattice-like lines involving the anterior stroma centrally and paracentrally. On occasion, lattice
161
SECTION 9 • Connective Tissue Disorders
lines may extend out to the periphery. This condition is not associated with any systemic abnormality. Primary gelatinous drop-like keratopathy (GDLD) is a rare amyloid disorder seen most commonly in individuals of Japanese ancestry. The inheritance pattern is thought to be autosomal recessive with a low degree of penetrance. Clinical findings consist primarily of numerous small to moderate-sized subepithelial gelatinous excrescences that give the corneal surface a ‘mulberry’ or ‘toad skin’ appearance. Patients with this disorder tend to present before the age of 20 with symptoms of photophobia, lacrimation, redness, and foreign body sensation. No systemic disorders are associated with this condition. As yet, the precise type of amyloid in gelatinous drop-like keratopathy has not been elucidated. The altered gene responsible for GDLD is M1S1 which is located on the short arm of chromosome 1. A variety of chronic systemic disorders may be accompanied by secondary systemic amyloidosis. Deposits are found chiefly in the spleen, kidney, and liver. Occasionally, the eyelid may be involved. Localized secondary amyloidosis may present as clinically detectable deposits in the lids, conjunctiva, and cornea. Clinically unrecognizable microdeposits of amyloid have been found in association with such conditions as basal cell carcinoma of the lid margin, conjunctival intraepithelial neoplasia, and conjunctival sarcoidosis. Microdeposits within the cornea have been seen with retinopathy of prematurity, phlyctenular keratoconjunctivitis, trachoma, trichiasis, keratoconus, and penetrating ocular trauma. Polymorphic amyloid degeneration, a condition typically seen in older patients without a history of ocular disease, is probably a form of primary localized amyloidosis.
Laboratory findings Corneal lesions have a characteristic clinical appearance, but most other lesions require pathologic evaluation for a defi nitive diagnosis. Histopathologic features crucial to the diagnosis of amyloidosis include: ● Distinctive fibrillar ultrastructure; ● Staining of pathologic specimens with Congo red; ● Apple-green birefringence under polarized light.
Differential diagnosis ● ● ● ● ● ●
Orbital tumors. Conjunctival sarcoidosis. Epibulbar rheumatoid nodulosis. Foreign body granuloma. Conjunctival lymphoid infiltrates (lymphomas, MALTomas). Multiple myeloma and cryoglobulin corneal deposits.
TREATMENT Systemic ●
●
●
162
All patients in this group require a thorough evaluation that includes the search for an underlying cause of the amyloidosis (i.e. inflammatory or neoplastic). Because some amyloid fibrils have an immunologic origin, therapeutic trials using melphalon, prednisone, colchicines or a combination of these have been tried. Chemotherapy with the iodinated anthracycline 4′-iodo-4′ deoxydoxorubicin has also demonstrated some clinical benefit in patients with immunocyte-derived (AL) amyloidosis.
●
The observation that transthyretin is synthesized predominantly by the liver has led to liver transplantation or combined liver-kidney transplantation as therapy for this disease (familial amyloid polyneuropathy).
Local ●
● ●
●
●
●
Localized disease is usually managed surgically; excision is performed for diagnostic as well as therapeutic reasons. The disease, however, has a strong tendency to recur. Reduced vision commonly leads to penetrating keratoplasty by the fourth or fi fth decade in patients with lattice dystrophy. Keratoplasty may also be helpful in patients with gelatinous drop-like dystrophy and diffuse familial amyloidosis. Polymorphic amyloid degeneration does not usually require therapy. Total vitrectomy appears to be the treatment of choice for amyloid patients with dense vitreous opacities that interfere with vision.
PRECAUTIONS There is a high incidence of recurrent amyloid deposition following surgery. This is particularly important when cosmetic surgery is planned. Regrafting or repeat vitrectomy is an option available to the patient with recurrent corneal and vitreal amyloidosis and visual deterioration.
COMMENTS Localized amyloid deposits are by far the most common form of ocular amyloidosis. In some cases, amyloid deposits involving the eye may actually be an early localized manifestation of a generalized amyloidosis. This is particularly true with eyelid and vitreal amyloid deposits. The possibility that these deposits may be associated with an underlying disease process or immunologic abnormalities must always be considered.
REFERENCES Brunt EM, Tiniakos DG: Metabolic storage diseases: amyloidosis. Clin Liver Disease 8:915–930, 2004. Doughman DJ: Ocular amyloidosis. Surv Ophthalmol 13:133–142, 1969. Falk RH, Comenzo RL, Skinner M, et al: The systemic amyloidoses. N Engl J Med 337:898, 1997. Gorevic PD, Muroz PE, Gorgone G, et al: Amyloidosis due to a mutation of the gelsolin gene in an American family with lattice corneal dystrophy, type II. N Engl J Med 325:1780–1785, 1991. Henderson JW: Orbital tumors. Philadelphia, WB Saunders, 1973: 602–608. Hitchings RA, Tripathi RC: Vitreous opacities in primary amyloid disease: a clinical, histochemical, and ultrastructural report. Br J Ophthalmol 60:41–54, 1976. Knowles DM II: Amyloidosis of the orbit and adnexae. Surv Ophthalmol 19:367–384, 1975. Mannis MJ, Krachmer JH, Rodrigues MM, et al: Polymorphic amyloid degeneration of the cornea: A clinical and histopathologic study. Arch Ophthalmol 99:1217–1223, 1981. Meretoja J: Familial systemic paramyloidosis with lattice dystrophy of the cornea, progressive cranial neuropathy, skin changes and various internal systems: a progressive, unrecognized, heritable syndrome. Ann Clin Res 1:310–312A, 1969.
TREATMENT
90 BEHÇET DISEASE 136.1 Ilknur Tugal-Tutkun, MD Istanbul, Turkey
Behçet disease is a multisystem inflammatory disorder of unknown etiology. Although it has a worldwide distribution, it is more prevalent in the Mediterranean area, the Middle East and the Far East. Behçet disease is closely associated with HLAB51 in endemic areas. Microbial antigens have long been proposed as the triggering factors. An antigen-driven specific inflammatory response superimposed on enhanced innate immune functions is implicated in the pathogenesis of vascular endothelial dysfunction and occlusive vasculitis.
In patients with only anterior uveitis topical corticosteroids and mydriatic agents are used. Local corticosteroid injections, including intravitreal injection of triamcinolone acetonide may be required for the treatment of severe panuveitis attacks and/or cystoid macular edema.
Systemic
Age of onset is usually around the end of the third decade. The frequency of ocular involvement is 50–70%. The disease has a relapsing remitting course. Male patients have a younger age of onset, more severe disease and a higher risk of visual loss compared to female patients. The risk of visual loss at 10 years has been estimated to be 30% in males and 17% in females. However, visual prognosis has improved in the last decade due to an earlier and more aggressive use of immunosuppressive therapy. Furthermore, a trend to milder disease and better visual outcomes has been reported from Japan. Mortality is associated with severe neurological, intestinal and cardiovascular involvement.
Corticosteroids are used for the treatment of uveitis attacks. Long-term immunosuppressive therapy is required in order to prevent recurrences in patients with posterior segment involvement. Colchicine does not have a proven effect on eye disease. Azathioprine (2 mg/kg/day) and cyclosporin A (5 mg/kg/day) have been found to be effective in controlled trials. Combination of cyclosporin A with antimetabolites is more effective than monotherapy. Ciclosporine is best avoided in patients with neuro-Behçet due to its potential neurotoxicity. Tacrolimus (FK506) (0.10–0.15 mg/kg/day) has an immunologic activity and side-effect profi le similar to cyclosporin A. Alkylating agents (cyclophosphamide and chlorambucil) have been reserved for cases refractory to initial treatment with cyclosporin A and antimetabolites. Encouraging results have been recently reported on the use of new biologic agents, including interferon alfa and anti-TNF alfa monoclonal antibody, infl iximab, in patients with uveitis resistant to conventional agents. Interferon alfa-2α is administered as monotherapy at an initial dose of 6 million units per day subcutaneously. The response rate has been reported to be 94%. Infl iximab infusions (5 mg/kg) are usually given at 8-week intervals following a loading dose. In open trials, it has been shown to have a rapid antiinflammatory effect and reduce the frequency of uveitis attacks.
DIAGNOSIS
COMPLICATIONS
Clinical signs and symptoms
Cataract, posterior synechiae, secondary glaucoma, maculopathy, optic atrophy, retinal atrophy and scarring, disc or retinal neovascularizations, retinal detachment and phthisis.
COURSE/PROGNOSIS
The diagnosis of Behçet disease is clinical. Systemic manifestations include recurrent oral and genital ulcers, skin lesions, arthritis, thrombophlebitis, arterial aneurysms, intestinal ulcers and neuropsychiatric symptoms. The typical form of ocular involvement is bilateral nongranuomatous panuveitis and retinal vasculitis. Explosive uveitis attacks and spontaneous remissions mark the disease course. Ocular findings include cells and flare in the anterior chamber, hypopyon, diffuse vitritis, retinal vasculitis, retinitis, retinal hemorrhages, retinal vein occlusions, macular edema, papilledema, papillitis, and rarely conjunctival ulcers, episcleritis, scleritis and keratitis.
Laboratory findings There are no laboratory findings specific for Behçet disease. HLA-B51 positivity may help to support a clinical diagnosis. Patients may have skin hyperreactivity, i.e. a positive pathergy test, defined as >2 mm erythema occurring 48 hours after a skin prick by a sterile needle. Patients may have leukocytosis, high erythrocyte sedimentation rates and high C-reactive protein levels during active disease.
Differential diagnosis HLA-B27-associated uveitis, sarcoidosis, syphilis, viral retinitis and endophthalmitis.
CHAPTER 90 • Behçet Disease
ETIOLOGY/INCIDENCE
Ocular
COMMENTS The etiopathogenesis of Behçet disease has not been elucidated yet. There are individual variations in disease course and severity. There is no single therapeutic regimen uniformly effective in all patients with Behçet disease.
REFERENCES Kötter I, Gunaydin I, Zierhut M, et al: The use of interferon alfa in Behçet disease: review of the literature. Semin Arthritis Rheum 33:320–335, 2004. Ohno S, Nakamura S, Hori S, et al: Efficacy, safety, and pharmacokinetics of multiple administration of infl iximab in Behçet’s disease with refractory uveoretinitis. J Rheumatol 31:1362–1368, 2004. Okada AA: Drug therapy in Behçet’s disease. Ocul Immunol Inflamm 8:85–91, 2000. Sfi kakis PP, Kaklamanis PH, Elezoglou A, et al: Infl iximab for recurrent, sight-threatening ocular inflammation in Adamantiades-Behçet disease. Ann Intern Med 140:404–406, 2004.
163
Tugal-Tutkun I, Onal S, Altan-Yaycioglu R, et al: Uveitis in Behçet disease: an analysis of 880 patients. Am J Ophthalmol 138:373–380, 2004. Verity DH, Wallace GR, Vaughan RW, et al: Behçet’s disease: from Hippocrates to the third millennium. Br J Ophthalmol 87:1175–1183, 2003. Yoshida A, Kawashima H, Motoyama Y, et al: Comparison of patients with Behçet’s disease in the 1980s and 1990s. Ophthalmology 111:810–815, 2004.
tagmus in 32%, oscillopsia in 15%, Ménière -like symptoms without hearing loss in 4%, and hearing loss in only 4%. Ocular symptoms and signs develop first in 50% of patients, vestibuloauditory complaints develop first in 25% of patients and both occur within 1 month of each other in 25% of patients. In 50% of patients, an antecedent upper respiratory illness has occurred.
SECTION 9 • Connective Tissue Disorders
Laboratory findings ●
91 COGAN SYNDROME 370.52 ●
Rex M. McCallum, MD Durham, North Carolina
● ● ● ●
ETIOLOGY/INCIDENCE Cogan syndrome is a rare clinical entity of unknown etiology and unknown incidence fi rst described by David Cogan, MD, in 1945. It occurs primarily in young adults and has an average age of onset of 28.6 in 47 patients evaluated at the National Institutes of Health and Duke University Medical Center.
●
●
●
●
COURSE/PROGNOSIS
Differential diagnosis ●
The primary ocular manifestation, interstitial keratitis, is either acute and recurrent or chronic. It may vary in intensity from day to day and from eye to eye. In the acute stages, conjunctival hyperemia and patchy white infi ltrates of the subepithelium are noted more often than deep or midcorneal stroma. Corneal infi ltrates are more prominent at the periphery. Epithelial defects can be seen. In the later stages, corneal vascularization and opacity may be noted, typically at the corneal periphery. Posterior uveitis and other forms of ocular inflammation are rarely found. Ocular outcome is excellent, with only 6% of patients having a visual acuity greater than 20/30 in either or both eyes. Auditory outcome, however, is less good; permanent loss of hearing occurs commonly, depending on use of oral corticosteroids. In patients not treated with oral corticosteroids, 17% had an auditory threshold of 7
>4 years
Systemic
−
Any
Any
Pauci or poly
(Rarely +)
≤7
After 7 years
Pauci or poly
+ or −
>7
After 4 years
Low
*American Academy of Pediatrics. Guidelines for examinations in children with Juvenile rheumatoid arthritis (RE9320). Pediatrics 92:295–296, 1993. High risk: ophthalmologic exam Q 3–4 months Moderate risk: ophthalmologic exam Q 6 months Low risk: ophthalmologic exam Q 12 months Recommendations for low-risk follow-up continue into adulthood.
181
allow the patients to be completely free of all recurrences of inflammation, while at the same time being free of all steroid use at all times.
●
Systemic ●
SECTION 9 • Connective Tissue Disorders
●
●
●
●
●
Systemic NSAIDs (e.g. naproxen at 10 to 15 mg/kg/day in divided doses) are used either as adjunctive therapy to help the steroid taper or as the sole systemic agent to supplement topical therapeutic measures. Long-term systemic treatment with corticosteroids is discouraged. A short course of systemic steroid therapy is occasionally used to supplement topical therapy in patients with significant inflammation. Systemic corticosteroid therapy retards linear growth in children, and most importantly, this effect can persist even after cessation of the corticosteroid therapy. Systemic steroid treatment (usually started at 0.5 to 1.0 mg/kg/day prednisone PO) is reserved for: ● Severe uveitis; ● Uveitis that is resistant to local treatment; ● Uveitis that involves posterior segment. Systemic chemotherapy is reserved for very severe cases that prove steroid-resistant and is used to limit complications resulting from prolonged use of systemic corticosteroids. The immunomodulatory drug of choice is methotrexate, which is often administered weekly. A second immunosuppressive medication is used when the chronic or recurrent uveitis not controlled with methotrexate as monotherapy. An alkylating agent such as chlorambucil has been shown to be effective and safe in patients with JIA-associated uveitis. Biological agents (infliximab, daclizumab) may have a role in the management of JIA-associated uveitis. Studies suggest that cyclosporine A, either as monotherapy or as an add-on agent to methotrexate immunomodulatory therapy program, is not the ideal agent for induction of durable remission of JIA-associated uveitis. Etanercept, which has been found to be efficacious in managing rheumatoid arthritis, has not been shown to be effective in managing uveitis such as that associated with JIA. All systemic immunosuppressive agents should be used in consultation with experts in the use of these agents in the pediatric population. It is strongly recommended that management of patients with JIA-associated uveitis be conducted by ocular immunologists/uveitis specialists whenever possible.
●
formation, maintain blood-aqueous barrier, and minimize visual disability from posterior subcapsular cataracts. Topical nonsteroidal anti-inflammatory drugs (NSAIDs) are employed as adjunctive therapy in patients at high risk for CME. Antiglaucoma therapy is necessary for patients with secondary ocular hypertension or glaucoma.
Surgical ● ● ●
● ●
Cataract surgery. Glaucoma surgery. Ethylenediaminetetraacetic acid (EDTA) chelation for band keratopathy. Core vitrectomy for clearing inflammatory debris. Pars plana vitrectomy and membrane peeling for cyclitic and epiretinal membranes.
COMPLICATIONS ● ● ●
● ● ●
●
●
Cataracts: 40% to 80%. Band keratopathy: 30% to 80%. Macular edema or epiretinal membrane formation: 30% to 50% in chronic cases. Vitreous haze/debris: 25%. Glaucoma: 15% to 30%. Chronic hypotony (ciliary body atrophy) and phthisis: 5% to 17%. Other posterior pole complications (disk neovascularization, ischemic optic neuropathy, macular hole): rare but can occur in chronic cases. Complications of treatments: ● Ocular hypertension caused by steroids; ● Growth stunting caused by oral corticosteroids; ● Infectious disease and organ toxicity in patients receiving immunosuppressive chemotherapy.
SUMMARY JIA-associated uveitis — the most common type of pediatric ocular inflammation — is, ironically, often asymptomatic in children with JIA, leading to insidious but progressive morbidity in a significant number of children with this serious disease:
Local ●
●
●
●
●
182
Corticosteroids (e.g. prednisolone acetate 1%) are the mainstay of therapy for patients with mild to moderate disease. Once disease activity is controlled, the frequency and potency of the regimen is reduced (e.g. to fluoromethalone 0.1%). About 20% of patients show little to no response to topical steroidal therapy. Periocular injections of corticosteroids (e.g. triamcinolone given as anterior sub-Tenon’s injections) or intravitreal injections are reserved for: ● More severe inflammation; ● Patients with more posterior inflammation; ● Patients with or at high risk for cystoid macular edema (CME). Prolonged therapy with steroids is associated with cataracts and glaucoma. Mydriatics (cycloplegics; e.g. scopolamine 0.25%) are used as adjunctive therapy to minimize posterior synechiae
FIGURE 99.1. Chronic JIA-associated uveitis, with low grade inflammation and synnechiae, often presented as a ‘white, quiet-appearing’ eye.
Wolf MD, Lichter PR, Ragsdale CG: Prognostic factors in the uveitis of juvenile rheumatoid arthritis. Ophthalmology 94:1242–1247, 1987.
100 WEGENER GRANULOMATOSIS 446.4
ETIOLOGY/INCIDENCE FIGURE 99.2. Improper management of JIA-associated uveitis may lead to formation of cataract, development of glaucoma, band keratopathy, among others, and eventual phthisis.
JIA-associated uveitis still blinds children. It is imperative that JIA patients with a high risk of developing eye disease (ANApositive girls with pauciarticular disease) be identified, screened, and followed closely. Similarly, once the diagnosis of JIA uveitis is made, every attempt should be made to eradicate the inflammation so as to minimize the chance of irreversible loss of vision (Figures 99.1 and 99.2).
REFERENCES Brewer EJ, Bass J, Baum J, et al: Current proposed revision of JRA criteria. Arthritis Rheum 20:195–199, 1977. Chen CS, Roberton D, Hammerton ME: Juvenile arthritis-associated uveitis: visual outcomes and prognosis. Can J Ophthalmol 39:614–620, 2004.
Wegener granulomatosis is a necrotizing, granulomatous vasculitis of the sinuses (upper respiratory tract), lungs (lower respiratory tract), and kidneys. A limited form of the disease exists in which renal lesions are not present. All age groups can be affected, and symptoms include rhinorrhea, sinus pain, cough, malaise and weight loss. There is no gender predilection; almost all affected patients are white. Although the etiology remains unknown, available evidence (deposition of immune complexes) indicates that immunopathogenic mechanisms are responsible.
COURSE/PROGNOSIS Most patients with Wegener granulomatosis initially have signs of upper respiratory tract inflammation that do not respond to treatment for commonly diagnosed conditions such as infection. Once the diagnosis has been established by biopsy, most affected patients have a relatively good prognosis with treatment; however, even with successful treatment, the disease is chronic, relapses occur and treatment complications are common.
Dana MR, Merayo-Lloves J, Schaumberg DA, Foster CS: Visual outcomes prognosticators in juvenile rheumatoid arthritis-associated uveitis. Ophthalmology 104:236–244, 1997.
DIAGNOSIS
Efthimiou P, Markenson JA: Role of biological agents in immune-mediated inflammatory diseases. South Med J 98:192–204, 2005.
Clinical signs and symptoms
Foster CS: Diagnosis and treatment of juvenile idiopathic arthritis-associated uveitis. Current Opinion in Ophthalmology 14:395–398, 2003. Giannini EH, Brower EJ, Kuzmind N, et al: Methotrexate in resistant juvenile rheumatoid arthritis: results of the U.S.A.-U.S.S.R. doubleblind, placebo-controlled trial. N Engl J Med 326:1043–1049, 1992. Kanski JJ, Shun-Shin A: Systemic uveitis syndromes in childhood: an analysis of 340 cases. Ophthalmology 91:1247–1252, 1984. Kanski JJ: Uveitis in juvenile chronic arthritis: incidence, clinical features and prognosis. Eye 2:641–645, 1988. Kanski JJ: Juvenile arthritis and uveitis. Surv Ophthalmol 34:253–267, 1990. Kimura SJ, Hogan MJ, Thygeson P: Uveitis in children. Arch Ophthalmol 51:80–88, 1954.
Because eye symptoms can be the initial manifestation of Wegener granulomatosis, ophthalmologists should be aware of this disorder. Ophthalmic manifestations include proptosis due to orbital involvement usually via extension from adjacent sinuses; dry eyes; conjunctivitis; superficial corneal infection and ulceration (secondary to proptosis) Figure 100.1; scleritis or episcleritis; and uveitis. Other reported eye or periocular abnormalities include obstruction of the nasolacrimal duct, optic neuritis, papilledema, central retinal artery occlusion, retinal vasculitis and choriocapillariitis.
Laboratory findings ●
Nguyen QD, Foster CS: Saving the vision of children with juvenile rheumatoid arthritis-associated uveitis. JAMA 280:1133–1134, 1998. Olson NY, Lindsley CB, Godfrey WA: Nonsteroidal anti-inflammatory drug therapy in chronic childhood iridocyclitis. Am J Dis Child 142:1289– 1292, 1988. Rosenberg AM: Uveitis associated with juvenile rheumatoid arthritis. Semin Arthritis Rheum 16:158–173, 1987. Smith JA, Thompson DJ, Whitcup SM, et al: A randomized, placebo-controlled, double-masked clinical trial of etanercept for the treatment of uveitis associated with juvenile idiopathic arthritis. Arthritis Rheum 53:18–23, 2005.
CHAPTER 100 • Wegener Granulomatosis
James L. Kinyoun, MD Seattle, Washington
●
●
Clinical findings: sinus and lung inflammation with or without renal involvement (e.g. proteinuria, hematuria, urinary casts). Histopathology: necrotizing, granulomatous vasculitis with infi ltrative neutrophils, lymphocytes, plasma cells, histiocytes and giant cells. Antineutrophil cytoplasmic antibody (cANCA).
Differential diagnosis ●
Upper respiratory infection (e.g. pulmonary infi ltrates, sinusitis).
183
SECTION 9 • Connective Tissue Disorders
cyte count should be followed closely during therapy (initially every other day and weekly during maintenance therapy) and should not decrease below 3000 cells/mm3. Granulocyte count below 1500 cells/mm3 increases the risk of infection. Dosages must be decreased at the first sign of bone marrow suppression because the full effect of the present dose will not manifest in the white blood cell count until 1 week later. Hemorrhagic cystitis can be minimized by adequate hydration to prevent concentrated urine. Fortunately, hair regrows in most patients who experience hair loss while taking cyclophosphamide. Complications of systemic corticosteroids include fluid retention, weight gain, moon face, hyperglycemia, osteoporosis, bone fractures, psychologic disturbances, peptic ulcers and infections. Side effects can be minimized by switching to treatment every other day and discontinuing steroids as soon as inflammation has been controlled. FIGURE 100.1. Wegener granulomatosis-corneal thinning.
COMMENTS ● ● ● ●
Glomerulonephritis. Otitis media. Orbital pseudotumor. Other small-vessel vasculitis (Churg–Strauss syndrome, microscopic polyangiitis, Henoch–Schönlein purpura, and essential cryoglobulinemic vasculitis).
TREATMENT
Ophthalmologists’ awareness of Wegener granulomatosis will lead to prompt referral to internists and early treatment with cytotoxic and immunosuppressant drugs. The promptness of diagnosis and successful treatment may not only save lives but also preserve useful vision. Affected patients will have to be followed by internists and ophthalmologists to monitor treatment effectiveness and the side effects of cytotoxic and immunosuppressive drugs. Depending on disease activity, follow-up examinations daily or at intervals of several months are appropriate.
Systemic ●
●
Cyclophosphamide 2 mg/kg PO qd and continuing for 1 year after active disease has subsided. Prednisone 1 mg/kg PO qd for 4 weeks, followed by a tapered dose and discontinuation.
Ocular ●
●
●
Topical eye lubricants (e.g. carboxymethylcellulose sodium 0.5%) every 30 minutes to 4 hours. Topical ophthalmic antibiotic solution or ointment (e.g. trimethoprim sulfate and polymyxin B sulfate) every 3 to 4 hours. Topical ophthalmic corticosteroid drops (e.g. prednisolone 1%) every 3 to 4 hours; cycloplegic eyedrops (e.g. tropicamide 1%) every 4 hours.
REFERENCES Harper SL, Letko E, Samson CM, et al: Wegener’s granulomatosis: the relationship between ocular and systemic disease. J Rheumatol 28:1025–1032, 2001. Hoffman GS, Kerr GS, Leavitt RY, et al: Wegener’s granulomatosis: an analysis of 158 patients. Ann Int Med 116:488–498, 1992. Jayne D, Rasmussen N, Andrassy K, et al: A randomized trial of maintenance therapy for vasculitis associated with antineutrophil cytoplasmic autoantibodies. N Engl J Med 349:36–44, 2003. Kinyoun JL, Kalina RE, Klein ML: Choroidal involvement in systemic necrotizing vasculitis. Arch Ophthalmol 105:939–942, 1987. Seo P, Stone JH: The antineutrophil cytoplasmic antibody-associated vasculitides. Am J Med 117:39–50, 2004
Surgical ●
●
Orbital decompression in patients with optic nerve compression that is unresponsive to medical treatment. Grafts (e.g. severe corneal ulceration).
Other ●
Methotrexate or azathioprine (may be useful for patients in remission who have serious side effects due to cyclophosphamide).
COMPLICATIONS Disease-related complications include vision loss, renal insufficiency, subglottic stenosis, and decreased hearing. Permanent morbidity occurs in a majority of patients. Complications of treatment with cyclophosphamide include bone marrow suppression, hemorrhagic cystitis, azoospermia, bladder carcinoma, nausea, vomiting and hair loss. The leuko-
184
101 WEILL–MARCHESANI SYNDROME 759.8 (Marchesani Syndrome, Spherophakia– Brachymorphia Syndrome) Teresa C. Chen, MD Boston, Massachusetts David Sellers Walton, MD Boston, Massachusetts
ETIOLOGY/INCIDENCE The Weill–Marchesani syndrome (WMS) is a very rare hereditary disorder that is manifested by microspherophakia, sublux-
ated lenses, high myopia, glaucoma, short stature, joint stiffness, and brachydactyly. It demonstrates both autosomal recessive and autosomal dominant transmission.
COURSE/PROGNOSIS ●
●
Adult dwarfism. Occasional heart defects. Glaucoma, the most serious ocular complication.
DIAGNOSIS Clinical signs and symptoms Diagnosis is made by recognizing ocular and systemic abnormalities. The affected lenses are small in diameter, are thickened, and often become dislocated anteriorly or inferiorly. Following shallowing of the anterior chamber, glaucoma may occur secondary to the pupillary block mechanism and appositional crowding of the angle due to a forward position of the lens iris diaphragm. The small stature of patients with this disorder can be striking and is associated with marked extremity abnormalities.
Patients at risk for pupillary block glaucoma should be followed regularly with gonioscopy. Iridotomy is indicated to prevent and relieve pupillary block. Following iridotomy, laser iridoplasty may be helpful to further open the angle. Goniosynechialysis may be necessary to remove an iris that is adherent to the trabecular meshwork so as to restore trabecular function. Early operation following angle closure is desirable. Other surgeries that may ultimately be needed for the treatment of glaucoma may include the following: pars plana lensectomy, anterior vitrectomy, sutured posterior chamber intraocular lens (PCIOL) placement and/or tube shunt surgery. Phacoemulsification with in-the-bag (modified or unmodified) capsular tension ring and PCIOL has also been performed.
COMPLICATIONS ● ● ●
Blindness secondary to glaucoma. Dwarfism. Clumsiness secondary to hand deformities.
COMMENTS Laboratory findings Delayed carpal ossification is revealed by radiography.
Differential diagnosis ● ● ● ●
Other causes of dwarfism. Mucopolysaccharidoses. Isolated hereditary lens subluxation and myopia. Hereditary microspherophakia.
CHAPTER 101 • Weill–Marchesani Syndrome
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Surgical
Genetic counseling is indicated. There is evidence of clinical homogeneity despite genetic heterogeneity in autosomal recessive (AR) and autosomal dominant (AD) families. These results underscore the difficulties for genetic counseling in supposed sporadic cases. Loci have been mapped in AR WMS (19p13.3-p13.2) and AD WMS (15q21.1). Systemic and ophthalmic screening should be performed to detect any previously unappreciated defects.
PROPHYLAXIS Laser iridotomy may be performed in cases in which there is threatened pupillary block and associated angle closure.
TREATMENT Ocular ● ●
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Optical correction for myopia and astigmatism. Glaucoma treatment: When glaucoma is present, topical βblockers, alpha adrenergics, carbonic anhydrase inhibitors, and prostaglandin agents may be helpful. Pupillary block glaucoma: In the absence of lens subluxation, miotics may induce or exacerbate pupillary block. Cycloplegics/mydriatics may relieve pupillary block but may also increase the risk of spontaneous lens dislocation into the anterior chamber.
REFERENCES Cionni RJ, Osher RH, Marques DM, et al: Modified capsular tension ring for patients with congenital loss of zonular support. J Cataract Refract Surg 29:1668–1673, 2003. Faivre L, Dollfus H, Lyonnet S, et al: Clinical homogeneity and genetic heterogeneity in Weill-Marchesani syndrome. Am J Med Genet 123A:204–207, 2003. Harasymowycz P, Wilson R: Surgical treatment of advanced chronic angle closure glaucoma in Weill-Marchesani syndrome. J Pediatr Ophthalmol Strabismus 41:295–299, 2004. Jensen AD, Cross HE, Paton D: Ocular complications in the Weill-Marchesani syndrome. Am J Ophthalmol 77:261–269, 1974. Ritch R, Wand M: Treatment of the Weill-Marchesani syndrome. Ann Ophthalmol 13:665–667, 1981.
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S E CTI ON
10
Skeletal Disorders
102 DOWN SYNDROME 758.0 (Trisomy 21) Natalio J. Izquierdo, MD San Juan, Puerto Rico
ETIOLOGY/INCIDENCE Various chromosomal abnormalities may lead to the Down syndrome including: a free trisomy 21 (94% of patients), translocation (4% of patients), and mosaicism (2% of patients). ● Free trisomy 21 results from nondisjunction during meiosis in one of the parents. This occurrence is correlated with advanced maternal and paternal age. The most common type of nondisjunction occurs in the maternal fi rst meiotic division. The percentage of errors during maternal second meiotic division is lower. The incidence of nondisjunction in the first and second meiotic division of the paternal gametogenesis is nearly equal. ● Translocation may occur de novo or be transmitted by one of the parents. Translocations are usually of the centric fusion type. They frequently involve chromosome 14 (14/21 translocation), 21 (21/21 translocation), or 22 (22/21 translocation). ● Mosaicism is considered a postzygotic event (following fertilization). Two cell lines are found; one with a free trisomy, and the other with a normal karyotype. This finding leads to patients with a great phenotypic variability, ranging from near normal to the classic trisomy 21 phenotype. Occurrence strongly depends on maternal age. For young mothers, the risk of a free trisomy is 1–2%. For mothers aged 20 years or younger, the occurrence is 1 per 2500 births. The risk increases considerably for mothers aged 35 years. For mothers aged 45 years or older, the occurrence is 1 per 55 live births.The risk for recurrence of Down syndrome in a patient’s siblings is also related to maternal age. Down syndrome occurs once in every 600–700 live births in the United States and Japanese populations.
COURSE/PROGNOSIS A primary care provider should lead and coordinate the multisystemic evaluation of patients with Down syndrome. Aware-
ness of systemic and ocular fi ndings is essential for managing patients with trisomy 21. ● Because of frequent congenital heart malformations, which occur in up to 60% of these patients, early cardiology consultation is desirable. ● Due to recurrent respiratory tract infections, a pediatric pneumologist should co-manage patients with Down syndrome. ● A child psychiatrist should lead liaison interventions, family therapies, and psychometric evaluations. Mental retardation is common in patients with trisomy 21; however, patients with mosaicism tend to have higher IQs. ● Up to 10% of patients with Down syndrome have epilepsy; therefore, neurological evaluation may be needed. ● Genetic counseling is indicated. ● Ophthalmic medical care for blepharitis, refractive errors, strabismus, corneal ectasias and cataracts is needed. ● Ophthalmic surgical indications used for non-handicapped patients are used for patients with Down syndrome. General anesthesia is desirable for patients with the syndrome who undergo surgery. Patients with Down syndrome have a shortened life expectancy. Early evaluation, diagnosis and intervention may prevent deaths due to congenital heart defects.
DIAGNOSIS Clinical signs and symptoms Eight or more of the characteristic clinical findings lead to a definite diagnosis. In doubtful cases, chromosomal analysis may be necessary. ● General physical features in patients with Down syndrome include shortened extremities, short limbs, short and broad hands, short fi fth middle phalanx, simian palmar creases, joint hyperextensibility or hyperflexibility, neuromuscular hypotonia, dry skin, premature aging, a wide range of intelligence quotients and congenital heart defects. ● Patients with the syndrome have characteristic craniofacial findings, such as flat occiput, a flattened facial appearance, anteriorly and posteriorly flattened head, dysplastic ears, small nose, depressed nasal bridge, protruding tongue, higharched palate, dental abnormalities, and a short and broad neck. ● Ocular signs in patients with the Down syndrome include: ● Lid anomalies such as prominent epicanthal folds, upward slanting of the palpebral fissures and congenital ectropion (rare) occur;
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SECTION 10 • Skeletal Disorders
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Lid infections, including blepharitis, blepharoconjunctivitis, chalazion, and hordeola. Because of recurrent external infections, inspect lids for collarettes, foamy secretions, Meibomian plugging, marginal erythema and scurf; Nasolacrimal duct obstruction; Amblyopia associated to strabismus, refractive errors, or media opacities; Strabismus occurs in up to 20% of patients; Evaluate corneas carefully for keratoconus or keratoglobus. Scissoring of the retinoscopic reflex is an early finding in patients with keratoconus. Use Placido disks, keratometers, or topographies to evaluate patients with Down syndrome who have keratoconus. Rizzuti and Munson signs appear later; Up to 90% of patients with the syndrome may have iris’ Brushfield spots. These spots are focal areas of iris stromal hyperplasia, surrounded by relative hypoplasia. These are more common in patients with lightly pigmented irides; Cataracts occur in patients with the syndrome. Lens opacities may be sutural, zonular, or complete. These may be congenital or may occur later in life; Glaucoma usually appears during infancy. Therefore, patients must be examined for corneal edema, megalocornea, increased intraocular pressure, progressive myopia, and optic nerve cupping; Retinal findings include: an increased number of retinal vessels crossing the disk margin, and retinal detachments; Patients with the syndrome may have refractive errors.
(Figure 102.1)
Laboratory findings Previous studies discuss the benefits of amniocentesis during pregnancy in mothers with low α-fetoprotein serum values during the beginning of the second trimester. Further, trisomy 21 may be diagnosed in the second and third trimester of pregnancy using prenatal echography. The following prenatal echographic findings are suggestive of Down syndrome and may be followed with amniocentesis and fetal chromosome analysis:
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Cystic hygroma colli; Cardiac defects; Duodenal obstruction; Hydrops fetalis; Prune belly anomaly.
Craniofacial radiographic findings in children with the syndrome may include: flattened facial features (including small or absent nasal bones), occiput, and brachycephaly. Echocardiography is advisable in patients with the syndrome.
TREATMENT Medical A primary care provider should lead and coordinate the multisystemic evaluation of patients with Down syndrome. Awareness of systemic and ocular fi ndings is essential for managing patients with trisomy 21. ● Medical therapy for blepharitis includes lid scrubs and topical antibiotics. ● Indications used for eyeglass prescription in nonhandicapped patients are used for patients with the syndrome. Glasses should be prescribed for patients at risk for amblyopia due to refractive errors, accommodative esotropia, aphakia, and pseudophakia.
Surgical Surgical indications used for nonhandicapped patients are used for patients with the syndrome. General anesthesia is advisable during surgical interventions. ● Systemic surgery: patients with congenital cardiac malformations as part of the syndrome may require early cardiovascular surgery. ● Ocular surgery: systemic evaluation, including a cardiovascular evaluation, is desirable prior to eye surgery. ● Patients with strabismus as part of the Down syndrome may benefit from strabismus surgery. ● Patients with corneal pathologies as part of the syndrome may develop corneal hydrops and perforation. Corneal transplants are indicated for severe scarring. ● Patients with trisomy 21 have a high incidence of cataracts. Cataract extraction is indicated when decreased vision affects quality of life. Extracapsular cataract extraction with intraocular lens implantation facilitates visual rehabilitation. Phacoemulsification offers the advantage of a small incision. ● Patients with the syndrome who develop keratoglobus are at increased risk of traumatic eye injuries. Traumatic ocular injuries are treated when required.
REFERENCES Berk AT, Saatci AO, Ercal MD: Ocular fi ndings in 55 patients with Down’s syndrome. Ophthalmic Genet 17(1):15–19, 1996. Caputo AR, Wagner RS, Reynolds DR: Down syndrome. Clinical review of ocular features. Clin Pediatr (Phila) 28(8):355–358, 1989. Copin H, Bremond-Gignac D: Ocular manifestations of Down syndrome and cytogenic aspects. J Fr Ophtalmol 27(8):958–959, 2004. da Cunha RP, Moreira JB: Ocular fi ndings in Down syndrome. Am J Ophthalmol 122(2):236–244, 1996.
FIGURE 102.1. Cataract in patient with Down syndrome.
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Frantz JM, Insler MS, Hagenah M: Penetrating keratoplasty for keratoconus in Down’s syndrome. Am J Ophthalmol 109(2):143–147, 1990.
Goto S, Yo M, Hayashi T: Intraocular lens implantation in severely mentally and physically handicapped patients. Jpn J Ophthalmol 39(2):187– 192, 1995. Haddow JE, Palomaki GE, Knight GJ: Prenatal screening for Down’s syndrome with use of maternal serum markers. N Engl J Med 327(9):588– 593, 1992. Jaeger EA: Ocular fi ndings in Down’s syndrome. Trans Am Ophthalmol Soc 78:808–845, 1980.
Roizen NJ, Mets MB, Blondis TA: Ophthalmic disorders in children with Down syndrome. Dev Med Child Neurol 36(7):594–600, 1994. Shapiro MB, France TD: The ocular features of Down’s syndrome. Am J Ophthalmol 99(6):659–663, 1985. Volker-Dieben HJ, Odenthal MT, D’Amaro J: Surgical treatment of corneal pathology in patients with Down’s syndrome. J Intellect Disabil Res 37(2):169–175, 1993.
CHAPTER 102 • Down Syndrome
189
SE CTION
11
Phakomatoses
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103 ANGIOMATOSIS RETINAE 759.6 (Angiomatosis of the Retina and Central Nervous System, Retinal and Optic Disk Capillary Hemangiomas, Retinal Capillary Hamartoma, Retinal Hemangioblastoma, von Hippel–Lindau Disease, von Hippel’s Disease)
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Proliferative vitreoretinopathy. Phthisis bulbi. Secondary glaucoma. Vision loss.
The ocular angiomas may develop in the retina (usually from the inner layers, as discrete angiomas – endophytic angiomas), in the optic nerve head, in the peripapillary retina (frequently from the outer layers – exophytic angiomas) where they are diffuse, or in the retrobulbar portion of the optic nerve.
Histologic findings Shiyoung Roh, MD Boston, Massachusetts John J. Weiter, MD, PhD Boston, Massachusetts
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ETIOLOGY/INCIDENCE Angiomatosis retinae (von Hippel’s disease) is characterized by congenital capillary angiomatous hamartomas of the retina and optic nerve. The retinal angiomas usually are diagnosed when the patient is between 10 and 30 years of age. Central nervous system (CNS) and visceral tumors are commonly noted after the ocular symptoms become manifest; if the CNS and viscera are involved, the condition is termed von Hippel–Lindau disease. The disorder is transmitted by autosomal dominant inheritance with incomplete penetrance and variable expressivity; there is no well-established predilection for gender or race. The retinal tumors often are multiple and are bilateral in more than 50% of cases; about 20% of patients with retinal angiomas develop CNS tumors.
DIAGNOSIS Clinical signs and symptoms Ocular ● ● ●
● ● ● ● ● ●
Angiomas of retina or optic nerve or both. Disk edema. Retinal or optic disk exudates, circinate retinopathy. Epiretinal membranes. Dilated, tortuous retinal vessels. Macular star exudation. Retinal hemorrhage. Retinal detachment. Vitreous hemorrhage.
exudative
Masses of capillaries exhibit an embryonic appearance (hemangioblastoma), often with abnormal fenestrations. Glial proliferation (of astrocytes) separates the vascular channels. Vascular channels frequently contain large lipid-filled vacuoles, most likely representing astrocytic phagocytosis of leaking plasma.
CLINICAL COURSE/PROGNOSIS Retinal tumors are usually at the equator or in the periphery, with a propensity for the temporal side. The tumor typically remains stable or grows very slowly. With gradual tumor growth, arteriovenous shunting occurs within the mass, resulting in an increasingly dilated, tortuous feeding artery and draining vein. With time, subretinal fluid and yellow exudate accumulate around the lesion and very often in the macula. Visual change resulting from the macular pooling of exudates often is the presenting sign. Endophytic tumors often produce vitreous traction that may lead to vitreous hemorrhage or tractional retinal detachment (rhegmatogenous or nonrhegmatogenous). Peripapillary angiomas tend to be exophytic and relatively flat, without feeding and draining vessels, resembling outer retinal telangiectasia. Multiple tumors tend to occur in the same retinal quadrant. The earliest endophytic tumors tend to be in the peripheral retina, with subsequent tumors appearing proximally in the same quadrant, having the same feeding and draining vessels. Fluorescein angiography shows arteriovenous shunting of blood through the tumor or tumors with an associated relative hypoperfusion of the retina peripheral to the tumor, suggestive of a vascular steal syndrome. Although not proven, the subsequent, more proximal angiomas may well represent a ‘neovascular angiomatous’ reaction in a susceptible vascular bed. Hemangiomas of the optic disk often mimic papilledema or disk edema; untreated retinal angiomatosis often leads to vitre-
191
ous hemorrhage, total retinal detachment, secondary glaucoma, and phthisis bulbi.
TREATMENT Surgical SECTION 11 • Phakomatoses
Angiomatosis retinae is usually a progressive disease, so therapy should begin as soon as diagnosis is made. The treatment selected depends on the size and location of the tumor or tumors, the clarity of the ocular media, and the associated ocular complications. In treating smaller tumors with a clear medium, argon laser photocoagulation has proven effective; treatment should consist of a large spot size and low-intensity and long-duration burns directed at the angioma itself. Multiple treatment sessions should be planned for all but the smallest tumors. The endpoint should be the obliteration of the tumor both by clinical observation and by fluorescein angiography. Once the tumor becomes yellowish (secondary to gliosis and lipid ingestion), photocoagulation becomes difficult because of poor penetration of the laser light. Anterior angiomas and larger posterior angiomas may be treated successfully with cryotherapy using a repetitive freezethaw technique. Only two or three freeze-thaw cycles should be used at each therapy session to minimize the risk of hemorrhage. Multiple treatment sessions usually are required. Eradication of the tumor or tumors by cryotherapy or photocoagulation usually results in resolution of the macular edema and improved visual acuity. For larger angiomas, angiomas unresponsive to cryotherapy or photocoagulation, and those associated with retinal detachment, penetrating diathermy under a lamellar scleral bed has proven effective. If there is extensive subretinal exudation, the fluid should be drained and a scleral buckling procedure considered. Frequently, large tumors develop surface membranes and vitreous traction that can lead to vitreous hemorrhage or rhegmatogenous retinal detachment; these complications may be amenable to treatment using the following: ● Vitreous surgery techniques; ● Endodiathermy; ● Scleral buckling procedures. The peripapillary and optic disk angiomas are difficult to treat without destroying useful central vision; diffuse exophytic peripapillary hemangiomas with associated visual loss may be considered for laser photocoagulation, using a wavelength that spares the inner retina and is well absorbed by blood; treatment should be conservative and aimed at the foci of greatest leakage.
tumor and to associated complications at the time therapy is initiated. Early detection of a peripheral tumor results in a good prognosis, whereas large tumors with an associated retinal detachment or angiomas of the optic nerve have a less favorable prognosis. These tumors are often multiple or bilateral or both, so close follow-up is important. Furthermore, because there is a familial tendency, other family members should be evaluated. The retinal angioma is the earliest and most common manifestation detected in screening examinations of families documented to have von Hippel–Lindau disease.
COMMENTS About 20% of patients presenting with retinal angiomas develop multiple systemic involvement (von Hippel–Lindau disease), so patients with angiomatosis retinae should have a thorough systemic evaluation. Cerebellar hemangioma is the typical CNS tumor in von Hippel–Lindau disease and it tends to occur somewhat later than the retinal angioma. The cerebellar tumor is similar to the retinal angioma in histologic appearance and in having large feeding and draining vessels. In von Hippel–Lindau disease, angiomas also may be found in the medulla oblongata, spinal cord, liver, or kidney. Cysts of the liver, pancreas, kidney, and epididymis occasionally are found as well, as is an elevated incidence of pheochromocytoma and renal cell carcinoma. In patients with von Hippel–Lindau disease, renal cell carcinoma is the most common cause of death, followed closely by cerebellar hemangioblastoma. Vasoproliferative angiomatous lesions are not infrequently found in the peripheral retina and can mimic von Hippel’s angiomas. There is evidence that both are related to upregulation of vascular endothelial growth factor (VEGF), and both may be amenable to treatment in the future with anti-VEGF agents. The gene for von Hippel–Lindau disease recently has been mapped to the short arm of chromosome 3 (3p25-p26) and appears to function at the molecular level as does the retinoblastoma gene-that is, as a recessive tumor-suppressor gene. Early detection is important for genetic counseling, and it improves the visual prognosis by allowing early treatment of retinal angiomas. Diagnosis using DNA markers allows relatives at low risk to be screened less often, thus enabling a focus on affected individuals and high-risk relatives.
SUPPORT GROUPS See internet www.vhl.org or email at
[email protected].
PRECAUTIONS Because these tumors are highly vascular, any form of treatment may cause further leakage or hemorrhage before the vascular channels are obliterated. This may result in further visual loss from macular exudation, vitreous hemorrhage and retinal detachment. Proliferative vitreoretinopathy frequently occurs after treatment of large tumors. Most of these complications are only exacerbations of the normal course of the disease process; however, many complications can be minimized by treating the angioma in multiple sessions rather than performing an aggressive single-session treatment. Treatment is best accomplished when the tumor is small. Prognosis for vision is related to the size and location of the
192
REFERENCES Annesley WJ, Jr, Leonard BC, Shields JA, et al: Fifteen-year review of treated cases of retinal angiomatosis. Trans Am Acad Ophthalmol Otolaryngol 83:446–453, 1977. Filling-Katz MR, Choyke PL, Oldfield E, et al: Central nervous system involvement in von Hippel-Lindau disease. Neurology 41:41–46, 1991. Gass JDM, Braunstein R: Sessile and exophytic capillary angiomas of the juxtapapillary retina and optic nerve head. Arch Ophthalmol 98:1790– 1797, 1980. Hardwig P, Robertson DM: von Hippel-Lindau disease: a familial, often lethal, multi-system phakomatosis. Ophthalmology 91:263–270, 1984.
Lindau A: Zur Frage der Angiomatosis Retinae und ihrer Hirnkomplikationen. Acta Ophthalmol 4:193–209, 1926. Machemer R, Williams JM, Sr: Pathogenesis and therapy of traction detachment in various retinal vascular diseases. Am J Ophthalmol 105:170– 181, 1988. Machmichael IM: von Hippel-Lindau’s disease of the optic disc. Trans Ophthalmol Soc UK 90:877–885, 1970.
Maher ER, Yates JRW, Harries R, et al: Clinical features and natural history of von Hippel-Lindau disease. QJ Med 77:1151–1163, 1990. Miyagawa Y, Nakazawa, M, Noda Y, et al: von Hippel-Lindau disease type 2A in a family with a duplicated 21-base-pair-in frame insertion mutation in the VHL gene. Graefes Arch Clin Exp Ophthalmol 241:241–244, 2003. Moore AT, Maher ER, Rosen P, et al: Ophthalmological screening for von Hippel-Lindau disease. Eye 5:723–728, 1991. Neumann HP, Wiestler OD: Clustering of features of von Hippel-Lindau syndrome: Evidence for a complex genetic locus. Lancet 337:1052– 1054, 1991.
COURSE AND PROGNOSIS Expressivity is highly variable and many patients with NF1 lead a normal life. Others, however, may have tumors of the central nervous system, structural abnormalities, or secondary malignancies. Visual prognosis depends on the presence or absence of optic pathway gliomas and orbital plexiform neurofibromas.
Nicholson DH, Green WR, Kenyon KR: Light and electron microscopic study of early lesions in angiomatosis retinae. Am J Ophthalmol 82:193–204, 1976.
DIAGNOSIS
Shields JA: Diagnosis and management of intraocular tumors. St Louis, CV Mosby, 1983:534–556.
Clinical signs and symptoms
von Hippel E: Uber eine sehr seltene Erkrankung der Netzhaut; Klinische Beobachtungen. Graefes Arch Clin Exp Ophthalmol 59:83–97, 1904. Welch RB: von Hippel-Lindau disease: The recognition and treatment of early angiomatosis retinae and the use of cyrosurgery as an adjunct to therapy. Trans Am Ophthalmol Soc 68:367–424, 1970. Wing GL, Weiter JJ, Kelly PJ, et al: von Hippel-Lindau disease angiomatosis of the retina and central nervous system. Ophthalmology 88:1311– 1314, 1981.
104 NEUROFIBROMATOSIS TYPE 1 237.7 (NF1, von Recklinghausen’s Disease, Peripheral Variant of Neurofibromatosis) Nastaran Rafiei, MD Baltimore, Maryland Cameron F. Parsa, MD Baltimore, Maryland
ETIOLOGY/INCIDENCE Neurofibromatosis (NF) is an autosomal dominant disorder predominantly affecting neuroectodermal derived tissue. It is characterized, thus, by the development of hamartomas of the skin and nervous system, increasing in number and size throughout life. In 1988, neurofibromatosis was reclassified into two distinct variants, NF1 and NF2. NF1 occurs in approximately 1 in 4000 individuals and generally features multiple café-au-lait spots, cutaneous neurofibromas and iris hamartomas (Sakurai–Lisch nodules). Half of affected individuals inherit the disease, while the others have novel mutations of predominantly paternal origin (with no apparent relation to paternal age).
CHAPTER 104 • Neurofibromatosis Type 1
Maher ER, Bentley E, Yates JRW, et al: Localization of the gene for von Hippel-Lindau disease to a small region of chromosome 3 confi rmed by genetic linkage analysis. Genomics 10:957–960, 1991.
The genetic mutation responsible for NF1 is in a tumor suppressor gene has been mapped to chromosome 17q11.2. The protein encoded by the gene, neurofibromin, is expressed at reduced levels in NF1, resulting in down-regulation of the ras protein (a protein that is involved in cell growth and differentiation) and dysregulated cell growth. Deletion of a second copy of this tumor-suppressing gene is necessary for development of malignancies.
The 1988 National Institute of Health Consensus Development Statement has suggested the presence of two or more of the following criteria for the diagnosis of NF1: ● Six or more café-au-lait spots, 5 mm or larger in prepubertal children, 15 mm or larger after puberty; ● Two or more neurofibromas of any type (e.g. placoid, nodular, pedunculated), or one plexiform neurofibroma; ● ‘Freckles’ in intertriginous areas; ● Glioma involving the anterior visual pathways; ● Two or more Sakurai–Lisch nodules; ● A distinctive osseous lesion such as sphenoid dysplasia or thinning of the cortex of the long bone (with or without pseudoarthrosis); ● A first-degree relative who has NF1 by these criteria.
Cutaneous manifestations Cutaneous manifestations include café-au-lait spots, neurofibromas and plexiform neurofibromas. Although over 10% of the general population may have one to three café-au-lait spots, nearly 99% of individuals with NF1 have multiple café-au-lait spots increasing in number and size with age. Neurofibromas are benign tumors consisting of Schwann cells admixed with nerve fibers, perineural cells and fibroblasts in various ratios accounting for differences in morphology. They grow around the time of puberty, continuing to enlarge throughout life. They contain increased numbers of mast cells and may be associated with pain, tenderness, or itchiness. Plexiform neurofibromas have markedly enlarged nerves surrounded by a thickened perineural sheath, and possess a ‘bag of worms’ consistency. Malignant degeneration of neurofibromas occurs in 5% of individuals.
Nervous system Juvenile pilocytic astrocytomas are common. While MRI studies have demonstrated the presence of gliomas in over 25% of patients with NF1, clinical symptoms occur in only a fraction of these. Occasionally, ependymomas, meningiomas and primitive neuroectodermal tumors may develop. Occasionally, mild cognitive impairment may result in various learning disabilities.
193
Optic nerve gliomas associated with NF1 often develop a perineural arachnoidal hyperplasia. The high water content of this tissue produces an image on T2-weighted MR imagery that looks like an expanded CSF space around the nerve. This socalled ‘pseudo-CSF signal’ is a specific marker of NF1. Although the NF1 gene has been cloned and characterized, its high mutation rate has limited the sensitivity and diagnostic value of laboratory-based genetic testing. SECTION 11 • Phakomatoses
Differential diagnosis
FIGURE 104.1. Multiple tan-colored and dome-shaped melanocytic hamartomas, Lisch–Sakurai nodules, are highly suggestive of NF1. They increase in number with age and may develop more commonly on the inferior aspect of the iris. The morphologic appearance, however, varies widely.
Ophthalmic involvement Sakurai–Lisch nodules, smooth, dome-shaped pigmented hamartomas of the iris, are not noted at birth, but are usually seen by age 10 years, and by age 30, are present in essentially all individuals with NF1. Although not pathognomonic, the presence of Sakurai–Lisch nodules is highly suggestive of NF1 and screening of family members is often warranted (Figure 104.1). Hamartomas of the conjunctiva, uveal tract or retina, and corkscrew retinal vascular abnormalities may be present. Indocyanine green angiography reveals hypofluorescent areas of the choroid. Proptosis may be present due to optic nerve glioma, orbital neurofibroma, or sphenoid bone defects. Periocular plexiform neurofibromas may cause glaucoma, ptosis and amblyopia.
Musculoskeletal involvement Musculoskeletal abnormalities include progressive kyphoscoliosis, pseudoarthrosis (often of the tibia), and hypoplasia of the sphenoid bone.
Other manifestations Other tumors of neural-crest origin such as pheochromocytoma and neuroblastoma also occur with increased frequency. However, as for the musculoskeletal manifestations of NF1 and for reasons not yet well understood, non-neural crest derived conditions such as rhabdomyosarcoma and myelogenous leukemia are also associated. Neurofibromin is expressed in endothelial cells and the NF1 gene plays an essential role in endothelial development with an increased incidence of congenital heart disease in those who harbor a mutation. Secondary hypertension occasionally develops from pheochromocytoma or renal artery stenosis.
Laboratory findings T2-weighted MRI images demonstrate multiple ‘bright lesions’ in the basal ganglia, cerebellum and brain stem in up to 80% of affected children — these decrease with age. Although a quarter of children imaged may also have gliomas, routine MR imaging for screening purposes is not recommended since the findings may not assist in management.
194
Ten times less frequent than NF1, NF2 (‘central’ or ‘acoustic’ neurofibromatosis) is characterized by vestibular schwannomas (acoustic neuromas) and the development of tumors typically involving neural coverings (meningiomas, schwannomas and ependymomas). Combined hamartomas of the retinal pigment epithelium and retina may be present. Sakurai–Lisch nodules are generally absent, but most affected individuals have presenile posterior lens opacities. Optic disc gliomas are rare, but highly suggestive of NF2. There is a relative lack of cutaneous findings. The genetic mutation has been mapped to the long arm of chromosome 22.
TREATMENT Observation with supportive treatment is generally recommended for optic pathway gliomas, which can regress spontaneously. Due to germline tumor-suppressor gene haploinsufficiency, treatment of NF1-associated tumors with alkylating agent chemotherapy and irradiation can produce somatic mutations throughout the body leading to subsequent malignant neoplasms. Plexiform neurofibromas affecting the orbit are generally diffuse and not fully excisable, with residua often leading to recurrences. Despite the cosmetic disfigurement, such tumors are often best left alone. Mast cell stabilizers such as oral ketotifen may reduce the itchiness, tenderness and pain associated with neurofibromas, and retard their growth. Occasionally, excision may be required. Anticipation and management of NF1 associated conditions such as secondary hypertension and malignancies is an important aspect of care, as is family counseling.
REFERENCES Arun D, Gutmann DH: Recent advances in neurofibromatosis type 1. Curr Opin Neurol 17:101–105, 2004. Beauchamp GR: Neurofibromatosis type 1 in children. Trans Am Ophthalmol Soc 93:445–472, 1995. Brodsky MC: The ‘pseudo-CSF’ signal of orbital optic glioma on magnetic resonance imaging: a signature of neurofibromatosis. Surv Ophthalmol 38:213–218, 1993. Critler AD, Zhu Y, Ismat FA, et al: NF1 has an essential role in endothelial cells. Nat Genet 33:75–79, 2003. DiMario FJ Jr, Ramsby G, Greenstein R, et al: Neurofibromatosis type 1: magnetic resonance imaging fi ndings. J Child Neurol 8:32–39, 1993. Jadayel D, Fain P, Upadhyaya M, et al: Paternal origin of new mutations in von Recklinghausen neurofibromatosis. Nature 343:558–559, 1990. Muci-Mendoza R, Ramella M, Fuenmayor-Rivera D: Corkscrew retinal vessels in neurofibromatosis type 1: report of 12 cases. Br J Ophthalmol 86:282–284, 2002. Riccardi VM: A controlled multiphase trial of ketotifen to minimize neurofibroma-associated pain and itching. Arch Dermatol 129:577–581, 1993. Sakurai T: Multiple neurofibroma patient showing multiple flecks on the anterior surface of the iris. Acta Soc Ophthal Jpn 39:87–93, 1935.
Yasunari T, Shiraki K, Hattori H, Miki T: Frequency of choroidal abnormalities in neurofibromatosis type 1. Lancet 356:988–992, 2000.
105 STURGE–WEBER SYNDROME 759.6
Monte A. Del Monte, MD Ann Arbor, Michigan Sturge–Weber syndrome (SWS) belongs to a group of disorders collectively known as phakomatoses (‘mother-spot’ diseases). It consists of congenital hamartomatous malformations that may affect the eyes, skin, and central nervous system at different times. SWS is classified into three categories: 1. Complete trisymptomatic SWS, in which all three organ systems are involved; 2. Incomplete bisymptomatic SWS, in which the involvement is either oculocutaneous or neurocutaneous; 3. Incomplete monosymptomatic SWS, in which there is only neural or cutaneous involvement. Patients without cutaneous involvement appear to be spared the ocular manifestations of the syndrome.
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ETIOLOGY/INCIDENCE The clinical manifestations of SWS have a common embryologic basis, the primary defect being a developmental insult affecting precursors of tissues that originate in the pro- and mesencephalic neural crest. These affected precursors then give rise to vascular and other tissue malformations in the meninges, the eyes and the dermis. Sources of the insult have been suggested to be: ● A somatic mutation in the precursors that may result in overproduction of an angiogenic factor; or ● A lethal gene, surviving by mosaicism. Incomplete SWS results from the same developmental defect but affects only those cells whose progeny are destined for the affected tissues. Unlike the other phakomatoses, which often have clear-cut hereditary patterns, the role of heredity in SWS has not been documented; to date, no gene defect has been associated with the syndrome. Several types of chromosomal abnormalities have been reported, but most SWS patients have normal karyotypes. The majority of SWS patients have a sporadic, nonfamilial disease. The syndrome occurs in all races, with no significant predilection for either sex. The incidence of SWS in the general population is unknown.
DIAGNOSIS Clinical signs and symptoms Systemic The hallmark of SWS is a facial cutaneous venous dilation, also referred to as nevus flammeus or port-wine stain, that occurs
CHAPTER 105 • Sturge–Weber Syndrome
(Encephalotrigeminal Angiomatosis Syndrome)
in as many as 96% of patients and is visible at birth. The nevus appears as one or more dull red patches of irregular outline, usually in the areas of the trigeminal nerve branches. Although it does not increase in size and is not medically threatening, the nevus does darken with age, and as a cosmetic blemish, it may carry psychologic impact. A leptomeningeal congenital venous angiomatosis, usually ipsilateral to the facial lesion and located most commonly in the meninges overlying the occipital and posterior parietal lobes, results in involvement of the central nervous system (CNS). Characteristic progressive calcifications in the external layers of the cerebral cortex beneath the angiomatosis are associated with cortical atrophy; occasionally, they extend anteriorly to the frontal and temporal lobes. Focal or generalized motor seizures occur in up to 85% of patients; they usually begin in the first year of life and may become profound, resulting in further neurologic and developmental deterioration. Early diagnosis and treatment are necessary to minimize permanent brain damage. Some degree of mental retardation is seen in about 60% of patients, as well as neurologic deficits such as: ● Hemiplegia; ● Homonymous hemianopsia.
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● ● ●
Eyelid hemangioma-like superficial changes that show, on histology, only venous dilation. Glaucoma, which is a significant cause of morbidity because of its early onset and resistance to conventional forms of treatment. Conjunctival and episcleral hemangiomas. Prominent, tortuous conjunctival and episcleral vascular plexi. Diffuse choroidal hemangiomas. Iris heterochromia. Tortuous retinal vessels, with occasional arteriovenous communications.
Glaucoma is estimated to occur in 30% to 70% of patients, with early onset (at birth or in early infancy) the rule, although it may present at any time. The glaucoma is almost always unilateral and ipsilateral to the port-wine stain, although contralateral or bilateral glaucoma with unilateral skin lesions have been reported. Occurrence of glaucoma has been noted especially when the facial skin changes involve both the upper and lower eyelids. As soon as SWS is suspected, a complete ophthalmic evaluation is essential to rule out glaucoma or to institute effective measures to control it, as the infant eye is quickly damaged by increased intraocular pressure (IOP). The earlier glaucoma can be detected and controlled, the less likely the patient is to suffer the secondary glaucomatous changes, including buphthalmos, increased corneal diameter, tears in Descemet’s membrane, corneal edema, and optic nerve damage that results in myopia, anisometropia, amblyopia, strabismus and visual field defects. All SWS patients require regular ophthalmic examination throughout life, even when no ocular abnormalities are initially detected, to avoid vision loss secondary to later-onset glaucoma. Amblyopia is an important cause of poor vision in patients with infantile glaucoma. It is usually anisometropic because of glaucoma-induced myopia or secondary to unilateral or bilateral pattern deprivation caused by cloudy corneas. Even when glaucomatous optic nerve damage is present, amblyopia may be
195
SECTION 11 • Phakomatoses
superimposed on the organic damage and a trial of amblyopia therapy is indicated. Prominent tortuous conjunctival and episcleral vascular plexi affect up to 70% of SWS patients and often correlate with increased episcleral venous pressure, probably resulting from arteriovenous shunts within the episcleral hemangiomas. Diffuse choroidal hemangioma (which appears as a circumscribed, isolated form in otherwise normal adults) is present in up to 50% of patients with SWS. Almost always unilateral, and ipsilateral to the port-wine stain, choroidal hemangiomas also have been reported as bilateral in association with bilateral nevus flammeus. These hemangiomas: ● Are flat; ● Commonly cover more than half the fundus; ● Involve the posterior pole; ● Extend into the equatorial zone; ● May show diffuse involvement of the entire uvea; ● Can have a striking reddish ‘tomato ketchup fundus’ appearance. Often a focal, perimacular area of the angioma is thickened and elevated, with dilation and tortuosity of the overlying retinal vessels and peripheral arteriovenous communications. Choroidal angiomatosis grows slowly and is usually asymptomatic in childhood, but during adolescence or adulthood a marked thickening of the choroid may become evident, with secondary changes to overlying ocular structures. These changes can range from mild atrophy of retinal pigment epithelium (RPE) and focal RPE proliferation with drusen formation to severe fibrous transformation and focal ossification of the RPE. The retina over the hemangioma may be attached and well preserved, attached but degenerated, or detached. Early-stage choroidal thickening and lifting of the retina may produce an increasing ipsilateral hyperopia. Degenerative retinal changes include focal chorioretinal adhesions, loss of photoreceptors, severe cystoid degeneration of the outer layers, and marked gliosis. Widespread serous detachment, retinal leakage, and edema may occur. Subretinal fibrosis near the macula and cystoid macular edema are associated with the most severe visual loss. Glaucomatous damage, degenerative changes in the outer retinal layers, and vascular abnormalities in the occipital lobe may cause visual field defects; careful examination with visual field perimetry is indicated. Iris heterochromia occurs in about 10% of SWS patients; the more deeply pigmented iris usually is ipsilateral to the portwine stain, indicating an increase in melanocyte numbers or activity.
Laboratory findings The three forms of SWS are generally diagnosed on clinical grounds by the association of the typical cutaneous, CNS, and ocular abnormalities. When a typical facial vascular skin lesion is found in a newborn, it should alert the physician to perform a complete ophthalmologic and systemic assessment for the potentially serious associated disorders. Neonates with bisymptomatic or trisymptomatic SWS may initially seem neurologically normal, without symptoms of glaucoma or other ocular problems; thus, in some instances the diagnosis may not become clear for some time. In young patients with suspected glaucoma, examination under anesthesia or deep sedation is necessary to confi rm the
196
diagnosis; careful assessment in each eye of intraocular pressure, corneal diameter, cycloplegic refraction, axial length, gonioscopy, and optic nerve cupping is mandatory. Ocular signs of infantile glaucoma associated with SWS include: ● Corneal diameter >12.0 mm during the first year of life; ● Corneal edema; ● Tears in Descemet’s membrane (Haab’s striae); ● Unilateral or bilateral myopic shift; ● Optic nerve cupping >0.3 or any cup asymmetry; ● Intraocular pressure >18 or 19 mm Hg. Increased conjunctival vascularity can be observed on a slitlamp examination or can be seen by the naked eye as a pinkish discoloration. However, the abnormal plexus of episcleral vessels may be hidden by the overlying tissue of Tenon’s capsule in infancy and appreciated clinically only in later childhood. Diagnosis of diffuse choroidal hemangioma is based on: ● Tumor appearance on binocular indirect ophthalmoscopy; ● A- and B-scan ultrasonography; A-scan shows high internal reflectivity, whereas B-scan typically shows a solid echogenic mass; ● Fluorescein angiography may reveal; ● Only a heightened background choroidal fluorescence early in the disease; ● Widespread irregular hyperfluorescence as dye leaks from the surface of a progressing tumor; ● A diffuse multilocalized pattern of fluorescein accumulation in the outer retina characteristic of polycystic degeneration and edema in more advanced disease. Diffuse choroidal hemangioma may easily be missed on ophthalmoscopic examination, especially in children, because the color of the hemangioma resembles that of the normal fundus, and the elevation may be minimal; comparison of the red reflex with the normal opposite eye can help in confirming the diagnosis. Central nervous system involvement can be confirmed by various neuroimaging methods: ● Plain skull radiographs are often adequate for diagnosis. ● Magnetic resonance imaging (MRI) allows detection of malformations affecting the CNS, including abnormal venous drainage and abnormal pial contrast enhancement associated with SWS angiomatous malformations, and it can detect cerebral volume reduction and ipsilateral choroid plexus enlargement; in addition, the technique can demonstrate the curvilinear posterior contrast enhancement of ocular choroidal angiomas, using intravenous contrast. ● Computed tomography (CT) is superior to MRI in detecting the characteristic double-lined gyroform pattern of calcifications paralleling cerebral convolutions, which are known to radiologists as the ‘railroad track’ sign; however, these calcifications usually are not detectable before 1 year of age and may not be seen until several years of age.
Differential diagnosis Disorders with clinical presentations similar to those of SWS must be included in differential diagnosis. They include the following: ● Klippel–Trenaunay–Weber (KTW) syndrome consists of port-wine stains of the extremities and face and hemihypertrophy of soft and bony tissues, as well as all the characteristics of SWS; KTW syndrome is sporadic, as is SWS. There is also an association in KTW syndrome between hemi-
●
hypertrophy and solid visceral tumors that most commonly affect the kidney, adrenal gland, or liver. Beckwith–Wiedemann syndrome consists of a facial portwine stain, macroglossia, omphalocele, and visceral hyperplasia; note that there is also some associated risk of visceral neoplasia. Also, severe hypoglycemia resulting from pancreatic islet cell hyperplasia is very common and may be life threatening.
When assessing the status of a uveal mass in a patient with SWS, the ophthalmologist must consider the possibility that the lesion may be something other than a choroidal hemangioma. ● The major clinical difficulty can be distinguishing a choroidal hemangioma from a choroidal melanoma. There are a few reports of patients with SWS who developed a choroidal tumor in the eye ipsilateral to the port-wine stain, and it eventually proved to be a malignant melanoma rather than a hemangioma. Simultaneous occurrence of uveal melanoma and choroidal hemangioma in a patient with SWS also has been described. The reddish-orange color of choroidal hemangiomas as viewed by binocular indirect ophthalmoscopy is an important diagnostic sign that differentiates them from metastatic carcinomas and amelanotic melanomas which have a white or creamy appearance. When uveal melanoma is suspected, both fluorescein angiography and A- and B-scan ultrasonography are essential. ● Other orange-colored fundus tumors that must be considered in a differential diagnosis of a diffuse choroidal hemangioma include. ● Serous or partly organized detachment of the retinal pigment epithelium. ● Osteoma of the choroids. ● Nodular scleritis. ● Exophytic retinal capillary hemangioma.
TREATMENT Ocular For small degrees of anisometropia, full optical correction of both eyes or at least full correction of the refractive difference between the eyes is desirable. In higher degrees of anisometropia
CHAPTER 105 • Sturge–Weber Syndrome
Neuroimaging findings similar to those of SWS may be found in several other conditions and should also be considered in the differential diagnosis: ● In Dyke–Davidoff–Masson syndrome, one cerebral hemisphere is partially or completely atrophic as a result of an intrauterine or perinatal carotid artery infarction; because the cerebral atrophy in SWS also occurs during infancy, changes similar to those of Dyke–Davidoff–Masson syndrome may be seen, including cerebral hemiatrophy with ipsilateral calvarial diploic space enlargement. ● Severe siderosis, prior to injection of contrast material, has MRI findings similar to those in SWS with cerebral hemiatrophy. The typical contrast enhancement and the abnormal veins seen with contrast injection easily differentiate the two conditions. ● Calcification secondary to intrathecal methotrexate therapy and meningitis also must be included in the CT differential diagnosis of cortical pattern calcification; neither of these, however, would demonstrate the specific unilateral geographic localization.
or if the child develops strabismus, treatment to prevent amblyopia and treat the strabismus should be initiated. Anisometropic amblyopia may require occlusion therapy along with correction of the refractive error; in some patients, a contact lens may be required to treat fusion difficulty due to aniseikonia. Medical treatment for SWS glaucoma usually fails with time but may be tried initially, as significant (albeit temporary) reduction in IOP may be achieved. Reduced IOP may clear the cornea and permit surgery to proceed or, in younger patients, delay the need for fi ltration surgery. This is especially important considering the excessive difficulties of operating on a small eye, as well as the tendency of the younger patient to scar at the site of the scleral flap, which may reduce long-term success. Medical therapy can also be used as an adjunct to surgery. Topical antiglaucoma therapy for extended periods is sometimes helpful postoperatively to further reduce borderline elevations in IOP without the need to reoperate. Initial medical therapy with a: ● Topical β-blocker, followed sequentially by the addition of a carbonic anhydrase inhibitor (systemic in infants and topical in older children), and an α-adrenergic agonist (bromonidine), or a topical prostaglandin receptor agonist (latanoprost) is a reasonable protocol in SWS patients. In recent years, few patients with diffuse choroidal hemangiomas associated with a bullous nonrhegmatogenous retinal detachment have been treated with radiation therapy such as: ● Brachytherapy; or ● External beam irradiation. Preliminary reports suggest that radiation therapy may be a reasonable alternative to the currently preferred photocoagulation in selected patients, but the ultimate risk-to-benefit ratio of this form of therapy is still unknown, as are its precise indications and contraindications.
Surgical Surgery, rather than medical therapy, is still considered by most ophthalmologists to be the mainstay for glaucoma therapy in SWS, with antiglaucoma medications being used primarily as adjuncts. The selection of surgical technique remains controversial, however, because the long-term results are often disappointing with any of the procedures, and none of them enjoys the success with SWS glaucoma that it may have when initially performed for primary infantile glaucoma. Because of the rarity of SWS, the published accounts of surgically treated cases have been uncontrolled, and no standard guidelines exist. The objective of therapy is rapid and permanent lowering of the IOP into the normal range (generally, 25 mm Hg for 6 days or >4 days of total hyphema); ● High risk of synechiae formation (large hyphema >50% of the anterior chamber for >8 days); ● High risk of optic atrophy (IOP > 24 mm Hg for >24 hours in sickle cell disease, IOP > 60 mm Hg for >2 days or >50 mm Hg for 5 days).
Daily examination for rebleeding; record vision, level of hyphema and corneal clarity. Check IOP if clinically indi-
Admit the patient to the hospital if not already admitted. Consider the rebleeding as a new hyphema and continue the daily examination and treatment for at least 5 more days. All of the criteria for initial management of the hyphema apply to the management of the secondary bleeding.
Follow up ●
Long term follow up of the hyphema patient is indicated for the detection of the late onset complications such as cataract and secondary glaucoma.
REFERENCES Crouch ER, Jr, Frenkel M: Aminocaproic acid in the treatment of traumatic hyphema. Am J Ophthalmol 81:355–360, 1976. Farber MD, Fiscella R, Goldberg MF: Aminocaproic acid versus prednisone for the treatment of traumatic hyphema. Ophthalmology 98:279–286, 1991. Goldberg MF: The diagnosis and treatment of sickled erythrocytes in human hyphema. Trans Am Ophthalmol Soc 76:481–501, 1978. Nasrullah A, Kerr NC: Sickle cell trait as a risk factor for secondary hemorrhage in children with traumatic hyphema. Am J Ophthalmol 123:783– 790, 1997. Rahmani B, Jahadi HR: Comparison of tranexamic acid and prednisolone in the treatment of traumatic hyphema: a randomized clinical trial. Ophthalmology 106:375–379, 1999. Rahmani B, Jahadi HR, Rajaeefard A: An analysis of risk for secondary hemorrhage in traumatic hyphema. Ophthalmology 106:380–385, 1999. Read J: Traumatic hyphema: surgical vs medical management. Ann Ophthalmol 7(5):659–670, 1975. Read J, Goldberg MF: Comparison of medical treatment for traumatic hyphema. Trans Am Acad Ophthalmol Otolaryngol 78:799–815, 1974. Recchia FM, Saluja RK, Hammel K, Jeffers JB: Outpatient management of traumatic microhyphema. Ophthalmology 109:1465–1470, 2002. Romano PE, Robinson JA: Traumatic hyphema: a comprehensive review of the past half century yields 8076 cases for which specific medical treatment reduces rebleeding 62%, from 13% to 5% (P < 0001). Binocul Vis Strabismus Q 15(2):175–186, 2000. Rynne MV, Romano PE: Systemic corticosteroids in the treatment of traumatic hyphema. J Pediatr Ophthalmol Strabismus 17:141–143, 1980. Sears ML: Surgical management of black ball hyphema. Trans Am Acad Ophthalmol Otolaryngol 74:820–826, 1970. Walton W, Von Hagen S, Grigorian R, Zarbin M: Management of traumatic hyphema. Surv Ophthalmol. 47(4):297–334, 2002. Yasuna E: Management of traumatic hyphema. Arch Ophthalmol 91:190– 191, 1974.
SE CTION
17
Choroid
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169 ANGIOID STREAKS 363.43 Robert C. Kwun, MD Park City, Utah
Indocyanine green angiography ●
ETIOLOGY/INCIDENCE Angioid streaks are irregular, jagged, curvilinear lines that radiate from the optic nerve in all directions. These lines were first described in 1889 by Doyne and later called angioid streaks by Knapp because of their resemblance to the branching pattern of blood vessels. The streaks lie beneath the retina and above the choroidal vasculature and are caused by breaks in the collagenous and elastic portion of Bruch’s membrane. These reddish-brown lesions are almost always bilateral and usually do not go past the equator. The streaks may be wide or narrow and may vary in length and number. Often, these lesions are associated with peripapillary chorioretinal changes. The clinical significance of angioid streaks is based on the common association with several systemic disorders, such as pseudoxanthoma elasticum (Gronblad–Strandberg syndrome), osteitis deformans (Paget’s disease), sickle cell anemia, senile elastosis of skin, hypertensive cardiovascular disorders and, rarely, fibrodysplasia hyperelastica (Ehlers–Danlos syndrome). In addition, streaks are associated with choroidal neovascularization, retinal pigment epithelial detachment and macular degeneration. Other associated findings include peau d’orange fundus changes, disc drusen, peripheral focal salmon spots and pigmentary changes along the streaks.
Streaks not seen clinically and associated choroidal neovascularization, retinal pigment epithelium detachments, and serous or hemorrhagic detachments may be demonstrated.
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●
There is early hypofluorescence of the streaks with later hyperfluorescence and staining. Tiny hyperfluorescence spots are seen at the borders of the streaks. There is high resolution of choroidal neovascularization around the streaks.
Histopathology ●
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Angioid streaks are discrete linear breaks in Bruch’s membrane that are often characterized by extensive calcific degeneration. Fibrovascular ingrowth may occur in some of these breaks. Salmon spots are isolated breaks in Bruch’s membrane with fibrovascular ingrowth. Optic nerve drusen with streaks is usually associated with pseudoxanthoma elasticum.
Related systemic diagnosis in patients with angioid streaks ● ● ● ● ●
Pseudoxanthoma elasticum (89%). Paget’s disease of bone (5%). Hemoglobinopathy (2%). Ehlers–Danlos syndrome (2%). Other (2%).
Differential diagnosis
COURSE/PROGNOSIS
● ●
The patient is usually asymptomatic early in the course of the disease. Visual loss with metamorphopsia occurs with time. Exudative macular degeneration develops. Minor trauma may cause subretinal hemorrhage.
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● ● ●
Macular degeneration. Choroidal sclerosis. Myopia and lacquer cracks. Pigment lines of reticular dystrophy of retinal pigment epithelium. Traumatic hemorrhage. Choroidal rupture. Chorioretinal folds.
DIAGNOSIS Laboratory findings Fluorescein angiography ●
●
Usually, early hyperfluorescence of the streaks is revealed with late staining. See Figure 169.1. Occasionally, hypofluorescence of the streaks is seen with hyperfluorescence of margins.
TREATMENT The use of safety glasses can prevent direct ocular trauma, and contact sports should be avoided. Low vision aids can be used.
315
170 CHOROIDAL DETACHMENT 363.70 (Ciliochoroidal Detachment)
SECTION 17 • Choroid
James W. Hung, MD Boston, Massachusetts A. Robert Bellows, MD Boston, Massachusetts
ETIOLOGY/INCIDENCE
FIGURE 169.1. Angiography shows irregular hyperfluorescence along the course of the angioid streaks.
There is a possible role for laser photocoagulation in welldefined juxtafoveal choroidal neovascularization associated with angioid streaks. Verteporfin photodynamic therapy of choroidal neovascularization in angioid streaks may limit visual loss.
REFERENCES Browning AC, Chung AK, Ghanchi F, et al: Verteporfi n photodynamic therapy of choroidal neovascularization in angioid streaks: one year results of a prospective case series. Ophthalmology 112:1227–1231, 2005. Clarkson JG, Altman RD: Angioid streaks. Surv Ophthalmol 26:235–246, 1982. Gelisken O, Hendrikse F, Deutmann AF: A long-term follow-up study of laser coagulation of neovascular membranes in angioid streaks. Am J Ophthalmol 195:299, 1988. Groenblad E: Angioid streaks-pseudoxanthoma elasticum: vorlaeufige Mitteilung. Acta Ophthalmol 7:329, 1929. Knapp H: On the formation of dark streaks as an unusual metamorphosis of retinal hemorrhage. Arch Ophthalmol 21:289–292, 1982. Lebwohl M, Phelps R, Yannuzzi L, et al: Diagnosis of pseudoxanthoma elasticum by scar biopsy in patients without characteristic skin lesions. N Engl J Med 317:347–350, 1987. Lim JI, Bressler NM, March MJ, Bressler SB: Laser treatment of choroidal neovascularization in patients with angioid streaks. Am J Ophthalmol 116:414–423, 1993 Paton D: The relation of angioid streaks to systemic disease. Springfield, Ill, Charles C Thomas, 1972. Quaranta M, Cohen SY, Krott R, et al: Indocyanine green videoangiography of angioid streaks. Am J Ophthalmol 119:136–142, 1995. Verhoeff FH: Histological fi ndings in a case of angioid streaks. Br J Ophthalmol 32:531, 1948.
316
Choroidal detachment is a clinical term used to describe the separation of the choroid and sclera created by a fluid accumulation between the two layers. Anatomically the suprachoroidal space is a potential space, normally containing less than 10 microliters of fluid and is limited anteriorly by the scleral spur and posteriorly by the vortex veins. When fluid accumulates in this space, anterior displacement of the ciliary body and lens iris diaphragm often occurs and is associated with anterior chamber shallowing. The term ciliochoroidal detachment can be used interchangeably, since it implicates both the ciliary body and the choroid. Although accumulation of any type of fluid can produce a choroidal detachment, the two most common forms are associated with the accumulation of serous and/or hemorrhagic fluids. The exact mechanism of any form of choroidal detachment is not fully understood, but intraocular hypotony is thought to be a primary contributor. When sufficient lowering of the intraocular pressure below episcleral venous pressure creates a pressure differential across the capillary bed, this gradient promotes the transudation of serous fluid from the choriocapillaris into the suprachoroidal space creating a detachment of the choroid and often retina from the sclera. Small and medium sized protein molecules move through intact cells with leaky junctions and accompanying the fluid into the suprachoroidal space. The drop in intraocular pressure creates a hydrostatic pressure gradient that can also produce mechanical traction on the arteries, veins and choroid when they emerge from the intrascleral canals. The rupture of these vessels is thought to be the etiology of hemorrhagic choroidal detachment referred to as a suprachoroidal hemorrhage. While there are many causes of hypotony it is most often found in the setting of ocular trauma, intraocular surgery, particularly glaucoma filtering surgery or tube shunt surgery, infrequently in cataract surgery and rarely in circumstances of aqueous suppressants or other pharmacologic agents. Other specific entities associated with the development of choroidal detachment include inflammation, vascular abnormalities and malignancy. Inflammation as manifested in scleritis, choroiditis, Vogt–Koyanagi–Harada syndrome, Wegener’s granulomatosis, orbital pseudotumor, and extensive panretinal photocoagulation frequently lead to the accumulation of serous fluid in the suprachoroidal space. Vascular malformations such as carotid-cavernous fistulas and Sturge Weber syndrome, as well as a unique ophthalmic syndrome associated with prominent episcleral vessels and elevated episcleral venous pressure. These vascular entities are associated with an increase in resistance of blood flow through the episcleral vessels and result in accumulation of fluid in the suprachoroidal space. Additional unusual anatomic variants such as nanophthalmos and the uveal effusion syndromes are associated with choroidal detachment as are ocular tumors, primary and secondary, that can cause a choroidal detachment.
choroidal detachment with no transillumination in solid tumors. Suprachoroidal hemorrhages may develop suddenly and present as large, very dark balloon-like elevations of the choroid. Occasionally B-scan ultrasonography can distinguish blood in the suprachoroidal space. Development of an intraocular hemorrhagic choroidal detachment is heralded by the patient expressing severe pain, often ‘breaking through’ apparent adequate local anesthesia. The surgeon may notice an alteration in the red reflex, often associated with shallowing of the anterior chamber and positive vitreous pressure in the presence of a large wound, extrusion of retina and the intraocular contents. Principal effort is directed to closing the wound to prevent egress of tissue.
Differential diagnosis ● ● ● ●
Serous choroidal detachment. Hemorrhagic choroidal detachment. Retinal detachment. Primary metastatic tumors.
PROPHYLAXIS
CHAPTER 170 • Choroidal Detachment
The risk factors of choroidal detachment include: advanced age, preoperative elevated intraocular pressure, high myopia, elevated episcleral venous pressure, severe hypertension, Valsalva maneuvers and aphakia. Choroidal detachments have also been documented to form spontaneously or related to medication. The risk factors of developing a suprachoroidal hemorrhage are many of the mentioned entities and, in addition, blood dyscrasias, anticoagulants, increased intraocular pressure that is lowered suddenly, fi ltering surgery and tube shunt procedures. The reported incidence of choroidal detachments vary widely depending on the etiology and clinical setting. It must be emphasized that the incidence of choroidal detachment is far less since the advent of sutured flap closure of glaucoma fi ltering procedures and tight wound maintenance and closure following cataract surgery. The use of antimetabolites has resulted in more successful lowering of intraocular pressure and surprisingly enough has not been associated with an increase in the incidence of choroidal detachment. The entity of hypotony maculopathy is more prevalent with hypotony following antimetabolites than is the development of a choroidal detachment. Serous choroidal detachments are more common following the postoperative periods of hypotony after glaucoma surgery. With the advent of phacoemulsification surgery the maintenance of intraocular pressure during surgery and tight wound closure following surgery has minimized postoperative hypotony with only the rare complication of choroidal detachment following cataract surgery. The more frequent use of glaucoma drainage implant surgery (tube shunt), both valve and nonvalve, has been associated with a higher incidence of choroidal detachment, particularly hemorrhagic choroidal detachments. The entity of an expulsive suprachoroidal hemorrhage during surgery is now rare because of the small incision tight wound closure associated with most cataract and glaucoma surgery. The incidence of choroidal detachment has also diminished in penetrating keratoplasty and vitreoretinal procedures.
The development of a serous or hemorrhagic choroidal detachment is difficult to predict and to prevent. However, meticulous preoperative evaluation of the patient as well as intraoperative efforts to minimize the degree of length of time of ocular hypotony can diminish the attendant risk. Preoperative systemic hypertension should be medically controlled. Administration of anticoagulants, aspirin containing medications or anything altering the blood clotting mechanism should be avoided if possible. Intraocular pressures should be lowered slowly with digital pressure or osmotic agents. The choice of anesthetic, general or local, is not usually associated with the development of a choroidal detachment. However, in patients with elevated venous pressure, alteration of the venous drainage system from the head during general anesthesia can cause elevation of pressure in the venous drainage system of the eye.
DIAGNOSIS Intraoperative Clinical signs and symptoms A serous choroidal detachment is usually painless unless associated with underlying inflammatory cause such as scleritis. However, a hemorrhagic choroidal detachment is often heralded by severe sudden pain that is often diagnostic. Choroidal detachments appear as large, brown, quadratic intraocular dome-shaped balloons that often exist circumferentially, most prominent nasal and temporal. Minimally elevated anterior choroidal detachments are often difficult to identify with an ophthalmoscope and are more often associated with shallowing of the anterior chamber. B-scan ultrasonography is helpful in documenting a posterior choroidal detachment but ultrasound biomicroscopy (UBM) is frequently necessary to identify anterior choroidal detachments. A recent study has utilized color Doppler imaging to identify choroidal detachments and distinguish them from retinal detachments. This distinction is often more accurately made during the clinical examination. Large choroidal detachments can lead to direct apposition of opposing retinal surfaces frequently referred to as ‘kissing’ choroidals and often require drainage. In an effort to distinguish a choroidal detachment from an intraocular tumor, transilluminating (Hagen’s sign) results in a transillumination of a
A paracentesis should be created to very slowly lower the intraocular pressure in order to slowly reduce the pressure gradient. Microsurgical techniques are necessary for visualization and appropriate closure of ocular tissues with fine suture material. The tight suture closure of trabeculectomy flaps or corneal incision and ligature sutures in non-valve tube shunt procedures can be utilized. Antimetabolite agents are always used with caution.
Postoperative The need to avoid prolonged hypotony is possible. Attempts are made to minimize coughing, straining, vomiting, heavy lifting and aggressive physical activity. Stool softeners, laxatives and anti-emetic agents are frequently recommended.
TREATMENT Ocular Serous or small hemorrhagic suprachoroidal detachment Serous and small hemorrhagic suprachoroidal detachments are usually self-limited. When the intraocular architecture is not
317
SECTION 17 • Choroid
significantly altered surgical therapy is not indicated. Medical therapy typically results in spontaneous absorption of fluid or blood products within a few postoperative days heralded by a gradual resolution of the choroidal detachment. Topical use of cycloplegic/mydriatic drops in addition to frequent topical steroids is necessary. A hemorrhagic choroidal detachment with blood in the suprachoroidal space is often associated with more significant inflammation and frequently dull, achy pain that persists for a week or longer. In this situation topical corticosteroid drops should be applied every 2–3 hours and extended cycloplegia is often helpful to minimize pain associated with inflammation and throughout the ciliary body spasm. Occasionally high dose systemic corticosteroids may be of value while the consideration of topical non-steroidal anti-inflammatory agents perhaps can be helpful. Excessive fi ltration following the filtration surgery might be diminished with a firm pressure patch early in the course or a large bandage contact lens or compressive shell.
advised to use an anterior chamber infusion cannula connected to balanced salt solution so that a controlled, steady intraocular pressure is maintained and the anterior chamber depth is unaltered during the procedure. If a cannula is not available, alternating reformation of the anterior chamber with balanced salt solution with release of fluid from the suprachoroidal space can be utilized. The eye must not be allowed to remain soft during this procedure since fragile vessels may bleed with tissue deformation. The drainage procedure continues until as much fluid as possible is released. When little or no fluid can be evacuated, the anterior chamber is reformed, the sclerostomy is left unsutured and the conjunctiva is closed with absorbable suture. Complications of choroidal tap include exacerbation of intraocular inflammation, bacterial endophthalmitis, recurrence of suprachoroidal hemorrhage or serous choroidal detachment, anterior chamber shallowing and flattening, corneal decompensation, cataract progression and the possibility of creating a cyclodialysis cleft.
Surgical Serous choroidal detachment and intraoperative serous choroidal detachment
318
Postoperative delayed suprachoroidal hemorrhage
If an active wound leak is discovered in the presence of choroidal detachment, the wound leak should be sutured. The indications for surgical intervention (choroidal tap) in the presence of a serous choroidal detachment include: ● Lens-corneal touch; ● Progressive corneal edema or rapid cataract formation; ● A flat anterior chamber with inflammation and a failing fi ltration bleb; ● Hemorrhagic choroidal detachment with a flat anterior chamber; ● Intraocular inflammation, a flat anterior chamber and aphakia or pseudophakia with no improvement in 3 to 5 days; ● A large pronounced choroidal detachment with appositional (kissing) choroidals for longer than 48 hours; ● Wound leak with flat anterior chamber and prominent choroidal detachment.
A small or moderate suprachoroidal hemorrhage is usually localized and will frequently resolve spontaneously. If the ocular architecture is not significantly disturbed, medical therapy and clinical observation are indicated. Larger hemorrhagic choroidal detachments associated with ocular inflammation or flat anterior chamber and elevated intraocular pressure as well as the potential for unresolved apposition of retinal surfaces requires surgical intervention. The management includes choroidal tap combined with pars plana vitrectomy and infusion of expansive gasses, perfluorocarbon liquids or even silicone oil. The surgery is best performed when maximum liquification of the suprachoroidal hemorrhage has occurred, usually in the 10–14 day period. Collaboration with a vitreoretinal surgeon is strongly advised since these techniques are a standard part of vitreoretinal surgery. The likelihood of recurrence of a hemorrhagic choroidal detachment following the use of intraocular gas is diminished significantly.
Choroidal tap
Intraoperative expulsive suprachoroidal hemorrhage
The tap is performed under local or general anesthesia. Paracentesis is necessary to reform the anterior chamber. The use of a preexisting paracentesis incision is often helpful since the eye may be soft and a new incision difficult to create. The conjunctiva and Tenon’s capsule are incised circumferentially approximately 3.5 mm from the visible limbus in the inferotemporal and inferonasal quadrants. Both quadrants should be tapped to remove fluid because one quadrant tap may not be sufficient to remove all of the fluid that usually extends to 360-degrees in the suprachoroidal space. Adequate hemostasis is established with cautery. A radial incision is made with a scratch-down maneuver and carried carefully into the suprachoroidal space. When entering the suprachoroidal space a copious amount of suprachoroidal fluid escapes. It is important that the incision be at least 1.5 to 2 mm long in order to facilitate the egress of fluid. In the presence of a serous detachment the fluid is xanthochromic while with hemorrhagic detachments, serous and serosanguinous fluid is released and frequently followed by dark, unclotted blood (‘crank case’ oil) that has a more viscous character. Alternating elevation and depression of each side of the incision facilitates the release of the suprachoroidal fluid. It is
Intraoperatively, all efforts are directed to rapidly close the wound and prevent extrusion of intraocular contents. Once this is accomplished it is wise to wait for liquification of the hemorrhagic clot and then proceed with drainage of the suprachoroidal space and the use of intraocular gas or perfluorocarbon. Aggressive management of intraocular pressure, pain control and inflammation is necessary. Given the guarded prognosis following the suprachoroidal hemorrhage a frank and sensitive discussion with the patient and the patient’s family is necessary.
COURSE/PROGNOSIS Serous choroidal detachment Serous choroidal detachment occurs in the early postoperative period from 2 to 7 days following glaucoma surgery or combined cataract and glaucoma surgery. With contemporary phacoemulsification cataract surgery choroidal detachment is a rare event. Intraoperative choroidal detachments occur most often in patients with prominent episcleral vessels and elevated venous pressure but can also occur in vascular anomalies such as
Sturge–Weber syndrome. Draining of the suprachoroidal space during the procedure is effective in minimizing the complications of an intraoperative choroidal detachment. Postoperative detachments are significant for painless visual symptoms related to hypotony, anterior chamber shallowing or awareness of a visual field defect from a large choroidal detachment. The prognosis of a serous choroidal detachment with or without drainage is usually associated with no significant change in functional vision. The development of cataract following choroidal detachment, particularly if drainage is necessary, is a common complication and may require cataract surgery.
Wu J, Zou L, Wu Z: High frequency color Doppler image of choroidal detachment. Yan Ke Xue Bao 16:61–64, 2000.
Hemorrhagic choroidal detachment
Choroidal folds represent folds in Bruch’s membrane and the anterior choroid with secondary folds in the overlying retina. They are a distinct and separate entity from retinal folds. Choroidal folds were fi rst described by Nettleship in 1884 as alternating light and dark striae in the posterior pole. They typically radiate horizontally from the temporal optic disc, but may also be vertical or oblique. Choroidal folds are of varying number, length, and width, and never extend beyond the equator.
John D. Bullock, MD, MPH, MSc Dayton, Ohio Ronald E. Warwar, MD Dayton, Ohio
ETIOLOGY ● ● ●
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COMMENTS Identification and management of serous choroidal detachment has changed minimally in the last three decades while recognition and aggressive management of hemorrhagic choroidal detachments that require surgery has improved as the technology of vitreoretinal surgery has made great strides. The incidence of both serous and hemorrhagic detachments has diminished due to surgical techniques that utilize small, seal sealing or sutured wounds with maintenance of the intraocular dynamics during surgery to reduce profound and prolonged hypotony. While a cautious guarded prognosis for a massive intra or postoperative hemorrhagic choroidal detachment remains, medical observation or current surgical techniques have resulted in a more favorable prognosis.
CHAPTER 171 • Choroidal Folds
Hemorrhage occurs either intraoperatively or postoperatively. Intraoperative hemorrhage, as mentioned, is quite uncommon with the advent of small incision surgery. When it occurs, it is a dramatic event associated with arterial bleeding, shallowing of the anterior chamber and loss of the red reflex with acute pain and possible extrusion of intraocular contents. A postoperative suprachoroidal hemorrhage is more common and characterized by the sudden onset of excruciating pain and vision loss during the early postoperative period. This most often occurs during some form of physical activity or Valsalva maneuvers associated with vomiting or coughing. It may be associated with flattening of the anterior chamber and elevation of the intraocular pressure. The prognosis of a hemorrhagic choroidal detachment is guarded and is dependent upon the functional status of the intraocular tissues following the event.
171 CHOROIDAL FOLDS 363.8
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Intraocular. Hypotony (after fistulizing surgery, cyclodialysis cleft). Scleral inflammation (posterior scleritis/uveitis) (Figure 171.1). Choroidal edema. Intraocular neoplasms. Choroidal neovascularization. ● Central serous choroidopathy. ● Endolaser photocoagulation. ● Previous scleral surgery. ● Retinal or choroidal detachment. ● Choroidal tumor. ● Endophthalmitis. ● Hyperopia. ● Steroid induced. ● Orbital.
REFERENCES Bellows AR, Chylack LT, Epstein DL, Hutchinson BT: Choroidal effusion during glaucoma surgery in patients with prominent episcleral vessels. Arch Ophthalmol 97:493–497, 1979. Bellows AR, Chylack LT, Hutchinson BT: Choroidal detachment: clinical manifestations, therapy and mechanism of formation. Ophthalmology 88:1107–1115, 1981. Brubaker RF, Pederson JE: Choroidal detachment. Surv Ophthalmol 27:281–289, 1983. Capper SA, Leopold IH: Mechanism of serous choroidal detachment: a review and experimental study. Arch Ophthalmol 55:101–113, 1956. Chylack LT, Bellows AR: Molecular sieving in suprachoroidal fluid formation in man. Invest Ophthalmol Vis Sci 17:240–247, 1978. Kuhn F, Morris R, Mester V: Choroidal detachment and expulsive choroidal hemorrhage. Ophthalmol Clinics of North Amer 14:639–650, 2001.
FIGURE 171.1. Choroidal folds in a patient with posterior scleritis.
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SECTION 17 • Choroid
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Traction on the optic nerve in the absence of scleral contact. Orbital tumors (hemangioma, meningioma). Thyroid orbitopathy. Orbital cellulitis/inflammation. Dural sinus fistula. Optic nerve edema/intracranial hypertension. Ethmoid sinus mucocele. Idiopathic.
Friberg TR: The etiology of choroidal folds: a biomechanical explanation. Graefes Arch Clin Exp Ophthalmol 227:459–464, 1989. Greibel SR, Kosmorsky GS: Choroidal folds associated with increased intracranial pressure. Am J Ophthalmol 129:513–516, 2000. Newell FW: Choroidal folds. Am J Ophthalmol 75:930–939, 1973. Newell FW: Fundus changes in persistent and recurrent choroidal folds. Br J Ophthalmol 68:32–35, 1984. Norton EWD: A characteristic fluorescein angiographic pattern in choroidal folds. Proc R Soc Med 62:119, 1969.
COURSE/PROGNOSIS ● ● ●
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Can occur in normal eyes. May not affect visual function. Possible decreased visual acuity and/or metamorphopsia due to macular involvement. Possible permanent visual loss due to long-term macular involvement. Variable location of folds not predictive of the underlying pathology. Characteristic pigmentation patterns due to persistent or recurrent folds: typically bead-like pigmentation lines on the slope of the fold.
DIAGNOSIS Laboratory findings ● ●
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Fluorescein angiogram. Early phase: alternating lines of hyperfluorescence and hypofluorescence corresponding to the density of the pigment epithelium at the peaks and valleys of the folds, respectively. Late phase: no leakage. Folds more visible angiographically than clinically. Computed tomography scanning or magnetic resonance imaging when orbital tumor or inflammation is suspected. Ultrasonography when posterior scleritis is suspected.
Differential diagnosis ● ●
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Retinal folds. Entirely separate entity rarely coinciding with choroidal folds. Appear finer on ophthalmoscopy. Associated with vitreoretinal disease and usually radiate from visible pathology in the retina. Fluorescein angiogram is normal (relative to the folds).
TREATMENT When possible, treatment is reversal of the underlying cause.
REFERENCES Bullock JD, Egbert PR: Experimental choroidal folds. Am J Ophthalmol 78:618–623, 1974. Bullock JD, Egbert PR: The origin of choroidal folds: a clinical, histopathological, and experimental study. Documenta Ophthalmol 37:261–293, 1974. Bullock JD, Waller RB: Choroidal folding in orbital disease. Proceedings of the Third International Symposium on Orbital Disorders, Amsterdam. 1977:483–488.
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Cangemi FE, Trempe CL, Walsh JB: Choroidal folds. Am J Ophthalmol 86:380–387, 1978.
Steuhl KP, Richard G, Weidle EG: Clinical observations concerning choroidal folds. Ophthalmologica 190:219–224, 1985.
172 CHOROIDAL RUPTURES 363.63 Scott D. Pendergast, MD Beachwood, Ohio
ETIOLOGY/INCIDENCE Choroidal rupture is characterized by tearing of Bruch’s membrane and the closely associated choriocapillaris and retinal pigment epithelium (RPE) after contusive ocular injury. Direct choroidal rupture occurs at the site of injury and typically is located anterior to the equator and is oriented parallel to the ora serrata. Indirect choroidal ruptures are frequently crescentshaped tears of the RPE-Bruch’s membrane-choriocapillaris complex that are concentric to the optic disk and occur in the posterior pole remote from the site of impact. In the acute stages, choroidal ruptures often are associated with hemorrhagic detachment of the RPE, subretinal or intraretinal hemorrhage, and retinal edema, which may obscure the presence and extent of choroidal rupture. As the retina edema and hemorrhagic components resolve, a subretinal yellow-white scar develops that is frequently associated with hyperplasia of the RPE. ● Direct choroidal ruptures probably result from compression necrosis of ocular tissues at the site of contusive injury. ● Indirect choroidal ruptures have been attributed to contrecoup forces that result in rapid anteroposterior compression and horizontal expansion of the globe. Bruch’s membrane is relatively inelastic and susceptible to rupture, whereas the relatively distensible retina and rigid sclera are less prone to rupture. ● The concentric configuration of most indirect choroidal ruptures may be due to a tethering effect of the optic nerve. ● Approximately 1% of patients evaluated at large eye clinics have choroidal rupture. ● The incidence of indirect choroidal rupture after blunt trauma is 5% to 10%. ● Multiple ruptures occur in approximately 25% of eyes. ● Rupture occurs temporal to the optic nerve in 80% of cases, with macular involvement in 66% of eyes. ● Indirect choroidal ruptures are more common than direct choroidal ruptures (80% versus 20%).
COURSE/PROGNOSIS ●
Based on histologic studies, direct and indirect choroidal ruptures heal 14 to 21 days after injury.
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DIAGNOSIS
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Laboratory findings
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Diagnosis is based on the characteristic clinical appearance as well as a history of preceding ocular trauma. ● If retinal edema, hemorrhage, or both are present and obscure findings, serial examinations may be necessary to establish a diagnosis of choroidal rupture. ● Fluorescein angiography (FA) often is helpful in confirming the presence, location, and extent of choroidal ruptures and demonstrates a hypofluorescent curvilinear streak in the early transit phase followed by hyperfluorescence in the late transit phase with variable hyperfluorescence in the recirculation phase. ● Indocyanine green angiography (ICGA) is useful in localizing major and minor choroidal ruptures and is particularly useful in identifying ruptures obscured by dense hemorrhage. Initial ICGA typically shows hypofluorescent streaks that become more apparent over time and are often more numerous that hyperfluorescent streaks identified on FA.
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COMPLICATIONS ●
PROPHYLAXIS ●
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Appropriate protective eyewear (e.g. polycarbonate lenses) worn while engaging in contact sports is the most effective prophylaxis. When Bruch’s membrane is abnormal, as in angioid streaks, pathologic myopia, or pre-existing choroidal rupture, relatively minor trauma can result in extensive choroidal ruptures. High-risk patients should be advised of the hazards associated with blunt ocular trauma related to contact sports and other activities.
TREATMENT ●
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There is no treatment for choroidal ruptures, but a careful examination is important to exclude other ocular injuries associated with blunt ocular trauma, such as commotio retinae, retinal dialysis, hyphema, angle recession and traumatic iritis. Inflammation of the anterior segment can be treated with topical steroids and cycloplegics.
Patients should be followed closely (e.g. monthly) for the first 6 months to detect complications such as retinal detachment and choroidal neovascularization (CNV). Retinal detachments that are progressive are usually repaired using standard scleral buckling techniques. In some instances, scar formation limits the detachment and may obviate the need for surgery. Choroidal neovascularization: ● The incidence is unknown, but it appears to be relatively common. ● This occurs 1 month to 4 years or more after injury and necessitates Amsler grid testing and long-term follow-up. ● Patients may note decreased central visual acuity, metamorphopsia or scotoma. ● Clinical signs include the presence of subretinal hemorrhage, fluid, or exudate or a pigmented subretinal lesion. ● FA and/or ICGA should be performed to confi rm the diagnosis and determine the extent and location of CNV relative to the fovea. No controlled studies are available and treatment remains somewhat controversial. Because choroidal rupture represents a focal abnormality of Bruch’s membrane as in presumed ocular histoplasmosis syndrome (POHS), results of photocoagulation for CNV associated with POHS may provide useful treatment guidelines for CNV associated with choroidal ruptures. Laser photocoagulation is frequently used to treat CNV, particularly when the center of the fovea is not involved. Photodynamic therapy has been used successfully to treat subfoveal CNV associated with traumatic choroidal rupture. Submacular surgery with excision of subfoveal CNV improved visual acuity to 20/30 or better in 3 patients in a small series. Because CNV has been reported to spontaneously resolve, some investigators advocate observation of CNV.
CHAPTER 172 • Choroidal Ruptures
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Retinal edema resolves in 2 to 3 weeks, whereas hemorrhage may persist for 2 to 3 months. A yellow-white subretinal scar develops that may be associated with hypopigmentation or hyperpigmentation of the surrounding RPE. Presenting visual acuity is frequently reduced to 20/200 or worse and ranges from 20/20 to light perception depending on the location of the choroidal rupture. Visual acuity improves in approximately 60% to 70% of cases, with mean final visual acuity ranging from 20/40 to 20/70 in recent series. Eyes with choroidal ruptures involving the fovea, the presence of dense subfoveal hemorrhage, and the development of extensive pigmentary changes in the macula portend a worse prognosis. However, a recent retrospective series found that eyes with foveal choroidal ruptures could maintain good central vision after 4 years of follow-up.
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Choroidal neovascularization is the most frequent late complication of choroidal ruptures. Retinal detachment is occasionally observed in cases of anterior choroidal ruptures. A variety of visual field defects have been observed. Chorioretinal vascular anastomosis is a rare complication of choroidal ruptures.
REFERENCES Bressler SB, Bressler NM: Traumatic maculopathies. In: Shingleton BJ, Hersh PS, Kenyon KR, eds: Eye trauma. St Louis, Mosby-Year Book, 1991:187–194. Conrath J, Forzano O, Ridings B: Phtodynamic therapy for subfoveal CNV complicating traumatic choroidal rupture. Eye 18:946–947, 2004. Gross JG, King LP, de Juan E, Jr, et al. Subfoveal neovascular membrane removal in patients with traumatic choroidal rupture. Ophthalmology 103:579–585, 1996. Kohno T, Miki T, Shiraki K, et al: Indocyanine green angiographic features of choroidal rupture and choroidal vascular injury after contusion ocular injury. Am J ophthalmol 129:38–46, 2000. Raman VR, Desai UR, Anderson S, et al: Visual prognosis in patients with traumatic choroidal rupture. Can J Ophthalmol 39:260–266, 2004.
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173 EXPULSIVE HEMORRHAGE 363.62 (Suprachoroidal Expulsive Hemorrhage)
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SECTION 17 • Choroid
Fumiki Okamoto, MD, PhD Ibaraki, Japan Sachiko Hommura, MD, PhD Ibaraki, Japan Expulsive hemorrhage is one of the most serious and catastrophic complications of intraocular surgery. It occurs suddenly, as a localized or sometimes generalized suprachoroidal hemorrhage, breaking into the vitreous and then extruding the intraocular contents through the surgical wound. Early detection of the problem and prompt, aggressive treatment are essential to save the patient’s vision; however, in many cases, even rapid remedial measures may fail to preserve useful vision. Prevention of the emergency by understanding the factors that may predispose a patient to experience an intraoperative expulsive hemorrhage is much preferable to attempting to deal with the after-effects.
ETIOLOGY/INCIDENCE Expulsive hemorrhage is fortunately rare; according to Ling, it occurs in approximately 0.04% of cataract surgery. Among other ocular surgical procedures, expulsive hemorrhage occurs in 0.15% of glaucoma operations, 0.12% of pars plana vitrectomy, and 0.56% of penetrating keratoplasty. The incidence of this complication is higher in elderly patients who have arteriosclerosis or hypertension and glaucoma. The exact cause of expulsive hemorrhage is unknown, but the immediate event occurs as a result of sudden drop in intraocular pressure gradient when the eye is opened. This sudden change may induce rupture of intraocular vessels if the vessel walls are fragile. The presence of necrotic artifacts in the walls of the short and long ciliary arteries is most important and contributes significantly to occurrence of expulsive hemorrhage. Risk factors for expulsive hemorrhage fall into two categories: vascular factors and intraoperative risks. Vascular factors include: ● Older age; ● Elevated arterial pressure before surgery; ● Chronic systemic hypertension; ● Generalized arteriosclerosis; ● Hyperlipidemia; ● Diabetes; ● Use of anticoagulant agents; ● High myopia; ● Glaucoma (elevated preoperative intraocular pressure). Many patients demonstrate combinations of two or more of these vascular factors; in our surgical experience, among 500 successful cataract procedures (controls) versus 5 cataract procedures that involved expulsive hemorrhage, the latter patients had higher numbers of vascular risk factors (four or five factors) compared with controls (only 3 in 500 had four risk factors and none had five factors). Intraoperative risk factors include: ● Intraoperative systolic hypertension; ● Ocular pain;
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Urge to urinate; Cough reflex; Vitreous loss; Idiopathic (unknown) factors.
Among these factors, poorly controlled intraoperative pain, unsuppressed cough, or the urge to urinate indicates elevation of venous return pressure, which may be a contributing cause of expulsive hemorrhage. Consideration also must be given to the type of surgical procedure; the procedure most commonly associated with expulsive hemorrhage is the penetrating keratoplasty, with vitreoretinal procedures, cataract extractions and glaucoma operations carrying somewhat lesser risk of expulsive hemorrhage. Penetrating keratoplasty is an ‘open sky’ procedure that induces prolonged hypotony, scleral collapse, and relative forward displacement of the intraocular contents; in retinal/vitreous operations, direct trauma to the choroid or the vortex vein may be responsible for precipitating expulsive hemorrhage. Glaucoma procedures carry a relatively low incidence of expulsive hemorrhage comparable with that of cataract surgery; in such cases, prolonged ocular hypotony probably results in rupture of the ciliary artery and subsequent massive bleeding. There also may be unknown factors in the patient’s medical background that increase the risk for expulsive hemorrhage during intraocular surgery. Wohlrab and associates report a recent case in which surgery was being performed for acute glaucoma and a mature cataract when expulsive hemorrhage occurred; after the operation, laboratory analysis of blood smears demonstrated a myelocytic proliferation, indicating the previously unsuspected presence of myelodysplastic syndrome. The operated eye was eventually enucleated due to extremely high intraocular pressure unresponsive to intensive antiglaucoma therapy; histopathologic examination revealed the retina and choroid were swollen due to leukemic cell infi ltration and choroidal hemorrhages. A second case, reported by Weissgold and coworkers, involved a penetrating keratoplasty being performed for delayed-onset fungal keratitis after fungal endophthalmitis; 3 months earlier, the patient had received aggressive therapy (vitrectomy and intraocular injection of antifungal drugs) for the endophthalmitis. Although the existing prosthetic intraocular lens was left in place after the vitrectomy, a posterior capsulectomy was performed. At the time of the penetrating keratoplasty and complicating expulsive hemorrhage, the eye could not be saved; histopathologic analysis of the eviscerated vitreous and the ulcerated cornea disclosed fungal elements of Acremonium kiliense, the causative organism of the original endophthalmitis. The authors conclude that despite aggressive therapy, fungal infections are particularly difficult to eradicate and may have exacerbated choroidal inflammation in this patient, perhaps increasing the risk of catastrophic expulsive hemorrhage.
COURSE/PROGNOSIS Unfortunately, visual outcome after expulsive hemorrhage often is severely compromised, despite the most up-to-date vitreoretinal surgery. Welch and coworkers assessed visual outcome in 30 patients after massive suprachoroidal hemorrhage and reported that more than half (18) of the patients had a final visual acuity of 20/200 or better; in 1 patient, visual acuity returned to 20/20. The remaining 12 patients experi-
DIAGNOSIS
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Sterile balanced saline solution may be injected carefully through a small limbal incision to re-form the anterior chamber.
When complete cessation of the subchoroidal hemorrhage has been confirmed, the surgical wound is reopened and: ● Anterior vitrectomy is performed to remove as much vitreous material as possible from the anterior chamber. If vitreous hemorrhage or retinal detachment is involved: ● Posterior vitrectomy should be attempted, followed by: ● SF6 or C3F8 gas injection; ● Silicone oil tamponade.
Clinical signs and symptoms Expulsive hemorrhage usually occurs during surgery, but it may occur as long as 24 hours after surgery; the patient typically complains of severe ocular pain at that time. When the complication occurs during a procedure, sometimes observed is: ● A dark, growing choroidal mass, visible through the pupil, if the hemorrhage begins slowly. If this warning sign does not appear, the first indications of an imminent expulsive hemorrhage are: ● A sudden shallowing of the anterior chamber; ● Firmness of the globe; ● Forward displacement of the intraocular contents; ● Gaping of the surgical incision. These events may be followed by: Iris prolapse; ● Spontaneous delivery of the lens, if present; ● Protrusion of the vitreous body and uveoretinal tissue; ● Profuse bleeding through the surgical wound. ●
If the suprachoroidal hemorrhage does not coagulate spontaneously. In the worst case, the entire intraocular contents may be lost.
If expulsive hemorrhage occurs during penetrating keratoplasty (the procedure with the highest incidence rate of this complication), it will typically occur after trephination of the host corneal button; in this circumstance, it is impossible to close the eye immediately. Taylor recommends having the assisting surgeon place a thumb over the corneal opening while the primary surgeon rapidly performs a posterior sclerotomy. After complete cessation of hemorrhage, it will be possible to suture the donor corneal button in place. Many eyes may be salvaged with this method.
CHAPTER 173 • Expulsive Hemorrhage
enced immediate retinal detachment, an inoperable sequela that resulted in loss of vision. Fortunately, none of these patients required evisceration or enucleation. Ling et al reported visual outcome in 118 cases after suprachoroidal hemorrhage complicating cataract surgery; best corrected visual acuity was 6/12 or better in 40%, 6/18 to 6/60 in 20%, 6/60 or worse in 40%, after a median follow up interval of 185 days. These results strongly suggest that expulsive hemorrhage may be one of the most intractable conditions from a therapeutic standpoint.
Systemic After surgical management of an expulsive hemorrhage, the patient is treated with systemic and topical corticosteroids to reduce intraocular inflammation: ● Prednisolone 30 to 40 mg/day PO; and ● Topical ophthalmic dexamethasone 0.1% or betamethasone 0.1% four to six times daily; ● Cycloplegic drops in addition. To forestall massive suprachoroidal hemorrhage, Bequet and colleagues recommend high-dose corticosteroid prophylaxis before surgery; patients in their studies were administered: ● Methylprednisolone 500 mg/day IV for 3 days before surgery; followed by ● Prednisolone 1 mg/kg/day PO.
TREATMENT Surgical The fundamental principle for response to an expulsive hemorrhage is to close the globe as soon as possible; this is most expeditiously done by suturing the corneoscleral incision. ● Interrupted sutures with 8-0 silk are the preferred technique to restore intraocular pressure, which serves as an effective tamponade to ruptured choroidal vessels. In cases in which the surgical wound cannot be closed immediately: ● A prompt and adequate posterior sclerotomy should be performed to release the subchoroidal blood. A scleral incision, T or Y shaped, should be made approximately 8 mm posterior to the limbus and, if possible, in the quadrant of the suspected source of bleeding. The subchoroidal blood, however, will find egress from a scleral opening at any quadrant, even if that quadrant does not correspond to the bleeding site; time should not be spent attempting to localize the burst vessel or vessels. It is advisable to keep the sclerotomy patent until subchoroidal bleeding ceases completely. After the surgical incision has been closed:
PRECAUTIONS It is very difficult to prevent expulsive hemorrhage, whose pathogenesis is multifactorial. To avoid this complication and decrease its incidence, every reasonable effort should be made to control risk factors because the prediction of fragile intraocular vessels is similarly difficult. First, special attention should be paid to patients with extensive vascular disease; such patients may routinely take hypotensive agents, vasodilators, anticoagulants, and so on. Insofar as is medically possible, these agents-especially anticoagulantsshould be stopped several days before surgery. In addition to hemostatic agents administered immediately before surgery, the use of a short-acting barbiturate sedative may be necessary for any patient who has anxiety in the operating room. Anxiety causes systolic hypertension and tachycardia, which increase the risk for expulsive hemorrhage. Careful monitoring of pulse rate and blood pressure is extremely important in these patients. Reduction of intraocular pressure before surgery is fundamental and of utmost importance. Acetazolamide (250 mg PO) is administered the previous night and early on the morning of
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surgery. Intravenous hyperosmotic agents, such as 200 mL of 20% mannitol or 10% glycerol, also may be given; this infusion should be begun 1 hour before surgery. In addition, decompression of the globe and orbit by mercury bag or by massage is helpful. At surgery, the intraocular pressure should be reduced to a minimum; it is equally necessary to prepare the patient properly for surgery, including voiding the urinary bladder, suppressing any cough reflex, and controlling the patient’s pain, all of which will minimize any rise in venous return pressure.
(Choroidal Melanoma, Ciliary Body Melanoma, Uveal Melanoma, Intraocular Melanoma) Paul A. Rundle, MBBS, FRCOphth Sheffield, England
COMMENTS ETIOLOGY/INCIDENCE Recent improvements in surgical procedure, especially in cataract surgery, should reduce the occurrence of expulsive hemorrhage. The recent literature contains no case reports of expulsive hemorrhage during surgery when the smaller or self-sealing incisions for phacoemulsification are used. Blumenthal and colleagues reported a method in which constant infusion inflow through an anterior chamber maintainer was used to maintain positive intraocular pressure during cataract extraction through a self-sealing tunnel incision. With this technique, there were no expulsive hemorrhages in 5600 eyes. The present closed-system techniques appear to be beneficial. Because of the risk of bilateral occurrence of this devastating complication, it is prudent to perform cataract extraction using the most current closed-eye technique for the fellow eye of any patient who has previously had an expulsive hemorrhage. Moreover, increased surgeon experience and shortened operation time may contribute to the elimination of intraoperative expulsive hemorrhage. It is extremely difficult to completely prevent an expulsive hemorrhage and to manage it regardless of circumstances; although subsequent visual loss is too common, proper management can lessen the possibility of blindness.
REFERENCES Bequet F, Caputo G, Mashhour B, et al: Management of delayed onset massive suprachoroidal hemorrhage: A clinical retrospective study. Eur J Ophthalmol 6:393–397, 1996. Blumenthal M, Grinbaum A, Assis EI: Preventing expulsive hemorrhage using an anterior chamber maintainer to eliminate hypotony. J Cataract Refract Surg 23:476–479, 1997. Ghoraba HH, Zayed AI: Suprachoroidal hemorrhage as a complication of vitrectomy. Ophthalmic Surg Lasers 32:281–288, 2001. Ling R, Cole M, Shaw S, et al: Suprachoroidal haemorrhage complicating cataract surgery in the UK: epidemiology, clinical features, management, and outcomes. Br J Ophthalmol 88:478–480, 2004 Sekine S, Takei K, Hommura S, et al: Survey of risk factors for expulsive choroidal hemorrhage: Case reports. Ophthalmologica 210:344–347, 1996. Speaker MG, Guerriero PN, Met JA, et al: A case-control study of risk factors for intraoperative suprachoroidal expulsive hemorrhage. Ophthalmology 98:202–210, 1991.
Uveal melanoma represents the commonest primary intraocular tumor in adults. It may arise from the melanocyte in any part of the uveal tract, either anterior (iris) or posterior (ciliary body and choroid). The choroid is the most frequent site accounting for approximately 75% of cases. Annual incidence is approximately 6 per million with a median age of 55 years. Melanoma occurs almost exclusively in Caucasian populations. Bilateral disease is exceptionally rare. Risk factors for the development of uveal melanoma include pre-existing nevi and ocular melanosis however unlike cutaneous melanoma there is no direct relationship with UV exposure.
COURSE/PROGNOSIS Whilst ocular treatment offers excellent rates of local control, ultimately many patients will succumb to metastatic disease. Despite this, at presentation only 2% patients will have detectable systemic metastases. Although metastasis from uveal melanoma usually presents within 5 years of enucleation, late-onset metastases have been recognized decades after treatment of the intraocular tumor. The liver, lung, and skin are the three most common sites for metastatic disease. Survival rates after enucleation of uveal melanoma have been reported to be 65% at 5-year, 52% at 10-year, and 46% at 15-year follow-up. In recent years the COMS study has compared brachytherapy and enucleation in the treatment of mediumsized melanomas and has shown comparable survival rates of approximately 81% at 5 years. Not surprisingly, overall survival rates correlate with tumor size and at 5-year followup, small melanoma has a mortality rate of approximately 16%; medium-sized melanoma, 32%; and large melanoma, 53%. Clinical risk factors for metastases of posterior uveal melanoma include: ● Tumor location in the ciliary body; ● Largest tumor dimension of 15 mm or larger.
Welch JC, Speath GL, Benson W: Massive suprachoroidal hemorrhage: follow-up and outcome of 30 cases. Ophthalmology 95:1202–1206, 1988.
Histopathologic risk factors for metastasis of posterior uveal melanoma include: ● Large tumor size; ● Ciliary body involvement; ● Epithelioid cell type; ● Specific cytogenetic abnormalities; ● Extrascleral extension of tumor; ● Vascular patterns within tumor.
Wohlrab TM, Pleyer U, Rohrbach JM, et al: Sudden increase in intraocular pressure as an initial manifestation of myelodysplastic syndrome. Am J Ophthalmol 119:370–372, 1995.
Clinical risk factors for growth of small uveal melanocytic tumors (3 mm thick or smaller) include:
Taylor DM: Expulsive hemorrhage. In: Fraunfelder FT, Roy FH, eds: Current ocular therapy. 4th edn. Philadelphia, WB Saunders, 1995:448–450. Weissgold DJ, Orlin SE, Sulewski ME, et al: Delayed-onset fungal keratitis after endophthalmitis. Ophthalmology 105:256–262, 1998.
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174 MALIGNANT MELANOMA OF THE POSTERIOR UVEA 190.6
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Tumor thickness of more than 2 mm; Tumor touching the optic disk; Presence of symptoms; Orange pigment; Subretinal fluid.
DIAGNOSIS Clinical signs and symptoms Uveal melanomas may give rise to symptoms (blurred vision, photopsia, metamorphopsia) or be detected during a routine eye examination. Melanomas tend to be dome-shaped but may appear flat and diffuse. Rupture of Bruch’s membrane produces a ‘collar-stud’ appearance (Figure 174.1). Pigmentation is variable although surface orange-pigment (lipofuschin) is characteristic. The diagnosis is largely made on clinical appearance on indirect ophthalmoscopy or slit-lamp examination.
Laboratory findings ●
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Ultrasonography: acoustically hollow uveal mass on B-scan and medium to low internal reflectivity within the mass on A-scan. Intravenous fluorescein angiography: patchy early fluorescence and diffuse late staining of the choroidal mass, often with a double circulation pattern. Indocyanine green angiography: gradual hyperfluorescence over 20 minutes, but patterns can vary. Computed tomography: moderately dense, noncalcified intraocular mass. Magnetic resonance imaging: an intraocular mass that is hyperintense to vitreous on T1-weighted images, hypointense to vitreous on T2-weighted images, and moderate enhancement with gadolinium contrast.
Microscopic histopathology: spindle or epithelioid cells according to the Callender classification.
Differential diagnosis Common differential diagnoses include: ● Uveal neoplasms: ● Nevus; ● Metastasis; ● Hemangioma; ● Lymphoid tumor; ● Osteoma. ● Retinal neoplasms: ● Retinal astrocytic hamartoma; ● Retinal capillary hemangioma; ● Combined hamartoma retina and retinal pigment epithelium; ● Vasoproliferative tumor of the fundus; ● Retinoblastoma. ● Pigment epithelial neoplasms: ● Pigment epithelial hypertrophy (CHRPE)/hyperplasia; ● Pigment epithelial adenoma; ● Medulloepithelioma. ● Non-neoplastic diseases: ● Subretinal hemorrhage secondary to age-related macular/ extramacular degeneration; ● Retinal arterial macroaneurysm; ● Choroidal hemorrhage/detachment; ● Posterior scleritis; ● Choroidal granuloma; ● Retinal detachment.
CHAPTER 174 • Malignant Melanoma of the Posterior Uvea
Clinical risk factors for metastasis of small uveal melanoma (3 mm thick or smaller) include: ● Tumor thickness of more than 2 mm; ● Documented growth; ● Tumor touching the optic disk; ● Presence of symptoms.
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TREATMENT Systemic A number of treatment options currently exist for metastatic melanoma, however, response rates are uniformly poor. Whilst patients with metastases to certain sites such as the skin may survive for several years, the majority of those with diffuse liver metastases die within 6 months. Owing to poor response rates intravenous therapy is often reserved for palliation of symptoms. Intrahepatic chemoembolization has been used for isolated liver metastases and similarly, focal metastases (in many organs) may be amenable to local surgical resection. Various groups have tried immunotherapy however a successful melanoma vaccine remains elusive.
Local The aims of treatment of uveal melanoma are: ● To eradicate the tumor before metastasis occurs; ● Preserve the eye; ● Preserve vision. The best form of treatment for any melanoma depends on many different variables including the size and apparent activity of the tumor, the health of the affected eye and it’s fellow and the age and general health of the patient. What might be ideal for a 35 year old airline pilot might be wholly inappropriate for a 90 year old in residential care.
Observation FIGURE 174.1. Typical ‘collar-stud’ melanoma. Note the amelanotic portion of the tumor that has breached Bruch’s membrane.
Periodic observation may be recommended to initially manage selected small melanomas that have dormant characteristics on ophthalmoscopic examination. Such a lesion should be care-
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SECTION 17 • Choroid
fully examined two or three times a year, and some form of active treatment should be instituted if growth of the tumor is subsequently documented. The diagnostic tests and the frequency of follow-up examinations depend on the size and the apparent activity of the tumor. If a patient has a tumor that is classified as a suspicious nevus or dormant melanoma, then a repeat examination should be performed in 3 to 4 months, with fundus photography and ultrasonography for documentation. If no growth is detected, examination should be repeated every 4 to 6 months thereafter. If the lesion remains quiescent then these intervals may be increased. If however growth is documented, or the lesion shows increasing orange pigment, subretinal fluid or symptoms active treatment is advisable. For those lesions that require treatment, the main therapeutic options consist of: ● Diode laser transpupillary thermotherapy; ● Brachytherapy (radioactive plaques); ● Charged particles (proton beam or Helium ion); ● Stereotactic radiosurgery; ● Local resection; ● Enucleation; ● Exenteration.
Transpupillary thermotherapy Over the last decade transpupillary thermotherapy (TTT) has supplanted argon laser photocoagulation as the treatment for small uveal melanomas (80%, especially boys, resolving by the late teens or early 20 s. Typically, there is no residual conjunctival scarring unless the disease was severe with persistent giant papillae or was treated with surgery or cryotherapy.
FIGURE 185.1. Giant papillae demonstrating the typical cobblestone (flat-topped) appearance of the upper tarsal conjunctiva.
COURSE/PROGNOSIS The initial years often show seasonal variation, with signs and symptoms being more severe during the spring and summer. Patients suffering for longer than 3 years, especially those with giant papillae or fibrosis, tend to lose their seasonal variation. In 2000 Bonini et al, in a long-term follow-up study on 151 patients, showed that 16% of patients with a mean disease duration of 3 years, evolved into chronic, perennial VKC. This study also showed that worsening or persistence of the disease could be predicted by the papillary size (>1 mm) and form (limbal worse than tarsal). These authors suggest that papillary size may be a reflection of the intensity and chronicity
FIGURE 185.2. Maxwell–Lyons sign.
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SECTION 18 • Conjunctiva
Eyelid signs include long and thick eyelashes, the mechanism of which is not fully understood. Ptosis may occur in active VKC. Blepharospasm suggests corneal involvement and potentially more severe disease. Tarsal conjunctival signs, in addition to those mentioned above, include the Maxwell-Lyons sign, a milky coating of fibrinous exudate over the cobblestone papillae that is enhanced by the heat of the slit lamp. Tarsal conjunctival fibrosis is the natural evolution of severe giant papillae. Unlike atopic keratoconjunctivitis, most cases of VKC resolve without tarsal conjunctival scarring. Bulbar or limbal VKC occurs in about 20% of Mediterranean series and is commoner in patients of African and Asian origin. Usually the superior limbus is more affected. Horner–Trantas’ dots (aggregates of epithelial cells and eosinophils at the limbus) occur in approximately 15% of active VKC. Epithelial keratopathy is very common and results from epithelial toxicity due to the release of eosinophilic major basic protein. Corneal shield ulcer, a vision threatening complication occurring in 3–11% of VKC, is characteristically a shallow, transversely oval, de-epithelialized area, located in the superior cornea. Mucous and epithelial cell plaque often cover the ulcer base. The surrounding epithelium is smooth and grayish. Superficial peripheral corneal vascularization is common in longstanding cases.
Laboratory findings Usually, the signs and symptoms are characteristic enough to make the diagnosis without laboratory tests. Conjunctival cytology scrapings are usually positive for eosinophils and free eosinophilic granules. Other immune tests have low sensitivites (negative in >50%) and are therefore not clinically useful for diagnosis of VKC. These include activated eosinophils in conjunctival biopsies, total and specific serum IgE and skin tests. In 2003, Pucci et al showed a positive correlation between giant papillae score and serum eosinophil response, independent of IgE-sensitization, and found serum eosinophil cationic protein to be a useful laboratory marker of disease activity. Limbal VKC has an even lower prevalence of IgE-sensitization than tarsal forms.
Differential diagnosis ● ● ●
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Seasonal and perennial allergic conjunctivitis. Atopic keratoconjunctivitis. Giant papillary conjunctivitis associated with contact lens wear. Giant papillae on the tarsal conjunctiva secondary to an exposed ocular suture or ocular prosthesis. Ligneous conjunctivitis may occasionally be confused with large cobblestone papillae in young patients. Toxic conjunctivitis secondary to chronic use of ophthalmic preparations: may result in bulbar follicles that may mimic limbal changes. Unlike VKC, the signs are more pronounced inferiorly.
TREATMENT Because VKC usually resolves without scarring or permanent loss of vision once the disease burns out, treatment should be as conservative as possible to achieve symptomatic relief, prevent structural damage to the ocular surface that may reduce vision, and minimize any iatrogenic complications.
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Nonspecific Although relocating to a cool moist climate is often effective, this is usually impractical. Concurrent blepharitis and dry eye should be treated.
Systemic Oral antihistamines (e.g. loratidine) and oral nonsteroidal antiinflammatory drugs (NSAIDs) may be useful in mild to moderate cases: the earlier for generalized hyper-reactivity and the latter for the inflammatory aspect of VKC. Oral prednisone 10 mg/day for 3–5 days in a 10-year-old child may be very useful in refractory VKC with corneal damage.
Ocular Cold compresses decrease itching by reducing superficial vasodilatation and c-fiber stimulation. Artificial tears dilute antigens and immunogenic factors. Refrigerating artificial tears further improves their soothing effect. Topical vasoconstrictors, such as naphazoline, should be restricted to t.i.d. for only a few days as rebound hyperemia is likely with longer use. Topical antihistamines and H1 antagonists have a rapid onset but short duration. Levocabastine (Livostin) and emedastine (Emadine) may be used 1–4 times daily for long periods. Newer antihistamines (H1 blockers) such as olopatadine (Patanol) also have mast cell-stabilizing properties. Topical NSAIDs, such as ketorolac (Acular), may provide symptomatic relief of itching. Their steroid sparing capability in VKC is yet to be determined. In the presence of any degree of keratitis, vasoconstrictors, antihistamines and NSAIDs alone are inadequate. Mast cell stabilizers, such as cromolyn (Opticrom, Crolom), lodoxamide (Alomide), nedocromil (Alocril) and pemirolast (Alamast) are the mainstay of therapy for most cases of VKC. Although more severe cases require short courses of topical steroids to control the inflammation, mast cell stabilizers have prophylactic use during quieter phases of the disease and enable steroid sparing. Unpreserved solutions are preferable for longterm use. Topical corticosteroids are the most effective therapy for VKC, especially with active keratopathy. Steroids inhibit epithelial toxic mediator biosynthesis by eosinophils and neutrophils, thus reversing corneal epithelial damage. Refractory symptoms, cobblestone papillae, limbal thickening, and shield ulcers are indications for steroid use. However, use should be strictly limited as prolonged use may cause cataract, increased intraocular pressure, and superinfection. High frequency intermittent (pulse) therapy (e.g. 2-hourly for 3–5 days) is effective and minimizes steroid complications. The steroid potency, such as 0.1% fluorometholone, 0.2% loteprednol or 1% prednisolone acetate, should be titrated against the severity of the inflammation. Patients and family members should be thoroughly educated regarding steroid complications. Topical cyclosporin A 2% in olive oil was shown by Pucci et al in a randomized clinical trial to be effective in severe VKC. Most of the therapeutic effect was achieved within 2 weeks. Besides mild irritation on instillation, no ocular or systemic complications were seen. Cyclosporin A binds to cyclophilin, an intracellular protein, inhibiting interleukin-2 production and blocking Th2 lymphocyte proliferation. It also appears to decrease eosinophil recruitment and conjunctival fibroblast proliferation. Effective doses range from 2–4 times/ day for 2–16 weeks. There is no need to check systemic blood levels.
Surgical
COMPLICATIONS Up to 6–10% of cases have a complication that causes visual impairment. Complications may be due to the disease itself (corneal vascularization and scarring after shield ulcers) or due to steroid use (cataract and glaucoma). In addition, keratoconus may be a late complication of VKC.
COMMENTS Mild VKC responds well to topical antiallergics, especially mast cell stabilizers and usually resolves within 2–10 years with no
ocular surface scarring. Severe VKC (giant papillae >1 mm or limbal forms) has fibrosis of the ocular surface, supposedly due to a Th2 lymphocyte driven mechanism, and requires steroid treatment. Continual effort to limit steroid side effects is necessary, such as mast cell stabilizers and cyclosporin A use.
REFERENCES Bielory L: Update on ocular allergy therapy. Expert Opin Pharmacother 3:541–553, 2002. Bonini S, Bonini S, Lambiase A, et al: Vernal keratoconjunctivitis revisited: a case series of 195 patients with long-term followup. Ophthalmology 107:1157–1163, 2000. Bonini S, Coassin M, Aronni S, Lambiase A: Vernal keratoconjunctivitis. Eye 18:345–351, 2004. Cameron JA: Shield ulcers and plaques of the cornea in vernal keratoconjunctivitis. Ophthalmology 103:985–993, 1995. Holsclaw DS, Whitcher JP, Wong IG, Margolis TP: Supratarsal injection of corticosteroid in the treatment of refractory vernal keratoconjunctivitis. Am J Ophthalmol 121:243–249, 1996. Pucci N, Novembre E, Cianferoni A, et al: Efficacy and safety of cyclosporine eyedrops in vernal keratoconjunctivitis.Ann Allergy Asthma Immunol 89:298–303, 2002. Pucci N, Novembre E, Lombardi E, et al: Atopy and serum eosinophil cationic protein in 110 white children with vernal keratoconjunctivitis: differences between tarsal and limbal forms. Clin Exp Allergy 33:325– 330, 2003.
CHAPTER 185 • Vernal Keratoconjunctivitis
Supratarsal injection of steroids is useful in cases refractory to pulsed topical steroids, with non-healing shield ulcers. Dexamethasone, triamcinolone and hydrocortisone are equally effective. Surgical removal of a plaque in the base of a vernal ulcer preventing re-epithelialization, by scraping the base and margins, may promote healing. Surgical excision, cryotherapy and beta-irradiation of giant papillae of the superior tarsus have been described. These procedures are not recommended as marked scarring and distortion of the upper eyelid often results.
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S ECT I O N
19
Cornea
186 BACTERIAL CORNEAL ULCERS 370.00 (Bacterial Keratitis) Irina S. Barequet, MD Tel Hashomer, Israel Bacterial infection of the cornea is a sight-threatening process. Corneal ulceration, stromal abscess formation, and anterior segment inflammation are features of the disease. A particular feature of bacterial keratitis is its rapid progression; corneal destruction may be complete in 24 to 48 hours. Less pathogenic bacteria may induce a slower disease process than that induced by virulent fungi. The suspicion of an infective process demands careful microbiologic assessment. Commonly, predisposing factors exist, such as contact lens wear (especially overnight wear), trauma, contaminated ocular medications, impaired defense mechanism, or altered ocular surface.
ETIOLOGY/INCIDENCE ●
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Pathogenic gram-positive cocci, principally Staphylococcus aureus and Streptococcus pneumoniae. Aerobic gram-negative bacilli, principally Pseudomonas aeruginosa, Haemophilus influenzae and Moraxella spp. Various enteric gram-negative bacilli. Colonization by normal skin flora, most commonly coagulase-negative staphylococci, viridans streptococci, and corynebacteria.
About 30,000 (10 in 100,000) Americans develop bacterial keratitis annually. Bacterial keratitis is a leading cause of corneal blindness in developing countries, usually caused by trauma, but the incidence is unclear.
tis. In some cases, corneal transplantation for visual rehabilitation may be considered.
DIAGNOSIS Clinical signs and symptoms Patients with bacterial keratitis usually present with an abrupt onset of pain, redness, decreased vision and photophobia. Findings usually include stromal suppurative inflammation with indistinct edges, a defect in the overlying epithelium, and stromal edema around the infi ltrate. An anterior chamber reaction or hypopyon can occur. Less virulent bacteria can cause a nonsuppurative infiltrate with intact epithelium.
Laboratory findings When bacterial keratitis is suspected, microbiological diagnostic tests should be considered prior to treatment initiation. Large or progressive corneal ulcers, or ulcers not responding to treatment should always undergo laboratory investigation to identify and confirm the causal organism.
Specimen collection Direct plating performed in a clinic with access to a microbiology service is preferred to sending a swab to an off-site facility. If local anesthesia is necessary, preservative-free drops are recommended. The advancing borders of the lesion are scraped with either a Kimura spatula, a needle, or rounded surgical blade. Inoculation onto microbiologic media (pre-warmed to room temperature) is immediately performed by small Cshaped streaks. One scrape per medium is preferred. A suggested protocol is to inoculate the following media in order: a chocolate agar plate; a slide for a Gram’s stain; a blood agar plate; a supplemented brain-heart infusion broth (‘special BHIB’); a cooked meat-glucose broth; and a slide for a Giemsa stain. A fungal medium (Sabouraud’s dextrose agar) should also be included. In addition, cultures of the contact lenses, cases, and solutions may add valuable information.
COURSE/PROGNOSIS Culture interpretation In many cases, bacterial infection of the cornea results in irreversible structural alteration. This compromises the visual outcome due to stromal scarring and irregular astigmatism. Infections caused by P. aeruginosa generally have a relatively poor outcome. Infections with S. aureus or S. pneumoniae typically leave a more focal, scarred area. About two thirds of patients retain vision of 20/200 or better after bacterial kerati-
An obvious pathogen will be isolated from perhaps 40% of corneal specimens. Sometimes, skin flora only will be isolated; commensals such as coagulase-negative staphylococci, viridans streptococci, and corynebacteria can colonize defects in the corneal epithelium and contribute to the pathology. In these instances, the isolate should be identified to at least genus level and reported to the clinician. Antibiotic treatment is considered
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on a case-by-case basis. If there is no growth or growth of commensals only in the presence of a worsening condition, further investigations for nonbacterial pathogens must be considered.
Antimicrobial susceptibility testing Susceptibility testing against particular antibiotics is normally performed on all significant bacterial isolates from the cornea. SECTION 19 • Cornea
Differential diagnosis ●
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Infectious keratitis due to other pathogens: yeasts, fi lamentous fungi, acanthamebae, parasites, viruses such as herpes simplex. Sterile corneal infi ltrates with contact lens wear induced by endotoxin or other microbial components. Marginal subepithelial infiltrates associated with staphylococcal blepharitis or acute conjunctivitis. Toxic keratopathy associated with chemical injury or overuse of topical drugs.
PROPHYLAXIS Prophylaxis with topical antibiotics is routinely given after traumatic injury to the cornea. An agent with a wide antimicrobial spectrum, such as a fluoroquinolone or chloramphenicol, is recommended. Antibiotic prophylaxis is also given before and/or after corneal surgery, such as transplantation or refractive procedures, but its value in reducing postoperative infection remains controversial.
TREATMENT Systemic Systemic administration of antibiotics is not indicated for bacterial keratitis unless structures beyond the cornea are directly involved.
Ocular The principles of the treatment of bacterial keratitis are to eliminate the replicating etiologic agent with specific antibiotics, to suppress destructive inflammation, and then to withdraw therapy so as not to hinder repair of the cornea.
Subconjunctival injections are usually reserved for scleral and/or intraocular extension of the infection, or in cases with questionable compliance with the treatment regimen. Initial topical broad-spectrum therapy is recommended until the microorganism is identified in culture. A combination of fortified antibiotic solutions effective against gram-positive and gram-negative bacteria is administered each hour, or even more frequently, for the first 24 hours: a fi rst-generation cephalosporin (cefazolin 50 mg/mL) and gentamicin or tobramycin (9– 14 mg/mL). The antibiotics chosen as initial therapy may be changed based on the clinical response. If the clinical response is favorable and the miroorganism has been identified, monotherapy may be considered. Topical fluoroquinolones may also be used for bacterial keratitis. Early clinical trials have shown that second-generation fluoroquinolones (ofloxacin and ciprofloxacin) have low ocular toxicity and were as effective as a combination of fortified antibiotics. They have excellent activity against most strains of staphylococci, P. aeruginosa, and enteric gram-negative bacilli. S. pneumoniae and other streptococci are less sensitive, and based on in vitro susceptibility, cefazolin may be a better choice for these infections. Although quinolones are effective for most corneal infections in most parts of the world, it is unwise to assume that all keratitis is bacterial and will respond to these agents. Emerging resistance of various strains has been reported. The fourth-generation fluoroquinolones (gatifloxacin and moxifloxacin) possess an expanded spectrum of activity, greater potency, and resistance-thwarting capabilities. Alternative agents according to culture result or the in vitro susceptibility profi le are considered only if there is no favorable clinical response, or toxicity signs from the initial antibiotics (Table 186.1). If no organisms are cultured but the clinical picture suggests an active infection, the concomitant use of a cephalosporin and an aminoglycoside should be continued. In addition, cycloplegic agents may be used to decrease synechiae formation, and reduce pain and ciliary spasm.
Surgical Penetrating keratoplasty is indicated if corneal perforation occurs during the course of the disease and the area of necrosis is resectable, or the keratitis is unresponsive to antimicrobial therapy. The infected area should be included in the removed button. The success rate of corneal transplants made under these circumstances is low. When extensive peripheral corneal
TABLE 186.1 – Antibiotics used in the treatment of bacterial corneal ulcers Organism
Antibiotic
Topical Concentration
Subconjunctival Dose in 0.5 mL
Gram-positive cocci
Cefazolin
50 mg/mL
100 mg
Vancomycin
15–50 mg/mL
Gram-negative rods
Fluoroquinolones
3 or 5 mg/mL
Gentamicin/tobramycin
9–14 mg/mL
Ceftazidime Fluoroquinolones Gram-negative cocci
3 or 5 mg/mL
— 20 mg 100 mg —
Ceftriaxone
50 mg/mL
100 mg
Ceftazidime
50 mg/mL
100 mg
Fluoroquinolones
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50 mg/mL
25 mg
3 mg/mL
—
necrosis occurs a conjunctival flap after a period of intensive chemotherapy often is the safest course of treatment.
Wilhelmus KR: Bacterial keratitis. In: Pepose JS, Holland GN, Wilhelmus KR, eds: Ocular infection and immunity. St Louis, Mosby, 1996: 970–1031.
Supportive
Williams KA, Muehlberg SM, Lewis RF, et al, eds: The Australian Corneal Graft Registry 1996 report. Adelaide, Mercury, 1997.
Close observation is mandatory. Progression of the condition may be rapid and blinding. Punctilious attention must be paid to treatment schedules. For these reasons, either hospital admission may be necessary or close follow-up is performed.
The use of topical corticosteroids in bacterial keratitis is controversial. Topical corticosteroids can suppress the inflammation and may reduce subsequent corneal scarring. Studies in animal models suggest that inflammation is inhibited without impairing the clearance of organisms provided an appropriate antibiotic is administered concurrently However, potential specific adverse effects include enhancement of bacterial growth by local immunosuppression, impairment of phagocytosis, or inhibition of collagen synthesis. It is probably safe to suppress anterior segment inflammation with topical steroids after the effectiveness of the antimicrobial therapy has been suggested by a nonprogressive clinical course.
(Epithelial Inclusion Cysts, Intrastromal Corneal Cysts) James C. Liu, MD, MBA San Jose, California
ETIOLOGY/INCIDENCE
Huang AJW, Wichiensin P, Yang MC: Bacterial keratitis. In: Krachmer JH, Mannis MJ, Holland EJ, eds: Cornea. 2nd edn. Elevier Mosby, 2005:1005–1033.
Intracorneal cysts are rare lesions that have been described after trauma and congenitally. This is a slowly progressive condition in young patients. The eyes are usually quiet and uninflamed. Individual cases were presumed to be congenital in origin, but recent reports have overwhelmingly documented trauma as the most likely cause of corneal cysts. They usually appear after trauma to the cornea or sclera and probably develop from surface epithelium that was implanted in the stroma during the injury. The ectopic epithelium proliferates and enlarges to form a corneal or sclerocorneal cyst, depending on the location of trauma. The desquamated material within the cyst settles and gives the cyst its typical appearance, that of a pseudohypopyon. Therapeutic success and the procedure largely depend on the location of the cyst and the patient’s visual impairment from the cystic lesion. Current discussion does not include epithelial cyst under the corneal flap following laser in situ keratomileusis (LASIK), reader should refer to a LASIK text for its treatment and management. ● The age of the patient at which the cyst is discovered varies significantly because the time of trauma varies. ● Most patients are young, in their first two decades of life. This finding may be attributed to the greater metabolic activity of corneal epithelial cells of young individuals. This enables the epithelium to survive and proliferate when implanted intrastromally. ● There is no gender predilection. ● Although in some cases there is no history of trauma, even minor corneal epithelial injury can cause implantation of epithelium in the stroma with subsequent development of intrastromal cyst, and these minor injuries can be easily forgotten or overlooked.
Hyndiuk RA, Eiferman RA, Caldwell DR, et al: Comparison of ciprofloxacin ophthalmic solution 0.3% to fortified tobramycin-cefazolin in treating bacterial corneal ulcers: Ciprofloxacin Bacterial Keratitis Study Group. Ophthalmology 103:1854–1862, 1996.
DIAGNOSIS
COMMENTS Continuation of the inflammation or the prolonged use of topical antibiotics can inhibit epithelial closure; thus, intensive medication should be maintained only until the clinical course suggests that bacterial growth is suppressed. Usually, only 2 or 3 days of intensive therapy are necessary, with careful reduction of medication over the next week. It often is possible for patients with a healing epithelial and stromal defect to be off the medication and under close supervision within 10 days. Positive clinical response includes blunting of the perimeter of the infiltrate and reduction of its density, reduction of the anterior chamber inflammation, stabilization of the stromal thinning and re-epithelialization.
REFERENCES Badenoch PR, Hay GJ, McDonald PJ, Coster DJ: A rat model of bacterial keratitis: effects of antibiotics and corticosteroid. Arch Ophthalmol 103:718–722, 1985. Christy NE, Sommer A: Antibiotic prophylaxis of postoperative endophthalmitis. Ann Ophthalmol 11:1261–1265, 1979.
McDonnell PJ: Empirical or culture-guided therapy for microbial keratitis? A plea for data. Arch Ophthalmol 114:84–87, 1996.
Clinical signs and symptoms
O’Brien TP, Maguire MG, Fink NE, et al: Efficacy of ofloxacin vs cefazolin and tobramycin in the therapy for bacterial keratitis: report from the Bacterial Keratitis Study Research Group. Arch Ophthalmol 113:1257– 1265, 1995.
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Stern GA, Schemmer GB, Farber RD, Gorovoy MS: Effect of topical antibiotic solutions on corneal epithelial wound healing. Arch Ophthalmol 101:644–647, 1983.
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CHAPTER 187 • Conjunctival, Corneal, or Scleral Cysts
187 CONJUNCTIVAL, CORNEAL, OR SCLERAL CYSTS 371.23
PRECAUTIONS
Most patients present with a history of trauma or a previous surgical procedure. The vision of the affected eye varies widely on presentation from 20/20 to light perception, depending on the size and location of the cyst. The appearance of the cyst depends on the stage of development. In the early stages, the cyst may look like a small
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SECTION 19 • Cornea
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nebulous opacity. In the advanced stages, the cyst becomes oval to round. The cyst may be single and round, or multiloculated. The color ranges from clear to opalescent; however, the majority of cysts have a hypopyon-like feature in which cloudy debris settles inferiorly and the top of the cyst is fi lled with clear fluid. The cyst may occupy different levels of stroma, but midstromal location appears most frequently in reports. It could extend horizontally into the limbus or sclera and posteriorly into the anterior chamber. Rarely, communication with the anterior chamber is formed. Isolated intrastromal cysts with no communication with anterior chamber is the hallmark. The size varies dramatically from a few millimeters in diameter to covering the entire cornea. The cysts tend to progressively enlarge at a slow pace, usually taking months to years to become noticeable. The surrounding tissue of the eye appears white and noninflamed. There may or may not be blood vessels around the cyst. The epithelial layer of the cornea above the cyst could be normal without fluorescein staining. In other patients, previous trauma may leave an obvious corneal scar over the cyst. The cysts typically do not cause significant pain or discomfort. Corneal cysts are usually unilateral, although Fox reported a bilateral corneal cyst in one patient.
Laboratory findings The development of intrastromal corneal cysts represents an aberration of the normal wound-healing process. After the penetrating or perforating laceration to the cornea, edema of the corneal stroma and fibrin plug formation usually occur. Later, fibroplastic proliferation into the clot begins with the adjacent stromal cells. This fibrous reaction forms a linear scar, and posteriorly to the endothelium it extends across the wound and lays down a thin membrane. On the anterior surface, as the wound heals, the initial epithelial downgrowth between the wound edges is gradually pushed toward the surface by the fibrous scar. Occasionally, epithelium becomes sequestered and isolated within the corneal stroma. Early authors speculated on different congenital and embryonic causes of the development of these cysts. When more recent reports are examined, the concept of congenital origin appears doubtful. These cysts are usually unilateral and are not associated with other congenital anomalies. They are not inherited, and they have a similar appearance to cysts of known traumatic cause. Therefore, the congenital origin of corneal cysts is very unlikely. The inciting trauma in these cases may be relatively minor, such as a pencil, a pen, scissors, or other sharp objects. Minor injuries heal quickly, cause minimal symptoms, and may go unnoticed until the cysts reach a clinically significant size. ● In most recent reported cases, a history of corneal trauma is well documented, ranging from minor corneal ulceration to severe trauma causing hyphema and cataracts. ● Frequently, intracorneal cysts develop after surgical procedures, including cataract surgery, lamellar keratoplasty, keratomileusis, penetrating keratoplasty, epikeratoplasty, radial keratotomy and strabismus surgery. ● Trauma and surgery also may cause epithelial downgrowth into the anterior chamber, so coexistence of epithelial downgrowth should be suspected if the eye is irritated or
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inflamed or there are signs of corneal edema from endothelial cell damage. Light microscopic examination of the cysts has been carried out by numerous authors, and the fi ndings have been similar. The surface epithelium and Bowman’s layer were normal. The stroma typically was nonvascularized and noninflamed. Occasional small vascular channels were observed. The epithelial cells lining the cysts varied in morphology, ranging from squamous to columnar and from one cell thick to multilaminar. The anterior cystic cells tend to be flattened or squamous, whereas the posterior cells are rounder or columnar. The epithelial cells were quiet without any signs of inflammation or malignant transformation. Desquamated cells were present in the cyst. There were no glandular structures or hair follicles.
TREATMENT The treatment of intracorneal cysts depends on the depth, size, and location of the cyst at the time of diagnosis. ● The conservative approach is advised if the cyst does not involve the pupil or central cornea and if the patient still has good vision. ● Simple observation is prudent. These cysts are indolent and enlarge slowly or not at all over the years. Spontaneous reabsorption of the cysts has been reported; however, in these cases, the cysts most likely rupture into the anterior chamber. Others have reported very slow enlargement or no change in the size of the cyst for as long as 6 years. ● When the cyst has achieved a significant size or if it is near the pupillary axis and affects visual acuity, a defi nitive procedure should be considered. ● A simple incision and drainage procedure or needle aspiration has no permanent effect. These procedures have been tried repeatedly, and the result has been the same; the cysts invariably refi ll over time. ● Marsupialization through removal of a portion of the anterior wall of the cyst followed by destruction of the epithelial cell with chemical cautery is highly successful. Different chemical solutions have been used for the destruction of epithelial cells, including 10% acetic acid, 1% trichloroacetic acid, 1% iodine and cocaine. ● After chemical cauterization of the cavity, fine temporary sutures, such as 10-0 nylon, may be used to hold the walls of the cavity together until they have sealed. This suture is tied on the corneal surface and the knots are rotated into the stroma. This suture can be removed after 3 weeks with the marsupialization technique. The marsupialization technique usually provides a high rate of success; in reported cases, the cysts either were destroyed completely or decreased significantly in size. Marsupialization could be difficult if the cyst is deep and centrally located; to provide visual rehabilitation in these cases, penetrating keratoplasty is the best procedure. During penetrating keratoplasty, the surgeon must avoid spilling the cyst contents into the anterior chamber. Copious irrigation should be performed. Cryotherapy can be applied to the cyst before penetrating keratoplasty to kill the epithelial cells. Anterior chamber cyst formation has been reported after penetrating keratoplasty for corneal cyst; in this case, the patient had a protracted and complicated course with poor visual outcome. No recurrence of corneal cysts has been reported after penetrating keratoplasty.
REFERENCES Al-Rajhi A, Al-Kharashi S: Epithelial inclusion cyst following epikeratoplasty. J Refract Surg 12:516–519, 1996. Avni I, Cahane M, Blumenthal M, Naveh N: Transformation of corneal epithelial cyst into anterior chamber implantation cyst and scleral cyst: A rare occurrence. J Pediatr Ophthalmol Strabismus 26:303–306, 1989.
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Bloomfield SE, Jakobiec FA, Iwamoto T: Traumatic intrastromal corneal cyst. Ophthalmology 87:951–955, 1980.
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Claiborne JH: Epithelial corneal cyst. Transam Ophthalmol 10:588–593, 1984. Fox LW: Bilateral cysts of the cornea. Br J Ophthalmol 12:249–254, 1928.
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Jester JV, Villasenor RA, Miyashiro J: Epithelial inclusion cysts following radial keratotomy. Arch Ophthalmol 101:611–615, 1983.
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Liakos GM: Intracorneal and sclerocorneal cysts. Br J Ophthalmol 62:155– 158, 1978.
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Purcell J, Brady H: Intrastromal epithelial corneal cyst. Ophthalmic Surg 14:491–499, 1983. Reed JW, Dahlman CH: Corneal cyst: a report of 8 cases. Arch Ophthalmol 86:648–652, 1971.
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Vrolijk M: Corneoscleral cyst. Acta Ophthalmol 19:44–51, 1941. Wood T: Corneal intrastromal cyst. Ann Ophthalmol 8:967–968, 1976. Yee RD, Hit TH: Corneal intrastromal cyst following lamellar keratoplasty. Am J Ophthalmol 7:644–646, 1975.
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188 CORNEAL ABRASIONS, CONTUSIONS, LACERATIONS 918.2, AND PERFORATIONS 370.06
TREATMENT ●
Guruswami Arunagiri, MD, FRCSEd Danville, Pennsylvania Rupan Trikha, MD Danville, Pennsylvania
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Corneal abrasions Corneal abrasion is the loss of part or all of the corneal epithelium, from direct or indirect injury. It is one of the most common reasons for new patient visits to the ophthalmic emergency room.
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ETIOLOGY ●
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Mechanical: fingernail, paper, foreign body, curling iron, mascara brush, plant, and contact lens. Chemical: hair sprays, alkali and acid exposure. Iatrogenic: eye patching, tonometry, ocular surgery, general anesthesia. Others: heat, ultraviolet light.
Visual acuity is decreased due to excessive tearing or abrasion in the visual axis. Conjunctival erythema, chemosis and lid edema can occur in severe cases. Using a slit lamp, the edges of the abrasion can be visualized with direct illumination and scleral scatter techniques. Corneal light reflex is blunted due to surface irregularity. Initially, an epithelial defect is present with clear underlying stroma. A very mild stromal infi latrate may be present with minimal anterior chamber cell and flare reaction 12 to 24 hours later. Fluorescein dye with a cobalt-blue light filter will enhance visualization of the abrasion. Topical anesthetics may be used if pain and photophobia limit examination. Multiple, vertical, linear corneal abrasions are usually due to an upper lid palpebral foreign body and examination by lid eversion should be performed. Stromal abrasions are rare and due to trauma from a sharp or abrasive object. Most commonly seen with fi ngernail injury in sports. Often a corneal flap of varying thickness may be seen. These injuries take longer to heal, and are often associated with edema below the involved area. Atypical presentations or cases not involving trauma require consideration of other causes, especially herpes simplex epithelial keratitis. High velocity objects can penetrate the cornea and leave minimal evidence except a small epithelial defect.
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Antibiotic prophylaxis with a broad-spectrum antibiotic (e.g. fluroquinolone, polysporin, erythromycin) is recommended in all cases, and may be in the form of an ointment or solution. For contact lens wearers, an antibiotic with pseudomonal coverage (e.g. fluroquinolone) should be used. Cycloplegic agents (e.g. cyclopentolate, homatropine) reduce discomfort from traumatic iritis. Topical nonsteroidal antiinflammatory drug drops can also be used for pain control (e.g. diclofenac, ketorolac). Oral non-narcotic or narcotic analgesia is rarely required. Steroid use for iritis in this setting is not recommended as it can hinder epithelial healing and increase risk of infection. Eye patch use is controversial and should not be used in patients with history of contact lens use or injury involving vegetable matter. Bandage soft contact lenses (BSCL) are very effective in reducing pain, but should only be used with topical antibiotic coverage. BSCL use is contraindicated in cases involving vegetable matter or artificial fingernails. Follow up examination should be performed at every 2–5 days, and sooner for high-risk cases, until the epithelial defect has healed.
CHAPTER 188 • Corneal Abrasions, Contusions, Lacerations and Perforations
Binder PS, Beale JP, Zavala EY: The histopathology of a case of keratophakia. Arch Ophthalmol 100:101–105, 1982.
Chan MY, Liao HR, Fong JC: Traumatic intracorneal cyst. Am J Ophthalmol 21:303–305, 1989.
Symptoms may be delayed for several hours with ultraviolet keratitis or contact lens related injury.
DIAGNOSIS Symptoms ●
Tearing, eye pain, and foreign body sensation, photophobia, and blephrospasm.
COMPLICATIONS Most superficial corneal abrasions heal within a few days. Rare complications include:
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SECTION 19 • Cornea
Infection. Corneal scaring. Recurrent corneal erosions: ● Occur due to poor adhesion of epithelium to underlying basement membrane; ● Treatment is the same as for any corneal abrasion; ● Prevention involves long-term lubrication with ointment at bedtime; ● In persistent cases, superficial keratectomy or micropuncture may be necessary for resolution.
Corneal contusions Corneal contusion results from blunt trauma to the cornea without penetration of the ocular surface.
ETIOLOGY Common causes include injury with rubber bands, bungee cords, automobile airbags and BB gun pellets.
DIAGNOSIS ● ●
Symptoms: pain, photophobia, and decreased vision. Signs: ● Focal edema at the site of impact, or rarely diffuse corneal edema with severe endothelial damage; ● Breaks in Descemet’s membrane can occur from severe stretching and bending of the cornea; ● Rarely, endothelial rings composed of damaged endothelial cells, fibrin, and leukocytes, surrounded by normal endothelium may be present. These resolve within a few days; ● Other ocular injury includes iritis, hyphema, iridodialysis, angle recession, traumatic cataract, vitreous hemorrhage, choroidal rupture, retinal detachment, and commotio retina.
TREATMENT Treatment of corneal contusions is initially conservative. In most cases the cornea regains its clarity in a few days, in spite of permanent endothelial cell loss. ● Topical steroid drops (e.g. Prednisolone Acetate) and hypertonic saline solutions (e.g. Hypertonic sodium chloride drops) have been used with little benefit. ● Penetrating keratoplasty is indicated for persistent corneal edema or stromal scar. ● Associated ocular injuries such as listed above should be managed appropriately.
Corneal laceration 918.2
ETIOLOGY Corneal lacerations result from a sharp object that cuts through corneal tissue. A common cause includes high-speed pieces of material released when grinding or cutting metal, wood, glass, or plastic.
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DIAGNOSIS History is crucial in the diagnosis and for medical-legal reasons. Information should be obtained of the time and place of injury, as well as the activity being done, uses of safety glasses, first aid measures undertaken, and additional injuries that occurred. ● Symptoms: eye pain, tearing, bleeding, foreign body sensation, photophobia, and decreased vision. ● Evaluation: ● Visual acuity should be measured with pinhole or corrective lens when possible; ● A wire lid speculum is useful when there is significant chemosis and ecchymosis; ● External pressure or manipulation of foreign bodies at the site of laceration should be avoided; ● Location, size, depth of the laceration, and prolapse of intraocular tissue should be noted. With prolapse of intraocular tissues, further examination is deferred until surgery; ● Seidel test using fluorescein with cobalt blue light may be necessary to identify occult leakage of aqueous; ● Further examination for lid laceration, hyphema, iritis, iridodialysis, disruption of the lens capsule and cataract, vitreous hemorrhage, intra-ocular foreign body must be done; ● In suspected cases of intra-ocular foreign body, CT scan or ultrasound in expert hands is recommended.
TREATMENT Treatment is dependent on whether the laceration is partial or full thickness. ● All patients require prophylaxis with broad-spectrum topical antibiotic (e.g. fluroquinolone) and a cycloplegic agent (e.g. homatropine, cyclopentolate). ● Partial thickness laceration: ● Medically treated with topical broad-spectrum antibiotics with or without a cycloplegic agent; ● Deep partial thickness lacerations may be sutured to reduce scaring, and risk of rupture. ● Full thickness lacerations: ● For lacerations less than 2 mm and with minimal tissue loss, a bandage contact lens with or without cyanoacrylate glue (not FDA approved) may be used; ● Lacerations larger than 2 mm or with tissue loss are repaired surgically. A shield is placed over the injured eye to prevent further damage, and the patient kept NPO. ● Use of systemic antibiotics is controversial. We give systemic antibiotics (ceftazidime and vancomycin) in the setting all full thickness corneal lacerations. Most agree with use of systemic prophylaxis in the presence of an intraocular foreign body. ● Antiemetic agents (e.g. promethazine, metaclopramide) should be used as needed to prevent Valsalva. ● Tetanus toxoid is recommended for all full thickness wounds. ● Postoperatively, patients are prescribed polycarbonate safety glasses for constant use to avoid injuries to either eye.
Surgical technique
General principles for repair ● ●
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Use 10-0 nylon for suturing. Sutures are placed at 90% depth on both sides of the wound. Suturing should be watertight, and induce minimal scarring or astigmatism. Limbal or peripheral sutures are placed fi rst. Wider spaced, long compressive sutures are applied peripherally to maintain flatter curvature. Suturing in the visual axis should be avoided, but if needed, short, minimally compressive sutures are applied to maintain steeper curvature. Knots should be trimmed and buried away from the visual axis. For perpendicular wounds, the length of each suture pass should be symmetrical from the anterior surface of the cornea. For oblique wounds, length of suture pass should be symmetrical from the posterior surface of the cornea. For combination wounds the perpendicular wounds are closed first. Watertight closure of the wound may be difficult in cases of tissue loss, puncture wounds, or unusual lacerations. In these cases, a X-shaped suture may be placed. Corneal patch or lamellar graft, or primary penetrating keratoplasty can be considered in severe or difficult cases. In traumas that are less than 24 to 36 hours with no signs of infection, viable uvea and retina are reposited through a paracentesis incision with viscoelastic device or cyclodialysis spatula. Nonviable tissue is excised. Vitreous prolapse is treated by vitrectomy with Wekcels and Wescott scissors or with automated vitrector. Surgery for cataract with an intact lens capsule is deferred for a later date. Cataract surgery is indicated for intumescent lens, anterior capsular rupture with release of lens material, but is performed after the corneal laceration is sutured. Intra ocular lens implantation is controversial. Vitreous hemorrhage, intraocular foreign body, retinal detachment should be managed by a retinal surgeon.
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Vitreous involvement predisposes to retinal detachment from direct traction or vitreal-fibrous proliferation and contraction. Direct damage to angle structures, or obstruction from inflammatory debris or cells can lead to glaucoma.
Corneal perforations 370.06 In addition to traumatic corneal injuries, corneal perforations can result from: ● Trauma; ● Corneal ulcers; ● Inflammatory diseases — connective tissue diseases, Mooren’s ulcer; ● Exposure keratopathy, neurotrophic disease; ● Ectatic disorders — kerataconus, keratoglobus, pellucid marginal degeneration; ● Xerosis (vitamin A deficiency, cicatricial ocular surface diseases); ● Degenerative disease — Terrien’s; ● Postsurgical. ● Symptoms: pain, decreased vision, tearing, photophobia. ● Signs: ● Shallow or flat anterior chamber; ● Radiating Descemet’s folds; ● Uveal tissue prolapse; ● Seidel test positive for aqueous leak; ● Central clear zone in area of infi ltrate; ● Hypotony.
TREATMENT Treatment is guided by the etiology of the corneal perforation. ● Small, non-traumatic perforations can be treated with cyanoacrylate glue and a bandage contact lens. ● Larger perforations require patch grafting or penetrating keratoplasty (PKP) to restore ocular integrity. ● Infectious perforations have a better outcome with PKP instead of glue. ● Ocular surface or immunologic disorders are more effectively treated with glue to delay or prevent PKP. ● Amniotic membrane transplant can also be used for treating perforations. This is a multi-step procedure and involves wound debridement, fi lling of wound with pieces of amniotic membrane tissue, followed by suturing two layers of amniotic membrane over the effected area. ● Intravitreal or subtenon’s antibiotics are highly recommended at the time of surgery in the setting of infectious causes. ● Treatment of the underlying medical condition, such as connective tissue disease or vitamin A deficiency, has to be addressed simultaneously.
CHAPTER 188 • Corneal Abrasions, Contusions, Lacerations and Perforations
Surgical repair in penetrating wounds should be performed in the operating room with general anesthesia. Depolarizing agents like succinylcholine, and retrobulbar anesthesia is avoided to prevent co-contraction of extraocular muscles and extrusion of intraocular contents. A detailed description of surgical technique is beyond the scope of this chapter. The primary goal of surgery is to restore the anatomic integrity of the globe. Visual restoration is only secondary.
COMPLICATIONS COMPLICATIONS ●
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The immediate injury can lead to iris prolapse, hyphema, cataract formation, lens disruption and vitreous loss. Secondary complications include infection, astigmatism, scarring, vascularization, chronic wound leak, epithelial ingrowth, iridocorneal adhesions and intraocular fibrous proliferation.
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Wound leak or dehiscence. Recurrent perforation due persistent underlying disease. Astigmatism, scarring, vascularization, epithelial ingrowth, iridocorneal adhesions and intraocular fibrous proliferation.
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REFERENCES
PATHOPHYSIOLOGY
Arunagiri G: Corneoscleral laceration. emedicine. Ophthalmology 5:1–10, 2004.
Kaiser PK: The corneal abrasion patching study group. A comparison of pressure patching versus no patching for corneal abrasions due to trauma or foreign body removal. Ophthalmology 102(12):1936–1942, 1995.
Regardless of the inciting factor, endothelial cell loss results in migration of endothelial cells from neighboring areas to cover depleted areas. When these cells are not able to compensate, they enlarge and are irregular in shape (polymegathism and pleomorphism), resulting in stromal hydration and eventually leading to keratocyte loss, attenuation of Bowman’s membrane and the epithelial basement membrane, and a decrease in glycosaminoglycans in the stroma. In response, epithelial cells, keratocytes, and fibroblasts produce βig-h3, tenascin-C, and fibrillin-1, which may contribute to the poor adhesive characteristics of the epithelium and the resulting epithelial bullae.
Kunimoto DY, Kanitkar KD, Makar MS, eds: Corneal laceration. In: Wills eye manual. 4th edn. Pennsylvania, Lippincott Williams & Wilkins, 2004.
COURSE/PROGNOSIS
Arunagiri G: Iris prolapse. emedicine. Ophthalmology 5:1–10, 2004. Beatty RF, Beatty RL: The repair of corneal and scleral lacerations. Sem Ophthalmol 9(3):165–176, 1994.
SECTION 19 • Cornea
Buzard KA: Compression sutures and penetrating corneal trauma. Ophthalmic Surgery 23(4):246–252, 1992. Hamill MB: Corneal and scleral trauma. Ophthalmol Clin N Am 15(2):185– 194, 2002.
Macsai MS: Surgical management and rehabilitation of anterior segment trauma. In Surgical management and rehabilitation of anterior segment trauma. In: Krachmer JH, Mannis MJ, Holland E, eds: Cornea. 2nd edn. London, Elsevier, 2005. Patrone G, Sacca SC, Macri A, Rolando M: Evaluation of the analgesic effect of 0.1% indomethacin solution on corneal abrasions. Ophthalmologica 213(6):350–354, 1999.
189 Corneal Edema 371.20 (Bullous Keratopathy, Epithelial Edema, Stromal Edema) Joel Sugar, MD Chicago, Illinois Rashmi Kapur, MD, ECFMG Chicago, Illinois
ETIOLOGY Corneal edema is the condition of excess corneal hydration that is caused by altered fluid transport across the cornea. Epithelial edema is most troubling to visual acuity because it induces anterior irregular astigmatism. In epithelial edema, fluid accumulates initially within basal cells and then between epithelial cells, causing microbullae; ultimately, fluid accumulates beneath the basal cell layer, lifting up the corneal surface to form bullae. Endothelial dysfunction, corneal hypoxia, and elevated intraocular pressure are the most common causes of corneal edema. Stromal infi ltration and inflammation can also cause corneal edema. Endothelial dysfunction may be due to Fuchs’ dystrophy, other endothelial disorders such as iridocorneal endothelial (ICE) syndrome, or endothelial damage from trauma, including cataract or other intraocular surgery. Endothelial dysfunction may also occur after uveitis, angle-closure glaucoma, prolonged contact with silicone oil, or with chronic hypotony and inadequate corneal endothelial nutrition. Herpetic disciform keratitis with endothelial inflammation can also produce corneal edema. Hypoxia from prolonged wear of contact lenses with poor oxygen transmissibility can lead to corneal edema. Acute or severe elevations in intraocular pressure (IOP) in the presence of endothelial dysfunction can lead to corneal edema. With high elevations of IOP in the presence of normal endothelial function, the stroma initially remains thin and clear, but there is the development of epithelial edema. Hypotony results in isolated stromal edema.
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Because the corneal endothelial cell density diminishes over time, corneal endothelial damage added to the normal attrition of endothelial cells with advancing age can lead to progressive corneal edema. Initial mild corneal edema may over months to years become chronic, visually disabling corneal edema. Prolonged corneal edema may lead to corneal vascularization and subepithelial pannus formation, which can complicate future surgical treatments.
DIAGNOSIS Clinical signs and symptoms Stromal edema is less disturbing to visual acuity and is manifest as thickening and hazy opacification of the corneal stroma with folding of Descemet’s membrane (Figure 189.1). Typically, the initial presentation of epithelial edema is blurred vision, which is most severe on awakening and decreases as the day progresses. As the severity increases, the visual acuity difficulty becomes persistent, and rupture of bullae may lead to recurrent pain, redness and photophobia. Anterior chamber inflammation may be seen as well, and secondary corneal infection can ensue.
Laboratory findings ●
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Epithelial edema and stromal edema are demonstrated at the slit-lamp examination or by pachymetry. Endothelial guttae or decreased endothelial cell density is demonstrated on slit-lamp evaluation, endothelial specular microscopy, or confocal microscopy.
FIGURE 189.1. Corneal edema with Descemet membrane folds.
TREATMENT ● ●
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Surgical ●
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Palliative anterior stromal puncture, corneal cautery, conjunctival flap placement, amniotic membrane transplantation, or phototherapeutic keratectomy (PTK) may be sufficient to provide comfort to patients with recurrent painful bullae in eyes with limited or no visual potential. Optical penetrating keratoplasty (PKP) may be combined with lens extraction in the face of cataract. Intraocular lens exchange and, if necessary, anterior vitrectomy may be indicated for corneal edema associated with intraocular lenses. Posterior lamellar keratoplasty (PLK) is an evolving procedure that involves surgical replacement of the endothelial cell layer with donor tissue, with minimal manipulation of the recipient corneal surface. Deep lamellar endothelial keratoplasty (DLEK) was initially described with instrument and procedural refinements over simple PLK and demonstrated successful results. However lamellar dissection of the recipient cornea still proved to be difficult for many surgeons. The current technique, Descemet’s stripping endothelial keratoplasty (DSEK) or Desecmet’s stripping automated endothelial keratoplasty (DSAEK) is a further technical advancement and involves scraping Descemet’s membrane and endothelium from the recipient cornea. The advantage over a traditional PKP is that these variants of PLK can result in smoother surface topography with minimal astigmatism and decreased risk of wound dehiscence. Also the post-operative corneal power can be more stable and predictable, which allows for accurate calculations of intraocular lens power. Because of the lack of issues regarding sutures, wound stability, and topography, these techniques may result in more rapid visual rehabilitation. For patients who have undergone multiple PKPs or have a high risk of graft failure, keratoprosthesis can be offered as a treatment modality. Recent studies have shown that the corneal endothelium is arrested in the G1-phase of the cell cycle and retains the capacity to proliferate in vivo, but is inhibited by factors such as TGF-B and p27kip1. In the future, this information may help us to induce endothelial cell proliferation in vivo and create better procedures for repopulation of endothelial cells.
COMPLICATIONS In addition to decreased vision and pain, patients may develop significant anterior segment inflammation when bullae rupture. This can lead to hypopyon formation in the absence of infection. Treatment with cycloplegic agents is very beneficial, in addition to the mentioned treatments. Secondary infection may also occur in the face of loss of epithelium due to the rupture
REFERENCES Adamis AP, Filatov V, Tripathi BJ, et al: Fuchs’ endothelial dystrophy of the cornea. Surv Ophthalmol 38:149–168, 1993. Akhtar S, Bron AJ, Hawksworth NR, et al: Ultrastructural morphology and expression of proteoglycans, βig-h3, tenascin-C, fibrillin-1, and fibronectin in bullous keratopathy. Br J Ophthalmol 85:720–731, 2001. Cormier G, Brunette I, Boisjoly HM, et al: Anterior stromal punctures for bullous keratopathy. Arch Ophthalmol 114:654–658, 1996. Flowers CW, Chang KY, McLeod SD, et al: Changing indications for penetrating keratoplasty, 1989–1993. Cornea 14:583–588, 1995. Hatton MP, Perez VL, Dohlman CH: Corneal oedema in ocular hypotony. Experimental Eye Research 78:549–552, 2004. Hicks CR, Crawford GJ, Lou X, et al. Corneal replacement using a synthetic hydrogel cornea, AlphaCorTM: device, preliminary outcomes and complications. Eye 17:385–392, 2003. Ishino Y, Sano Y, Nakamura T, et al: Amniotic membrane as a carrier for cultivated human corneal endothelial cell transplantation. Invest Ophthalmol Vis Sci 45:800–806, 2004. Joyce NC: Proliferative capacity of the corneal endothelium Progress in Retinal and Eye Research 22:359–389, 2003. Kangas TA, Edelhauser HF, Twining SS, et al: Loss of stromal glycosaminoglycans during corneal edema. Invest Ophthalmol Vis Sci 31:1994– 2002, 1990.
CHAPTER 190 • Corneal Mucous Plaques
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When elevated, intraocular pressure should be controlled. When inflammation is the source of the edema, it should be controlled. Corneal dehydration should be sought for patients with early or mild edema with hypertonic saline drops or ointments (usually drops as frequently as needed during the day and ointment at bedtime). A hairdryer held at arm’s length for stimulation of tear evaporation on awakening in the morning may be helpful. Soft contact lenses should be used for painful recurrent bullae or for early mild irregular astigmatism.
of bullae and has been reported at a rate of 4.7% in bullous keratopathy patients.
Levenson JE: Corneal Edema: Cause and treatment. Surv Ophthalmol 20:190–204, 1975. Luchs JI, Cohen EJ, Rapuano CJ, et al: Ulcerative keratitis in bullous keratopathy. Ophthalmology 104:816–822, 1997. Maini R, Sullivan L, Snibson GR, et al: A comparison of different depth ablations in the treatment of painful bullous keratopathy with phototherapeutic keratectomy. Br J Ophthalmol 85:912–915, 2001. McMahon TT, Polse KA, McNamara N, et al: Recovery from induced corneal edema and endothelial morphology after long-term PMMA contact lens wear. Optometry Vision Sci 73:184–188, 1996. Mohay J, Lange DM, Soltau JB, et al: Transplantation of corneal endothelial cells using a cell carrier device. Cornea 13:173–182, 1994. Pires RTF, Tseng SCG, Prabhasawat P, et al: Amniotic membrane transplantation for symptomatic bullous keratopathy. Arch Ophthalmol 117:1291–1297, 1999. Terry MA, Ousley PJ: Replacing the endothelium without corneal surface incisions or sutures: The fi rst United States clinical series using the deep lamellar endothelial keratoplasty procedure. Ophthalmology 110:755–764, 2003. Waring GO, 3rd, Bourne WM, Edelhauser HF, et al: The corneal endothelium: normal and pathologic structure and function. Ophthalmology 89:531–590, 1982. Melles GR. Posterior lamellar keratoplasty: DLEK to DSEK to DMEK. Cornea 25:879–881, 2006.
190 CORNEAL MUCOUS PLAQUES 371.44 Ramesh C. Tripathi, MD, PhD, FACS, FRCOphth Columbia, South Carolina Brenda J. Tripathi, PhD Columbia, South Carolina Richard M. Davis, MD Columbia, South Carolina Corneal mucous plaques are abnormal collections of a mixture of mucus, epithelial cells, and proteinaceous and lipoidal material that adhere firmly to the corneal surface. The plaques may
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SECTION 19 • Cornea
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defects; because of its physicochemical property, the mucous plaque enmeshes the desquamated epithelial cells. The viscosity of the mucus may increase due to dehydration or an increase in its sialomucin component, or secondarily because of infection with staphylococci, which liberate enzymes that can lyse the mucoprotein and glycosaminoglycan components of mucus produced normally by the conjunctival goblet cells. Corneal mucous plaques occur primarily in patients with keratoconjunctivitis sicca but may also occur with herpes zoster, vernal keratoconjunctivitis, and other forms of keratitis, especially in patients with neuroparalytic or neurotrophic keratitis or after local radiation exposure in whom corneal sensation is defective. Corneal mucous plaques and fi lamentary keratitis may coexist in the above conditions and also after Lasik, Lasek and, more frequently, penetrating keratoplasty at the donorrecipient interface. In fi lamentary keratitis, the corneal epithelial cells use the mucin strand as a substrate to grow along the fi lament, whereas, the cells are enmeshed in the corneal mucous plaque and the plaque remains flat and only slightly elevated from the corneal surface. Delayed plaques and pseudodendrites associated with herpes zoster may also be infectious, as they are positive for zoster DNA by polymerase chain reaction. Ciliary or conjunctival injection, mild iritis, with or without keratic precipitates, and epithelial and stromal edema are associated findings.
b
FIGURE 190.1. Corneal mucous plaques. a) Clinical photograph of multiple corneal mucous plaques of varying sizes and shapes in a patient with keratoconjunctivitis sicca. Fluorescein staining reveals breakup of the tear film over the plaques, which are slightly elevated from the corneal surface. b) Photomicrograph of 1 μm thick, toluidine blue stained section of a debrided mucous plaque that consists of desquamated degenerating epithelial cells (arrows), lipid globules (L), mucin (M) and foreign bodies. Original magnification × 160.
DIAGNOSIS Clinical signs and symptoms ●
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also enmesh calcareous granules and bacteria, as well as dust particles and other foreign bodies. The mucous plaques are translucent to opaque and may vary in size and shape from multiple small islands to bizarre patterns that may involve more than half the corneal surface (Figure 190.1).
TREATMENT ●
ETIOLOGY/INCIDENCE ● ●
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An abnormality of the exposed surface of the superficial corneal epithelial cells and of tears with excessive mucus formation and the presence of epithelial receptor sites for the plaque elements predispose to this condition. The normal desquamation of epithelial cells beneath the plaque is retarded, and exfoliating surface cells become incorporated in the plaque. The plaque is formed when highviscosity mucus and proteinaceous material adhere to the deeper squamous cells of the cornea or even to Bowman’s layer through the intercellular spaces, as well as through abnormally formed transcellular aperture and epithelial
Symptoms associated with the plaques vary from blurring of vision to foreign body sensation and marked pain; except when severe, they are often indistinguishable from the symptoms of keratoconjunctivitis sicca with or without Sjögren syndrome. These symptoms may also occur with herpes zoster keratitis and in patients using extended-wear soft contact lenses and in recurrent erosion syndrome. This entity is also associated with systemic disease, primarily rheumatoid arthritis or other collagen diseases.
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Topically applied 10% to 20% acetylcysteine drops qd to q.i.d. can rapidly loosen the adherent plaque and dissolve its mucoid component and may prevent reformation. Mucous plaques causing severe symptoms may be removed surgically by debridment, scraping or pulled out with forceps or by rolling up with cotton swabs or Weck-cel sponge. A bandage gas permeable soft contact lens may be applied to the cornea. In some patients, a soft contact lens is also of therapeutic or preventive value. However, because of associated dry eye problems and deposit formation, the contact lenses may need frequent replacement or cleaning. Staphylococcal blepharitis may occur in association with corneal mucous plaques and may predispose patients to this condition. Treatment should also include the control of associated local microbial infections.
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Conjunctiva: conjunctivitis, fornix fi laments, hyperemia, mucoid discharge. Cornea: fi lamentary keratitis, keratoconjunctivis sicca, mucous plaques, keratic precipitates associated with mild iritis. Eyelids: chronic blepharitis, blepharospasm.
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Because of variations in the frequency and severity of corneal mucous plaques, the use and concentration of topical mucolytic agents, such as acetylcysteine, should be individualized. Often, bandage soft contact lenses are subject to deposit formation and spoilage secondary to alterations in tear function (including rapid tear break-up time), associated necrosis of keratoconjunctival tissue and the plaque exposure. Therefore periodic cleaning or change of the soft contact lens may be required. Because treatment with topical steroids may delay healing and long-term use may induce or exacerbate open-angle glaucoma, these agents should be used with caution.
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Thickened plaques with a dry surface may appear elevated well above the tear fi lm and may even cause dellen (Fuchs’ dimples) formation.
REFERENCES Avisar R, Robinson A, Appel I, Yassur Y, Weinberger D: Dicolfenac sodium, 0.1% (Voltaren Ophtha), versus sodium chloride, 5%, in the treatment of fi lamentary keratitis. Cornea 19:145–147, 2000. Cameron JA, Antonios SR, Badr IA: Excimer laser phototherapeutic keratectomy for shield ulcers and corneal plaques in vernal keratoconjunctivitis. J Refract Surg 11:31–35, 1995. Fraunfelder FT, Wright P, Tripathi RC: Corneal mucus plaques. Am J Ophthalmol 83:191–197, 1977. Grinbaum A, Yassur I, Avni I: The beneficial effect of diclofenac sodium in the treatment of fi lamentary keratitis. Arch Ophthalmol 119:926– 927, 2001. Marsh RJ, Fraunfelder FT, McGill JI: Herpetic corneal epithelial disease. Arch Ophthalmol 6:1899–1902, 1976. Pavan-Langston D, Yamamoto S, Dunkel EC: Delayed herpes zoster pseudodendrites: Polymerase chain reaction detection of viral DNA and a role for antiviral therapy. Arch Ophthalmol 113:1381–1385, 1995. Perry HD, Doshi-Carneavale S, Donnenfeld ED: Topical cyclopsorin A 0.5% as a possible new treatment for superior limbic keratitis. Ophthalmology 110:1578–1581, 2003. Rotkis WM, Chandler JW, Forstot SL: Filamentary keratitis following penetrating keratoplasty. Ophthalmology 89:946–949, 1982.
CHAPTER 191 • Corneal Neovascularization
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Artificial tear preparations may be indicated for the treatment of dry eye. In the presence of fi lamentary keratitis and the formation of excessive mucus, hypotonic artificial tear substitutes (rather than the mucoid or viscous type of tear substitutes) may be combined with acetylcysteine. As cyclosporin A, non-steroidal anti-inflammatory agents and topical low-potency corticosteroids are used in the treatment of dry eye and filamentary keratitis, these agents could be another avenue for the medical management of corneal mucous plaques, which are often associated with a varying degree of inflammation. Delayed plaques and pseudodendrites associated with herpes zoster may be responsive to certain antiviral therapy. Because preservatives, such as benzylkonium chloride, chlorobutanol and thimerosol, adversely affect the corneal epithelium, the use of preservative-free tear substitutes or lubricants is preferable. Excimer laser phototherapeutic keratectomy may be a useful adjunct in the treatment of shield-shaped corneal ulcers and plaques in associated conditions such as vernal keratoconjunctivitis.
Shaw EL, Gasset AR: Management of an unusual case of keratitis mucosa with hydrophilic contact lenses and N-acetyl-cysteine. Ann Ophthalmol 6:1054–1056, 1974. Tripathi BJ, Tripathi RC, Kolli SP: Cytotoxicity of ophthalmic preservatives on human corneal epithelium. Lens Eye Tox Res 9:361–374, 1993. Tripathi RC, Tripathi BJ, Frankel RA: Corneal mucus plaques. In: FT Fraunfelder, FH Roy, eds: Current ocular therapy. 5th edn. WB Saunders, Philadelphia, 1999:352–353. Tripathi RC, Tripathi BJ, Haggerty C: Drug-induced glaucomas: mechanism and management. Drug Safety 26:749–767, 2003. Tripathi RC, Tripathi BJ, Silverman RA, Rao GN: Contact lens deposits and spoilage: Identification and management. Int Ophthalmol Clin 31:91–120, 1991.
191 CORNEAL NEOVASCULARIZATION 370.60 F. Hampton Roy, MD, FACS Little Rock, Arkansas
COMMENTS ETIOLOGY ●
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In some cases, corneal mucous plaques recur when the mucolytic agent is discontinued. Plaques may occur even in those patients receiving acetylcysteine, but usually they are smaller or remain on the corneal surface for shorter periods of time than those in patients who did not receive therapy. In some patients, plaques may recur if the soft contact lens is discontinued. Multiple plaques, which are frequently bilateral, are common. When a plaque has adhered to the cornea, it remains for a few days or weeks; recurrences may appear but seldom in the same location.
Corneal neovascularization can be defi ned as a pathologic state in which new blood vessels extend from the limbus into the superficial or deep areas of the cornea and is the result of various causes, including trauma, inflammation, infection, toxic insult, and underlying inherited corneal dystrophy or degeneration. The normal cornea is a physiologically capillary-free and optically transparent tissue that supports optimal visual function. The normal cornea is devoid of blood vessels; this characteristic, combined with some other structural facts in the anatomy of the cornea, is responsible for the transparency of this tissue.
365
COURSE
SECTION 19 • Cornea
Three potential mechanisms for the pathogenesis of corneal neovascularization have been proposed: ● A corneal injury inactivates a restraint that the normal cornea exerts on cell division and migration of the vascular cells of the pericorneal plexus. ● Corneal edema loosens corneal stromal tissue and therefore permits the ingrowth of vessels normally restrained by its composition. ● Corneal neovascularization is related to the production of locally generated angiogenic factors. The most noted of these angiogenic factors are epidermal growth factor, fibroblast growth factor, urokinase-like plasminogen activator, interleukin I, interleukin II, and many other angiogenic factors and cascades yet to be discovered. Increasing basic science research has been aimed at the identification of these angiogenic factors and the cells producing these substances in attempts to improve the prognosis of corneal neovascularization.
products perpetuate the cycle and subsequent progression of corneal neovascularization.
Differential diagnosis ● ● ● ● ● ●
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ANGIOGENESIS
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Angiogenesis as a multistep process involving: ● Extravasation of plasma proteins; ● Degradation of extracellular matrix; ● Endothelial cell migration and proliferation; ● Capillary tube formation.
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This angiogenic process is mediated by a wide array of cytokines and growth factors to which both the extracellular matrix and endothelial cells (and in inflammation, infi ltrating inflammatory cells) contribute. Accumulating evidence suggests significant codependence between angiogenesis and inflammation in many models of neovascularization. Proinflammatory molecules can stimulate the production of collagenases and lead to degradation of basement membrane, as well as being directly mitogenic for endothelial cells. Furthermore, the chemotactic activity of proinflammatory cytokines can enhance migration (and activation) of inflammatory cells (e.g. neutrophils and macrophages), which can in turn stimulate more angiogenesis and the recruitment of yet more inflammatory cells to the site of inflammation. Corneal neovascularization leads to the loss of immune privilege in the anterior segment manifested as the inability to sustain anterior chamber-associated immune deviation. Moreover, topical angiostatic strategies can lead to the restoration of immune privilege when instituted sufficiently early in the course of the neovascular response.
TREATMENT
DIAGNOSIS Neovascularization can be as simple as a micropannus, which is a superficial fibrovascular proliferation that extends 1 to 2 mm beyond the normal vascular arcade. In contrast, a superficial vascular pannus that extends more than 2 mm beyond the normal vascular arcade is considered a gross pannus. New vessels can be made based on the phases of action. Initially, there is a stimulus. Then, there is localized fragmentation of the basal membrane and the extracellular matrix around the vessel involved. Endothelial cell migration occurs through the vessel wall, and lysis of the extracellular matrix continues, promoting new vessel growth. Multiple enzymes and blood
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Pterygium. Keratoconjunctivitis sicca (inflammatory). Vernal conjunctivitis (inflammatory). Pellagra (inflammatory). Vitamin B deficiency (inflammatory). Aphakic/pseudophakic bullous keratopathy (inflammatory). Fuchs’ dystrophy (degenerative/inflammatory). Glaucoma (degenerative). Infectious keratoconjunctivitis (infectious/inflammatory). Contact lens use (infectious/inflammatory). Rosacea (infectious/inflammatory). Phlyctenular keratoconjunctivitis (infectious/inflammatory). Molluscum contagiosum (infectious). Lymphopathia venereum (infectious). Leishmaniasis (infectious). Onchocerciasis (infectious). Trachoma (infectious). Leprosy (infectious). Herpes simplex keratitis (infectious). Herpes zoster keratitis (infectious). Alkali burns (toxic). Acid burns (toxic).
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Supportive Particularly in patients with a micropannus, observation rather than treatment of the underlying condition is indicated. When the micropannus proceeds to gross corneal neovascularization, treatments may be instituted other than simply treating the underlying disease process.
Ocular The primary treatment of NV is eliminating the underlying cause. Various regimens have been proposed for the treatment of active, corneal vascularization. Sometimes just elimination of the inciting insult will lead to resolution, as is typically seen with contact lens wearers. The mainstay of the ocular treatment is corticosteroid therapy. Topically applied prednisolone acetate may be administered liberally, except when used in cases with infectious causes. Its judicious use is indicated in infectious cases to prevent collagenase activation and the associated melting of the cornea. In severe cases, subconjunctival injections of corticosteroids may be considered, but their benefit beyond that of topical administration is limited, and complications associated with subconjunctival injections may be potentiated by this therapy. Vascularization that has been present for a long time, particularly when located in the deeper layers of the cornea, is usually resistant to any form of treatment.
Surgical Various surgical procedures have been recommended in the treatment of corneal neovascularization. Initially, diathermy of large feeding vessels into the cornea has been advised by some clinicians. More recently, corneal laser photocoagulation for the treatment of neovascularization has included the use of the
PRECAUTIONS It is important to keep in mind that prolonged topical ophthalmic treatment with corticosteroids can increase intraocular pressure and cataract formation. It is essential to follow these patients closely. As mentioned, the treatment of certain infectious states with corticosteroids alone can potentiate collagenase activity and exacerbate corneal melting. Radiation, diathermy, and cryotherapy have all been used in an attempt to treat corneal neovascularization, but none of these methods has been found to be any more effective than corticosteroids. For deep, long-standing corneal neovascularization, most of these methods are unsuccessful.
COMPLICATIONS ● ● ● ● ● ● ● ● ● ● ●
Tissue scarring. Opacification. Lipid keratopathy. Persistent inflammation. Immune corneal melting. Cicatrization. Edema. Exudates. Infi ltration. Visual loss. Blindness.
COMMENTS As knowledge of the biochemical pathogenesis of corneal neovascularization improves, so will treatment. Current research in arachidonic acid metabolism has shown that corticosteroids and cyclo-oxygenase inhibitors applied topically can significantly decrease the neovascular response to various insults.
Attempts to use lipoxygenase and lipoxygenase inhibitors have not proved to be successful in decreasing the neovascular response in an animal model of corneal neovascularization. An understanding of interleukin and T cell associations has led to the use of cyclosporin A to suppress corneal neovascularization. Also, evaluation of collagenase inhibitors in alkali burns has shown that reducing the initial injury and the associated response of the body can limit the associated disruption of normal corneal architecture. The use of tissue-matched corneas in corneal transplantation has been successful in ABO-matched tissue but not with the HLA-associated markers. Finally, extended contact lens use, either the disposable or nondisposable form, will continue to cause corneal neovascularization via the mechanisms of hypoxia and lactic acid accumulation. Identification of these problems early can be rewarding when closer follow-up of the patients is implemented. In addition, contact lens technology continues to change rapidly, thereby reducing the problems. The response of the cornea to injury or inflammation and the associated corneal neovascularization that may follow have plagued the ophthalmic surgeon and diagnostician for years. Continued research and the development of new topically applied agents and preventive mechanisms should reduce the prevalence of this potentially devastating ocular pathologic process.
REFERENCES Baer JC, Foster S: Corneal laser photocoagulation for treatment of neovascularization: efficacy of 577 NM yellow dye laser. Ophthalmology 99:173–179, 1992.
CHAPTER 192 • Detachment of Descemet’s Membrane
argon and the yellow dye laser. Both of these methods depend primarily on energy absorption by hemoglobin and oxyhemoglobin. Results from these studies show that many subsets of patients with corneal neovascularization can be treated effectively with laser photocoagulation; however, recurrence of the neovascularization has been an associated problem. Penetrating keratoplasty in vascularized corneas can be very difficult. Some authors have advised pretreatment of the recipient bed with diathermy of large feeder vessels into the cornea. In addition, diathermy of the inside graft edge must be done with extreme caution to prevent induced postoperative astigmatism. Early suture removal has been advocated because sutures have been implicated as a source of irritation and increased neovascularization with associated corneal graft rejection. In the past, the use of ß-irradiation was advocated; but this practice has been abandoned because the use of corticosteroids and immunosuppressive agents achieves better results. The suppression of corneal neovascularization with topical cyclosporin A has also been demonstrated. Investigators have treated corneal NV with argon laser obliteration of the vessel lumen. This can be achieved in the corneal part of the vessels (accessible to be lasered) but usually has a short-term effect, as the vessel lumen invariably reopens. Argon laser pannus obliteration is mainly a temporizing measure. Hyperbaric oxygen treatment has been used with limited success. This treatment modality aims to suppress angiogenesis by supplying the corneal tissue with redundant oxygen supply.
Boyd BD, ed: Highlights of ophthalmology. New York, Arcata Book Group, 1998. Collaborative Corneal Transplantation Studies: Effectiveness of histocompatibility matching in high risk corneal transplantation. Arch Ophthalmol 110:1392–1403, 1992. Dana MR, Streilein JW: Loss and restoration of immune privilege in eyes with corneal neovascularization. Invest Ophthalmol Vis Sci 37:2485– 2494, 1996. Dana MR, Zhu SN, Yamada J: Topical modulation of interleukin-1 activity in corneal neovascularization. Cornea 17:403–409, 1998. Folkman J, Shing Y: Angiogenesis. J Biol Chem 267:10931–10934, 1992. Jackson JR, Seed MP, Kircher CH, et al: The codependence of angiogenesis and chronic inflammation. FASEB J 11:457–465, 1997. Klintworth GK: Corneal angiogenesis: a comprehensive critical review. New York, Springer-Verlag, 1991. Lipman RM, Epstein RJ, Hendricks RL: Suppression of corneal neovascularization with cyclosporine. Arch Ophthalmol 110:405–407, 1992.
192 DETACHMENT OF DESCEMET’S MEMBRANE 371.33 Alexandre S. Marcon, MD Porto Alegre, Brazil Italo M. Marcon, MD, PhD Porto Alegre, Brazil Christopher J. Rapuano, MD Philadelphia, Pennsylvania Descemet’s membrane (DM), which is approximately 10 μm thick in adults, is the basement membrane of the corneal endo-
367
thelium. Descemet’s membrane detachment (DMD) is an uncommon but serious complication of intraocular surgery.
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Ocular discomfort/pain secondary to corneal edema or infection of ruptured corneal bullae. Anterior stromal haze may result from prolonged corneal edema.
ETIOLOGY ●
SECTION 19 • Cornea
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DMD has most often been reported after cataract extraction, surgical iridectomy, cyclodialisis, trabeculectomy, holmium laser sclerostomy, penetrating keratoplasty, lamellar keratoplasty, pars plana vitrectomy and viscocanalostomy. It can also be caused by external corneal trauma such as forceps delivery. The most important mechanisms implicated in causing DMD are probably the use of dull blades, engaging Descemet’s during intraocular lens implantation or with the aspiration/irrigation device, injection of viscoelastic and insertion of instruments between Descemet’s and stroma, and the creation of clear-corneal incisions.
COMMENTS DMD appear to be increasing and this may be explained by clear-corneal cataract procedures. They do not require urgent surgical repair and waiting several months before attempting it is acceptable. The decision on when to intervene in DMDs must be made on a case-by-case basis after evaluating the configuration of the detachment, the risks of additional intervention, and the need for rapid rehabilitation of vision.
REFERENCES Assia EI, Levkovich-Verbin H, Blumenthal M: Management of Descemet’s membrane detachment. J Cataract Refract Surg 21:714–717, 1995.
COURSE/PROGNOSIS ●
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Small incidental DMDs near the surgical wound are common. The vast majority are self-limited and of little visual consequence. Nonscrolled and planar DMDs (DM separated from stroma by ≤1 mm) are most likely to spontaneously reattach in several weeks to months, in contrast to scrolled and nonplanar DMDs (DM separated from stroma by >1 mm).
Gault JA, Raber IM: Repair of Descemet’s membrane detachment with intracameral injection of 20% sulfur hexafluoride gas. Cornea 15:483– 489, 1996. Macsai MS, Gainer KM, Chisholm L: Repair of Descemet’s membrane detachment with perfluoropropane (C3F8). Cornea 17:129–134, 1998. Mahmood MA, Teichmann KD, Tomey KF, et al: Detachment of Descemet’s membrane. J Cataract Refract Surg 24:827–833, 1998. Marcon AS, Rapuano CJ, Laibson PR, et al: Descemet’s membrane detachment after cataract surgery: management and outcome. Ophthalmology 12:2325–2330, 2002.
DIAGNOSIS The diagnosis of a DMD can be difficult to make due to corneal edema. Also, most detachments are self-limited and peripheral, only seen by gonioscopy. A high index of suspicion should be kept. High-magnification, high-light intensity slit-lamp examination can help. Ultrasound biomicroscopy can aid.
TREATMENT Nonscrolled DMDs will often spontaneously reattach thus observation for several weeks to months is acceptable. Topical hyperosmotic agents can also be administered. In some cases, surgical intervention may be necessary.
193 EPITHELIAL BASEMENT MEMBRANE DYSTROPHY 371.52 (Cogan’s Microcystic Corneal Dystrophy; Map, Dot, Fingerprint Dystrophy)
AND RECURRENT EROSION 371.42 (Recurrent Epithelial Erosion) Peter R. Laibson, MD Philadelphia, Pennsylvania
Surgical ●
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Injection of air or viscoelastic in the anterior chamber can be performed if DMD is noticed during surgery and sulfur hexafluoride (SF6) or perfluoropropane (C3F8) are not available. Air often reabsorbs too rapidly to work and big bubbles can cause pupilary block. Intracameral injection of 20% SF6 or 14% C3F8 should be the treatment of choice and do not seem to expand or damage the endothelium. Full-thickness suturing of DM to the cornea can be tried for recalcitrant cases. Occasionally penetrating keratoplasty is needed.
COMPLICATIONS ●
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Persistent endothelial dysfunction and corneal edema with visual loss.
ETIOLOGY/PROGNOSIS Corneal erosion and recurrent corneal erosion are common ocular disorders that are sometimes preceded by trauma but may occur spontaneously. After trauma involving the epithelium and basement membrane, recurrent corneal erosion probably occurs as a result of inadequate basement membrane healing, either because the basal epithelial cells fail to produce proper basement membrane complexes to attach to Bowman’s membrane and stroma or because of faulty basement membrane adherence. A traumatic cause has a better eventual prognosis for full recovery than does the spontaneous form. In the case of spontaneous corneal erosion, the underlying disease process may be an epithelial basement membrane corneal dystrophy. Recent studies with electron microscopic
Epithelial basement membrane dystrophy is usually bilateral and characterized by: ● Various patterns of dots, parallel lines that mimic fi ngerprints, and random linear pattern that resemble maps, which usually appear in the epithelium of the central twothirds of the cornea. These intraepithelial cyst patterns are composed of opaque, putty-gray cysts, termed: ● Cogan’s cysts, which are made up of cytoplasmic and nuclear debris and range in size from pinpoints to as much as 2 mm across. Individual microcysts may be oval, oblong, or comma-shaped and rarely appear along but are usually associated with map and less often fingerprint patterns. The map and fingerprint patterns, on the other hand, frequently appear without ‘dots,’ or individual microcysts. Map and fingerprint alterations in corneal epithelium are not rare and can be found in asymptomatic individuals without a prior history of trauma or ocular disease; in face, the literature suggests that these epithelial changes are more diffuse than previously recognized. They are frequently seen in conditions involving: ● Corneal edema. This localized edema may occur near a healing cataract surgical incision or in the central cornea associated with Fuchs’ corneal dystrophy.
traumatic) recurrent erosions, there may be an inherent structural weakness of the corneal basement membrane with respect to the synthesis and deposition of type IV collagen.
DIAGNOSIS Clinical signs and symptoms At least 80% to 90% of patients who have epithelial basement membrane dystrophy are asymptomatic. Symptoms, when they occur, consist of one or more of the following: ● Slightly blurred vision (when epithelial and basement membrane changes are in the visual axis); ● Visual acuity loss due to irregular astigmatism; ● Epithelial blebs; ● Foreign body sensation with recurrent erosion, when the epithelium loosens and detaches; ● Sudden sharp pain, often in the early morning during sleep or on awakening, when a frank epithelial defect occurs prompted by eyelid movement across loosened epithelium. This commonly is the fi rst symptom of a recurrent erosion, and in rare cases, a patient who has previously experienced this pain on awakening is so fearful of the pain that he or she is unable to sleep well. The pain is fleeting in most cases, lasting only seconds, but it may last for some minutes to 1 or 2 hours and is a warning that the epithelium is not healed.
Laboratory findings
CHAPTER 193 • Epithelial Basement Membrane Dystrophy
analysis of adhesion mechanisms of the corneal epithelium during recurrent erosion episodes have shown separation of the anchoring system at the level of the epithelial cell membrane or below the level of the anchoring plaques. Normal and degenerate polymorphonuclear leukocytes (PMNs) were found within and between the epithelial cells and within the anchoring layer. The degenerate PMNs may secrete metalloproteinases that cleave Bowman’s membrane below the anchoring system. Epithelial basement membrane dystrophy and recurrent corneal erosions occur: ● In adults of each sex, although slightly more often in women; ● Usually after the fourth decade of life, although literature has associated recurrent corneal erosion with; ● Juvenile Alport’s syndrome, an X-linked condition that also presents with anterior lenticonus and retinal flecks, as well as renal complications.
In one study, patients with a history of recurrent corneal erosion (12 eyes) presented with signs suggestive of microbial keratitis. They had developed: ● An acute corneal stromal infi ltrate beneath the epithelial defect and this was associated with, an intense anterior uveitis; and ● Hypopyon in three eyes. Bacterial cultures of these corneas, however, revealed a positive isolate in just two eyes; treatment with topical antibiotics and topical corticosteroid rapidly resolved these episodes with good visual outcomes, frequently with a complete resolution of the recurrent erosion as well.
PROPHYLAXIS Epithelial basement membrane dystrophy, and recurrent erosion, are: ● Probably hereditary, with variable penetrance. In a large study population, 6% of patient treated for a variety of other ocular non corneal conditions and diseases also demonstrated map, dot, and fingerprint changes in the epithelium. Even when frank epithelial defects or opaque microcysts are absent or undetectable with biomicroscopy, computed videokeratography may reveal the presence of corneal epithelial ‘lagoons,’ or micro depressions, indicative of microscopic folding and redundancies in basement membrane, especially in posttraumatic recurrent erosion syndrome. Fingerprint lines and map-like patterns are histologically similar, both have: ● An aberrant or a multilaminar basement membrane produced by the basal epithelial cells of the corneal epithelium. The literature suggests that especially in spontaneous (non
Precautionary measure for patients with recurrent corneal erosion associated with epithelial basement membrane dystrophy include: ● Avoidance of rubbing the eyes through the eyelids, especially upon awakening; ● Liberal use of ointment medications at bedtime during an erosion episode. Some times these measures must be followed for several months after resolution of the episode.
TREATMENT Ocular Of first importance for the patient with epithelial basement membrane dystrophy is minimization of the pain associated
369
with recurrent corneal erosion. If the erosion is small, it will heal spontaneously or with the aid of: ● A pressure patch, placed on the eye for 1 or 2 days; ● An antibiotic ointment, such as bacitracin or erythromycin, which can be used beneath the patch.
SECTION 19 • Cornea
The literature suggests that patching for longer than 2 days can introduce hypoxia or a lacrimal hyposecretion, or both, that may actually inhibit healing. Minor corneal erosions can be treated with: ● Lubricating ointment alone, for several weeks to months, to control symptoms; ● Bandage soft contact lenses, which have been helpful in some cases of multiple recurrent erosion; however, concerns persist about overnight use of extended-wear soft contact lenses due to the risk of infectious keratitis. In some cases, the recurrence of very mild corneal erosion may be prevented with: ● Sodium chloride drops 2% or 5% several times during the day; and ● Sodium chloride ointment 5% at bedtime. Many patients believe that sodium chloride ointment is no more effective than a lubricant ointment or an ointment without preservatives. Each patient must establish a regimen of medication that seems to control his or her symptoms most effectively. This might involve using a medication only when symptoms recur, or in some instances, daily application for many months after the resolution of an erosion episode to prevent further recurrences. Resistant case may require: ● Mechanical debridement, with or without chemical cautery, depending on the size of the defect and the amount of ocular irritation; ● Local cycloplegic agents; ● A diamond burr, which is used to ‘polish’ Bowman’s membrane after mechanical debridement (has proved to be very effective in preventing recurrence). With the more severe cases of recurrent corneal erosion that do not seem to respond to any of the above therapies, the use of: ● Anterior stromal puncture has been advocated. The procedure involves making 75 to 150 small punctures with a bent 23 needle through the epithelium and Bowman’s membrane into the anterior stroma. The needle tip is inserted through the loosened epithelium, making momentary micro depressions in the cornea to enter the stroma; the bent tip limits the excursion of the needle tip and permits the micropunctures to affect only the anterior stroma. Patients who have had multiple recurrent erosion episodes, unresponsive to debridement alone or debridement with cautery, have shown significant improvements with anterior stromal puncture. Used correctly, the technique is effective in 90% of cases with recalcitrant recurrent erosion with the first application; a few patients may require a second application of anterior stromal puncture.
Surgical For spontaneous recurrent erosions and erosions secondary to corneal dystrophies such as Reis-Bücklers’ dystrophy, lattice dystrophy, and the superficial variant of granular dystrophy, as well as epithelial basement membrane dystrophy.
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Excimer laser photoablation (phototherapeutic keratectomy, or PTK) of the epithelium, the basement membrane, and just into Bowman’s membrane has been performed with some success, although it is more expensive that mechanical debridement.
PRECAUTIONS Treatment should be as simple as possible with the use of as few drugs as necessary. Some drugs, such as local anesthetic agents, have been shown to delay epithelial wound healing. For this reason, it is imperative to never prescribe a topical anesthetic agent for the patient’s own use, even when symptoms are severe; ointments, bandage soft contact lenses, or patching should suffice to manage pain while initiating healing. Indications for chemical cautery or lamellar keratectomy for resistant erosions have become almost non existent with the advent of therapeutic soft contact lenses, anterior stromal puncture, and PTK. In fact, due to the cost of bandage contact lenses and the frequent follow-up visits required, as well as the potential for corneal infections with long-term use, contact lens therapy should be postponed until milder forms of treatment prove to be ineffective. Anterior stromal puncture or PTK is preferred for treatment of the most severe cases of recurrent corneal erosion that do not resolve with ointments and patching.
COMMENTS Systemic disease does not seem to play a role in epithelial basement membrane dystrophy or recurrent corneal erosion.
REFERENCES Baum JL: Prolonged eyelid closure is a risk to the cornea. The Castroviejo Lecture, 1997. Cornea 16:602–611, 1997. Brunette I, Boisjoly HM: Should we patch corneal erosions?[letter] Arch Ophthalmology 115(12):1607, 1997. Heyworth P, Morlet N, Rayner S, et al: Natural history of recurrent erosion syndrome-A 4-year review of 117 patients. Br J Ophthalmol. 82:537– 540, 1998. Ionides AC, Tuft SJ, Ferguson VM, et al: Corneal infi ltration after recurrent corneal erosion. Br J Ophthalmol 81:537–540, 1997. Laibson PR: Microcystic corneal dystrophy. Trans Am Ophthalmol Soc 74:488–531, 1976. Liu C, Buckley R: The role of the therapeutic contact lens in the management of recurrent corneal erosions: a review of treatment strategies. CLAO 22:79–82, 1996. Maine R, Loughman MS: Phototherapeutic keratectomy re-treatment for recurrent corneal erosion syndrome [letter]. BJ Ophthalmology 86(3):270–272, 2002. McDonnell PJ, Seiler T: Phototherapeutic keratectomy with excimer laser for Reis-Buckler corneal dystrophy. Refract Corneal Surg 8:306–310, 1992. McGhee CN, Bryce IG, Anastas CN: Corneal topographic lagoons: a potential new marker for post-traumatic recurrent corneal erosion syndrome. Aust NZ J Ophthalmol 24:27–31, 1996. McLean EN, MacRae SM, Rich LP: Recurrent erosion: treatment by anterior stromal puncture. Ophthalmology 93:784–788, 1986. Park AJ, Rapuano CJ: Diamond burr treatment of recurrent erosions. Techniques in Ophthalmology 2(3):114–117, 2004. Rapuano CJ: Excimer laser phototherapeutic keratectomy: long-term results and practical considerations. Cornea 16:151–157, 1997.
Reidy JJ, Paulus MP, Suma G: Recurrent erosions of the cornea: epidemiology and treatment. Cornea 19(6):767–771, 2000.
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Rhys C, Snyers B, Pirson Y: Recurrent corneal erosion associated with Alport’s syndrome: Rapid communication. Kidney Int 52:208–211, 1997.
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Soong H Kaz, Farjo E, Meyer RF, Sugar A: Diamond burr superficial keratectomy for recurrent corneal erosions. BJ Ophthalmology 86(3):296– 298, 2002.
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194 FILAMENTARY KERATITIS 370.23 William R. Morris, MD Memphis, Tennessee
Large angle strabismus. Beta-irradiation. Ectodermal dysplasia. Psoriasis. Neurotrophic keratitis. Hereditary hemorrhagic telangiectasia (Rendu–Osler–Weber disease). Trachoma. Acquired nystagmus treated with retrobulbar botulinum toxin. Acquired strabismus after surgical correction. Anticardiolipin antibodies.
COURSE ● ●
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Most acute cases resolve within a few days. Most cases associated with keratoconjunctivitis sicca resolve within one month. Chronic cases may require continued therapy.
DESCRIPTION Filamentary keratitis is a condition in which fi ne fi laments develop on the anterior surface of the cornea. These fi laments are gelatinous and refractile, varying from 0.5 to 10.0 mm long. They move freely and twist with blinking while remaining attached to the cornea at their base. Gray subepithelial opacities may occur at the base of the fi laments. The fi laments are composed of degenerated epithelial cells and mucoid debris. There may be single or multiple fi laments; the condition may be acute or chronic. Symptoms may include foreign body sensation, tearing, photophobia or blepharospasm.
TREATMENT Local ● ●
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ETIOLOGY ● ●
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Unknown. Possibly an increased ratio of mucus to aqueous tear components. Detachment of corneal epithelial basement membrane with elevation of epithelium, providing attachment points for mucus and degenerated epithelial cells.
ASSOCIATED CONDITIONS ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ●
Keratoconjunctivitis sicca. Prolonged lid closure (patching or ptosis). Superior limbic keratoconjunctivitis. Post-operative states (intraocular or extraocular surgery). Brain stem injury or stroke. Radiation therapy. Atopic dermatitis. Sarcoidosis. Ocular pemphigoid. Recurrent corneal erosion. Soft contact lens wear. Corneal edema. Ligneous conjunctivitis. Carcinoma of conjunctiva. Epidemic keratoconjunctivitis (EKC). Nodular degeneration of cornea. Antihistamines. Topical antiviral medication.
CHAPTER 194 • Filamentary Keratitis
Trobe JD, Laibson PR: Dystrophic changes in the anterior cornea. Arch Ophthalmol 87:378–382, 1972.
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Treat underlying disease. Debridement of filaments — fine forceps, cotton tip applicator or cellulose acetate fi lter paper. Sodium chloride 5% ophthalmic drops four times daily. Sodium chloride 5% ophthalmic ointment at bedtime. Diclofenac sodium 0.1% four times daily. Hypotonic artificial tears frequently. Soft contact lens for: ● Post-operative cataract; ● Post-operative penetrating keratoplasty; ● Brain-stem injury or stroke. Surgical: ● Punctal occlusion in patients with keratoconjunctivitis sicca.
REFERENCES Arora I, Singhvi S: Impression debridement of corneal lesions. Ophthalmology 101(12):1935–1940, 1994. Avisar R, Robinson A, Appel I, et al: Diclofenac sodium, 0.1% (Voltaren Ophtha), versus sodium chloride, 5%, in the treatment of fi lamentary keratitis. Cornea 19(2):145–147, 2000. Baum JL: The Castroviejo Lecture. Prolonged eyelid closure is a risk to the cornea. Cornea 16:602–611, 1997. Davis WG, Drewry RD, Wood TO: Filamentary keratitis and stromal neovascularization associated with brain-stem injury. Am J Ophthalmol 90:489–491, 1980. Fakadej AF, Plotnik RD: Filamentary keratitis. In: Krachmer JH, Mannis MJ, Holland EJ, eds: Cornea. St Louis: Mosby; 1997:1327–1332. Hamilton W, Wood TO: Filamentary keratitis. Am J Ophthalmol 93:466– 469, 1982. Lemp MA, Gold JB, Wong S, et al: An in vivo study of corneal surface morphologic features in patients with keratoconjunctivitis sicca. Am J Ophthalmol 98:426–428, 1984. Lohman LE, Rao GN, Aquavella JV: In vivo microscopic observations of human corneal epithelial abnormalities. Am J Ophthalmol 93:210–217, 1982. Miserocchi E, Baltatzis S, Foster CS: Ocular features associated with anticardiolipin antibodies: a descriptive study. Am J Ophthalmol 131(4):451– 456, 2001.
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Pons ME, Rosenberg SE: Filamentary keratitis occurring after strabismus surgery. JAAPOS 8:190–191, 2004.
Clinical stages
Tomsak RL, Remler BF, Averbuch-Heller L, et al: Unsatisfactory treatment of acquired nystagmus with retrobulbar injection of botulinum toxin. Am J Ophthalmol 119(4):489–496, 1995.
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Stage I Central corneal guttae, with or without pigment on the posterior cornea, with a gray and thickened appearance of Descemet’s membrane. Asymptomatic.
SECTION 19 • Cornea
Wolper J, Laibson PR: Hereditary hemorrhagic telangiectasis (Rendu-OslerWeber disease). Arch Ophthalmol 81(2):272–277, 1969.
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Zaidman GW, Geeraets R, Paylor RR, Ferry AP: The histopathology of fi lamentary keratitis. Arch Ophthalmol 103(8):1178–1181, 1985.
Stage II ● ● ● ●
195 FUCHS’ CORNEAL DYSTROPHY 371.57 (Fuchs’ Endothelial Dystrophy of the Cornea, Combined Dystrophy of Fuchs, Endothelial Dystrophy of the Cornea, Epithelial Dystrophy of Fuchs, Fuchs’ Epithelial-Endothelial Dystrophy)
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Stage III ●
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Microcystic or bullous epithelial and subepithelial edema seen best with flourescein dye application. Irritation or pain. Vision worse (20/60 to 20/400).
Stage IV ● ●
Mark A. Terry, MD Portland, Oregon
Same as stage I, but with stromal edema. Painless. Mild decreased vision (20/25 to 20/50). Increased glare. Symptoms often worse on awakening.
●
Severe vision loss (20/400 to hand motion). Subepithelial fibrous scarring. Often pain free.
Differential diagnosis ●
ETIOLOGY/INCIDENCE
● ●
Fuchs’ dystrophy is a bilateral, slowly progressive, primary corneal disease which results in vision loss due to corneal edema. Often asymmetric, this genetic disease is autosomal dominant with a high degree of penetrance and variable expressivity. Females are more severely affected than males, but not more frequently. The primary physiologic defect is a gradual decline in the density of the ATPase pump sites of the diseased endothelium. This results in progressive stromal and, in advanced cases, epithelial edema which usually does not become clinically evident until the fourth or fi fth decade of life. Associated conditions include keratoconus, axial hypermetropia, cardiovascular disease, glaucoma, and age-related macular degeneration. Due to the spectrum of disease severity and asymptomatic nature of most affected individuals, the incidence of Fuchs’ dystrophy is unknown.
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Posterior polymorphous dystrophy. Peripheral Hassall–Henle warts. Pseudoguttae due to trauma, infection or toxins. Disciform keratitis. Pseudophakic bullous keratopathy. Chandler syndrome. Congenital hereditary endothelial dystrophy.
TREATMENT Systemic None. Systemic oral carbonic anhydrase inhibitors are contraindicated due to their possible suppression of the Na-K ATPase pump and long term systemic risks.
Local ●
DIAGNOSIS ●
Endothelial dysfunction results in corneal edema and this is the basis of the signs and symptoms of the disease. The endothelium produces an abnormal, banded, posterior layer of Descemet’s membrane with characteristic central guttae excrescences which are a hallmark of this disease. Progressive endothelial cell loss with endothelial polymegathism and pleomorphism can be documented by specular or by confocal microscopy. With the presence of stromal edema found by slitlamp biomicroscopy or by sequential corneal ultrasonography, the diagnosis of Fuchs’ dystrophy is made. Characteristically, initial visual loss is noted by the patient upon awakening with clearing of the vision during the day. As stromal edema spills over into epithelial edema, the patient may note a sudden dramatic decrease in vision. Untreated, epithelial edema leads to surface scarring and severe visual loss.
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Sodium choride 5% solution or ointment up to eight times a daily and tailored to the patients visual symptoms for osmotic dehydration of epithelial edema. Use of a hair dryer at arm’s length with a low heat setting for tear fi lm evaporation and corneal detergescence. Lower intraocular pressure with standard glaucoma topical medications.
Surgical ● ●
●
Corneal transplantation. Traditional full thickness PK is highly successful (>90%) for clear grafts but often results in high irregular astigmatism and other refractive problems. Long term complications of wound dehiscence and globe rupture can occur between 5% and 17%. Endothelial Keratoplasty (EK) with Deep Lamellar Endothelial Keratoplasty (DLEK) or Descemet’s Stripping Endothelial Keratoplasty (DSEK) represents a new surgical approach that avoids surface corneal incisions or sutures. EK has
Chiou AG-Y, Kaufman SC, Beuerman RW, et al: Confocal microscopy in corneal guttata and Fuchs’ endothelial dystrophy. Br J Ophthalmology 83:185–189, 1999. Egan CA, Hodge DO, McLaren JW, Bourne WM: Effect of dorzolamide on corneal endothelial function in normal human eyes. Invest Ophthalmol Vis Sci 39:23–29, 1998. Elder MJ, Stack RR: Globe rupture following penetrating keratoplasty: how often, why, and what can we do to prevent it? Cornea 23:776–780, 2004.
Terry MA, Ousley PJ: Small incision deep lamellar endothelial keratoplasty (DLEK): 6-month results in the fi rst prospective clinical study. Cornea 2005 (in press). Terry MA: Deep lamellar endothelial keratoplasty (DLEK): pursuing the ideal goals of endothelial replacement. Eye 17:982–988, 2003.
a
Terry MA, Ousley PJ: Deep lamellar endothelial keratoplasty (DLEK): Visual acvity, astigmatism, and endothelial survival in a large prospective series. Ophthalmology 112:1541–1549, 2005. Terry MA: Endothelial keratoplasty (EK): History, Current State, and Future Directions. Cornea 25:873–878, 2006 (Editorial).
CHAPTER 196 • Fuchs’ Dellen
McCartney RK, Wood TO, McLaughin BJ: Moderate Fuchs’ endothelial dystrophy ATPase pump site density. Invest Ophthalmol Vis Sci 30:1560–1564, 1989.
196 FUCHS’ DELLEN 371.41 (Facets, Fuchs’ Dimples) F. Hampton Roy, MD, FACS Little Rock, Arkansas
ETIOLOGY/INCIDENCE
b
FIGURE 195.1. a) Cornea with Fuchs’ dystrophy stage III corneal edema pre-operatively showing large surface bullae extending onto lower lid and painful red eye. b) Post-operatively at 6 months after deep lamellar endothelial keratoplasty (DLEK) the cornea is clear with no sutures, there are no bullae, and the eye is comfortable.
faster visual rehabilitation than PK and may avoid the short and long term complications.
Painful corneal epithelial bullae with no light perception vision Cautery, Gunderson flap, and amniotic membrane surgery have all been useful for pain control.
COMMENTS Fuchs’ dystrophy is a slowly progressive disease which can be observed until the patients symptoms warrant treatment. Every effort should be made to reduce endothelial damage from episodes of intraocular inflammation (iritis) or surgical trauma (cataract surgery). Medical management is best until visual acuity is compromised to the point of interfering with activities essential to daily life. While PK is highly successful, new methods of selective corneal transplantation (DLEK and DSEK) may offer topographic, refractive and tectonic advantages.
Dellen are paralimbal corneal ulcerations that occur at the base of abnormal conjunctiva or corneal elevations. These ellipsoid depressions, or dells, in the cornea represent a common but not well known phenomenon. Dellen are usually elliptic and saucer shaped with clearly defi ned edges. Although transient dellen are superficial and purely epithelial, they may last several weeks and become deep. Cicatrization normally follows, often with reduction in corneal thickness (facets). Abnormal paralimbic conjunctival elevation is associated with: ● Filtering bleb; ● Hematoma; ● Chemosis; ● Conjunctival tumor; ● Rectus muscle surgery; ● Conjunctival autograft; ● Pterygium. Abnormal corneal elevations can be seen secondary to: Localized graft displacement or edema; ● Corneal sutures that are too tight; ● Corneal tumor. ●
Poor palpebral congruence prevents the lids from normally spreading the tears, which causes a break in the oily fi lm. This break and the resulting desiccation can be aggravated by a trapped air bubble that sometimes bursts when the lids open.
REFERENCES Bergmanson JP, Sheldon TM, Goosey JD: Fuchs’ endothelial dystrophy: a fresh look at an aging disease. Ophthalmic Physiol Opt 19:210–222, 1999. Borboli S, Colby K: Mechanisms of disease: Fuchs’ endothelial dystrophy. Ophthalmol Clin N Am 15:17–25, 2002.
COURSE/PROGNOSIS ● ●
Possible perforation. Astigmatism.
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TREATMENT ● ●
● ●
SECTION 19 • Cornea
● ●
● ●
Elimination of the cause. Pressure dressing to control any abnormal conjunctival elevation. Surgery rarely necessary to remove the elevation. Topical corticosteroids when the elevation is of inflammatory origin. Treatment of the ulceration. Ocular lubricants to avoid desiccation of the ulcer and to coat it. New anticollagenase eyedrops to reduce collagen necrosis. Antibiotic eyedrops to avoid secondary infections.
COURSE/PROGNOSIS The onset of a fungal infection is slow. As the fungus invades corneal tissue, it establishes a progressive inflammation over a period of weeks. The clinical signs initially may be subtle. Infi ltrate develops slowly, and the epithelium may heal over the superficial defect. As the infection becomes more severe, hypopyon may develop. Yeast infections tend to remain localized in the more superficial layers of the cornea; fi lamentous fungal infections steadily progress to invade the anterior chamber, cornea, and surrounding structures. Untreated, the prognosis is poor, with blindness or loss of the eye as the usual outcome.
COMMENTS
DIAGNOSIS
Dellen are more common than is commonly thought. They are usually benign but occasionally present difficulties. In almost all cases, they heal well with the use of the simple techniques described.
Laboratory findings
REFERENCES
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●
● ●
Fuchs A: Pathological dimples (‘Dellen’) of the cornea. Am J Ophthalmol 12:877–883, 1929. Insler MS, Tauber S, Packer A: Descemetocele formation in a patient with a postoperative corneal dellen. Cornea 8:129–130, 1989.
Differential diagnosis ●
Lagoutte F, Gauthier L, Comte P: A fibrin sealant for perforated and preperforated corneal ulcers. Br J Ophthalmol 73:757–761, 1989. Soong HK, Quigley HA: Dellen associated with fi ltering blebs. Arch Ophthalmol;101:385–387, 1983.
Corneal smear: Giemsa, KOH, or Gomori’s methenamine silver stains. Culture: Sabouraud dextrose agar, brain-heart infusion broth (no inhibitors). Prolonged incubation possibly necessary (weeks). Possible contamination of culture (use C streaks to identify inoculum).
Bacterial and protozoal infections, herpes simplex, or herpes zoster keratitis.
TREATMENT Yeast infections Topical 0.15% amphotericin every hour while awake for 48 hours and then every 2 hours (prolonged treatment necessary).
197 FUNGAL KERATITIS 111.1 Filamentous fungi Denis M. O’Day, MD, FACS Nashville, Tennessee
Topical 5% natamycin suspension every hour while awake for 48 hours and then every 2 hours (prolonged treatment necessary).
Subconjunctival therapy
374
ETIOLOGY/INCIDENCE
No evidence of efficacy.
Fungi invade the cornea as a result of a break in the natural host defenses of the eye. This occurs either after trauma or when there is a breakdown of local or general defense mechanisms. Unless the trauma has penetrated the deep layers of the cornea, infection is initially superficial. It progresses slowly to invade the deeper cornea and may involve the adjacent sclera, anterior chamber, and intraocular structures. Fungal infections are most common in tropical and subtropical climates, where the most frequent isolates are the filamentous fungi Fusarium solani and Aspergillus spp. The majority of cases involve minor trauma, usually with vegetable material as the inciting event. In temperate and colder climates, the infectious agent most often is a yeast. Such infections, however, are rare and are usually associated with reduced immunocompetence, immunosuppression, or severe structural alteration of the cornea and adnexa. In tropical climates, fungal keratitis is a major cause of corneal blindness.
Systemic therapy ● ●
Yeasts: none indicated. Filamentous fungi: some evidence in deep corneal progressive infections for the efficacy of systemic itraconazole or fluconazole (especially for Aspergillus spp. infection).
Surgical Excisional keratoplasty indicated when disease progresses despite medical treatment.
COMPLICATIONS ● ● ● ●
Perforation. Anterior endophthalmitis. Fungal scleritis. Fungal glaucoma.
COMMENTS The signs of disease progress or regress slowly. Antifungal agents can be toxic to the cornea and may mask response. Steroids have no place in treatment. If a patient is receiving topical steroids at the time of diagnosis, withdraw them slowly.
Forster RK: Fungal keratitis and conjunctivitis: clinical disease. In: Smolin G, Thoft RD, eds: The cornea: scientific foundations and clinical practice. Boston, Little, Brown, 1994:228–240. Killingsworth DW, Stern GA, Driebe WT, et al: Results of therapeutic penetrating keratoplasty. Ophthalmology 100:534–541, 1993. O’Day DM: Fungal keratitis. In: Pepose JS, Holland GN, Wilhelmus KR, eds: Ocular infections and immunity. St Louis, Mosby, 1996:1048–1061. O’Day DM, Ray WA, Head WS, et al: Influence of corticosteroids on experimentally induced keratomycosis. Arch Ophthalmol 109:1601–1604, 1991.
COURSE/PROGNOSIS ● ●
Onset is early in the first decade of life. Visual acuity is minimally affected until the second decade.
198 GRANULAR CORNEAL DYSTROPHY 371.53
CHAPTER 198 • Granular Corneal Dystrophy
REFERENCES
intervening spaces are noted between these corneal deposits. Throughout life, these deposits increase in size and number eventually coalescing to obliterate the clear intervening areas. Initially, these deposits appear in the central anterior stroma, however, over time, they extend posterior and peripherally. Despite their outward expansion, the outlying peripheral corneal stroma remains clear at least 2 mm in from the limbus. On light microscopy, eosinophilic hyaline deposits appear bright red with Masson’s trichrome stain. Electron microscopy (EM) reveals 100 μm to 500 μm sized rod-shaped extracellular phospholipid structures surrounded by microfibrillar proteins. Proposed etiologic theories suggest an epithelial genesis of GCD based on the prominent epithelial-like whirl pattern noted in corneal transplant graft recurrence.
Joseph D. Iuorno, MD Minneapolis MN, USA Jay H. Krachmer, MD Minneapolis MN, USA
EITIOLOGY/GENETICS/INCIDENCE Granular dystrophy is an autosomal dominant inherited dystrophy affecting the corneal stroma. First named Groenouw type I in 1890, the etiology of granular corneal dystrophy (GCD) is still evolving. Recent understandings of molecular genetics have organized GCD into four subtypes. Each subtype has been associated with mutations (Table 198.1) in beta transforming growth factor induced gene in human clone 3 (bIG H3) also known as transforming growth factor beta induced gene (TGFbI). This gene produces an abnormal protein called TGFβI protein (kerato-epithelin) in all four types of granular dystrophy. Classic GCD type I is characterized by the deposition of small, grayish-white, sharply demarcated opacities mostly in the anterior corneal stroma that can resemble breadcrumb, snowflake or popcorn shapes (Figure 198.1). Characteristic clear
FIGURE 198.1. Granular corneal dystrophy. Note the grayish-white, sharply demarcated opacities mostly in the anterior corneal stroma that can resemble breadcrumb, snowflake or popcorn shapes. Characteristic clear intervening spaces are noted between these corneal deposits.
TABLE 198.1 – Granular corneal dystrophy GCD type
Pseudonyms
Mutation in TGF beta-I
I
Classic GCD, Groenouw Type I
R555W, R124S
II
Avellino dystrohy, combined lattice/granular
R124H
III
Superficial GCD, Reis-Bücklers’ corneal dystrophy, corneal dystrophy of Bowman’s layer type I
R124L, R555Q, G623N Exon12 del F540
IV
French varient similar to GCD III
R124L plus del T125 and E126
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●
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SECTION 19 • Cornea
● ●
Photophobia is a common symptom. Corneal erosions, especially with superficial subtypes (GCD type III), occur less commonly than in patients with lattice dystrophy. As opacities increase in size and number, the clear intervening areas become cloudy and visual acuity is compromised. Generally, this does not occur until the 5th decade. The epithelium, basement membrane and far peripheral corneal stroma are typically spared. The prognosis with penetrating keratoplasty is excellent. Recurrences are common and typically have an epitheliallike whirl pattern.
199 JUVENILE CORNEAL EPITHELIAL DYSTROPHY 371.51 (Meesmann’s Corneal Dystrophy) Peter R. Kastl, MD, PhD New Orleans, Louisiana
ETIOLOGY/INCIDENCE Meesmann’s corneal dystrophy has autosomal dominant inheritance, as do most corneal dystrophies. This rare disease infrequently causes discomfort and minimal (if any) visual loss.
DIAGNOSIS ●
● ● ●
Observation of distinct central, anterior and mid stromal opacities with clear intervening spaces not extending to the limbus. Autosomal dominant inheritance. Mason’s trichrome stain of eosinophilic hyaline deposits. EM findings of rod-shape bodies.
COURSE/PROGNOSIS Mild discomfort and slightly decreased vision may occur in later life.
DIAGNOSIS Clinical signs and symptoms
TREATMENT ● ● ●
●
For mild cases, observation and recurrent erosion therapy. Soft contact lenses can be helpful. When reduced vision, photophobia and recurrent corneal erosions combine to sufficiently reduce the quality of life, penetrating keratoplasty is recommended. Graft recurrences are treated by superficial keratectomy, phototherapeutic keratectomy, or repeat penetrating keratoplasty.
SUMMARY Granular dystrophy is an autosomal dominant stromal dystrophy which starts in the first decade of life in the anterior central corneal stroma and spreads to more posterior and peripheral areas. Later in life, as the clear intervening stromal areas become overwhelmed by the increasing number of enlarging opacities, visual acuity can be compromised. Penetrating keratoplasty is effective but often followed by recurrence in the donor tissue.
REFERENCES Dinh R, Rapuano CJ, Cohen EJ, Laibson PR: Recurrence of corneal dystrophy after excimer laser phototherapeutic keratectomy. Ophthalmology 106(8):1490–1497, 1999. Klintworth GK: The molecular genetics of the corneal dystrophies-current status. Front in Bioscience 8:678–713, 2003. Krachmer JH, Mannis MJ, Holland EJ: Cornea. 2nd edn: Philadelphia, Elsevier Mosby, 2005:907–909. Lyons CJ, McCartney AC, Kirkness CM, et al: Granular corneal dystrophy. Visual results and pattern of recurrence after lamellar or penetrating keratoplasty. Ophthalmology 101(11):1812–1817, 1994. Rodrigues MM, Streeten BW, Krachmer JH, et al: Microfibrillar protein and phospholipid in granular corneal dystrophy. Arch Ophthalmol 101(5):802–810, 1983.
376
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Corneal fi ndings include epithelial cysts, irregular astigmatism, superficial haze. Other clinical findings include decreased vision, ocular irritation.
Laboratory findings Slit-lamp examination findings include epithelial bleb-like lesions that appear to direct illumination as whitish-gray, small punctate opacities but that on retroillumination appear as clear, spherical vesicles. The overlying epithelium is clear. Histopathologically, small cysts are found throughout the epithelium, which are the vesicles seen on retroillumination. These contain debris and are most numerous in the anterior one-third of the epithelium. Electron microscopy demonstrates a ‘peculiar substance’ in the cytoplasm that is seen more often in the basal cells. This substance appears to be fibrillogranular material, probably derived from degenerated cytoplasmic filaments.
TREATMENT Treatment is not usually required. The use of bandage soft contact lenses can reduce any symptoms. If the vision is markedly decreased, debridement or even lamellar keratoplasty can be performed.
COMPLICATIONS Corneal debridement can cause scarring and infection. The prolonged wearing of soft contact lenses can result in infection. Patients wearing soft lenses on a long-term basis should be examined periodically for lens wear side effects.
REFERENCES Alkemade PP, Balen AV: Hereditary epithelial dystrophy of the cornea: Meesmann type. Br J Ophthalmol 50:603–605, 1966.
Fine BS, Yanoff M, Pitts E, Slaughter FD: Meesmann’s epithelial dystrophy of the cornea. Am J Ophthalmol 83:633–642, 1977.
DIAGNOSIS
Irvine AD, Corden LD, Swensson O, et al: Mutations in cornea-specific keratin K3 or K12 genes cause Meesmann’s corneal dystrophy. Nat Genet 16:184–187, 1997.
Clinical signs and symptoms
Meesmann A: Über eine bisher nicht beschreibene dominant vererbte Dystrophia epithelialis corneae. Ber Dtsch Ophthalmol Ges 52:154, 1938.
Roca PD: Meesmann’s hereditary epithelial dystrophy (differential diagnosis). Eye Ear Nose Throat Mon 48:424–425, 1969. Swensson O, Swensson B, Nolle B, et al: [Mutations in the keratin gene as a cause of Meesman-Wilke corneal dystrophy and autosomal dominant skin cornification disorders]. Klinische Monatsblatter für Augenheilkunde 217(1):43–51, 2000. Thiel HJ, Behnke H: [On the extent of variation of hereditary epithelial corneal dystrophy (Meesmann-Wilke type)]. Ophthalmologica 155:81– 86, 1968. Thiel HJ, Caesar R: [Histologic and electron microscopic studies of hereditary corneal epithelial dystrophy (Meesmann-Wilke)]. Albrecht Von Graefes Arch Klin Exp Ophthalmol 174:134–142, 1967. Tremblay M, Dube I: Meesmann’s corneal dystrophy: ultrastructural features. Can J Ophthalmol 17:24–28, 1982.
200 KERATOCONJUNCTIVITIS SICCA AND SJÖGREN’S SYNDROME 370.33 James V. Aquavella, MD Rochester, NY
ETIOLOGY/INCIDENCE Sjögren syndrome is an autoimmune disease consisting of xerostomia (dry mouth), keratoconjunctivitis sicca, often associated with dryness of the nasal and genital mucosa. Primary Sjögren’s is seen in individuals with the systemic immune dysfunction in the absence of connective tissue disease as well as in individuals lacking both systemic dysfunction and connective tissue disease. Secondary Sjögren’s includes patients with defined connective tissue disease (rheumatoid arthritis, lupus). The exact incidence is unknown; one Swedish study suggests 0.4% prevalence. Estimates for the United States are between 1 and 2%. There is a nine to one prevalence for females, and the condition is most often seen in postmenopausal women although there are a number of reports of women afflicted in their 20 s and 30 s. One of the prime findings is lymphocyte infi ltration of secretory glands. While the lachrymal and salivary glands are most frequently effected a more widespread involvement of secretory glands is not unusual.
Laboratory findings Positive lip and lachrymal grand biopsy in conjunction with positive antinuclear antibody (ANA), rheumatoid factor (RF), anti-Ro (Sjögern specific A), and anti-La (Sjögern specific B) assist in establishing the diagnosis. Helper T cells are the predominant lymphocyte infi ltrator along with B and CD4 lymphocytes. Epstein–Barr virus may play a role. An elevated IgG level has been shown to have a high specificity and positive predication value in predicting positive biopsy results.
TREATMENT Systemic Immunosuppressive agents such as cyclosporin A, trenonin, and corticosteroids have been utilized in severe cases. Oral bromhexine or pilocarpine has been advocate to improve lachrymal function.
CHAPTER 200 • Keratoconjunctivitis Sicca and Sjögren’s Syndrome
Pameijer JK: Über eine fremdartige familiare oberflächliche Hornhautveränderung. Klin Monatsbl Augenheilkd 95:516, 1935.
Ocular signs and symptoms are similar to those of other dry eye conditions. Burning, itching, foreign body (sandy) sensation, mucous discharge, photophobia and blurred vision may be present. The condition usually is more comfortable in the early AM with exacerbating symptomatology as the day progresses. Desiccating environmental factors may be implicated with symptom fluctuation. While there have been European and American diagnostic criteria promulgated, in general dry mouth, dry eye and autoimmune disease constitute the diagnostic triad. The most comprehensive factors are decreased salivary flow, decreased lachrymal flow, lymphocyte glandular infi ltration, the absence of nasal stimulated reflex tearing and the presence of serum antibodies.
Topical The mainstay continues to be frequent application of tear substitutes (often non-preserved to avoid secondary irritation). For recurrent inflammation judicious use of topical steroids may be indicated. Existing tears may be conserved with punctual occlusion and the use of moist chamber goggles. Cyclosporin A may have a role in increasing lachrymal function. Antibiotics may be necessary in secondary infection.
Other adjuncts Hydrophilic bandage lenses, partial tarsorrhaphy, amniotic membranes have all been utilized with varying success. Controlling environmental humidification and airflow is helpful.
COMPLICATIONS Secondary bacterial infection/ulceration and perforation can occur. The incidence of lymphoma in Sjögren’s is elevated.
COURSE/PROGNOSIS COMMENTS While the prognosis is good, severe dry eyes can result in infection, ulceration, perforation and diffuse corneal scarring and vascularization leading to a much more guarded visual prognosis.
This is a condition which is often managed well with minimal lifestyle modifications but which has the potential for debilitating corneal blindness. Aggressive management, involvement of
377
other disciplines (rheumatology, immunology, oral biology, dentistry, OBGYN) can create the comprehensive approach, which will produce the best results over the long term.
REFERENCES SECTION 19 • Cornea
Daniels TE, Whitcher JP: Assocaiton of patterns of labial salivary gland inflammation with keratoconjunctivitis sicca. Arthrtis Rheum 37:869– 877, 1994. Pepose JS, Akata RF, Pflugfelder SC, Vopight W: Mononuclear cell phenotypes and immunoglobulin gene rearrangements in lacrimal gland biopsies from patients with Sjörgren’s syndrome. Ophthalmology 97(12):1599–605, 1990. Pflugfelder SC: Lacrimal gland epithelial and immunopathology of Sjögren’s syndrome. In: Homma M, ed: Proceedings of the IV International Sjögren’s Syndrome Syposium, Kugler. Am Steleveen, 1994.
201 KERATOCONUS 371.60 Brandon D. Ayres, MD Philadelphia, PA Christopher J. Rapuano, MD Philadelphia, PA
ETIOLOGY/INCIDENCE Keratoconus is a noninflammatory corneal disorder that involves abnormal thinning of the corneal stroma; thinning usually occurs in either the central or inferior cornea. It is most often bilateral, although severity can be very asymmetric. True unilateral keratoconus is infrequent. Keratoconus affects approximately 1 in 2000 and is the second most common cause of primary corneal transplants. In approximately 10% of cases, there is a familial history with an autosomal dominant inheritance pattern. It also can be associated with systemic conditions such as osteogenesis imperfecta, Down syndrome and atopic disease. The biochemical cause of the corneal thinning in keratoconus is not fully understood. Altered proteoglycan synthesis has been implicated as has alteration in the nitric oxide pathway allowing activation of proteolytic enzymes that weaken and thin the cornea and decreased activity of corneal enzyme inhibitors. Contact lens wear and eye rubbing have also been implicated as primary causes of keratoconus.
The hydrops usually resolves spontaneously over 3 to 6 months. In the acute phase, patching the eye relieves the discomfort in most cases. Interestingly, the episode often results in scarring and flattening of the cone and occasionally the return of functional visual acuity; however, if resolution is not apparent after 6 months, penetrating keratoplasty may be required.
DIAGNOSIS Examination and laboratory findings The distinctive patterns of keratoconus revealed with computerized corneal topography usually show inferior steepening with central irregularities. Rigid contact lens wear (especially of long duration) can confuse the diagnosis by inducing irregular astigmatism that may be permanent. This condition, corneal warpage, is classically associated with PMMA hard contact lenses. Diagnosis may require corneal mapping at intervals with the lenses not being worn over an extended period (several months). Other diagnostic signs of keratoconus include: ● Irregularity and doubling of keratometer mires (early sign); ● Scissors reflex on retinoscopy (early sign); ● Fleischer’s ring (a partial or complete ring of hemosiderin pigment in deep epithelium, at the cone base); ● Vogt’s striae (stress lines in the steep axis in posterior cornea); ● Corneal scarring at the apex of the cone; ● Prominent corneal nerves (uncommon); ● Annulus of the cone on retroillumination (moderate and advanced keratoconus); ● Munson’s sign on downgaze (protrusion of lower eyelid) in severe cases.
Differential diagnosis ●
●
●
●
Pellucid marginal degeneration: inferior thinning with flat central cornea. Keratoglobus: entire peripheral cornea steep and thinned; can be extremely thin in the periphery. Posterior keratoconus: accentuated posterior corneal steeping and thinning. Terrien’s marginal degeneration: peripheral corneal thinning with lipid deposition which can cause irregular astigmatism.
All of these possible alternative diagnoses are relatively rare.
TREATMENT Local
COURSE/PROGNOSIS The first symptom of keratoconus often appears between the ages of 15 and 30 years and is a slow progressive decrease in vision in one or both eyes. In the early stages, keratoconus is painless, and the eyes appear quiet; the condition may progress slowly for 10 to 20 years, often becoming stationary. As the condition progresses, the corneal mires become increasingly irregular, and thinning may extend to the limbus in advanced cases. Rarely, a rupture occurs in Descemet’s membrane, resulting in: ● Acute hydrops (profound local corneal edema); ● Pain; ● Sudden deterioration of vision.
378
In early keratoconus, spectacle correction may be sufficient. As the disease advances, corrective spectacle lenses become increasingly heavy and objectionable to many patients, who then require contact lens correction. Hard contact lenses such as rigid gas-permeable lenses are usually required for good visual acuity in patients with keratoconus. Ninty percent of patients do well with contact lenses. During progression of the condition, the patient may require frequent changes in lenses, with each successive pair requiring careful fitting, to permit the lens to move but also to resist ejection by normal blinking. Contact lenses themselves have been implicated in the exacerbation of corneal thinning, subepithelial scarring, and recurrent corneal erosion. Eye rubbing is thought by many physicians to aggravate keratoconus. All patients should be told not to rub their eyes.
● ● ● ● ● ● ●
For episodes of allergic reactions/atopy, the patient should be discouraged from rubbing the eyes; additional symptomatic treatment includes: ● Cold compresses; ● Antihistamine eyedrops or pills; ● Mast cell stabilizer eyedrops; ● Nonsteroidal anti-inflammatory drops.
202 LATTICE CORNEAL DYSTROPHY 371.54 (Lattice Dystrophy Type I, Lattice Dystrophy Type II, Lattice Dystrophy Type III, LCD-I, LCD-II, LCD-III, Meretoja’s Syndrome, Biber-HaabDimmer Dystrophy, Familial Amyloid Polyneuropathy Type IV)
AND AVELLINO DYSTROPHY 371.54 Douglas L. Meier, MD Portland, Oregon
Lattice corneal dystrophy type I
Surgical Penetrating keratoplasty is performed when the patient’s vision or tolerance of contact lenses deteriorates; there is a greater than 95% success rate. Corneal scarring and high keratometric values have been implicated as risk factors in progression of disease ultimately leading to corneal transplant. Postoperatively, many patients will still require contact lenses for best visual acuity, but the correction will usually be milder and well tolerated. Lamellar keratectomy, either with a blade or excimer laser, can be used to remove raised superficial scars at the apex of the cone, which may improve contact lens tolerance. Lamellar keratoplasty is advantageous in that it avoids the problem of endothelial rejection, however, is technically very difficult and the final vision may be suboptimal. Alternatives such as: ● Thermokeratoplasty; ● Epikeratoplasty; ● Intrastromal corneal ring segment implantation (Intacs) are used in special circumstances but rarely achieve as good a visual outcome as a full-thickness graft.
ETIOLOGY Lattice corneal dystrophy type I (LCD-I) is an autosomal dominant dystrophy that usually affects both eyes symmetrically. It is characterized by a localized corneal deposition of amyloid that is unrelated to systemic disease.
CHAPTER 202 • Lattice Corneal Dystrophy
Hydrops treatment involves the following: Discontinue contact lens wear; NaCl 5% drops and ointment; Patching; Some advocate short course of topical steroids; Cycloplegia for pain; Conservative follow up; Penetrating keratoplasty if edema does not resolve (uncommon) or visually significant scarring occurs (common).
COURSE/PROGNOSIS It appears in the first or second decade of life as characteristic refractile anterior stromal branching filamentous lines, focal white dots or dashes, or faint central stromal opacities. The deposits are prominent centrally and spare the peripheral 2 to 3 mm of cornea. The dystrophy is slowly progressive, with the lesions involving the deeper cornea and the opacity becoming denser and visually disabling, usually by the third or fourth decade. Occasionally, the fi rst symptoms of the disease are noted in childhood or in the sixth or seventh decade; there is a considerable variation among affected family members in the age at which symptoms appear.
SUPPORT GROUP National Keratoconus Foundation 733 Beverly Blvd., Suite 201 Los Angeles, CA 90048 www.nkcf.org FAX (310) 360-9712 E-mail:
[email protected] REFERENCES Bron AJ: Keratoconus. Cornea 7:163–169, 1988. Ihalainen A: Clinical and epidemiological features of keratoconus genetic and external factors in the pathogenesis of the disease. Acta Ophthalmol Suppl 178:1–64, 1986. Kenney MC, Nesburn AB, Burgeson RE, et al: Abnormalities of the extracellular matrix in keratoconus corneas. Cornea 16:345–351, 1997. Krachmer JH, Feder RS, Belin MW: Keratoconus and related noninflammatory corneal thinning disorders. Surv Ophthalmol 28:293–322, 1984. Rabinowitz YS: Keratoconus. Surv Ophthalmol 42:297–319, 1998. Sray WA, Cohen EJ, Rapuano CJ, et al: Factors associated with the need for penetrating keratoplasty in keratoconus. Cornea 21:784–786, 2002.
DIAGNOSIS Clinical signs and symptoms Symptoms of photophobia, foreign body sensation, and pain from recurrent corneal epithelial erosions may be prominent in some patients. As corneal sensation decreases, the recurrent erosions become less painful. Irregular surface corneal astigmatism further decreases functional vision.
Laboratory findings The characteristic histologic finding in the stroma is a fusiform deposit of amyloid that pushes aside the collagen lamellae, probably corresponding to the lattice lines and dots seen clinically. A degenerative pannus is seen with portions of Bowman’s membrane replaced by the deposits and irregular connective tissue. Clinically, these changes are associated with recurrent erosions. The stromal deposits stain orange-red with Congo red and demonstrate apple-green birefringence when viewed with polarized light. Red-green dichroism is seen with a green fi lter and a polarizing fi lter. Metachromasia can be demonstrated
379
SECTION 19 • Cornea
after staining with crystal violet. The deposits also stain with periodic acid-Schiff, Masson’s trichrome, and fluorochrome thioflavin T. Electron microscopy of the lesions shows a felt-like mass of fine (8 to 10 nm in diameter), nonbranching short fibrils without periodicity that are approximately half the size of adjacent collagen. The fibrils are sometimes associated with an amorphous electron-dense elastoid material. The source of the amyloid is not certain but probably is from abnormally functioning keratocytes. The keratocytes often have a prominent endoplasmic reticulum; they are decreased in number and show degeneration. Descemet’s membrane and the endothelium are normal.
Lattice corneal dystrophy type II
ETIOLOGY Lattice corneal dystrophy type II (LCD-II, Meretoja’s syndrome, familial amyloid polyneuropathy type IV) is an autosomal dominant form of LCD with an onset of clinical signs in the third decade. It is most common in Scandinavia.
various types of lattice corneal dystrophy. Most of the autosomal dominant corneal dystrophies are caused by the irregularities of the bIGH3 (or TGFbI) gene, which is located on chromosome 5q31. The gene is responsible for the production of the protein, keratoepithelin. Keratoepithelin is produced by the corneal epithelium but is predominantly present in the corneal stroma, especially Bowman’s layer. Keratoepithelin appears to be involved in cell adhesion or corneal wound healing by blocking epithelial cell proliferation. Keratoepithelin accumulates in the corneal stroma with those dystrophies associated with mutations of the 5q31 gene. Type I lattice dystrophy results from a mutation at codon 124, leading to a substitution of cysteine for arginine. Gelsolin is an actin fi lament-binding protein. The gelsolin gene appears to be affected in type II, with the Asp187Asn mutation causing the findings in systemic amyloidosis. Different mutations have been implicated in several other presentations of lattice dystrophy. Given this, our current classification of lattice corneal dystrophy by phenotype and histology (i.e. LCD-I, LCD-II, etc.) as reliable as once thought.
Differential diagnosis ●
DIAGNOSIS
● ●
LCD-II is associated with systemic amyloidosis, including signs of progressive cranial and peripheral nerve palsies, dry skin, blepharochalasis, protruding lips, mask-like facies, and bundlebranch block-all of which usually develop after the age of 40. The vision is not usually as reduced as it is in LCD-I. Recurrent erosions are uncommon. The lattice lines are fewer in number and are most dense in the midperiphery extending to the limbus with relative axial sparing. Glaucoma and pseudoexfoliation (with or without glaucoma) are common. Histologically, the corneal deposits are similar to those in LCD-I, but Bowman’s membrane is intact. Systemically, amyloid deposits are found in skin, nerves, arteries, and other tissues.
●
Reis–Bückler dystrophy. Herpes simplex or zoster. Avellino dystrophy. Polymorphic amyloid degeneration.
TREATMENT ●
●
●
Nonsurgical: artificial tears, lubricating ointments, soft contact lenses, pressure patching. Phototherapeutic keratectomy: useful for superficial lesions and recurrent erosions. Penetrating keratoplasty: highly successful (90%), recurrent disease not uncommon but mild and occasionally requires regrafting after 10 to 15 years.
Lattice corneal dystrophy type III Avellino dystrophy
ETIOLOGY Lattice corneal dystrophy type III (LCD-III) has a later onset and an autosomal recessive inheritance. It was first described in Japan.
DIAGNOSIS The lattice lines are thicker and ropy, extending from limbus to limbus. Recurrent epithelial erosions are not seen. Histologically, the amyloid deposits are in the midstroma, and Bowman’s membrane is only minimally disrupted. LCD-IIIA may be a variant of type III. It occurs in whites, is associated with corneal erosions, and has an autosomal dominant pattern of inheritance.
GENETICS In the last decade advances in genetic analyses have documented several DNA mutations which are associated with the
380
ETIOLOGY/INCIDENCE Avellino dystrophy is a condition with clinical and histologic features of both lattice and granular corneal dystrophies. It was initially described in four patients from three families, all of whom trace their ancestry to Avellino, Italy. It is inherited as an autosomal dominant trait.
COURSE Clinically, the lesions demonstrate three characteristics: anterior stromal discrete, gray-white granular deposits; mid to posterior stromal lattice lesions; and anterior stromal haze. The granular deposits are seen fi rst, followed by the lattice lesions. In a series of 27 patients, none developed lattice lesions without first demonstrating granular lesions. The last of these three signs to appear is the stromal haze, which develops after the fi fth decade. All three of these lesions become more pronounced with age.
COURSE/PROGNOSIS
The symptoms of Avellino dystrophy include foreign body sensation, photophobia, and pain, most likely from recurrent corneal epithelial erosions. In this respect, Avellino dystrophy is more like LCD-I (in which erosions are common) than granular corneal dystrophy (in which erosions are uncommon). There has been recurrence of the granular lesion in two of three patients who have had a penetrating keratoplasty for this condition.
Corneal changes are noted in the first decade of life as a diffuse clouding in central superficial stroma. With time these grayishwhite spots with blurry edges extend peripherally up to the limbus and into deeper stroma. Later, opacities become denser and can result in irregularity of the epithelium and in guttate appearance of Descemet’s membrane. Visual loss progresses to legal blindness by age 40 to 50.
REFERENCES Chau HM, Ha NT, Cung LX, et al: H626R and R124C mutations of the TGFbI (bIGH3) gene caused lattice corneal dystrophy in Vietnamese people. Br J Ophthalmol 87:686–689, 2003. Folberg R, Stone EM, Sheffield VC, et al: The relationship between granular, lattice type 1, and Avellino corneal dystrophies: a histopathologic study. Arch Ophthalmol 112:1080–1085, 1994. Hayashida-Hibino S, Watanabe H, Nishida K, et al: The effect of TGF-B1 on differential gene expression profi les in human corneal epithelium studied by cDNA expression array. Invest Ophthalmol Vis Sc 42:1691– 1697, 2001. Hida T, Tsubota K, Kigasawa K, et al: Clinical features of a newly recognized lattice corneal dystrophy. Am J Ophthalmol 104:241–248, 1987. Hirano K, Hotta Y, Nakamura M, et al: Late-onset form of lattice corneal dystrophy caused by leu527Arg mutation of the TGFbI gene. Cornea 20:525–529, 2001. Holland EJ, Daya SM, Stone EM, et al: Avellino corneal dystrophy: clinical manifestations and natural history. Ophthalmology 99:1564–1568, 1992.
DIAGNOSIS Clinical signs and symptoms ●
● ●
●
Corneal fi ndings include small, multiple, gray-white, pleomorphic opacities with irregular borders. The stroma is thinner than normal. Other clinical fi ndings include loss of vision and photophobia. Endothelial decompensation and subsequent corneal edema can also occur.
Laboratory findings ●
●
● ●
Meisler DM, Fine M: Recurrence of the clinical signs of lattice corneal dystrophy (type I) in corneal transplants. Am J Ophthalmol 97:210– 214, 1984.
The gene for macular corneal dystrophy is a carbohydrate sulfotransferase gene (CHST6) on chromossome 16 (16q22). Histologically macular dsystrophy is characterized by the accumulation of glycosaminoglycans. Lesions stain with Alcian blue, colloidal iron and PAS. Serum or immunohistochemical evaluation of keratan sulfate (KS) can divide the dystrophy in type 1 (KS negative) or type 2 (KS positive).
Meretoja J: Lattice corneal dystrophy-Two different types. Ophthalmologica 165:15–37, 1972.
TREATMENT
Nassaralla BA, Garbus J, McDonnell PJ: Phototherapeutic keratectomy for granular and lattice corneal dystrophies at 1.5 to 4 years. J Refract Surg 12:795–800, 1996.
Ocular ●
Rodrigues MM, Krachmer JH: Recent advances in corneal stromal dystrophies. Cornea 7:19–29, 1988. Stock EL, Feder RS, O’Grady RB, et al: Lattice corneal dystrophy type IIIA: clinical and histopathologic correlations. Arch Ophthalmol 109:354– 358, 1991.
203 MACULAR CORNEAL DYSTROPHY 371.55 (Groenouw’s Dystrophy Type II) Alexandre S. Marcon, MD Porto Alegre, Brazil Italo M. Marcon, MD, PhD Porto Alegre, Brazil Edward J. Holland, MD Cincinnati, Ohio
ETIOLOGY Of the three classic stromal dystrophies (the other two are granular and lattice), macular dystrophy is the only autosomal recessive and the most severe.
CHAPTER 203 • Macular Corneal Dystrophy
DIAGNOSIS
A contact lens may slightly improve vision by ‘smoothing’ the corneal surface.
Surgical ● ●
Phototherapeutic keratectomy may help in early stages. Penetrating corneal transplantation is the treatment of choice (lamellar can be tried in selected cases).
COMPLICATIONS ● ●
Graft rejection. Disease recurrence (with any form of treatment).
REFERENCES Akova YA, Kirkness CM, McCartney ACE, et al: Recurrent macular corneal dystrophy following penetrating keratoplasty. Eye 4:698–705, 1990. Aldave AJ, Yellore VS, Thonar EJ, et al: Novel mutations in the carbohydrate sulfotransferase gene (CHST6) in american patients with macular corneal dystrophy. Am J Ophthalmol 137(3):465–473, 2004. Klintworth GK, Vogel FS: Macular corneal dystrophy: an inherited acid mucopolysaccharide storage disease of the corneal fibroblast. Am J Pathol 45:565–586, 1964. Marcon AS, Cohen EJ, Rapuano CJ, et al: Recurrence of corneal stromal dystrophies after penetrating keratoplasty. Cornea 22(1):19–21, 2003. Morgan G: Macular dystrophy of the cornea. Brit J Ophthal 50:57–67, 1966.
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COURSE/PROGNOSIS
204 MOOREN’S ULCER 370.07 (Chronic Serpiginous Ulcer of the Cornea, Ulcus Rodens)
SECTION 19 • Cornea
Steven E. Wilson, MD Cleveland, Ohio Marcelo V. Netto, MD Cleveland Ohio
Mooren’s ulcer typically begins with patchy stromal infi ltrates in the periphery of the cornea. Most patients have moderate to severe pain associated with the infi ltration and epithelial defects that may occur. As the disease progresses, the infi ltrates usually coalesce and stromal tissue breakdown results in the formation of peri-limbal marginal ulceration. Over time the ulceration may extend for 360 degrees and progress centrally to involve the mid-peripheral and central cornea. Other ocular conditions such as episcleritis, scleritis, and iritis may be associated with the corneal ulcers in some patients.
ETIOLOGY/INCIDENCE Mooren’s ulcer is a chronic, painful, and progressive disorder of the cornea, which often is bilateral and commonly leads to severe vision loss or even loss of the eye. Ulceration and tissue destruction are initially confined to the periphery of the cornea, but may progress in some patients to involve the entire cornea. There is usually undermining and infi ltration of the leading edge of the circumferential peri-limbal ulceration. The cornea often becomes thinned and opacified by vascularization as the disease progresses. Although various forms of treatment have been proposed, some cases are refractory to all forms of therapy. The etiology of this disease remains uncertain in the majority of cases, although autoimmunity has been suggested to play a role in the pathophysiology of the disease based on reports of cell-mediated and humoral responses to Bowman’s membrane, stromal and epithelial antigens, or even molecular mimicry responses against foreign antigens that resemble those in the cornea. Importantly, some patients have been identified who have an underlying chronic hepatitis due to hepatitis C virus infection and this should be excluded in every patient because it alters therapy and the potential outcome of treatment (Figure 204.1). The majority of cases, however, appear to be idiopathic. In these patients the disorder is a diagnosis of exclusion. Some other conditions that have been associated with Mooren’s ulcer include trauma, alkali burns, herpes zoster, herpes simplex, parasitic infections, and cataract and corneal surgery.
DIAGNOSIS The diagnosis is one of exclusion that requires an extensive search for an occult and potentially lethal connective tissue disease. A thorough review of systems and a medical examination are mandatory. Laboratory investigation includes a complete blood cell count with differential, erythrocyte sedimentation rate, rheumatoid factor, complement fi xation, antinuclear antibodies, antineutrophil cytoplasmic antibody, circulating immune complexes, liver function tests, treponemal antibody absorption test, blood urea nitrogen and creatinine, serum electrophoresis, urinalysis, and chest radiograph. In addition, testing for chronic hepatitis C infection should be done. HCV antibodies are detected using EIA test and if these are present, supplemental testing with Western blotting or HCV-RNA detection can positively confirm infection. Many of these patients are asymptomatic from a systemic point of view and have minimal or no increases in blood liver enzymes. If there is a high index of suspicion, then a liver specialist should be consulted for possible biopsy to rule out chronic hepatitis
Differential diagnosis ●
●
●
●
Infectious peripheral corneal ulcerations (Staphylococcus aureus, Haemophilus influenzae, Moraxella spp., herpetic, fungal). Peripheral corneal degenerations (Terrien’s marginal degeneration, pellucid degeneration). Immune peripheral corneal infi ltrates (staphylococcal marginal keratitis, acne rosacea, tuberculosis). Systemic autoimmune diseases (Wegener’s granulomatosis, polyarteritis nodosa rheumatoid arthritis, systemic lupus erythematosus, relapsing polychondritis, Sjögren’s syndrome, inflammatory bowel disease, a1-antitrypsin deficiency). Some of these conditions are life-threatening and must be excluded by consultation with other specialists.
TREATMENT
FIGURE 204.1. Hepatitis C virus-associated Mooren’s like ulcer prior to treatment. The contralateral eye had similar marginal ulceration with undermining of the leading edge. (Reprinted by permission from Wilson SE, Lee WM, Murakami C, et al: Mooren’s-type hepatitis C virus (HCV)-associated corneal ulceration. Ophthalmology 101:736– 745, 1994.)
382
The treatment of Mooren’s ulcer is often unsatisfactory, especially the bilateral aggressive form. The goal of therapy is to arrest the progression of the ulcerative keratitis and to reepithelialize the cornea.
Systemic In cases in which underlying chronic hepatitis C virus (HCV) infection is confi rmed, systemic treatment with interferon alpha, marketed as Intron A by Schering Corp. and Roferon-A
After several weeks of treatment the oral prednisone can be tapered. Frequent monitoring is needed to monitor the local response and systemic side effects of systemic immunosupression.
Local ● ●
● ●
● ●
●
Cycloplegic agents (e.g. 0.5% scopolamine t.i.d.). Topical steroids (e.g. 1% prednisolone acetate or 1% prednisolone phosphate every hour). Topical cyclosporin A 0.05% twice a day. Prophylactic broad-spectrum topical antibiotics (e.g. 0.3% gatifloxacin q.i.d.). Bandage contact lens. Cyanoacrylate glue over small perforations may allow healing. Treatment of any concomitant eye disease (e.g. meibomianitis, blepharitis, dry eyes).
REHABILITATION A large tectonic graft and then a central therapeutic graft may be attempted if all other systemic and local treatment measures fail. Lamellar tectonic grafts may add structural integrity to the thinned cornea. Conjunctival flaps may be necessary for severely thinned corneas. The use of contact lenses can correct irregular astigmatism in quiescent cases.
COMMENTS Any later surgical interventions should be performed with concurrent immunosuppression, even in apparently burnt-out diseases because of a risk of recurrence. Corneal transplantation success is typically limited by vascularization of the cornea leading to a high-risk of transplant rejection.
REFERENCES Brown SI, Mondino BJ: Penetrating keratoplasty in Mooren’s ulcer. Am J Ophthalmol 89:255–258, 1980. Foster CS: Systemic immunosuppressive therapy of progressive bilateral Mooren’s ulcer. Ophthalmology 92:1436–1439, 1985.
CHAPTER 205 • Neuroparalytic Keratitis
by Roche Laboratories, Inc. should be instituted. Amgen Inc. also has an approved drug derived from interferon alpha called Infergen. The drug is injected subcutaneously three times a week. The authors have noted marked responses of Mooren’slike ulcers to interferon alpha in patients with confi rmed HCV infection. Many of these patients had been unresponsive to other forms of treatment. A newer treatment option is Rebetron, a Schering product that combines interferon with the antiviral drug ribavirin. A liver specialist should be consulted and participate in treatment, but the ophthalmologist should be prepared to impress on other specialists the severity of the Mooren’s ulcers if there is resistance to treatment because liver or other manifestations of the disease are minimal. If chronic HCV infection is ruled out, then systemic immunosuppressive treatment can be considered, if local treatment measures are ineffective. Obviously, systemic immunosupression would likely be contraindicated in a patient with chronic HCV infection, so it is important to exclude this fi rst. Systemic steroids should be administered fi rst because immunosupression with chemotherapeutic agents does not take effect for several weeks. All systemic treatments should be performed in consultation with specialists knowledgeable in immunosupression. ● Initial treatment methylprednisolone 1 g/day IV in four divided doses; switch to 1 mg/kg/day prednisone PO with one of the following chemotherapeutic agents: ● Cyclosporin A 3 to 5 mg/kg/day; ● mMethotrexate 7.5 to 10 mg PO once a week administered with 1 mg/day folic acid; ● Azathioprine 2 mg/kg/day; ● Cyclophosphamide 2 mg/kg/day.
Moazami G, Auran JD, Florakis GJ, et al: Interferon treatment of Mooren’s ulcers associated with hepatitis C. Am J Ophthalmol 119:365–366, 1995. Wilson SE, Lee WM, Murakami C, et al: Mooren’s corneal ulcers and hepatitis C virus infection: A New Association. N Engl J Med 329:62, 1993. Wilson SE, Lee WM, Murakami C, et al: Mooren’s-type hepatitis C virus (HCV)-associated corneal ulceration. Ophthalmology 1994;101:736– 745, 1994.
205 NEUROPARALYTIC KERATITIS 370.35 (Neurotrophic Keratitis, Trigeminal Neuropathic Keratopathy) Ian A. Mackie, MBChB, DO, FRCS, FRCOphth London, England Neuroparalytic keratitis is a disease that is the potential sequela to anesthesia administration in the region of the trigeminal nerve.
ETIOLOGY Surgical ● ●
● ●
Conjunctival recession/resection. Conjunctival excision may be considered if the ulcer progresses despite local and systemic medical treatment. With the patient under topical or subconjunctival anesthesia, the conjunctiva is excised extending 2 clock-hours to either side of the ulcer and 3 to 4 mm posteriorly, leaving bare sclera. The use of topical antibiotics and steroids should be continued. Tissue adhesives and a therapeutic contact lens may be beneficial. Superficial lamellar keratectomy. A central island of anterior corneal stroma can be excised to arrest the inflammatory process and to promote reepithelialization. A lamellar corneal graft may be required.
The three most common reasons for administering trigeminal anesthesia are surgery of the trigeminal neuralgias, surgery of acoustic neuromata, and herpes zoster ophthalmicus. In the course of treatment for the latter disease, about 8% of patients develop neuroparalytic keratitis. Other infrequent causes are trauma, tumors, multiple sclerosis, toxic chemical reactions, leprosy, and brain stem strokes and hemorrhages. Congenital forms, occurring notably in familial dysautonomia, (the Riley– Day syndrome) which occurs as a recessive disease in Ashkenazi Jews, may also be found. An idiopathic form has been described. There is a notion that the disease is caused by dust and foreign matter lodging in an anesthetic eye, and protective
383
spectacles are often fitted. These contribute very little to the management of the disease.
COURSE/PROGNOSIS
SECTION 19 • Cornea
A number of studies have shown that about 15% of patients with anesthetic eyes develop serious complications. These complications may develop soon or many years after the initiation of trigeminal insensitivity. The potential for neuroparalytic keratitis associated with trigeminal insensitivity can wax and wane. This is an important concept in the long-term management of these patients.
TREATMENT DIAGNOSIS To develop a true neuroparalytic keratitis, one probably must have an insensitive eye in an insensitive environment. In other words, one must have an insensitive conjunctiva as well as an insensitive cornea for the typical pathologic process to present. Sensation in either the cornea or the conjunctiva, which may occur after trigeminal nerve or gasserian ganglion destruction and which is often present after herpes zoster infection, spares the patient from the disease. Conjunctival sensation should be tested by gently applying the tip of a hypodermic needle to the palpebral conjunctiva above and below. This test, together with the assessment of corneal sensitivity with a wisp of cotton wool or the corner of a folded paper tissue, has important practical considerations in diagnosis and prognosis. It is, for example, sometimes difficult to differentiate the viral epitheliopathy of herpes zoster from that of neuroparalytic keratitis. In this case, the demonstration of sensation in either the cornea or the conjunctiva implies a viral etiology. Furthermore, the prognosis for the cornea after an attack of herpes zoster or after a neurosurgical procedure can be established. All patients with anesthesia of the eye and its environment produce excess mucus. The discharge often clings to the lashes. It is important to recognize this mucus as a feature of the anesthetic condition of the eye. It does not imply infection and it does not seem to be related to the presence or absence of keratopathy. The mucus comes from conjunctival subsurface vesicles, which are greatly increased in number in this condition. The entire palpebral conjunctiva may stain with rose bengal after gasserian ganglion destruction. This staining is probably an index of increased conjunctival cell death. It does not mean that the eye is dry and it does not seem to be related to the development of keratopathy. About 50% of patients with trigeminal anesthesia have abnormalities of the tear fi lm and cornea. With fluorescein, geographic drying areas are often seen in the cornea, and transient blurring of vision is common at this level of the disease. Punctate erosive corneal epitheliopathy is also common. It may have a geographic distribution and may be extensive enough to lead to a drop in visual acuity. These signs so far described can be considered stage I of the disease. Stage II develops as an acute episode and is characterized by epithelial detachment. The patient is usually fi rst aware of a drop in visual acuity, and the eye may be somewhat hyperemic.
384
Discomfort or pain, of course, is not a feature at this stage. For this reason patients should be instructed to test their vision in the affected eye frequently. Such epithelial detachments can appear in an area of cornea covered by the top lid. A gap is seen in the epithelium that is surrounded by an area of undermined epithelium extending some distance beyond the gap, and folds rapidly appear in Descemet’s membrane. An aqueous flare and cells may be present. Stage III develops when stromal lysis occurs. This may or may not be associated with infection, an early indication of which is a halo of cells in the stroma surrounding the stromal gap.
Stage I When severe, the punctate epitheliopathy is best treated with intermittent patching of the eye with tape, such as Blenderm (3M Health Care Ltd., Loughborough, LE11 1AP, England.) For a start, the eye may be patched for the whole of the wakeful day, but not during the night for fear of the tape coming in contact with the cornea. When the corneal epitheliopathy has been seen to disappear, the patching can be discontinued for one third of the wakeful day. The patient can pick the time for this uncovering to fit his or her social schedule. When again the cornea is seen to be clear, the patching can be discontinued for two-thirds of the wakeful day. As has been said before, the potential for having keratopathy waxes and wanes, and many patients will be able to proceed to uncovering the eye for the whole of the wakeful day. The tape used should be 2.5 cm wide and 6.25 cm long. The eye is shut by closing it with the top lid only, avoiding the tendency to squeeze the eye shut. The tape is held along the forefinger with about 1 cm in length being in front and unsupported by the fi nger. It is applied horizontally at first, to gain anchorage on the side of the nose, and then across the closed lids so that one third of the width of the tape adheres to the upper lid and two-thirds to the lower lid. Cutting the upper lid lashes greatly facilitates the application and retention of the tape. Smearing the scissors blades with petroleum jelly ensures that the cut lashes adhere to the blades and do not fall into the eye. Patients should be told to carry a mirror for periodic inspection of the closure. In the opinion of the author, mucomimetic drops do not have any influence on the punctate keratopathy of the insensitive cornea, but they seem to have some action in preventing the onset of the acute stage II of the disease. The administration of oral tetracycline 250 mg twice daily or, better for compliance, doxycycline 100 mg on alternate days seems to diminish the amount of mucus produced by these insensitive eyes and may be continued for long periods. Contact lenses have been advocated to control the keratopathy at this stage. However, they have several disadvantages; patients often lose their lenses during sleep, the keratopathy is difficult to assess under a contact lens, and fluorescein cannot be used without removing the lens and subsequently flushing the eye out with saline, for fear of staining the lens. The overwhelming disadvantage is the relatively frequent incidence of suppurative keratopathy. The patient is given no warning by way of pain, and the abscess is frequently well developed before a doctor is consulted. Even then, the wrong antibiotics may be prescribed by a doctor who is not familiar with the treatment of suppurative keratopathy in anesthetic, contact lens-wearing
Stage II This stage can be reached on the same day as a destructive procedure on the trigeminal nerve or its ganglion. It is an indication for urgent treatment. Atropine 1% should be instilled and the eye should be closed immediately with Blenderm or a temporary tarsorrhaphy. The injection of botulinum toxin into the levator palpebrae superioris may be indicated, but this takes about 3 days to take effect. The use of botulinum toxin to close the eye can be done in all three stages of the disease. The dose of toxin differs according to the toxin used. Botox, manufactured by Allergan and measured in mouse units, is approximately three times more powerful than Dysport, manufactured by Ipsen Ltd., also measured in mouse units. The dose for Dysport, which has been used by the author, is 10 to 20 mouse units. If a vial contains 500 units and is made up to a solution with 2.5 mL normal saline, 0.05 mL to 0.10 mL of this solution would be injected. In the case of Botox, 3 to 6 mouse units should perhaps be injected. This entails adding 2 mL of normal saline to a 100-mouse unit vial and injecting 0.06 mL to 0.12 mL. The levator palpebrae superioris is reached by passing a 25gauge, 2.5-mm-long needle through the skin of the upper lid, midway and just under the superior orbital rim. The needle is tracked along the roof of the orbit to avoid perforating the globe. The needle is introduced as far as it will go before the toxin is injected. This procedure produces a profound ptosis in 3 days that lasts up to 6 weeks. On no account should a therapeutic soft contact lens be inserted at this stage. If it is, within 12 hours a very red eye, a massive hypopyon, and thick aqueous flare will surely be present. This happens in the absence of manifest corneal infection.
Stage III The principal treatment is closure. This may be done with Blenderm tape, a temporary tarsorrhaphy, or botulinum toxin, as detailed above. Atropine should be instilled, and an appropriate antibiotic, such as ofloxacin, used topically. There is a case
for a systemic antibiotic, and this should probably be ciprofloxacin 500 mg, twice daily in tablet form. This antibiotic is secreted by the lacrimal gland and penetrates the eye. Topical corticosteroids are contraindicated because they potentiate collagenase activity. Permanent tarsorrhaphy, or repeated botulinum toxin injections into the levator palpebra are sometimes necessary for economic reasons in chronic relapsing disease. Lateral tarsorrhaphy has, in the opinion of the author, no place here. It inhibits natural blinking, and the disease process marches steadily on, concentrating on the exposed area of eye. Instead, a thin, central pillar tarsorrhaphy should be done. This can be thinned even further later on so that an ‘elastic band’ tarsorrhaphy remains. In this way the eye can still see when looking to either side and may have some acuity looking straight ahead.
COMMENTS Neuroparalytic keratitis is probably a disease of abnormal corneal epithelial cell turnover. Epithelial thinning, but not stromal thinning, has been shown in monkeys after destruction of the nerve or its ganglion. This did not occur with tarsorrhaphy alone. The thinned epithelium had fewer cells. Scanning electron microscopy of the conjunctiva has shown irregularity of epithelial cells and abnormalities of epithelial microvilli. Trophic changes in the corneal epithelium have been shown after controlled thermocoagulation of the trigeminal ganglion in rabbits. This denervation was found to markedly affect the proliferative activity of the epithelium, and mitosis was sparse. The cyclic nucleotides, the ‘second messengers’ of hormone action, are involved in the regulation of corneal epithelial cell turnover. There is an imbalance in the anesthetic eye, leading to a decreased cellular turnover. Cyclic AMP has been shown to produce quiescence in cells. Cyclic GMP has been shown to initiate mitosis. Cholinergic stimulation has been shown to be associated with rapid accumulation of cellular cyclic GMP. The normal corneal epithelium is rich in acetylcholine, but the anesthetic corneal epithelium has been shown to have depleted acetylcholine. This raises exciting possibilities for topical treatment with drugs that influence the cyclic nucleotide imbalance. Blockage at the level of adenylate cyclase, which catalyses the formation of cyclic AMP, is a possibility. Beta-adrenergic-blocking drugs are obvious choices for investigation. The β receptor blocking agent pindolol has been reported to accelerate the healing of corneal epithelial defects in rabbits. This drug has been used in several corneal conditions (including neuroparalytic keratitis) with claimed success. Antiprostaglandins may also work at this level. Unfortunately, the search for topical drugs to treat neuroparalytic keratitis does not make much economic sense. It is a relatively rare condition. Existing drugs must be tried. Another avenue of approach may be via the cyclic nucleotide phosphodiesterases. This may be a more fertile approach owing to the apparent sensitivity of the phosphodiesterases to a wider selection of chemical structures. Dipyridamole is a phosphodiesterase inhibitor used in cardiac stress testing and as an adjunct to oral anticoagulants. Sildenafi l (Viagra; Pfi zer) is a type 5 selective inhibitor of cyclic GMP-specific phosphodiesterase. It also happens to be a type 6 selective inhibitor and is involved in the phototransduction of the visual cascade.
CHAPTER 205 • Neuroparalytic Keratitis
eyes. Admittedly, it is often difficult to grow organisms from these anesthetic eyes, but a broad-spectrum antibiotic, or antibiotics, against Pseudomonas aeruginosa infection should be chosen. This organism is known to have an affi nity for contact lenses and especially those worn on an extended basis. The ideal treatment for this developing suppurative keratopathy in neuroparalytic keratitis is first removal of the contact lens and then ofloxacin (0.3%) every 15 minutes for six hours, then every 30 minutes for the next 18 hours. On day two this is reduced to two drops hourly. On day three the frequency can be reduced to four hourly. Ceftazidime 5%, should also be used every two hours, in addition. The latter antibiotic is a thirdgeneration cephalosporin that is highly effective against Pseudomonas. The incorporation of this second medication is advisable, if at all possible, because a number of Pseudomonas organisms (figures of 20% have been quoted) are resistant to ciprofloxacin. Untreated, stage I of the disease can become chronic and lead to epithelial hyperplasia and underlying stromal nebulae that may be vascularized. Band keratopathy can develop. Considerable resolution of epithelial hyperplasia can be brought about by total daily closure with Blenderm tape over a number of weeks, and this should always be tried before a corneal transplant is contemplated.
385
REFERENCES
DIAGNOSIS
Kahan A, Hammer H: Pindolol in the treatment of corneal disorders. In: The cornea in health and disease (VI Congress of the European Society of Ophthalmology), Royal Society of Medicine, International Congress and Symposium Series No. 40, London, Academic Press, 1981: 1073–1075.
Laboratory findings
SECTION 19 • Cornea
Mackie IA: Neuroparalytic (neurotrophic) keratitis. In: Black CI, et al, eds: Symposium on contact lenses. St Louis, CV Mosby, 1973: 125–142. Mackie IA: The role of the corneal nerves in destructive diseases of the cornea. Trans Ophthalmol Soc UK 98:343–347, 1978. Schimmelpfennig B, Beuerman RW: Trophic changes in corneal epithelium after controlled thermocoagulation of the trigeminal ganglion. In: The cornea in health and disease (VI Congress of the European Society of Ophthalmology), Royal Society of Medicine, International Congress and Symposium Series No. 40, London, Academic Press, 1981: 840–843.
206 PELLUCID MARGINAL DEGENERATION 371.48
Videokeratography is extremely useful in making the diagnosis and for detecting early disease that might not readily be detectable on slit-lamp examination. Videokeratography shows low corneal power along the central vertical axis, increased power as the inferior cornea is approached, and high corneal power along the inferior oblique meridians, giving the videokeratographic pattern a classic butterfly appearance (Figure 206.1). Keratometry demonstrates marked against-the-rule astigmatism. The disease is usually asymptomatic except for the progressive deterioration in vision caused by irregular astigmatism induced by the corneal ectasia. Histological examination shows a normal endothelium and Descemet’s membrane. The stroma is thinned, and Bowman’s layer may have breaks or be completely absent in the affected area. Diagnosis is made by finding typical features on slit-lamp examination and confi rmed by finding a classic videokeratographic pattern.
Differential diagnosis Karim Rasheed, MD, MSc, MRCOphth Templeton, California Yaron S. Rabinowitz, MD Los Angeles, California
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ETIOLOGY/INCIDENCE The term pellucid marginal degeneration was first coined by Schalaeppi in 1957 to describe a progressive, noninflammatory peripheral corneal thinning disorder characterized by a peripheral band of thinning of the inferior cornea from the 4 o’clock to the 8 o’clock position. This thinning is accompanied by 1 to 2 mm of normal corneal tissue between the limbus and the area of thinning. The corneal ectasia is most marked centripetal to the band of thinning. The central cornea is usually of normal thickness, and the epithelium overlying the area of thinning is intact. Usually both eyes are affected, but the degree of involvement may be asymmetric. The cause of this disorder has not been clearly established, but collagen abnormalities such as occur in keratoconus have been reported. Patients are usually 20 to 40 years old at the time of clinical presentation, and there appears to be a greater incidence in males. The condition is rare, but there may be a considerable underestimation of the incidence because patients with this condition are often misdiagnosed as having keratoconus, and ‘early’ cases may be diagnosed only with videokeratography.
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COURSE/PROGNOSIS As in keratoconus, this disorder is progressive. Eyes with severe disease exhibit marked corneal protrusion, which makes differentiation from keratoconus difficult in advanced cases. The area of thinning is typically epithelialized, clear, avascular and lacking lipid deposits. On careful slit-lamp examination, prominent lymphatic vessels are often detected at the inferior limbus parallel to the area of thinning. Vertical striations at the level of Descemet’s membrane (similar to Vogt’s striae) also may be seen in rare instances. Acute hydrops, similar to that noted in keratoconus, has been reported, but as in keratoconus, spontaneous perforation of the cornea is extremely rare.
386
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Pellucid marginal degeneration may be differentiated from keratoconus in most cases by the inferior band-like location of the thinning on slit-lamp examination and by the classic butterfly pattern on videokeratography. Keratoglobus causes generalized thinning of the cornea, with the thinning more marked at the limbus circumferentially for 360 degrees, and the entire cornea protrudes compared with regional thinning that occurs in keratoconus and inferior paralimbal thinning in pellucid marginal degeneration. Terrien’s marginal degeneration affects a similar age group and can be bilateral. Although it also can be associated with large amounts of astigmatism, it can be differentiated from pellucid marginal degeneration because the superior cornea is predominantly affected and the area of thinning often is associated with vascularization and lipid deposition. Furrow degeneration has some of the features of pellucid marginal degeneration in that there is an intact epithelium and the area of corneal thinning is not vascularized, at least not in the acute phase. The differentiating feature is that the area of thinning is much closer to the limbus with virtually no intervening zone of normal cornea. Furrow degeneration may on occasion involve the superior cornea, and there may be an associated adjacent area of scleritis. The edges of the furrow are steeper than the gradual attenuation seen in pellucid marginal degeneration, and there may be a corneal infi ltrate adjacent to the area of thinning. In addition, there appears to be a strong association with rheumatoid arthritis. Peripheral corneal melting disorders such as Mooren’s ulcer or peripheral melting secondary to rheumatologic disorders are characterized by pain, which may be severe in Mooren’s ulcer, and are accompanied by an epithelial defect over the area of thinning, as well as corneal vascularization adjacent to the area of thinning in the acute phase.
Reports in the medical literature suggest that keratoconus and pellucid marginal degeneration may exist in the same eye and in different eyes of the same patient.
CHAPTER 206 • Pellucid Marginal Degeneration
FIGURE 206.1. Corneal topography of early pellucid marginal deneration (right eye) and advance pellucid marginal degeneration (left eye).
TREATMENT Spectacle correction usually fails very early in the course of this disease as the degree of irregular astigmatism increases. In early to moderate cases, contact lenses are beneficial in providing visual rehabilitation. Rigid gas-permeable contact lenses are often hard to fit in patients with pellucid marginal degeneration. The problems in fitting result from the flattening of the superior cornea and the high degree of against-the-rule astigmatism that often causes the lens to dislocate inferiorly. Large diameter rigid gas permeable lenses which extend almost up to the limbus and scleral lenses made from gas permeable materials are making resurgence. A recent study found that 88.2% of eyes were successfully managed without having to resort to surgery. Of the 11.8% of patients undergoing corneal transplantation, all were able to maintain clear grafts after an average follow-up period of 9 years. These impressive results were achieved at a tertiary referral center and probably represent the best results that can currently be achieved for patients with this condition. In patients who cannot tolerate contact lenses or in whom the ectasia is of such a degree that rigid contact lenses do not provide adequate visual acuity, surgery may be considered. A number of surgical procedures have been performed in an attempt to provide visual rehabilitation. Standard-sized penetrating keratoplasty may result in poor results because the inferior edge of the transplant must be sutured to abnormally thin cornea; this results in a high degree of postkeratoplasty
astigmatism in the short term, and continued thinning of the host cornea inferiorly in the long term, which produces a situation similar to that which first necessitated surgery. Large-diameter grafts have been tried in an attempt to remove as much of the affected cornea as possible; however, because of the proximity to the limbus and its blood vessels, these grafts are more prone to rejection. Grafts that are deliberately decentered inferiorly also work poorly because decentering causes a large degree of astigmatism and because of a higher incidence of rejection, again due to proximity to the limbus. Thermokeratoplasty and epikeratophakia are of historical interest only because the results obtained with these techniques are extremely poor. Excision of a crescentic wedge of corneal tissue from the inferior cornea followed by tight suturing also has been reported to reduce the corneal ectasia. The procedure is usually well tolerated, but in our experience, the effect has been short lived and the thinning and ectasia recur. In addition, this procedure may be hazardous in inexperienced hands; we have noted several instances of wound dehiscence and resulting flat anterior chambers with their attendant problems when this procedure has been attempted. Crescentic lamellar keratoplasty in which a crescentic transplant is performed to reinforce the area of thinning also has been reported, but this may result in a high degree of astigmatism that necessitates a subsequent central penetrating keratoplasty. The performance of peripheral lamellar crescentic keratoplasty followed after a few months by a central penetrating
387
SECTION 19 • Cornea
keratoplasty is the favored surgical treatment. The lamellar transplant restores normal thickness to the inferior cornea and enables good edge-to-edge apposition at the time of penetrating keratoplasty, which reduces the possibility of high postkeratoplasty astigmatism. Furthermore, the central graft that is sutured to a normal-thickness host can be treated with videokeratography-guided selective removal of sutures and astigmatic keratotomy in the usual way to reduce any residual astigmatism. Although they are technically difficult, we have performed the two operations in the same sitting with encouraging results. Performing two keratoplasty procedures at different times necessitates the use of two separate corneas. By performing these procedures at the same time, we have been able to use tissue from the same donor, potentially reducing the antigenic load. This technique also significantly decreases the time needed to attain best-corrected acuity, which is important in these patients, who often are young and in the active working phase of their lives. The trend for progressive increase in the ‘against the rule astigmatism,’ which is a hallmark of this disease, appears to be abolished. Long-term follow-up will determine whether this is the optimal surgery for advanced disease. Recently, the use of intra-corneal ring segments has been reported in patients with early to moderate disease. The early results appear encouraging. With the increase in refractive surgery, it is extremely important to detect these patients early, because very poor results, with central corneal scarring and irregular astigmatism, have been reported for photorefractive keratectomy in undetected early cases. Incisional techniques such as astigmatic keratotomy also are contraindicated because they are highly unlikely to correct the irregular astigmatism and might result in corneal perforation in unsuspected cases.
REFERENCES Krachmer JH: Pellucid marginal corneal degeneration. Arch Ophthalmol 96:1217–1221, 1978. Kremer I, Sperber LT, Laibson PR: Pellucid marginal degeneration treated by lamellar and penetrating keratoplasty (Letter). Arch Ophthalmol 111:169–170, 1993. Maguire LJ, Klyce SD, McDonald MB, Kaufman HE: Corneal topography of pellucid marginal degeneration. Ophthalmology 94:519–524, 1987.
is a Greek word that means ‘blister.’ A cell-mediated immunity (delayed hypersensitivity) response occurs to microbial antigens. ● Bacteria: ● Staphylococcus aureus; ● Mycobacterium tuberculosis. ● Fungi: ● Candida albicans; ● Coccidioides immitis; ● Chlamydia: ● Chlamydia lymphogranulomatis. ● Parasites: ● Leishmania spp.; ● Ascaris lumbricoides; ● Ancylostoma duodenale; ● Hymenolepis nana. ● Other. Phlyctenulosis has a worldwide distribution. It is more common in areas in which tuberculosis is endemic. The disease occurs most frequently in children or young adults. There is a higher prevalence among females than males. Phlyctenulosis occurs more frequently in spring and summer than in autumn or winter.
COURSE/PROGNOSIS Patients with phlyctenulosis present with photophobia, redness of the eye, irritation, and tearing. The conjunctival phlyctenule leaves no scarring, whereas corneal phlyctenule may develop localized gray infiltrates with subsequent scarring. Phlyctenulosis associated with staphylococcal antigens is triggered by active blepharitis. The most frequent site of phlyctenulosis is the limbus, and it usually occurs in the inferior quadrants of the cornea. Phlyctenulosis may result in minimal or extensive multiple nummular scars of the cornea. Salzmann’s nodular degeneration may occur after healing of phlyctenulosis. When the center of the cornea is involved, corneal scarring may lead to a decrease in vision. In severe cases, corneal involvement may result in ulceration, scarring and, rarely, perforation.
Rabinowitz YS: Keratoconus. Surv Ophthalmol 42:297–319, 1998. Tzelikis PF, Cohen EJ, Rapuano CJ, et al: Management of pellucid marginal corneal degeneration. Cornea 24(5):555–560, 2005.
DIAGNOSIS
Varley GA, Macsai MS, Krachmer JH: The results of penetrating keratoplasty for pellucid marginal corneal degeneration. Am J Ophthalmol 110:149–152, 1990.
Clinical signs and symptoms
207 PHLYCTENULOSIS 370.3 Khalid F. Tabbara, MD, ABO, FRCOphth Riyadh, Saudi Arabia
ETIOLOGY/INCIDENCE Phlyctenulosis is an inflammation of the cornea and conjunctiva that is induced by microbial antigens. The term phlyctena
388
Conjunctival phlyctenulosis Conjunctival phlyctenulosis begins as single or multiple lesions of 0.5 to 3 mm in diameter. They appear as small, elevated, hard, pinkish lesions surrounded by a zone of conjunctival hyperemia. The lesion occurs over the bulbar conjunctiva and most frequently near the limbus. Over a few days, the nodule appears gray and soft and may develop a central necrotic lesion that may ulcerate. The lesion heals rapidly over 10 to 12 days, leaving no scar in the conjunctiva.
Corneal phlyctenulosis Phlyctenules appear as unilateral or bilateral localized infi ltrates measuring 0.5 to 2 mm. The lesion occurs at the limbus or the corneal periphery and over a period of a few days may lead to ulceration in the center. The corneal phlyctenules attract a leech of new blood vessels. Some phlyctenules show a tendency to migrate and wander in the cornea.
In severe cases, multiple phlyctenules may be seen in the cornea and may affect the visual axis, leading to scarring and a decrease in vision. Stromal involvement is typically superficial; deeper involvement may occur in staphylococcal phlyctenulosis and may rarely lead to corneal perforation. Most nodules of phlyctenulosis start in the limbus with dilated conjunctival vessels. The infi ltration may travel toward the center of the cornea, with progressive necrosis and grayish infi ltrates with superficial ulceration. Scarring of the phlyctenules may take the form of a spade at the limbus with a triangular scar. In severe cases, multiple phlyctenules are seen in the cornea, and Salzmann’s nodular degeneration may occur subsequently.
bral conjunctiva, and conjunctival scrapings show the presence of eosinophils. Patients have marked itching and may develop superficial punctate keratitis.
Laboratory findings
Local
In patients with staphylococcal blepharitis, culture of the lids reveals Staphylococcus spp. In patients with tuberculosis, the tuberculin skin test is positive. Conjunctival and corneal scrapings of phlyctenules initially may show evidence of mononuclear cells; in the late course of the disease, patients have polymorphonuclear cells. The epithelium shows degenerative epithelial cells. Usually, no eosinophils are seen in the scrapings. Biopsy specimens of limbal phlyctenules show mononuclear cellular infiltration and polymorphonuclear cells in the epithelium and stroma. The mononuclear cells are predominantly T lymphocytes, monocytes/macrophages and dendritic cells. The T lymphocytes are mostly T helper/inducer cells. B lymphocytes and plasma cells are uncommon. The basal cell layers express HLA-DR antigens. The findings in phlyctenules are comparable to those observed in the human skin tuberculin reaction, which are considered to be classic examples of the delayed-type hypersensitivity response in humans.
The lids should be carefully evaluated in cases of chronic staphylococcal blepharitis. Patients should receive a vigorous regimen of lid scrubs with an antibiotic/steroid ointment to be placed twice daily for a period of 2 to 4 weeks. This may be by cleaning of the lid margin with effective baby shampoo during showers. Baby shampoo may be used to scrub the lid margin, and eyelash scales should be removed with an effective antidandruff preparation. In young children, erythromycin ophthalmic ointment may be applied twice daily at the lid margin. In addition, 0.1% topical fluorometholone eyedrops or rimexolone (Vexol) eyedrops three times daily may be given for the corneal and conjunctival phlyctenules. The treatment of corneal and conjunctival phlyctenulosis may consist of 0.1% topical fluorometholone eyedrops or rimexolone eyedrops to be given every 6 hours for a period of 10 days. The topical treatment may be tapered to once daily over a period of 4 weeks. The intraocular pressure (IOP) should be monitored for steroidinduced glaucoma. A cycloplegic agent in the form of 1% tropicamide eyedrops may be given to patients with severe corneal involvement.
TREATMENT In staphylococcal blepharitis, patients older than 7 years can receive 100 mg doxycycline qd for 1 month. Patients with tuberculosis should be given the appropriate systemic therapy for tuberculosis.
CHAPTER 207 • Phlyctenulosis
Systemic
Differential diagnosis ● ● ● ● ● ● ●
Pingueculitis (inflamed pinguecula). Sterile peripheral corneal infi ltrates. Marginal ulcers. Acne rosacea. Trachomatous pustule. Vernal keratoconjunctivitis. Infected peripheral ulcer.
COMPLICATIONS ● ● ● ●
The differential diagnosis of phlyctenulosis is important so as to initiate appropriate therapy. The corneal lesions of acne rosacea may closely resemble phlyctenulosis but have associated skin findings. Pingueculitis shows no microinfiltrates. An increase in the amount of collagen in the substantia propria is seen after the pingueculitis subsides. There usually is a single lesion, there is no tendency to migrate into the cornea and there is no ulceration. In cases of infected corneal ulcers, there is a demarcating margin with a tendency to infi ltrate the center of the cornea. In cases of peripheral corneal infi ltrates, secondary to contact lenses, there is a history of contact lens use. The lesion shows no ulceration and does not migrate into the cornea. In patients with vernal keratoconjunctivitis, the lesions are multiple with limbal hypertrophy and gelatinous infi ltration of the limbus. The typical giant papillae are seen over the palpe-
Peripheral corneal scarring with vascularization. Central scarring in central corneal phlyctenules. Rarely corneal perforation. Loss of vision.
In patients with severe corneal scarring, penetrating keratoplasty may be required for visual rehabilitation.
REFERENCES Abu El-Asrar AM, Van Den Oord JJ, Geboes K, et al: Phenotypic characterization of inflammatory cells in phlyctenular eye disease. Doc Ophthalmol 70:352–362, 1988. Culbertson WW, Huang AJW, Mandelbaum SH, et al: Effective treatment of phlyctenular keratoconjunctivitis with oral tetracycline. Ophthalmology 100:1358–1366, 1993. Helm CJ, Holland GN: Ocular tuberculosis. Surv Ophthalmol 38(3):229– 256, 1993. Mondino BJ, Kowalski RP: Phlyctenulae and catarrhal infi ltrates. Occurrences in rabbits immunized with staphylococcol cell walls. Arch Ophthalmol 100:1968–1971, 1982. Ostler HB: Corneal perforation in nontuberculous (staphylococcal) phlyctenular keratoconjunctivitis. Am J Ophthalmol 79:446–448, 1975.
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208 POSTERIOR POLYMORPHOUS DYSTROPHY 371.58 Nicole J. Anderson, MD Flowood, Mississippi R. Doyle Stulting, MD, PhD Atlanta, Georgia
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Histologic study of Descemet’s membrane shows a normal anterior banded zone in cases presenting after birth. The posterior non-banded zone is diminished or absent and is replaced by an abnormal posterior collagenous layer. Specular microscopy in vesicular PPD shows circular dark rings with scalloped edges around a light center. Band lesions appear as broad, mottled strips delineated by narrow, dark scalloped borders.
SECTION 19 • Cornea
Differential diagnosis
ETIOLOGY/INCIDENCE Posterior polymorphous dystrophy (PPD) is a rare bilateral corneal disorder of Descemet’s membrane and the corneal endothelium. It is typically non-progressive and often noted as an incidental finding on ophthalmic examination. It can rarely cause reduced vision from corneal edema and glaucoma. ● Inheritance is autosomal dominant with variable expression. Some cases of autosomal recessive inheritance have been reported. ● The gene locus has been identified on the long arm of chromosome 20 (20q11) and is the same locus as that involved in autosomal dominant congenital hereditary endothelial dystrophy (CHED). ● Associations have been reported with Alport’s syndrome and keratoconus. ● The pathogenesis is believed to be a local metaplasia of endothelial cells to abnormal epithelial-like cells.
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Iridocorneal endothelial (ICE) syndrome usually is unilateral and acquired. Endothelial cells are large and pleomorphic in ICE, rather than epithelial-like. There can be an overlap between ICE and posterior polymorphous dystrophy, causing speculation as to whether they represent different clinical entities or a spectrum of the same disease. Posterior corneal vesicle syndrome shows vesicles and band lesions similar to those of posterior polymorphous dystrophy, but it is unilateral and nonfamilial. Haab’s striae resemble band lesions but have scrolled, thickened edges with smooth areas within and do not have associated vesicles. In children born with cloudy corneas caused by posterior polymorphous dystrophy, the differential diagnosis includes congenital hereditary endothelial dystrophy, congenital hereditary stromal dystrophy, congenital glaucoma, birth trauma, congenital infection, metabolic disorders and sclerocornea.
COURSE/PROGNOSIS TREATMENT ●
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Typical corneal findings are present from an early age, but diagnosis is not usually made until the second or third decade. Most cases are asymptomatic and non-progressive. Corneal edema may develop in mid-life, or rarely at birth. Glaucoma, either open-angle or closed-angle, may occur. Glaucoma can result from overgrowth and contraction of the abnormal endothelium and basement membrane over the anterior chamber angle.
In most cases, no treatment is necessary, as the disorder is usually non-progressive.
Ocular ●
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In mild corneal decompensation, topical sodium chloride drops or ointment can be administered. Elevated intraocular pressure should be treated medically or surgically.
Surgical
DIAGNOSIS
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Clinical signs and symptoms ●
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Slit-lamp examination shows one of three forms of the disorder. In the vesicular variant, small, round, vesicular lesions surrounded by a ring opacity are seen at the level of Descemet’s membrane. Band PPD is characterized by elongated bands of roughened Descemet’s membrane, with narrow, opaque, irregular ridges. In diffuse PPD, a large portion of the posterior corneal surface is invaded with a swirled pattern of thickened and opacified Descemet’s membrane. Peripheral anterior synechia, glaucoma, iris atrophy, or corectopia may be present.
Laboratory findings ●
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Histologic study of the endothelium reveals multi-layered epithelial-like cells with abundant microvilli, tonofi laments and desmosomes. These cytokeratin-expressing cells arise when normal endothelial cells lose their characteristic phenotype and become epithelioid.
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In patients with corneal edema, penetrating keratoplasty may be necessary. Eyes with peripheral anterior synechia, elevated intraocular pressure, or both have a poor visual prognosis after penetrating keratoplasty. Posterior polymorphous dystrophy may recur in the graft after penetrating keratoplasty.
REFERENCES Anderson NJ, Badawi DY, Grossniklaus HE, et al: Posterior polymorphous membranous dystrophy with overlapping features of iridocorneal endothelial syndrome. Arch Ophthalmol 119:624–625, 2001. Háon E, Greenberg A, Kopp KK, et al: VSX1: a gene for posterior polymorphous dystrophy and keratoconus. Hum Mol Genet 11:1029–1036, 2002. Krachmer JH: Posterior polymorphous corneal dystrophy: a disease characterized by epithelial-like endothelial cells which influence management and prognosis. Trans Am Ophthalmol Soc 83:413–475, 1985. Laganowski HC, Sherrard ES, Muir MG: The posterior corneal surface in posterior polymorphous dystrophy: a specular microscopical study. Cornea 10:224–232, 1991.
209 REIS–BÜCKLERS CORNEAL DYSTROPHY 371.52
David Matthew Bushley, MD Durham, North Carolina Natalie A. Afshari, MD Durham, North Carolina
ETIOLOGY/INCIDENCE Reis–Bücklers dystrophy is a bilateral, progressive, autosomal dominant corneal dystrophy with early onset affecting Bowman’s layer, epithelium, basement membrane and anterior stroma. It is linked in some cases with R124L and G623D mutations in the transforming growth factor beta-induced (TGFbI) gene on chromosome 5q31. Reis–Bücklers dystrophy is relatively rare, though the incidence is unknown.
DIFFERENTIAL DIAGNOSIS The differential diagnosis includes the corneal epithelial dystrophies, Thiel–Behnke honeycomb dystrophy (CDB-II), and superficial corneal scarring.
PROPHYLAXIS Prophylaxis aims at reducing the frequency of recurrent corneal erosion and includes artificial tears, lubricating ointment and hypertonic agents (e.g. sodium chloride 5%).
COURSE/PROGNOSIS
TREATMENT
Reis–Bücklers manifests in early childhood, usually within the first and second decade of life. The initial symptom is typically recurrent corneal epithelial erosions; over time, corneal scarring and opacification occurs at the level of Bowman’s layer and superficial stroma. Marked loss of vision usually occurs during the second and third decades of life.
Systemic
DIAGNOSIS Clinical signs and symptoms The young patient usually presents with symptoms of pain, foreign body sensation and photophobia associated with recurrent corneal epithelial erosions. Clinical exam typically reveals a rough and irregular corneal surface with fi ne granular opacities forming a geographic pattern (rings and disc-shaped opacities) at the level of Bowman’s layer. The central cornea tends to be preferentially affected, and the lesions may extend into the superficial stroma. Whereas Reis–Bücklers (CDB-I) is phenotypically similar to Thiel–Behnke honeycomb corneal dystrophy (CDB-II), electron microscopy is needed to differentiate the two clinical entities. Compared to Thiel–Behnke honeycomb corneal dystrophy, Reis–Bücklers occurs at a younger age, causes more corneal scarring, more visual impairment and exhibits a higher frequency of recurrence.
Laboratory findings Genetically, CDB-I has mapped to a R124L mutation in TGFbI gene on chromosome 5q31 in many cases. Less common is a G623D mutation in the same gene. CDB-II has mapped to a R555Q mutation in TGFbI gene on chromosome 5q31 though another locus has been mapped to chromosome 10q23-q24. Histopathology and light microscopy in CDB-I show bandshaped granular, Masson-positive, subepithelial deposits at the
CHAPTER 209 • Reis–Bücklers Corneal Dystrophy
(Corneal Dystrophy of Bowman’s Layer Type 1, CDB-I, Superficial Variant of Granular Dystrophy, Granular Corneal Dystrophy Type III)
level of Bowman’s layer, causing epithelial irregularity, destruction of Bowman’s layer, and intermittently absent or thickened basement membrane. Transmission electron microscopy in both CDB-I and CDB-II reveals fibrocellular scar tissue (‘sawtooth’ configuration) which replaces Bowman’s layer, epithelial basement membrane and hemidesmosomal complexes. The two entities are differentiated by the fi ndings in CDB-I of ultrastructural deposits of rod-like bodies whereas in CDB-II, arcuate or rounded ‘curly fibers’ appear in the region of Bowman’s layer.
There are no known systemic treatments for Reis–Bücklers dystrophy.
Ocular Treatment is supportive and consists of artificial tears, lubricating ointment and hyperosmotic agents. For patients with corneal erosions, topical antibiotics and a cycloplegic agent should be added. Consideration for debridement of loose epithelium, the use of a therapeutic soft contact lens, and possible anterior stromal micropuncture are appropriate. Surgical intervention should be considered for recurrent corneal erosions or reduced visual acuity. Excimer laser phototherapeutic keratectomy (PTK) is the treatment of choice as it allows for restoration of a smooth corneal surface although some corneal opacities may remain. Unfortunately, recurrences are common. Alternatively, superficial keratectomy with a blade and peeling can be considered. Lamellar keratoplasty can be considered for deeper scarring and opacities. Options include manual (freehand) and microkeratome-assisted anterior lamellar keratoplasty (ALK). Penetrating keratoplasty (PKP) can be considered as a last resort, and recurrences in the graft are common.
COMPLICATIONS Recurrent corneal erosions can be refractory to treatment and patients are at risk for infectious keratitis. Scarring and corneal opacification resulting from recurrent episodes may lead to reduced visual acuity and irregular astigmatism. Risks associated with PTK and other surgical interventions include loss of best-corrected visual acuity, infection, scarring, irregular astigmatism, recurrence, and, in PKP, graft rejection. Recurrence of disease is common following any of the surgical treatments.
391
COMMENTS
SECTION 19 • Cornea
Reis–Bücklers(CDB-I) and Thiel–Behnke honeycomb dystrophy (CDB-II) are dystrophies of Bowman’s layer that appear similar clinically. In the past, our understanding of these two entities was significantly impaired and confused by a lack of histologic and electron microscopic descriptions in the literature. Over the past decade, in large part due to advances in molecular genetics and the work of researchers in Europe and the United States, these dystrophies of Bowman’s layer have been redefi ned as two distinct entities.
REFERENCES Afshari NA, Mullally JE, Afshari MA, et al: Survey of patients with granular, lattice, avellino, and Reis-Bücklers corneal dystrophies for mutations in the bIGH3 and gelsolin genes. Arch Ophthalmol 119(1):16–22, 2001. Dighiero P, Valleix S, D’Hermies F, et al: Clinical, histologic, and ultrastructural features of the corneal dystrophy caused by the R124L mutation of the bIGH3 gene. Ophthalmology 107(7):1353–1357, 2000. Klintworth GK: Advance in the molecular genetics of corneal dystrophies. Am J Ophthalmol 128(6):747–754, 1999. Krachmer JH, Mannis MJ, Holland EJ: Cornea. 2nd edn: Philadelphia, Elsevier Mosby, 2005. Küchle M, Green WR, Völcker HE, Barraquer J: Re-evaluation of corneal dystrophies of Bowman’s layer and the anterior stroma (Reis-Bücklers’ and Thiel-Behnke types): a light and electron microscopic study of eight corneas and a review of the literature. Cornea 14:333–354, 1995. Mashima Y, Nakamura Y, Noda K, et al: A novel mutation at codon 124 (R124L) in the bIGH3 gene is associated with a superficial variant of granular corneal dystrophy. Arch Ophthalmol 117(1):90–93, 1999.
210 SCHNYDER’S CRYSTALLINE CORNEAL DYSTROPHY 371.56
more diffuse systemic abnormality. The gene for the dystrophy has been mapped to human chromosome 1p36.2-36.3.
COURSE/PROGNOSIS The corneal dystrophy progresses with age. Patients in their twenties demonstrate only a central corneal opacity, which may involve the entire stroma, central subepithelial cholesterol crystals, or both. These patients have excellent visual acuity with normal corneal sensation. By age thirty, affected patients develop arcus lipoides. They may begin to note slight visual acuity reduction. Visual acuity is often considerably better than one would estimate based on slit-lamp appearance. The examination may detect the loss of Snellen visual acuity only if measured under daylight conditions. Corneal sensation also begins to decrease. Usually by age forty, patients develop a midperipheral panstromal corneal haze that fi lls in the donut-shaped area between the central opacity and the peripheral arcus. There will usually be some further reduction in visual acuity and corneal sensation. Often, arcus lipoides is so dense that it can be noted without the use of slitlamp examination. By their fi fties, patients may require corneal transplantation because of the increased glare and decreased vision in the daylight. Despite the name, only 51% of affected patients have crystalline deposits. This subset of patients without corneal crystalline deposition has been identified as having Schnyder’s crystalline dystrophy sine crystals. However, patients have been reported to have crystalline deposition in only one eye. Schnyder’s crystalline dystrophy may be detected as early as the first decade, but the diagnosis of Schnyder’s crystalline dystrophy sine crystals is more challenging and has been reported to be delayed up to the fourth decade.
DIAGNOSIS Clinical signs and symptoms
Kristin M. Hammersmith, MD Philadelphia, Pennsylvania Peter R. Laibson, MD Philadelphia, Pennsylvania
ETIOLOGY/INCIDENCE
The clinical signs of the dystrophy may include a central corneal haze, subepithelial cholesterol crystal deposition, midperipheral panstromal haze and arcus lipoides. Systemic findings may include genu valgum and hypercholesterolemia.
Laboratory findings ●
Schnyder’s crystalline dystrophy is a rare autosomal dominant disorder in which there is an abnormal bilateral deposition of cholesterol and lipid in the cornea. There are no reports on the incidence of this dystrophy in the general population; the world’s largest pedigree of patients with Schnyder’s crystalline dystrophy has a Swede– Finn heritage and has been traced to the southwest coast of Finland. The pathogenesis of the corneal changes is unknown, but it is thought to result from a localized defect of lipid metabolism. Abnormal elevations of serum lipid levels have been found in both affected and unaffected members of Schnyder’s pedigrees, but some affected members may also have normal serum lipid and cholesterol measurements. Abnormal lipid storage has been reported in the skin fibroblasts of affected patients, implying a
392
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Although rare sporadic cases have been reported, the vast majority of patients demonstrate a clear autosomal dominant inheritance. The corneal findings are predictable on the basis of patient age. The diagnosis may be more difficult in patients who do not demonstrate cholesterol crystals. Affected and unaffected patients should have serum lipid analysis because hyperlipidemias are frequent and should be treated. The loss of corneal sensation may be profound in more advanced cases.
Confocal microscopy has demonstrated loss of corneal nerves, large extracellular deposits and accumulation of highly reflective extracellular matrix.
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Differential diagnosis ●
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The differential diagnosis is made up of systemic abnormalities affecting lipid metabolism and resulting in central corneal clouding including lecithin-cholesterol acyltransferase deficiency, fish eye disease and Tangier disease. These diseases are differentiated because they are of autosomal recessive inheritance, they do not demonstrate anterior stromal crystalline deposits, and they have low levels of serum high-density lipoprotein. Other diseases with corneal crystals include cystinosis, dysproteinemias, multiple myeloma, porphyria, hyperuricemia, primary or secondary lipid keratopathy and other metabolic defects.
211 SUPERIOR LIMBIC KERATOCONJUNCTIVITIS 370.32 (Theodore’s Superior Limbic Keratoconjunctivitis; SLK) Timothy Y. Chou, MD Rockville Centre, New York Henry D. Perry, MD, FACS Rockville Centre, New York Eric D. Donnenfeld, MD, FACS Rockville Centre, New York Superior limbic keratoconjunctivitis (SLK) was fi rst described by Theodore and Thygeson in the early 1960s. The disease is characterized by hyperemia and thickening of the upper bulbar conjunctiva in a ‘corridor’-like distribution, a fi ne papillary inflammation of the superior palpebral conjunctiva, punctuate erosions over the superior and perilimbal cornea, and frequently superior fi lamentary keratopathy.
ETIOLOGY/INCIDENCE TREATMENT ●
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There is no local or systemic medical treatment that halts the progression of the corneal lipid deposition in this dystrophy. An alteration in serum cholesterol level has not been found to alter progression of the ocular disease. Penetrating keratoplasty surgery can be performed successfully in more advanced cases. The dystrophy can recur in the transplant; however, unlike lattice and granular dystrophy, it usually recurs many years after transplantation. Phototherapeutic keratectomy can be used to treat subepithelial crystals if they are causing decreased vision.
REFERENCES Garner A, Tripathi RC: Hereditary crystalline stromal dystrophy of Schnyder. II. Histopathy and ultrastructure. Br J Ophthalmol 56:400–408, 1972. Theendakara V, Tromp G, Kuivaniemi H, et al: Fine mapping of the Schnyder’s crystalline corneal dystrophy locus. Human Genetics 114:594– 600, 2004. Weiss JS, Rodrigues MN, Kruth HS, et al: Panstromal Schnyder’s corneal dystrophy: Ultrastructural and histochemical studies. Ophthalmology 99:1072–1081, 1992. Weiss JS: Schnyder’s crystalline dystrophy sine crystals: recommendation for a revision of nomenclature. Ophthalmology 103:465–473, 1996. Weiss JS: Schnyder’s dystrophy of the cornea: a Swede-Finn connection. Cornea 11:93–101, 1992.
The cause of SLK is unknown. A viral etiology was suggested early on, but no viral particles have ever been identified histologically. There is an associated increase in incidence of thyroid dysfunction, but no other evidence that this is an autoimmune process. An allergic process is unlikely, as itching is not a typical symptom, topical corticosteroids have little benefit, and conjunctival scrapings reveal no eosinophils. Darrell described identical twins with SLK, proposing a possible genetic basis. Many seem to prefer an anatomical and mechanical explanation of the disease. Cher has attributed the development of SLK to ‘blink-related microtrauma’ of the eyelid against the bulbar conjunctiva. Along the same lines, Wilson and Ostler have theorized that SLK results from tight apposition of the upper eyelid, due to thyroid disease or inflammation, against a lax superior bulbar conjunctiva. The latter might be either agerelated or congenital. The resulting chronic rubbing and abnormal movement of the conjunctiva would then result in characteristic findings of SLK. The condition is usually bilateral, but it may be unilateral and is often asymmetrical. This disease is most commonly seen in patients between the ages of 20 and 67, with a mean age of 49 years. It occurs more frequently in women than men by a 3 : 1 ratio. There is no seasonal, geographic, or racial predilection. Thyroid dysfunction is found in one-quarter to onehalf of patients, most often hypothyroidism or else severe Graves ophthalmopathy. One case of SLK was reported in a patient with hyperparathyroidism due to a parathyroid adenoma, with resolution of the condition following resection of the tumor. Dry eye (keratoconjunctivitis sicca) is commonly encountered, in up to half of patients.
CHAPTER 211 • Superior Limbic Keratoconjunctivitis
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Histopathologic examination of corneal transplant specimens demonstrates panstromal deposition of unesterified and esterified cholesterol and lipids. Abnormal lipid deposition has rarely been found in basal epithelium and endothelial cells. Compared with normal corneas, cholesterol and phospholipid contents in affected corneas are increased more than 10- and 5-fold. Apolipoproteins accumulate in the affected corneas, indicating preferential deposition of high-density lipoprotein.
COURSE/PROGNOSIS SLK is a chronic condition that may last from 1–10 years or more, with a characteristic course of remissions and exacerbations. Individual attacks may last from days to months, and
393
involve one eye or both. In most cases, periods of remission gradually lengthen until the condition eventually resolves spontaneously. Vision is not usually affected. A superior limbal pannus may develop, and scarring of the superior tarsal conjunctiva is occasionally observed, but in general there are no other serious ocular sequelae.
SECTION 19 • Cornea
DIAGNOSIS Clinical signs and symptoms Patients with SLK usually complain of burning, irritation, tearing, foreign body sensation, pain, photophobia, mucus discharge, blepharospasm and ptosis. Subjective discomfort often seems greater than the actual clinical fi ndings. When fi laments are present, symptoms tend to be exacerbated even more (Figure 211.1). An important initial step to properly diagnosing SLK is to have the patient look downward while the examiner elevates the upper eyelids. In this way, the characteristic superior bulbar injection is observed (Figure 211.2). It is centered at 12 o’clock,
and typically arcs around the limbus for about 10 mm in the shape of an inverted trapezoid. On biomicroscopy, eversion of the upper eyelid reveals a nearly pathognomonic velvety papillary reaction along the tarsal conjunctiva. The superior bulbar conjunctiva is thickened and lusterless. Its tissue may be redundant and hypermobile. Superior limbal tissue is likewise thickened. The superior and paralimbal corneal epithelium demonstrates a fine punctate keratopathy and pannus. Filaments occur at the superior limbus and cornea in about one-third of cases. The abnormal superior conjunctival, as well as limbal and corneal surfaces stain intensively with rose bengal, and to a lesser degree with fluorescein. Corneal sensation and tear secretion, as measured by Schirmer testing, may be decreased.
Laboratory findings Diagnosis is made based on history and characteristic clinical findings. Examination of scrapings of the involved bulbar conjunctiva may be helpful. Theodore and Ferry verified Thygeson’s observation that Giemsa-stained scrapings demonstrate keratinized epithelial cells. Scrapings of the upper palpebral conjunctiva show polymorphonuclear leukocytes. Biopsy of the involved bulbar conjunctiva reveals epithelial keratinization, dyskeratosis, acanthosis, balloon degeneration of the nuclei, intracellular accumulation of glycogen and hyalinized cytoplasm. There is stromal edema, as well as infi ltration with polymorphonuclear leukocytes, lymphocytes and plasma cells. Goblet cells are markedly decreased. Electron microscopic examination shows a variety of nonspecific (degenerative) abnormalities within the nuclei of epithelial cells. Patients should be advised to consult with their internists about thyroid function testing.
Differential diagnosis
FIGURE 211.1. SLK with associated filamentary keratitis.
FIGURE 211.2. Classical injection pattern of the superior bulbar conjunctiva.
394
The differential diagnosis is composed of conditions affecting the upper bulbar conjunctiva and cornea, and the upper palpebral conjunctiva, including the following: ● Contact lens-induced keratoconjunctivitis (CLK); ● Herpes simplex virus keratoconjunctivitis; ● Trachoma; ● Staphylococcal limbal keratoconjunctivitis; ● Floppy eyelid syndrome; ● Giant papillary conjunctivitis; ● Phlyctenular keratoconjunctivitis; ● Rosacea keratoconjunctivitis; ● Limbal vernal keratoconjunctivitis; ● Dysplasia; ● Neoplasm (case reported of sebaceous cell carcinoma misdiagnosed as SLK); ● Keratoconjunctivitis sicca; ● Retained superior perilimbal sutures.
Contact lenses can cause a keratoconjunctivitis that is clinically similar to SLK. There may be hyperemia of the superior bulbar conjunctiva, as well as irregular staining of and subepithelial infi ltrates in the superior cornea. This masquerade syndrome may be related at least in part to thimerosal sensitivity and toxicity, and is not associated with thyroid dysfunction. In contrast to SLK, discontinuation of the contact lens in CLK is usually curative.
TREATMENT Treatment remains a significant problem because there may be recurrences after the successful application of any of the following therapies.
Ocular
Surgical Patients not responding to more conservative measures may be candidates for more aggressive treatment approaches. The superior bulbar conjunctiva may be treated with 30–50 brief focal applications of thermal cautery, after instilling topical anesthetic. Enough thermal energy should be used to burn the conjunctival epithelium and shrink the stroma, but not so much as to damage the sclera. Udell and colleagues reported success in the treatment of 8 of 11 patients (73%) with this method. Recession or resection of the involved superior bulbar conjunctiva has been recommended for more severe cases. An arcuate 2- to 8-mm segment of conjunctiva and Tenon’s tissue is removed from the 10 to 2 o’clock meridian superiorly after a peritomy incision. The remaining superior edge of the conjunc-
OTHER Associated conditions such as chronic blepharitis and dry eye may aggravate symptoms; these conditions should be treated.
Dry eye ● ● ●
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Preservative-free artificial tears and ointments. Punctal occlusion. Avoidance of contributing environmental factors such as wind, smoke and pollution. Restasis used twice daily in patients with associated keratoconjunctivitis sicca.
Blepharitis ● ● ●
Eyelid scrubs. Topical antibiotics to eyelid margins. Systemic tetracycline or tetracycline derivatives or systemic erythromycin.
CHAPTER 211 • Superior Limbic Keratoconjunctivitis
In patients with dry eye, initial treatment can include nonpreserved artificial tears, gels and ointments. Punctal occlusion has also been found to be useful. Silver nitrate 0.25% to 1.0% solution is applied with a cottontipped applicator to the upper tarsal conjunctiva and upper bulbar conjunctiva after the instillation of a topical anesthetic agent. Irrigating solution may be used 1 minute after application. This can be repeated after 5 to 7 days and at 2- to 6-week intervals. Scraping the superior bulbar conjunctiva with a platinum spatula may relieve symptoms for several weeks to a few months, presumably by debriding the keratinized tissue. The worse eye may be pressure patched daily for a full week. The next week, the nonpatched eye may be patched for 1 week, with the patch changed every day. This alternate patching technique has also been used successfully in conjunction with the use of a bandage contact lens in the nonpatched eye. Mast cell stabilizers such as cromolyn sodium 4%, lodoxamide tromethamine 0.1%, and ketotifen fumarate drops applied to the involved eye or eyes 4 times daily have been reported to be beneficial for some patients with SLK. When treatment is successful, it must be continued on a long-term basis because there may be recurrences upon discontinuation of the medication. The actual mechanism of how these mast cell stabilizers improve SLK is unclear. Perry and colleagues showed improvement of symptoms and findings in 5 out of 5 patients with SLK for whom treatment with prednisolone acetate 1% and silver nitrate 1/2% was ineffective, utilizing cyclosporin A 0.5% 4 times a day instead. This dose was also effective in maintaining clinical improvement when used long-term twice daily. Vitamin A can reverse ocular keratinization. With this in mind, Ohashi and co-workers found vitamin A eye drops to be helpful in 10 of 12 patients with SLK. Vitamin A 1,500 IU/mL was more effective than 500 IU/mL. N-acetylcysteine 10% or 20% 3–5 times a day can be used to treat the excess mucus that is related to fi lament formation. It may help decrease the symptoms when mucus and fi laments are prominent. Bandage contact lenses may also be used when the fi laments predominate.
tiva may be sutured to the episclera with interrupted sutures or left alone. An alternative surgical approach was described by Yokoi et al. They resected the redundant conjunctival tissue adjacent to the area of conjunctival abnormality as defi ned by rose bengal staining, and successfully treated 2 of 2 eyes. Cryotherapy for the involved superior bulbar conjunctiva has been advocated for the relief of symptoms. As with the use of silver nitrate and surgical resection, however, the symptoms may recur in days to months after treatment.
COMPLICATONS Because this condition is chronic, the use of corticosteroids, which have little effect, should be avoided or at least minimized. The condition does not respond to antibiotics or antiviral agents; these also should be avoided because of their potential toxicity. Caution should be taken when evaluating ptosis in patients with SLK, to ensure that they do not actually have a pseudoptosis secondary to SLK. Ptosis surgery in such patients may cause a significant increase in symptoms. Extra precautions must be taken when treating patients who have associated decreased tear production. Close follow-up is necessary when bandage contact lenses are used, because complications from these contact lenses are more likely in patients with dry eyes. In addition, conjunctival recession or resection may not be as successful in patients who have significantly reduced tearing. Scleral melting may occur in the exposed section of the sclera after conjunctival resection in patients with severe dry eye. Management of patients with SLK who also have dry eyes should generally be more conservative.
COMMENTS As the cause of the condition is unknown and the characteristic natural history of the disease includes periods of exacerbation and remission, care must be taken in implementing the numerous therapies recommended for this condition. This is especially true because the condition can disappear without treatment. For these reasons long-term therapy with corticosteroids should be avoided in favor of less toxic approaches
395
including lubrication, ciclosporin.
punctual
occlusion
and
topical
Passons GA, Wood TO: Conjunctival resection for superior limbic keratoconjunctivitis. Ophthalmology 91:966–968, 1984.
oblique axis (pseudopterygium) has also been described as an early clinical sign. Gradually, the stroma starts to thin in a clear zone of cornea between the marginal opacities and the limbus, forming a gutter-like furrow. The furrow remains covered with epithelium and has a sloping peripheral edge and a steel central edge. Yellow-white deposits, which appear to be lipid, are seen at the edge of the deepening furrow. The paralimbal thinning often progresses across the superior cornea. It may extend into the inferior cornea or even circumferentially, but usually the interpalpebral cornea is spared. The epithelium remains intact throughout the progression of the thinning, and patients do not typically complain of pain. Patients become symptomatic as the ectasia results in against-the-rule astigmatism. In 10% to 15% of cases, severely thinned areas may perforate, either spontaneously or with minor trauma. Occasionally, patients experience pain associated with episodic inflammation that resemble conjunctivitis, episcleritis, or scleritis. This may be treated with topical steroids.
Perry HD, Doshi-Carnevale S, Donnenfeld ED, et al: Topical cyclosporin A 0.5% as a possible new treatment for superior limbic keratoconjunctivitis. Ophthalmology 110:1578–1581, 2003.
DIAGNOSIS
REFERENCES Confi no J, Brown SI: Treatment of superior limbic keratoconjunctivitis with topical cromolyn sodium. Ann Ophthalmol 19:129–131, 1987.
SECTION 19 • Cornea
Donshik PC, Collin HB, Foster CS, et al: Conjunctival resection treatment and ultrastructural histopathology of superior limbic keratoconjunctivitis. Am J Ophthalmol 85:101–110, 1978. Grutzmacher RD, Foster RS, Feiler LS: Lodoxamide tromethamine treatment for superior limbic keratoconjunctivitis. Am J Ophthalmol 120:400–402, 1995. Mondino BJ, Zaidman GW, Salamon SW: Use of pressure patching and soft contact lenses in superior limbic keratoconjunctivitis. Arch Ophthalmol 100:1932–1934, 1982. Ohashi Y, Watanabe H, Kinoshita S, et al: Vitamin A eyedrops for superior limbic keratoconjunctivitis. Am J Ophthalmol 105:523–527, 1988.
Udell IJ, Kenyon KR, Sawa M, et al: Treatment of superior limbic keratoconjunctivitis by thermocauterization of the superior bulbar conjunctiva. Ophthalmology 93:162–166, 1986.
212 TERRIEN’S MARGINAL DEGENERATION 371.48 (Furrow Dystrophy, Marginal Extasia, Peripheral Furrow Keratitis)
The typical slit lamp appearance includes peripheral corneal thinning, sparing the limbus and most often occurring superonasally and progressing circumferentially; corneal vascularization with lipid deposits at the leading edge of the gutter; and an intact epithelium (compare with Mooren’s ulcer) (Figure 212.1). There is severe against-the-rule astigmatism. Histopathology demonstrates intact epithelium with Bowman’s layer fragmentation and fibrillar degeneration of stromal collagen. Descemet breaks are seen in areas of thinning.
Clinical signs and symptoms Thomas L. Steinemann, MD Cleveland, Ohio
Ocular or periocular ●
ETIOLOGY/INCIDENCE Terrien’s marginal degeneration is an uncommon, slowly progressive thinning of the peripheral cornea. First described by Terrien in 1881 as a noninflammatory degeneration, its cause is still unknown. Subsequent reports have described a less common ‘inflammatory’ type of Terrien’s degeneration that may occur in as many as one-third of affected (usually younger) individuals. The disease is commonly bilateral, but it may be asymmetric. It occurs more often in males. Patients may become symptomatic at any age, but earlier literature has described more cases occurring in middle-aged and older patients. More recent series suggest that the disease is more common in the 20- to 40-year-old age group. It has even been described in children younger than 10 years. It is usually asymptomatic unless astigmatism develops.
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Cornea: flattening of the corneal curvature in the vertical meridian, perforation (usually after minor trauma), peripheral thinning and ectasia with an overlying epithelium, peripheral vascularization and lipid deposition, corneal hydrops, intralamellar cyst, pseudopterygium. Other: episodic inflammation resembling conjunctivitis, episcleritis, or scleritis; high astigmatism and blurred vision.
Differential diagnosis ●
Mooren’s ulcer.
COURSE/PROGNOSIS Progression of the marginal ectasia usually occurs gradually over many years. Initially, the disease process is noted superonasally, heralded by fi ne peripheral superficial vessels and punctate stromal opacities that coalesce gradually. At this stage, usually no thinning is noted, and the disease may resemble arcus senilis. An atypical pterygium occurring in an unusual
396
FIGURE 212.1. Terrien’s marginal degeneration.
TREATMENT Supportive No medical therapy is effective in preventing the progression of corneal thinning. In the early stages, supportive therapy consists of spectacle correction of astigmatic refractive errors. With the progression of astigmatism, rigid contact lenses or ‘piggyback’ soft/rigid lens systems may be necessary.
In advanced cases of Terrien’s marginal degeneration, contact lens fitting may no longer be possible. In addition, ectatic areas may become dangerously thin. At this stage, surgical repair may be indicated both to decrease visually handicapping astigmatism and to prevent the rupture of ectatic areas through tectonic reinforcement. Various surgical techniques have been suggested. One approach involves the excision of ectatic tissue, followed by suturing of the freshened edges of normal-thickness stroma. In another technique, a large eccentric penetrating keratoplasty is placed, although the increased possibility of graft rejection in such large transplants increases the chance of graft failure. An annular peripheral penetrating keratoplasty technique has also been described. Inlay lamellar crescent keratoplasty has been used to treat severe thinning or perforation. With this technique, donor lamellar tissue-stroma, Bowman’s layer, and, in some cases, epithelium-may be obtained by hand dissection from a whole eye. An alternative method involves the use of a trephine that conforms to the size and curvature of the leading edge of corneal thinning. A central donor corneal button is punched using the same size of trephine; only the peripheral cornea is retained to fill the crescent-shaped defect in the host corneal bed. A lamellar graft is anchored to one edge of the keratectomy bed and alternately, cut freehand and sutured in a stepwise fashion to fi ll the defect.
COMPLICATIONS In the majority of cases, conservative management is indicated. Because of the thinning and ectasia in more advanced cases, mild trauma can result in rupture of the cornea. Patients should therefore be instructed to avoid situations in which the eye might be traumatized. The use of protective eyewear may be warranted. Patients should be cautioned to seek attention for any abrupt change in visual status or for the development of pain in the eye. Because of the high risk of corneal perforation, surgeons should avoid excising a pseudopterygium in patients with Terrien’s degeneration. In addition, surgery for corneal ectasia should be restricted to patients in whom astigmatism is severe and disabling or if perforation occurs or is imminent.
REFERENCES Caldwell DR, Insler MS, Boutros G, et al: Primary surgical repair of severe marginal ectasia in Terrien’s degeneration. Am J Ophthalmol 97:332– 336, 1984. Goldman KN, Kaufman HE: Atypical pterygium: a clinical feature of Terrien’s marginal degeneration. Arch Ophthalmol 96:1027–1029, 1978. Kaufman HE, McDonald MB, Barron BA, Wilson SE: Color atlas of ophthalmic surgery: corneal and refractive surgery. Philadelphia, JB Lippincott, 1992:147–166. Robin JB, Sclanzlin DJ, Verity SM, et al: Peripheral corneal disorder. Surv Ophthalmol 31:1–36, 1986. Wollensak G, Spoerl E, Seiler T: Riboflavin/ultraviolet A-induced collagen cross-linking for the treatment of keratoconus. AmJ Ophthalmol. 135:620–627, 2003.
213 THYGESON’S SUPERFICIAL PUNCTATE KERATOPATHY 370.21 (Thygeson’s Superficial Punctate Keratitis)
CHAPTER 213 • Thygeson’s Superficial Punctate Keratopathy
Surgical
nique causes the collagen to thicken, increasing the cornea’s stiffness and resistance to distortion and perhaps enzymatic digestion. Although the technique was described for treatment of keratoconus, itmay be applicable to Terrien’s degeneration as well. This slowly progressive, generally noninflammatory disease can usually be managed conservatively, but patients must be followed periodically for progression of thinning, which can threaten the integrity of the globe.
Parveen K. Nagra, MD Philadelphia, Pennsylvania Thygeson’s superficial punctate keratopathy (TSPK) is a distinct clinical entity characterized by episodes of bilateral, coarse, granular, punctate epithelial opacities occurring without any ocular inflammation. Symptoms include a variable degree of ocular pain or discomfort, foreign body sensation, photophobia, and blurred vision.
ETIOLOGY/INCIDENCE The cause is unknown. Association with viral infections has been suggested, although no defi nitive causation has been found. The prolonged disease course with steroid treatment may represent an altered immune response to a slow virus infection. A dyskeratosis has been postulated because of the steroidal response and the lack of inflammation in the eye. TSPK has been associated with HLA-DR3. This keratopathy is very uncommon, affecting all races worldwide. Patients of both genders and all ages, including children, are affected.
COMMENTS Although Terrien’s degeneration is a rare disorder, it typically presents either when the patient becomes visually symptomatic because of progressive astigmatism or after recurrent episodes of ocular irritation. Recently a technique of collagen cross-linking with riboflavin and UVA light has been described in a rabbit model. This tech-
COURSE/PROGNOSIS TSPK is a chronic disease characterized by exacerbations and remissions. The lesions are transient, and the rate of recurrences is variable, although they often occur at weekly to monthly intervals. The natural history may be of eventual reso-
397
lution within 4 years. However, in patients treated with steroids, the morbidity may last decades. There are no corneal abnormalities between attacks. While the vision may be minimally affected during episodes, the long-term visual prognosis is excellent.
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Patients should have regular evaluations to assess for improvement, evaluate for complications of treatment, and taper steroids. Cyclosporin A and therapeutic soft contact lens are effective therapies to be considered initially, when difficulty arises in tapering steroids, or steroid-related complications are noted.
DIAGNOSIS SECTION 19 • Cornea
Surgical Clinical signs and symptoms ●
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Punctate, scattered, epithelial lesions, with normal epithelium between lesions. No inflammation in the conjunctiva or anterior chamber; mild corneal stromal inflammation underlying the lesions may be present. Normal corneal sensation. Bilateral or unilateral.
Laboratory findings ●
● ●
Lesions have elevated clusters of tiny gray dots, usually staining with rose bengal and fluorescein. May have a stellate appearance. Mucous fi laments are not seen. No lab tests indicated.
Differential diagnosis ● ● ● ● ●
Herpes simplex keratitis. Adenoviral keratitis. Staphylococcal keratoconjunctivitis. Keratoconjunctivitis sicca. Rosacea keratitis.
TREATMENT Medical Lubricants and topical steroids are the mainstay of treatment. Other treatments include topical cyclosporin A and therapeutic soft contact lenses. Following initiation of topical steroids, the lesions and symptoms improve rapidly. ● Fluorometholone 0.1% four times a day with slow taper over months. ● Alternatives include loteprednol 0.2%, loteprednol 0.5%, rimexolone 1%, or in advanced cases, prednisone acetate 1%.
398
Epithelial debridement results in a rapid recurrence of lesions. Resolution has been reported following photorefractive keratectomy but not laser in situ keratomileusis.
COMPLICATIONS The potential complications of steroid therapy and extendedwear contact lenses must always be borne in mind. The use of idoxuridine eyedrops in TSPK may result in subepithelial opacities.
COMMENTS TSPK is not a common or communicable condition. Because it is frequently misdiagnosed and is a periodically remitting disorder, numerous ocular drugs have been used with unmerited successes and not unexpected failures. Fortunately, there is usually no residual scarring and patients have an excellent long-term visual prognosis.
REFERENCES Darrell RW: Thygeson’s superficial punctate keratitis: Natural history and association with HLA DR3. Trans Am Ophthalmol Soc 79:486–516, 1981. Fite SW, Chodosh J: Photorefractive keratectomy for myopia in the setting of Thygeson’s superficial punctuate keratitis. Cornea 20:425–426, 2001. Goldberg DB, Schanzlin DJ, Brown SI: Management of Thygeson’s superficial punctate keratitis. Am J Ophthalmol 89:22–24, 1980. Thygeson P: Clinical and laboratory observations on superficial punctate keratitis. Am J Ophthalmol 61:1344–1349, 1966. Nagra PK, Rapuano CJ, Cohen EJ, et al. Thygeson’s superficial punctate keratitis: ten years’ experience. Ophthalmology. 111:34–37, 2004.
S ECT I O N
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Extraocular Muscles
214 A-PATTERN STRABISMUS 378.02, 378.06, 378.12, 378.16 Ann U. Stout, MD Portland, Oregon A-pattern strabismus refers to a vertically incomitant horizontal strabismus in which the horizontal separation of the visual axes becomes progressively greater as gaze shifts from up to down. The A-pattern can be associated with esotropia, where the deviation is greatest in upgaze, or with exotropia, where the deviation is greatest in downgaze. Patients with A-pattern esotropia may adopt a chin-up head posture to facilitate fusion. Patients with A-pattern exotropia may use a chin-down posture if fusion can be obtained only in upgaze.
ETIOLOGY
A-pattern esotropia without oblique dysfunction ●
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A-pattern esotropia with significant superior oblique overaction ●
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There are standard prism-cover measurements in the primary position, upgaze and downgaze. Upgaze and downgaze are measured 25 to 30 degrees from the primary position. A difference between upgaze and downgaze of more than 10 prism diopters is significant. A-pattern esotropia is more common in patients with upslanting fissures, while A-pattern exotropia is more common in patients with downslanting fissures.
TREATMENT For the clinician, determination of whether the A-pattern is due to significant superior oblique muscle overaction is imperative. In general, if a large A-pattern is present in association with superior oblique overaction, the superior oblique must be weakened to correct the pattern. Conversely, if no superior oblique overaction is present in the setting of an A-pattern, the superior oblique should not be operated on, especially if inferior oblique overaction exists.
Recess the LR bilaterally with downshift. If unilateral surgery, recess the LR with downshift, and resect the MR with upshift.
A-pattern exotropia with superior oblique overaction ●
DIAGNOSIS
Recess the MR bilaterally (or recess the MR and resect the LR unilaterally) for esotropia in the primary position. Weaken the superior oblique bilaterally (see Complications). Weakening can be by spacer placement, tenotomy, or tenectomy. A-pattern should be 25 prism diopters or more if superior oblique weakening is done to avoid overcorrection.
A-pattern exotropia without oblique dysfunction ●
The numerous possible causes proposed for A-pattern strabismus include dysfunction of any of the six extraocular muscles (oblique, horizontal and vertical recti), orbital rotation or globe rotation, connective tissue (pulley) anomalies and muscle insertion anomalies.
Recess the medial rectus muscle (MR) bilaterally with upshift. If unilateral surgery, recess the MR with upshift and resect the lateral rectus muscle (LR) with downshift.
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Recess the LR bilaterally (or recess the LR and resect the MR unilaterally) for exotropia in the primary position. Weaken the superior oblique bilaterally (see Complications). Weakening can be by spacer, tenotomy, or tenectomy. A-pattern should be 25 prism diopters or more if superior oblique weakening is done.
A-pattern exotropia with superior oblique overaction and dissociated vertical deviation ●
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This classic triad can occur as a primary strabismus entity or secondary to previous strabismus surgery, such as after MR recession for esotropia. Treat as A-pattern exotropia with superior oblique overaction, but superior rectus recession bilaterally can be added for dissociated vertical deviation.
A-pattern with craniofacial syndromes ●
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Craniofacial syndromes such as Crouzon’s syndrome are frequently associated with A-pattern (or V-pattern) strabismus. The probable cause is orbital and/or muscle insertion rotation.
399
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These syndromes frequently fail to respond to oblique weakening alone. Oblique weakening and horizontal rectus shifts may be required.
COURSE/PROGNOSIS Prognosis varies with etiology. Cases with a vascular etiology usually resolve completely, while sixth nerve palsies arising from other causes have a more guarded prognosis. A minimum of six months is given for spontaneous resolution.
COMPLICATIONS SECTION 20 • Extraocular Muscles
DIAGNOSIS ● ●
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A-pattern can be converted to V-pattern. Conversion of A-pattern to V-pattern after superior oblique weakening is less likely if inferior oblique underaction was present before surgery. Torsional diplopia can occur after superior oblique weakening. The risk is significant if the patient has high-grade fusion before surgery. Superior oblique weakening should be done judiciously if patient has measurable stereopsis before surgery. Superior oblique weakening should not be done if patient has normal stereopsis (e.g. 40 seconds arc stereo or better) because torsional diplopia may occur. Graded superior oblique weakening with spacers may reduce the risk of this compared to tenotomies or tenectomies.
REFERENCES Helveston EM: A-exotropia, alternating sursumduction and superior oblique overaction. Am J Ophthalmol 67:377–380, 1969. Urist MJ: The etiology of the so-called A and V patterns. Am J Ophthalmol 46:825, 1958. von Noorden GK: Binocular vision and ocular motility. 5th edn. St Louis, CV Mosby, 1996. Wright K: Superior oblique silicon expander for Brown syndrome and superior oblique overaction. J Pediatr Ophthalmol Strabismus 28:101–107, 1991.
215 ABDUCENS (SIXTH NERVE) PARALYSIS 378.54 Raghu Mudumbai, MD Seattle, Washington Sixth nerve palsy is a common neuro-ophthalmic disorder. Because of the long intracranial course of the sixth nerve, abducens function may be compromised by multiple etiologies. Palsies may be unilateral or bilateral. They may be treated both medically, for example with prisms or injections of botulinum toxin, and surgically, for example by recess/resect and transposition procedures.
ETIOLOGY/INCIDENCE In childhood, several etiologies – congenital, neoplasm, raised intracranial pressure, trauma, and post-infection – are common. Etiologies are similar in adult patients, but vasculopathies such as hypertension and diabetes are also significant causes. Sixth nerve palsy is a rare initial presentation of multiple sclerosis.
400
Clinical signs and symptoms Symptoms include diplopia, worse in the field of the palsy and better on the opposite side except in bilateral cases. Esotropia is maximum in the field of the palsy and decreases at near. If mild, diplopia may be resolved when the patient looks towards the side opposite the palsy. Diplopia may not be present if the eye is directed towards the nose, which can block binocularity.
Differential diagnosis Thyroid-related ophthalmopathy commonly involves the medial rectus muscle to produce a restrictive esotropia. Forced ductions or differential intraocular pressure measurements may be helpful signs. Myasthenia gravis is produced by acetylcholine receptor antibodies leading to any combination of ptosis, orbicularis weakness and extraocular muscle weakness, including isolated lateral rectus involvement. Forced generation testing reveals the weakness. Edrophonium chloride testing, the ice test and laboratory testing for acetylcholine receptor antibodies are helpful in the diagnosis. Blow-out fracture of the medial wall of the orbit can lead to entrapment of the medial rectus muscle and a restrictive esotropia. Forced ductions reveal a restriction. Duane’s syndrome (Type 1), due to malformation of the sixth nerve nucleus and abnormal innervation of the lateral rectus by the third nerve, leads to unilateral or bilateral esotropia, limited abduction, enophthalmos, and narrowing of the lid fissure on abduction. Multiple sclerosis commonly produces internuclear ophthalmoplegia, which is a lesion of the medial longitudinal fasiculus and not a sixth nerve palsy. It is distinguished by contralateral abduction nystagmus and ipsilateral adduction deficit. Sixth nerve palsy can occur in combination with other deficits leading to defi nable syndromes. Bilateral congenital sixth and and seventh nerve palsies occur in Mobius syndrome. In Gradenigo’s syndrome, inflammation of the petrous bone, most commonly from an otitis media, leads to a sixth and seventh nerve palsies. Cavernous sinus syndrome includes third, fourth, oculosympathetic, and first division trigeminal palsies. Orbital apex syndrome adds vision loss. One and a half syndrome, resulting from a lesion of the sixth nerve nucleus and the medial longitudinal fasciculus, is recognized by an ipsilateral horizontal gaze palsy and a contralateral internuclear ophthalmoplegia. Sixth nerve palsy may be the first sign of a cavernous sinus syndrome, as the nerve travels within the substance of the sinus and thus may be the first nerve affected. Other nerves affected can include the III, IV, V1, V2 and the sympathetics. Orbital apex syndrome is similar, except that it does not involve V2 and includes optic neuropathy.
TREATMENT Ocular Patients with mild palsies may compensate with a head turn toward the palsied side in order to maintain fusion. Large
Surgical Once it is clear that no more improvement will occur (6 to 12 months), surgical options can be employed. With time, the incomitant deviation becomes more comitant, a phenomenon known as spread of comitance. When there is some residual forced generation found in the lateral rectus, a horizontal recess/resect of the medial and lateral recti can be attempted. In complete sixth nerve palsies, a medial rectus recession can be combined with transposition of the superior and inferior recti to the lateral rectus muscle. Use of the adjustable suture technique can help improve outcomes. An appropriate preoperative evaluation should be carried out prior to surgery. Necessary components include measurement of the deviation and evaluation of the relative strength of the lateral and medial recti. The deviation should be measured in primary, left and right gaze. Upgaze and downgaze measurements are helpful in determining if a V or A pattern is present. Muscle tone can be measured by comparing the active forced generation of the medial and lateral recti. Estimating saccadic velocity by observation or with electro-oculography may also be beneficial to gauge the amount of sixth nerve paresis. Abduction past the midline is also helpful in judging lateral rectus function. Forced duction can provide information as to whether contracture of the medial rectus is present. In patients found to have medial rectus contraction, recession of the medial rectus should be part of the surgical plan. Maximum recession is 12 millimeters from the limbus, and additional effect can be achieved by recessing the overlying conjunctiva and Tenon’s to the original insertion. The medial rectus can be placed on an adjustable suture and its resection can be combined with a resection of the lateral rectus up to 9 millimeters. When there is minimal lateral rectus function, a transposition procedure of the vertical recti to the lateral rectus will probably be required. Transposition can either be total or by the Jensen procedure. In this procedure, the vertical recti are split and joined to adjacent halves of the lateral rectus but without disinsertion. This has the theoretical advantage of preserving anterior ciliary artery circulation to the anterior segment. There can be simultaneous medial rectus recession on an adjustable suture. Single binocular vision in primary gaze with a limited range of fusion is a reasonable goal. Patients adapt by learning to
maintain fi xation in primary gaze by head rotation, a partially successful strategy. Patients, especially those with traumatic sixth nerve palsy from head trauma, should be warned that central disruption of fusion is a possibility even with good alignment.
COMMENTS Sixth nerve palsy can result from numerous etiologies due to the long intracranial course of the nerve. Careful history taking and clinical examination supplemented by appropriate neuroimaging and laboratory testing usually leads to the correct diagnosis. While waiting for resolution, patients can be managed in the short term by patching, prism or selective use of botulinum toxin. In cases of non-resolving sixth nerve palsy, surgical improvement may be obtained with recess/resect procedures or a transposition procedure. Adjustable suture technique may also be of benefit, given the variability of recovery of lateral rectus function.
REFERENCES Ellis FD, Helveston EM: Special considerations and techniques in strabismus surgery. Int Ophthalmol Clin 16:247–254, 1976.
CHAPTER 216 • Accommodative Esotropia
palsies or bilateral involvement may lead to voluntary closing of one eye to prevent diplopia. In cases where there is a high likelihood of improvement, occlusion by fogging one lens with tape or the use of a patch is highly useful to prevent diplopia as the amount of esotropia decreases with time. In patients unlikely to improve or who have reached maximal improvement with small residual deviation, base out prism may benefit to help patients maintain fusion. It can also be placed over the non-involved eye to decrease contracture of the medial rectus on the involved side. Permanent ground in prism is limited by the weight of the glasses and optical aberrations induced by the prism. Botulinum toxin type A has been used in acute cases of sixth nerve palsy. Its effect lasts from weeks to several months. Two and a half to 5 units are injected into the antagonist medial rectus muscle (treatment is localized with the aid of an electromyographic electrode). This treatment may prevent long term contracture and aid in resolution of the deviation. It is more useful with smaller deviations of less than 30–40 prism diopters.
Hotchkiss MG, Miller NR, Clark AW, et al: Bilateral Duane’s retraction syndrome: a clinical-pathologic case report. Arch Ophthalmol 98:870– 874, 1980. Lee MS, Galetta SL, Volpe NJ, et al: Sixth nerve palsies in children. Pediatr Neurol 20:49–52, 1999 Miller NR, Newman NJ, eds: Walsh and Hoyt’s clinical neuro-ophthalmology. 6th edn. Maryland, Lippincott, Williams and Wilkins, 2004. Sanders SK, Kawasaki A, Purvin VA: Long-term prognosis in patients with vasculopathic sixth nerve palsy. Am J Ophthalmol 134:81–84, 2002.
216 ACCOMMODATIVE ESOTROPIA 378.35 Henry S. O’Halloran, MD, DOphth, FRCSI San Diego, California William Barry Lee, MD Atlanta, Georgia
INTRODUCTION Accommodative esotropia is one of the most common types of strabismus occurring in childhood. The incidence of this disorder is estimated at 0.67% to 2% in the population; however, the deviation has been found to occur as infrequently as 1 in 373 cases in some studied populations. Accommodative esotropia represents an acquired esodeviation with variable severity and intermittent onset with potential progression to a constant deviation. The disorder is most commonly hereditary in nature with some studies finding nearly 80% of affected first-or seconddegree relatives, yet no pattern of inheritance or genetic locus have been identified. Less commonly, trauma or illness may be a precipitating factor. The typical age of onset is between 6 months and 5 years, with an average age of onset at 2.5 years and reports of this disease in children as young as 3 months old.
401
COURSE/PROGNOSIS
SECTION 20 • Extraocular Muscles
The natural history of accommodative esotropia with regard to spontaneous improvement or progression to nonaccommodative esotropia remains unknown. The esodeviation usually begins as an intermittent crossing of the eyes but often progresses to a constant deviation. The consequences of this deviation can result in amblyopia. Diplopia can occur but may disappear with development of a suppression scotoma in the deviating eye. Several series have quoted a high rate of monofi xation (peripheral fusion with absence of central binocular fi xation).
CLINICAL DIAGNOSIS The diagnosis of refractive accommodative esotropia consists of uncorrected hyperopia in association with insufficient fusional divergence. The hyperopia averages 5 diopters with a range from 3 to 10 diopters and the angle of esotropia is approximately equal at near and distant fi xation. The accommodative convergence-to accommodation (AC/A) ratio is normal. Nonrefractive accommodative esotropia consists of a high AC/A ratio. The refractive error is generally low hyperopia with an average of 2 diopters, but it can range from myopia to high hyperopia. The esotropia is greater at near fi xation where greater accommodation is needed in comparison to distance fi xation targets. Partially accommodative or decompensated esotropia represents an esotropia that is partially corrected with spectacle correction or an esotropia that develops from decompensation following an initially fully corrected deviation with spectacles. This form of accommodative esotropia often occurs with delayed correction.
add that will restore normal ocular alignment at near with a maximum strength of up to 3.5 diopters of add. Bifocals are ordered in an executive style or large flat-top segment, with the top of the bifocal set high near the midpupil level. Progressive add bifocals commonly have the bifocal segment too low for a desirable effect. The authors use a rough rule of thumb that if the esotropia for near exceeds that for distance by 25 prism diopters, bifocals may be needed. Deviations of less than this amount may require a second office visit and assessment of esotropia for near using trial lenses. The timing of the reduction in hyperopic correction is somewhat controversial and varies among practitioners. The authors attempt reduction of spectacle correction on a yearly basis provided that the patient is orthophoric for near and distant fi xation, and each reduction is followed by a repeat examination at 6 weeks to ensure stable alignment with the weaker spectacle correction.
Contact lenses Contact lenses may be used for treatment of accommodative esotropia in certain conditions. ● Contact lenses can include regular or toric soft contacts, rigid gas permeable contacts, and bifocal contacts. ● Advantages include reduction of accommodative effort at near and eradication of ring scotomas and prismatic effect associated with spectacle correction. ● Disadvantages include contact lens intolerance, corneal complications such as infection, and the need for strict compliance with contact lens wear and cleaning regimens. ● All lenses should be removed on a daily basis to limit risk of infection and corneal complications.
Pharmacologic agents ●
TREATMENT Treatment of accommodative esotropia includes prevention of amblyopia with preservation of normal visual acuity, restoration of normal ocular alignment, maintenance of binocular vision and stereopsis, and striving for an emmetropic state for both eyes. Treatment with spectacle correction is often successful in maintenance of appropriate ocular alignment, but surgical correction remains necessary in an estimated 30% of cases.
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Medical
Pharmacologic agents can be used alone or in combination with glasses. Miotics work by inducing ciliary muscle contraction and reducing accommodative effort and the need for convergence. Agents used include echothiophate iodide (most frequent) and demecarium bromide, both long-acting cholinesterase inhibitors. Commonly used to replace spectacles in the summer when swimming and other activities tend to reduce the amount of time for spectacle wear. Potential side effects exist including iris cysts, conjunctival hyperemia, myopia, and prolonged anesthesia with depolarizing muscle relaxants.
Spectacle correction Spectacle correction is considered the initial treatment of choice for accommodative esotropia. The amount of correction is derived from a cycloplegic refraction with an appropriate cycloplegic agent such as cyclopentolate or atropine, and the full hyperopic correction is prescribed if a constant or intermittent esotropia is present. The ultimate aim is to provide the minimum correction that will maintain orthophoria under binocular conditions to encourage and expand the degree of fusional divergence. The correction is usually gradually decreased to an amount of correction that maintains orthophoria with a followup visit scheduled no more than 2 months after each reduction. Single vision spectacles are used for the majority of cases; however, patients with a high AC/A ratio who have esotropia at near of 10 or more diopters should use bifocal correction. Bifocal spectacle correction should use the smallest amount of
402
Surgical Despite maximal optical and pharmacologic support, some patients develop a nonrefractive component to the esotropia. Studies estimate this occurs in 13% to 48% of patients. The goal of strabismus surgery is to correct the non-accommodative component of the esotropia.
Strabismus surgery ●
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Optimal correction of amblyopia before surgical correction is recommended. Surgical correction is recommended only when, despite full refractive correction, there is a constant esotropia of more than 10 prism diopters, precluding binocular vision and stereopsis Surgical results can be improved by the use of prism adaptation in which Fresnel prisms are worn in the preoperative
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Prism Adaptation Study Research Group: Efficacy of prism adaptation in the surgical management of acquired esotropia. Arch Ophthalmol 108:1248–1256, 1990. Weakley DR, Holand DR: Effect on ongoing treatment of amblyopia on surgical outcome in esotropia. J Pediatr Ophthalmol Strabismus 34:275–278, 1997. Wilson ME, Bluestein EC, Parks MM: Binocularity in accommodative esotropia. J Pediatr Ophthalmol Strabismus 30:233–236, 1993.
217 ACQUIRED NONACCOMMODATIVE ESOTROPIA 378.00
Refractive surgery ●
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A method to restore ocular alignment without spectacle correction in purely refractive accommodative esotropia. Surgical treatment in older children and adults to correct hyperopia and hyperopic astigmatism using an excimer laser. Treatment can include up to 6 diopters of hyperopia and up to 6 diopters of astigmatism. Remains controversial in children.
AMBLYOPIA MANAGEMENT Amblyopia associated with accommodative esotropia is usually mild and is more common when the deviation becomes constant or when anisometropia exists, particularly astigmatic anisometropia. The prognosis for vision is usually good because these children frequently have some degree of fusion before the onset of their esotropia. A standard patching regimen (i.e. 1 week of full-time patching per year of age) can be an effective means of treatment in patients that do develop amblyopia. Alternatively, part-time patching or atropine penalization therapy is used to encourage the development of fusion and stereopsis. Frequent follow-up is imperative to ensure occlusion amblyopia does not develop. Part-time patching may be indicated until 10 years of age in cases where full-time patching may pose a risk of occlusion amblyopia.
COMMENTS The optimal agent for cycloplegia is the subject of perennial controversy. For children, we use a mixture of 1% cyclopentolate and phenylephrine 2.5%. Atropine is used when repeat refractions differ greatly or when repeated instillation of cyclopentolate is ineffective. We advise against the use of atropine before sleep because the signs and symptoms of atropine toxicity would not be noticed. Atropine penalization is an excellent alternative to patching for amblyopia therapy. One study has shown that success with amblyopia treatment is linked to a higher socioeconomic status of the parents or caregivers, and this should be considered before embarking on a complicated amblyopia regimen.
F. Hampton Roy, MD, FACS Little Rock, Arkansas
ETIOLOGY/INCIDENCE Acquired nonaccommodative esotropia is a convergent deviation with onset after the age of 6 months. This deviation is approximately the same in all directions of gaze. It is not significantly affected by accommodation. Because normal binocular vision often exists before the onset of this disease, the prognosis for binocular function in patients with acquired nonaccommodative esotropia is better than that for those with congenital esotropia. One eye may prefer fi xation in this condition. Amblyopia will develop if the deviation is unilateral and the onset occurs in childhood. The cause of nonaccommodative acquired esodeviation is believed to be both neurogenic and anatomic. The neurogenic or innervational cause may be excessive tonic convergence or deficient tonic divergence. Anatomic factors may be anomalous medial recti insertions. Other causes of acquired nonaccommodative esotropia include stress, organic lesions, and anisometropia. Stress-induced acquired esodeviation may be precipitated by illness and emotional factors that cause a breakdown of preciously adequate fusional divergence. Patients under stress may also undergo a spasm of the near synkinetic reflex, resulting in sustained convergence with accommodative spasm and miosis. Any monocular organic lesion, such as cataract, optic atrophy, or corneal scarring, may result in an esodeviation, especially if the onset occurs before the age of 4 years. Amblyopia secondary to an asymmetric refractive error (anisometropia) may result in a secondary esodeviation. An acutely acquired esodeviation that is worse at distance should be suspected for divergence paralysis and may indicate an early lateral rectus palsy secondary to underlying neurologic disease, such as pontine tumor or head trauma. Acquired esotropia may rarely be cyclic in pattern, such as occurring every other day.
CHAPTER 217 • Acquired Nonaccommodative Esotropia
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period and the strength of the prisms increased as the esotropia increases or until fusion is demonstrated. Surgical correction is then performed for the fully adapted esotropia angle. The surgical option of choice is bilateral medical rectus recessions, with monocular recess-resect procedures performed only when severe amblyopia is present. Several studies have shown a high degree of binocularity after surgery in up to 70% of patients. The amount of surgery to perform is controversial. Some surgeons recommend correcting the residual esotropia at distance while others use an augmented approach, correcting the average of the near deviation with and without correction.
TREATMENT Ocular
REFERENCES
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Lambert SR: Accommodative esotropia. Ophth Clin North Am 14:425– 432, 2001. Ludwig IH, Imberman SP, Thompson HW, Parks MM: Long-term study of accommodative esotropia. Trans Am Ophthalmol Soc 101:155–161, 2003.
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Occlusion therapy is accomplished best at an early age (younger than 7 years). As a general rule, the schedule for rechecking patients after patching should be 1 week per year of life to ensure that amblyopia does not develop in the patched eye. Eyeglasses should be prescribed for significant refractive errors that may disrupt fusion. Asymmetric refractive errors
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are treated with eyeglasses or contact lenses to reduce image disparity. Organic lesions that occlude vision, such as congenital cataracts, are treated as early as possible, followed by aggressive amblyopia therapy. Orthoptics may be indicated to eliminate sensory adaptations, such as suppression or abnormal retinal correspondence, that may have developed secondary to the esodeviation.
SECTION 20 • Extraocular Muscles
Surgical ●
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Strabismus surgery is indicated for any significant esodeviation that is still present after the completion of amblyopia therapy, refractive lens correction, and orthoptics. The surgery may be unilateral or bilateral depending on the surgeon’s preference and whether the eyes freely alternate. Unilateral surgery consists of weakening (recession) of the medial rectus muscle and strengthening (resection) of the lateral rectus muscle. Some surgeons prefer performing unilateral surgery on patients who have a strong preference for fi xation in one eye. In these cases, surgery is usually performed on the nonfi xating eye. Bilateral medial rectus recessions are performed depending on the surgeon’s preference or if the eyes are freely alternating. Small deviations (less than 15 prism diopters) may require a recession of only one medial rectus muscle. Deviations between 15 and 45 prism diopters usually require surgery on two muscles (recession-resection on one eye or bilateral recessions). Deviations of more than 45 prism diopters may require surgery on three or four muscles depending on the severity of the angle; however, some surgeons prefer to operate on only two muscles during the initial operation regardless of the size of the deviation. The use of adjustable sutures in strabismus surgery in older children and adults has significantly improved the postoperative result; this can be done with topical anesthesia at the time of surgery or within 1 day after the surgical procedure. Botulinum toxin type A (Oculinum) injection into an ocular muscle creates an intentional temporary paralysis that may result in improved alignment in carefully selected cases. Prism adaptation therapy, in which prisms are used before surgery, has been found to improve the results of surgery for acquired esotropia. Fresnel prisms are placed on eyeglasses until the angle of deviation is neutralized or fusion is obtained. This ‘adapted’ angle becomes the goal for a surgical correction and may reduce the reoperation rate. No surgery should be attempted unless preoperative measurements are accurate and consistent. At least three sets of measurements should be taken before strabismus surgery is undertaken.
Early detection ●
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404
Early detection of strabismus and amblyopia is vitally important. Children treated at an early age for amblyopia respond better to occlusion therapy than do older children. If amblyopia cannot be reversed, the prognosis for alignment of the eyes and fusion is significantly worsened. In patients requiring surgery, fusional results are significantly better in children who underwent surgery at an early age. In addition, obvious psychologic sequelae have been noted in children with late surgical treatment of a longstanding and cosmetically displeasing esodeviation.
COMMENTS The treatment of acquired nonaccommodative esotropia requires a specific management plan to achieve the best possible fusional results. This plan should include a thorough ophthalmologic and strabismic evaluation, early amblyopia detection and therapy, orthoptics, and, if necessary, strabismus surgery.
REFERENCES Abel LA, Troost BT: Acquired cyclic esotropia in an adult eye. Am J Ophthalmol 91:805–806, 1981. Biglan AW, Burnstine RA, Rogers GL, Saunders RA: Management of strabismus with botulinum A toxin. Ophthalmology 96:935–943, 1989. Dankner SR, Mash AJ, Jampolsky A: Intentional surgical overcorrection of acquired esotropia. Arch Ophthalmol 96:1848–1852, 1978. Delisle P, Strasfeld M, Pelletier D: The prism adaptation test in the preoperative evaluation of esodeviations. Can J Ophthalmol 23:208–212, 1988. Eino D, Kraft SP: Postoperative drifts after adjustable suture strabismus surgery. Can J Ophthalmol 32:163–169, 1997. Helveston EM: Atlas of strabismus surgery. 4th edn. St Louis, CV Mosby, 1992. Jampolsky A: Current techniques of adjustable strabismus surgery. Am J Ophthalmol 88:406–418, 1979. Kani K: Magnetic resonance imaging measurements of extraocular musclepath shift and posterior eyeball prolapse from the muscle cone in acquired estropia with high myopia. Am J Ophthalmol 136:482–489, 2003. Kitzmann AS, Mohney BG, Diehl NN: Short-term motor and sensory outcomes in acquired nonaccommodative estropia of childhood. Strabismus. 13:109–114, 2005. Kraft SP, Enzenauer RW, Weston B: Stability of the postoperative alignment in adjustable-suture strabismus surgery. J Pediatr Ophthalmol 28:206– 211, 1991. Metz HS: Acquired cyclic esotropia in an adult eye. Am J Ophthalmol 91:804–805, 1981. Parks MM, Mitchel PR, Wheeler MB: Ocular motility and strabismus. In: Duane TD, ed: Clinical ophthalmology. Philadelphia, JB Lippincott, 1990. Prism Adaptation Study Research Group: Efficacy of prism adaptation in the surgical management of acquired esotropia. Arch Ophthalmol 108:148–156, 1990. Repka MX, Wentworth D: Predictors of prism response during prism adaptation. J Pediatr Ophthalmol Strabismus 28:202–205, 1991. Rosenbaum AL: The current use of botulinum toxin therapy in strabismus. Arch Ophthalmol 114:213–214, 1996. Scott AB: Botulinum toxin injection into extraocular muscle as an alternative to strabismus surgery. J Pediatr Ophthalmol Strabismus 17:21–25, 1980. von Noorden GK: Binocular vision and ocular motility: theory and management of strabismus. 5th edn. St Louis, CV Mosby, 1995. Ward JB, Niffenegger AS, Lavin CW, et al: The use of propofol and mivacurium anesthetic technique for the immediate postoperative adjustment of sutures in strabismus surgery. Ophthalmology 102:122– 128, 1998.
218 BASIC AND INTERMITTENT EXOTROPIA 378.10, 378.23 Michael P. Clarke, FRCS, FRCOphth Newcastle Upon Tyne, England Sarah R. Richardson, DBO Newcastle Upon Tyne, England
Exotropia describes a divergent misalignment of the visual axes. Exotropia is less common than esotropia and is more common in the middle east, subequatorial Africa and other places with high levels of sunlight. The overall prevalence of exo deviations has been reported to be 0.4%. Exotropias are associated with ophthalmic and neuro-ophthalmic disease, particularly when these cause visual field defects, and with craniofacial syndromes. Classification of exotropias is hampered by a lack of understanding of the biological basis of the condition, but it has proved useful to subdivide primary exotropias based on a proposed etiology of convergence and divergence mechanisms (Box 218.1). Constant exotropias include those of infantile onset, decompensated exophorias and decompensated intermittent exotropias. Intermittent Exotropia, X(T) for short, describes an intermittent divergent misalignment of the visual axes which is initially observed when fi xation is at distance rather than near, and during periods of fatigue and inattention. In intermittent distance exotropia (the so called divergence excess type) the distance deviation is 15 or more prism dioptres greater than the near deviation. In some apparent intermittent distance exotropias (the so called simulated divergence excess pattern) the near deviation increases to within 15 dioptres of the distance deviation when accommodative or convergence mechanisms are suspended. When the near deviation is within 15 dioptres of the distance deviation without the use of special tests, it is called basic, or non specific, exotropia. Intermittent
BOX 218.1 – Classification of exotropia 1. Primary Constant a. Infantile b. Decompensated Intermittent c. Decompensated Exophoria Intermittent a. Convergence Insufficiency (i) Primary (ii) Undercorrected myopia b. Distance (i) True (ii) Simulated High AC/A Normal AC/A c. Basic 2. Secondary (Sensory) 3. Consecutive Spontaneous Postoperative
COURSE/PROGNOSIS X(T) has traditionally been held to be a progressive condition, with increasing frequency of the observed distance deviation leading to an intermittent and ultimately constant deviation at near. This may then lead to loss of binocular function and stereopsis at near. This view has recently been challenged, and it now seems evident that many if not most cases of X(T) are non progressive.
DIAGNOSIS Clinical signs and symptoms Onset is usually before the age of 5 years, and may occur as early as the first year of life. Children with X(T) usually present to medical attention because of the observed deviation. An alternative manifestation of the condition is monocular eye closure which occurs in bright illumination. Why this occurs is unknown; it is not thought to be a means of avoiding diplopia. Children with X(T) do not generally complain of diplopia, although they sometimes notice panoramic vision. How diplopia is avoided is unclear, as the size of the misalignment varies constantly as the viewing distance changes. The prevailing theory is that suppression of the whole of the temporal hemifield of one eye occurs under binocular conditions, when the deviation is present. Despite the presence of suppression, amblyopia is rare, as the eyes typically remain aligned fi xing at near, usually with good binocular functions and stereopsis at this viewing distance. The significance of the functional disability associated with a distance divergent deviation is also obscure. The physiological value of ocular alignment, binocular functions and stereopsis when viewing distant targets is not known. Defects of stereopsis at distance have been described in association with X(T) but it is not known if these are associated with visual disability or if they are a useful indication for treatment. Binocular visual acuity may be reduced at distance if accommodation is exerted to control the distance deviation, inducing myopia. Convergence and motor fusional amplitudes may also be affected.
CHAPTER 218 • Basic and Intermittent Exotropia
ETIOLOGY/INCIDENCE
exotropia can evolve into basic exotropia if the near deviation increases as the condition deteriorates. This chapter is concerned with basic and intermittent exotropia excluding convergence insufficiency.
Differential diagnosis The differential diagnosis includes infantile exotropia, decompensated exophoria, near exotropia (convergence insufficiency), sensory and consecutive exotropia. Patients with infantile, sensory and consecutive exotropia generally have poor binocular functions, except in the case of sensory exotropia caused by visual field loss. Infantile exotropias may cause dissociated strabismus complex. Near exotropia has a larger angle at near fi xation and good binocular functions can be demonstrated for distance fi xation. It is characterized by equal vision, poor binocular convergence, normal sensory fusion and poor positive motor fusion. Patients who have decompensated exophoria present with symptoms of blurred vision, diplopia and asthenopia. Normal binocular single vision is demonstrable but
405
often with a reduced positive fusion amplitude and reduced convergence.
TABLE 218.1 – The Newcastle control score for intermittent exotropia HOME CONTROL
TREATMENT/COMPLICATIONS
SECTION 20 • Extraocular Muscles
The clinical management of X(T) presents a dilemma. Conservative treatments are often ineffective and surgery may be required. However, surgical overcorrection is common, especially in younger patients, and while there may be a good cosmetic outcome despite a small overcorrection, this will be at the expense of impaired near binocular functions. Treatment is usually requested because of the cosmetic appearance of the observed deviation. The treating physician may be concerned about the possibility of deteriorating binocular function if the strabismus is not treated. Usually the child has straight eyes and good binocular vision for near fi xation, for example when reading. As the fi xation distance increases, there is an increasing tendency for the eyes to diverge.
Squint/monocular eye closure never noticed
1
Squint/monocular eye closure seen occasionally for distance
2
Squint/monocular eye closure seen frequently for distance
3
Squint/monocular eye closure seen for distance & also near
CLINIC CONTROL NEAR 0
Manifest only after cover test and resumes fusion without need for blink or refixation
1
Blink or refixate to control after CT
2
Manifest spontaneously or with any form of fusion disruption without recovery
Ocular Conservative treatments for X(T) include minus lenses, prisms, orthoptic exercises and occlusion. They may be used in isolation, or as a temporising measure in young children vulnerable to the effects of surgical overcorrection. Significant refractive errors, even hyperopic ones, should be corrected in intermittent exotropia as this will sharpen the retinal images and improve fusion. Minus lenses are sometimes used to stimulate accommodative convergence. They may be particularly helpful in patients with high AC/A ratios. Small angle X(T) (measuring 20 prism dioptres) are usually treated, especially if there is evidence of deterioration. Traditionally, surgical treatment has been recommended for such squints if they are observed by carers to be present at least 50% of waking hours and are poorly controlled on clinical examination. Measurements of home and clinic control of the strabismus can be combined into a score which can be used to monitor progression and as a guide to surgery (Table 218.1). While there are clear functional indications for surgery in those children who have deteriorating control of the deviation for near fi xation, accompanied by deteriorating near stereoacuity, for most children with X(T) measuring >20 prism dioptres at distance fi xation, the criteria for, and the benefits of, surgical intervention are poorly defined. Most interventions, however, particularly surgery, affect the alignment of the visual axes at near almost as much as at distance. This leads to the common postoperative problem of overcorrection of the deviation at near, with potential loss of stereopsis and amblyopia, especially in younger children. Surgical conservatism, however, leads to undercorrection with a recurrence of the deviation, thought to be because of persistence of suppression mechanisms. The desired result is said to be a small initial postoperative overcorrection in order that the suppression mechanisms are disrupted, followed by a drift to alignment of the eyes over days to weeks. It is well recognized that achieving such results is difficult and unpredictable, partly because of the influence of convergence mechanisms. Surgical tables for exotropia tend not to distinguish between different types of exotropia. The figures used by the authors,
406
0 score
CLINIC CONTROL DISTANCE 0
Manifest only after cover test and resumes fusion without need for blink or refixation
1
Blink or refixate to control after CT
2
Manifest spontaneously or with any form of fusion disruption without recovery
NCS TOTAL (HOME + CLINIC NEAR + CLINIC DISTANCE) =
TABLE 218.2 – Suggested surgical numbers for intermittent exotropia Angle
LR Recession
MR Resection
Bilat LR Recession
20
4
3
4.5
25
5
4
5
30
5.5
4
6
35
6.5
4.5
6.5
40
7
4.5
7
50
8
4.5
8
who aim at a small initial postoperative overcorrection, are shown in Table 218.2. These should be used as a guide and individual surgeons should audit their results and alter practice accordingly. The surgical procedure should probably be bilateral lateral rectus recessions for true divergence excess exotropias, but for simulated divergence excess and basic intermittent exotropias, recess resect procedures have been demonstrated to be equally effective. Bilateral lateral rectus recessions allow easy access to the inferior oblique muscles, should there be significant oblique overaction. While many cases of intermittent exotropia have a small V pattern, oblique surgery is usually not necessary unless there is significant oblique overaction.
REFERENCES Abroms A, Mohney B, Rush D, et al: Timely surgery in intermittent and constant exotropia for superior sensory outcome. Am J Ophthalmol 131:111–116, 2001. Campos E, Cipolli C: Binocularity and photophobia in intermittent exotropia. Percept Mot Skills 74:1168–1170, 1992. Cooper EL, Layman IA: The management of intermittent exotropia: a comparison of the results of surgical and nonsurgical treatment. American Orthoptic Journal 27:61–67, 1977. Graham P: Epidemiology of strabismus. Brit J Ophthalmol 58:224–231, 1974. Haggerty H, Richardson S, Clarke M, et al: The Newcastle Control Score: a new method of grading the severity of intermittent exotropia. Brit J Ophthalmol 88(2):233–235, 2004.
219 BROWN’S SYNDROME 378.61 Raghu Mudumbai, MD Seattle, Washington Christopher N. Singh, MD Seattle, Washington Peter Youssef, MD Seattle, Washington
ETIOLOGY Brown’s syndrome results from a mechanical restriction of the superior oblique tendon that may be congenital or acquired. Symptoms may include head tilt or diplopia. It may be transitory or permanent.
DIAGNOSIS Clinical signs and symptoms Brown’s syndrome is characterized by limitation of elevation in adduction. Limited elevation may also be present to a lesser degree in abduction. Other common clinical signs include V pattern exotropia and widening of the palpebral fissure width on attempted elevation in adduction. Most patients will be orthophoric in primary gaze. However, some patients have a hypotropia with a compensatory chin-up position or face turn. Amblyopia may be present.
Congenital Brown’s original description postulated the defect to be congenital shortening of the sheath around the reflected tendon of the superior oblique muscle. Further investigation indicates that a congenitally tight superior oblique tendon is usually responsible.
Acquired Brown’s syndrome is a secondary effect of many disorders. Iatrogenic surgical causes include procedures performed on or near the superior oblique tendon, including tuck and scleral buckling procedures and placement of glaucoma drainage devices in the superonasal quadrant. Patients with juvenile or adult rheumatoid arthritis may present with a trochleitis leading to an acquired Brown’s syndrome that may be painful. Trauma with damage to the trochlea, hemorrhage into the superior oblique sheath, or entrapment of the inferior oblique muscle may also be responsible.
CHAPTER 219 • Brown’s Syndrome
Ideally, X(T) surgery should result in a reduction or a complete correction of the tendency for the eyes to diverge however reported cure rates are poor, averaging 51%, with one report quoting a figure as low as 31%. There is some evidence of long term loss of effect following surgery, leading to recurrent exotropia. Although successful surgery improves binocular alignment and distance stereoacuity, permanent overcorrection with total loss of BSV for distance and near is a possible complication, particularly for children operated on under the age of 5. This may lead to amblyopia in vulnerable age groups, which is not usually a feature of X(T). Reported rates of this complication vary from 0 to 40%. Patients with high AC/A ratios may be particularly susceptible to this complication. The optimal timing of surgery is controversial: early surgery (on patients 4 years of age or younger) is advocated by some authors who believe that it produces a higher cure rate. However it is associated with a higher rate of complications, including permanent surgical over-correction with loss of BSV. Advocates of late surgery argue that better functional results are obtainable and the risk of permanent over-correction and amblyopia is greatly reduced. If overcorrection does occur, then unless there is gross mechanical limitation a period of observation is usually appropriate. Prisms or hypermetropic correction may be of benefit. Botulinum injection into the medial rectus muscle is often effective but further surgery is necessary in some cases.
TREATMENT Patients who are asymptomatic and maintain fusion in primary gaze without head turn can be managed without surgery. These patients often learn to avoid the adduction in upgaze in the involved eye that leads to diplopia.
Surgical The goals of surgery in Brown’s syndrome must be clearly identified in order to ensure reasonable expectations. When a horizontal deviation is also present or when binocular vision is absent, successful realignment may be more difficult. Intervention is reasonable if there is a hypotropia in primary gaze, if there is abnormal head position, or if diplopia is present. It is also important to note whether the Brown’s syndrome is congenital and stable, or acquired and may change. Surgical options include superior oblique tenotomy and tenectomy, simultaneous surgery on the superior and inferior oblique muscles, and the use of silicon expanders. The goal of surgery is to establish binocular function when there is hypotropia in primary gaze. Both tenotomy and tenonectomy of the superior oblique are effective in releasing the restriction to elevation. However, both procedures lead to superior oblique palsy in the majority of cases. Therefore, concomitant weakening of the ipsilateral inferior oblique muscle has also been recommended. A newer approach relieves the restriction of the superior oblique tendon by means of an expander. Techniques have included a suture bridge between the cut ends of the tendon after a tenotomy, but Wright introduced the use of a no. 240 silicone retinal band as a more ideal spacer. With these procedures, great care must be taken to preserve the floor of the
407
tendon capsule. If the floor is compromised, scarring between the sclera and the silicone may result, leading to a recurrence of the restriction of the superior oblique tendon. The benefits of tissue expanders include less surgery, greater range of movement and reversibility.
congenital esotropia is unknown and is thought to be multifactorial. Controversy exists as to whether the primary abnormality is in the motor control system or the binocular sensory system.
COURSE/PROGNOSIS COMPLICATIONS SECTION 20 • Extraocular Muscles
Possible complications from surgery should always be kept in mind. These include overaction of the inferior oblique muscle from superior oblique tenotomy, which may require addition surgery on the inferior oblique muscle. The superior oblique must be completely isolated in order to prevent inadequate surgery from missed fibers. Ptosis of the upper lid may ensue. Careful dissection that stays close to the superior rectus muscle must be performed to prevent orbital fat from herniating and scarring which can lead to ocular restriction.
DIAGNOSIS Clinical signs and symptoms
COMMENTS Brown’s syndrome is defined by limitation, both actively and passively, of upgaze in adduction. The congenital form is secondary to a tight superior oblique tendon. Acquired Brown’s syndrome may occur in after an operation that disrupts the function of the superior oblique, as well as from inflammation of the superior oblique tendon as in rheumatoid arthritis. If the patient is asymptomatic, observation is appropriate. If diplopia, hypotropia in primary position, or a head turn is present, multiple surgical options are available. They include superior oblique weakening procedures with or without concomitant ipsilateral inferior oblique weakening procedures and the use of spacers to increase the length of the superior oblique tendon.
REFERENCES Moore AT, Morin JD: Bilateral acquired inflammatory Brown’s syndrome. J Pediatr Ophthalmol Strabismus 22:26, 1985. Sprunger DT, von Noorden GK, Helveston EM: Surgical results in Brown syndrome. J Pediatr Ophthalmol Strabismus 28:164–167, 1991. von Noorden GK, Oliver P: Superior oblique tenectomy in Brown’s syndrome. Ophthalmology 89:303, 1982. Wilson ME, Eustis HS Jr, Parks MM: Brown’s syndrome. Surv Ophthalmol 34:153–72, 1989 Wright KW: Results of the superior oblique elongation procedure for severe Brown’s syndrome. Trans Am Ophthalmol Soc 98:41–48, 2000
220 CONGENITAL ESOTROPIA 743.69 (Infantile Esotropia) Laura B. Enyedi, MD Durham, North Carolina Edward G. Buckley, MD Durham, North Carolina
ETIOLOGY/INCIDENCE Congenital esotropia is the most common childhood strabismus, occurring in approximately 1% of children. The cause of
408
These children are at a significant risk for developing amblyopia, although some patients maintain equal vision by alternating fi xation between the two eyes (cross-fi xation). Early diagnosis and treatment can result in the restoration of normal function and a delay in treatment beyond 2 years of age is associated with poor binocularity, absent fusion and no stereopsis.
The crossing is rarely present at birth, but usually develops by the end of the third month and is present, by defi nition, by age 6 months. The esotropia is large angle (30 to 70 prism diopters), constant and does not resolve with hyperopic correction. Although most patients are otherwise healthy, some have associated ocular or neurologic abnormalities that require further evaluation. There is no clear inheritance pattern, but congenital esotropia can be familial and infants with a strong family history should be observed closely for the development of strabismus. Prematurity and perinatal hypoxia are also risk factors for congenital esotropia.
Laboratory findings The opththalmologic examination includes visual function testing by fi xation preference, fi x and follow response and/or preferential looking tests. The deviation is measured using prisms and alternate cover testing if possible. Krimsky or Hirschberg testing may also be used to estimate the angle of esotropia. Duction testing may reveal mild limitations of abduction and versions are examined for A- or V- patterns, indicating overaction of superior or inferior oblique muscles, respectively. Dissociated vertical deviation is commonly associated with congenital esotropia, but is not often seen on presentation. Cycloplegic refraction may reveal significant refractive errors, especially hyperopia, which may need to be corrected with spectacles prior to surgical alignment. Complete anterior segment and fundus examinations are critical to rule out structural abnormalities (e.g. cataract, coloboma, optic nerve hypoplasia, or retinoblastoma) which may cause sensory esotropia.
Differential diagnosis The differential diagnosis of congenital esotropia includes common disorders such as psedoesotropia and accommodative esotropia as well as less common disorders such as Duane’s syndrome, nystagmus blockage syndrome, sixth nerve palsy and Mobius syndrome. Sensory esotropia secondary to loss of vision from ocular or optic nerve disease must always be considered. Pseudoesotropia in which epicanthal folds and a wide nasal bridge create the false appearance of esotropia is frequently mistaken for true esotropia. Accommodative esotropia in which there is high hyperopia and / or a high ratio of accommodative convergence to accommodation usually presents in toddlers, but may also be seen in infants. The distinguishing
TABLE 220.1 – Amounts of surgical correction Bimedial Rectus Muscle Recessions (mm)
Medial Rectus Muscle Recession (mm)
and
Lateral Rectus Muscle Resection* (mm)
20
4.0
4.0
4.5
25
4.5
5.0
5.0
30
5.0
5.0
6.0
35
5.5
6.0
6.5
40
6.0
6.0
7.0
50
6.5
6.0
8.0
>50
Three-muscle surgery
*For bilateral lateral rectus resection, perform the unilateral amount listed for each eye.
features of Duane’s syndrome include decreased abduction and palpebral fissure narrowing on attempted adduction. Esotropia in nystagmus blockage syndrome occurs because nystagmus is dampened by keeping the fi xating eye in adduction and worsens on attempted abduction. Sixth nerve palsies present with incomitant esotropia, decreased or absent abduction and possibly other neurologic findings. Möbius syndrome is the combination of sixth nerve palsy with facial weakness, tongue abnormalities and mental retardation.
perforation can occur as the muscle is reattached to the globe and can rarely cause retinal detachment or endopthalmitis. Ocular perforations may benefit from intraoperative retinal cryotherapy or laser to prevent rhegmatogenous retinal detachment. Postoperative infection of the surgical site is heralded by increased redness, chemosis and purulent discharge while increased pain and decreased vision signal may indicate a more serious intraocular infection (endopthalmitis). Careful conjunctival closure is critical to avoid conjunctival cysts, conjunctival scarring and dellen formation.
CHAPTER 220 • Congenital Esotropia
Deviation (Prism Diopters)
TREATMENT COMMENTS Initial treatment focuses on correcting significant refractive errors and treating amblyopia. Hyperopia greater than 3 diopters should be corrected to rule out any accommodative component to the esotropia. Phospholine iodide drops may be helpful for variable deviations or deviations which are much greater at near than at distance. Definitive treatment is generally surgical and may include medial rectus recession and/or lateral rectus resection on one or both eyes. A- or V-patterns and dissociated vertical deviations, if present, may be surgically addressed simultaneously with horizontal muscle surgery. The sooner the eyes are restored to proper alignment, the better the chance for a stable long-term result (Table 220.1).
Close follow-up of patients after surgery is crucial because these children are still at a high risk for amblyopia and often develop other motility abnormalities such as dissociated vertical deviation and overacting inferior oblique muscles. Approximately 30% will eventually require additional surgery. Treatment results are influenced by the age at surgery, the duration of misalignment and the development of associated motility disturbances, but the majority of patients have cosmetically aligned eyes, peripheral fusion and good visual function.
REFERENCES COMPLICATIONS The most common complications from strabismus surgery are under or over corrections. A marked under or over correction, especially with a duction lag, may indicate a slipped or lost muscle. Overcorrection may be treated with prisms if the exotropia is less than 10 prism diopters. If the patient has 12 or more prism diopters of exotropia 6 to 8 weeks postoperatively, surgical repair may be necessary. Residual esotropia may be treated with spectacles if there are 2 or more diopters of hyperopia. Ten or less prism diopters of residual esotropia may be amenable to prism therapy. If the patient has 12 or more prism diopters of esotropia 6 to 8 weeks postoperatively, additional strabismus surgery may be necessary. An inadvertent ocular
Helveston EM: The 19th Annual Frank Costenbader Lecture: the origins of congenital esotropia. J Pediatr Ophthalmol Strabismus 30:215, 1993. Ing MR: The timing of surgical alignment for congenital (infantile) esotropia. J Pediatr Ophthalmol Strabismus 36:61–68, 1999. Kushner BJ, Morton GV: A randomized comparison of surgical procedures for infantile esotropia. Am J Ophthalmol 98:50, 1984. Parks MM: The monofi xation syndrome. Trans Am Ophthalmol Soc 67:609, 1969. Pediatric Eye Disease Investigator Group. The clinical spectrum of earlyonset esotropia: experience of the congenital esotropia observational study. Am J Ophthalmol 133:102–108, 2002. von Noorden GK: The XLIV Edward Jackson Memorial Lecture: A reassessment of infantile esotropia. Am J Ophthalmol 105:1–10, 1988.
409
221 CONGENITAL FIBROSIS OF THE EXTRAOCULAR MUSCLES 378.62 Forrest James Ellis, MD Cleveland, Ohio
SECTION 20 • Extraocular Muscles
ETIOLOGY/INCIDENCE Congenital fibrosis of the extraocular muscles (CFEOM) is a rare condition characterized by hypoplasia and fibrosis of the extraocular muscles. CFEOM falls in the group of syndromes characterized by congenital limitation of eye and eyelid movements (congenital cranial nerve dysinnervation syndromes). Primary neurodevelopmental abnormalities of cranial nerve nuclei occur in CFEOM type 2, while genetic defects affecting axonal transport of molecules necessary for normal extraocular muscle function and development occur in CFEOM type 1. Possible prenatal orbital penetration has been reported in isolated unilateral cases. Three genetic subtypes of CFEOM have been identified. ● CFEOM 1 is characterized by congenital bilateral ptosis with the eyes fi xed in a position of 20 to 30 degrees infraduction. Affected individuals often adopt a chin-lift posture. Passive movement of the globes is significantly limited with forced ductions. Volitional eye movements are often limited, and convergent or divergent movements may occur with attempted vertical or horizontal gaze. Amblyopia and refractive errors are common. Penetrance appears to be complete with striking phenotypic homogeneity. The CFEOM 1 genetic locus is in the centromeric region of human chromosome 12. There is a missense mutation in an axonal transport kinesin motor protein encoded by KIF21A. The absence of the superior division of the oculomotor nerve and its corresponding midbrain a motor neurons have been described at necropsy. ● CFEOM 2 is an autosomal recessive disorder. Affected individuals have bilateral congenital ptosis and restricted extraocular movements with the eyes positioned in abduction. The locus for CFEOM 2 has been mapped to chromosome 11q13 and involves the ARIX gene. This is believed to result in hypoplasia of the III and IV cranial nerve nuclei. ● CFEOM 3 is an autosomal dominant disorder with incomplete penetrance and variable expressivity. Affected individuals demonstrate ptosis with the eyes fi xed in abduction and infraduction. This disorder is clinically and genetically distinct from CFEOM 1 and CFEOM 2. The gene maps to markers on chromosome 16q.
During examination at the time of a surgical intervention, the extraocular muscles are typically thin and inelastic. Histopathologic examination of the affected extraocular muscles has demonstrated a reduced number of muscle fibers and increased fibrous tissue. CFEOM is typically an isolated phenomenon, although cases in association with other systemic disorders have been reported. Whereas most other myopathies are progressive, CFEOM is congenital and non-progressive. ● Congenital nonprogressive condition. ● Typically bilateral, but may be unilateral. ● Limitation of ocular motility, typically with ptosis of the eyelid. ● Positive forced duction. ● Synkinetic eye movements in some cases. ● A reduced number of muscle fibers and increased fibrous tissue on histopathologic examination of the affected extraocular muscles. ● Examination of family members for similar abnormalities of ocular motility. ● Family history for autosomal dominant inheritance common. ● Radiologic imaging possibly helpful in the evaluation of selected patients.
Differential diagnosis ● ● ● ● ● ● ● ●
● ● ●
Duane’s syndrome. Double elevator palsy. Brown’s syndrome. Progressive external ophthalmoplegia. Progressive dystrophic ophthalmoplegia. Möbius syndrome. Myasthenia gravis. Congenital or acquired paralysis of the extraocular muscles. Congenital or acquired ptosis. Extraocular muscle entrapment (orbital fracture). Thyroid-related strabismus.
TREATMENT Systemic ● ●
Genetic counseling. Physical and neurologic examinations.
Ocular ● ● ●
Correction of refractive error. Occlusion or penalization therapy for amblyopia. Lubrication for exposure keratopathy.
Surgical
COURSE/PROGNOSIS ● ● ●
Nonprogressive. No spontaneous improvement. Vision affected by amblyopia.
●
●
● ●
DIAGNOSIS Clinical signs and symptoms Clinical findings vary from bilateral generalized fibrosis to fibrosis of only a single extraocular muscle. The ophthalmic findings are present at birth and are typically nonprogressive.
410
Goal of achieving a functional position of the eyes and eyelids; horizontal and vertical binocular alignment with the eyes in a position of slight infraduction. Large rectus muscle recessions typically required and preferred to rectus muscle resections. Conjunctival recessions augment rectus muscle surgery. Frontalis suspension procedures typically required for ptosis repair.
REFERENCES Crawford JS: Congenital fibrosis syndrome. Can J Ophthalmol 5:331–336, 1970.
Engle EC, Goumnerov BC, McKeown CA, et al: Oculomotor nerve and muscle abnormalities in congenital fibrosis of the extraocular muscles. Ann Neurol 41:314–325, 1997.
●
Engle EC, Kunkel LM, Sprecht LA, Beggs AH: Mapping a gene for congenital fibrosis of the extraocular muscles to the centromeric region of chromosome 12. Nat Genet 7:69–73, 1994. Hertle RW, Katowitz JA, Young TL, et al: Congenital unilateral fibrosis, blepharoptosis, and enophthalmos syndrome. Ophthalmology 99:347– 355, 1992.
222 CONVERGENCE INSUFFICIENCY 378.83
●
Stephen P. Christiansen, MD Minneapolis, Minnesota
ETIOLOGY/INCIDENCE Convergence insufficiency is a common ocular motility disturbance characterized by an exophoria or intermittent exotropia that is greatest at near fi xation. It is one of the most common ocular motility causes of asthenopia. Convergence insufficiency is caused by poor fusional convergence at near fi xation.
CHAPTER 222 • Convergence Insufficiency
Traboulsi El, Jaafar M, Kattan HM, Parks MM: Congenital fibrosis of the extraocular muscles: Report of 24 cases illustrating the clinical spectrum and surgical management. Am Orthop J 43:45–53, 1993.
the bifocal may be sufficient to make the patient symptomatic. Convergence insufficiency associated with accommodative insufficiency. Patients with combined convergence and accommodative insufficiency are usually more symptomatic than those with convergence insufficiency alone. However, symptoms alone are not sufficient to distinguish between these two entities, and all patients who present with convergence insufficiency should have accommodative amplitudes checked since satisfactory treatment will depend on a correct diagnosis. Anticholinergic drugs, closed head trauma, and viral encephalopathies should be considered in the pathogenesis of this disorder. In addition to treating the convergence weakness, plus lenses should be prescribed for reading in these patients. Convergence paralysis. In this condition, the patient is able to adduct the eyes, but cannot converge, and has constant diplopia at near. This is usually a result of significant closed head trauma, but can also result from a lesion in the midbrain, toxic encephalopathy, or from encephalitis. It may or may not be associated with accommodative insufficiency. Base-in Fresnel prisms in the reading add of the bifocals or ground-in prisms in a separate pair of reading glasses may be useful in restoring binocularity at near in these patients.
TREATMENT Medical/orthoptics ●
COURSE/PROGNOSIS Patients typically present in their teens or early adulthood and complain of gradually worsening eyestrain, periocular headache, blurred vision after brief periods of reading, and sometimes crossed diplopia with near work. It is not unusual for the patient to squint one eye while reading to relieve the blurring or diplopia. Few, if any, symptoms are present at distance fi xation. Symptoms are aggravated by illness, fatigue, anxiety, and prolonged near work. Untreated, the exophoria at near may break down to a poorly controlled intermittent exotropia. In most cases, convergence insufficiency is very amenable to orthoptic treatment.
●
●
DIAGNOSIS
Near point of convergence exercises. An accommodative target such as the point of a pencil (hence, pencil push-ups) is placed remote to the patient’s near point of convergence and gradually brought toward the tip of the nose with the patient converging to avoid diplopia. Just before there is a break in fusion, the patient holds fi xation on the target for ten seconds. The ‘push-up’ is repeated ten times, two to four times a day until he is able to hold fi xation to the tip of the nose. The exercises can be tapered and then used on an as-needed basis when the patient notices a recurrence of symptoms. Other forms of convergence training. Base-out prism reading, and stereogram cards may also be used by the orthoptist to improve fusional convergence. Base-in prisms for near only. These prisms can be ground into a separate pair of reading glasses or Fresnel membrane prisms can be fitted over the reading segment of the patient’s bifocals.
Clinical signs and symptoms ●
●
● ● ●
Remote near point of convergence. Patients are unable to maintain fi xation on a fusional target as it is brought up to the tip of their nose. Significant exophoria or intermittent exotropia at near. More rarely, patients will be orthophoric or even exhibit a small degree of esophoria at near. However, all will have a remote near point of convergence. Small to non-existent exophoria at distance. May have reduced stereo-acuity at near. Normal near point of accommodation.
Differential diagnosis ● ●
Uncorrected high hypermetropia or myopia. Early presbyopia. When bifocals are worn for the fi rst time, the decrease in accommodative convergence afforded by
Surgical ●
The decision to proceed with surgery should be made with caution, and only after all orthoptic efforts have failed. Bilateral medial rectus resections are usually the most effective operation for this condition. However, the patient should be warned about the possibility of uncrossed diplopia at distance fi xation after surgery. This typically resolves within one to three months post-operatively. The exophoria at near usually recurs after several years although most patients remain asymptomatic.
REFERENCES Brown B: The convergence insufficiency masquerade. Am Orthoptic J 40:94–97, 1990.
411
Hermann JS: Surgical therapy for convergence insufficiency. J Ped Ophthalmol 18:28, 1981.
DIAGNOSIS
Nemet P, Stolovitch C: Biased resection of the medial recti: a new surgical approach to convergence insufficiency. Binoc Vis 5:213, 1990.
Clinical signs and symptoms ●
Phillips PH, Fray KJ, Brodsky MC: Intermittent exotropia increasing with near fi xation: a ‘soft’ sign of neurological disease. Br J Ophthalmol 89:1120–1122, 2005.
SECTION 20 • Extraocular Muscles
Von Noorden GK, Campos EC: Binocular vision and ocular motility — theory and management of strabismus. 6th edn. St Louis, Mosby, 2002. ●
●
223 DISSOCIATED VERTICAL DEVIATION 378.9 (Dissociated Strabismus Complex, Alternating Sursumduction, Dissociated Vertical Divergence, Double-Dissociated Hypertropia, Occlusion Hypertropia, Dissociated Torsional Deviation, Dissociated Horizontal Deviation) Richard J. Olson, MD Iowa City, Iowa Ronald V. Keech, MD Iowa City, Iowa
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ETIOLOGY/INCIDENCE Dissociated vertical deviation (DVD) is an ocular misalignment characterized by elevation, abduction, and excyclotorsion. In most cases, the vertical deviation is the primary manifestation. Rarely, a dissociated horizontal deviation (DHD) is the predominant or only apparent feature. DVD is usually comitant and bilateral but asymmetric. It may present as an intermittent or constant tropia or as a phoria that occurs only when fi xation is disrupted. The ocular movements associated with DVD are slow and variable compared with nondissociated horizontal or vertical deviations. Most patients with DVD have sensory suppression and do not have diplopia or visual confusion. DVD is almost always associated with infantile strabismus. The incidence of DVD in infantile esotropia is as high as 90%, though it is usually not apparent during the first year. DVD is often accompanied by a head tilt, which can be either toward or away from the eye with DVD. Inferior oblique overaction and latent nystagmus are also common. Innervational, muscular and sensory abnormalities have all been considered, but the cause is unknown. Recent theories include Guyton’s proposal that DVD is the result of damping a cyclovertical latent nystagmus, Brodsky’s proposal that it is the result of a usually unexpressed dorsal light reflex, and van Rijn’s proposal that it is related to asymmetry of vertical phorias also found in normals. DVD is closely linked to subnormal fusion. It is not clear whether the lack of fusion causes the deviation or whether both conditions occur as a result of another abnormality.
412
The detection and measurement of DVD can be difficult because it is often superimposed on a nondissociated horizontal or vertical deviation. Dissociated deviations should be considered when the deviation is slow to develop or variable with cover testing, especially when associated with the onset of strabismus in infancy. DVD may be distinguished from other vertical strabismus by the lack of a corresponding hypodeviation of the contralateral eye on alternate-cover testing. DHD may be distinguished from other horizontal strabismus by the lack of a corresponding exodeviation of the contralateral eye on alternate-cover testing. Determining the size of the DVD can aid surgical planning. If an eye has dense amblyopia, a prism light reflex test (Krimsky’s test) may be used. If the visual acuity in the affected eye is good, the DVD can be measured by a modification of the prism cover test. Increasing amounts of basedown prism are placed in front of the DVD eye until no further downward movement of that eye is seen with alternate cover testing. A hypodeviation will be induced in the contralateral eye by the test and can be ignored. To assess a horizontal dissociated deviation, the same procedure is performed with base-in prism over the DHD eye until no further inward movement of that eye is seen. Movement of the contralateral eye with this test can be ignored. For a combined dissociated and nondissociated vertical deviation, measure the nondissociated component by adding base-up prism over the non-DVD eye until the hypodeviation is neutralized during the alternate-cover test. The next step is to measure the vertical deviation as previously described for a dissociated deviation. The actual dissociated deviation measurement is the difference between the two steps.
Differential diagnosis ●
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Inferior oblique overaction associated with infantile esotropia is commonly confused with DVD. The V-pattern strabismus and incomitant vertical deviation found on lateral gazes are not usually present with a pure DVD. Depending on the underlying strabismus condition, DHD can be confused with an intermittent exotropia, a variable angle esodeviation, or a secondary deviation after strabismus surgery.
TREATMENT Ocular ●
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The correction of any ocular abnormalities that limit binocular vision may improve a coexisting DVD. This may include occlusion for amblyopia, glasses or surgery for horizontal strabismus, or orthoptics for heterophorias. If the vision in each eye is nearly equal and the DVD is smallest in the fi xing eye, then causing a fi xation switch can be helpful, either by patching or by overcorrecting or undercorrecting a refractive error with glasses or contact lenses.
Surgical ●
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Residual DVD after large superior rectus recession may benefit from a small (5 mm or less) resection of the inferior rectus muscle. Recently, nasal myectomy of the inferior oblique muscle has been advocated if the inferior oblique muscle has previously been recessed and anteriorized. Other surgical approaches reported in the literature include posterior fi xation of the superior rectus muscle with or without recession, botulinum toxin type A injection into the superior rectus muscle, weakening of both the superior rectus and inferior oblique muscles, graded resection with anteriorization of the inferior oblique and weakening of all four oblique muscles ● DHD may be treated with lateral rectus muscle recession of 3 to 8 mm on the affected side (or ipsilateral side).
REFERENCES Brodsky MC: Dissociated vertical divergence: a righting reflex gone wrong. Arch Ophthalmol 117:1216, 1999. Burke JP, Scott WE, Kutschke PJ: Anterior transposition of the inferior oblique muscle for dissociated vertical deviation. Ophthalmology 100:245, 1993. Guyton DL: Dissociated vertical deviation: etiology, mechanism, and associated phenomena. Costenbader Lecture. J Aapos 4:131, 2000. Schwartz T, Scott WE: Unilateral superior rectus recession for the treatment of dissociated vertical deviation. J Pediatr Ophthalmol Strabismus 28:219, 1991.
224 DUANE’S RETRACTION SYNDROME 378.71 (Stilling–Turk–Duane Syndrome, or Duane’s Syndrome) Shawn Goodman, MD Lake Oswego, Oregon
ETIOLOGY/INCIDENCE COMPLICATIONS Although uncommon, complications from surgery for DVD include limitation of elevation (especially with the inferior oblique muscle recession with anteriorization technique) overcorrection, abnormal torsion, changes in eyelid position, and secondary overaction of the contralateral inferior oblique muscle.
COMMENTS ●
Anteriorization of the inferior oblique muscle changes the muscle action from elevation to depression. Its neurovascular bundle may tether the globe causing the anti-elevation syndrome with a larger hypertropia in the contralateral eye. Many surgeons avoid unilateral inferior oblique anteriorization in part because of this complication.
It can be difficult to determine whether surgery should be performed on one or both eyes. Limiting surgery to the worst eye is effective when the patient rarely fi xates with that eye. However, should the operated eye take up fi xation after unilateral surgery, a large vertical deviation will result in the opposite eye. Under these circumstances, bilateral surgery may be a better choice. ● When bilateral DVDs are very asymmetric, even if bilateral surgery is performed asymmetrically, the eye with the larger DVD may be significantly undercorrected. DVD is a common companion of early-onset strabismus, and involves elevation, abduction and excyclotorsion. Its cause is still debated. Most dissociated deviations are latent or of small magnitude and do not require treatment. Treatment is indicated when the appearance of the ocular misalignment or the resulting visual symptoms are unacceptable to the patient. Complete elimination of the deviation is difficult, especially when there is bilateral involvement.
CHAPTER 224 • Duane’s Retraction Syndrome
The most commonly used procedure for DVD is a superior rectus muscle recession of 5 to 16 mm from the insertion. Recession and anterior displacement of the inferior oblique muscle near the temporal pole of inferior rectus muscle is another common procedure for DVD. Some surgeons recommend this surgery for isolated DVD, however, most experts prefer this approach when the DVD is associated with concomitant inferior oblique muscle overaction.
Duane’s retraction syndrome (DRS) is a congenital, incomitant ocular motility disorder characterized by abnormal function of the lateral rectus muscle in the affected eye, together with retraction of the globe and narrowing of the palpebral fissure on attempted adduction. Generally, the lateral rectus does not abduct the eye, but instead contracts at the same time as the medial rectus on adduction. It is this simultaneous cocontraction of the medial and lateral rectus muscles on attempted adduction that causes the retraction of the globe and narrowing of the palpebral fissure when the eye is adducted. In the primary position the ocular alignment is most commonly esotropic, but the syndrome can be present with no ocular deviation in the primary position and a minority of patients with DRS may be exotropic in primary position. EMG testing finds reduced electrical activity of the lateral rectus muscle on abduction and simultaneous electrical activity of the medial and lateral recti on adduction. Head turns to maintain binocularity are common. Marked upward or downward deviations of the eye in adduction may be seen. DRS is most commonly unilateral, but can be bilateral. For unknown reasons, it affects the left eye more frequently (approximately 60% incidence), and approximately 60% of patients with DRS are female. There is occasionally familial inheritance, but most cases are sporadic. DRS is believed to be due to maldevelopment or congenital absence of the sixth nerve nucleus, so that the lateral rectus muscle is instead abnormally innervated by branches of the third nerve. In the minority of patients with DRS and good abduction, it may be that the sixth nerve arrives in the orbit to innervate the lateral rectus only after branches of the third nerve have already done so. The maldevelopment or injury to developing structures probably occurs between the 4th and 8th weeks of embryogenesis, when the cranial nerves and extraocular muscles are forming. This timing also coincides with other defects in embryogenesis that can be associated with the occurrence of Duane syndrome in a minority of patients. The clinical result of this maldevelopment of the abducens nerve is a
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SECTION 20 • Extraocular Muscles
spectrum of innervational abnormalities, with varying degrees of lateral rectus muscle paresis and aberrant innervation by the oculomotor nerve. Secondary fibrosis of non-innervated portions of the lateral rectus muscle may develop, further limiting adduction, as well as contributing to the upshoots and downshoots in adduction that are frequently seen. This has been referred to as a ‘leash effect’ of the tight lateral rectus muscle. A less common explanation for upshoots and downshoots is the suggestion that oculomotor branches that innervate the superior or inferior rectus muscle are contributing innervation to the lateral rectus muscle, while the oculomotor subnucleus to the medial rectus is then also contributing to vertical rectus innervation. Thus, when the eye is adducting, a vertical rectus is stimulated to contract as well, leading to an upshoot or downshoot of the eye in adduction. This latter explanation does not account for the fact that vertical rectus recessions do not successfully treat upshoots or downshoots. Rarely the medial rectus may have subnormally-developed innervation, resulting in non-innervated and fibrotic areas in the medial rectus muscle also. The medial rectus is frequently described at surgery as being tight or fibrotic, though this may also be a secondary change due to the lack of opposing normal lateral rectus function. DRS is present in 1–4% of strabismus patients. There are a variety of clinical findings in patients with DRS, generally divided into 3 types. The clinical spectrum across these types results from the variability of innervation of the affected lateral rectus muscle. That is, the balance of subnormal sixth nerve innervation, abnormal third nerve innervation and fibrosis in noninnervated portions of the lateral rectus muscle determines the abnormalities in ocular movements seen.
adduction together with narrowing of the palpebral fissure on adduction. The following classification system is commonly used:
COURSE/PROGNOSIS
FIGURE 224.1. Type I Duane’s, left eye, in adduction. Note narrowed palpebral fissure on the left.
Many patients with DRS are able to adopt a head turn to maintain binocularity, and do so. In esotropic Type I DRS, the head turn is usually towards the affected eye, to utilize the affected eye in adduction. In exotropic Type II DRS, the head turn is usually toward the normal side, to use the affected eye in abduction. For the most part, the deviation is stable, but one study documented a progression of the findings in many patients with DRS during the fi rst 6 years of life. Limitation of abduction and narrowing of the palpebral fissure were seen fi rst, with upshoot and downshoot on adduction appearing later. Marked retraction associated with enopthalmos in the primary position has been observed to be more common in adults than in children, suggesting that this finding can also be progressive over time.
Type I Type I represents 70–85% of patients with DRS. It is characterized by marked to moderate limitation of abduction of the affected eye (Figure 224.3) and relatively normal adduction (Figure 224.1). There is retraction of the globe and narrowing of the palpebral fissure in adduction, due to simultaneous contraction of the medial and lateral recti (both innervated by the third cranial nerve). On attempted abduction, impulses coming from the third cranial nerve subnucleus that normally subserves the medial rectus are inhibited, and the medial rectus and lateral rectus muscles of the Duane’s eye relax. This allows the globe to move forward and the palpebral fissure to widen on attempted abduction. A generally small angle of esotropia is present in the primary position (Figure 224.2). Larger angles of esotropia are occasionally seen, and exotropia occurs in about 5% of patients with type I DRS. Upshoot or downshoot of the eye in adduction may be present.
FIGURE 224.2. Type I Duane’s, left eye, esotropia in primary position.
DIAGNOSIS Even though the abnormal innervations in the orbit that cause DRS occur early in embryonic life, DRS can be difficult to diagnose in a very young child. The child with binocularity will often avoid gazing in the direction of ocular misalignment, and parents will often report the abnormality as being present in the normal eye, since there is an appearance of marked overaction of the normally functioning eye if the child does look in the direction of the limitation in the affected eye. The diagnosis of DRS can usually be made on the testing of versions. The examiner must look for limited abduction or
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FIGURE 224.3. Type I Duane’s, left eye, limited abduction.
Type II
Type III One to fi fteen percent of patients with DRS have type III. This type has been defined as limitation of both adduction and abduction, but type III is electrophysiologically identical to a type I with severe cocontraction. Retraction of the globe on attempted adduction is present. There may be little deviation in the primary position. The above classification system is simplistic, and in approaching an individual patient the clinician must make detailed observations regarding anomalous head position, deviation in primary position, evidence of severity of co-contraction including globe retraction and overshoots, and possible bilaterality. Further motility evaluation of the patient with DRS includes the following: The degree of face turn can be measured by having the patient fi xate on a distant target (letters or a movie) and by holding a pocket laser pointer above the patient’s head, aligning the pointer with the center of the forehead anteriorly and the vertex of the posterior surface of the head posteriorly. Trigonometry reveals that at 20 feet, 21 inches to the side of fi xation equals 5 degrees, 42 inches equals 10 degrees, and so on. Assessing the location and size of the patient’s single binocular field helps in defi ning the need for treatment in patients with DRS. Watching the child with DRS as he or she is reading or looking at pictures in the book can be a valuable diagnostic test. For instance, a child with a large exotropia in downgaze may have little face turn in the primary position, but will hold the book up directly in front of the eyes instead of down in the usual reading position. The severity of cocontraction can be estimated by examining the degree of slowing of adduction saccadic velocities and, more practically, by recording the following parameters: ● Exodeviation in gaze opposite the eye with DRS (DRS eye in adduction) more than 3 prism diopters; ● Palpebral fissure width narrowing of 1.5 mm or more as the eye with DRS moves from the primary position (straight ahead) to full adduction; ● Near point of convergence remote beyond 6 cm; ● Upshoot or downshoot of the eye with DRS moving into adduction as the normal eye is directed into abduction and elevation or depression.
Differential diagnosis In the majority patients with DRS, there is no other abnormality. Perhaps as many as 30% of patients with the sporadic form of DRS may have other congenital abnormalities, which can include skeletal, auricular, ocular and neural findings. Ocular anomalies, such as iris dysplasia, heterochromia, crocodile tears and morning-glory syndrome have been reported with DRS. Systemic abnormalities such as Goldenhar syndrome,
Klippel–Feil syndrome, cleft palate, spina bifida, radial dysplasia, renal dysplasia, Okihiro syndrome, and deafness have all been associated with DRS. As in DRS, an abduction deficit is also seen in sixth nerve palsy, but this only rarely occurs on a congenital basis. In complete sixth nerve palsy the resulting esotropia in primary position is large. In contrast, the esotropia in DRS, when present, is usually a small angle. Additionally, DRS has the characteristic narrowing of the palpebral fissure in adduction, a finding which is not present in sixth nerve palsy. Although unnecessary in most cases to establish the diagnosis of DRS, saccadic velocities may be measured as a defi nitive diagnostic test. In DRS, both the adduction and the abduction saccadic velocities are slowed; in sixth cranial nerve palsies, only the abduction saccadic velocities are slower than normal. Moebius syndrome has bilateral abducens palsy, but includes facial diplegia, a feature not present in DRS. It is also extremely rare.
TREATMENT Patients with DRS need to be evaluated for refractive errors, particularly anisometropia and hyperopia. These can contribute to amblyopia and occasionally to accommodative esotropia and need to be treated prior to any surgical intervention. The majority of DRS patients have unilateral Type 1, and these children generally maintain good binocular function and stereopsis, possibly with a head turn. For these patients any contemplated surgery is best delayed until age 5–6 or older, to avoid disrupting normal binocular development. Indications for surgery may include anomalous head posture, strabismus in primary gaze, significant upshoot or downshoot in adduction, and cosmetically significant palpebral fissure narrowing in adduction. Surgeon and patient need to be aware of the necessarily limited goals of strabismus surgery in DRS, and that no surgery will normalize absent abduction, for instance. In planning surgery, the lateral rectus function must be carefully analyzed, looking at the degree of anomalous innervation, and also carefully looking for the presence of any normal abducens function. Forceps force testing can be helpful to further distinguish the active, anomalous and restrictive forces in the affected eye. In a cooperative awake patient, active force generation (the examiner observes or palpates that the eye can actively abduct) and forced augmentation testing (the examiner determines whether the eye can be brought further into abduction with forceps than the patient can voluntarily move it, distinguishing restriction from paralysis), assist in determining the best surgical procedure for the patient. Under topical surgical anesthesia in a difficult management case, a patient can be asked to look in certain directions after selected muscles have been detached, to assist in predicting the results.
CHAPTER 224 • Duane’s Retraction Syndrome
Type II DRS comprises approximately 7% of patients. Adduction is severely limited, and there is narrowing of the palpebral fissure on adduction. Abduction is good. Exotropia usually exists in the primary position. In patients with the rare type II DRS, the sixth cranial nerve is normal and is present, but presumably it arrived at the orbit so late in embryogenesis that the anatomic adaptations (incorrect innervations) associated with type I DRS already occurred by the time the sixth cranial nerve penetrated and began to innervate the lateral rectus muscle. Thus, even though the medial rectus is normally innervated, the co-contraction of the lateral rectus markedly limits adduction.
Surgical Resection of the involved lateral rectus is generally not recommended, as resection intensifies the anomalous actions of the lateral rectus such as worsening globe retraction, while not improving abduction. For Type 1 DRS (absent abduction, esotropia in primary position, and a head turn towards the affected side to fuse with the affected eye in adduction): ● The most commonly performed surgery is a medial rectus muscle recession of the affected eye. This usually reduces
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SECTION 20 • Extraocular Muscles
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the head turn, but will not improve abduction beyond the midline. A large recession may reduce the binocular field by limiting adduction in the affected eye, particularly if there is significant lateral rectus co-contraction on adduction. A better alternative may be asymmetric medial rectus recessions, recessing the medial rectus of the unaffected eye more than that of the eye with DRS. This will better correct the esotropia in primary, and produce a ‘fi xation duress’ in the unaffected fellow eye. This latter reduces the likelihood of recurrent contracture of the medial rectus in the involved eye. Caveat: if the lateral rectus has some normal abduction function, a large recession of the unaffected medial rectus may cause a large exotropia in the DRS eye, due to Hering’s law. Transposition of all or of the lateral 1/2 of the superior and inferior recti temporally, with or without posterior fi xation sutures (Foster modification) has also been advocated. Transposition of the lateral half of the vertical muscles is done to preserve anterior segment circulation if the medial rectus muscle has been or will also be recessed.
For DRS with exotropia: Recession of the lateral rectus on the involved side may be performed for a small exotropia (less than 25 diopters). ● With a large exotropia, a large lateral rectus recession must be performed in the involved eye. Often a lateral rectus recession in the uninvolved eye is also recommended. ● Caveat: recessing the normal lateral rectus may, by Hering’s law, increase stimulation to the medial rectus in the affected eye, and thus to the anomalously-acting lateral rectus in the DRS eye, increasing co-contraction not only in adduction but in primary position. ● Adding a resection of the medial rectus (i.e. a recess/resect procedure) in the affected eye for exotropic DRS is controversial. It will improve alignment but make the abduction deficit more noticeable. Medial rectus resection can also exacerbate retraction of the globe in cases with significant co-contraction.
For A and V patterns: ● The lateral rectus muscles may be transposed downward with the recession for an exotropia with an A pattern. ● The medial rectus muscles may be transposed downward together with recession for a V pattern esotropia.
COMPLICATIONS ●
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For retraction of the globe: ● Recessing both the medial and lateral rectus muscles in the affected eye is helpful. This may need to be combined with a medial rectus recession in the uninvolved eye if esotropia is present pre-operatively. For upshoots and downshoots seen in the DRS eye in adduction: ● Recessing the lateral rectus muscle 7–12 mm is effective in reducing this feature of co-contraction of the lateral rectus muscle (less recession is required in a more fibrotic muscle, more recession is required in a non-fibrotic muscle). ● Alternatively, a posterior fi xation suture on the lateral rectus muscle can be used to reduce upshoots and downshoots. ● Y-splitting of the lateral rectus muscle (longitudinally splitting the muscle and vertically transposing the superior half superiorly and the inferior half inferiorly so that they are spread wider apart than the width of the original insertion), usually with a small recession, also improves upshoots and downshoots, and can be combined with a medial rectus recession for esotropic DRS. ● Surgery on the vertical rectus muscles is not effective in treating upshoots or downshoots.
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Large medial rectus muscle recession in the involved DRS eye, especially in the face of preoperative limitation of adduction, can markedly compromise adduction and produce a postoperative exotropia. New vertical deviations may be induced by lateral transposition of the vertical rectus muscles. Transposing the vertical rectus muscles laterally can exacerbate the unwanted actions of a severely anomalous lateral rectus such as worsening the signs of co-contraction. Anterior segment ischemia may occur when the vertical rectus muscles are transposed laterally at the same time as the medial rectus muscle is recessed. The risk of this may be reduced by transposing only the lateral halves of the vertical muscles (preserving the medial vessel in the unoperated medial half of each vertical muscle), or by performing the medial rectus recession as a separate procedure 4–6 months after the transposition. Misdiagnosis of DRS as a sixth cranial nerve palsy and subsequent large recession/resection of the horizontal rectus muscles of the eye with DRS can result in a disastrous overcorrection with exotropia in the primary position, newly induced hypertropias, intractable diplopia, and, in some cases, abduction of the eye with DRS on attempted adduction (‘the splits’).
REFERENCES Barbe ME, Scott WE, Kutschke PJ: A simplified approach to the treatment of Duane’s syndrome. Br J Ophthalmol 88:131–138, 2004. Hotchkiss MG, Muller NR, Clark AW, et al: Bilateral Duane’s syndrome: a clinicopathologic case report. Arch Ophthalmol 98:870–874, 1980. Huber A: Electrophysiology of the retraction syndromes. Br J Ophthalmol 98:870–874, 1980. Isenberg S, Urist MJ: Clinical observations in 101 consecutive patients with Duane’s retraction syndrome. Am J Ophthalmol 84:419–425, 1977. Jampolsky A: Duane Syndrome. In: Rosenbaum A, Santiago AP, eds: Clinical strabismus management. Philadelphia, WB Saunders, 1999: 325–346. MacDonald AL, Crawford JS, Smith DR: Duane’s retraction syndrome: an evaluation of the sensory status. Can J Ophthalmol 9:458–462, 1974. Metz HS, Scott AB, Scott WE: Horizontal saccadic velocities in Duane’s syndrome. Am J Ophthalmol 80:901–906, 1975. Mims JL III: Duane’s retraction syndrome in Fraunfelder and Roy (Eds), Current Ocular Therapy 5th edn, 1999. Mims JL III: Choice of surgery for Duane’s retraction syndrome. In: van Heuren WAJ, Zwaan JT, eds: Decision making in ophthalmology. St Louis, CV Mosby, 1998:112. O’Malley ER, Helveston EM, Ellis FD: Duane’s retraction syndrome-plus. J Pediatr Ophthalmol Strabismus 19:161–165, 1982. Rosenbaum AL: The efficacy of rectus muscle transposition surgery in esotropic Duane syndrome and VI nerve palsy. Costenbader Lecture. J AAPOS 8:409–419, 2004. Saunders RA, Wilson ME, Bluestein EC, Sinatra RB: Surgery on the normal eye in Duane retraction syndrome. J Pediatr Ophthalmol Strabismus 31:162–169, 1994.
Differential diagnosis
225 ESOTROPIA: HIGH ACCOMMODATIVE CONVERGENCE-TOACCOMMODATION RATIO 378.35
The ratio of accommodative convergence (AC) to accommodation (A) [AC/A] is a measure of responsiveness of convergence for each diopter of accommodation.
ETIOLOGY/INCIDENCE A high AC/A ratio is characterized by excessive accommodative convergence for the amount of accommodation required to focus clearly at a certain distance. Depending on available fusional divergence mechanisms, the excessive accommodative convergence results in esophoria or intermittent or constant esotropia. A high AC/A ratio occurs in as many as 50% of childhood esotropes.
COURSE/PROGNOSIS
TREATMENT The goal of treatment is to achieve alignment at both distance and near, to less than 8 PD of esotropia. This allows peripheral fusion, and expansion of fusional amplitudes.
Ocular Single-vision lens
The risk of deterioration of esotropia after successful alignment with glasses is greater in patients with a high AC/A ratio than is the risk of esotropia associated with high hyperopia alone.
DIAGNOSIS Clinical signs and symptoms A high AC/A ratio may develop at any age, but it usually occurs between the ages of 1 and 7 years, when the reading demand increases. It is especially common in students. Asthenopic symptoms, which are common, include eyestrain and headache. Diplopia at near is reported occasionally. Clinically, the esodeviation at near exceeds distance deviation. A high AC/A ratio may develop in hyperopic, myopic, and emmetropic patients. Amblyopia is usually not severe, unless there is concomitant anisometropic hyperopia.
The full cycloplegic correction must be tried if the patient is young enough to tolerate the full prescription (usually younger than 5–7 years); otherwise, the maximum tolerated manifest hyperopic refraction is prescribed initially. This plus correction is pushed higher, to as close to cycloplegic refraction as possible, to control residual esodeviation before prescribing bifocals. When moderate hyperopia is corrected, both distance and near deviations are decreased. This may reduce the near deviation to esophoria or infrequent intermittent esotropia with few or no symptoms. In patients older than 10 years who have nonrefractive esotropia with high AC/A, monovision contact lenses may be effective in reducing near-angle esodeviation. This method compromises stereoacuity and may be accompanied by asthenopia. If there is little or no hyperopia or if single-vision correction is unsuccessful, bifocals, miotics, or both may be required.
CHAPTER 225 • Esotropia: High Accommodative Convergence-to-Accommodation Ratio
Alvina Pauline Dy Santiago, MD Metro-Manila, Philippines Arthur L. Rosenbaum, MD Los Angeles, California
Nonaccommodative convergence excess refers to a condition in which patients are orthotropic or have a small-angle esotropia at distance and in whom esotropia at near exceeds distance deviation by at least 15 prism diopters. The esodeviation at near does not respond to additional spherical plus lenses, which contrasts with patients with a true high AC/A ratio. The AC/A ratio is low or normal when measured using the gradient method. In these patients, tonic convergence is suspected to cause increased esotropia at near. Undercorrected hyperopia in patients who did not receive adequate cycloplegia prior to determination of refractive error may present clinically with esotropia at near that exceeds distance deviation despite wearing the correction. Repeat cycloplegic refraction is warranted and may uncover more hyperopia than previously discovered. The best agent for cycloplegic refraction in patients with esotropia is atropine. Prolonged discomfort with atropine has prompted some ophthalmologists to use intermediate agents such as cyclopentolate that may not uncover full hyperopia.
Bifocals
Laboratory findings In evaluating the patient with the high AC/A, perform coveruncover testing with the full refractive error corrected. Use an accommodative target with sufficient detail to eliminate the variability of accommodation. Near measurements should be taken in primary position. Be careful not to confuse high AC/A with an increased esotropia in downgaze or the reading position that may be due to a V-pattern. The methods of determining the AC/A ratio include the heterophoria method, the gradient method, and the fi xation disparity method. The details of computations are discussed more thoroughly elsewhere. In most clinical citations, esodeviation at near that exceeds distance deviation by at least 10PD may be considered to have a high AC/A ratio. Caution should be exercised, however, in labeling patients with a high AC/A when no actual computation has been performed.
Prescribe bifocals only when evidence of fusion at distance (less than 10PD) can be demonstrated; the goal of bifocals is to create the same fusional situation at near. Ensure that the full cycloplegic refraction is worn and has remained unchanged before considering the use of bifocals in these situations. This has to be verified with repeat determination of cycloplegic refraction, preferably using atropine. Use only the amount of bifocal power that is required to control the near deviation (abolish the esotropia at near or convert it to a small esophoria). Bifocal power varies between +1.50 and +3.00 diopters. In children younger than 7 years, prescribe executive or D-type lenses with a segment height that bisects the pupil to ensure the use of the bifocals at near. In adults and older children, the bifocal height may be lowered to the level of the lower lid. Fresnel membrane (add-on) prisms may be used as bifocal trials to determine effectivity and power requirements; a few days may be required
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to judge the effect. Periodically reduce the strength of the bifocals gradually (increments of +0.75 to +1.00D) if possible, especially in patients older than 12, with the ultimate goal of eliminating the segment. There is a risk of dependency on bifocals and of prolonged hypoaccommodation. In some cases, the use of bifocals may not improve sensory fusion. Orthoptics should be used to build fusional divergence amplitudes, especially if the correction with glasses is only partially successful. Experience with rigid gas permeable bifocal lenses has shown conflicting results in controlling both the distance and near esodeviations. At best, these provide an alternative for patients who prefer not to use bifocals Progressive-type lenses or no-line bifocals may not achieve the desired result.
Medical Miotics are infrequently used because of their variable efficacy and limited indications. The ideal patient is an infant or a young child who does not have significant hyperopia but has esotropia at near only and resists wearing bifocal glasses. They are used only when there is a possibility of fusion if the near deviation is improved. These are best tolerated by young esotropic patients with a high AC/A ratio. Commonly, an anticholinesterase is administered at bedtime to reduce accommodative spasm. Echothiophate iodide (phospholine iodide) 0.03% to 0.125% daily and isofluorophate (Floropyl) ointment 0.025% every other day are some of the agents used. The need for innervationally-produced cholinesterase in the ciliary body is reduced by these agents, thereby decreasing the required accommodative effort, and lowering accommodative convergence. Side effects include pupillary constriction and accommodative spasm that limit the clinical usefulness in older children and adults. Iris tags or cysts may develop with prolonged use, although they are rarely large enough to warrant discontinuing the medication. They are minimized by the concomitant use of 2.5% phenylephrine eyedrops and are reversible with cessation of treatment. Lenticular changes, retinal detachment, and precipitation of angle closure attack occur rarely, and are observed more often in adults than in children. Systemic side effects include nausea, vomiting, abdominal cramps, micturition, and diarrhea. There is a known drug interaction with succinylcholine and other agents used as muscle relaxants in patients undergoing general anesthesia. See Complications for information on the use of succinylcholine and other agents.
Surgical Surgery may be required when optical means, miotics, and orthoptics fail to relieve the symptoms. An improved outcome may be achieved with prism adaptation. The application of neutralizing membrane prisms to glasses allows rudimentary fusion to develop and improves outcome Indications for surgery include restoration of fusion at near (fusion at distance should be demonstrated), motor alignment, and the possibility of increasing binocular visual field at near. Surgical procedures for near esodeviation of more than 10 PD and distance deviation that is orthotropic or within monofi xational esotropic range (fewer than 8 PD) include bilateral medial rectus muscle recession. This procedure yields the most predictable resultsDespite surgery for near deviation, the distance deviation remains controlled by (at least peripheral) fusional mechanisms. Other procedures described include a medial
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rectus recession up to 8 mm; and posterior fi xation suture (fadenoperation) performed alone or combined with recession of both medial rectus muscles. There is a higher risk of overcorrection if the fadenoperation is combined with a recession. The posterior fi xation suture placed on the medial rectus pulley may be as effective as a posterior fi xation suture placed on the sclera. For distance esodeviation of more than 15 PD and near esodeviation that exceeds distance deviation by at least 15 prism diopters, we perform prism adaptation, operating on the (larger) prism-adapted angle of deviation. In patients who did not demonstrate fusion before prism adaptation, prism adaptation improves sensory and motor outcome without increasing the risk for overcorrection. Other enhanced medial rectus muscle recession procedures based on the near deviation and the distance deviationwith and without correction have also been advocated. Despite excellent bifoveal fi xation at distance, only 16% of patients achieved bifoveal fusion at near after surgery.
COMPLICATIONS Succinylcholine, a common anesthetic agent, may result in prolonged respiratory paralysis and should not be used in patients also treated with echothiophate iodide or isofluorophate. Anticholinesterase inhibitors inactivate or deplete levels in the body of cholinesterase, an enzyme that is required to degrade cholinergic compounds such as succinylcholine. Alternative muscle relaxants that are not dependent on cholinesterase should be used. Parents should be clearly warned about this problem in case the child requires emergency surgery.
REFERENCES Breinin GM: Accommodative strabismus and the AC-A ratio. Am J Ophthalmol 1:303–311, 1971. Clark RA, Ariyasu R, Demer JL: Medial rectus pulley posterior fi xation is as effective as scleral posterior fi xation for acquired esotropia with a high AC/A ratio. Am J Ophthalmol 137:1026–1033, 2004. Eustis HS, Mungan NK: Monovision for treatment of accommodative esotropia with a high AC/A ratio. J AAPOS 3:87–90, 1999. Jotterand VH, Isenberg SJ: Enhancing surgery for acquired esotropia. Ophthalmic Surg 19:263–266, 1988. Kushner BJ, Preslan MW, Morton GV: Treatment of partly accommodative esotropia with a high accommodative convergence-accommodation ratio. Arch Ophthalmol 105:815–818, 1987. Kushner BJ: Fifteen-year outcome of surgery for the near angle in patients with accommodative esotropia and a high accommodative convergence to accommodation ratio. Arch Ophthalmol 119:1150–1153, 2001. Leitch RJ, Burke JP, Strachan IM: Convergence excess esotropia treated surgically with fadenoperation and medical rectus muscle recessions. Br J Ophthalmol 74:278–279, 1990. Parks MM: Abnormal accommodative convergence in squint. Arch Ophthalmol 59:364–380, 1958. Parks MM: The monofi xation syndrome. Trans Am Ophthalmol Soc 67:609–657, 1969. Pratt-Johnson JA, Tillson G: The management of esotropia with high AC/A ratio (convergence excess). J Pediatr Ophthalmol Strabismus 22:238– 242, 1985. Prism Adaptation Study Research Group: Efficacy of prism adaptation in the surgical management of acquired esotropia. Arch Ophthalmol 108:1248–1256, 1990.
Procianoy E, Justo DM: Results of unilateral medial rectus recession in high AC/A ratio esotropia. J Pediatr Ophthalmol Strabismus 28:212– 214, 1991. Repka MX, Connett JE, Baker JD, Rosenbaum AL: Surgery in the prism adaptation study: accuracy and dose response. Prism Adaptation Study Research Group. J Pediatr Ophthalmol Strabismus 29:150–156, 1992. Rosenbaum AL, Bateman JB, Bremer DL, Liu PY: Cycloplegic refraction in esotropic children. Cyclopentolate versus atropine. Ophthalmology 88:1031–1034, 1981.
von Noorden GK, Avilla CW: Nonaccommodative convergence excess. Am J Ophthalmol 101:70–73, 1986.
226 EXTRAOCULAR MUSCLE LACERATIONS 871.4 Krista A. Hunter, MD Portland, Oregon David T. Wheeler, MD Portland, Oregon
ETIOLOGY/INCIDENCE Lacerations of extraocular muscles or their tendons without damage to the globe, eyelid and adjacent structures are extremely rare. Laceration of rectus muscles occurs more frequently as the oblique muscles insert on the posterior sclera and enjoy greater protection. The inferior rectus and medial rectus are the most frequently injured due to the fact that when the eye is threatened, forced closure of the eyelid is accompanied by Bell’s phenomenon with upward and outward movement of the eye. This places these muscles more anteriorly and renders them more susceptible to injury. If ocular trauma involves an upper lid avulsion or penetration of the superomedial orbit, the superior oblique tendon may be lacerated. In addition to ocular trauma, there have been reports of damage to the medial rectus during endoscopic sinus surgery due to the close proximity of this muscle to the ethmoid sinus and the relatively thin medial orbital wall.
Ideally, reattachment of the lacerated ends of the muscle or tendon should occur promptly after the acute injury. If repair is delayed, scarring and fibrosis can lead to increased difficulty finding and repairing the muscle. However, in selected cases repair may be attempted even if significant time has passed. When a muscle is lacerated at or near its insertion, the muscle sheath and attachment to posterior Tenon’s capsule prevent the muscle from retracting deeply into the orbit. In this case, the free end of the muscle or tendon may be located by following the empty sheath ‘hand over hand’ into the orbit. It is helpful to recall that the normal course of rectus muscles parallels the orbital wall, rather than the sclera. Painstaking effort at identifying muscle tissue is warranted. Retropulsing the globe may occasionally bring the lacerated muscle into view. Alternative approaches for recovering a lost muscle deeper in the orbit include an anterior orbitotomy through a fornix-based transconjunctival incision and, in the case of medial rectus or superior oblique muscles, endoscopic surgery through the ethmoid sinus. The assistance of an orbital surgeon may be particularly helpful in these scenarios. If no muscle tissue can be found for reattachment, a transposition procedure may be indicated. Full or partial tendon transfer of the two adjacent rectus muscles, with or without posterior fi xation (the ‘Foster modification’), may be done with retention of the anterior ciliary artery in the remaining rectus muscle. If significant concern exists about anterior segment ischemia, a muscle splitting or vessel-sparing muscle transfer technique may be used. If there is restriction of the antagonist, a subsequent recession or injection of botulinum toxin can be done.
CHAPTER 226 • Extraocular Muscle Lacerations
Rosenbaum AL, Jampolsky A, Scott AB: Bimedial recession in high AC/A esotropia. A long-term follow-up. Arch Ophthalmol 91:251–253, 1974.
TREATMENT
COMMMENTS In any case in which extraocular muscle laceration is suspected, a full and meticulous eye exam should be performed to determine the extent of the injury and rule out globe damage, fractures, or the presence of foreign bodies. Surgical exploration is frequently required.
REFERENCES DIAGNOSIS A lacerated extraocular muscle can be difficult to diagnose but should be suspected when profound motility disturbance is found in the setting of ocular trauma. Additional causes of trauma-related motility disturbance should be considered: orbital fracture leading to muscle entrapment, damage to a cranial nerve, and mechanical restriction from edema or hemorrhage associated with the injury. Forced ductions should be performed and would generally be free in cases of laceration although significant edema or hemorrhage could cause restriction. If the examination is delayed significantly from the time of injury, fibrosis and scarring can also lead to restriction. Imaging studies can occasionally be a helpful adjunct but definitive diagnosis may not be possible without surgical exploration.
Foster RS: Vertical muscle transpositions augmented with lateral fi xation. J Am Assoc Pediatric Ophthalmol Strabismus 1:20, 1997. Helveston EM, Grossman RD: Extraocular muscle lacerations. Am J Ophthalmol 81:754–760, 1976. McKeown CA: Anterior ciliary vessel sparing procedure. In: Rosenbaum AL, Santiago AP, eds: Clinical strabismus management: principles and surgical techniques. Philadelphia, WB Saunders, 1999:39:516– 528. Santiago AP, Rosenbaum AL: Selected transposition procedures. In: Rosenbaum AL, Santiago AP, eds: Clinical strabismus management: principles and surgical techniques. Philadelphia, WB Saunders, 1999:36: 476–489. Thacker NM, Velez FG, Demer JL, Rosenbaum AL: Strabismic complications following endoscopic sinus surgery: diagnosis and surgical management. J Am Assoc Pediatric Ophthalmol Strabismus 8:488–494, 2004.
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227 INFERIOR RECTUS MUSCLE PALSY 378.81 Richard A. Saunders, MD Charleston, South Carolina Richard L. Golub, MD Phoenix, Arizona
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SECTION 20 • Extraocular Muscles
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DIAGNOSIS ETIOLOGY ●
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Congenital/idiopathic: long-standing condition of undetermined onset, usually diagnosed in early childhood. Neurogenic: oculomotor (third cranial nerve) lesions, rarely fascicular (multiple sclerosis and midbrain metastasis), nuclear or supranuclear, but may be seen in skew deviation. Post viral: ● Myasthenia gravis: typically will have a fluctuating course with a history of other extraocular muscle weakness; the orbicularis oculi are usually involved. Orbital trauma: ● Blowout fracture (typically posterior) with muscle entrapment or injury to the oculomotor nerve; ● Inferior rectus muscle laceration (penetrating object, dog bite) (Figure 227.1); ● Inadvertent orbital entry during endoscopic sinus surgery. Ocular surgery: ● Extraocular muscle surgery involving: ● Excessive recession of the inferior rectus muscle; ● Lost or slipped muscle; ● Muscle belly rupture in elderly patients (pulled-in-two syndrome, or ‘PITS’);
FIGURE 227.1. Traumatic rupture of left inferior rectus muscle from dog bite with absent depression of the left eye.
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Inferior rectus muscle palsy is an uncommon clinical entity that is almost always associated with abnormalities of one or more additional extraocular muscles. When presenting as an isolated condition, it is characterized by hypertropia of the involved eye in primary gaze position. The deviation is incomitant and becomes greater in the field of action of the involved inferior rectus muscle (i.e. when the globe is abducted and depressed). Adult patients are usually symptomatic and complain of vertical diplopia, especially in down gaze.
Inadvertent inferior rectus muscle injury during inferior oblique muscle myectomy. Retrobulbar anesthetic agents injected directly into the inferior rectus muscle (may initially result in paresis with ipsilateral hypertropia followed by muscle contracture and a permanent hypotropia). Placement of traction suture. Scleral buckle. Orbital surgery, such as fat pad removal. Miscellaneous orbital processes potentially causing rectus muscle paresis: ● Chronic progressive external ophthalmoplegia; ● Orbital neoplasm; ● Rectus muscle myositis; ● Thyroid-related immune orbitopathy: usually causes restriction but may have paretic component or association with myasthenia gravis. ●
Like other cyclovertical muscle disorders, isolated inferior rectus palsy is diagnosed after a thorough history and a careful ocular motility examination. Prism and cover or Maddox rod measurements in the diagnostic gaze positions, as well as an evaluation of ocular torsion and sensory status, are essential.
Clinical signs and symptoms ●
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Hypertropia typically greatest in the field of action of the involved inferior rectus muscle. Duction limitation (not due to a restrictive process). Possibly a compensatory chin-down head posture with face turn toward the involved eye. Mild incyclotropia may be seen on sensory testing, but is rarely symptomatic. Bielschowsky’s head-tilt test: positive, negative, or paradoxic results. Forced duction testing typically negative in cases of true inferior rectus muscle palsy, although paresis and restriction can coexist. Active force-generation testing demonstrating decreased muscle force necessary to confi rm the diagnosis.
Differential diagnosis Other ocular pathology may present a clinical picture similar to inferior rectus palsy. For instance, superior rectus muscle restriction (e.g. Graves disease or myositis) may cause a hypertropia with down gaze limitation. The orbital floor adherence syndrome may also present with hypertropia, most pronounced or exclusively present in down gaze. It is most often seen after orbital floor fracture and represents a pseudoparesis of the inferior rectus muscle. The reduced infraduction is caused by mechanical limitation of the muscle excursion posteriorly along the orbital floor, simulating muscle ‘weakness.’ Patients with chronic hypertropia (e.g. longstanding superior oblique muscle palsy or skew deviation) may have limited infraduction on version testing. This problem is distinguished from inferior rectus muscle palsy by the clinical context. Duction testing can differentiate an inferior rectus paresis from a contralateral superior oblique muscle over action; ductions will shows a difference in the ability to depress the involved eye when the fellow eye is covered. Saccadic velocity elicited by optokinetic testing also
can be helpful, showing a slowed saccade with inferior rectus paresis, but a normal saccade with skew deviation.
von Noorden GK, Hansell R: Clinical characteristics and treatment of isolated inferior rectus paralysis. Ophthalmology 98:253–257, 1991.
TREATMENT
(Microtropia, Microstrabismus, Subnormal Binocular Vision, Parks’ Syndrome)
Ocular For those patients with long-standing, small angle hypertropia, prisms may be beneficial. Monocular occlusion or temporary prisms may be used for patients in whom spontaneous recovery is anticipated.
M. Edward Wilson, MD Charleston, South Carolina
Medical Chemodenervation (botulinum toxin) of the ipsilateral superior rectus muscle is rarely indicated because of the nearly universal and often severe postinjection ptosis.
Surgical The surgical management of inferior rectus muscle palsy should be guided by measurements in diagnostic gaze positions and results of passive duction and generated muscle force testing. Surgical options include ipsilateral superior rectus muscle recession with or without inferior rectus muscle resection, and recession or posterior fi xation of the contralateral inferior rectus muscle. Weakening of the contralateral superior oblique muscle with free tenotomy is rarely indicated due to the potential for postoperative torsional diplopia and symptomatic superior oblique muscle palsy. When ductions deficits are −3 or greater, a transposition of the horizontal rectus muscles (modified Jensen or Hummelsheim procedure) may be employed. This can be especially helpful in patients with a lost inferior rectus muscle. More recently, success with anterior transposition of the inferior oblique muscle has been described for traumatic injury or lost inferior rectus muscle.
COMMENTS The treatment of inferior rectus muscle palsy depends on its clinical context and associated symptoms and, most importantly, on whether it presents as an isolated fi nding. Surgical intervention is guided by measurements in diagnostic gaze positions, the presence or absence of down gaze restriction, and the degree of rectus muscle weakness. Satisfactory outcome usually requires ocular alignment in the primary gaze and reading positions.
It is clinically useful to divide binocular vision into central and peripheral components. Central, or macular, binocular vision involves the conscious processing of the central 3 to 5 degrees of the visual field, the ‘object of regard,’ by the two eyes simultaneously. Peripheral, or extramacular, binocular vision involves the processing of the remainder of the visual field beyond the central 3 to 5 degrees. Patients with monofi xation syndrome can be conceptualized as having peripheral binocular vision but no central binocular vision. The term bifi xation has often been used to connote simultaneous fi xation with both foveae. When a facultative scotoma prevents a patient from fi xating with both eyes simultaneously, the term monofi xation has been applied. When monofi xation (absent central binocular vision) is combined with evidence of intact peripheral binocular vision, the patient is said to have monofi xation syndrome. As the term implies, only one fovea is fi xating at a time even though the extramacular portions of the retinas are functioning simultaneously and cooperatively. Unlike patients with bifi xation, these individuals often have a small angle esotropia of up to 8 or 10 prism diopters. Peripheral binocular vision does not have rigid requirements for orthotropia secondary to large receptive fields serving the peripheral retina. In contrast to the looser ‘point-to-area’ retinal correspondence in the periphery, the small size and large number of cortical receptive fields serving macular vision require a tighter ‘point-to-point’ retinal correspondence centrally. Therefore, a small angle tropia is compatible with intact peripheral fusion but incompatible with intact central fusion. For this reason, microtropia or microstrabismus has been used at times interchangeably with monofi xation syndrome.
ETIOLOGY ●
REFERENCES
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Brodsky MC, Fritz KJ, Carney SH: Iatrogenic inferior rectus palsy. J Pediatr Ophthalmol Strabismus 29:113–115, 1992. Greenwald MJ, Ticho BH, Engel JM: Extraocular muscle surgery. In: Krupin T, Kolker AE, eds. Atlas of complications in strabismus surgery. London, Mosby; 1993:9:10–9.11. Olitsky SE, Notaro S: Anterior transposition of the inferior oblique for the treatment of a lost inferior rectus muscle. J of Pediatr Ophthalmol Strabismus 37:50–51, 2000. Van Dalen JTW, Van Mourik-Noodernbos AM: Isolated inferior rectus palsy: a report of six cases. Neuro-ophthalmology 4:89–94, 1984.
CHAPTER 228 • Monofixation Syndrome
228 MONOFIXATION SYNDROME 378.34
Therapy for inferior rectus muscle palsy may be optical, surgical or chemical.
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This syndrome may represent a congenital absence of central binocular vision. Alternatively, infants with normal binocular vision potential at birth may lose bifi xation due to prolonged strabismus (>60 days in an infant, >90 days in an older child), retaining (after the eyes are straightened by surgery or glasses) only peripheral binocular vision. Monofi xation syndrome is seen and diagnosed most commonly after surgical realignment in childhood strabismus. This syndrome can also be secondary to anisometropic amblyopia. An idiopathic ‘primary’ form of monofi xation syndrome can be seen, often in relatives of patients with congenital esotropia.
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SECTION 20 • Extraocular Muscles
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Monofi xation syndrome, once established, is permanent. Congenital absence of central binocular vision (primary monofi xation syndrome) may predispose to strabismus just as strabismus may predispose to monofi xation syndrome. Children with congenital esotropia most commonly develop monofi xation syndrome (peripheral fusion without central fusion) when they are operated early in life. Newer studies suggest that post-operative stereopsis is better when the duration of esotropia is reduced. Bifi xation (central binocular vision) may be achievable in some of these infants if the eyes are straightened within 60 days of the onset of constant esotropia. Monofi xation syndrome promotes better stability of alignment (orthotropia or microtropia) compared with no binocular vision, but manifest strabismus of more than 8 prism diopters may recur with time. Central binocular vision, even when normal at birth, is tenous and easily lost if the two foveae are not stimulated simultaneously. Constant strabismus lasting a few months or longer may result in the permanent loss of bifi xation, even in older children and adults. Peripheral fusion, in contrast, is more durable and usually returns postoperatively even after years of constant strabismus, resulting in monofi xation syndrome as the postoperative sensory state of the eyes.
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Small angle tropia is usually present, measuring up to 8 to 10 prism diopters; however, as many as one third of patients with monofi xation syndrome are orthotropic. Amblyopia often (but not always) coexists with monofi xation syndrome. A history of prior surgery for infantile/congenital or childhood-onset strabismus often is present. This syndrome can occur without any prior history of strabismus, often in relatives of patients with congenital esotropia. For a definitive diagnosis, both the presence of peripheral fusion and the absence of central fusion must be established. The presence of peripheral fusion is indicated by the following: ● There is subnormal (gross) stereopsis; ● A fusion response to the Worth-four-dot at 0.33 m occurs; ● There is tropia by simultaneous prism and cover test with overlying phoria by alternate-cover test; ● Fusional vergence amplitudes are measurable. The absence of central fusion is indicated by the following: ● Microtropia is a manifest tropia on the cover test or simultaneous prism and cover test of 1 to 10 prism diopters; larger tropias are not considered microtropias and are incompatible with monofi xation syndrome -the examiner should not be misled by phorias that may overlie a microtropia; ● Facultative macular scotoma is shown on the Worthfour-dot (patient sees two or three dots at distance despite seeing four dots at near) or Bagolini glasses
(patient sees two oblique lines that form an X but with a central gap in the line from the lens over the nonfi xating eye); Facultative macular scotoma is shown by the deletion of letters viewed by the nonfi xating eye via vectographic projection of Snellen letters (BVAT II BVS, Mentor O and O or vectographic projector chart slide, American Optical Company); There is a positive 4-prism diopter base-out test (no vergence movement); this is the least reliable method and is not recommended.
Strabismus with pathologic cortical suppression and abnormal retinal correspondence (ARC) is characterized by the following: ● There is no stereopsis; ● Patients see two or three lights when viewing Worthfour-dot test at 0.33 m, rather than four as in monofi xation syndrome, but may give a four-light response at 6 inches or closer (suppression scotoma in large angle esotropia is often about 6 degrees as opposed to 3 degrees with monofi xation syndrome; therefore, lights must be much closer to the patient to project onto the peripheral retina outside of the larger scotoma); ● The deviation is more than 8 to 10 prism diopters; ● There is no phoria overlying the tropia; ● There are no measurable fusional vergence amplitudes. Intermittent strabismus with bifi xation is characterized by the following: ● Patients with intermittent deviations may show suppression and ARC when deviated but retain central binocular vision when orthotropic. Perform sensory testing early in the examination, when alignment control is better; ● Some sensory tests require glasses or goggles, which may disrupt strabismus control and fail to show bifi xation.
PROPHYLAXIS ●
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When normal binocular vision is present in infancy, the loss of central binocular vision, and thus the development of monofi xation syndrome, can be prevented by promptly correcting any acquired constant eye misalignment (with the use of glasses, surgery, prisms). Surgical overcorrections in the treatment of intermittent exotropia are usually constant and can result in the loss of central binocular vision if not corrected within a few months. Use glasses or prisms to promote fusion temporarily if spontaneous resolution does not occur in the first few weeks after surgery and the decision for repeat operation will be delayed. Infants with classic congenital/infantile esotropia have been thought to have a congenital absence of central binocular vision. For this reason, monofi xation syndrome has been the desired outcome. Monofi xation syndrome can be achieved with surgery within 18–24 months. Some patients, however, may retain the potential for central binocular vision. For this reason, the duration of esotropia has taken on increased significance. Monofi xation syndrome may be avoided if the duration of infantile esotropia does not exceed 60 days.
TREATMENT ●
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REFERENCES Arthur BW, Smith JT, Scott WE: Long-term stability of alignment in the monofi xation syndrome. J Pediatr Ophthalmol Strabismus 26:224–231, 1989. Eustis HS, Parks MM: Acquired monofi xation syndrome. J Pediatr Ophthalmol Strabismus 26:169–172, 1989. Ing MR: Early surgical alignment for congenital esotropia. Trans Am Ophthalmol Soc 74:625–659, 1981. Ing MR, Okino LM: Outcome of stereopsis in relation to duration of misalignment in congenital esotropia. J AAPOS, 6:3–8, 2002. Parks MM: Monofi xation syndrome. Trans Am Ophthalmol Soc 67:609– 657, 1969. Parks MM: Monofi xation syndrome. In: Tasman W, Jeager EA, eds: Duane’s clinical ophthalmology. Philadelphia, JB Lippincott, 1998:I:1–14. Tychsen L: Can ophthalmologists repair the brain in infantile esotropia? Early surgery, stereopsis, monofi xation syndrome, and the legacy of Marshall Parks. J AAPOS 9, 2006. Wilson ME: Monofi xation syndrome. In: Margo CE, Hamed LM, Mames RN, eds: Diagnostic problems in clinical ophthalmology. Philadelphia, WB Saunders, 1994:763–768.
229 NYSTAGMUS 379.50 Theodore H. Curtis, MD Portland, Oregon David T. Wheeler, MD Portland, Oregon Nystagmus and related ocular oscillations are repetitive involuntary eye movements that often indicate an underlying ocular or neurologic disorder. Movement can be in any direction (or more than one direction simultaneously) and may be congenital or acquired at any age. It is important to remember that nystagmus is a clinical sign that may take many different forms and about which much has been written but little is understood. This chapter will confi ne itself to a discussion of the more common and clinically relevant forms of nystagmus.
The evaluation of nystagmus requires descriptive nomenclature. Most forms involve two phases: the first (slow drift) causes the image to move away from the fovea, and the second attempts to return gaze to the target. There are two classic types: pendular, in which these phases are of equal velocity, and jerk, in which the second phase is a more rapid saccadic movement. Direction (when present) always refers to this fast phase, although it should be recognized that the slow phase reflects the abnormality. Movement can be in any plane (horizontal, vertical, oblique or rotary) and has a relative amplitude and frequency. Nystagmus may be conjugate or dissociated and may vary with the direction of gaze; the field in which its intensity is minimal is referred to as the null zone. Alexander’s Law states that jerk nystagmus increases as the eyes move in the direction of the fast component. Asking an older child or adult if they perceive movement of the environment (oscillopsia) helps to determine age of onset; oscillopsia is absent in congenital and early acquired forms. Associated signs and symptoms may aid in localizing the lesion in acquired nystagmus to the vestibular apparatus, brainstem or cerebellum. These include hearing loss, tinnitus, vertigo, ear pain, weakness or poor coordination, numbness or paresthesias, or imbalance. Eye movement recordings and other testing as noted below may be helpful. Several types of nystagmus are presented.
CHAPTER 229 • Nystagmus
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Monofi xation syndrome, once established, cannot be cured with orthoptic exercises or surgery. In hopes of preserving bifi xation, infantile esotropia patients should be operated (if possible) within 60 days of the onset of constant large-angle esotropia. The onset of congenital/ infantile esotropia is usually between 2 to 6 months of age. Treatment of amblyopia may improve the stability of alignment over time in patients with monofi xation syndrome. When possible, monofi xation syndrome should be prevented by preserving bifi xation. If not, monofi xation syndrome (peripheral fusion) should be the goal of strabismus treatment. Peripheral binocular vision, once established, is durable and can be restored even after many years of misalignment. Monofi xation syndrome is an achievable functional goal of strabismus surgery even in adults whose eyes have been misaligned since childhood.
ETIOLOGY/INCIDENCE
Physiologic nystagmus There are several forms of nystagmus associated with normal functioning of the ocular motor system. End-position nystagmus can be seen in normal individuals after prolonged gaze in extreme deviation. Optokinetic nystagmus (OKN) is a compensatory mechanism that functions to keep images of stationary objects on the retina during prolonged rotation of the head. The fi rst phase (smooth pursuit) follows the target and the fast phase (saccade) resets fi xation to the next image. The presence or absence of OKN is useful in assessing visual function of non-verbal and malingering patients. Caloric nystagmus is used in comatose patients to evaluate the vestibular system; one or both auditory canals are irrigated with either hot or cold water. Rotational nystagmus is useful in evaluating the ocular motor system in infants; while holding the infant in outstretched arms, the examiner pivots in place. During rotation, the fast phase is in the direction of rotation; upon stopping rotation, the fast phase reverses. Since this maneuver depends on an intact vestibular apparatus, it is an impure test of extraocular movements. Lastly, many patients can elicit voluntary nystagmus, which are rapid, back-to-back horizontal saccades that cannot be sustained for over 30 seconds. This ability is found in 5–8% of the population and may be familial.
Congenital (infantile) nystagmus Few patients have onset of nystagmus precisely at birth; the term infantile is more accurate and includes nystagmus present within the first few months of life. This category is broadly divided into afferent nystagmus (due to poor vision) and efferent nystagmus (due to ocular motor disturbance); at least 90% of cases are afferent. Eye movement recordings have conclusively shown that waveform alone is not a reliable method of distinguishing between these two types; therefore, it is imperative that all infants with nystagmus undergo thorough
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SECTION 20 • Extraocular Muscles
evaluation for a primary sensory cause. Conditions known to be associated with afferent infantile nystagmus include, among others, early (usually bilateral) visual deprivation (congenital cataracts, severe glaucoma, Peter’s anomaly), foveal hypoplasia (albinism, aniridia), retinal disease (Leber’s congenital amaurosis, achromatopsia, macular toxoplasmosis), retinal detachment (severe retinopathy of prematurity, persistent fetal vasculature, familial exudative vitreoretinopathy) and congenital optic nerve abnormalities (coloboma, atrophy, hypoplasia). It can also accompany cortical visual impairment from a perinatal insult. The nystagmus is typically binocular and conjugate, dampened by convergence, increased with fi xation effort, and abolished in sleep. Improved visual function with convergence often translates to better near acuity, and is the basis for treating with base-out prism glasses, which sometimes improve distance acuity. Patients with high refractive errors usually benefit from contact lens correction to minimize the aberration from constant ocular movement behind thick spectacles. Attempts to reduce the amplitude and/or frequency of the nystagmus and increase foveation time have involved medication (e.g. baclofen), recession of multiple rectus muscles simultaneously, and injection of botulinum toxin (Botox) into the muscle cone. All have had limited success. Patients with efferent nystagmus (historically known as congenital motor nystagmus but recently termed idiopathic infantile nystagmus) often have a null point in an eccentric position of gaze and manifest an anomalous head position to maximize visual acuity. Strabismus surgery, specifically an Anderson or Kestenbaum procedure, may place this null zone in primary position, thereby reducing or eliminating the head position. Variations of this technique are employed if there is accompanying strabismus or if the head position has a vertical or torsional component. Latent nystagmus is a benign condition that appears only when one eye is covered, or when light stimulus to one eye is diminished, but can coexist with manifest nystagmus (in which case the nystagmus amplitude increases with occlusion). This is a jerk nystagmus with the fast phase toward the side of the fi xing eye; it is often seen following surgery for infantile esotropia and probably results from subnormal binocular interaction. Visual acuity measurement should be performed using the polarized vectograph or blurring one eye with a high plus lens to avoid iatrogenic reduction of acuity with occlusion. So-called manifest latent nystagmus can occur if monocular visual loss occurs in this setting.
Acquired nystagmus Spasmus nutans classically presents as a triad of nystagmus, head nodding and torticollis between 4 months and 3 years of age, and usually resolves within a year. The nystagmus is usually very fine, rapid and pendular, but may be vertical or rotary. It is usually asymmetric, may appear monocular, and varies over time and with position of gaze. Head nodding is inconstant and irregular, and tilting or turning of the head occurs less frequently. Pathogenesis is unknown and no treatment exists, but the condition appears to be self-limited. It is associated with strabismus and refractive error. Chiasmal glioma can present in a manner identical to spasmus nutans, prior to visibly affecting the anterior visual pathways. Some authors recommend that all patients with this condition undergo neuro-imaging; this is particularly important in the setting of visual loss, afferent pupillary defect, papilledema or optic atrophy.
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Vestibular nystagmus can be divided into peripheral and central types. The etiology of peripheral disease includes labyrinthitis, acoustic neuronitis, ischemia, trauma and toxicity; the nystagmus is frequently associated with vertigo, tinnitus or deafness. It is invariably a jerk nystagmus, usually with a horizontal and rotary component, and the fast phase is toward the normal side. Central vestibular nystagmus is due to bilateral brainstem dysfunction from tumor, stroke, trauma or demyelination. This nystagmus may be purely horizontal, vertical or rotary and may change with the direction of gaze. Treatment is primarily aimed at reducing the vertigo and may include anticholinergics, monoaminergics, antihistamines, phenothiazines, benzodiazepines and butyrophenones. The sheer number of drugs involved reflects the lack of effective treatment. Seesaw nystagmus is a dissociated pendular nystagmus in which one eye elevates while the other depresses. In the acquired form, the rising eye intorts while the falling eye extorts. In the less common congenital form, these torsional movements are reversed. Etiologies include parasellar tumors, trauma, and vertebrobasilar insufficiency; it has been reported in septo-optic dysplasia and even with severe visual loss from progressive cone-rod retinal dystrophy. Visual field results are helpful in considering neoplastic or vascular etiologies. The use of baclofen, a GABA analog, may be beneficial. In upbeat nystagmus, the upgoing fast phase may be of large or small amplitude but is always present in primary position. Most patients have intrinsic brainstem or cerebellar disease. Associated conditions include multiple sclerosis, cerebellar degeneration, tumors or infarction of the medulla or midbrain, and infection or toxicity of the brainstem, such as Wernicke’s encephalopathy. Treatment is directed at identification and resolution of the underlying cause. Downbeat nystagmus is commonly seen with disease affecting the cerebellum or craniocervical junction such as cerebellar degeneration, Arnold–Chiari malformation, multiple sclerosis, trauma, tumor, infarction and many toxic-metabolic entities. The use of clonazepam, a GABA agonist, may decrease amplitude and oscillopsia. MRI may indicate a surgically correctable lesion. Periodic alternating nystagmus (PAN) is a continuous, horizontal nystagmus in which the fast component spontaneously reverses direction approximately every two minutes. It may be congenital or indicate vestibulo-cerebellar dysfunction from stroke, tumor, multiple sclerosis, trauma, infection, drug intoxication or degenerative disease. It has also occurred with severe, acquired bilateral visual loss from cataract, vitreous hemorrhage, or optic atrophy. Correction of the visual loss may abolish the nystagmus. Other patients have responded to treatment with baclofen. The hallmark of gaze-evoked nystagmus is its absence in primary position. The fast component is in the direction of gaze but its presence does not signify location or etiology. It is commonly drug-induced by anticonvulsants, sedatives, ethanol and other recreational drugs. It can also be seen with posterior fossa disease (tumor, trauma, infarct, demyelination) and is called Bruns’ nystagmus in the setting of cerebellopontine tumors; in this case, the nystagmus is slow and coarse when looking toward the side of the lesion and fast and fine in the opposite field of gaze. Gaze-evoked nystagmus can also be seen with cranial nerve palsies, myasthenia gravis, and restrictive muscle disease such as thyroid ophthalmopathy. Gaze-paretic nystagmus is a type of gaze-evoked nystagmus seen in patients recovering from a gaze palsy and is character-
tralateral dentate nucleus. GABA agonists such as valproate have been reported to decrease the movement. Two final ocular oscillations are usually observed in comatose patients. Ocular bobbing is characterized by a fast, conjugate, downward movement followed by a slow drift back up to primary position, usually in the absence of any horizontal eye movement. Patients typically have a massive pontine lesion, or metabolic encephalopathy. Ping-pong gaze is periodic, horizontal deviation of the eyes with the direction alternating every few seconds. It is seen with bilateral infarction of the cerebral hemispheres, but the etiology is unknown.
DIAGNOSIS Related ocular oscillations Superior oblique myokymia is caused by rapid, torsional, monocular movements due to isolated, intermittent contraction of the superior oblique muscle. Patients report brief episodes of vertical or torsional diplopia and oscillopsia. It is best appreciated at the slit lamp or during fundoscopy and may be exacerbated with gaze into the field of action of the affected muscle. It is generally benign but may follow trochlear palsy or head trauma, and has been reported in multiple sclerosis and occasionally with cerebellar tumor. Treatment with carbamazepine may be beneficial; surgical weakening of the affected muscle is sometimes required. Convergence retraction ‘nystagmus’ is seen in Parinaud’s (dorsal midbrain) syndrome and is due to co-contraction of the extraocular muscles with attempted convergence or upgaze. It is a saccadic disorder, rather than a form of nystagmus, and is best seen with fi xation on down-going OKN targets. Other findings in the dorsal midbrain syndrome are impaired vertical gaze, pupillary light-near dissociation, lid retraction, abnormal convergence and accommodation, and skew deviation. J. Lawton Smith has given the following age-differential: in infancy, congenital aqueductal stenosis; 10 years old, pinealoma; 20 years old, head trauma; 30 years old, brainstem vascular malformation; 40 years old, long-standing multiple sclerosis; and 50 years old, basilar artery stroke. Several fi xation instabilities are frequently seen in patients with cerebellar disease. Square-wave jerks are back-to-back macrosaccades that fi rst interrupt fi xation and then bring about refoveation. Ocular dysmetria is the ocular equivalent of ‘past-pointing’ seen with an intention tremor: as the eyes return to primary position, they overshoot the target and oscillate about the new fi xation point before coming to rest. Ocular flutter is a spontaneous intermittent burst of several conjugate micro-oscillations while maintaining fi xation in primary position. Opsoclonus refers to rapid, involuntary, chaotic, conjugate eye movements known as ‘saccadomania’ that may signal an occult neuroblastoma in children. It has also been seen in infants with an autoimmune disorder that responds to ACTH, and as a paraneoplastic manifestation in adults with visceral carcinoma. Other causes include multiple sclerosis and head trauma; it may be a benign, self-limited finding after viral encephalopathy. It is believed due to impairment of function in the pontine pause cells that normally inhibit saccadic burst cells. Ocular myoclonus is a vertical pendular oscillation that persists during sleep and is often associated with synchronous contraction of the face, palate, pharynx and diaphragm. This is due to a lesion in the ‘myoclonic triangle’ which connects the red nucleus with the ipsilateral inferior olive and the con-
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Thorough understanding of the normal mechanisms for gaze stability and the difference between physiologic and pathologic nystagmus is required. Meticulous history and careful clinical observation, along with a consistent method of recording the nystagmus, is essential. Clinical maneuvers – such as caloric, positional, and optokinetic stimulation – can be used to induce nystagmus for diagnostic purposes. If an eye movement recording laboratory is available, more accurate categorization of the abnormal eye movement can be obtained. Use of MRI search coil technique with a calibrated contact lens has moved from the research arena into clinical application.
CHAPTER 229 • Nystagmus
ized by slow frequency and large amplitude. As with all types of gaze-evoked nystagmus, it is due to dysfunction of the neural network that integrates pursuit, saccade and vestibular signals. When this mechanism fails, the eyes drift back toward midline from an eccentric position of gaze; displacement of the image from the fovea triggers a saccadic movement to regain fi xation. Two other types of gaze-evoked nystagmus are rebound nystagmus and the dissociated nystagmus seen in internuclear ophthalmoplegia. Rebound nystagmus can occur after prolonged eccentric gaze, with reversal of the fast phase (toward primary position), or can be seen transiently when the eyes return to primary position following sustained eccentric gaze. Both types are associated with ataxia and cerebellar disease.
Differential diagnosis ●
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Many forms of nystagmus indicate underlying neurologic disease. The role of the ophthalmologist is to identify the nystagmus and its localizing value so that appropriate diagnostic steps (neuro-imaging, etc.) may be undertaken. The concept of differential diagnosis is only meaningful following initial examination. The differential diagnosis of afferent infantile nystagmus is broad and often requires additional steps such as examination under anesthesia, ocular echography, electroretinography, visual evoked response and MRI. MRI should be considered in patients presenting with spasmus nutans in order to rule out glioma, especially if there is any evidence of anterior visual pathway or hypothalamic disease. Previously well children with opsoclonus should undergo measurement of urine vanillylmandelic acid and abdominal CT to rule out neuroblastoma.
TREATMENT Our limited knowledge of the pathogenesis of nystagmus hinders optimal treatment. Except for the use of baclofen in PAN, few controlled clinical trials have been performed for any intervention. Careful evaluation before and during therapy, particularly noting distance and near visual acuity, is warranted. Eye movement recordings with video and/or magnetic search coils are of value.
Systemic ●
Pharmacologic agents are primarily GABA agonists and potentiate the inhibitory effect of this neurotransmitter on ocular motor pathways. These drugs include baclofen,
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gabapentin, clonazepam, valproate and carbamazepine, among others. Alternative measures such as biofeedback, acupuncture, or cutaneous head and neck stimulation have been reported to decrease nystagmus in select patients.
Ocular ●
SECTION 20 • Extraocular Muscles
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Refraction with full correction should be done, as seemingly mild refractive correction can significantly improve vision in these patients. Optical therapies utilize prisms to place the eyes in a position of least nystagmus and thereby maximize foveation time and visual acuity. Another approach has been retinal image stabilization, which consists of high-plus spectacle lenses worn in combination with high-minus contact lenses; this is useful for monocular viewing when the patient is stationary. Contact lens wear alone has been noted to diminish congenital nystagmus, presumably by a trigeminal efferent pathway.
Medical ●
Retrobulbar or intramuscular injection of botulinum toxin (Botox) has been demonstrated to abolish nystagmus temporarily, but patient satisfaction has been poor due to side effects such as ptosis or diplopia, and the need for re-injection.
Burde RM, Savino PJ, Trobe JD: Clinical decisions in neuro-ophthalmology. 2nd edn. St Louis, Mosby — Year Book, 1992:289–320. Helveston AM, Ellis FD, Plager DA: Large recession of the horizontal recti for treatment of nystagmus. Ophthalmology 98:1302–1305, 1991. Hertel RW, Dell’osso LF, Fitzgibbon EJ, et al: Horizontal rectus muscle tenotomy in children with infantile nystagmus syndrome: a pilot study. J AAPOS 8:539–48, 2004. Leigh RJ, Averbuch-Heller L: Nystagmus and related ocular motility disorders. In: Miller NR, Newman NJ, eds: Walsh & Hoyt’s clinical neuro-ophthalmology. 5th edn. Baltimore, Williams & Wilkins, 1998: 1461–1505. Pratt-Johnson JA: Results of surgery to modify the null-zone position in congenital nystagmus. Can J Ophthalmol 26:219–223, 1991. Reinecke RD: Idiopathic infantile nystagmus: Diagnosis and treatment. J AAPOS 1:67–82, 1997. Tychsen L: Pediatric ocular motility disorders of neuro-ophthalmic significance. Ophthalmol Clin North America 4:615–643, 1991.
230 OCULOMOTOR (THIRD NERVE) PARALYSIS 378.51 Ann U. Stout, MD Portland, Oregon
ETIOLOGY/INCIDENCE Surgical ●
Strabismus surgery has been utilized in certain forms of nystagmus with varying degrees of success. Anderson or Kestenbaum procedures are used to move the eyes into the ‘null zone’ to diminish an anomalous head position. Recessions of all four horizontal recti have been performed with mixed preliminary results. Four-muscle tenotomy has been suggested, but some studies show clinical improvement, while others show no statistically significant effect. Surgery is occasionally needed in superior oblique myokymia. In secondary nystagmus, removal of the offending lesion can improve symptoms.
COMPLICATIONS Medical treatment should be administered by persons familiar with potential adverse drug effects. Carbamazepine can cause bone marrow suppression, baclofen is not approved for children, and clonazepam may be teratogenic; these agents should probably not be given to children or pregnant females. Surgery carries the risk of anesthesia, as well as potential loss of vision; this consideration becomes more important when potential benefits are less certain. Alternative therapy is probably harmless at worst, but should not delay diagnosis or treatment of an underlying disorder.
REFERENCES Arnoldi KA, Tychsen L: Prevalence of intracranial lesions in children initially diagnosed with disconjugate nystagmus (spasmus nutans). J Pediatr Ophthalmol Strabismus 32:296–301, 1995. Averbuch-Heller L, Leigh RJ: Medical treatments for abnormal eye movements: pharmacological, optical and immunological strategies. Aust New Zealand J Ophthalmol 25:7–13, 1997. Breen LA: Nystagmus and related ocular oscillations. In: Walsh TJ: Neuroophthalmology: Clinical signs and symptoms. 4th edn. Baltimore, Williams & Wilkins, 1997:504–520.
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Paralysis of the oculomotor nerve may be congenital or acquired. An oculomotor palsy may occur in association with atrochlear nerve palsy. This is significant both diagnostically and in the choice of surgical procedure.
DIAGNOSIS Clinical signs and symptoms Patients with this disorder typically present with symptoms of crossed diplopia with or without blurred vision. The patient may assume a head position to enable fusion. The findings are primarily ipsilateral to the lesion. A complete paralysis includes four of the six extraocular muscles (superior, medial, and inferior rectus, as well as inferior oblique) with exotropia, hypotropia, and incyclotropia of the involved eye; paralysis of the ciliary muscle and iris sphincter, resulting in absent accommodation and a dilated pupil; and paralysis of the levator, resulting in blepharoptosis. A partial form, or paresis, produces an intermediate degree of weakness of these muscles. The upper division can be involved alone, producing a double elevator paresis with true or pseudoptosis. The lower division may be selectively involved, sparing the superior rectus and levator. A diabetic oculomotor paresis frequently involves partial pupillary function. A sufficiently discrete nuclear lesion may involve the contralateral instead of the ipsilateral superior rectus muscle and may produce bilateral partial ptosis, although these findings are exceedingly rare.
TREATMENT Ocular If there is a field of single vision, bifocal correction for near vision may be needed if accommodation is impaired. If the
patient is in the amblyopic age range, patching and refractive correction are required. Surgical realignment is best deferred until after amblyopia therapy is completed. Prism correction may help if the vertical deviation is small. Deformity resulting from anisocoria is particularly troubling to blue-eyed patients, and may be treated with a cosmetic contact lens painted with a pupil and an iris.
The goal of surgery is to realign the eyes at or close to primary position. The choice of procedure depends on which muscles are involved and the completeness of the paralysis. Paresis of the vertical rectus muscles may cancel out, leaving a minimal vertical deviation, which is readily controlled with a mild head position or with prisms. In partial paralysis, there may be sufficient medial rectus function to respond well to a resection of the medial rectus muscle and recession of the ipsilateral lateral rectus muscle. Single vision across a maximum range of horizontal gaze directions is achieved by including recession of both horizontal rectus muscles on the other eye, with adjustable sutures being placed on selected or all four muscles. With very poor to no medial rectus function, if there is significant vertical rectus muscle function, the vertical rectus muscles can be transposed to the medial rectus muscle, combined with a resection and recession of these muscles for any vertical deviation. Adjustable sutures are useful here as well. In complete paralysis of the third nerve, medial rectus function can be replaced to some extent by the transposition of a sound superior oblique muscle. The superior oblique must be weakened to alleviate the incyclotropia. The superior oblique does not respond to horizontal gaze innervation but will provide an adducting force that opposes the abducting action of the recessed lateral rectus and improves ocular alignment. The tendon can be released from the trochlea by cutting the trochlea with scissors (technically difficult). Care must be taken to avoid crushing the tendon. If the tendon is severed, then the surgeon proceeds as though the superior oblique were also paralyzed. The free tendon is resected until it is snug and sutured to the insertion of the medial rectus muscle. The new superior oblique insertion is optimally placed under the medial rectus muscle at the axis of vertical rotation (to avoid an inadvertent hypertropia). An alternative approach to transposition of the superior oblique is to leave the trochlea intact and relocate the superior oblique tendon 2 to 3 mm anterior to the medial end of the superior rectus insertion, accompanied by the right amount of resection. To optimize results, the lateral conjunctiva and Tenon’s capsule can be recessed all the way to the orbital margin and the lateral rectus muscle should be recessed as far as practically possible. The eye can also be anchored in an adducted position for 2 weeks with orbital fi xation sutures. This is especially important if the superior oblique tendon has been lost and cannot provide an adducting force. There is no value in resecting the medial rectus muscle unless it has some residual function. Surgical elevation of the lid may be required if the ptosis is sufficiently severe. This should be deferred until after the eye is aligned. A maximal levator resection with a transcutaneous approach can suspend the upper lid; however, a frontalis sling is preferable for setting the correct lid height. Since the protective Bell’s reflex is usually impaired, the ptosis should be corrected to cover only half of the cornea with the brow relaxed. Frequent blinking and moisturizing drops must be relied on to
Supportive Accurate diagnosis and appropriate medical treatment are necessary. Prism therapy is generally of limited benefit because of marked incomitance. The involved eye is occluded, if necessary, for relief of diplopia. urgery should be deferred for as long as 6 to 9 months because spontaneous recovery may occur. If so, it must be followed to its end; surgery should be considered only for the remaining deviation.
COMPLICATIONS
CHAPTER 230 • Oculomotor (Third Nerve) Paralysis
Surgical
prevent corneal drying. Children tolerate corneal exposure better than adults. In double elevator paresis without resistance to passive elevation, a full tendon transposition of the medial and lateral rectus to the insertion of the superior rectus is the operation of choice (Knapp procedure). The ptosis may be a pseudoptosis caused by the hypotropia and should not be corrected until after the strabismus repair. If it is a real ptosis, elevation of the eye will aggravate the ptosis and the patient or family should be forewarned. A paralysis of the lower division of the third nerve (affecting the medial rectus, inferior rectus, and inferior oblique muscles) is treated by transferring the functioning superior rectus to the medial rectus muscle, the lateral rectus to the inferior rectus muscle, and tenectomizing the superior oblique muscle.
Because of the severe loss of function of extraocular muscles in third nerve paralysis, the only attainable goal is realignment of the eye in primary position. In patients with incomplete paralysis, a small horizontal and vertical range of fusion may be obtained, but care must be taken that the lid is not elevated too far and corneal function is not compromised. Children learn to suppress the double image; however, adults frequently require an occlusive lens because of the absence of fusion anywhere except in one direction of gaze.
COMMENTS Total third nerve paralysis is devastating to oculomotor function, and even the limited goal of repositioning the eye near primary position is a considerable achievement. Useful function of the eye in a binocular context can be obtained only in some cases of partial paralysis. Accurate diagnosis and the ruling out of other neurological involvement are essential before any consideration can be given to surgical repair.
REFERENCES Buckley EG, Townshend LM: A simple transposition procedure for complicated strabismus. Am J Ophthalmol 111:302–306, 1991. Glaser JS: Infranuclear disorders of eye movements. In: Duane TD, ed: Clinical ophthalmology. Hagerstown, Harper & Row, 1982:12:1–38. Gottlob I, Catalano RA, Reinecke RD: Surgical management of oculomotor nerve palsy. Am J Ophthalmol 111:71–76, 1991. Peter LC: The use of the superior oblique as an internal rotator in thirdnerve paralysis. Trans Am Ophthalmol Soc 31:232–237, 1933. Scott AB: Transposition of the superior oblique. Am Orthoptics J 5:11–14, 1977.
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231 SUPERIOR OBLIQUE MYOKYMIA 358.8 Andrea C. Tongue, MD Lake Oswego, Oregon
ETIOLOGY SECTION 20 • Extraocular Muscles
Superior oblique myokymia is a rare disorder reported almost exclusively in adults. Although Duane first described this condition in 1906, Hoyt and Keane, in 1970, were the fi rst to refer to it as superior oblique myokymia, based on the clinical fi ndings in five patients and EMG studies in one. The signs and symptoms include bouts of oscillopsia (microtremor, twitching), and vertical and/or torsional diplopia due to unilateral superior oblique muscle contractions. The disorder is often chronic and is rarely associated with any life-threatening intracranial mischief. It was considered a benign, although aggravating, disorder of unknown etiology until MRI showed that vascular compression of the fourth nerve at the root exit zone (REZ) may be one etiologic factor. Other extremely rare associated factors or potential etiologies cited are preceding superior oblique paralysis, tumors, AV fistula, demyelinating disease, adrenoleukodystrophy, lead poisoning, and stroke. All of these disorders can cause injury to the trochlear nerve and it has been postulated that the myokymia is caused by discharge of regenerating or regenerated motor neurons of the fourth cranial nerved.
COURSE/PROGNOSIS The course appears to be chronic, with spontaneous remissions and recurrences which may be years apart. In recent years MRI studies in multiple cases have shown compression at the root exit zone of the fourth cranial nerve by a blood vessel. It appears that the right side is more frequently affected than the left in these cases
TREATMENT Systemic Pharmacologic agents used in the treatment of this disorder include oral carbamazepine (tegretol), gabapentin, propanolol, phenytoin and baclofen. It is difficult to assess the effect of these medications because of the variable course of this disease in any individual and between individuals. The drugs may also be associated with serious and significant side effects and require ongoing and frequent laboratory and medical monitoring. Anyone prescribing these drugs should be familiar with the reported adverse effects, contraindications, and required monitoring of the patients.
Topical Use of topical betoxalol has also been reported with varying success.
Surgical Surgery is reserved for patients who are unable to tolerate their symptoms and do not respond or have adverse effects to medical therapy. Extra-ocular surgical procedures are directed at weakening the affected superior oblique and ipsilateral inferior oblique. Post-operative superior oblique paralysis may occur, leading to diplopia, which in some cases spontaneously resolves and in some requires further surgery. Recently the newest surgical intervention for SOM reported in the literature is intracranial micro-vascular decompression. This is a neurosurgical procedure involving a craniectomy. However, it is a procedure that attempts to correct the cause of the disease in cases where micro-vascular compression at the REZ is identified by special MRI studies. Temporary as well as lasting superior oblique paralysis (one year follow-up) has been reported in cases after micro-vascular decompression.
REFERENCES Hashimoto M, Ohtsuka K, Suzuki Y, et al: Superior oblique myokymia caused by vascular compression. J Neuro-Ophthalmol 24:3327, 2004. Katz SE, Anderson DP: Superior oblique myokymia as a bilateral subjective phenomenon. Can J Ophthalmol 32:256, 1997.
DIAGNOSIS
Palmer EA, Shults TW: Superior oblique myokymia: preliminary results of surgical treatment. J Pediatr Ophthalmol Strabismus 21:96, 1984.
Clinical signs and symptoms
Scharwey, K, Krzizok T, Sarnii M, et al: Remission of superior oblique myokymia after vascular decompression. Ophthalmologica 214:425, 2000.
The clinical sign of oscillopsia is subtle and may be best detected by slit lamp examination or video photography. Symptoms include intermittent or episodic vertical jumping, shimmering, twitching, or blurring of images. Diplopia may also be present. The symptoms are usually unilateral but have been reported to be perceived as bilateral. Signs are unilateral in that no case of bilateral superior oblique myokymia has been described. Usually individual bursts of superior oblique contraction last seconds but may recur continuously for hours or days at a time. In some patients the symptoms may be provoked by down gaze and may be most easily recognized on slit lamp examination.
Laboratory findings MRI is essential in identifying vascular compression. It should be noted that vascular contact with the trochlear nerve at the REZ was found in 14% of 30 normal volunteer subjects. Magnetic search coil technique can be used to measure the rotations of the eye during periods of superior oblique contraction. In the past, EMG studies have also shown superior oblique contraction.
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Yousry I, Dieterich M, Naidich TP, et al: Superior oblique myokymia: magnetic resonance imaging support for the neurovascular compression hypothesis. Ann Neurol 51:361, 2002.
232 SUPERIOR OBLIQUE (FOURTH NERVE) PALSY 378.53 Ann U. Stout, MD Portland, Oregon
ETIOLOGY Superior oblique palsy is the most commonly occurring cranial nerve palsy encountered by the strabismologist. The length and
pathway of the trochlear nerve across the edge of the dura (tentorium) makes it highly susceptible to minor head trauma. Other causes of superior oblique palsy are less common and include: ● Tumor; ● Vascular abnormality; ● Diabetes; ● Iatrogenic (after sinus or orbital surgery).
COURSE/PROGNOSIS As with other cranial nerve palsies, acquired superior oblique palsy (bilateral or unilateral) may resolve weeks to months after the onset; however, any deviation that persists after 6 months may be considered permanent.
DIAGNOSIS Evaluation of the patient suspected of having superior oblique palsy should begin with a careful history, and especially with inquiry about any prior head trauma. Questions should be directed toward the presence or absence of abnormal head posture, vertical diplopia, and torsional diplopia.
Clinical signs and symptoms Superior oblique palsy manifests in children as: ● Abnormal head posture (head tilt); ● Facial asymmetry; ● V-pattern esotropia with vertical component; ● In congenital absence of the superior oblique tendon, symptoms may include significant horizontal deviation, amblyopia, ptosis, and asymmetry of the orbits or face. In adults, there may be additional features: ● Intermittent diplopia, which may be horizontal and vertical; ● A chin depression to avoid diplopia in bilateral cases; ● Spontaneous torsional diplopia with horizontal displacement of the tilted images in most bilateral acquired cases; ● A head tilt and turn to the side opposite the affected eye in unilateral cases.
Three-step test An initial qualitative evaluation is carried out using a simple two-step test (Parks). A third step (Bielschowsky) includes noting whether the hyperdeviation is greater on right or left head tilt. Together these tests make up the three-step test to help in diagnosing a paresis of any of the vertically acting muscles.
Step 1 Determine which eye is hypertropic; this narrows the paretic muscle choices to four: ● The depressors on the hypertropic eye (inferior rectus, superior obique); or ● The elevators on the hypotropic eye (superior rectus, inferior oblique).
Determine if the vertical deviation is greatest in right or left gaze: ● Right gaze involves the right vertical recti as well as the left obliques; ● Left gaze involves the left vertical recti and the right obliques; ● The gaze direction with the larger deviation will further narrow the paretic muscle choice to two, a vertical rectus and an oblique, after factoring in the results of step 1.
Step 3 (Bielschowsky head-tilt test) The head is tilted to one side and then the other while the deviation is measured. (Bielschowsky head-tilt test). If the vertical deviation increases when the head is tilted toward the higher eye, the oblique muscle arrived at in step 2 is considered paretic. If the vertical deviation increases when the head is tilted toward the side of the lower eye, the rectus muscle identified in step 2 is considered paretic. In general, a unilateral superior oblique palsy will create an ipsilateral hypertropia that is worse on lateral gaze away from the affected side and on head tilt towards the affected side. Prism and cover testing should next be carried out in the nine diagnostic positions to provide a quantified evaluation.
Maddox double rod test An essential part of evaluating the patient with suspected superior oblique palsy is the Maddox double rod test for torsion. A red Maddox rod, with the cylinders vertically oriented, is placed in front of the patient’s right eye, and a similarly oriented white Maddox rod is placed in front of the left eye. The patient is asked to view a point source of light in a darkened room. The Maddox rods are then adjusted if necessary so that red and white lines appear to be parallel to the patient. The ocular torsion expressed in degrees is read directly from the trial frame holding the Maddox rods. ● Congenital or early acquired superior oblique palsy: no measurable torsion and no spontaneous complaint of torsional diplopia; facial asymmetry is commonly seen in the congenital form of the condition, with the fuller side of the face on the affected side. Asymmetry is secondary to head posture. Anomalies of the superior oblique tendon may be found. ● Acquired unilateral superior oblique palsy: measurable torsion less than 15 degrees but no spontaneous complaint of torsional diplopia; the tendon may be normal, and its condition can be assessed accurately in most cases with the use of the superior oblique traction test done at the time of surgery. ● Bilateral superior oblique palsy: the patient complains of torsional diplopia with horizontally separated images or has cyclotropia of more than 15 degrees, right hypertropia in left gaze, left hypertropia in right gaze, and V-pattern.
CHAPTER 232 • Superior Oblique (Fourth Nerve) Palsy
Superior oblique palsy may be unilateral or bilateral and congenital or acquired. The superior oblique tendon is also the tendon most frequently noted to be anomalous or absent.
Step 2
TREATMENT Surgical The prism and cover measurements obtained in the nine diagnostic positions in a patient with superior oblique palsy may be recorded and interpreted according to a scheme devised by Knapp:
429
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SECTION 20 • Extraocular Muscles
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Class I has the greatest vertical deviation in the field of action of the antagonist inferior oblique muscle; it is treated with inferior oblique weakening. Class II has the greatest vertical deviation in the field of action of the underacting paretic superior oblique; it is treated with superior oblique strengthening (if the tendon is lax). Class III is an equal vertical deviation in the field of action of the antagonist inferior oblique and the paretic superior oblique; deviations of less than 20 prism diopters are treated with inferior oblique weakening and those of more than 20 prism diopters are treated with inferior oblique weakening combined with either superior oblique strengthening (if the tendon is lax), or recession of the contralateral inferior rectus. Class IV is characterized by an L-shaped pattern, with a vertical deviation in the field of action of the paretic superior oblique, the antagonist inferior oblique, and the ipsilateral inferior rectus muscles. It is treated by superior oblique strengthening (if the tendon is lax), inferior oblique weakening, and weakening of the ipsilateral superior rectus. Class V superior oblique palsy shows a greater vertical deviation in all fields of downgaze. The ipsilateral superior rectus is recessed, and with more than 20 prism diopters of hypertropia, the superior oblique is tucked (if lax) or the contralateral inferior rectus is recessed. Class VI is bilateral superior oblique palsy, characterized by a V-pattern, chin depression, bilaterally positive Bielschowsky test, right hypertropia in left gaze, left hypertropia in right gaze, and complaints of torsional diplopia with the tilted images separated horizontally. Measured cyclotropia is often more than 15 degrees. This is treated with bilateral inferior rectus recession, bimedial rectus downshift, bilateral superior oblique tucks, or a combination. Class VII is termed ‘canine tooth syndrome’ and displays underaction of the superior oblique muscle and of the inferior oblique muscle on the same side. Its origin can be trochlear trauma (resulting in a ‘double Brown syndrome’), iatrogenic (e.g. an acquired Brown syndrome secondary to strengthening the superior oblique along with a residual superior oblique palsy), or local trochlear trauma complicated by closed head trauma producing a fourth nerve palsy.
Class VII is extremely difficult to treat. If the patient is able to fuse in primary gaze and has some range of fusion above and below, probably no treatment is indicated. If Brown syndrome is the most severe problem, surgical relief of the trochlear restriction may be tried with or without recession of the ipsilateral inferior rectus muscle. Iatrogenic Brown syndrome may require takedown of the tuck or recession of the resected superior oblique tendon, along with recession of the contralateral inferior rectus muscle. ● Certain types of superior oblique palsy are characterized by fairly severe torsional defects with very little vertical tropia; they may occur unilaterally or bilaterally. In such cases, the patient may benefit from anterior transposition of the superior oblique tendon by shifting the whole tendon or just the anterior fibers; an adjustable suture may be used in the procedure (Harada–Ito technique). ● Absent or anomalous superior oblique tendon may be treated by recession of the antagonist inferior oblique and of the
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ipsilateral superior rectus muscle, and by appropriate treatment of any coexisting horizontal deviation.
COMPLICATIONS Surgery to strengthen the superior oblique tendon frequently produces an iatrogenic mechanical limitation of elevation in adduction (Brown syndrome). For this reason, tucking of the superior oblique tendon should be done in fairly small increments, graded according to the laxity of the tendon noted at surgery. In acquired superior oblique palsy, alternatives to superior oblique strengthening should be considered. In cases of superior oblique palsy after closed head trauma, it is prudent to suspect that the condition is bilateral unless this can be definitely ruled out; this will permit the treatment of both eyes (if both are involved) without subjecting the patient to a second operation. Prism therapy may be effective for small vertical deviations, though this is often limited by incomitance and torsion. Surgical treatment of superior oblique myokymia may necessitate creating a superior oblique palsy. Patients with myokymia present with intermittent symptomatic oscillopsia and careful evaluation may reveal rhythmic intorsion of one eye accompanied by cyclodiplopia. This superior oblique myokymia may be transient, or it may persist and be extremely troublesome. Although superior oblique tenectomy has been suggested as a suitable treatment, this procedure may in turn result in superior oblique underaction. In this case, inferior oblique weakening may be done at the time of superior oblique myectomy or during a second procedure.
COMMENTS Significant systemic disease is rarely associated with this condition, and extensive workup is not indicated unless other neurologic complaints warrant it. Surgical treatment can be very successful, and the assessment scheme devised by Knapp has been very useful.
REFERENCES Ellis FD, Helveston EM: Superior oblique palsy: diagnosis and classification. Int Ophthalmol Clin 16:127–135, 1976. Helveston EM, Giangiacomo JG, Ellis FD: Congenital absence of the superior oblique tendon. Trans Am Ophthalmol Soc 79:123–135, 1981. Helveston EM, Krach D, Plager DA, Ellis FD: A new classification of superior oblique palsy based on congenital variations in the tendon. Ophthalmology 99:1609–1615, 1992. Metz HS, Lerner H: The adjustable Harada-Ito procedure. Arch Ophthalmol 99:624–626, 1981. Plager DA: Traction testing in superior oblique palsy. J Pediatr Ophthalmol Strabismus 27:136–140, 1990.
233 V-PATTERN STRABISMUS 378.03, 378.12 Jorge Alberto F. Caldeira, MD São Paulo, Brazil
Patients with a horizontal strabismus that becomes incomitant in vertical gaze, with more divergence of at least 15 prism diopters in the upward position as compared to the downward, are considered to have a significant V-pattern strabismus (Figure 233.1). Horizontal, vertical and oblique muscle dysfunctions, orbital factors, and anomalies of muscle insertions (followed or preceded by cyclotorsion of the globes) can cause this incomitance. Loss of fusion may also predispose to cyclodeviations which, in turn, can produce a V-pattern. Heterotopia of extraocular muscle pulleys may be responsible for elevation or depression in adduction and a V- or A-pattern. It is of paramount importance that a significant V-pattern is identified, properly characterized, and adequately corrected to obtain a good result, whether or not in conjunction with horizontal surgery. V-pattern is the most common anomaly among the alphabetical strabismus patterns. The relation of Vpattern : A-pattern is approximately 2 : 1.
COURSE/PROGNOSIS Anomalous head posture is not rare in patients with a Vpattern. V esotropia with fusion in upward gaze can cause a chin depression; conversely, a patient with V exotropia and fusion in downward gaze may hold the chin in an elevated position. If the reward of fusion is not attained in any position of gaze the head posture is normal, unless there is a vertical imbalance in primary position. A V-pattern is frequently found in association with Brown syndrome. The same holds true for bilateral paralysis of the trochlear nerve, although in some cases of unilateral paralysis the V-pattern can also be observed. In both instances, excyclotropia is a common sign, detected with the Maddox double-rod test and fundus examination.
FIGURE 233.1. V-pattern strabismus.
If fusion is present in one postion of gaze, the effort to maintain it for a long time may cause asthenopia and/or diplopia. The deviation should be measured in the nine diagnostic positions of gaze, with the patient wearing the full refractive correction. Accommodation should be controlled with appropriate targets during the measurements. The above requirements are mandatory to avoid the appearance of a pseudo V-pattern or the concealment of a true V-pattern. Measurements should be made at distance (6 meters) in primary position and with the eyes in position of 25 degrees elevation and 35 degrees depression, while fi xating an accommodative target. The head is tilted backward or forward to obtain depression or elevation of the eyes. In very young patients an accurate prism-and-cover test in the diagnostic positions of gaze may be impossible. In this situation the examiner can move the head passively up and down, while the patient fi xates a distant accommodative target. The deviation for near is measured at 33 centimeters. In examining the binocular rotations the patient is encouraged to make extreme effort in the secondary and tertiary positions. Possible elevation in adduction, overaction of each inferior oblique and underaction of each superior oblique should be carefully registered. The triad of bilateral elevation in adduction, bilateral overaction of the inferior oblique, and bilateral underaction of the superior oblique is more consistent in V-esotropia than in Vexotropia. Overaction of the superior oblique, bilateral or unilateral, is very seldom seen in V-esotropia, but is not rare in V-exotropia. The significance of a V-pattern depends not only on its amount but also on whether it is functionally significant, interfering or not in the important primary and downward positions.
CHAPTER 233 • V-pattern Strabismus
ETIOLOGY/INCIDENCE
DIAGNOSIS
TREATMENT Surgical. In most patients, an oblique muscle dysfunction is apparent and horizontal surgery should be combined with procedures on the inferior oblique muscles. Weakening surgeries on the inferior obliques have no significant effect on the deviation in primary position. Graded recession of the overacting inferior oblique muscles is the weakening procedure of choice. Underacting superior oblique muscles frequently return to normal function after recession of the inferior obliques. Disinsertion, myotomy, or myectomy offer less predictable results than recession. The recession can be enhanced by anteriorization of the new insertion, but keeping it parallel to the temporal border of the inferior rectus. Recession and transposition (with the new insertion parallel to the insertion of the inferior rectus) usually causes some limitation of elevation. A denervation of the inferior oblique or its extirpation is very seldom indicated. If the inferior obliques are not overacting they should not be touched. In case of a V esotropia, if both medial rectus muscles are to be recessed a downward one-half width or full tendon width transposition is indicated. If an uniocular recessionresection is planned, downward transposition of the medial rectus and upward transposition of the lateral rectus are indicated.
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V exotropia without overacting inferior obliques is uncommon. Faced with a basic type of exodeviation requiring recession of the lateral rectus and resection of the medial rectus, the former is transposed upward and the latter, downward.
COMMENTS SECTION 20 • Extraocular Muscles
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V-pattern incomitance is a common finding in horizontal deviations. It requires a painstaking measurement of the deviation and investigation of overacting and underacting oblique muscles. A neglected significant V-pattern may transform a potentially good functional case into a disastrous one.
REFERENCES Caldeira JAF: Some clinical characteristics of V-pattern exotropia and surgical outcome after bilateral recession of the inferior oblique muscle: A
retrospective study of 22 consecutive patients and a comparison with V-pattern esotropia. Binocul Vis Strabismus Q 19:139–149, 2004. Caldeira JAF: V-pattern esotropia: A review; and a study of the outcome after bilateral recession of the inferior oblique muscle: A retrospective study of 78 consecutive patients. Binocul Vis Strabismus Q 18:35–48, 2003. Elliot RL, Nankin SJ: Anterior transposition of the inferior oblique. J Pediatr Ophthalmol Strabismus 18:35–38, 1981. Goldstein JH: Monocular vertical displacement of the horizontal rectus muscles in the A and V patterns. Am J Ophthalmol 64:265–267, 1967. Parks MM: The weakening surgical procedures for eliminating overaction of the inferior oblique muscle. Am J Ophthalmol 73:107–122, 1972.
S ECT I O N
21
Eyelids
234 BLEPHAROCHALASIS 374.34 John H. Sullivan, MD San Jose, California
of elastin fibers in the quiescent stage. Fat atrophy eventually results in deep superior sulcus and a thin atrophic bronzecolored eyelid skin which resembles parchment. Multiple fi ne telangiectatic subcutaneous vessels are present and blepharoptosis results from thinning and atrophy of levator aponeurosis. Dehiscence of lateral canthal tendon causes horizontal phimosis and rounding of the lateral canthus.
ETIOLOGY DIAGNOSIS Blepharochalasis, a term coined by Fuchs a century ago, is a rare condition characterized by recurrent, episodic, painless periorbital edema, either unilateral or bilateral, which in its acute phase resembles angioedema. Evidence suggests an immunopathogenic mechanism, but the cause remains unknown. After repeated attacks, the eyelid skin loses elasticity and develops a characteristic thin, discolored appearance that resembles wrinkled cigarette paper or parchment. The upper eyelid fat pads may eventually atrophy, causing a typical skin concavity and psuedoepicanthal fold. The term blepharochalasis is frequently misused to indicate redundant skin of the aging eyelid, a common condition more accurately termed dermatochalasis. ● The pathogenesis is uncertain, but this condition may be immunogenic. Abundant IgA deposits are found around elastin fibers. ● Infrequently, occurrence is familial. ● There is an equal sex distribution. ● Sometimes blepharochalasis is associated with systemic illness, such as amyloidosis, dermatomyositis, or leukemia. ● There is an association with edema of the lips and thyroid enlargement in Laffer-Ascher syndrome.
The diagnosis is established by history and clinical features. There are no characteristic laboratory fi ndings.
Differential diagnosis ●
●
●
●
●
Angioedema: usually older age of onset; edema is seldom limited to the upper eyelids. There is an association with complement 1-esterase inhibitor deficiency and autoantibodies. Idiopathic lymphedema: unremitting brawny edema, usually in older patients. Dermatochalasis: a common aging process with redundant skin and fat prolapse. Tumor: progressively enlarging mass; the diagnosis is confirmed by biopsy results. Floppy lid syndrome: typically found in older, obese men; there is an association with papillary conjunctivitis.
TREATMENT Active/acute phase: supportive ● ●
Cold compresses can be used. Topical and systemic steroids are of limited value.
Quiescent/late stage: surgical
COURSE/PROGNOSIS
● ●
The initial onset is usually before the age of 20 with unilateral or bilateral swelling of the eyelids and conjunctiva which can last hours to several days. Proptosis indicates orbital involvement and the frequency and severity of repeated episodes tend to lessen with age. Occasionally, attacks are aggravated by a triggering event, such as fever, upper respiratory infection, menstruation, or weeping. Lacrimal gland prolapse is common and in the early phase, atrophy of the skin and orbital septum exposes the fat pads. There are perivascular inflammatory infi ltrates during the acute stage and loss
● ●
Excise the redundant skin. Reposition the ectopic lacrimal gland. Reconstruct the lateral canthal tendon. The repair of blepharoptosis is often challenging.
COMMENTS Little can be done to ameliorate the acute phase of blepharochalasis. The avoidance of triggering mechanisms, when present, may diminish the frequency of attacks. Immunopathologic studies are of interest, but as yet have not elucidated the
433
cause or provided a rational form of treatment. Although not always possible, it is preferred to delay surgical reconstruction until the active phase is in complete remission. An episode of recurrent edema may spoil a satisfactory result.
REFERENCES SECTION 21 • Eyelids
Bartley GB, Gibson L: Blepharochalasis associated with dermatomyositis and acute lymphocytic leukemia (Letter). Am J Ophthalmol 113:727– 728, 1992. Bergin DJ, McCord CD, Berger T, et al: Blepharochalasis. Br J Ophthalmol 72:863–867, 1988. Custer PL, Tenzel RR, Kowalczyk AP: Blepharochalasis syndrome. Am J Ophthalmol 15;99:424–428, 1985. Ghose S, Kalra BR, Dayal Y: Blepharochalasis with multiple system involvement. Br J Ophthalmol 68:529–532, 1984. Held JL, Schneiderman P: A review of blepharochalasis and other causes of the lax, wrinkled eyelid. Cutis 45:91–94, 1990.
duration than those of other types of blepharoconjunctivitis. Patients with staphylococcal blepharitis are younger (mean age, 42 years), compared to a mean age of 51 years for other types of blepharitis. Eighty percent of cases occur in women. This condition is treatable and curable, in contrast to other forms of the disease that can only be controlled.
Mixed seborrheic/staphylococcal conjunctivitis Characteristically, these patients have a chronic history due to the seborrheic component, with periods of increased symptoms when the bacterial component becomes active.
Meibomian gland dysfunction It is important for patients to understand that this chronic condition will require long-term lid hygiene and more aggressive treatment during exacerbations.
DIAGNOSIS Clinical signs and symptoms Chronic staphylococcal blepharoconjunctivitis
235 BLEPHAROCONJUNCTIVITIS 372.20 R. Doyle Stulting MD, PhD Atlanta, Georgia Evan S. Loft, MD Atlanta, Georgia
ETIOLOGY Blepharoconjunctivitis is one of the most commonly encountered diseases in ophthalmology. In 1982, a classification of chronic blepharitis was introduced that has served as a useful framework on which to build an understanding of this disease. This classification scheme of six clinically distinguishable groups was based on careful ophthalmologic and dermatologic examinations, cultures of the lids and conjunctiva, and lipid studies. The categories are: 1. Staphylococcal; 2. Seborrheic; 3. Mixed seborrheic/staphylococcal; 4. Seborrheic with meibomian seborrhea; 5. Seborrheic with secondary meibomianitis; and 6. Meibomian keratoconjunctivitis.
Mixed seborrheic/staphylococcal conjunctivitis
COURSE
Mixed seborrheic/staphylococcal blepharoconjunctivitis exhibits signs of both types of blepharitis and an equal male/female distribution. The debris is characteristically an oily, greasy crusting on the anterior lid and collarettes on the lashes. Patients typically have more inflammation than those with seborrheic blepharoconjunctivitis alone. Approximately 35% of patients with mixed seborrheic/staphylococcal blepharoconjunctivitis have associated keratoconjunctivitis sicca, and most patients also have seborrheic dermatitis. Keratoconjunctivitis is common in mixed seborrheic/staphylococcal blepharoconjunctivitis with mild inferior tarsal conjunctival papillary hypertrophy, bulbar conjunctival injection, punctate epithelial erosions over the inferior third of the cornea, and, rarely, follicular hypertrophy over the inferior tarsal conjunctiva.
Staphylococcal blepharoconjunctivitis
Meibomian gland dysfunction
The symptoms of chronic staphylococcal blepharoconjunctivitis typically wax and wane, and they are usually of shorter
Meibomian gland dysfunction is most common in fair-skinned individuals, and there is an equal male/female ratio. The inci-
Any combination of the aforementioned entities may occur in any one patient. The latter three subtypes are commonly grouped together into one category referred to as meibomian gland dysfunction.
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Clinical features of staphylococcal blepharoconjunctivitis include eyelid inflammation, erythema, possibly edema along the anterior ciliary portion of the lid, and, rarely, madarosis. The eyelid margin is frequently involved. There may be telangiectatic blood vessels along the lid margin. Crusting of the lashes occurs with collarettes surrounding individual cilia. Anterior or posterior hordeola occur intermittently. Fifteen percent of patients develop bulbar and tarsal conjunctival changes, including injection and, when chronic, papillary hypertrophy of the tarsal conjunctiva. With acute exacerbation, a follicular response may develop over the inferior tarsal plate. A keratitis characterized by punctate epithelial erosions involving the inferior third of the cornea may occur, and may be secondary to staphylococcal exotoxin. Other possible causes of this keratitis include an abnormal blink mechanism and destabilization of the tear film. Marginal corneal infi ltrates, phlyctenules, and corneal ulcers can also occur. Fifty percent of patients with staphylococcal blepharoconjunctivitis also have keratoconjunctivitis sicca that may have an associated corneal punctate epitheliopathy.
Laboratory findings Currently, specific diagnostic tests for blepharoconjunctivitis are not available. Eyelid and conjunctival cultures may be performed in cases of suspected staphylococcal blepharitis, especially if the condition is chronic or worsening with treatment. Antibiotics should be discontinued before culture. Of eyelid cultures from patients with chronic blepharitis, 96% were positive for S. epidermidis, 93% were positive for Propionibacterium acnes, 77% were positive for Corynebacterium sp., 11% were positive for Acinetobacter sp., and 10.5% were positive for S. aureus. Results of aerobic and anaerobic cultures from lids and conjunctiva showed that the only group of patients with blepharitis who had a significant percentage of positive cultures for S. aureus were those with clinically defi ned staphylococcal and mixed staphylococcal/seborrheic blepharitis. More than 80% of patients in the mixed group have positive eyelid cultures for S. aureus, and 50% have positive conjunctival cultures.
should result in significant improvement of keratitis medicamentosa. Alternative medical treatments must be considered in patients with specific known drug allergies or intolerance to drug-induced side effects. Use of tetracyclines during pregnancy is contraindicated. Occasionally, more severe keratitis, phlyctenules, and corneal ulceration may require more intensive therapy.
COMMENTS Blepharoconjunctivitis is commonly encountered by the ophthalmologist. Close observation of the specific eyelid, conjunctival, and corneal changes will help determine the type of blepharoconjunctivitis present and thus determine the type of treatment regimen best suited for the individual patient. Eyelid hygiene and topical antibiotics will cure or control staphylococcal or mixed seborrheic/staphylococcal blepharoconjunctivitis. When these therapies fail, attention should be given to other possible diagnoses or additional underlying problems. Discontinuation of all therapy and culturing or reculturing of the eyelids and conjunctiva may be indicated.
CHAPTER 236 • Distichiasis
dence of this disease increases with age. Keratoconjunctivitis sicca, seborrheic dermatitis and acne rosacea are frequently observed along with meibomian dysfunction. Chalazion incidence is higher in these patients. Tear break-up time is usually reduced. Various lid margin fi ndings may be observed on examination, including erythema, architectural irregularity, thickening, injection and telangiectasia. Meibomian gland apertures may be displaced, irregular, decreased in numbers, pouting with secretions, or plugged with yellow concretions. In meibomian dysfunction, pressure applied to the lid margins may not expulse Meibomian secretions or it can produce large amounts of cloudy or foamy secretions.
REFERENCES Bowman RW, Dougherty JM, McCulley JP: Chronic blepharitis and dry eyes. Int Ophthalmol Clin 27:27–35, 1987. Bowman RW, Miller K, McCulley JP: Diagnosis and treatment of chronic blepharitis. In: Focal points: clinical modules for ophthalmologists. San Francisco, American Academy of Ophthalmology, 1988. Driver PJ, Lemp MA: Meibomian gland dysfunction. Surv Ophthalmol 40:343–367, 1996.
TREATMENT
Groden LR, Murphy B, Rodnite J, et al: Lid flora in blepharitis. Cornea 10:50–53, 1991.
Systemic
McCulley JP: Blepharoconjunctivitis. Int Ophthalmol Clin 24:65–77, 1984.
●
Systemic antibiotics (occasionally for severe cases), such as tetracycline.
Ocular ● ●
●
●
●
●
Warm compresses to eyelids for 5 to 10 minutes b.i.d. Eyelid scrubs using baby shampoo or a commercial lid scrub b.i.d. Bacitracin (first choice) or erythromycin ointment to the lid margins after lid scrubs and to the cul-de-sac at bedtime. Rarely, short-term topical steroids for hypersensitivity corneal infi ltrates. Preservative-free artificial tears and other dry eye treatments. Dermatologic consultation for seborrheic dermatitis.
McCulley JP, Dougherty J, Deneau DG: Classification of chronic blepharitis. Ophthalmology 89:1173–1180, 1982. Smolin G, Okumoto MA: Staphylococcal blepharitis. Arch Ophthalmol 95:812–816, 1977.
236 DISTICHIASIS 743.63 Phillip Hyunchul Choo, MD Sacramento, California Sumaira A. Arain, MD Sacramento, California
PRECAUTIONS Conjunctivitis medicamentosa may occur, especially in patients with associated keratoconjunctivitis sicca. Eyelid scrubs, soaps, and artificial tear preservatives may also cause hypersensitivity and allergic reactions. The use of preservative-free tears is recommended. Discontinuation of all potentially toxic medication
Distichiasis is a condition in which lashes grow posterior to the normal row of lashes. It can be either congenital or acquired and may present as only a few isolated eyelashes, or as a complete accessory row of lashes. These lashes often rub directly on or become matted against the cornea, causing persistent eye pain and corneal damage.
435
SECTION 21 • Eyelids
ETIOLOGY/INCIDENCE
TREATMENT
Congenital distichiasis
Medical
This is a rare condition, which may occur sporadically or as an autosomal dominant trait with variable expressivity and high penetrance. It is a developmental anomaly in which embryonic pilosebaceous units differentiate into hair follicles rather than into meibomian glands. Congenital distichiasis can be isolated or occur in association with some forms of familial lymphedema, especially the 4th type of late-onset hereditary lymphedema that presents during adolescence. Other associated abnormalities include entropion, ptosis, congenital corneal hypesthesia, cleft lip and palate, vertebral anomalies, extradural cysts, webbed neck, yellow nails, peripheral vascular anomalies, trisomy 18, congenital heart defects, blepharocheilodontic syndrome and other systemic anomalies.
No treatment may be necessary if the patient is asymptomatic and without keratopathy. For temporary symptomatic relief of epithelial breakdown of the cornea, lubricating drops and ointment are useful. Therapeutic soft contact lenses may also be helpful to protect the cornea in cases of corneal epithelial breakdown, as well as to provide symptomatic relief.
Acquired distichiasis This is a more common form, and is often seen secondary to certain stimuli that provoke a metaplastic change within or near the meibomian gland. This metaplastic change can occur with diseases that affect both the eyelid margin and the conjunctiva, such as chronic blepharitis, staphylococcal hypersensitivity, meibomian gland dysfunction and meibomianitis, Stevens-Johnson syndrome, ocular cicatricial pemphigoid and chemical ocular injuries.
COURSE/PROGNOSIS Distichiasis, if left untreated, may lead to corneal thinning, scarring, or even ulceration.
DIAGNOSIS On slit-lamp examination, abnormal lashes are noted arising from or near the meibomian gland orifices. The cornea should be evaluated for any epithelial defects or signs of permanent scarring.
Clinical signs and symptoms Symptoms may include decrease in vision, eye pain and irritation, foreign body sensation and tearing. A penlight or slit lamp examination should reveal eyelashes growing posteriorly (along where one would expect the orifices of the meibomian glands to be) to the normal row of lashes. There may be secondary signs such as epithelial breakdown of the cornea, corneal scarring or pannus formation, and conjunctival injection and chemosis.
Differential diagnosis Distichiasis should be differentiated from trichiasis and entropion. Trichiasis is a condition in which eyelashes grow from the normal anterior portion of the eyelid margin but are turned in or misdirected towards the eye. Entropion is a condition in which the entire eyelid margin turns inward.
PROPHYLAXIS Proper and chronic treatment of diseases such as blepharitis and ocular cicatricial pemphigoid will decrease the stimuli to create the formation of acquired distichiatic eyelashes.
436
Surgical Various surgical procedures have been described for the treatment of distichiasis. Epilation with electrolysis is useful in treating small numbers or a focal area of distichiatic lashes. This procedure is often done in the office with a local infi ltrative block, while general anesthesia is required in treating infants and young children. With the aid of a slit-lamp or an operating microscope, the distichiatic eyelashes are identified and electrolysized. Various instruments such as the Ellman Surgitron (Ellman International Inc., Oceanside, NY) are commercially available for performing electrolysis of eyelashes. While performing electrolysis, it is important to treat the entire hair follicle. The eyelash should pull out effortlessly from the eyelid margin after treatment. If it does not, the follicle should be retreated. The success rate for trichiatic eyelashes is approximately 60–70%, and thus repeat treatment may be necessary, especially when treating multiple eyelashes. Cryosurgery is an option for the treatment of a wider area of distichiasis. A double freeze-thaw treatment down to −20ºC is recommended for permanent destruction of the lash follicles. Since temperatures of −30ºC and lower may cause tissue necrosis and subsequent scarring, the use of a thermocouple to monitor actual tissue temperature is recommended. Furthermore, this approach is non-selective. The normal, more anterior eyelashes may also be permanently damaged by cryotherapy, leading to complete madarosis. For this reason, eyelid splitting approaches are more commonly used to treat wide areas of distichiatic eyelashes. Lid splitting procedures involve an incision made in the eyelid margin immediately anterior to the row of distichiatic eyelashes. The use of a chalazion clamp and an ocular surgery blade are helpful. The incision is continued to about 3 mm in depth to expose the entire distichiatic eyelash follicle. Depending on the surgeon’s preference, the distichiatic lash follicles can then be treated either with direct application of electrolysis, direct excision, or cryotherapy applied to the conjunctival side of the eyelid margin. Later, the incision may be closed directly with sutures, or the anterior lamella can be recessed approximately 2 mm in relation to the posterior lamella and fi xated to the tarsal plate. In 1993, O’Donnell and Collin reviewed a series of 24 patients with distichiasis who underwent treatment with epilation, cryotherapy, or a lid splitting procedure followed by cryotherapy to the posterior lamella. They found that lid splitting with cryotherapy relieved symptoms without retreatment in 87% of patients. In 1997, Vaughn and others reported the results of an eyelid splitting procedure in 17 eyelids of 5 patients with distichiasis. After the lid was split, each aberrant eyelash follicle was individually excised or microhyphrecated and subsequently removed. This approach yielded excellent functional and cosmetic results. Furthermore, White in 1975 described a surgery in which the posterior portion of the eyelid margin containing the distichiatic eyelashes was directly excised. A mucous membrane graft was then sutured in place to cover the defect.
COMPLICATIONS
REFERENCES Anderson RL, Harvey JT: Lid splitting and posterior lamella cryosurgery for congenital and acquired distichiasis. Arch Ophthalmol 99:631–634, 1981. Choo PH: Distichiasis, trichiasis, and entropion: advances in management. Int Opthalmol Clin 42(2):75–87, 2002.
CHAPTER 237 • Ectropion
All of the above treatments could result in recurrence of distichiasis, formation of trichiasis, lid notching and cicatricial entropion. Cryotherapy may result in significant post-operative swelling of the lid and the conjunctiva. Furthermore, cryotherapy applied to the conjunctiva may aggravate an underlying conjunctival disorder, as well as cause conjunctival scarring and shortening. In addition, lid necrosis can occur if the treatment temperature is −30ºC or less. Eyelid splitting procedures may also lead to some potential complications. These include prolonged eyelid edema, keratinization of the posterior eyelid margin, and recurrence of the distichiatic eyelashes. Lastly, one should avoid damage to the normal eyelash follicles to avoid permanent madarosis. Supported by an unrestricted grant from Research to Prevent Blindness, Inc., New York, New York.
tendon, dehiscence of the lower lid retractors, atrophy of the orbicularis muscle, and hypertrophy of the tarsus with fragmentation of its elastic and collagen fibers result in an outward turning of the lid. Involutional enophthalmos may exacerbate the condition. Although the upper eyelid can be affected in a condition called floppy eyelid syndrome, involutional ectropion usually is described for the lower eyelid. Paralytic ectropion is caused by facial nerve palsy and is often unilateral. Bell’s palsy, trauma, cerebrovascular accidents, and damage to the peripheral seventh nerve during tumor removal are the most frequent causes. Loss of orbicularis muscle tone and decreased support to gravitational pull by stretching of the canthal tendons results in ectropion which becomes more pronounced with time. Cicatricial ectropion is the result of scarring or contracture of the skin and/or orbicularis muscle causing vertical shortening of the eyelid due to trauma, inflammatory processes or skin disorders. Overzealous blepharoplasty of the lower lid can result in a cicatricial ectropion or lid retraction. Mechanical ectropion is caused by the weight of a mass on the anterior lamella or mid-face ptosis, pulling the lid down. A tumor of the lower eyelid, fluid accumulation secondary to sinusitis, thyroid disease, lupus, or other medical problems can result in mechanical ectropion. Patients with mid-face ptosis can have sagging of the cheek and face, resulting in a mechanical ectropion.
Frueh BR: Treatment of distichiasis with cryotherapy. Surg Ophthalmol 12:100–103, 1981. O’Donnell BA, Collin JR: Distichiasis: management with cryotherapy to the posterior lamella. Br J Ophthalmol 77:289–292, 1993.
COURSE/PROGNOSIS
White JH: Correction of distichiasis by tarsal resection and mucous membrane grafting. Am J Ophthalmol 80:507–508, 1975.
All forms of ectropion, especially involutional and paralytic, worsen with time if untreated, resulting in conjunctival hypertrophy and keratinization. The increased exposure of the ocular surface may result in poor lubrication of the corneal epithelium with an increased risk of exposure keratopathy and infection. Punctum eversion, sagging of the lid and lacrimal pump failure usually result in chronic epiphora.
237 ECTROPION 374.10 Kostas G. Boboridis, MD, PhD Thessaloniki, Greece
DIAGNOSIS Clinical signs and symptoms
Ectropion is an eyelid malposition presenting from simple horizontal laxity to an outward turning of the lid margin away from its normal apposition to the globe. It may involve either eyelid but it mainly affects the lower.
ETIOLOGY/INCIDENCE Ectropion is classified as both congenital and acquired. Acquired ectropion is further classified into four categories according to the underlying etiology, as involutional, paralytic, cictricial, or mechanical (Figure 237.1). Congenital ectropion is caused by vertical shortage of the anterior lamella on the lateral third of the lower eyelid often combined with canthal tendon laxity. It is frequently associated with additional facial abnormalities as in Down syndrome, blepharophimosis and Möbius syndrome or lamellar ichthyosis. Isolated ectropion due to horizontal lid laxity is very rare congenital condition called euryblepharon. Involutional, or senile, ectropion is the most common type encountered in the aging population. Senile stretching or weakening of the medial and more frequently the lateral canthal
The main symptoms are chronic epiphora and recurrent conjunctivitis. Examination of the eyelid position and contour, punctum position and size, orbicularis function, Bell’s phenomenon, tear film stability and patency of the lacrimal system as well as recognition of cicatricial components are all necessary in evaluating ectropion. The degree of horizontal laxity is assessed with the distraction test, by drawing the center of the eyelid away from the globe and measuring the distance. More than 8–10 mm is considered abnormal. The eyelid elasticity and orbicularis tone are assessed with the snap back test by pulling the lid from the globe and releasing it. An eyelid that snaps back only after the patient has blinked is considered abnormal. A lateral pull on the lid reveals medial canthal tendon laxity when the punctum is drawn to or beyond the medial limbus. Medial pull reveals lateral canthal tendon laxity when the palpebral angle is pulled for more than 10 mm from the lateral orbital rim.
TREATMENT There is no systemic treatment.
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SECTION 21 • Eyelids a
c
b
d
FIGURE 237.1. a) Involutional. b) Paralytic. c) Cicatricial. d) Mechanical.
Ocular Asymptomatic or mild cases require only topical artificial tear drops. Intense lubrication and antibiotic ointment are indicated for symptomatic patients with chronic conjunctivitis. The eyelids may need to be taped closed at bedtime, especially in paralytic cases. Softening of the skin and lid margin with topical steroid ointment is beneficial in advanced cases. Intralesional steroid injection may soften the scar in cicatricial ectropion. Surgical intervention is reserved for chronic symptomatic cases that require permanent solution.
Surgical Congenital Severe and symptomatic cases require a full-thickness skin graft for vertical lengthening of anterior lamella combined with canthal tendon tightening.
Involutional For mild cases, the inverting suture technique can shorten the posterior lamella and provide temporary relief. Three doublearmed sutures are passed in mattress fashion through the lid,
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from the palpebral conjunctiva at the inferior border of the tarsus out cutaneously at the level of the orbital rim. For generalized horizontal laxity, tightening of the lid can be performed by resecting a full-thickness wedge of the eyelid at the lateral canthal angle, as described by Bick. However, this does not address and rather exacerbates canthal tendon laxity resulting in rounding of the fissure. For punctum eversion a medial spindle procedure is performed, in which a diamond-shaped excision of tarsoconjunctiva is performed in the posterior lamella bellow the punctum. A double armed absorbable suture engaging the retractors closes the defect and exits through the skin below the level of incision, effectively acting as an inverting and posterior lamella shortening suture. When there is punctum eversion with horizontal laxity, the ‘lazy T’ procedure is indicated in which the medial spindle is combined with a medial full thickness wedge excision. If medial tendon laxity is present a canthal ligament (anterior or posterior limp) plication is also performed. The method of choice to correct involutional ectropion and any form of horizontal laxity is the lateral tarsal strip or canthal
type of ectropion as well as the specific anatomical structure that requires surgical intervention. In all cases of ectropion, the eye is at an increased risk for exposure keratopathy and epithelial breakdown, which may result in infection, ulceration, scarring and permanent visual loss. Patients with ectropion must be observed and correctly treated when indicated to prevent potential complications from ocular surface exposure.
Paralytic
Leatherbarrow B: Lower eyelid ectropion. Oculoplastic surgery. London, Martin Dunitz, 2002:69–83.
Paralytic horizontal laxity may be transient and should be observed with conservative treatment for 3 to 6 months if the ocular surface is stable and not at risk for exposure and infection. Surgical repair is similar to that for involutional ectropion. A medial cantholpasty with the Otis Lee procedure and/or lateral tarsorrhaphy may be necessary to correct corneal exposure due to lagophthalmos and ectropion. A fascia lata sling can be used to support the eyelid in advanced cases.The fascia strip is sutured to the medial canthal tendon, placed between the orbicularis muscle and the lower lid tarsus and then attached to the lateral canthal tendon and orbital rim. Synthetic material may also used. Temporalis muscle transfer can be performed along with other reconstructive facial surgery to reanimate the lids with better functional and cosmetic results.
Cicatricial Cicatricial ectropion is corrected by lengthening the contracted anterior lamella. Z-plasty can address an isolated scar in a particular direction. Full-thickness skin grafts or flaps from the lateral upper eyelid are necessary to relieve generalized tension and also lengthen the lid vertically.
Mechanical Removal of the lesion causing increased weight is the treatment of choice. Tumor excision and horizontal tightening of the reconstructed lid is indicated in other cases. Occasionally, a suborbicularis oculi fat (SOOF) lift is indicated in patients with mid-face ptosis with sagging of the cheek and face causing vertical shortage of the lid.
REFERENCES Anderson RL, Gordy DD: The tarsal strip procedure. Arch Ophthalmol 97:2192–2196, 1979. Bick MW: Surgical management of orbital tarsal disparity. Arch Ophthalmol 75:386–389, 1966. Collin JRO: Ectropion. A manual of systematic eyelid surgery. London, Churchill Livingstone, 1995: 27–40.
Smith B: The ‘Lazy-T’ correction of entropion of the lower punctum. Arch Ophthalmol 94:171–2, 1976.
238 ENTROPION 370.00 Roger A. Dailey, MD Portland, Oregon Robert N. Tower, MD Seattle, Washington
INTRODUCTION Entropion of the eyelids is defined as an inversion of the eyelid margin so that the margin itself, the cilia, and sometimes the external keratinizing squamous epithelium of the eyelid are brought into contact with the surface of the eye, producing irritation and abrasion. This discussion is directed toward involutional entropion of the lower eyelid unless otherwise specified. The references provide more specific information regarding upper lid and cicatricial entropion.
ETIOLOGY ●
COMPLICATIONS ●
Possible complications of an untreated ectropion include the following: ● Epiphora and chronic conjunctivitis; ● Conjunctival hyperemia and hypertrophy with keratinization; ● Exposure keratopathy and epithelial breakdown; ● Corneal infection with ulceration.
CHAPTER 238 • Entropion
sling procedure. This addresses the most common cause of ectropion, which is laxity of the lateral canthal tendon. A lateral canthotomy and an inferior cantholysis are performed with separation of the anterior and posterior lamellae. A tarsal strip is fashioned from the lateral tarsus by removal of skin, orbicularis and conjunctival epithelium. The lid is shortened horizontally, and the shortened tarsal strip is reattached anatomically with a nonabsorbable suture to the periosteum of Whitnall’s tubercle 2 mm inside of the lateral orbital rim. The canthal angle and the skin incision are reconstructed with suture. In addition to the tarsal strip procedure and in combination to any of the above, some surgeons believe the lower eyelid retractors must be reattached to the inferior border of the tarsus for vertical shortening of the eyelid similar to entropion repair.
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The lower lid retractors lose control of the inferior margin of the tarsus, allowing it to rotate anteriorly and superiorly. The preseptal muscle tends to override the pretarsal muscle. Horizontal lid laxity increases the ability of the eyelid to turn in. Enophthalmos as occurs in aging was once thought to be a factor in this process, but this has been shown to be incorrect.
COURSE/PROGNOSIS COMMENTS Many procedures have been described for the treatment of ectropion. Before the appropriate treatment can be instituted, the surgeon must accurately diagnose the causative factor and
Entropion can occur in either the upper or lower eyelid. This condition is irritating and potentially sight-threatening in that the skin and lashes can mechanically abrade the corneal epithelium, causing pain, photophobia, and increased
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SECTION 21 • Eyelids
susceptibility to infectious corneal infi ltration that could lead to scarring or progress to endophthalmitis. Patients typically present with complaints of eye irritation, photophobia, and foreign body sensation. Occasionally, patients have noticed the in-turning of the lid and lashes; they may be using tape to keep the lid everted. With appropriate surgical management, the prognosis for full recovery is excellent with rare recurrence after surgery. Cicatricial variants (e.g. cicatricial pemphigoid) progress, and treatment tends to be more aggressive and have a lower long-term success rate. Associated corneal abnormalities usually require topical antibiotics and tear substitutes.
DIAGNOSIS ●
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A broad classification scheme includes congenital, cicatricial, spastic and involutional. The differential diagnosis includes epiblepharon, epicanthal folds, trichiasis and distichiasis. The history includes pain, irritation, chronic allergies, chronic glaucoma medication use, eyelid observed turning in, and associated systemic disease. The physical examination reveals lower eyelid laxity, conjunctival scarring with or without keratinization, eyelid observed turning in, trichiasis and superficial punctate keratitis. If actual lower eyelid turning-in is not see, the clinician should have the patient look up and the grasp the patient’s preseptal muscle as in a ‘snap test.’ Then, the patient should look down, squeezing orbicularis, as the clinician lets go. This will demonstrate the entropion.
incision to accomplish the same thing, particularly if there is no significant horizontal lid laxity and horizontal shortening is not necessary. Correction of cicatricial entropion generally involves the placement of a spacer in the posterior aspect of the lower lid after transconjunctival incision. Acellular dermis or hard palate mucosa is an excellent choice; others include sclera, fascia, autogenous tarsus, nasal septal mucosa, and buccal mucosa.
COMMENTS Involutional and cicatricial entropion requires definitive surgical treatment to avoid sight-threatening secondary corneal complications. The success rate of this surgery when performed by experienced physicians is extremely high.
REFERENCES Anderson RL: The tarsal strip. In: Transactions of the New Orleans Academy of Ophthalmology. St Louis, CV Mosby, 1982:352–363. D’Ostroph AO, Dailey RA: Cicatricial entropion associated with chronic dipivefrin application. Ophthalmic Plast Reconstr Surg 17(5):328–31, 2001. Jones LT, Reeh MJ, Wobig JL: Senile entropion. A new concept for correction. Am J Ophthalmol 74:321–329, 1972. Quickert MH, Wilkes DI, Dryden RM: Non-incisional correction of epiblepharon and congenital entropion. Arch Ophthalmol 101:778–781, 1981. Weiss FA: Surgical treatment of entropion. J Int Coll Surg 21:758–760, 1954.
TREATMENT
239 EPICANTHUS 743.63
Medical Be sure to manage any associated ocular surface problems with the appropriate topical antibiotics and/or lubricants. Temporary taping of the eyelid into a better position will help avoid further keratitis until a more definitive procedure can be performed.
Roger A. Dailey, MD Portland, Oregon John D. Ng, MD, MS, FACS Portland, Oregon
Surgical Quickert sutures can be placed with the use of local anesthesia. This is a quick method to relieve the entropion and can be done in the examination lane or at the bedside. It should not be considered definitive but can last for weeks to months. One needle of double-armed suture of 5-0 chromic catgut or 5-0 Vicryl suture is placed deep in the conjunctival fornix and brought anteriorly and superiorly through the lid tissues so it exits the skin near the lid margin, beneath the lash line. The second needle is then passed in a similar fashion 3 to 4 mm lateral. Two additional double-armed sutures are placed: one medially and one laterally. The sutures are tied, causing an eversion of the lid margin. A definitive approach to involutional entropion involves a lateral cantholysis followed by transconjunctival incision just inferior to the tarsus. The inferior retractors are then isolated and reattached to the anterior/inferior portion of the tarsus with multiple interrupted sutures. The lid then can be shortened using a tarsal strip procedure. The lateral canthus is reformed with tarsus-to-lateral rim periosteal sutures, ensuring that the tarsus is slightly posterior to the rim. Closure of the skin is completed. An alternative would be to use a subciliary
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The term epicanthus refers to a vertical fold of skin that is located between the medial canthus and the nose and may cover part or all of the inner canthus of the eye.
ETIOLOGY/INCIDENCE ●
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Epicanthal folds are common in infants and children of all races but are a characteristic finding in persons of all ages with Asian ancestry. Fetal alcohol syndrome often exhibits epicanthus. Rarely, the blepharophimosis tetrad can occur as a developmental anomaly, but more commonly it is transmitted as an autosomal dominant trait, linked to the 3q21-24 gene, with 100% penetrance. Structurally, the folds appear to be related to tension in underlying excessive orbicularis muscle, with a relative lack of attachment of the skin to the underlying structures. Differential growth rates of skin in the medial canthal area and tension placed on the skin by the underlying orbicularis also may play roles.
COURSE/PROGNOSIS ●
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DIAGNOSIS ●
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The diagnosis of epicanthus is easily made on external examination. Amblyopia is rare in association with epicanthus and is usually associated with other problems, such as anisometropia and astigmatism. No spinal abnormalities have been reported from patients who have had compensatory head tilt from blepharoptosis for many years.
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COMMENTS Types of epicanthus Epicanthus supraciliaris is a vertical fold of skin that extends from just below the brow to an area just over the infraorbital rim, usually obscuring the caruncle. In epicanthus palpebralis, the skin fold extends from the medial aspect of the upper lid to the medial aspect of the lower lid in a nearly symmetric fashion and often obscures the caruncle. This is the most common configuration. Epicanthus tarsalis refers to a condition in which a fold begins laterally and extends over the entire eyelid, ending in the medial canthus. This is the typical Asian upper lid configuration. Epiblepharon of the upper lids is distinguished from epicanthus tarsalis by its lack of true superior palpebral fold and the presence of a fold of skin that overlaps the eyelid margin and presses the lashes against the cornea. Epicanthus inversus is similar to epicanthus tarsalis but involves the lower lid. It usually occurs as a part of Komoto’s tetrad of blepharoptosis, blepharophimosis, telecanthus, and epicanthus inversus; blepharophimosis refers to narrowing of the palpebral aperture in its horizontal dimension.
Epicanthus supraciliaris, palpebralis, and tarsalis tend to regress spontaneously with maturity and only occasionally require surgery. Typically, this requires only resection of underlying muscle and then deep skin fi xation. Epicanthus inversus rarely improves with age and generally responds to surgical managements such as a Y-to-V procedure, Z-plasties, or the fi ve-flap technique. Amblyopia can occur in these patients and should be checked for at regular examinations in the early years of the patient’s life.
TREATMENT
Stromland K: Visual impairment and ocular abnormalities in children with fetal alcohol syndrome. Addict Biol 9:153–7, 2004.
CHAPTER 240 • Eyelid Contusions, Lacerations, and Avulsions
The majority of children of Asian ancestry will lose these folds during and after puberty, but the folds persist in 2% to 5% of whites. Surgical management relieves the condition in as many as 90% of cases. Surgical complications include visible scars, asymmetry, recurrence, and, rarely, infection.
at an early age and difficult to work with surgically but becomes more amenable to intervention at a later age. This condition generally responds best to Verwey’s Y-to-V operation, double Z-plasty, Mustard’s technique, or the five-flap procedure. Spaeth’s technique, which involves excision of a portion of the fold of skin, is generally reserved for mild cases of epicanthus inversus. In 1989, Anderson and Nowinski described the five-flap technique, which they consider to be the best application for epicanthus inversus. This is a modified Y-to-V procedure combined with a double Z-plasty. It has the advantage of being simple to mark out on the lid, and the flaps are small and relatively easy to transpose. In cases in which there is associated telecanthus, it should be repaired at the same time with medial canthal tendon resection or transnasal wiring. It is important to avoid injuring the canaliculus or lacrimal sac. A lateral canthoplasty can be performed at the same time in cases of blepharophimosis.
REFERENCES Callahan A: Surgical correction of the blepharophimosis syndromes. Trans Am Acad Ophthalmol Otolaryngol 77:687–695, 1973. Hughes WL: Surgical treatment of congenital palpebral phimosis: the Y-V operation. Arch Ophthalmol 54:586–590, 1955. Johnson CC: Epicanthus and epiblepharon. Arch Ophthalmol 96:1030– 1033, 1978. Jordan DR, Anderson RL: Epicanthal folds: a deep tissue approach. Arch Ophthalmol 107:1532–1535, 1989.
Surgical In general, epicanthus tarsalis, palpebralis, and supraciliaris will diminish with age as the child’s nasal dorsum becomes more prominent. If ptosis repair must be performed and significantly worsens the fold, the fold can be repaired simultaneously. Often, consideration is given to surgery before the child is of school age or soon after starting school to avoid or at least minimize some of the psychologic problems regarding body image and self-esteem that can arise. Older children can be operated on with mild sedation, and the results are more predictable. ● Skin resection should be avoided in the surgical management of epicanthus tarsalis, palpebralis, and supraciliaris because it can actually accentuate the anomaly. A preferred approach is to incise the skin directly over the fold, remove the orbicularis muscle in this area, and close the skin with deep attachments to maintain a crease and remove the fold. The crease will soften with time, but the fold should not recur. ● Epicanthus inversus typically shows little improvement with age. In these children, the skin tends to be very stiff
240 EYELID CONTUSIONS 921.1, LACERATIONS 870.8, AND AVULSIONS 871.3 Robert C. Della Rocca, MD, FACS New York, New York David A. Della Rocca, MD New York, New York John Nassif, MD Clearwater, Florida John Koh, MD Southfield, Michigan Eyelid contusions, lacerations, and canthal avulsions may result in severe functional or structural abnormalities. Complete
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ocular evaluation and prompt determination of the extent of adnexal injury and the absence or presence of canalicular laceration allows for appropriate and timely repair of the injury. This will promote optimum functional and cosmetic results while limiting the possibility of early and late complications.
DIAGNOSIS SECTION 21 • Eyelids
Clinical signs and symptoms On inspection of the eyelids and periorbital region, ecchymosis and edema can be very significant, obscuring the location and extent of lacerations. It is important to rule out direct or indirect ocular injury. A careful history will help in raising suspicion that systemic, ocular or orbital injury may have occurred. Visual assessment, including visual acuity testing and pupil and ocular motility evaluation should be done, in addition to slit lamp microscopy, tonometry and ophthalmoscopy. This assessment, which should include adnexal evaluation, may be limited by significant periorbital and eyelid edema. Supportive measures including the use of cool compresses can be helpful prior to detailed ocular and adnexal examination. In some cases, thorough evaluation must be delayed until anesthesia is available in the operating room. Canalicular involvement and canthal displacement must be recognized to allow for appropriate surgical planning. Ptosis is common with upper eyelid lacerations and may be due to edema or direct injury to the levator complex.
Laboratory findings Computed tomography scanning is advised if an orbital fracture is suspected. Orbital fractures are suggested by the presence of extraocular motility dysfunction, infraorbital anesthesia, globe displacement, marked periorbital edema or signs of orbital emphysema. Magnetic resonance imaging (MRI) gives excellent soft tissue contrast, but is less effective in defi ning orbital fractures. B-scan ultrasonography or the other scanning modalities listed above are helpful in evaluation of the globe and optic nerve if the eyelids can not be opened secondary to edema.
TREATMENT Severe pain is uncommon with injury to adnexal tissue. If pain control is needed we recommend acetaminophen or acetaminophen in combination with codeine. Tetanus immunization may be necessary if the patient has not had a tetanus booster within the last 5 years. Broad-spectrum antibiotics are recommended, especially in the context of animal or human bites. If a wound is older than 2 days, we consider debridement of the granulation tissue from the wound edges at the start of the case. We recommend primary repair of the tissues unless there is significant bacterial contamination or extensive tissue loss. Simple partial lacerations of the skin can be repaired with 6-0 nylon or silk sutures in an interrupted fashion. Full thickness lacerations are repaired in a stepwise fashion. First, the lid margin is closed using 6-0 silk sutures in 3 interrupted passes through the meibomian gland orifices, lash line and at the grey line sequentially. It is important to make sure that the placement of the first silk suture approximates the tarsal plate neatly. These three sutures are tied and left long for later tying to the skin closing sutures (away from the cornea). Next, the tarsal
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plate, distal to the lid margin, is closed with 5-0 absorbable suture. Last, the skin is closed with interrupted 6-0 silk sutures. Full thickness tissue loss is uncommon and can be mimicked by edema and wound contracture. Minimal tissue loss characterized by loss of up to one-quarter of the eyelid may be managed by a full thickness closure combined with a lateral canthotomy and cantholysis. Moderate tissue loss (one quarter to one half of the eyelid) might necessitate a skin advancement flap of Tenzel to extend the length of the eyelid prior to closure. Severe tissue loss of greater than half of the eyelid length would usually necessitate an eyelid sharing procedure such as the Hughes procedure for inferior eyelid loss or the Cutler–Beard flap for upper eyelid loss. Avulsions or lacerations of the canthus indicate the reattachment of the tissues to the appropriate level of periostium. Injury to the lateral canthus can be repaired by the creation of a lateral tarsal strip with or without a periostial flap. A medial avulsion requires the reattachment of the posterior limb of the medial canthal tendon to the posterior lacrimal crest periorbita. The use of transnasal wiring may be necessary if there is severe tissue or bone destruction.
COMPLICATIONS ●
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Ptosis: due to levator complex injury, severe traumatic edema (levator aponeurosis stretching and dehiscence), or on a neurogenic basis. Epiphora: due to canalicular laceration, lacrimal sac injury, or punctal eversion. Corneal exposure: due to post-repair eyelid malpositions or lagophthalmos. Eyelid malpositions: ectropion, entropion, eyelid retraction. Scar hypertrophy or depigmentation.
COMMENTS On an emergent basis, concurrent with adnexal and canthal injuries, the presence of symptomatic and compressive orbital hemorrhage must be treated promptly with a lateral canthotomy and cantholysis. Following the cantholysis, the periorbita is opened to evacuate the hemorrhage and clots. When possible, avoid discarding apparently devitalized tissue, whether partially or completely avulsed. Periorbital tissue has extensive vascularity and may survive trauma otherwise deemed unsurvivable. This tissue may be reattached at the site of the defect.
REFERENCES Collin JR, Tyers AG: Colour atlas of ophthalmic plastic surgery. Churchill Livingstone, 1998:9–16:11–26. Della Rocca RC, Bedrossian EH, Arthurs BP: Ophthalmic plastic surgery: decisions making and techniques. New York, McGraw-Hill, 2002:25–41:153–161:181–187. Lemke BN, Della Rocca RC: Surgery of the eyelid and orbit an anatomical approach. Norwalk, Appleton and Lange, 1990:199–212. Smith BC, Della Rocca RC, Nesi FA, Lisman RD: Ophthalmic plastic and reconstructive surgery. St Louis, CV Mosby, 1976:8–17:39–78:129– 140.
241 FACIAL MOVEMENT DISORDERS (Benign Essential Blepharospasm 333.81, Hemifacial Spasm 351.8)
ETIOLOGY/INCIDENCE
TREATMENT
Benign essential blepharospasm and hemifacial spasm are facial movement disorders that primarily affect older individuals. Benign essential blepharospasm is virtually always bilateral, but hemifacial spasm is usually unilateral. Hemifacial spasm begins with twitches in a single region of the orbicularis muscle that lasts from seconds to minutes; typically, the twitches are rather irregular and tonic in pattern. The spasm rarely recruits or extends over seconds or minutes. In contrast, benign essential blepharospasm is characterized by involuntary, tonic, sometimes-forceful closure of the eyelids that can be either intermittent or continuous. It is often associated with orofacial dyskinesia and may be associated with other movement disorders involving the trunk and the neck. These disorders are almost always axial. It is helpful to differentiate these disorders from other causes of facial spasm. Some individuals have a psychogenic cause for their blepharospasm and other individuals have dry eye conditions and other types of keratitis that stimulate a blepharospasm, particularly in response to light. Benign essential blepharospasm is related to a central nervous system disorder that remains poorly understood. It is sometimes part of, or found in conjunction with, Parkinson’s disease and it is assumed that a common cause is shared with Parkinson’s disease in these cases. Hemifacial spasm is attributed to compression of the facial nerve by an aberrant blood vessel. It may also be caused by lesions that compress the facial nerve extra-axially, by an aneurysm or an arteriovenous malformation, or by a neoplasm that involves the cerebellopontine angle.
Systemic
COURSE/PROGNOSIS All of these conditions are usually slowly progressive but may occasionally spontaneously remit. Waxing and waning over months is not unheard of. When a patient has hemifacial spasm, serious central nervous conditions must be ruled out. Synkinesis is observed with hemifacial spasm but not with facial myokymia. Facial myokymia is almost always a benign condition that involves a single muscle. Some patients with multiple sclerosis or brain stem tumors may have facial myokymia as a presenting sign; in this case, it usually persists indefinitely. More benign myokymias are always intermittent.
DIAGNOSIS The hallmark of benign essential blepharospasm is the involuntary, tonic, and forceful closure of the eyelids. Often, this
Anticholinergic agents, such as trihexyphenidyl hydrochloride (Artane), may be useful in treating many patients with benign essential blepharospasm. Typically, this drug is used at a dosage of 2 mg PO b.i.d., which is slowly increased. Many patients who titrate the medicine appropriately will be able to tolerate the blepharospasm and find the medicine useful; however, side effects, including dry mouth, dry eye and drowsiness, limit the usefulness of this drug. After anticholinergic therapy, a trial with other drugs, such as clonazepam, is sometimes warranted, but many patients are happier proceeding to botulinum toxin. No medication has been identified as specifically curative for this condition, although medical failures are often due more to failures to attempt medical titration than to failure of the medicine to work. For hemifacial spasm, there is virtually no successful systemic therapy, although carbamazepine has been estimated to benefit as many as 30 patients with this disorder.
CHAPTER 241 • Facial Movement Disorders
John R. Samples, MD Portland, Oregon
occurs to such a degree that it interferes with the patient’s lifestyle or vision. Symptoms are typically made worse by stress, fatigue, bright lights, and driving, and symptoms are usually relieved by sleep and relaxation. Patients may have idiosyncratic factors that precipitate or alleviate their symptoms. Hemifacial spasm tends to be more idiosyncratic in terms of its onset. Spasms are often precipitated or made worse by fatigue and stress.
Local Injections with botulinum toxin type A provide relief for most patients with benign essential blepharospasm and hemifacial spasm. The toxin works by interfering with acetylcholine release from nerve terminals. It may provide relief from spasm for 3 months or longer. It is generally well tolerated, although some patients develop ptosis or diplopia, especially if doses are given centrally or along the midline. A typical pattern of injection places 5 units SC at each of the two sites over the brow, 5 units at each of two sites well off the midline in the upper lid, and 5 units at each of two sites in the lower lid, for a total of six injections on a side. Injections can be tailored to the individual patient’s spasm. Complications of botulinum toxin type A include ptosis, ectropion, corneal exposure, and tearing. It appears that a tolerance to toxin does not develop. Antibodies to botulinum toxin type A do not develop with the dose commonly used for these conditions.
Surgical In benign essential blepharospasm, surgery should be reserved for individuals for whom trials with medication and botulinum toxin type A were not successful. Also, patients need to be cautioned that they may not obtain complete relief. The most effective technique is to resect the orbicularis oculi muscles. This was initially popularized by Gillum and Anderson in 1981. The technique involves the meticulous extirpation of all of the accessible orbicularis oculi, procerus, corrugator, superciliaris, and facial nerves in post orbicular fascia. Numerous refinements have been discussed.
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SECTION 21 • Eyelids
Decompression of the facial nerve in symptomatic cases is effective for hemifacial spasm. Surgery for cryptogenic cases and decompression of the facial nerve from aberrant blood vessels have been recommended. The surgical approach for hemifacial spasm requires a retromastoid craniectomy and microneurosurgical techniques and should not be undertaken unless symptoms warrant. Although some patients are extremely grateful to have had this surgery, the potential risks cannot be overlooked.
242 FLOPPY EYELID SYNDROME 374.9 Lee K. Schwartz, MD San Francisco, California Gary L. Aguilar, MD San Francisco, California
ETIOLOGY/INCIDENCE Supportive Most patients are helped by support groups, although a few patients have been adversely affected by participation when they have been exposed to patients with disease that was far more severe than their own. Because there is substantial variability in the severity of blepharospasm, the referral of patients should be individualized so as not to increase patient anxiety.
COMMENTS The treatment of benign essential blepharospasm has three phases: a medical phase, the trial of botulinum toxin type A, and the surgical phase. Hemifacial spasm responds best to botulinum toxin type A and, if this fails, to surgical decompression. There is no role for medication. Individuals show a substantial variation in their symptoms and their responses to medication. Both doses of medication and toxin injections require careful titration. Often several trials of toxin are required to find the dose and pattern that suits the patient best.
SUPPORT GROUP Benign Essential Blepharospasm Research Foundation 755 Howell Street Beaumont, TX 77706
REFERENCES Frueh BR, Felt DP, Wojno TH, et al: Treatment of blepharospasm with botulinum toxin: a preliminary report. Arch Ophthalmol 102:1464– 1468, 1984. Gillum WN, Anderson RL: Blepharospasm surgery: An anatomical approach. Arch Ophthalmol 99:1056–1062, 1981. Jankovic J: Clinical features, differential diagnosis and pathogenesis of blepharospasm and cranial cervical dystonia. In: Bosniak SL, Smith BC, eds: Advances in ophthalmic plastic and reconstructive surgeryblepharospasm. New York, Pergamon, 1985:4. Jones FTW, Samples JR, Waller RR: The treatment of essential blepharospasm. Mayo Clin Proc 60:663–666, 1985. Lingua RW: Sequelae of botulinum toxin injection. Am J Ophthalmol 100:305–307, 1985.
The floppy eyelid syndrome (FES) is an uncommon and frequently unrecognized cause of noninfectious, chronic unilateral or bilateral papillary conjunctivitis. The condition is characterized by loose, ‘floppy’ eyelids associated with punctate epithelial keratopathy (PEK), ptosis of lateral eyelashes and the typical conjunctival changes. The diagnosis has been made in patients of both sexes ranging in age from 2 to 80, but the disorder most commonly affects the middle-aged, and in particular middle-aged, obese males. The floppiness of the eyelids is due to laxity of the tarsus, which is a consequence of a decrease in tarsal elastin. There may be several pathways that lead to FES. The primary cause of the tarsal laxity has been explained by the frequent observation that the affected side in unilateral cases corresponds to the side the patient preferentially sleeps on. Pressure on the dependent eyelid during sleep may result in local ischemia and lid eversion, and may provoke the patient to rub the eyelid, exacerbating the ischemia while stretching the tarsal plate. Patients with bilateral disease commonly alternate sides while asleep or sleep face down. Studies have shown a significant decrease in the amount of elastin within the tarsal plate and eyelid skin as compared to normal controls. It is thought that the up regulation of elastolytic enzymes, most probably induced by repeated mechanical stress, associated with eye rubbing or by sleeping habits, participates in elastic fiber degradation and subsequent tarsal laxity and eyelash ptosis in FES. Also poor contact of the lax eyelid with the globe in conjunction with meibomian gland and tear fi lm abnormalities may contribute further to the syndrome. Patients with more severe symptoms tend to have floppier eyelids. A contributing factor to the syndrome appears to be an abnormality in tear film dynamics. Tear fi lm abnormalities have been shown to be prevalent in patients with FES and are characterized by a lipid deficiency, with a consequent rapid rate of tear evaporation. The eyelid skin of FES patients is remarkable for its high temperature, high water evaporation rate, and a tendency toward hyperpigmentation. In addition obstructive sleep apnea (OSA) may contribute to the development of FES. The physician should inquire about the presence of symptoms of nocturnal breathing disorder. OSA may contribute to local eyelid ischemia that may play an important role in the development of FES. This ischemia may be exacerbated by the hypoventilation of OSA. In addition the pressure that is placed on the dependent eyelid during sleep and/or the act of rubbing the eyelid may also contribute to the syndrome.
COURSE/PROGNOSIS While excessive eyelid laxity has been reported in virtually all age groups, the typical FES patient is an obese middle-aged male
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(37% of patients are females) who presents with a chronic red eye with a mucoid discharge. By the time the diagnosis is finally made, the patient has usually received multiple ocular medications. The duration of symptoms before diagnosis has ranged from 8 months to 14 years.
Associated systemic disorders not present in all patients ● ● ● ● ●
DIAGNOSIS
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The syndrome is characterized by a triad of diffuse papillary conjunctivitis, a loose upper eyelid that readily everts by pulling it upward (positive lid eversion sign), and a soft rubbery tarsus that can be easily folded on itself. The lower eyelids may also be involved. Lash ptosis is common, usually involving the lateral lashes of the upper eyelid. The consequences of untreated FES can be serious. Staphylococcus aureus corneal ulceration has been described, as has bilateral corneal neovascularization. Corneal scarring may occur necessitating a penetrating keratoplasty in rare cases. A case has been reported of a patient with FES and rheumatoid arthritis who had dry eyes and who developed a corneal melt with perforation; ultimately requiring evisceration after endopthalmitis supervened. This highlights the fact that comorbities may complicate FES with severe clinical consequences. The diagnosis is often missed because patients usually present complaining of nonspecific ocular irritation and so can be confused with patients suffering from dry eyes. Typically, patients complain of a red eye(s), a foreign body sensation, eyelid swelling, dryness and a mucoid discharge. Symptoms are usually worse on waking. Patients often come in with multiple ocular medications that have been prescribed by previous physicians without success. The syndrome may be masked or complicated by a toxic medicamentosa from the numerous eye medications. The lids may appear swollen with mucus discharge. A diffuse, velvety, papillary conjunctivitis is present in the tarsus of one or both eyelids. The upper lid may be thickened and is easily everted, (positive lid eversion sign). The eyelashes may be nonparallel and ptotic, especially laterally, tending to curl toward the globe. The cornea may show punctate epithelial keratopathy, corneal neovascularization, even ulceration.
Associated ocular findings not present in all patients ● ● ● ● ● ● ● ● ●
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PEK (41% to 45%). Keratoconus (10% to 16%). Blepharitis. Blepharochalasis. Blepharoptosis. Corneal ulcers and neovascularization. Dermatochalasis. Eyelash ptosis (loss of parallelism of cilia). Endotheliopathy (Chandler’s syndrome, non-guttate endothelial dystrophy). Filamentary keratitis. Infectious keratitis. Keratotorus. Lower lid laxity and ectropion. Meibomian gland dysfunction. Pseudo-ptyrigium. Recurrent corneal erosion. Tear dysfunction. Trichiasis.
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Nocturnal ectropion of the upper eyelid is probably responsible for the clinical manifestations in most patients. It is not clear that all cases of FES represent the same syndrome. It is possible that a clinical picture similar to FES occurs in patients with lax upper eyelids of any cause.
CHAPTER 242 • Floppy Eyelid Syndrome
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Clinical signs and symptoms
Arteriosclerotic heart disease. Corneal perforation associated with rheumatoid arthritis. Chronic bronchitis. Diabetes mellitus. Epibulbar fasciitis. Gout. Hay fever. Hyperextensibility and hypermobility of joints. Hyperglycinemia. Hyperlipidemia. Hypertension. Interstitial pneumonitis. Mental retardation. Nephrolithiasis. Obesity. Obstructive sleep apnea. Psoriasis.
Laboratory findings Conjunctival scrapings reveal keratinized epithelial cells. Bacterial cultures of the conjunctiva should be obtained, and treatment should be instituted if appropriate. Histopathologic investigations have revealed chronic conjunctival inflammation and fibrosis and scarring. Meibomian gland cystic degeneration and squamous metaplasia have been noted, along with abnormal keratinization and granuloma formation. There is no definite association with systemic diseases of collagen or elastic tissue. Various associations have been reported with keratoconus, hyperglycinemia, and other disorders. Consider FES patients for sleep studies if OSA is suspected. Symptoms may include snoring, daytime somnolence, waking up feeling un-refreshed, apnea during sleep observed by others, waking gasping for air during the night and morning headache.
Differential diagnosis A study of 58 patients with chronic conjunctivitis of more than 2 weeks’ duration revealed that FES was the cause of chronic conjunctivitis in 2% of patients. In 31% of patients with chronic conjunctivitis, no specific cause was detected. Because these patients often present with multiple eye medications, a toxic medicamentosa conjunctivitis and keratitis may also be present, and the underlying disorder may be missed. Laxity of the eyelid, in general, can occur from a variety of processes, including natural ageing, hyper-elasticity syndromes, blepharochalasis and as a post-inflammatory response. Common to all these syndromes are symptoms and signs of chronic non-specific ocular surface irritation, which resolves with surgical correction of the eyelid laxity. Other conditions to consider are lax eyelid syndrome, cutis laxa, blepharochalasis syndrome, and eyelid imbrication syndrome.
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TREATMENT
SUMMARY
Ocular
The accurate diagnosis of FES is often initially overlooked. Ocular medicamentosa may mask the correct diagnosis. During surgical correction, the ductules of the lacrimal glands must be avoided. Early recognition will spare the patient corneal complications and unnecessary diagnostic procedures and treatment. Consider sleep studies if obstructive sleep apnea is suspected, and evaluate the patient for keratoconus.
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Prevention of the probable nocturnal eyelid eversion. Eye shield while sleeping. Lids taped closed at night. Ocular medications tapered or discontinued. Ocular lubricants.
SECTION 21 • Eyelids
Surgical Not all symptoms are relieved by local treatment. Because the cause is simply one of excessive eyelid laxity, a surgical cure via an eyelid-tightening procedure is often necessary. An upper and a lower pentagonal eyelid resection is simple and effective. The tarsal strip or Bick procedure may also be used.
Full-thickness upper and lower eyelid resection When performing a standard full-thickness eyelid resection on a patient with FES, it is best to treat both the upper and lower eyelids because both are affected. The principal caveat is to avoid injury to the lacrimal secretory ductules, which lie approximately 5 mm above the lateral extreme of the upper tarsus. When performing full thickness eyelid resections, the vertical excision must extend through the top of the tarsus to avoid an unsightly buckling in the upper eyelid. Back-tapering both the tarsal wedge resection posteriorly and the resection of the anterior lamella anteriorly can further enhance cosmesis. In most cases, the wedge should be taken laterally, that is, from the area of the lateral third and medial two thirds of the eyelid. However, there are cases in which the greatest laxity occurs medially. For these cases, a new technique has been described in which a tapered, full thickness resection of 10-mm to 12-mm of eyelid is performed medially, a procedure that addresses both the laxity and cosmetic concerns.
REFERENCES Anderson R, Gordy DD: The tarsal strip procedure. Arch Ophthalmol 97:2192–2196, 1979. Bick MW: Surgical management of orbital tarsal disparity. Arch Ophthalmol 75:386, 1966. Culbertson WW, Ostler HB: The floppy eyelid syndrome. Am J Ophthalmol 92:568–575, 1981. Culbertson WW, Tseng SC: Corneal disorders in floppy eyelid syndrome. Cornea 13:33–42, 1994. Dutton JJ: Surgical management of floppy eyelid syndrome. Am J Ophthalmol 99:557–560, 1985. Netland PA, Sugrue SP, Albert DM, Shore JW: Histopathologic features of the floppy eyelid syndrome: Involvement of tarsal elastin. Ophthalmology 101:174–181, 1994.
243 HORDEOLUM 373.1 (Internal Hordeolum [Acute Meibomitis], External Hordeolum [Stye], Acute Infection of the Glands of Zeis or Moll’s Glands)
Tarsal strip and bick procedures The tarsal strip procedure, as described by Anderson and Gordy, also is effective. After a lateral canthotomy and lysis of both the upper and lower tendons, the upper and lower lateral eyelids are shortened. ‘Tarsal strips’ are fashioned from surgically thinned lateral tarsus tissue after a determination is made on the table of how much tarsus must be excised to achieve the desired tightening. The tarsal strips – cleaned of skin anteriorly, the lid margin superiorly and mucosa posteriorly – are sutured to the inner, lateral orbital periosteum, just above the lateral orbital tubercle. The Bick procedure is much like the tarsal strip procedure and is equally efficacious. After lateral canthotomy and upper and lower cantholysis, the amount of eyelid laxity is determined. The redundant full-thickness eyelid is excised without creating tarsal strips. The tarsal edges are then affi xed to the periosteum in the customary fashion.
Kevin S. Michels, MD Portland, Oregon
ETIOLOGY/INCIDENCE Hordeolum is usually an acute staphylococcal infection of the sebaceous glands of the eyelids. External hordeolum (stye) is caused by stasis with subsequent bacterial infection of the glands of Zeis’ or Moll’s glands. Internal hordeolum usually results from a secondary staphylococcal infection of a meibomian gland in the tarsal plate. Both internal and external hordeola are common sequelae of infectious blepharitis, and the most common infectious agent is Staphylococcus aureus. Rare cases of Pseudomonas aeruginosa may occur. Hordeola are more common in patients with chronic lid or skin disease or with systemic diseases such as diabetes mellitus.
Systemic Treatment for OSA may improve the symptoms of FES. If obesity is present weight loss may be helpful. A change in sleep habits to avoid mechanical trauma may further support the treatment success of surgical correction.
COMPLICATIONS The severe complications of the syndrome have included corneal neovascularization, corneal ulcer, scarring, perforation and endophthalmitis.
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COURSE/PROGNOSIS Hordeola usually begin with painful swelling and edema of the eyelid, which becomes localized. The purulent exudate of external hordeola often breaks through the skin near the eyelash line; the suppuration of the internal hordeolum occurs on the conjunctival side of the eyelid. The prognosis is excellent unless an orbital cellulitis develops or the preauricular or submandibular nodes are involved. Hordeolum can often spontaneously improve over a 1–2 week period.
DIAGNOSIS
REFERENCES
The diagnosis is made clinically by a localized area of tenderness in the region of obvious inflammation, but may require confirmation based on culture or biopsy results if complications occur.
Briner AM: Surgical treatment of a chalazion or hordeolum internum. Aust Fam Phys 16:834–835, 1987.
Differential diagnosis
PROPHYLAXIS Prophylaxis is based on lid hygiene, control of associated skin or systemic disease, and improved overall general health.
TREATMENT Systemic ●
●
If multiple hordeola, recurrent hordeola, or adenopathy occur, consider systemic antibiotics: 250 mg erythromycin q.i.d., 125 to 250 mg dicloxacillin, or 500 mg cloxacillan q.i.d. for as long as 2 weeks In chronic cases, administer prophylactic 250 mg tetracycline q.i.d. or 50 to 100 mg doxycycline qd.
Diegel JT: Eyelid problems: Blepharitis, hordeola, and chalazia. Postgrad Med 80:271–272, 1986. Wilson LA: Bacterial conjunctivitis. In: Duane TD, ed: Clinical ophthalmology. Philadelphia, Harper & Row, 1979:IV:12–16.
244 LAGOPHTHALMOS 374.2 Eric A. Steele, MD Portland, Oregon Roger A. Dailey, MD Portland, Oregon
CHAPTER 244 • Lagophthalmos
When the lesion does not resolve with appropriate therapy then preseptal cellulitis, sebaceous cell carcinoma, and pyogenic granuloma should be considered.
Briner AM: Treatment of common eyelid cyst. Aust Fam Phys 16:828–830, 1987.
ETIOLOGY Lagophthalmos, which is the inability to fully close the eyelids, can occur for a number of reasons, including excessive projection of the eye in the orbit, inadequate vertical dimensions of either lid, contraction of the eyelid retractors or malfunction of the orbicularis oculi.
Periocular ● ● ●
●
●
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Hot moist compresses for 5 to 15 minutes hourly or q.i.d. Removal of eyelashes in area to enhance suppuration. Once drainage occurs, topical ocular antibiotic solutions or ointments: bacitracin, erythromycin, gentamicin, tobramycin, ciloxin, and others applied q.i.d. during the acute phase. Topical steroids not indicated except when there is a fear of structural changes to the lid. Steroid injection can be considered for rare cases when excision of the lesion could lead to damage of the lacrimal apparatus, but steroids can lead to permanent skin discoloration. Lid hygiene.
Surgical ● ●
● ●
The gland usually drains spontaneously. Stab incision, from either skin or palpebral conjunctiva depending on where the lesion is pointing, may spread infection if the incision is made before the eyelid skin or palpebral conjunctiva appears white or cream colored. Multiple pockets may be present; all must be incised. Occasionally, a fi rm central abscess core occurs and must be removed or the lesion will not easily heal.
If a local anesthetic is used, the injection is not administered directly in the area of inflammation but either above the upper border of the upper tarsus or below the lower border of the lower tarsus. A chalazion clamp is applied, and a horizontal incision is made over the pointing area if it is on the skin, or a vertical incision is made if the lesion is conjunctival. The lash margins should be avoided so as not to cause a lid margin defect or injury to the lash roots. The wound edges are not sutured, and postoperative warm compresses and antibiotic ointment are used until closure occurs spontaneously.
COURSE/PROGNOSIS The presence of lagophthalmos often requires prompt efforts to protect the eye. Neglect of lagophthalmos can result in decreased vision, painful dryness, keratoconjunctivitis, corneal erosion, ulceration, and even endophthalmitis and loss of the eye.
DIAGNOSIS Clinical signs and symptoms The patient often presents with foreign body sensation and tearing, but may be asymptomatic if corneal hypoesthesia is present. On examination, there is incomplete closure of the eyelids. There may be associated corneal epithelial irregularities, or even ulceration with frank perforation.
TREATMENT Appropriate therapy is dependent on an accurate diagnosis. Proptosis may be caused by congenital deformity, tumor, trauma, or thyroid related immune orbitopathy. Lid retraction can result from traumatic loss of eyelid tissue or cicatrization from many causes. Paralytic lagophthalmos secondary to decreased orbicularis oculi muscle tone commonly occurs with Bell’s palsy.
Ocular The maintenance of a moist surface on the eye is critical to the management of lagophthalmos. Treatment begins with artificial tears. Lubricating ointments protect the ocular surface longer, but cause bothersome blurring of vision, and may be best tolerated at bedtime. Punctal plugs or thermal occlusion
447
of the puncta may be helpful, and moisture chambers or specially designed spectacles can prevent evaporative drying. A bandage contact lens can occasionally be useful in chronic irritative conditions caused by mild or partially corrected lagophthalmos, or a patch can be used for short periods of time. Long term patching has been associated with fungal infections, and even short term patching can be dangerous if corneal hypoesthesia is present. SECTION 21 • Eyelids
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Surgical When the condition is severe, and protection is needed quickly prior to defi nitive repair, a tarsorrhaphy can be considered. A simple, effective method is to anesthetize the temporal aspect of the upper and lower eyelids with 2% lidocaine with epinephrine and use 5-0 fast absorbing gut suture (Ethicon, Somerville, NJ) to approximate the lid margins. Suture is placed beginning approximately 5 mm above the upper lid margin and passed out of the lid at the gray line and then into the opposite lid at the gray line and out through the skin approximately 5 mm below the margin. It then returns approximately 1 cm from the first pass by the opposite identical route through both lids and the ends are tied together. This provides effective corneal protection and lasts approximately one week. A similar technique using 5-0 nylon suture (Sherwood Medical, St Louis, MO) and bolsters to protect from skin breakdown can be used for a few weeks. The best permanent tarsorrhaphy (used if the other options listed below are not indicated or effective) involves creating pedicle flaps at the temporal and nasal limbus from the superior tarsus down to the inferior tarsus. This provides excellent closure while still allowing the eye to be opened for examination or administration of eye drops. An accurate diagnosis and thorough understanding of the responsible pathology is critical for planning more defi nitive surgical corrections for the management of lagophthalmos. Treatment usually involves various combinations of lowering the upper eyelid, raising the lower eyelid, and providing better eyelid movement. When exophthalmos is the culprit, treatment is directed at the orbit. The upper eyelid retraction of TRIO responds well to upper lid levator recession and graded muellerectomy. Upper or lower lid retraction from loss of tissue or cicatrisation requires pedicle flaps or anterior/posterior lamellae grafting techniques. Posterior lamellae can be reconstructed from hard palate mucosal grafting (in the lower eyelid only) or acellular dermal allograft. Patients with facial nerve palsies can be difficult to treat. Often these patients require a gold weight implant to help with upper eyelid closure. Placement of an orbital gold weight provides excellent function and low morbidity compared to pretarsal placement. Many patients need ectropion repair via a lid shortening procedure along with midface lifting and or placement of a full thickness skin graft to the anterior lamella to allow the lower lid to maintain an acceptable position. Suborbicularis oculi fat (SOOF) lifts can be accomplished in the preperiosteal or subperiosteal plane depending on the extent of elevation needed. Conditions that cause exposure from exophthalmos are treated by efforts to reduce tumor mass or enlarge the space available in the orbit. Systemic or local injection of steroids can help with inflammatory diseases, and chemotherapy or radiation can be effective in treating certain tumors and inflammatory conditions. The proptosis of thyroid related immune orbitopathy (TRIO) can be treated by radiation, but generally excellent outcomes are achieved with orbital decompression.
COMPLICATIONS Although successful attempts at improving lid closure by attaching springs have been reported, problems with these devices exist. Difficulties in the adjustment and tension maintenance of the stainless-steel spring may develop, and the likelihood that the spring will eventually migrate, extrude, or break necessitates the patient’s continuous proximity to a surgeon familiar with the technique. Likewise, the elastic force of a silicon rubber loop may ultimately stretch the tissue through which it passes and cause loss of some tension. While nerve anastomosis, muscle transfers, static suspension and other more exotic and definitive measures for the correction of facial paralysis can be successful, these techniques often confer some degree of facial deformity and do not always achieve sufficient ocular protection to preclude the measures outlined here.
COMMENTS The treatment of lagophthalmos requires a logical, stepwise approach. Application of the techniques discussed in this chapter can prevent the serious complications that result from chronic ocular exposure.
REFERENCES Bailey KL, Tower RN, Dailey RA: Customized, single-incision, three wall orbital decompression. Ophthal Plast Reconstr Surg 21 (1):1–9, 2005. Tower RN, Dailey RA: Gold weight implantation: a better way? Ophthal Plast Reconstr Surg 20(3):202–206, 2004. Wobig JL, Dailey RA: Oculofacial plastic surgery. New York, Thieme, 2004.
245 LID MYOKYMIA 333.2 Byron L. Lam, MD Miami, Florida
ETIOLOGY/INCIDENCE Myokymia is the spontaneous fi ne fascicular contraction of muscle without muscular atrophy or weakness. Eyelid myokymia typically involves the orbicularis oculi of one of the lower eyelids, although occasionally the upper eyelids can also be affected. These irregular contractions are usually unilateral and intermittent, and they may persist for weeks to months. Eyelid myokymia is generally benign, self-limited, and not associated with any disease. Possible precipitating factors include stress, fatigue, and excessive caffeine or alcohol intake. Rarely, eyelid myokymia may occur as a precursor or as part of facial myokymia that is characterized by continuous, involuntary movements of the facial muscles associated with multiple sclerosis and brain stem tumors.
DIAGNOSIS Patients typically report eyelid jumping or twitching. These symptoms often improve when the eyelid is pulled manually.
Fine contractions of the eyelid are visible but are usually more apparent to the patient than to the observer. Rarely, the contractions may be vigorous enough to cause movement of the globe, producing oscillopsia and pseudonystagmus. The focus of irritation is most likely the nerve fibers within the muscle.
●
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Reassurance and reduction in precipitating factors, if identifiable, are appropriate for most patients. Subcutaneous injections of botulinum toxin type A consisting of local injections of 2.5 to 5.0 units each to the affected eyelid region usually provide adequate relief lasting 12 to 16 weeks. Adverse effects include temporary lid laxity, which may produce lagophthalmos and exposure keratopathy. Oral quinine, antihistamines, clonazepam, or baclofen may be tried in the unlikely event that botulinum toxin type A is unsuccessful, but the efficacy of these agents has not been proved. In addition, quinine has numerous side effects and is contraindicated in pregnancy.
REFERENCES Givner I, Jaffe NS: Myokymia of the eyelids: a suggestion as to therapy: preliminary report. Am J Ophthalmol 32:51–55, 1949. Lowe R: Facial twitching. Trans Ophthalmol Soc Aust 11:129–133, 1951. Reinecke RD: Translated myokymia of the lower eyelid causing uniocular vertical pseudonystagmus. Am J Ophthalmol 75:150–151, 1973. Scott AB: Botulinum toxin for blepharospasm. In: Spaeth G, Katz LJ, Parker KW, eds: Current therapy in ophthalmic surgery. Toronto, Decker, 1989:322–324. Sogg RL, Hoyt WF, Boldrey E: Spastic paretic facial contracture: a rare sign of brain stem tumor. Neurology 13:607–612, 1963.
246 LID RETRACTION 374.41 Dale R. Meyer, MD, FACS Albany, New York
Clinical signs and symptoms The normal resting upper eyelid position is approximately 4.0 to 4.5 mm above the central corneal light reflex, and the normal lower eyelid position is approximately 5.5 mm below the central corneal light reflex. Normally, eyelid position is symmetric (within 1 mm of the contralateral eyelid). Significant deviation of the eyelid from normal may be considered eyelid retraction. When the upper eyelid is affected, the resting position of the upper eyelid is at a higher-than-normal level, and when the lower eyelid is affected, it is at a lower-than-normal level. Typically, inferior scleral show occurs when the lower eyelid is affected, and superior scleral show occurs with more advanced upper eyelid retraction. Upper eyelid retraction makes the person appear as if he or she is staring and can produce the illusion of exophthalmos (Figure 246.1). Eyelid position can be affected by both vertical and horizontal gaze. In downgaze, the upper eyelid normally drops slightly or stays at the same level relative to the mid cornea or visual axis. The term lid lag describes the situation in which the upper eyelid assumes a higher position when the eyes are in downgaze. Lid lag is not to be confused with von Graefe’s sign, which is a dynamic sign describing the pause or retarded descent of the eyelid when the eye moves from primary position to downgaze. Stellwag’s sign describes retraction of the upper eyelid or eyelids associated with infrequent or incomplete blinking. Dalrymple’s sign describes an abnormal vertical wideness of the palpebral fissure. Resting eyelid position is determined by a balance of the eyelid protractors and retractors. The primary protractor of the eyelids is the orbicularis oculi muscle, which is responsible for eyelid closure and blinking. In the resting position, the orbicularis oculi muscle exhibits low-grade tonic activity only. The retractors of the upper eyelid are the levator palpebrae superioris muscle innervated by the third cranial (oculomotor) nerve and Müller’s muscle, which is smooth muscle innervated by sympathetics. The lower eyelid retractors are more rudimentary and include the capsulopalpebral fascia (an extension of the capsulopalpebral head from the inferior rectus muscle) and the inferior tarsal muscle, which is also smooth muscle innervated by sympathetics. Determination of the underlying cause of eyelid retraction is usually straightforward. History regarding previous surgery or
CHAPTER 246 • Lid Retraction
TREATMENT
DIAGNOSIS
Lid retraction is a disorder of eyelid position that can affect the upper eyelid, lower eyelid, or both, and may be unilateral or bilateral.
ETIOLOGY/INCIDENCE Eyelid retraction can result from an increase in retractor force, as well as from scarring or other mechanical forces. The most common cause of eyelid retraction is Graves’ disease (Graves’ ophthalmopathy). Eyelid retraction due to Graves’ ophthalmopathy may be unilateral or bilateral, affecting the upper eyelids, lower eyelids, or both. An uncommon but important cause of upper eyelid retraction is dorsal midbrain disease. Upper eyelid retraction tends to be bilateral with midbrain conditions and when present is referred to as Collier’s sign; often, there is associated conjugate upgaze and convergence paralysis, as well as light-near pupillary dissociation and retraction-nystagmus on attempted upgaze, the Parinaud’s syndrome.
FIGURE 246.1. Congenital right upper eyelid retraction.
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trauma, concomitant systemic diseases, and familial disorders should be elicited.
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SECTION 21 • Eyelids
Laboratory findings
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If the diagnosis of Graves’ disease is suspected, serologic testing for total thyroxine, thyroid-stimulating hormone, and thyroidstimulating immunoglobulins should be obtained. Orbital and head neuroimaging is not usually necessary unless the clinical and laboratory investigations do not establish the diagnosis.
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Differential diagnosis The broader differential diagnosis of eyelid retraction is diverse but can be generally classified under three categories: neurogenic, myogenic, and mechanical.
Neurogenic ● ● ● ● ● ● ● ● ●
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Dorsal midbrain lesions (e.g. pinealoma). Hydrocephalus. Encephalitis. Bulbar poliomyelitis. Multiple sclerosis. Closed head injury. Coma (‘coma vigil’). Epilepsy. Marcus Gunn (jaw-winking syndrome) trigemino-oculomotor synkinesis. Aberrant innervation/regeneration cranial nerve III (oculomotor nerve). Pseudoretraction associated with contralateral blepharoptosis. Weakness of orbicularis oculi (e.g. facial nerve palsy). Orbital floor fracture (globe hypotropia, increased innervation to superior rectus/levator). Sympathomimetic eyedrops (phenylephrine, aproclonidine). Volitional.
Myogenic ● ● ● ● ● ● ● ● ● ● ● ●
Graves’ ophthalmopathy. Congenital upper or lower eyelid retraction. Congenital hyperthyroidism. Congenital myotonia, myotonic dystrophy. Hyperkalemic. Periodic paralysis. Myasthenia gravis. Postsurgical. Inferior rectus recession (lower eyelid). Superior rectus recession (upper eyelid). Overcorrection blepharoptosis. Enucleation.
Mechanical ● ● ● ● ● ● ● ● ● ● ● ●
450
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Postsurgical. Blepharoplasty. Orbicularis myectomy. Scleral buckle. Osteoplastic frontal sinusotomy. Glaucoma fi ltering procedure. Extracapsular cataract extraction. Orbital floor exploration. Maxillectomy. Cheek flap.
Graves’ ophthalmopathy. Exophthalmos (proptosis). Buphthalmos. High myopia. Craniosynostosis. Eyelid neoplasms. Herpes zoster ophthalmicus. Smallpox. Atopic dermatitis. Burns (thermal or chemical). After irradiation. Contact lens wear (or imbedded contact lens).
PROPHYLAXIS Prophylaxis of eyelid retraction is possible in some surgical procedures that may induce eyelid retraction. ● Blepharoplasty: avoidance of excessive skin excision is recommended. For lower eyelid blepharoplasty, a transconjunctival approach carries less risk of eyelid retraction than a transcutaneous approach. ● Orbitotomy: an infraciliary incision is frequently used to approach the inferior portion of the orbit for procedures such as orbital fracture repair, orbital decompression or orbital exploration, and tumor excision. Meticulous closure of the wound with avoidance of ‘catching’ the lower eyelid retractors or septum in the more anterior closure is recommended. It is acknowledged that even with meticulous closure, eyelid retraction of a mild nature may still occur. For this reason, whenever possible, a transconjunctival approach is recommended. ● Inferior rectus recession: lower eyelid retraction after inferior rectus recession may occur and is more likely to occur with recessions of more than 3 mm. Several surgical techniques to minimize or prevent lower eyelid retraction after inferior rectus muscle recession have been described, including extensive dissection of the inferior rectus muscle with lysis of surrounding check ligaments. Because simple wide dissection may not be adequate, more recent techniques have suggested application of countertraction at the level of the capsulopalpebral head (by advancement or suspension) at the time of the inferior rectus recession. Alternatively, primary lysis of the lower eyelid retractors 3 to 4 mm beneath the tarsus can also be performed. This procedure has the advantage of being technically simpler and is not compromised by large inferior rectus muscle recessions.
TREATMENT The treatment of eyelid retraction will vary depending on the cause and severity. Aside from the disfigurement caused by eyelid retraction, corneal exposure is the most common complication that should be addressed.
Systemic Systemic abnormalities contributing to eyelid retraction should be sought and corrected. For patients with Graves’ disease, thyroid function should be stabilized and eyelid position should be stable for at least 6 months before elective eyelid surgery is considered.
Local ●
Topical ocular lubrication (artificial tears or ointments) is used when exposure keratopathy is present.
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●
Guanethidine eyedrops are not usually recommended due to variable effectiveness. Botulinum type A (2.5–10.0 units) injected transconjunctivally just above the superior tarsal border can temporarily reduce lid retraction. The individual response to treatment is variable. Effects generally last 3–4 months. Diplopia and overcorrection (ptosis) are potential side-effects.
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Approaches vary for upper eyelid, lower eyelid, and severity of lid retraction. The upper eyelid usually requires recession of Müller’s muscle, levator aponeurosis, or both. The lower eyelid usually requires recession of lower eyelid retractors; advanced cases also require spacer graft (hard palate, ear cartilage, eye bank sclera, or other). A cheek suspension procedure may also be considered.
Upper eyelid retraction surgery ●
Posterior (internal) approach.
CHAPTER 246 • Lid Retraction
Surgical
the lid is returned to a normal position. Dissection is carried down to the orbital septum, which is opened to reveal the preaponeurotic fat, which is then excised if desired. The levator aponeurosis then is disinserted from the tarsus, with less dissection performed medially than laterally to avoid overcorrection. The patient is placed in the sitting position, and the lid position is assessed. If further lowering of the eyelid is desired, Müller’s muscle can be recessed/extirpated. The plane between Müller’s muscle and conjunctiva is infi ltrated with 2% xylocaine with 1 : 100,000 epinephrine; then, Müller’s muscle is undermined and excised. With the anterior approach, the conjunctiva is usually preserved. The patient is again placed in the sitting position, and the eyelid position is checked. Further recession of the levator aponeurosis and Müller’s muscle can be performed with blunt dissection. The levator aponeurosis can be secured in its recessed position with an absorbable suture. The skin is closed in the usual fashion, and the lid crease can be sutured to the superior portion of the tarsus with deeper bites to re-establish the eyelid crease.
Lower eyelid retraction surgery A 4-0 silk suture is placed through the eyelid margin, and the lid is everted over a Desmarres retractor. Local anesthetic (2% xylocaine with 1 : 100,000 epinephrine) is infi ltrated in the subconjunctival space above the superior tarsal border. The conjunctiva is grasped 2 to 3 mm above the superior tarsal border, and a small ‘buttonhole’ incision is made with Stevens scissors through the conjunctiva and Müller’s muscle. The surgical plane between Müller’s muscle and the levator aponeurosis is undermined with Stevens scissors, and the conjunctiva and Müller’s muscle are then incised medially and laterally. The extent of the medial dissection is somewhat less than laterally to avoid overcorrection. Müller’s muscle can be excised directly with Stevens scissors. The patient is placed in the sitting position, and the lid position is assessed. Usually, simple recession/extirpation of Müller’s muscle, as described, will produce approximately 2-mm lowering of the eyelid margin. If further lowering of the eyelid is required, the levator aponeurosis itself can be disinserted from the tarsus via the posterior approach and recessed. The patient is placed in the sitting position, and further recession of the levator aponeurosis usually can be performed through additional blunt dissection to achieve the desired eyelid position. Some surgeons suture back together the conjunctiva at the end of the procedure, but this author has not found this to be necessary or desirable. The conjunctiva usually reepithelializes in approximately 1 week. The silk suture at the lid margin can be taped down to the cheek for several days, but for less advanced cases of upper eyelid retraction, this is not necessary. Although spacer grafts have also been used to treat upper eyelid retraction, they usually are not necessary. Postoperative eyelid position can vary somewhat (either upward or downward) but usually approximates the position noted at the end of surgery. ● Anterior (external) approach. The levator aponeurosis and Müller’s muscle also can be approached from an anterior eyelid crease incision. The advantage of the anterior approach is that blepharoplasty, if desired, can be performed with further debulking of excess orbital fat. The procedure is performed after the eyelid crease is marked with a skin-marking pen, and if blepharoplasty is planned, a skin pinch technique is used to assess the amount of redundant tissue. Caution should be taken not to excise too much skin because the amount of apparent redundancy may be less when
Surgical correction of lower eyelid retraction can be divided into three approaches: 1. Lower eyelid retractor lysis/recession (extirpation). 2. Recession with spacers (e.g. hard palate mucosa, cartilage, sclera, acellular dermis). 3. Orbicularis/prezygomatic cheek flap advancement and fi xation. Eyelid retraction procedures are frequently coupled with horizontal eyelid tightening (e.g. tarsal strip procedure or ‘lateral canthoplasty’). These techniques generally involve a conjunctival incision, with identification of the lower eyelid retractors. The eyelid retractors can be dissected from the conjunctiva, followed by recession or extirpation; alternatively, the conjunctiva and retractors can be recessed together, which is this author’s favored approach. In virtually all techniques for the correction of lower eyelid retraction, some type of upward traction (usually via a Frost suture) is applied postoperatively to the lower eyelid for several days. Because gravity ‘works against’ lower eyelid surgery, it may be necessary to place a spacer between the recessed conjunctiva/retractors and the tarsus, particularly if the lower retraction is more than 2 mm. Hard palate mucosa grafts and auricular cartilage, as well as commercially prepared acellular dermis are useful for this purpose. Eye bank sclera can also be used, but results may be less predictable because of reabsorption and fibrosis. Finally, if lower eyelid retraction is due to a deficiency of skin such as occurs after lower eyelid blepharoplasty or burns, consideration must be given to advancement of the remaining eyelid and cheek skin, usually via dissection and mobilization of a composite cheek flap (e.g. ‘SOOF lift’). In cases of extreme vertical skin deficiency, a full-thickness skin graft, usually obtained from behind the ear, may be required to adequately reposition the lower eyelid.
COMPLICATIONS ●
●
The main complication of eyelid retraction is corneal exposure. Failure of eyelid retraction surgery to adequately correct eyelid retraction requires more aggressive secondary surgery, including further recession of the eyelid retractors,
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SECTION 21 • Eyelids
consideration of spacer graft (or larger spacer), wider mobilization of skin and adjacent tissues or placement of a fullthickness skin graft, or a combination, depending on what tissue layer or layers remain ‘tight.’ Occasionally, ‘overcorrection’ of eyelid retraction occurs, involving the entire eyelid or segment (upper eyelid is too low or lower eyelid is too high). In the case of the upper eyelid, this can be treated with the techniques described for ptosis repair. In the case of the lower eyelid, resection/plication of the conjunctiva and underlying retractors is usually sufficient to lower the eyelid.
COMMENTS Usually, the cause of eyelid retraction is fairly obvious based on the clinical setting and history. Graves’ ophthalmopathy is the most common cause, and surgical management is aimed at weakening the eyelid retractors. Midbrain disease is an important but less common cause of upper eyelid retraction; typically, the patient has other neurologic findings that point to this cause of eyelid retraction. Postsurgical scarring and deficiency of the eyelid skin or orbital septum also may produce eyelid retraction, requiring that the shortage of these tissues be addressed. The goal of therapy is to maintain the health of the ocular surface and reduce the disfigurement associated with eyelid retraction.
REFERENCES Bartley GB: The differential diagnosis and classification of eyelid retraction. Ophthalmology 103:168–176, 1996. Harvey JT, Anderson RL: The aponeurotic approach to eyelid retraction. Ophthalmology 88:513–524, 1981. Morgenstern KE, Evanchan J, Foster JA, et al: Botulinum toxin type a for dysthyroid upper eyelid retraction. Ophthal Plast Reconstr Surg; 20:181–185, 2004. Small RG, Scott M: The tight retracted lower eyelid. Arch Ophthalmol 108:438–444, 1990.
247 MADAROSIS 374.55 (Loss of Eyelashes) Allen M. Putterman, MD Chicago, Illinois
ETIOLOGY/INCIDENCE Madarosis, the loss of eyelashes, can be an undesirable cosmetic deformity. It can be caused by systemic or topical infections and inflammations, eyelid tumors, the hysteric plucking of hairs, surgery, and trauma. The hair loss may involve the entire lid but frequently involves only a segment.
DIAGNOSIS Systemic causes of madarosis include generalized disorders, such as alopecia areata (characterized by an area or areas of sharply defined baldness) and alopecia artefacta (baldness due
452
to the neurotic plucking of hairs or cilia). Other systemic causes of madarosis are lupus erythematosus, psoriasis, and seborrhea in which loss of eyelashes follows inflammation of the lids, as well as leprosy, syphilis, tuberculosis, sickle cell anemia, and endocrine disorders. Topical infections and inflammations, such as ulcerative and allergic blepharitis, frequently lead to the loss of cilia that is usually segmental. Madarosis also is a complication of eyelid surgery. Absent lashes frequently occur when full-thickness segments of the lids are excised in the treatment of eyelid carcinoma. In other eyelid surgery, especially that related to the treatment of ptosis and benign tumors, lashes can be lost because of the undermining of skin from orbicularis within 2 mm of the lid margin. Traumatic lid lacerations and avulsions also are causes of madarosis.
TREATMENT Systemic Therapy for madarosis is aimed at treating the underlying etiologies. Medical management of systemic problems, including the emotional problems involved in alopecia artefacta, frequently leads to regrowth of the cilia. In general, lid hygiene, lid scrubs with baby shampoo, and the application of topical antibiotics (e.g. erythromycin) to the lid margins will control seborrheic blepharitis and prevent further loss of lashes. Allergic blepharitis is treated through the elimination of the offending antigens and the application of topical steroids.
Medical The treatment of absent cilia after surgery or trauma and the control of systemic and topical infections and inflammation are difficult. Certainly, the need for treatment varies because many patients have a cosmetically acceptable appearance without lashes, especially if madarosis involves a small segment of the lid or even the entire lower lid. The easiest treatment is achieved with makeup. Eyelid liner, mascara, and false eyelashes can camouflage the defect and frequently produce a better cosmetic appearance than that achieved surgically. False eyelashes can be applied to a segment of the lid. In addition, makeup experts can attach false lashes to surrounding normal cilia through a weaving process.
Surgical The most pleasing surgical results are achieved in patients who have had a segmental loss of lashes. The treatment consists of an eyelid excision of a full-thickness pentagon segment in the area without lashes. The surrounding normal lid segments are then connected. Three 6-0 black-silk double-armed sutures are placed through the lid margins. One suture is placed through the squared corners where the conjunctiva meets the tarsus, entering through the posterior aspect of the tarsus. The second suture is placed through the gray line. The third suture is placed through the most posterior row of cilia. The suture enters and exits from similar areas on each edge of the wound to avoid lid notching after surgery. Sutures are triple-tied, and the ends of the posterior two sutures are tied over the cilia suture, so when all six ends are cut, they point away from the cornea to avoid suture keratopathy. Two or three 6-0 Vicryl double-armed sutures are then passed through the pretarsal fascia and the anterior aspect of the tarsus on each side of the wound below the lid margin. The skin is closed with a continuous 6-0 black-silk suture.
REFERENCES Levine M: Blepharopigmentation. In: Putterman A, ed: Cosmetic oculoplastic surgery. 2nd edn. Philadelphia, WB Saunders, 1993:324–333. Naugle T: Cited by Caldwell D: Eyelash loss corrected by ciliary transplantation. Ophthalmol Times 7:52–53, 1982. Putterman AM: Basic oculoplastic surgery. In: Peyman GA, Sanders DR, Goldberg MF, eds: Principles and practice of ophthalmology. Philadelphia, WB Saunders, 1980:2292–2295. Putterman AM: Simplified reconstruction of the eyelids. In: Tandy ME, Jr, ed: Head and neck surgery. Face, nose and facial skull, part 1. Thierre, ER Kastenbauer, 1995:1:228–237. Putterman AM, Migliori ME: Elective excision of permanent eyeliner. Arch Ophthalmol 106:1034, 1988.
248 MARCUS GUNN SYNDROME 742.8 Roger A. Dailey, MD Portland, Oregon John D. Ng, MD, MS, FACS Portland, Oregon
ETIOLOGY/INCIDENCE
The transplantation of eyebrow hairs into the eyelid must not be considered a cure for madarosis. The relatively high incidence of postoperative loss of transplanted brow hairs and the frequently conspicuous appearance of the brow hairs that remain should alert the surgeon to surgical failure. Blepharopigmentation initially was a popular technique but presently is used only occasionally. One of the main problems has been the difficulty of removing pigment in patients who do not like the density or the areas to which it was applied.
The jaw-winking syndrome, described by Marcus Gunn in 1883, is one type of congenital ptosis of a synkinetic nature that classically consists of ptosis of the upper eyelid associated with involuntary retraction of the lid during contraction of the ipsilateral pterygoid muscle. This syndrome accounts for 4% to 6% of all cases of congenital ptosis. ● The condition is usually sporadic, but familial cases have been reported. ● It is almost always unilateral and more severe in downgaze. ● The often-bizarre manifestations of this syndrome are due to a congenital misdirection of part of the fi fth cranial nerve that aberrantly supplies the levator muscle; therefore, stimulation to the jaw sends impulses to the variably innervated levator. ● Electromyographic studies demonstrate a synkinetic relationship between the external pterygoid muscle and the levator muscle. The lid elevates with the jaw thrusting to the opposite side (ipsilateral external pterygoid) or with the jaw projecting forward or mouth opening (bilateral external pterygoid). ● A less common type is the internal pterygoid levator synkinetic group in which the lid elevates with the muscle closing or teeth clenching. The ptosis, as well as the retraction (‘winking’), varies in severity from minimal to cosmetically unacceptable, and either component may dominate the clinical picture.
SUMMARY
COURSE/PROGNOSIS
Madarosis (loss of eyelashes) has systemic, local, hysteric, traumatic, and surgical causes. The fi rst three categories can be treated medically. Makeup, horizontal lid shortening, and brow and lid grafts can be used to treat traumatic and surgical causes.
The Marcus Gunn syndrome is persistent throughout life, although it is may become less conspicuous with time as patients learn to control or mask its features. Surgical correction can provide significant improvement in the ptosis, but the synkinetic movement persists unless the levator muscle is
COMPLICATIONS
CHAPTER 248 • Marcus Gunn Syndrome
If the normal lid segments connect with too much tension, a lateral canthotomy and cantholysis with or without a semicircular temporal flap may be needed. This is especially important in the upper eyelid, where a tight eyelid can cause ptosis. Also, it is possible to attach a segment of the lid with normal cilia to the lid segment that has a few absent cilia. Doing so decreases the area of madarosis, and a small area of absent lashes is usually acceptable. The lateral canthotomy and cantholysis and semicircular flap will leave the temporal lid segment without lashes. This also is more cosmetically acceptable than absent central lashes. Transplantation of hairs from the eyebrow to the eyelid is another treatment of madarosis. An incision is made at the junction of the skin-lid margin over the absent lash area. The direction of the brow hairs is studied, and the hairs pointing in the desired direction are chosen. A portion of the eyebrow that is equivalent in length and width to the lid with absent cilia and consisting of four rows of hairs is excised from the eyebrow. The correct depth of the graft is critical; it must include the hair follicles while avoiding too much subcutaneous tissue. The graft is sutured to surrounding skin and lid margin so the hairs are pointing away from the cornea and correspond to the direction of the adjacent normal cilia. Usually, the outer two rows of hairs eventually slough off. This procedure commonly leads to the loss of hairs over parts of the graft and usually unsatisfactory cosmetic results. Another alternative to lash transplantation is the removal of a segment of the normal temporal lashes and placement of them, as described, into the area of madarosis. Naugle advocated this approach and claims good results. Again, the loss of temporal lashes to create central lashes is a cosmetically desirable tradeoff. Good results have also been achieved with the placement of individual lash grafts into areas of madarosis. Blepharopigmentation is a technique in which pigment is tattooed into the eyelids. It is chiefly advocated to simulate eyeliner or to enhance the eyelashes. However, it can also be used to simulate eyelashes and is especially effective if the eyelashes are sparse rather than totally absent. Equipment and pigment are available through Dioptics (Irvine, CA) and Alcon Surgical (Irvine, CA). Pigment is applied beneath the skin in the desired density with a rapidly pulsating needle that is covered with pigment.
453
completely removed from the lid and attached to the superior orbital rim at the arcus marginalis or extirpated.
DIAGNOSIS ●
SECTION 21 • Eyelids
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The initial presentation typically occurs soon after birth, when the infant begins to nurse. The ptotic lid is noted to rhythmically jerk upward. The retraction is most commonly demonstrated by opening and closing the mouth or by moving the jaw from side to side. It is rarely demonstrated by coughing, smiling, the Valsalva maneuver, swallowing, inspiration, or contraction of the platysma muscle. Several series have reported significant associations with other ocular problems, including strabismus, anisometropia, amblyopia, and Duane’s syndrome. The frequency of strabismus has been reported to be as high as 58% and includes superior rectus palsies, double elevator palsies, and horizontal deviations. Trigeminal-Abducens synkinesis has been reported.
TREATMENT If amblyopia is present, it must be treated vigorously, and anisometropia must be corrected if it is significant. Because the patient with Marcus Gunn syndrome brings to the clinician two separate problems (ptosis and jaw winking), the satisfactory elimination of both often is a challenging endeavor. In the evaluation of a patient, one must decide which component is more cosmetically intolerable-only then can the surgical plan be tailored accordingly and the best results obtained. A discussion with the patient or parents is important to ensure that they have realistic expectations and are aware that a compromise may be necessary. In patients with very mild ptosis (less than 2 mm) and mild jaw wink (3 to 4 mm), one can perform a Müller’s muscle conjunctival resection as described by Putterman or a levator resection; even no treatment may be acceptable. If the ptosis is moderate and the jaw winking is minimal, a levator resection is the treatment of choice. Undercorrection of the ptosis has been a complication of this approach, and it is recommended that the resection be greater (4 to 5 mm more) than in the usual case of congenital ptosis. More predictable elevation may be achieved with a combined levator resection, Muellerectomy and conjunctivotarsectomy from an anterior approach. Unfortunately, an exacerbation of the jaw wink may occur because this procedure strengthens the levator muscle and the eyelid excursion then begins at a higher level. When the jaw-winking component is severe, a levator resection exacerbates the wink. In this case, the jaw wink must be obliterated through release of the levator aponeurosis followed by a frontalis suspension. Dryden and coworkers described a reversible technique of suturing the levator aponeurosis to the arcus marginalis of the upper orbital rim to ensure its deactivation. Bilateral levator release with fascia lata suspension of both eyelids is the procedure of choice because the often-marked asymmetry of unilateral surgery is avoided. Bilateral frontalis suspension combined with only unilateral levator excision of the affected eye also is advocated (‘chicken-beard’ operation). If the patient or parents refuse bilateral surgery, the frontalis suspension may be performed on the affected eye with or without prior levator release.
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To effect a levator release, a skin crease incision is made, and a small amount of preseptal orbicularis is resected. The underlying septum is identified, and nearly its entire length is incised horizontally. This allows identification of the levator aponeurosis, which is released from the tarsus and attached to the arcus marginalis with multiple 5-0 Dacron sutures. Care should be taken to avoid the supraorbital neurovascular bundle. A frontalis sling of the surgeon’s choice can then be performed. A double rhomboid as described by Beard is an excellent choice in this setting. In cases in which the wink is not prominent and the levator does not have to be released, a transconjunctival frontalis suspension is an excellent option. Before the age of 3, the use of a synthetic sling is suggested, such as silicone rods or tubing. Banked fascia can be used, but in the authors’ experience, this material has not been satisfactory. After the age of 3, the child’s fascia lata has developed sufficiently to enable harvesting from either the midthigh or the hip area. A stab incision is made at the upper edge of the brow where elevation of the eyelid by the surgeon’s fi nger gives the most pleasing cosmetic appearance. This incision need not be carried down to the periosteum. A small amount of skin undermining will ensure good closure over the fascia or silicone knot later. The eyelid is then everted over a Desmarres retractor and held in place with a forceps. A fascia lata strip measuring approximately 3 mm in width and 12 to 15 cm in length is loaded on a half-circle, reverse-cutting needle (Richard Allen no. 2164-4) and passed horizontally through the lid just anterior to the superior tarsal border. This horizontal limb should measure approximately 6 to 10 mm depending on the patient’s size. An attempt is made to incorporate the tarsal plate. The needle is then placed back in the lid, where it has just exited, and driven in a slightly posterior direction to an area immediately behind the superior orbital rim, ‘walked’ anteriorly over the rim, and brought out through the brow incision. Before this vertical fascia limb is pulled through, a small piece of 4-0 silk is placed as a marker suture at the junction of the horizontal and vertical limbs to facilitate removal of the vertical portion should repositioning of the fascia be necessary. The needle is reloaded with the opposite end of the fascia, brought through the entry site of the horizontal limb, and then directed superiorly to the brow incision in the same fashion. The result is a triangle-shaped sling with its base at the anterosuperior tarsal margin. The two vertical limbs can now be elevated to check lid margin height, contour, and symmetry. Any adjustments are made, and then the fascia is secured in the frontalis with a square knot. A 5-0 Dacron is sewn through the knot to ensure it will not slip. At this point, a good lid crease should be present, and the lid margin should be 1 to 2 mm above the desired postoperative level and in apposition with the globe. Several modifications of the frontalis suspension have been advocated. The author favors the transconjunctival suspension in cases in which the levator has not been released. The advantages of this approach include a lesser chance of infection because it avoids low anterior skin incisions near the lash line, avoidance of visible traction lines below the skin, and facilitation of crease formation because the fascia is placed posteriorly to the orbital septum. In addition, normal attachments of the levator to the tarsus and skin are preserved so that when the frontalis muscle elevates the brow, the lid is indirectly raised and normal lid margin contour and apposition to the globe are maintained. This procedure is also inherently safer because the needle used to pass the fascia lata is never directed toward the eyeball, therefore minimizing the chance of ocular penetration.
COMMENTS The jaw-winking syndrome is one type of congenital ptosis of a synkinetic nature that classically consists of ptosis of the upper eyelid associated with involuntary retraction of the lid during contraction of the ipsilateral pterygoid muscle. In general, the wink tends to become less noticeable with age, so if it is minimal and the patient has more than 4 mm of levator function, a standard levator resection should be highly successful. In cases of poor levator function, a frontalis suspension of some type should be used; if the wink is severe, the levator should be released from the tarsus and tacked to the arcus marginalis, followed by frontalis suspension.
REFERENCES Beyer-Machule CK, Johnson CC, Pratt SG, Smith BR: The Marcus Gunn phenomenon. Orbit 4:15, 1985. Bullock JD: Marcus Gunn jaw-winking ptosis: classification and surgical management. J Pediatric Ophthalmol Strabismus 17:375, 1980. Dailey RA, Wilson DJ, Wobig JL: Transconjunctival frontalis suspension (TCFS). Ophthalmol Plast Reconstr Surg 7, 1991. Darcet TW, Crawford JS: The quantification, natural course, and surgical results in 57 eyes with Marcus Gunn (jaw-winking) syndrome. Am J Ophthalmol 92:702–707, 1981. Dryden RM, Fleuringer JL, Quickert MH: Levator transposition and frontalis sling procedure in severe unilateral ptosis and paradoxically innervated levator. Arch Ophthalmol 100:462, 1982. Kodsi S: Marcus Gunn jaw winking with trigemino-abducens synkinesis. J AAPOS 4:316–7, 2000.
249 MELANOCYTIC LESIONS OF THE EYELIDS 172.1 (Ephelis, Lentigo, Nevocellular Nevus, Dermal Melanocytosis, Malignant Melanoma) Steven A. McCormick, MD, FACP New York, New York Tatyana Milman, MD, FAAO New York, New York
ETIOLOGY Benign melanocytic lesions of the eyelids are a diverse group of congenital and acquired lesions derived from neural crest mela-
nocytes. Three distinct cells of origin-epidermal melanocytes, nevocellular nevus cells, and dermal melanocytes-result in a variety of clinically distinct pigmented lesions of the skin. Classification schemes should distinguish among these three cell types and the location of origin. All of these cells have the capacity to synthesize and excrete melanin, the primary cutaneous pigment.
CLINICAL DIAGNOSIS Examination should be performed in good light; the wide beam of the slit lamp is ideal. Size, location, and description of the lesion (height, surface and border characteristics, color, and so on) should be carefully recorded. The goal of the examination is to determine whether the lesion is likely to be a benign or malignant melanocytic lesion or another pigmented lesion of nonmelanocytic origin, such as seborrheic keratosis or pigmented basal or squamous cell carcinoma. Photographs of suspicious lesions are helpful in documenting the growth or changes in coloration that may signal malignancy. The clinicopathologic features of these entities are discussed to assist the examiner in establishing the correct clinical diagnosis and in affecting appropriate management.
BENIGN LESIONS
CHAPTER 249 • Melanocytic Lesions of the Eyelids
In cases of unilateral ptosis in which the levator is released, a promising technique involving the advancement of a flap of frontalis muscle to the superior tarsus has been successful. The long-term results have not been published, but it appears to be far more successful than the corrugator muscle transpositions used in the 1960s. When an anterior approach is performed, the sling material is sutured to the tarsal surface. The Richard Allen needle is used to pass the free ends in a post-septal plane and out the suprabrow incision in the same manner as the transconjunctival approach. Fixation sutures may be used to evert the eyelashes prior to skin closure to avoid lash ptosis that can occur with frontalis suspensions.
Benign lesions derived from the epidermal melanocytes include the ephelis (common freckle), lentigo simplex, and solar lentigo (‘age spot’). All commonly affect the periocular skin, as well as skin elsewhere. Ephelides are not truly tumors, but are perhaps the most common of all skin lesions, affecting all whites to some degree, as well as pigmented races. Solar lentigines are also common in whites with excessive sun exposure. Benign tumors composed of nevocellular nevus cells are referred to as melanocytic nevi (clinically, the simple term nevus is usually applied). Nevi are classified as junctional, intradermal, or compound based on the histologic location of the nevocellular proliferation. Most of the brown to black coloration results from melanin in the superficial skin, whereas tumefaction results from a dermal component. Location in the basal epidermis (junctional component) usually imparts a darker color (black to brown) than when the proliferation is limited to the dermis (intradermal nevus). When nevus cells are present in both locations, the term compound nevus is applied. Common nevi tend to evolve throughout life, beginning usually as pigmented macules or papules, increasing in height and/or pigmentation (especially under the hormonal influences of puberty or pregnancy), and finally regressing with depigmentation, fat infi ltration, and fibrosis. Some larger nevi may harbor hair follicles or have a papillomatous surface. Most nevi are noted at birth or in early childhood, and it is often difficult to determine whether a given lesion is congenital or acquired. Unlike ‘typical’ nevi, large congenital nevi (1 cm or more in diameter and evident at birth) are treated aggressively because of their propensity to give rise to malignant melanoma in approximately 12% of the cases. An example of congenital nevus affecting the eyelids is the ‘kissing’ nevus, which develops in utero before the normal development of the eyelid fissure. The nevus, thus, is located on apposed areas of the upper and lower eyelids. These, like other bulky nevi, are usually removed for cosmetic or mechanical reasons.
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SECTION 21 • Eyelids
Another special variant is the Spitz nevus, or spindle and epithelioid cell nevus. This tumor commonly presents on the face of children and young adults as a small, sharply demarcated, symmetrical, dome-shaped papule, seated in the dermis. It may be erythematous and hyperpigmented, and may enlarge rapidly (up to 10 mm), mimicking malignant melanoma. Despite its aggressive histologic appearance, this lesion is benign and self-limited. A controversial category is the dysplastic nevus, occurring in as many as 8% of the population. These nevi are macules that are usually larger than typical nevi (more than 4 mm) and present with less distinct borders and mottled pigmentation. Some have been compared morphologically to a ‘fried egg.’ Dysplastic nevi may occur in two clinical settings: in patients with a familial autosomal dominant dysplastic nevus syndrome (B-K mole syndrome), and as a sporadic condition (sporadic dysplastic nevus syndrome). In B-K mole syndrome the lifetime risk for the development of malignant melanoma approaches 100%. The lifetime risk for malignant transformation in a sporadic dysplastic nevus syndrome has been estimated between 18–20%, but the majority of experts believe that most sporadic dysplastic nevi will never transform into melanoma, and do not qualify them as precancerous lesions. The histologic parameters for these lesions are likewise debated. Caution suggests close observation and excision if change or growth is documented. Benign lesions derived from dermal melanocytes include the blue nevus and nevus of Ota. The blue nevus results from a focal proliferation of dermal melanocytes in the deeper layers of the dermis. Pigment thus situated results in slate-gray to blue coloration through the Tyndall phenomenon. The nevus of Ota is a larger area of similar skin coloration that results from a less dense distribution of dermal melanocytes (dermal melanocytosis). Ipsilateral ocular melanocytosis usually is also present, imparting slate-gray pigmentation of the sclera and increased pigmentation in the uveal tract. These patients have no increased risk for the development of cutaneous malignant melanoma, but there is a reported increased risk of uveal, orbital, and CNS malignant melanoma; therefore, regular ophthalmic examinations should be performed.
Solar lentigo ●
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Melanocytic (nevocellular) nevi ●
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Etiology: threshold dose of UV exposure leading to the development in genetically predisposed individuals; freckles darkening with additional sun exposure; no increase in melanocytes (only increased melanin production). Clinical fi ndings: small tan to brown macules on sunexposed skin (less than 1 to 3 mm). Treatment: no treatment.
Lentigo simplex ●
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Etiology: no predilection for sun-exposed skin; no darkening of the lesions with UV exposure; multiple lesions suggesting an association with systemic syndromes (e.g. Peutz–Jeghers, LAMB, or leopard syndromes); histologically, increase in number of epidermal melanocytes; regarded by some as a form of evolving melanocytic nevus. Clinical findings: small brown to black macules, darker and larger than ephelis; clinically indistinguishable from a junctional nevus Treatment: no treatment
Etiology: hamartia of melanoblasts arrested in their normal migration and development into epidermal melanocytes; ubiquitous and affect all races; sun exposure and hormonal factors may be operative (often enlarge at puberty and in pregnancy). Clinical findings: morphology and pigmentation vary from small, flat macules to elevated, dome-shaped lesions; may be pedunculated and papillomatous; pigmentation ranges from tan to black; usually evenly pigmented; may increase in size over time. Classification: junctional, intradermal, or compound types (histologically); dysplastic nevus is a controversial subtype that may possibly be a precursor for melanoma; other special types includes Spitz nevus, balloon cell nevus, and congenital melanocytic nevus. Treatment: excisional biopsy, if indicated, or observation.
Lesions of dermal melanocytes ●
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Lesions of epidermal melanocytes Ephelis (common freckle)
Etiology: accumulative UV exposure leading to the development on sun-exposed skin of older individuals (hence the previous term ‘senile lentigo’). Clinical findings: multiple large, evenly pigmented macules on sun-exposed skin (1 to 7 mm); may gradually enlarge and coalesce; in xeroderma pigmentosum, often appear by adolescence; histologically, no obvious (or minimal) increase in the number of epidermal melanocytes (increased melanin production). Treatment: both UV protection and avoidance of sun exposure.
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Etiology: increased numbers of dermal melanocytes, forming focal tumors (blue nevi) or diffuse distribution of melanocytes (nevus of Ota). Clinical findings: blue nevi with slate-gray to blue pigmentation due to the deep-seated pigmentation (Tyndall’s phenomenon); common in head and neck region; may be slightly raised, but epidermis not affected; nevus of Ota not usually elevated, but displays diffuse slate-gray pigmentation in distribution of the trigeminal nerve; may be bilateral; ipsilateral scleral pigmentation usually present; increased risk of uveal, orbital, CNS melanoma. Treatment: excisional biopsy of blue nevus if tumefaction is large or cosmetically undesirable; no practical treatment available for nevus of Ota.
MALIGNANT AND PREMALIGNANT LESIONS Primary malignant melanoma of the eyelid and periocular skin is relatively rare, representing 1% to 5% of all eyelid malignancies. The incidence of cutaneous melanoma has been increasing at an alarming rate (more than 600% increase from 1950 to 2000), and undoubtedly so will the incidence of eyelid melanoma. Most melanomas arise de novo from transformed, atypical basal melanocytes, but in 25% to 35% of cases, histologic remnants of a benign nevus may be detected. The clinician must be suspicious of the ‘changing mole’ or any newly recognized pigmented lesion. The practitioner’s task is to recognize the surface characteristics that are harbingers of malignancy. Malignant lesions tend to display irregular or notched borders rather than the smooth, symmetric borders of nevi and other pigmented lesions. They often display variegated pigmentation,
disease. In regional disease, the number of involved lymph nodes, tumor burden within the lymph nodes, and ulceration within the primary tumor are important predictors of survival.
Lentigo maligna and lentigo maligna melanomas ●
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Etiology: may occur as a result of chronic, cumulative sun exposure; atypical melanocytes proliferate in the basal regions of the epidermis in Hutchinson’s freckle; invasion in 5%–50% (lenitgo maligna melanoma), but usually only after many years of evolution. Clinical fi ndings: slowly enlarging irregular pigmented macule or macules with irregular borders that evolve over several years; frequently involve the lateral canthal region and lower eyelid; induration, elevation, and change in coloration possible signs of invasion. Treatment: excision, especially if nodularity develops within the macule.
Malignant melanoma (superficial spreading or nodular) ●
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Etiology: may be caused by episodic, intense sun exposure; malignant transformation of basal epidermal melanocytes (or less commonly, malignant degeneration of nevus cells); growth proceeds from an in situ phase (recognized in superficial spreading melanoma) to invasive growth, which proceeds more rapidly in nodular melanoma. Clinical findings: the ABCDE rule (asymmetry, border irregularity, variation in color, diameter of more than 5 mm, evolution) is useful; pigmented macules with these features should be considered suspicious for superficial spreading melanoma; nodular melanomas present as enlarging, elevated lesions with variable dark pigmentation; evolution may be noted in up to 80%; induration and changing pigmentation are harbingers of malignancy. Treatment: excisional biopsy of suspicious lesions, preferably with up to 1-cm margins of resection; incisional biopsy of large lesions if the diagnosis is in question; sentinel lymph node biopsy for lesions with tumor thickness greater than 1 mm; regional lymph node dissection if positive nodes are identified.
CHAPTER 249 • Melanocytic Lesions of the Eyelids
ranging from pink/red to brown/black, whereas nevi tend to be uniformly pigmented. Acquired nevi tend to be less than 5 mm in diameter; malignant lesions are usually larger. However, other pigmented, nonmelanocytic lesions (e.g. seborrheic keratosis and keratoacanthoma) may be large. Change in clinical appearance and symptoms (i.e. evolution) of the lesion are uncommon in nevi, but are frequently observed in cutaneous malignant melanoma. The ‘ABCDE rule’ of clinical signs is a helpful mnemonic: asymmetry, border irregularity, variation in color, diameter of more than 5 mm, and evolution. Lentigo maligna (Hutchinson’s freckle) may be considered a premalignant lesion that has a natural history unlike the other types of malignant melanoma. It is a relatively common fi nding on the face in elderly Caucasian individuals, and often involves the lower eyelid and lateral canthal region. Lentigo maligna begins as one or more pigmented patches with irregular borders, and enlarges slowly (over several years). As the lesion expands, the pigmentation may change as some areas regress and others proliferate. Lentigo maligna may, after this protracted in situ phase, progress to lentigo malignant melanoma, probably the most common melanoma type affecting the eyelid skin. The appearance of nodularity within the lesion is often an indicator of progression to the invasive stage. The risk of progression appears to be low (variable lifetime risk figures are quoted: from 5% to 50%). Malignant melanoma of the periocular skin, arising de novo or within a pre-existing acquired or congenital nevus, is classified as either superficial spreading melanoma or nodular melanoma. Superficial spreading melanoma, the most common melanoma subtype of the head and neck region, begins as a brown to gray or rose-colored, minimally elevated in situ lesion with irregular, notched borders. Unlike with lentigo maligna, the lesion is rarely more than a few centimeters in its radial growth phase and becomes minimally invasive much earlier (typically within 1 year). It is important to recognize and excise the lesion at this stage. Induration, elevation, and mottling are early signs of invasion. Nodular malignant melanoma begins as an elevated, often darkly pigmented tumor that increases in bulk rapidly and, unlike superficial spreading melanoma, often ulcerates and bleeds. A radial growth phase is not usually recognized; an in situ lesion is not included in the classification. Because the vertical invasion occurs early, nodular melanoma usually presents with a smaller diameter than superficial spreading melanoma (often less than 1 cm). As a result of its early and aggressive invasive growth, this type of cutaneous melanoma carries the worst prognosis. Staging schemes separate patients with local disease only (stages I and II), with local nodal metastases (stage III), or with distant nodal or visceral metastases (stage IV). Approximately 80–90% of cases are diagnosed in stages I and II, with a 5-year survival rate of around 90%. Prognosis in localized disease is gauged on the depth of invasion as measured microscopically. Breslow found that tumors of less than 0.76 mm in thickness (measured from the granular cell layer of the epidermis to the deepest extent of invasion) did not metastasize (and therefore did not require regional node dissection). In patients with tumors of more than 1.5 mm, survival rates are doubled if regional lymphadenectomy is performed. Sentinel lymph node biopsy is currently recommended for localized lesions with tumor thickness greater than 1 mm; if positive, the biopsy is followed by regional lymph node dissection. Prognosis is poor for stages III and IV; 5-year survival rates are reported as 60% for regional (stage III) disease, and 14% for distal metastatic
SUMMARY Pigmented lesions of the eyelid and periocular skin present a challenge to the ophthalmologist, but the importance of recognizing suspicious tumors cannot be overemphasized. Lesions removed early in their course carry an extremely favorable prognosis, and surgical extirpation in the facial region is accomplished with limited cosmetic effects when lesions are small. The task of the clinician is to differentiate among benign, premalignant, and malignant lesions with the use of clinical examination and review of the patient’s historical observations of the lesion. The clinician must also recognize that several nonmelanocytic lesions may present as pigmented tumors; these include pigmented basal cell carcinoma, actinic keratosis, keratoacanthoma, seborrheic keratosis, and dermatofibroma. Suspicious lesions should be biopsied.
REFERENCES Abbasi NR, Shaw HM, Rigel DS, et al: Early diagnosis of cutaneous melanoma: revisiting the ABCD criteria. JAMA 292(22):2771–2776, 2004.
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Balmaceda CM, Fetell MR, O’Brien JL, et al: Nevus of Ota and leptomeningeal melanocytic lesions. Neurology 43(2):381–386, 1993.
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Clark WH, Elder DE, Guerry D, et al: A study of tumor progression: the precursor lesions of superficial spreading and nodular melanoma. Hum Pathol 15:1147–1165, 1984.
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Cramer SF: The histogenesis of acquired melanocytic nevi. Based on a new concept of melanocytic differentiation. Am J Dermatopathol 6 Suppl: 289–298, 1984.
SECTION 21 • Eyelids
Cramer SF: The origin of epidermal melanocytes: implications for the histogenesis of nevi and melanomas. Arch Pathol Lab Med 115:115–119, 1991. Crowson AN, Magro CM, Sanchez-Carpintero I, et al: The precursors of malignant melanoma. Recent Results Cancer Res160:75–84, 2002. Elder DE, Murphy GF: Atlas of tumor pathology: melanocytic tumors of the skin (third series, fascicle 2). Washington, DC, Armed Forces Institute of Pathology, 1991. Grossniklaus HE, McLean IW: Cutaneous melanoma of the eyelid: clinicopathologic features. Ophthalmology 98:1867–1873, 1991.
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DIAGNOSIS The diagnosis is made on the basis of careful general medical and ophthalmologic history and clinical examination. An examination of eyelid fullness is made by palpation and ballottement of the globe with observation of the fat pads.
Differential diagnosis
Kienstra MA, Padhya TA: Head and neck melanoma. Cancer Control 12(4):242–247, 2005.
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Le AD, Fenske NA, Glass LF, et al: Malignant melanoma: differential diagnosis of pigmented lesions. J Fla Med Assoc 84(3):166–174, 1997.
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Lever WF, Schaumberg-Lever G: Histopathology of the skin. Philadelphia, JB Lippincott, 1990, pp. 756–805.
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Lopransi S, Mihm MC: Clinical and pathological correlation of malignant melanoma. J Cutan Pathol 6:180–194, 1979. Rager EL, Bridgeford EP, Ollila DW: Cutaneous melanoma: update on prevention, screening, diagnosis, and treatment. Am Fam Physician 72(2):269–276, 2005. Spencer WH (ed): Ophthalmic pathology: an atlas and text. Philadelphia, WB Saunders, 1996:2261–2278. Stevenson O, Ahmed I: Lentigo maligna : prognosis and treatment options. Am J Clin Dermatol 6(3):151–164, 2005. Vaziri M, Buffam FV, Martinka M, et al: Clinicopathologic features and behavior of cutaneous eyelid melanoma. Ophthalmology 109(5):901– 908, 2002.
The thin nature of the orbital septum allows hereditary or involutional herniation of orbital fat. Thyroid immune-related orbitopathy may increase the volume of fat and lead to prolapse in the upper and lower eyelids. Posterior sub-Tenon injection of triamcinolone may cause ptosis and/or orbital fat prolapse.
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Dermatochalasis. Prolapsed lacrimal gland. Eyelid edema or blepharochalasis. Thyroid immune related orbitopathy. Festoons or cheek bags.
All of the above may be present in conjunction with orbital fat prolapse.
TREATMENT Local ●
Make-up applied by a skilled aesthetician may slightly improve the cosmetic appearance.
Surgical Upper eyelid ●
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250 ORBITAL FAT HERNIATION 374.34 (Eyelid Fat Prolapse, Orbital Fat Prolapse, Adipose Palpebral Bags, Baggy Eyelids) Eric A. Steele, MD Portland, Oregon Roger A. Dailey, MD Portland, Oregon
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ETIOLOGY ●
Fullness of either the upper or lower eyelid can result from the herniation of orbital fat through the orbital septum, fluid retention or accumulation in the periocular tissues, prolapse of the lacrimal gland, or excess skin (dermatochalasis). Orbital fat herniation results from atrophy and dehiscence of the orbital septum allowing for forward prolapse of the orbital fat pads. In the upper eyelid, orbital fat prolapse may contribute to mechanical ptosis, as well as pose cosmetic concerns in conjunction with dermatochalasis. In the lower eyelid, fat prolapse will result in cosmetic deformity based on underlying bony anatomy and the status of other mid facial soft tissues.
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Surgical intervention in the upper eyelid will often involve simultaneous treatment of dermatochalasis. Surgery is performed most commonly with the patient under local or monitored anesthesia. After infi ltration with a local anesthetic agent containing epinephrine, the amount of skin to be excised is marked. The lower border of skin excision coincides with the eyelid crease. Incision through skin and muscle is made with a scalpel or CO2 laser. Skin and muscle are excised either in one flap or separately. The orbital septum is identified and incised in a complete horizontal ‘open sky’ fashion to expose the preaponeurotic fat pads. After supplemental injection of fat pads with anesthetic agent if necessary, the medial and central fat pads are excised as needed to obtain the desired result. Clamping of the fat pads can be used; meticulous hemostasis is mandatory. Care is taken to avoid resection of the lacrimal gland or overzealous resection of fat, especially in the medial central pad, to avoid an A-frame deformity or hollowed appearance after surgery. The skin edges are closed with a running nylon suture (6-0 or 7-0); the septum is not sutured. Crease formation stitches through the levator aponeurosis are used as desired.
Lower eyelid: transcutaneous ●
The transcutaneous approach can be used where excessive skin (dermatochalasis) accompanies orbital fat herniation. Anesthesia is performed as described for the upper eyelid.
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Lower eyelid: transconjunctival ●
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Transconjunctival lower eyelid blepharoplasty is the procedure of choice for most cases of pure orbital fat prolapse without significant dermatochalasis. After appropriate anesthesia, the globe is protected with a Jaeger lid plate using gentle pressure to prolapse the fat pads. The lower lid is pulled down by the assistant, and an incision is made through the conjunctiva and capsulopalpebral fascia to reach the orbital fat pads. The incision is placed approximately midway between the inferior border of the lower tarsus and the inferior fornix and can be made with scissors, scalpel, cutting cautery, radiofrequency, or CO2 laser. The tarsus is retracted inferiorly with a Desmarres retractor, and the capsulopalpebral fascia is retracted superiorly with a traction suture. The fat pads are identified and teased from their respective capsules. Care is taken to identify and avoid damage to the inferior oblique muscle between the central and medial fat pads. Fat is removed in a graded fashion to obtain the desired result. Options include release of the arcus marginalis and repositioning of orbital fat across the orbital rim to correct midfacial contour abnormalities or tear trough deformity. The repositioned fat can be fi xed with buried absorbable sutures or with externalized sutures removed in the postoperative period. The conjunctival incision is not closed.
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Superior sulcus deformity (excessive fat removal); Ptosis; Lacrimal gland injury; Blindness (orbital hemorrhage).
COMMENTS Orbital fat prolapse is primarily a cosmetic concern; thus, care for these patients should be undertaken with a thorough knowledge of anatomy, patient expectations, and surgical technique. State-of-the-art care includes the use of CO2 laser and attention to fat preservation and repositioning techniques.
REFERENCES Baylis HI, Long JA, Groth MJ: Transconjunctival lower eyelid blepharoplasty: technique and complications. Ophthalmology 96:1027–1032, 1989.
CHAPTER 251 • Ptosis
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A subciliary incision is placed 2 to 3 mm below the lashes of the lower eyelid. Skin and muscle are incised with a scalpel or CO2 laser. The skin-orbicularis flap is then dissected inferiorly to expose the orbital septum. Stab incisions or wide incision of the septum is made over the prolapsing fat pads. The fat pads (medial, central, and temporal) are teased out of their capsules and excised as needed with any combination of clamping, cautery and CO2 laser. Meticulous hemostasis is used. Options at this point include a release of the arcus marginalis and draping of excess orbital fat over the orbital rim to improve contour deformities in the midface and the tear trough deformity. The redraped orbital fat can be fi xed to the suborbicularis oculi fat pad or periosteum as desired with an absorbable suture. The septum is not closed, and the skin-orbicularis flap is draped back over the residual fat pads; then, skin, muscle, or both are excised as necessary. Care must be taken to have the patient look up and open the mouth to determine the safe amount of skin and muscle to be excised.
Dailey RA, Wobig JL: Eyelid anatomy. J Dermatol Surg Oncol 18:1023–1027, 1992. Del Canto AJ, Downs-Kelly E, Perry JD: Ptosis and orbital fat prolapse after posterior sub-Tenon’s capsule triamcinolone injection. Ophthalmology 112:1092–1097, 2005. Hamra ST: Arcus marginalis release and orbital fat preservation in midface rejuvenation. Plast Reconst Surg 96:354–362, 1995. Wobig JL, Dailey RA: Oculofacial plastic surgery. New York, Thieme, 2004.
251 PTOSIS 374.30 (Blepharoptosis) Eric A. Steele, MD Portland, Oregon Roger A. Dailey, MD Portland, Oregon The term blepharoptosis refers to an abnormally low upper eyelid. The retractors of the upper lid are the levator palpebrae superioris, innervated by the superior division of the oculomotor nerve and responsible for the majority of lid elevation, and the superior tarsal (Müller’s) muscle, a smooth, sympathetically innervated muscle responsible for approximately 1 to 2 mm of lid elevation. The protractor of the eyelids is the orbicularis oculi muscle, and lid position is determined by the balance of these forces.
COMPLICATIONS
ETIOLOGY
Complications can result from an incomplete preoperative workup or poor surgical planning. Failure to recognize preexisting conditions such as lid laxity, lid edema, metabolic conditions (e.g. thyroid conditions, allergy, sodium imbalance), hypertrophy of orbicularis oculi, relative prominence of the globe, blepharochalasis, or lid malpositions will compromise the surgical result and patient satisfaction. Complications include: ● Lower lid ectropion and/or retraction; ● Rounding of the lateral canthal angle; ● Upper eyelid retraction and lagophthalmos;
Ptosis has traditionally been categorized as congenital versus acquired. A mechanistic classification may be more useful in distinguishing types of ptosis and the appropriate surgical intervention. Accordingly, ptosis may be divided into myogenic, neurogenic, aponeurotic, or mechanical causes.
Myogenic ptosis ●
Myogenic causes include any disorder with reduced or absent levator palpebrae muscle function secondary to maldevelopment, dystrophy, degeneration, or injury of the levator muscle.
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SECTION 21 • Eyelids ●
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Congenital ptosis is usually myogenic and thought to result from abnormal development of the levator muscle (fibrofatty replacement of the normal striated muscle fibers). It may be unilateral or bilateral and is generally characterized by reduced levator muscle function, lid lag on downgaze, poor or absent lid crease, and lagophthalmos (incomplete closure). Congenital ptosis may occasionally be inherited as an autosomal dominant trait, but it is usually an isolated congenital anomaly. Ptosis is associated with many syndromes, including the blepharophimosis syndrome (an autosomal dominant condition typified by bilateral ptosis, telecanthus, epicanthus inversus, and phimosis). In addition, congenital ptosis may be associated with superior rectus dysfunction, amblyopia, astigmatism, anisometropia, and strabismus. Amblyopia, when seen with ptosis, is usually secondary to induced astigmatism or anisometropia and only rarely results from sensory deprivation. Occlusion or other treatment modalities should be continued after ptosis repair. Other causes of myogenic ptosis include chronic progressive external ophthalmoplegia, congenital fibrosis syndrome, disorders of the neuromuscular junction (e.g. myasthenia gravis), and muscular dystrophies such as oculopharyngeal muscular dystrophy and myotonic dystrophy. Occasionally, trauma may primarily damage the levator muscle itself without affecting its aponeurosis or innervation.
Neurogenic ptosis ●
Neurogenic causes of ptosis include cranial nerve III dysfunction (with partial or complete ptosis depending on the site and degree of nerve involvement), Horner’s syndrome (loss of sympathetic innervation to Müller’s muscle, typically resulting in 2 mm or less of ptosis), Marcus Gunn jaw-winking syndrome (unilateral ptosis with synkinesis of the ipsilateral pterygoid and levator muscles such that jaw movement may result in retraction of the ptotic lid), Guillain–Barré syndrome (especially the Miller–Fisher variant in which ptosis may occur in association with ophthalmoplegia, mydriasis, ataxia, and areflexia), botulism (characterized by dilated, sluggish pupils, dry mouth, flaccid paresis, and ptosis), multiple sclerosis, and ophthalmoplegic migraine. Of course, trauma with resultant sympathetic or cranial nerve III damage may also cause ptosis on a neurogenic basis.
DIAGNOSIS Clinical signs and symptoms ●
The evaluation of ptosis requires a careful history to determine the age of onset, familial incidence, rate of progression, variability/fatigability, and association with other ocular findings.
Laboratory findings ●
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As part of a complete ophthalmologic evaluation, motility assessment, pupillary testing, and inspection of Bell’s phenomenon should be performed. Palpebral fissure measurement (9 mm is considered normal), margin-reflex (from upper lid to the light reflex) distance measurement, and estimation of levator excursion while immobilizing the frontalis muscle (to evaluate levator palpebrae muscle function) will determine the type of surgical intervention best suited for the patient. It is also helpful to manually elevate the ptotic lid to eliminate the effect of Hering’s law and assess the amount of ptosis in the contralateral eye. Should any variability or fatigability be elicited, a Tensilon test and serologic evaluation for acetylcholine receptor antibodies may be helpful in diagnosing myasthenia gravis. In patients with mild ptosis (2 mm or less), testing with 2.5% phenylephrine eyedrops can help determine the expected result of ptosis repair via a conjunctiva-Müller’s resection (see below). Visual field testing with ptosis and then with manual elevation of the eyelid can be used to determine the degree of visual field loss associated with ptosis. Documentation of field loss and preoperative photographs are usually required by health insurance carriers before authorization for surgical repair.
Differential diagnosis ●
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True ptosis must be distinguished from pseudoptosis, in which an abnormally low upper eyelid is caused by factors other than dysfunction of the lid elevators. Conditions that mimic ptosis include vertical misalignment, as occurs in hypotropia, blepharospasm, or squinting, and contralateral lid retraction, as occurs in thyroid eye disease and dermatochalasis. The systemic conditions and congenital syndromes associated with ptosis should be sought, and the appropriate treatment should be instituted.
Aponeurogenic ptosis ●
Aponeurotic or aponeurogenic ptosis is the most common cause of acquired ptosis. Stretching of the levator aponeurosis or dehiscence of its insertion onto the tarsal plate (as occurs with aging, trauma, or hard contact lens wear or after ocular surgery with a lid speculum) causes acquired ptosis, characterized by normal levator function, a high lid crease, deep supratarsal sulcus, and increased ptosis on downgaze.
Mechanical ptosis ●
460
Mechanical causes of ptosis include cicatricial changes, lid masses, dermatochalasis, brow ptosis, and microphthalmos or enophthalmos. Floppy eyelid syndrome, characterized by lid laxity, chronic papillary conjunctivitis, and lash ptosis, may also present with ptosis.
TREATMENT Surgical ●
In the majority of patients with acquired ptosis, good levator function (8 mm or more) can be demonstrated, and the preferred method of repair is an external lid crease incision with reattachment or advancement of the levator aponeurosis to the tarsal plate. The lid crease should be carefully marked before infi ltration of the eyelid with a local anesthetic agent. After a skin incision at the lid crease, the dissection is carried through the orbicularis muscle and orbital septum, exposing the preaponeurotic adipose tissue anterior to the levator aponeurosis. The aponeurosis is then separated from its attachments to the overlying adipose tissue and the underlying Müller’s muscle. The tarsal plate is exposed, and the aponeurosis is reattached to the tarsus
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COMPLICATIONS The complications of surgical ptosis management may be divided into the categories of overcorrection, undercorrection, improper suture placement, and tissue reaction. ● In general, overcorrection causes exposure keratitis and therefore necessitates early adjustment. The external levator approach allows loosening or removal of the sutures in the levator aponeurosis, and this adjustment can easily be performed in the outpatient clinic under local anesthesia during the early postoperative period. Overcorrection after any method of ptosis repair may cause severe exposure keratopathy and should especially be avoided in patients with poor Bell’s phenomenon and weak orbicularis function, as occurs with chronic progressive external ophthalmoplegia, dystrophies, and congenital fibrosis syndrome. Occasionally, the lid must be lowered to a less functional and cosmetically appealing height to prevent keratopathy. ● Undercorrection is common in congenital ptosis and may necessitate repeat surgery depending on the needs and expectations of the patient and family. ● If the sutures attaching the frontalis sling or levator aponeurosis to the tarsus are placed too high or too low, entropion or ectropion may result. Careful attention to incorporation of levator aponeurosis within lid crease fi xation sutures may also avoid lid malpositions. ● With large levator resections, conjunctival prolapse may result and can be treated with patching, suturing of the palpebral conjunctiva up into the fornix, or excision of the redundant tissue.
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In patients with frontalis slings, there may be exposure of silicone rods or early reabsorption of banked fascia lata, necessitating repeat surgery. Patients with concomitant strabismus should have their extraocular muscle surgery fi rst because changes in extraocular muscle placement may affect lid position. In addition, if the strabismus cannot be satisfactorily treated in adults, intractable diplopia may result from elevation of the lid to a normal height.
COMMENTS Ptosis is a complex and challenging disorder, requiring careful evaluation of the causative mechanism and surgical options to devise the most appropriate treatment strategy for each patient.
REFERENCES Anderson RL: Aponeurotic ptosis surgery. Arch Ophthalmol 97:1123, 1979. Callahan M, Beard C: Ptosis. 4th edn. Birmingham, Aesculapius, 1990.
CHAPTER 252 • Seborrheic Blepharitis
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with sutures. When surgery is performed under local anesthesia, the patient should be raised to a sitting position to assess the lid height and contour. With fair levator function (5 to 7 mm), a large external levator resection (up to Whitnall’s ligament in many cases) may be necessary to achieve the desired result. The procedure is similar to the external approach for levator repair. Resection of the superior tarsus is an additional technique for maximal elevation of the eyelid. Ptosis with poor levator function (4 mm or less) generally requires frontalis suspension. This can be performed either transcutaneously or transconjunctivally, utilizing autogenous or banked fascia lata or synthetic materials such as silicone rods. These materials are used to suspend the eyelid directly from the frontalis muscle to allow the brow to efficiently raise the eyelid. When the ptosis is unilateral, some advocate disinsertion of the (normal) contralateral levator aponeurosis combined with bilateral frontalis suspension to further stimulate frontalis use and to achieve symmetry on downgaze. The decision to modify a normal eyelid is controversial and requires thorough preoperative discussion. In patients with mild ptosis, excellent levator function, and a positive phenylephrine test, a conjunctiva-Möller’s resection via an internal approach is effective. The lid is everted, and a segment of conjunctiva and Müller’s muscle is resected using a Putterman clamp. The cut edges of the incision are sutured with 6-0 plain suture. For patients in whom surgery is not an option, ptosis crutches may be attached to the upper posterior rim of eyeglasses and used to mechanically elevate the lid. The lid may not close properly, however, and the patient could develop exposure keratopathy.
Frueh BR: The mechanistic classification of ptosis. Ophthalmology 87:1019, 1980. Wobig JL, Dailey RA: Oculofacial plastic surgery. New York, Thieme, 2004.
252 SEBORRHEIC BLEPHARITIS 372.20 Peter B. Marsh, MD Portland, Oregon
ETIOLOGY Seborrheic blepharitis is a common cause of eyelid inflammation which may affect the anterior or posterior lamella of the eyelids, or both, and cause significant ocular discomfort. It is frequently seen in patients with seborrheic dermatitis. Seborrheic blepharitis alone presents with inflammation of the anterior lid margin with greasy sebum secretions near the eyelashes. Posteriorly, involvement of the meibomian glands is one cause of meibomian gland dysfunction. In contrast to seborrheic blepharitis alone, this may lead to patchy inflammation of the meibomian glands which in turn can cause blockage of the glands with inspissated secretions and significant periods of exacerbation of symptoms. The exact etiology is not known. However, an altered meibum composition may be responsible, along with increased Staphylococcus aureus colonization of the eyelid. Although usually a chronic condition, treatment can improve symptoms, especially during times of exacerbation.
DIAGNOSIS Clinical signs and symptoms Patients with seborrheic blepharitis present with symptoms of ocular irritation, including burning, itching, redness, and mildly decreased vision. Meibomian keratoconjunctivitis is
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SECTION 21 • Eyelids
distinguished from other types of seborrheic blepharitis by a shorter duration of symptoms at the time of presentation and a more pronounced inflammation of the eyelids. The anterior aspects of the lids frequently are only minimally involved with deposition of an oily scurf. The prominent feature is diffuse inflammation around the meibomian glands, which are dilated with retained meibum that is not easily expressed. The orifices of the glands are obstructed and pout with these secretions. There is a marked inflammation around the meibomian glands and the orifices. Tear breakup time is frequently shortened due to the abnormal composition of the lipid tear layer. In addition to the lid findings, an important associated condition found in these patients is aqueous tear deficiency (ATD). The symptoms of ATD are similar to those in (and may be masked by the complaints of) patients whose predominant problems are related to blepharitis. Patients with chronic blepharitis, however, have been shown to have changes in the composition of meibum, which may lead to alterations in the tear fi lm, thereby predisposing these patients to associated ocular surface problems related to an unstable tear fi lm. Studies have documented concurrent ATD in a high percentage of patients with chronic blepharitis. It is important to look for an accompanying dry-eye state in these patients and to treat it when present.
Laboratory findings Although diagnosis is usually made clinically without laboratory testing, research has shown alterations in bacterial colonization and composition of meibum in patients with this condition. Aerobic and anaerobic culturing of healthy control patients and patients with each form of chronic blepharitis has revealed a significantly greater incidence of colonization, with Staphylococcus aureus only in the seborrheic subgroups. There was no significant difference in the incidence of coagulase negative Staphylococcus (C-NS), Propionibacterium acnes, or any other bacteria isolated in any of the various patient subgroups compared with control patients. The cultures of meibum revealed no evidence to support its role as a reservoir for bacterial colonization in any form of chronic blepharitis. The possible role of bacterial lipases in modifying the composition of meibum and differences in the biochemical composition of meibum in the various subgroups of chronic blepharitis have also been examined by McCulley et al. Studies have shown that there is a higher percentage of C-NS species capable of de-esterifying fatty waxes and cholesteryl esters in the types of chronic blepharitis with meibomian gland involvement. The exact role of these various meibum components has not been fully defined, but they may provide new avenues for more definitive therapeutic intervention.
TREATMENT Systemic When meibomian gland dysfunction is present in patients with seborrheic blepharitis, systemic treatment with tetracycline may be indicated. Usual dosage is tetracycline 250 mg PO q. i.d., doxycycline 50 mg PO b.i.d., or minocycline 50 mg PO b.i.d. These medications may improve this condition by decreasing bacterial flora on the eyelid or by decreasing bacterial lipase activity, thereby altering the composition of meibum. Nutritional supplementation with omega-3 fatty acids (fish oil or flax seed oil) may be helpful in decreasing the inflammatory component of blepharitis and meibomitis.
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Ocular Warm compresses to the eyelids for 5 to 10 minutes b.i.d. This may be done with a warm wet washcloth or with 1 cup of dry rice in a clean sock heated in a microwave for approximately 45 seconds. Eyelid scrubs with dilute baby shampoo or a commercial lid scrub b.i.d. Bacitracin or erythromycin ointment applied to the lid margins after lid scrubs and to the cul-de-sac at bedtime. Rarely, short-term topical steroids. Topical cyclosporin A drops have been shown to decrease objective signs of meibomitis. Preservative-free artificial tears, and punctal occlusion for associated keratoconjunctivitis sicca. Dermatologic consultation for manifestations of seborrheic dermatitis.
COMPLICATIONS Tetracycline or doxycycline should not be administered to children because of the effect on dental enamel; in addition, it is contraindicated in pregnant women and lactating mothers. Tetracycline should be taken on an empty stomach, such as 1 hour before or 2 hours after meals. If associated gastrointestinal irritation presents as a side effect, 100 mg of doxycycline b.i.d., which may be taken with food, can be substituted. When tetracycline is contraindicated, erythromycin is a suitable alternative.
COMMENTS Seborrheic blepharitis is usually a chronic disease, which may have bothersome exacerbations especially if associated with meibomian gland inflammation. However, with proper diagnosis and treatment, patients can usually experience significant improvement in their symptoms. Nevertheless, the chronic nature of the disease needs to be explained to patients initially so false expections are not created. Careful examination for coexisting conditions such as dry eye and other eyelid conditions is important so that specific treatment may be initiated.
REFERENCES Dougherty JM, McCulley JP, Silvany RE, Meyer DR: The role of tetracycline in chronic blepharitis. Invest Ophthalmol Vis Sci 32:2970–29075, 1991. McCulley JP, Dougherty JM: Bacterial aspects of chronic blepharitis. Trans Ophthalmol Soc UK 105:314–318, 1986. McCulley JP, Dougherty JM, Deneau DG: Classification of chronic blepharitis. Ophthalmology 189:1173–1180, 1983. Perry HD, Doshi-Carnevale S, Donnenfeld ED, et al: Efficacy of commercially available topical cyclosporine a 0.05% in the treatment of meibomian gland dysfunction. Cornea 25(2):171–175, 2006. Ta CN, Shine WE, McCulley JP, et al: Effects of minocycline on the ocular flora of patients with acne rosacea or seborrheic blepharitis. Cornea 22(6):545–548, 2003.
Surgical
253 TRICHIASIS 374.05
The mainstay of treatment is surgery, usually aimed at destroying the eyelash follicle.
Anuja Bhandari, MD, FRCOphth Seattle, Washington James C. Orcutt, MD, PhD Seattle, Washington
Epilation
Trichiasis is an acquired condition in which previously normal eyelashes are misdirected toward the globe and irritate the cornea and conjunctiva. Ectropion may be associated or trichiasis may occur in isolation. Trichiasis can occur secondary to chronic eyelid inflammation (blepharitis) or infections, e.g. trachoma, herpes simplex or zoster, or Hansen’s disease. Systemic diseases such as ocular cicatricial pemphigoid, Stevens–Johnson syndrome, and toxic epidermal necrolysis are known to cause trichiasis. Trichiasis can also be the result of treatment with medications such as travaprost, pilocarpine, epinephrine, trifluridine, idoxuridine and vidarabine. Finally, mechanical or chemical trauma to the eyelids can result in trichiasis.
COURSE/PROGNOSIS Trichiasis may lead to corneal opacification by: ● Keratinization of the conjunctiva and cornea; ● Vascularization and scarring of the cornea; ● Corneal abrasion or ulcer; and ● Corneal thinning and perforation. Visual loss may be concurrent with these pathologic changes if they extend into the visual axis.
DIAGNOSIS Clinical signs and symptoms Symptoms consist of foreign body sensation, pain, photophobia, chronic irritation and decreased vision. The diagnosis is clinical, based on recognition of misdirected eyelashes emanating from the eyelid, directed toward the globe.
Differential diagnosis Other conditions in the differential diagnosis are entropion and distichasis. Trichiasis is differentiated from entropion by the normal position of the eyelid margin. In distichiasis, a second row of eyelashes grows posterior to the normal row of eyelashes, at or near the meibomian gland orifices.
TREATMENT Medical Appropriate medical management of the underlying disease process (blepharitis, ocular cicatricial pemphigoid) is important in the prevention of trichiasis in untreated areas of the lids. A bandage contact lens may be worn temporarily to provide comfort and prevent corneal abrasions.
Argon laser ablation The argon laser provides focused energy with minimal damage to surrounding tissue, minimizing post-treatment swelling and inflammation. Local anesthetic (1% xylocaine with 1 : 100,000 epinephrine mixed with 0.5% bupivicaine) is injected. The laser is directed parallel to the shaft of the cilia and applied to a depth of 2 to 3 mm to destroy the eyelash follicle. Treatment is performed with a spot size of 50 to 100 μm, of 0.1 to 0.5 second duration at 0.3 to 2.0 W power. Forty to 50 applications per eyelash may be needed. Success rate is reported between 55 to 89%. Complications include recurrence, dimpling, notching and hypopigmentation.
CHAPTER 253 • Trichiasis
ETIOLOGY
Eyelashes return as early as 2 weeks after surgery.
Cryosurgery Cryosurgery is most suitable when multiple, contiguous eyelashes are involved. Local anesthetic (1% xylocaine with 1 : 100,000 epinephrine mixed with 0.5% bupivicaine) is injected. A cryoprobe (with nitrous oxide as the coolant) is used. A high-flow, large surfaced probe is preferable to the retinal cryoprobe. The affected part of the lid is frozen for 30 to 60 seconds. After a complete thaw, the procedure is repeated for a total of two freeze-thaw cycles. The tissue temperature at the level of the eyelash follicle can be monitored using a thermocouple (−15º to −30ºC). Success rate is reported as greater than 90% if two freeze-thaw cycles are applied. Complications include recurrence, depigmentation, hyperpigmentation, eyelid thinning or notching, eyelid edema, symblepharon, and keratinization, with activation of cicatricial ocular pemphigoid reported in one series of patients. Patients should be warned that blistering of the eyelid may follow the cryotreatment and given a topical antibiotic ointment to apply if this occurs.
Radiosurgery The Ellman Surgitron delivers energy at 3.8MHz. Local anesthetic (1% xylocaine with 1 : 100,000 epinephrine mixed with 0.5% bupivicaine) is injected. The needle tip of the Surgitron is either inserted into the eyelash follicle (by directing it along the eyelash base) directly or used to split the lid margin along the grey line. The cut mode is used in the former technique and the cut and coagulate mode is used in the latter technique for eyelash extirpation. Success rate is reported between 67% and 83%. Complications include recurrence, lid notching, and granuloma formation.
Hyfrecation Electrolysis of individual eyelashes has been advocated in the past. This procedure should, however, be avoided as it can result in entropion. Moreover, hyfrecation may induce heat and lead to scarring with subsequent trichiasis of adjacent eyelashes. This form of treatment should be limited to no more than 3 eyelashes total per eyelid to avoid this complicaton.
Conventional surgical techniques Full-thickness wedge resection can be carried out where multiple contiguous eyelashes are involved, particularly in the presence of distorted eyelid margin anatomy.
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Eyelid margin rotation procedures, e.g. the Lagleyze or Weis procedures, can be considered for trichiasis associated with cicatricial entropion. Lid-splitting procedures (at the gray line) with or without insertion of a mucus membrane or amniotic membrane graft are alternatives for trichiasis associated with cicatricial entropion. SECTION 21 • Eyelids
COMMENTS For trichiasis treatment to be effective, it is important to recognize and treat any underlying pathology. The extent of the abnormal eyelashes and the underlying cause generally dictate the treatment modality. Several abnormal eyelashes may be treated with laser ablation or cryosurgery. Cryosurgery is more effective for larger eyelashes as compared with fine lanugo hair. Larger patches of eyelashes may require cryosurgery or surgery. Extensive trichiasis, with ongoing cicatricial disease, is best treated with excision and mucous membrane grafting. Timely delivery of treatment provides the best outcome for the patient and decreases the risk of corneal vascularization, scarring, and visual loss.
REFERENCES Bearden W, Anderson R: Trichiasis associated with prostaglandin analog use. Ophthalmic Plast Reconstr Surg 20:320–322, 2004. Berry J: Recurrent trichiasis: treatment with laser photocoagulation. Ophthalmic Surg 10:36–38, 1979. Gossman MD, Brightwell JR, Huntington AC, et al: Experimental comparison of laser and cryosurgical cilia destruction. Ophthalmic Surg 23:179–182, 1992. Johnson RLC, Collin JRO: Treatment of trichiasis with a lid cryoprobe. Br J Ophthalmol 69:267–270, 1985. Rosner M, Bourla N, Rosen N: Eyelid splitting and extirpation of hair follicles using a radiosurgical technique for treatment of trichiasis. Ophthal Lasers Imaging 35:116, 2004.
associated with aging or hormonal changes. The age of onset ranges from 15 to 73 years old, with the peak in the fourth and fi fth decades. One-third of patients have a family history of this condition. Xanthelasma has been known to occur as a result of hyperlipemia, hypercholesteremia, obesity, and cardiovascular changes. Approximately 33% of men and 40% of women with xanthelasma have elevated cholesterol levels. Obesity was found in 26% (in women more than in men), and vascular changes were found in 18% of adults. One study, which involved 8000 healthy men and women, found xanthelasma in 1.1% of women and 0.3% of men with hyperlipidemia. It has also been associated with familial hyperlipoproteinemia type 2 and, rarely, type 3. It may be seen with xanthoma tuberosum or eruptive xanthomatoses. Patients with normal levels of serum lipids have been known to have xanthoma disseminatum. It has also been described in histiocytosis X, most commonly the Hand-Schöller–Christian type. Association with other xanthomas elsewhere is usually less than 2%.
COURSE/PROGNOSIS With excision, the 1-year recurrence rate is 26%. The younger patients had an earlier recurrence. If all four lids are involved, the recurrence rate with excision is approximately 70% to 80%. Once plaques are established, they will remain static or increase in size. Patients with first-time excision should be advised of a 40% to 50% success rate. Higher recurrence rates are associated with systemic hyperlipemia, the involvement of all four eyelids, and more than one recurrence after surgery.
DIAGNOSIS Types ● ● ● ●
254 XANTHELASMA 374.51 (Xanthelasma Palpebrarum)
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Geoffrey Gladstone, MD, FAACS Southfield, Michigan Shoib Myint, DO, FAACS Royal Oak, Michigan
ETIOLOGY/INCIDENCE Xanthelasma palpebrarum, or simply xanthelasma, is a raised, soft, yellow, plaque-like, velvety lesion most commonly occurring in the medial canthal area of the eyelid. Erasmus Wilson originally described the term xanthelasma 100 years ago. It is derived from the Greek xanthos, meaning ‘yellow,’ and elasma, meaning ‘beaten metal plate.’ These lesions will rarely enlarge so as to obstruct vision. Xanthelasma was considered at one time to be a degenerative phenomenon, which involved the subcutaneous and muscular tissue. Histologic studies, however, have shown it to be a pathologic change confined to the skin. Most agree that this condition commonly occurs as an isolated disorder. It has not been
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Xanthelasma with lipemia, acquired or inherited. Hypercholesteremia, frequent. Hyperneutrolipemia, rare. Xanthelasma with normolipemia. Local. Generalized. Xanthoma disseminatum. Histiocytosis X. Reticulohistiocytoma cutis.
Laboratory findings Xanthomas are foam cells with lipid found in the superficial reticular dermis. Occasionally, multinucleated giant cells (toutan cells) and fibrosis are observed. A tumor of epidermal origin is possible.
Differential diagnosis ● ● ● ● ●
Myxedema. Cirrhosis. Diabetes mellitus. Plasma protein abnormalities. Amyloidosis.
TREATMENT ●
Various treatment methods include dietary, medical, dermatologic, surgical, and laser.
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COMMENTS Xanthoma palpebrarum can be a challenging condition to manage. An underlying systemic condition should be sought, although most cases are isolated. Each patient is different with different expectations; therefore, the physician should accommodate the treatment to the needs of the patient. The results can be aesthetically pleasing in the right setting if done properly. The tremendous advances in medical technology should allow more efficient means of treating disorders such as this.
REFERENCES Gladstone GJ: CO2 laser excision of xanthelasma promotes hemostasis. Clin Laser Monthly 4:35–45, 1986. Gladstone GJ, Beckman H, Elson LM: CO2 laser excision of xanthelasmic lesions. Arch Ophthalmol 103:440–442, 1985. Mendelson BC, Masson JK: Xanthelasma: follow-up on results after surgical excision. Plast Reconstruct Surg 58:535–538, 1976. Parkes ML, Waller TS: Xanthelasma palpebrarum. Laryngoscope 94: 1238– 1240, 1984.
CHAPTER 254 • Xanthelasma
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Patients with xanthelasma who are best treated with diet include those whose disease is associated with obesity and increased triglyceride levels. Dermatologic treatment includes 75% solution trichloroacetic acid, which coagulates tissue. An advantage is that it is nonsurgical and simple. Disadvantages include ectropion in lower lids, scar formation, and a recurrence rate of 50%. Surgical treatment involves the use of a blepharoplasty incision. Serial staged excisions should be included unless the xanthelasma is soft or immature, in which case direct elliptical excision in toto is recommended. Problems include fold asymmetry, skin shortage, webbing, scar formation ectropion, and recurrence. Ablation with a CO2 laser has been used for conditions such as basal cell carcinoma, malignant melanoma, warts, acne, condylomata, hemangioma, tattoo keratoacanthoma, seborrheic keratosis, and papilloma. It has been successful in treating xanthelasma. The advantages are superior hemostasis, no suturing, no reconstructive procedure, and a high degree of patient satisfaction with minimal to no pain. A problem is that patients can get mild hypopigmentation. Scarring can be prevented because under good surgeon control, the laser will not penetrate beyond the reticular layer. After surgery, the patients can be given Aquaphor cream for 1 week.
Pedace JF, Winkelman RK: Xanthelasma palpebrarum. JAMA 193; 121– 122, 1965.
465
S ECT I O N
22
Globe
COURSE/PROGNOSIS
255 ANOPHTHALMOS 743.00
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Nick Mamalis, MD Salt Lake City, Utah Brian A. Hunter, MD Salt Lake City, Utah
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ETIOLOGY/INCIDENCE ●
True or primary anophthalmos is very rare and occurs when the neuroectoderm of the primary optic vesicle fails to develop from the anterior neural plate of the neural tube during embryologic development. The diagnosis of true anophthalmos can be made only with complete absence of ocular tissue within the orbit. Secondary anophthalmos refers to the failure of the optic vesicle to form in the presence of anatomic malformations within the ventral forebrain. More commonly, children who are born with a unilaterally small orbit and no visible eye have a very small or microphthalmic globe present within the orbital soft tissue. Microphthalmos can occur due to a problem in the development of the globe at various stages of growth of the optic vesicle. The presence of an eye is necessary in utero to stimulate growth of the orbit, lids, and ocular fornices. A child born with anophthalmia commonly has a small orbit with narrowed palpebral fissure and a shrunken fornix. ● Prevalence range 0.3 to 1.9 per 10,000 live births. ● Idiopathic/sporadic or inherited (recessive, dominant, or sex linked). ● Trisomy 9, 13 through 15. ● Gene deletions chromosome 3, 7, 14. Deletions involving SOX2 and SIX6. ● Gene rearrangements (balanced de novo translocations) 46 XXt(1;2)(p31.2;q23); 46 XY (t8;12)(q22;q21); 46,XX, t(3;11). ● Prenatal exposures to TORCH infections (toxoplasmosis, rubella, cytomegalovirus, herpes) as well as alcohol, thalidomide, retinoic acid, hydantoin, and lysergic acid diethylamide (LSD). ● Syndromes associated with abnormalities of the CNS, genitourinary system, and in association with limb anomalies (i.e. SOX2, anopthalmia-oesophageal-genital syndrome (AEG), oligodactyly-ophthalmo-acromelic syndrome (OAS); micropthalmia-anaopthalmia-coloboma (MAC); Waardenburg anophthalmia syndrome (WAS), Lenz syndrome XLR). ● Associated with multiple syndromes with hemifacial microsomia and other craniofacial malformations (i.e. Goldenhar’s syndrome, Hallermann–Streiff syndrome).
True anophthalmos is a pediatric ocular emergency. The growth and development of the bony orbit are correlated with the growth of the globe. The lack of an eye or a microphthalmic eye prevents the orbit from developing properly. A small bony orbital cavity results not only in a cosmetic deformity but also does not allow for proper fitting of a prosthesis. Anophthalmos may be unilateral or bilateral.
DIAGNOSIS Clinical signs and symptoms Orbital ● ● ● ● ●
Reduced size of the bony orbital cavity. Small orbital rim. Small or maldeveloped optic foramen. Lacrimal gland and ducts may be absent. Extraocular muscles usually absent.
Eyelids ●
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Microblepharism: a foreshortening of the eyelids in all directions. Contraction of the orbicularis oculi muscle. Absent or decreased levator function and lid folds. Shallowing of the inferior conjunctival fornix.
Globe ● ●
Completely absent in primary anophthalmos. Very small, malformed globe in microphthalmos.
Laboratory findings ●
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On computed tomography scanning and magnetic resonance imaging, patients with bilateral anophthalmos often have an associated absence of the optic chiasm, diminished size of the posterior optic pathways, and agenesis or dysgenesis of the corpus callosum. Ultrasound imaging using B-scan showing complete absence of ocular tissue in anophthalmos. A-scan shows decreased axial length in microphthalmos. Transvaginal ultrasound can detect eye malformations after 22 weeks gestation; however, the sensitivity for use in detecting anopthalmia is not known. Patients with unilateral anophthalmos often have severe craniofacial anomalies.
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Differential diagnosis ● ●
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SECTION 22 • Globe
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Primary anophthalmos versus secondary anophthalmos. Microphthalmos: a globe with a total axial length (TAL) at least two standard deviations below the mean for age (mean TAL neonate 17 mm, adult 23.8 mm). Cryptophthalmos: abnormal fusion of entire eyelid margin with maldevelopement of cornea and microphthalmia. Condition is usually bilateral and associated with multiple malformations. Cystic eye: the failure of invagination of the optic vesicle in utero. Imaging studies reveal the presence of intraorbital cyst and intact extraocular muscles, without an optic nerve. Neuroimaging or histopathology may be necessary to document the true absence of ocular tissue.
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Last, the eyelids need to be lengthened; this is usually accomplished by a combination of skin, mucosal, or cartilage grafts.
COMPLICATIONS ●
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Significant cosmetic deformities are possible if the anophthalmic orbit is not treated early. Even after treatment, results often are cosmetically disappointing. However, cosmetic scleral shells may be useful in microphthalmos. Fitted prostheses are immobile. Eyelids also are often short and immobile with significant malformations.
TREATMENT
COMMENTS
Ocular/Orbital
Anophthalmos may cause serious psychologic problems not only due to the lack of an eye but also secondary to disfigurement of the orbit, lids, and socket. Early treatment with conformers, as well as inflatable expanders and surgery when necessary, will help decrease severe asymmetry and other cosmetic deformities.
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The current preferred method for orbital expansion is to use serial implants in the growing orbit. Initially a solid conformer can be placed to stimulate bony orbital growth and enlarge the orbital cavity to attempt to attain normal proportions. Progressively increasing the size of the conformers will help progressively increase the size of the orbit to properly fit a hydroxyapatite prosthesis. The increase in the size of a conformer often is limited by the shortening of the eyelids and the palpebral fissure that no longer permits passage of a larger conformer. The horizontal length of the palpebral fissure may be increased surgically at this point by performing a lateral canthotomy from the lateral canthus to the lateral orbital wall. A dermis-fat graft may be placed and has the potential for post-surgical growth. If conformers are not tolerated, an inflatable expander (silicone balloon, or hydrophilic polymers) may be placed. The expander works best if placed relatively early in life (first year). The inflatable silicone expander is placed deep into the orbit and accessed by a tube that is usually placed through the lateral orbital wall. The expander is gradually fi lled (usually with saline) on a weekly or biweekly basis. The inflatable expander may allow more rapid and extensive orbital tissue expansion than the solid orbital conformers.
SUPPORT GROUPS International Children’s Anophthalmia Network (ICAN). Albert Eisntein Medical Center c/o Genetics. 5501 Old York Road Philadelphia, PA 19141. Phone 800-580-4226. Email:
[email protected] URL: www.ioi.com/ican/ National Federation of the Blind (NFB). 1800 Johnson Street Baltimore, MD 21230. Phone 410-659-9314, Email
[email protected]. URL: www.nfb.org
REFERENCES Albernaz VS, Castillo M, Hudgins PA, et al: Imaging fi ndings in patients with clinical anophthalmos. Am J Neuroradiol 18:555–561, 1997. Cepela MA, Nunery WR, Martin RT, et al: Stimulation of orbital growth by the use of expandable implants in the anophthalmic cat orbit. Ophthalm Plast Reconstr Surg 8:157–169, 1992. Krastinova D, Kelly MB, Mihaylova M: Surgical management of the anophthalmic orbit, part 1: congenital. Plast Reconstr Surg 108(4):817–826, 2001. Marchac D, Cophignon J, Archard E, et al: Orbital expansion for anophthalmia and micro-orbitism. Plast Reconstr Surg 59:486–491, 1977. Tucker SM, Sapp N, Collin R, et al: Orbital expansion of the congenitally anophthalmic socket. Br J Ophthalmol 79:667–671, 1995.
Surgical ●
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468
Surgical intervention should be considered after 6 months of age to adequately assess postnatal growth of the orbit. If conformers and expanders are not successful, the bony orbit may need to be expanded surgically. Osteotomy is the current preferred method for orbital expansion in cases of late referral or insufficient orbital volume in the older child. It is possible to enlarge the orbit in three directions-laterally, inferiorly and superiorly. This surgical expansion is accomplished by dividing the bony orbital rim in three parts in a stepwise fashion. A bicoronal approach through the scalp is often necessary when the orbital roof has to be elevated.
256 BACTERIAL ENDOPHTHALMITIS 360.0 Mohan N. Iyer, MD Houston, Texas Eric R. Holz, MD Houston, Texas Endophthalmitis is defined as intraocular inflammation, and clinically, the term has come to mean intraocular infection.
ETIOLOGY/INCIDENCE Bacterial endophthalmitis is classified based on the route of infection as either exogenous or endogenous. Exogenous endophthalmitis can occur following intraocular surgery, penetrating injury, or less commonly from microbial keratitis, scleritis, or an infected scleral buckle. A recent development is the occurrence of exogenous endophthalmitis following intravitreal injections of steroids or other drugs. The incidence of postoperative endophthalmitis has been reported to be: ● 0.07% to 0.12% after routine cataract surgery; ● 0.36% after secondary intraocular lens placement; ● 0.17% after penetrating keratoplasty; ● 0.06% to 1.8% after glaucoma fi ltering surgery. Incidence of bleb-related endophthalmitis is greater with the use of antifibrotics because of thinner blebs, and with inferiorly located blebs presumably because of greater exposure of the bleb to bacteria-laden tear fi lm in this location. The causative organisms in postoperative endophthalmitis are usually part of the normal ocular bacterial flora. The incidence of endophthalmitis after penetrating trauma is approximately 7%, greater in the presence of an intraocular foreign body (9% to 11%) and can be as high as 30% in the setting of rural penetrating trauma. The incidence of intravitreal injection-related endophthalmitis after triamcinolone injections is between 0.0% and 0.87%, and after ganciclovir injections is up to 0.6%. Endogenous endophthalmitis, also called metastatic endophthalmitis, occurs by hematogenous spread of the organism in patients with sepsis, immunosuppression, or intravenous drug use. Endogenous endophthalmitis is less common and accounts for 2–6% of all cases of bacterial endophthalmitis.
after treatment, 53% of eyes had a visual acuity of 20/40 or better, 74% had visual acuity of 20/100 or better, 15% had visual acuity of 5/200 or worse, and 5% had no light perception (LP). The most important risk factor for poor visual outcome in the EVS was an initial visual acuity of light perception (LP) only, with only 23% of patients with LP achieving 20/40 or better vision compared with 64% of patients presenting with better than LP vision. Other factors associated with poor outcome included: ● Small pupil size after maximal dilation; ● Absence of a red reflex; ● Presence of rubeosis irides; ● Findings of an afferent papillary defect; ● Corneal infi ltrate or ring ulcer; ● Abnormal intraocular pressure; ● Poor media clarity with inability to distinguish any retinal vessels; ● Type of organism grown in culture. The leading cause of final vision less than 20/40 was an abnormality of the macula. The prognosis for retaining good vision is generally better in cases that are culture-negative or culture-positive for coagulasenegative staphylococci, and in cases of chronic or delayed-onset endophthalmitis, i.e. those presenting 6 weeks after cataract surgery. However, the prognosis for patients with bleb-associated, post-traumatic, and endogenous endophthalmitis is generally worse than for patients with acute postoperative endophthalmitis. In bleb-associated endophthalmitis, infection with more virulent organisms is more frequent, and pre-existing glaucoma may limit fi nal vision. Post-traumatic endophthalmitis is associated with a poor visual prognosis with approximately 30% of patients achieving visual acuity better than 20/400. Cases associated with Bacillus cereus or with rural trauma portend an especially poor prognosis. Traumainduced changes may also directly affect the final outcome. Poor prognosis in endogenous endophthalmitis has been attributed to delay in diagnosis, diffuse infection (panophthalmitis), and infection with virulent and in particular,gram-negative organisms. Pooled analysis of cases reported between 1976 and 1985 showed that only 41% of patients had counting fi ngers (CF) or better vision, 26% had no light perception, and 29% required evisceration, a trend that has remained unchanged in analyses since 1986. In addition, a 5% mortality rate due to extraocular spread of infection has been reported.
CHAPTER 256 • Bacterial Endophthalmitis
Acute bacterial endophthalmitis is a serious and vision-threatening intraocular infection that requires emergent treatment. The Endophthalmitis Vitrectomy Study (EVS) was a landmark study that evaluated the roles of immediate vitrectomy and systemic antibiotics in the treatment of acute post-cataract extraction endophthalmitis. Injection of intravitreal antibiotics is the mainstay of treatment for exogenous endophthalmitis. Systemic treatment and occasionally vitrectomy and intravitreal antibiotics are required for endogenous endophthalmitis. Prophylaxis of postoperative endophthalmitis remains a controversial issue, and current recommendations include lid scrubs, use of povidone-iodine in the conjunctival fornices, and adequate aseptic technique.
DIAGNOSIS COURSE/PROGNOSIS The course and prognosis depend on: ● The type of endophthalmitis; ● Duration of time to presentation and treatment; ● Virulence of the organism.
The diagnosis of endophthalmitis is usually made on clinical grounds. Vitreous inflammation greater than expected is the key diagnostic finding that should lead to the suspicion of endophthalmitis.
Clinical signs and symptoms ●
The prognosis for achieving good final visual acuity has increased substantially with the introduction of intravitreal antibiotics. Prior to the introduction of intravitreal antibiotics, intravenous and topical antibiotics were administered and, in a survey of cases from the years 1944–1966, 73% had final vision of hand motions or worse. In the EVS, which evaluated cases of acute postoperative endophthalmitis, at 9 to 12 months
Acute postoperative endophthalmitis.
Presenting symptoms in the EVS ● ● ● ● ●
Decreased vision. Pain. Red eye. Swollen lid. Hypopyon.
469
Examination findings revealed ● ● ● ●
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SECTION 22 • Globe
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Visual acuity less than 5/200 (86%). Light perception (26%). Hypopyon (86%). No retinal vessel visible by indirect ophthalmoscopy (79%). Afferent pupillary defect (12%). Corneal wound abnormality (5%). Corneal infi ltrate or ring ulcer (5%).
While pain is generally considered a key presenting symptom, it should be noted that nearly a quarter of the patients in the EVS presented without pain. In addition, hypopyon was absent in 14% of the patients. ● Chronic postoperative endophthalmitis usually presents as an anterior uveitis weeks to months after the intraocular procedure. It may respond transiently to corticosteroid treatment. The presence of vitreous inflammation and posterior capsular opacities or plaques are highly suggestive of chronic endophthalmitis. ● Bleb-related endophthalmitis. Patients can present with bleb-related endophthalmitis months to years after glaucoma filtering surgery with symptoms of: ● Ocular pain; ● Redness; ● Decreased vision; ● Clinical signs. ● Bleb leak. ● Conjunctival injection and chemosis. ● Inflamed bleb. ● Hypopyon. ● Anterior and vitreal inflammation. It is important to distinguish blebitis from bleb-related endophthalmitis because treatment methods are different for the two entities. When the inflammation is localized to the bleb with the absence of a hypopyon or vitreal inflammation, it is termed ‘blebitis.’ ● Post-traumatic endophthalmitis. Patients with penetrating injuries and with intraocular foreign bodies may have intraocular inflammation and signs similar to acute postoperative endophthalmitis on presentation or after primary repair. Endophthalmitis is suspected mainly on clinical grounds in these cases. ● Intravitreal injection-related endophthalmitis. Patients may present with anterior and vitreal inflammation within one week of an intravitreal injection. Pseudo-endophthalmitis, presumably as a result of reaction to the concomitant vehicle or dispersion of steroid particles into the anterior chamber simulating a hypopyon, should be cautiously distinguished from endophthalmitis by the lack of significant decrease in vision, significant pain, and severe vitreal inflammation.
Laboratory findings Microbiologic studies of vitreous and anterior chamber specimens obtained are recommended, mainly to determine the infectious organism and to direct treatment in the event of need for reinjection of intravitreal antibiotics. Bacterial endophthalmitis is a clinical diagnosis, and empiric treatment with broadspectrum antibiotics is initiated emergently well before microbiology results become available. In addition, the rate of culture-negative vitreous samples, whether or not a vitrectomy is performed, is approximately 30%. Gram stain, aerobic and anaerobic cultures are routinely obtained. Based on fi ndings of
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the EVS, gram stain results should not be used solely in determining the choice of antibiotics in the treatment of endophthalmitis, and vitrectomy does not result in a greater rate of culture-positive specimens. Cultures of conjunctiva or cornea may theoretically have a role in post-traumatic endophthalmitis cases, but are not expected to add information when aqueous and vitreal samples are obtained. Patients with endogenous endophthalmitis should have a work-up for infectious diseases to identify an extraocular focus of infection. This should include cultures of blood and urine as well as evaluation of indwelling intravenous lines, and other studies determined by history and physical findings. In reported series of endogenous endophthalmitis, blood cultures were more likely to be positive than vitreous cultures. However, in the absence of positive cultures from extraocular studies, aqueous and vitreal cultures are recommended to aid in diagnosis. The microbial spectrum in the different types of endophthalmitis is as follows: ● Acute postoperative (EVS): ● Gram-positive coagulase-negative micrococci (mostly Staphylococcus epidermidis) (70%); ● Other gram-positive (24.2%); ● Staphylococcus aureus (9.9%); ● Streptococcus (9%); ● Enterococcus (2.2%); ● Miscellaneous (3.1%). ● Chronic postoperative endophthalmitis: ● Gram-positive coagulase-negative micrococci, mostly Staphylococcus epidermidis; ● Other gram-positive organisms, Staphylococcus aureus, Streptococcus spp.; ● Propionibacterium acnes; ● Corynebacterium spp.; ● Actinomyces spp.; ● Nocardia; ● Fungi. ● Bleb-related endophthalmitis: ● Staphylococcus spp., Streptococcus spp.; ● Haemophilus influenzae; ● Enterococcus spp.; ● Fastidious gram-negative rods; ● Pseudomona aeruginosa. ● Post-traumatic endophthalmitis: ● Coagulase-negative Staphylococci spp.; ● Staphylococcus aureus, Streptococcus spp.; ● Bacillus cereus; ● Propionibacterium acnes; ● Fungi; ● Others. ● Endogenous endophthalmitis: gram-positive organisms, mainly: ● Streptococcus pneumoniae; ● Staphylococcus aureus; ● Group A and group B Streptococci; ● Bacillus ceres. Gram-negative organisms: ● Klebsiella spp.; ● E. coli; ● Pseudomonas spp.; ● N. meningitides; ● Serratia marcescens; ● Listeria monocytogenes; ● N. asteroids.
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Intravitreal injection-related endophthalmitis: ● Gram-positive coagulase-negative Staphylococcus spp.; ● Streptococcus spp.; ● Mycobacterium chelonae.
Differential diagnosis ●
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PROPHYLAXIS Preoperative and intraoperative preventive measures have been proposed and employed in an attempt to decrease the incidence of endophthalmitis. Since the source of organisms in postopera-
CHAPTER 256 • Bacterial Endophthalmitis
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Acute postoperative endophthalmitis: ● Phacoanaphylactic endophthalmitis, a granulomatous inflammation with keratic precipitates as a result of immune reaction to lens proteins; ● Aseptic endophthalmitis, a severe sterile uveitis that may present with a hypopyon and mild vitreous inflammation. Pain and progressive vision loss are not characteristic. This condition usually resolves with topical steroid treatment. Chronic postoperative endophthalmitis: ● Pre-existing uveitis; ● Sterile inflammation attributed to reaction to contaminants on the intraocular lens, such as polishing compounds; ● Rebound inflammation related to abrupt discontinuation of steroid drops; ● Iris or vitreous incarceration in the wound, resulting in a low-grade inflammation; ● Uveitis-glaucoma-hyphema syndrome; ● Fungal endophthalmitis. Bleb-related endophthalmitis: ● Blebitis, presenting classically as ‘white on red,’ with the bleb appearing white against inflamed conjunctiva; ● Anterior uveitis; ● Uveitis-glaucoma-hyphema syndrome. Post-traumatic endophthalmitis: ● Phacoanaphylactic endophthalmitis; ● Sterile inflammatory reaction to uveal incarceration or intraocular foreign body; ● Sympathetic ophthalmia with bilateral anterior uveitis with keratic precipitates, vitreous inflammation, presence of depigmented nodules (Dalen–Fuchs’ nodules) at the level of the retinal pigment epithelium, and choroidal thickening on B-scan ultrasonography. Endogenous endophthalmitis: ● Non-infectious anterior uveitis; ● Fungal endophthalmitis; ● Intraocular lymphoma; ● Retinoblastoma in children. Intravitreal injection-related endophthalmitis: ● ‘Pseudo-endophthalmitis,’ or non-infectious endophthalmitis, seen after intravitreal triamcinolone injection, presumably as a result of toxic or inflammatory reaction to the drug, the vehicle in which the drug is suspended, or a contaminant in the preparation. This condition is seen in the immediate post-injection period, typically within two days. The presenting signs of hypopyon, anterior and vitreal inflammation, and decreased vision make it difficult to distinguish this entity from infectious endophthalmitis. With observation, the inflammation resolves within one week.
tive endophthalmitis is most commonly the patient’s ocular flora, the goal is to reduce the bacterial load and treat any external eye disease prior to operating. An evidence-based assessment of bacterial endophthalmitis prophylaxis found that several measures have been considered, including preoperative povidone-iodine, lash trimming, saline irrigation, topical antibiotics, antibiotic-containing irrigating solutions, and postoperative subconjunctival antibiotics. The use of preoperative povidone-iodine received the strongest recommendation. Preoperative measures include: ● Treatment of blepharitis, conjunctivitis, dacryocystitis, and periocular infections; ● Use of adequate aseptic techniques with sterile preparation of eyelashes, eyelids, and periocular skin, and draping of eyelashes and lid margins; ● 5% povidone-iodine solution instilled in the conjunctival fornices; ● Topical preoperative antibiotics, which are widely used and theoretically lead to decreased bacterial load on the ocular surface. Some antibiotics, such as fluoroquinolones, may have adequate aqueous penetration. However, despite these theoretical considerations and routine use, clinical studies are yet to demonstrate their efficacy in preventing endophthalmitis. Intraoperative measures include: ● Use of meticulous aseptic technique; ● Avoidance of placement of intraocular lens on the ocular surface prior to introduction into the eye; ● Use of heparin surface-modified intraocular lenses, based on demonstration of decreased bacterial adherence in vitro. The use of low molecular weight heparin in the irrigating fluid failed to demonstrate a statistically significant reduction in the rate of culture-positive anterior chamber aspirates; ● Placement of a 10-0 nylon suture in the incisional wound if there is capsular rupture, vitreous loss, or any concern about wound integrity. Recent evidence suggests an increased risk of postoperative endophthalmitis with sutureless corneal incisions; thus, a low threshold for placement of suture to avoid microleaks from the wound is recommended; ● Subconjunctival injection of antibiotics, which remains controversial. This method has been shown to reduce ocular flora more than topical antibiotics. However, in a retrospective 10-year review of the incidence of postoperative endophthalmitis, 23 out of 54 (42%) patients with culture-positive endophthalmitis had received prophylactic subconjunctival antibiotics at the end of their surgeries, and of these, 14 (61%) were sensitive to the antibiotics used. Subconjunctival gentamicin, in particular, should be avoided given the risk of irreversible macular infarction; ● Postoperative topical antibiotics, which are in routine use despite the lack of data proving their benefit in the prevention of endophthalmitis; ● Use of antibiotics in the irrigating fluid, not recommended by the authors. The Center for Disease Control and Prevention recommends against the routine use of vancomycin in the irrigating fluid given the risk of emerging vancomycin resistance. The use of aminoglycosides in the irrigating fluid should be avoided given the risk of macular toxicity from incorrect dilution of the antibiotic. Cases of endophthalmitis have been reported despite the use of this measure.
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Other prophylactic measures recommended include avoidance of an inferior bleb in glaucoma fi ltering surgery, use of aseptic techniques with povidone-iodine and isolation of lashes with a lid speculum for in-office intravitreal drug injections. In trauma cases, identification and removal of intraocular foreign bodies, prophylactic intravitreal injection, and systemic prophylaxis in high risk cases, such as rural injuries or contaminated wounds, are recommended.
Surgical Obtaining specimens for microbiology ●
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SECTION 22 • Globe
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TREATMENT The EVS laid the foundation for current practice in the treatment of acute post-cataract extraction endophthalmitis. The findings of the EVS cannot be strictly extrapolated to blebrelated endophthalmitis, post-traumatic endophthalmitis, or endogenous endophthalmitis. Variations in presentation and organisms in these other entities predicate the methods of treatment. The antibiotics for intravitreal injections have essentially remained unchanged for over a decade. Fourthgeneration fluoroquinolones, moxifloxacin and gatifloxacin, are recently developed broad-spectrum antibiotics with effective gram-positive and gram-negative coverage. Oral gatifloxacin has been shown to achieve adequate intravitreal concentrations in humans. Studies conducted in animals have documented that intravitreal moxifloxacin appears safe in doses up to 150 micrograms/ml, and may have a role in the treatment of endophthalmitis following further study (unpublished data).
Intravitreal injections ●
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Separate injections of vancomycin (1 mg in 0.1 cc) plus ceftazidime (2.25 mg in 0.1 cc). Amikacin (400 mcg in 0.1 cc) may be substituted for ceftazidime, if the patient is allergic to beta-lactam antibiotics. Dexamethasone 400 mcg/0.1 cc — not routinely used because of conflicting reports of its efficacy.
Subconjunctival antibiotics ●
Acute postoperative endophthalmitis
Use is controversial and generally not recommended given poor penetration into the vitreous cavity. May consider in cases of wound abscess, or other anterior segment infections. Vancomycin 25 mg and ceftazidime 100 mg (used in the EVS).
The EVS showed that systemic antibiotics did not confer a benefit in the treatment of acute postoperative endophthalmitis. Furthermore, the study showed a benefit from immediate vitrectomy only in patients presenting with visual acuity of light perception (LP). For patients who presented with light perception vision, immediate vitrectomy with intravitreal antibiotics results in a three-fold increase in the rate of achieving a visual acuity of 20/40 or better, a two-fold increase in the rate of achieving a visual acuity of 20/100 or better, and a decrease by half in the rate of severe visual loss to less than 5/200. For patients presenting with hand motions or better vision at 2feet, immediate vitrectomy did not confer a benefit over vitreous tap.
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Systemic
Chronic postoperative endophthalmitis
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Systemic antibiotics are not recommended based on EVS findings, but may be considered in severe cases, especially with orbital involvement. Prednisone 1mg/kg/day PO for 5 to 10 days with rapid taper may be considered if there are no contraindications.
Local Topical antibiotics ●
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Anterior chamber tap: 0.1 to 0.2 cc of aqueous fluid aspirated with a 27–30-gauge needle attached to a tuberculin syringe and inserted through the limbus. Vitreous needle tap biopsy: 0.1 to 0.3 cc of vitreous fluid aspirated with a 22–27-gauge needle inserted via the pars plana. If the tap is dry, the patient will need a mechanized vitreous biopsy. Pars plana vitrectomy and mechanized vitreous biopsy: A 20-gauge pars plana sclerotomy is made followed by introduction of a vitreous cutter/aspirator (or a disposable 23gauge vitrector) attached to a 1–3 cc syringe, and 0.5 cc of vitreous fluid is manually aspirated while the vitrector is cutting. Pars plana vitrectomy is then performed and the vitreous cassette is also submitted for microbiological studies.
Fluoroquinolones (e.g. ciprofloxacin, ofloxacin, or the newer fluoroquinolones, gatifloxacin or moxifloxacin) q.i.d. to q1-2 hour dosing. Fortified drops, especially in cases with wound abscesses (e.g. 50 mg/mL vancomycin and 50 mg/mL ceftazidime) qid to q1-2 hour dosing. Topical steroids (e.g. 1% prednisolone acetate) qid to q1-2 hour dosing. Topical cycloplegics (e.g. cyclopentolate 1%, 0.25% scopolamine hydrobromide, or 1% atropine sulfate) b.i.d.
Additional procedures ●
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If no improvement or stabilization is seen by 36 to 60 hours after intravitreal antibiotic injections, repeat antibiotic injections guided by culture results are recommended. In this timeframe in the EVS, nearly 9% had an additional procedure performed. If not initially performed, a vitrectomy should be considered. Additional late procedures include vitrectomy for media clearance, macular pucker or retinal detachment, posterior capsulotomy, scleral buckling, and glaucoma surgery.
This condition presents as recurrent or persistent postoperative intraocular inflammation that may be partially steroid responsive. Commonly, posterior capsular opacities or plaques may be seen. A vitrectomy is almost always indicated in this situation, and the timing of the surgery may be determined based on the severity of the inflammation.
Systemic Systemic antibiotics and steroids not usually indicated.
Local Topical antibiotics, steroids and cycloplegics as described above for acute postoperative endophthalmitis.
Surgical ●
Anterior chamber and vitreous tap with intravitreal antibiotics may be adequate if no sequestration of organisms in the capsular bag is noted.
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Bleb-related endophthalmitis In cases of blebitis, where the infection is limited to the bleb without intraocular involvement, topical and systemic therapy is typically curative. In early-onset bleb-associated endophthalmitis, the organisms are similar to acute post-cataract endophthalmitis and the visual prognosis is likewise favorable. In delayed-onset endophthalmitis, which is the more common situation, the organisms are more virulent, including Streptococcus spp. and Haemophilus influenzae, with resultant poor prognosis. Aggressive treatment of bleb-associated endophthalmitis is recommended, with vitrectomy irrespective of the presenting visual acuity, intravitreal antibiotics, and systemic antibiotics, despite their lack of clinical efficacy in the EVS.
Systemic ●
Vancomycin 1 g every 12 hours IV, plus either 1 g of ceftazidime IV every 12 hours, or ciprofloxacin 750 mg PO every 12 hours, or gatifloxacin 400 mg qd.
be determined by available blood culture results. Endogenous fungal endophthalmitis can usually be clinically distinguished from bacterial endophthalmitis, but in cases in which no underlying systemic infection is known and the vitreous involvement is severe, vitrectomy with intravitreal injection of antibiotics with or without amphotericin (5 micrograms in 0.1 mL) may be indicated.
Intravitreal injection-related endophthalmitis There have been few case reports of this entity. In one study, 3 of the 8 culture-positive cases ended up with no light perception vision, and two of those eyes had undergone vitrectomy with intravitreal antibiotics. The choice of treatment methods for this condition must be based on the judgment of the clinician, with early vitrectomy, intravitreal antibiotics, and systemic antibiotics offered in clinically severe cases.
COMPLICATIONS Complications of endophthalmitis include corneal edema or decompensation, persistent intraocular inflammation, cataract, glaucoma, hypotony, residual vitreous opacity, retinal toxicity (due to enzyme and toxin release and rarely due to antibiotic treatment), cystoid macular edema, and epiretinal membrane. Retinal detachment occurs in 5 to 21% of cases. In the EVS, a final visual acuity of no light perception was noted in 5% of cases, and phthisis occurred in 2% of the patients. Contiguous spread and development of panophthalmitis is a possible complication that may require enucleation.
CHAPTER 256 • Bacterial Endophthalmitis
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Cases with sequestration of infected material in the capsular bag require a partial capsulectomy and removal of any residual cortex, combined with vitrectomy and injection of vancomycin (1 mg in 0.1 cc) and ceftazidime (2.25 mg in 0.1 cc) into the capsular bag/vitreous cavity. If the infection persists despite this measure, a complete capsulectomy with intraocular lens explantation and reinjection of intravitreal antibiotics as guided by culture results is recommended. Antibiotic irrigation of the capsular bag, without capsulectomy or intraocular lens removal, has been reportedly successful in some cases.
Local ●
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Topical vancomycin (50 mg/mL) and ceftazidime (50 mg/mL). Topical steroids and cycloplegics as described.
Surgical ●
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Immediate vitrectomy, anterior chamber and vitreous biopsies, and intravitreal vancomycin (1 mg in 0.1 cc) and ceftazidime (2.25 mg in 0.1 cc). Subconjunctival vancomycin 25 mg and ceftazidime 100 mg.
Post-traumatic endophthalmitis Early vitrectomy with intravitreal, subconjunctival, topical, and systemic antibiotics should be used in the doses listed above. Immediate vitrectomy in suspected cases is recommended over vitreous tap and inject even if the presenting vision is better than LP. Retained intraocular foreign bodies should be suspected and ruled out with ultrasound and computed tomography scans. Prompt removal of any retained intraocular foreign body is indicated.
Endogenous endophthalmitis A concerted effort to identify the source of the infection must be made, if not already known. In a review of a large series of reported cases, only about half were treated with intravitreal antibiotics. Systemic intravenous antibiotics are fi rst initiated, as this condition is caused by hematogenous spread of organisms. In patients who develop or fail to have improvement of endogenous bacterial endophthalmitis while on appropriate systemic antibiotics despite therapeutic blood levels for 24 to 36 hours, vitreous tap/inject or vitrectomy with intravitreal antibiotic injection is indicated. The choice of antibiotics may
COMMENTS Bacterial endophthalmitis is a vision-threatening intraocular infection requiring prompt diagnosis and treatment. Intravitreal injection of antibiotics is the mainstay in the treatment of endophthalmitis. The EVS showed that in cases of acute postcataract extraction endophthalmitis, systemic antibiotics conferred no additional benefit, and that immediate vitrectomy was only beneficial for patients with LP vision on presentation. However, these recommendations should not be strictly extrapolated to other types of endophthalmitis. The decisions for vitrectomy and the use of systemic antibiotics should be based on the type of endophthalmitis and severity of vitreous involvement.
REFERENCES Benz MS, Scott IU, Flynn HW, Jr, et al: Endophthalmitis isolates and antibiotic sensitivities: a 6-year review of culture-proven cases. Am J Ophthalmol 137:38–42, 2004. Ciulla TA, Starr MB, Masket S: Bacterial endophthalmitis prophylaxis for cataract surgery: an evidence-based update. Ophthalmology 109:13–24, 2002. Endophthalmitis Vitrectomy Study Group: Results of the Endophthalmitis Vitrectomy Study: a randomized trial of immediate vitrectomy and of intravenous antibiotics for the treatment of postoperative bacterial endophthalmitis. Arch Ophthalmol 113:1479–1496, 1995. Han DP, Wisniewski SR, Wilson LA, et al: Spectrum and susceptibilities of microbiologic isolates in the Endophthalmitis Vitrectomy Study. Am J Ophthalmol 122:1–17, 1996. Hariprasad SM, Mieler WF, Holz ER: Vitreous and aqueous penetration of orally administered gatifloxacin in humans. Arch Ophthalmol 121:345–350, 2003.
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Jackson TL, Eykyn SJ, Graham EM, et al: Endogenous bacterial endophthalmitis: a 17-year prospective series and review of 267 reported cases. Surv Ophthalmol 48:403–423, 2003. Kresloff MS, Castellarin AA, Zarbin MA: Endophthalmitis. Surv Ophthalmol 43:193–224, 1998. Mac I, Soltau JB: Glaucoma-fi ltering bleb infections. Curr Opin Ophthalmol 14:91–94, 2003.
SECTION 22 • Globe
Moshfeghi DM, Kaiser PK, Scott IU, et al: Acute endophthalmitis following intravitreal triamcinolone acetonide injection. Am J Ophthalmol 136:791–796, 2003. Nelson ML, Tennant MTS, Sivalingam A, et al: Infectious and presumed noninfectious endophthalmitis after intravitreal triamcinolone acetonide injection. Retina 23:686–691, 2003. Olson RJ: Reducing the risk of postoperative endophthalmitis. Surv Ophthalmol 49:S55–S61, 2004. Reynolds DS, Flynn HW Jr: Endophthalmitis after penetrating ocular trauma. Current Opin Ophthalmol 8:32–38, 1997. Speaker MG, Menikoff JA: Prophylaxis of endophthalmitis with topical povidone-iodine. Ophthalmology 98:1769–1775, 1991.
257 FUNGAL ENDOPHTHALMITIS 360.1 Rohit R. Lakhanpal, MD Houston, Texas Thomas A. Albini, MD Houston, Texas Eric R. Holz, MD Houston, Texas
ETIOLOGY/INCIDENCE Fungal endophthalmitis is classified according to its source. It is classified as exogenous when associated with an external source such as penetrating trauma, previous intraocular surgery (cataract extraction, penetrating keratoplasty, fi ltering bleb procedures or vitrectomy), or direct spread from corneal or scleral fungal infection. Exogenous fungal infections occur in immunocompetent individuals and are frequently seen in agricultural workers or in patients with organic foreign bodies, such as soil, leaves, or twigs in their eyes. Endogenous fungal endophthalmitis results from the hematogenous spread of fungal infection to the eye from elsewhere in the body. Sources for endogenous fungal endophthalmitis include: ● Systemic opportunistic infections in immunocomprised hosts, as seen in: ● AIDS; ● Renal failure; ● Severe burns; ● Prolonged corticosteroid use; ● Chemotherapeutics; ● Hyperalimentation; ● Solid organ or bone marrow transplantation. ● Endocarditis (especially after cardiac valvular surgery). ● Gastrointestinal ulceration or surgery. ● Indwelling or long-term IV catheters. ● Shunts or prostheses. ● IV drug abuse. Often the source cannot be identified, and as many as half of patients with presumed endogenous fungal endophthalmitis
474
have negative blood cultures and negative systemic evaluations. Obtaining a careful history will be helpful in determining the most likely organism. For example: ● Candida species (yeasts) may cause endogenous or exogenous endophthalmitis and are more commonly associated with indwelling catheters, chronic antibiotic use, abdominal surgery, diabetes, immunosuppression with high dose corticosteroids or cytotoxic agents, intravenous drug abuse, and perioperative post-surgical endophthalmitis secondary to contamination of lens implants or irrigation fluids. ● Aspergillus species (septate fi lamentous fungi) may be associated with exogenous (grain farmers, poultry breeders, trauma) or endogenous endophthalmitis (intravenous drug abuse, cardiac surgery, liver transplantation, and leukopenia). ● Fusarium species (septate fi lamentous fungi) are associated with leukopenia, intravenous drug abuse, ocular surgery and predisposing keratitis. ● Blastomycosis species and Cryptococcus species may cause ocular infection through endogenous spread and may occasionally spread to the central nervous system. The incidence of exogenous fungal endophthalmitis varies from 2–13% of all cases of exogenous endophthalmitis. The visual prognosis in exogenous fungal endophthalmitis is worse than that in endogenous disease, especially in those cases of endophthalmitis initially presenting as fungal keratitis. Organisms identified in exogenous fungal endophthalmitis associated with visual outcome 20/400 or better include Cylinrocarpon, Tubercularia, Aspergillus, Paecilomyces, and Candida; on the other hand, Acremonium and Fusarium species are associated with worse final visual acuity. Candida and Aspergillus are the most common cause of endogenous endophthalmitis, but Cryptococcus neoformans, Pseudoallescheria boydii, and other fungi have been reported. The incidence of endogenous fungal endophthalmitis has increased in the last few decades, correlating with the increased prevalence of the sources of endogenous infections listed above. Although the visual prognosis for patients with endogenous endophthalmitis has improved with more aggressive therapy, half of patients treated at one tertiary care center had final visual acuity of 20/50 or worse in spite of aggressive management. In multiple studies, high mortality rates, as high as 77% at two months, have been seen in patients with endogenous fungal endophthalmitis.
PATHOPHYSIOLOGY The mechanism of exogenous fungal infections begins with the traumatic or surgical breakdown of conjunctival or corneal epithelium, providing the organism with a site of entry. Ulceration and abscess formation may follow. Localized immunosuppression, typically from topical corticosteroids, increases the likelihood of invasive fungal infections. Unlike bacterial keratitis, fungal organisms more often penetrate through the cornea into the anterior chamber causing progressive hypopyon and anterior chamber inflammatory membranes. This endophthalmitis can subsequently spread to include vitritis and chorioretinitis. In endogenous fungal endophthalmitis, fungi gain access to the eye most often via the choroidal or retinal circulations. Patients with candidemia are at higher risk for this complication, with the rate of Candida endophthalmitis in these patients
DIAGNOSIS Clinical signs and symptoms Fungal endophthalmitis presentation varies depending upon the: ● Size of the intraocular inoculation; ● Patient’s relative immunocompetency; ● Concomitant administration of corticosteroids and antifungal agents during the initial infection period. Most often, patients present 7 to 14 days after inoculation with: ● Conjunctival injection; ● Varying levels of pain (mild or absent); ● Often only mildly decreased vision. The presentation of fungal endophthalmitis is typically more indolent than that seen with bacterial endophthalmitis, with a slower onset and more chronic course. Anterior chamber reaction, including hypopyon, and vitritis with whitish plaques on the pars plana, lens capsule or intraocular lens may develop. Alternatively, the eye may be white and quiet. Typically, exogenous endophthalmitis excites more pronounced pain and anterior segment inflammation, while endogenous endophthalmitis produces less pain and a quieter anterior segment. More fulminant infections may cause: ● Fibrinous membranes in the anterior chamber; ● Vitreous veils, snowballs, and/or calcific plaques in the posterior segment. Endogenous fungal endophthalmitis may also be associated with: ● White, fluffy retinal infi ltrates; ● Retinal hemorrhages. Funduscopy of Candida endophthalmitis characteristically reveals focal white superficial retinal lesions associated with a fluffy white overlying vitritis. Multiple white-centered superficial retinal hemorrhages can also be seen. Subretinal infi ltrates sometimes coalesce into a white subretinal nodule. In contrast, Aspergillus endophthalmitis produces a more severe chorioretinitis, with more rapidly progressing larger lesions, as well as vasculitis and areas of retinal necrosis and retinal hemorrhage. A large yellow macular infi ltrate often develops, with preretinal or subretinal exudative layering to form a pseudohypopyon of the posterior pole. Other fungi may produce a chorioretinitis similar to that seen with Candida. Often, initial examination of patients at risk for fungal endophthalmitis by an ophthalmologist may be unremarkable;
however, days to weeks later, fungal endophthalmitis develops in spite of continuous systemic antifungal treatment. For this reason, some authorities recommend repeat examination of patients with candidemia two weeks after an initial negative exam.
Laboratory findings A thorough history and ophthalmologic examination often strongly suggest the causative pathogen. Obtaining a fungal culture prior to the initiation of antifungal therapy is essential; this may be the only way to determine the identity of the infectious fi lamentous fungus or yeast while allowing for drug sensitivity testing, if necessary. Fungal culture may not be necessary in those cases where systemic cultures have already isolated the pathogen. Acquisition of vitreous fluid either by aspiration alone (i.e. vitreous tap) or during vitrectomy provides a higher yield than aqueous fluid from the anterior chamber. In the Endophthalmitis Vitrectomy Study, there was no added benefit of vitrectomy over aspiration alone. However, diagnostic vitrectomy is preferable to vitreous tap because aspiration without vitrectomy induces traction at points of vitreoretinal adhesion and may miss a focal vitritis. Syringes containing intraocular fluids are capped and taken directly to the microbiology laboratory for smears and inoculation of culture media. The vitrectomy canister is sealed and sent for vacuum fi ltration or centrifugation. If only a small amount of vitreous is available, tryptic soy broth (usually used for swabs) can be drawn into the specimen syringe along with a small air bubble, and mixed. Smears are best prepared by placing one drop of each specimen on a glass slide and using a spatula to spread in a circular area 1 cm in diameter. These are then left to dry and carried to the microbiology laboratory for fi xation and staining. Gomori’s methenamine silver (GMS) and calcofluor white, and Acridine Orange stains may be used to stain for organisms. Blood agar and Sabouraud’s dextrose agar containing gentamicin are the preferred culture media. One drop of specimen can be placed in brain heart infusion broth warmed to room temperature. Two specimen drops are placed on a calcium alginate swab, which can then be placed in the bottom of a Thioglycolate broth warmed to room temperature. Aspirates may also be sent for PCR for fungal DNA if available to facilitate early preliminary identification. In every case, fungal cultures should be incubated at least 4 to 6 weeks for observation. Some laboratories routinely discard cultures that have no growth after 48 hours, but some fastidious organisms may be quite slow growing; cultures for suspected fungal endophthalmitis discarded before 28 days may be falsely read as negative.
CHAPTER 257 • Fungal Endophthalmitis
between 28 and 45% of cases. Infection typically begins as a chorioretinitis. On histopathology, Candida endophthalmitis is characterized by small foci of retinal and uveal infection and suppurative granulomatous inflammation with multiple small foci of suppurative vitritis and infection. In contrast, Aspergillus endophthalmitis is most often localized to the subretinal and subretinal pigment epithelial spaces, and is associated with foci of deep retinal necrosis or chorioretinitis, vascular invasion, and a single larger area of suppurative vitritis. These characteristics are consistent with the clinical fi ndings that visual recovery is less common with Aspergillus and positive vitreous cultures are more often obtained with Candida.
TREATMENT Therapy for fungal endophthalmitis may be instituted medically and/or surgically. Initially, removal of infecting exogenous agents (e.g. indwelling catheter), treatment of an external fungal infection (e.g. keratitis), and/or treatment of systemic conditions that may predispose to endogenous endophthalmitis (e.g. neutropenia secondary to chemotherapeutics) is warranted.
Medical Medical therapy may be ocular or systemic. Prior to instituting therapy, however, aqueous and vitreous cultures are sent to microbiology for sensitivities.
475
Ocular Ocular therapy for fungal endophthalmitis may be: ● Topical; ● Subconjunctival; ● Intravitreal.
SECTION 22 • Globe
Topical ophthalmic antifungal agents, while effective for fungal keratitis or scleritis (e.g. natamycin 5% ophthalmic suspension), do not provide adequate intravitreal drug levels required for the treatment of endophthalmitis. Poor vitreous penetration is also seen following subconjunctival deposition of antifungal agents. In addition, this route of administration has a higher risk of local side effects, such as pain at the site of injection. Intravitreal injection is then performed. Amphotericin B (5 μg in 0.1 mL) may be effective for most forms of fungal endophthalmitis. If a patient has not undergone pars plana vitrectomy (PPV), then the half-life of intraocular amphotericin B is approximately one week, and one should not repeat injection until that time has elapsed. In contrast, if a patient has undergone PPV, the drug is cleared within 24 hours of administration.
Systemic Systemic therapy may be: ● Parenteral; ● Oral. Intravenous drugs currently available for fungal endophthalmitis include: ● Amphotericin B; ● Fluconazole. Both agents are effective against a wide spectrum of fungi and act by binding to sterols in fungal cell membranes, increasing cell membrane permeability and causing leakage of cell contents leading to cell death. Amphotericin B is given intravenously in doses of 0.5 mg/kg/day or 1 mg/kg every other day in a single infusion over 4 hours. The patient also must be premedicated with ibuprofen and diphenhydramine for some of the uncomfortable side effects. Fluconazole is a third-generation imidazole that may be administered either parenterally or orally in doses ranging from 200 mg to 400 mg/day. In the past, the most effective oral agents against fungal endophthalmitis have been: ● Flucytosine is effective against Candida and Cryptococcus species, particularly when added to amphotericin B. However, resistance has been noted in over 50% of fungal isolates tested against the drug. In addition, there have been side effects reported, the most serious of which is pancytopenia; others include elevated liver function tests and hepatomegaly; ● Fluconazole has good antifungal activity, but after several weeks the physician must be aware of clinical depression setting in, which may necessitate discontinuance of the drug; ● Ketoconazole is another effective antifungal agent, particularly against Blastomyces and Histoplasma species; ● Itraconazole, another third-generation imidazole, is effective when combined with amphotericin B against Aspergillus, Cryptococcus, Blastomyces, and Histoplasma species. Recently, a new antifungal agent, voriconazole, has been approved by the Food and Drug Administration (FDA) for systemic fungal infection. Voriconazole is a second-generation
476
synthetic derivative of fluconazole, differing from this drug by the addition of a methyl group to the propyl backbone and by the substitution of a triazole moiety with a fluoropyrimidine group. These structural changes result in a higher affinity for the fungal enzyme lanosterol 14-a-demethylase, thus preventing the conversion of lanosterol to ergosterol. Since ergosterol is essential to fungal cell membrane synthesis, depletion causes disruption of the membrane and cell lysis. Voriconazole has demonstrated greater activity against all Candida and Aspergillus species than all other antifungals currently available. Also, all endemic fungal pathogens, such as Fusarium, Histoplasma, Blastomyces, Paracoccidioides, and Cryptococcus species, are fully susceptible to voriconazole. Voriconazole achieves therapeutic concentrations in both the aqueous and vitreous both after oral and intravitreal administration. Examination of the safety of intravitreal use of voriconazole showed: normal adult rats were injected with differing concentrations of voriconazole in one eye while the fellow eye was injected with saline, thus serving as a control. Serial electroretinogram (ERG) measurements of maximum scotopic b-wave, bmax, intensity needed for half saturation, I0.5, and saturated a-wave amplitude were measured in all eyes. Determination was made that there was no statistically significant difference in these parameters recorded between control eyes and voriconazole-injected eyes in any concentration groups. Histologic examination with light microscopy did not reveal any retinal abnormality in the eyes with 5 to 25vμg/mL intravitreal voriconazole. No statistically significant difference was noted between eyes treated with different concentrations of voriconazole versus the fellow control eyes treated with saline in terms of ERG findings. Thus, because of its broad spectrum of coverage, low MIC90 levels for the organisms of concern, good tolerability, and excellent bioavailability with oral administration, voriconazole may represent a major advance in the prophylaxis or management of both exogenous and endogenous fungal endophthalmitis.
Surgical In most cases of fungal endophthalmitis, pars plana vitrectomy may be helpful to: ● Retrieve vitreous samples for culture of the causative organisms; ● Remove the bulk of infective material; ● Sterilize the vitreous cavity; ● Improve aqueous circulation into the vitreous to circulate therapeutic drug molecules and to wash out offending fungal elements. When there is no specific vitreous pathology, one must search for fungal elements to culture from all sites. Often, centrifugation or fi ltration of vitreous specimens can concentrate organisms and improve the chances of obtaining a positive culture. In cases of recurrent infection or inflammation in patients with an intraocular lens, removal and culture of the intraocular lens implant and the entire capsular bag should be considered to reduce potential scaffolding for infection. Iridectomy may also be indicated if suspicion exists. In general, the chances of obtaining a positive culture increase greatly with aspiration of white, fluffy opacities, calcific plaques, or opacified portions of residual capsule rather than the relatively low yield of obtaining clear vitreous. In most cases, pars plana vitrectomy must be combined with intravitreal injection of antifungal agents and concomitant oral or intravenous therapy. The prevailing treatment of choice cur-
rently is PPV with intravitreal injection of amphotericin B plus oral voriconazole, thus achieving adequate vitreous concentration of two fungicidal drugs after clearing the infectious debris. Choosing an agent that has a low risk of retinal toxicity is important; this is another important reason that voriconazole is an effective choice.
Generally, final outcomes after the development of fungal endophthalmitis depend upon a variety of factors: ● Timing of trauma or surgery to presentation; ● Type of matter inoculated (i.e. vegetable matter has poorer prognosis); ● Relative immunocompetency of the individual; ● Timing of administration of immunosuppressive agents and antifungals; ● Isolation of organism by culture; ● Access to medical care. If all factors are equal, some fungi have better prognosis than others do. For example, in exogenous endophthalmitis, visual outcome of 20/400 or better is more likely when isolates include: ● Cylinrocarpon; ● Tubercularia; ● Aspergillus; ● Paecilomyces; ● Candida. On the other hand, these species are associated with worse fi nal visual acuity: ● Acremonium; ● Aspergillus; ● Fusarium.
Cryptococcus neoformans, Pseudoallescheria boydii as well as other fungi have been reported.
Patients with Candida tend to have better outcomes than those with Aspergillus due to the fact that Candida infections are more accessible (i.e. in the vitreous versus in the deep retina and RPE). However, all patients with endogenous endophthalmitis are very ill. In fact, as stated earlier, high mortality rates, as high as 77% at two months, have been reported in multiple studies. Thus, mortality tends to be much higher in the endogenous versus the exogenous group.
REFERENCES Barza M, Pavan PR, Doft BH, et al: Evaluation of microbiological diagnostic techniques in postoperative endophthalmitis in the Endophthalmitis Vitrectomy Study. Arch Ophthalmol 115:1142–1150, 1997. Binder MI, Chua J, Kaiser PK, et al: Endogenous endophthalmitis: an 18year review of culture-positive cases at a tertiary care center. Medicine 82:97–105, 2003. Flynn HW, Jr: The clinical challenge of endogenous endophthalmitis. Retina 21:572–574, 2001. Hua G, Pennesi M, Shah K, et al: Safety of intravitreal voriconazole: electroretinographic and histopathologic studies. Trans Am Ophthalmol Soc 101:183–189, 2003.
CHAPTER 257 • Fungal Endophthalmitis
COMMENTS
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Pettit TH, Olson RJ, Foos RY, et al: Fungal endophthalmitis following intraocular lens implantation: a surgical epidemic. Arch Ophthalmol 98:1025–1039, 1980. Pflugfelder SC, Flynn HW Jr, Zwickey TA, et al: Exogenous fungal endophthalmitis. Ophthalmology 95:19–30, 1988. Rao NA, Hidayat AA: Endogenous mycotic endophthalmitis: variations in clinical and histopathologic changes in candidiasis compared with aspergillosis. Am J Ophthalmol 132:244–251, 2001. Stern WH, Tamura E, Jacobs RA, et al: Epidemic postsurgical Candida parapsilosis endophthalmitis: clinical fi ndings and management of 15 consecutive cases. Ophthalmology 92:1701–1709, 1985.
In endogenous endophthalmitis: ● Candida and Aspergillus species are the most common causes;
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S ECT I O N
23
Intraocular Pressure
258 ANGLE RECESSION GLAUCOMA 921.3 Sarwat Salim, MD, FACS Memphis, Tennessee Raghu Mudumbai, MD Seattle, Washington
Spaeth et al showed that approximately 50% of patients with traumatic glaucoma developed open angle glaucoma in the unaffected, nontraumatized eye, suggesting that patients who develop angle recession glaucoma may have an underlying predisposition to developing glaucoma, which may be accelerated by the additional insult of trauma. Since angle recession glaucoma may not occur for months or years after the original trauma, these patients need to be followed regularly.
ETIOLOGY DIAGNOSIS Angle recession glaucoma is one of the manifestations of blunt ocular trauma. The contusion leads to shearing forces between the anterior uvea and its various attachments. Damage can occur to the iris, trabecular meshwork (TM), or ciliary body. Angle recession involves rupture of the face of the ciliary body, resulting in a tear between the longitudinal and circular fibers of the ciliary muscle. Initially, this may be masked by the concomitant presence of hyphema, a common clinical presentation that occurrs after anterior segment trauma. Although a large percentage of patients may exhibit some level of angle recession on gonioscopy, only 4%–10% of these patients will develop angle recession glaucoma. The term angle recession glaucoma is somewhat misleading because the resultant glaucoma is not secondary to angle recession, but due to the initial trauma to the trabecular meshwork. Tears in the trabecular meshwork, along with degenerative changes and scarring, can lead to obstruction of aqueous outflow.
COURSE Acutely, patients may have elevated intraocular pressure (IOP) from associated co-morbidities, such as hyphema, iridocyclitis, or pupillary block resulting from ectopia lentis with or without vitreous prolapse. In some cases, the IOP may be low secondary to decreased production of aqueous humor from associated inflammation, transient increase in outflow facility from disruption of structures in the angle, or due to the presence of a cyclodialysis cleft. As previously mentioned, only a small minority of these patients develop late glaucoma. The risk of glaucoma appears to be related to the extent of angle recession. Usually, angle recession greater than 180º is deemed a considerable risk. In addition to the aforementioned changes described in the TM, another mechanism leading to chronic IOP elevation is due to formation of a Descemet’s-like membrane lined by endothelial cells over the drainage angle.
Clinical signs and symptoms Acutely, the eye may be difficult to examine because of inflammation and hyphema. Once the view has cleared, attention should be paid to anterior chamber depth. The affected eye may appear deeper. On gonioscopy, characteristic fi ndings of angle recession include widening of the ciliary body band, torn iris processes with resultant whitening of the scleral spur, and irregular and darker pigmentation in the angle. Peripheral anterior synechiae may be present. It is prudent to compare the angle appearance between the two eyes to evaluate subtle differences. Also, different quadrants within the same eye should be inspected carefully. Other angle abnormalities from trauma such as iridodialysis (tear of the iris root) or cyclodialysis cleft (separation of the ciliary body from the scleral spur) may be detected. Corneal blood staining, cataract, lens subluxation or dislocation, vitreous hemorrhage, retinal commotion, and retinal dialysis may be concomitantly present and accompany glaucoma.
Differential diagnosis Acutely, many factors may contribute to elevated intraocular pressure. The trabecular meshwork may be overwhelmed by red blood cells and their byproducts or by inflammatory cells from iridocyclitis. Later, ghost cell glaucoma may develop. Chronic treatment with steroids can lead to steroid-induced glaucoma. Other differential diagnoses for unilateral glaucoma should be entertained, including pseudoexfoliative glaucoma and neovascular glaucoma. Unrelated open angle glaucoma and uveitic glaucoma should also be considered.
TREATMENT In the acute setting, treatment should be directed at lowering intraocular pressure and controlling inflammation.
479
Ocular Topical steroids with cycloplegic agents may be helpful for both inflammation and pain control. Aqueous suppressants, including beta blockers, carbonic anhydrase inhibitors, and alpha agonist agents should be used to control IOP. Osmotic agents, by reducing vitreous volume, may provide acute but transient pressure reduction. SECTION 23 • Intraocular Pressure
Medical
Salmon JF, Mermoud A, Ivey A, et al: The detection of post-traumatic angle recession by gonioscopy in a population-based glaucoma survey. Ophthalmology 101:1844, 1994. Shields MB: Textbook of glaucoma. 4th ed. Baltimore, Williams & Wilkins, 1997:339–344. Spaeth GL: Traumatic hyphema, angle recession, dexamethasone hypertension and glaucoma. Arch Ophthalmol 78:714–721, 1967. Tumbocon JA, Latina MA: Angle recession glaucoma. Int Ophthalmol Clin 42:69–78, 2002.
With chronic IOP elevation, medical therapy with aqueous suppressants should be attempted first. Miotics are usually ineffective in these cases and can actually cause paradoxical rise in pressure. Prostaglandin analogs may provide the benefit of bypassing the compromised trabecular meshwork and increase the uveoscleral outflow.
Surgical Laser trabeculoplasty is usually not successful due to distortion of the angle anatomy and TM scarring. Filtration surgery with the use of antimetabolites is the most effective surgical procedure in these cases. Glaucoma drainage devices play a role in cases of failed fi ltering surgery or in patients who are not candidates for trabeculectomy due to excessive scarring from the initial trauma. In eyes with limited visual potential, a cyclodestructive procedure may be an alternative option.
COMPLICATIONS The clinician should be mindful of complications associated with medical and surgical intervention. These include worsening of asthma and heart failure with beta blockers, allergic reactions to alpha2 agonists, and paresthesias, acidosis, fatigue, renal stones, and other adverse effects of carbonic anhydrase inhibitors. Filtration surgery poses risks of late onset bleb leaks with hypotony maculopathy and infection. Drainage implants can present a different set of problems, including corneal decompensation, tube retraction and erosion, and strabismus. Proper instruction ofpatients combined with a good clinical exam and frequent follow-up visits can, we hope, detect or prevent these problems.
COMMENTS The clinician should be cognizant of both the short-term and long-term risks of glaucoma in patients who have suffered blunt ocular trauma. Patients presenting with hyphema should be evaluated with gonioscopy at an appropriate time to check for the presence of angle recession and other abnormalities. Usually, angle involvement of greater than 180º confers approximately a 10% risk for development of angle recession glaucoma. Since glaucoma can occur at any time after injury, regular follow-up examinations are mandatory for these patients, with particular attention to tonometry, gonioscopy, and optic nerve examination.
259 CORTICOSTEROID-INDUCED GLAUCOMA 365.31 John R. Samples, MD Portland, Oregon
ETIOLOGY/INCIDENCE Corticosteroids may cause elevated intraocular pressure (IOP) through any route of administration, including oral, inhaled, topical, and periocular. Individuals vary a great deal in sensitivity to corticosteroids. Pulmonologists are sometimes skeptical that inhaled steroids will raise pressure, and it may be best to recommend that the patient get checked two weeks after this medication is started. Approximately one-third of otherwise healthy individuals will have some type of IOP elevation in response to the use of corticosteroids. Age may be an important factor in determining this; children may be particularly susceptible. Steroid-induced glaucoma in children has been reported, and in some instances, congenital glaucoma may be corticosteroid related. The popularity of intravitreal corticosteroid injections by retinal specialists has increased the occurrence of steroidinduced glaucoma. It may be warranted to check such patients two or three weeks after an injection. Patients with already compromised optic nerves should be followed especially closely. In addition to the age of the patient, the magnitude and duration of IOP elevation is determined by dose, route of administration, frequency, duration of exposure, and predisposition of the individual to respond to corticosteroids. (The time of onset suggests a biochemical mechanism.) Because most individuals have normal optic nerves, patients with elevated IOP secondary to corticosteroid therapy may not have glaucomatous damage. The elevation of IOP is related to biochemical abnormality in the trabecular meshwork. Several specific hypotheses have been put forward. Impaired outflow may be related to impaired enzymes in the trabecular meshwork.
COURSE The course remits with discontinuation of corticosteroid and may be altered with decreased potency of drug. In some instances where the response to the intravitreal injection of steroid is aromatically effective, it may be best just to continue the injections and treat the glaucoma.
REFERENCES Girkin CA, McGwin G, Jr, Long C, et al: Glaucoma after ocular contusion: a cohort study of the United States Eye Injury Registry. J Glaucoma 14:470–473, 2005. Kaufman JH, Tolpin DW: Glaucoma after traumatic angle recession: a tenyear prospective study. Am J Ophthalmol 78:648–654, 1974. Mermoud A, Salmon JF, Barron A, et al: Surgical management of posttraumatic angle recession glaucoma. Ophthalmology 100:634, 1993.
480
DIAGNOSIS Clinical signs and symptoms Ocular or periocular ● ● ●
Eyelids: slight ptosis. Lens: cataracts, particularly posterior subcapsular cataracts. Other: increased intraocular pressure; visual field loss.
COMPLICATIONS
Ocular
Whenever a patient undergoes corticosteroid therapy, a baseline examination and close follow-up are mandatory. Patients who are treated with oral prednisone on a long-term basis or who have recurrent intravitreal corticosteroid injections may be particularly at risk and should have an eye examination to ensure that they have not developed steroid-induced glaucoma. In addition to the side effects of corticosteroids, steroid injections can also cause problems due to the preservatives used and due to the direct toxicity of high steroid concentration on certain cell types. Periocular methyl prednisone preparations may causesteroid-related effects for longer than is generally appreciated.
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Discontinue the use of corticosteroids when steroid-induced glaucoma is suspected if the underlying condition permits. Whether the IOP falls will depend on the concurrent presence of uveitis or other conditions that raise the IOP. Most pressure reductions occur two weeks after steroid is discontinued. Alteration in the trabecular cells and in the cellular events surrounding outflow may occur as a result of corticosteroid use. Patients with corticosteroid-induced IOP elevations respond to the usual antiglaucoma medications, including miotics, epinephrine, dipivefrin, β-adrenergic antagonists, and carbonic anhydrase inhibitors. As with ocular hypertension, there may be no need to treat mildly elevated pressure if the optic nerve is normal. Corticosteroid glaucoma generally does not respond to laser trabeculoplasty. If a topical ocular steroid is needed, it is sometimes useful to use a weaker synthetic steroid, such as fluorometholone or loteprednol etabonate, which will cause less pressure elevation for a given amount of antiinflammatory effect. Topical nonsteroidal anti-inflammatory drugs that are sufficiently potent to penetrate the eye and have significant anti-inflammatory action are available. Topical nonsteroidal anti-inflammatory drugs may have significant potency as well as a useful anti-inflammatory effect when used four times a day in lieu of a corticosteroid. The metabolism of steroids in systemic tissues, as well as the eye, seems to be a major determinant of steroid effects and side effects. A major part of the increased potency of steroids, such as dexamethasone, systemically is due to substitutions occurring on the cortisol molecule, some of which decrease degradation and others of which increase binding to steroid receptors. In direct contrast, steroids that are synthesized using progesterone rather than cortisol as the foundation molecule, such as fluorometholone and medrysone, seem to be particularly susceptible to degradation. In the eye, both medrysone and fluorometholone have a lesser tendency to raise the IOP, but they are not considered as efficacious, probably because of the inactivation due to metabolism.
Surgical ●
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Corticosteroid-induced glaucomas may require fi ltering surgery if they do not remit. Any decision to perform surgery must be based on the appearance of the visual field, as well as that of the optic nerve. Occasionally, corticosteroidinduced glaucomas are observed in the presence of a functioning fi lter or a Seton procedure. Glaucomatologists vary in their opinions on whether steroid-induced pressure elevations can be a significant problem when an outflow-enhancing procedure, such as trabeculectomy or a Seton procedure, has been performed. The diagnosis of steroid-induced IOP elevation after fi ltration should include consideration of other causes of bleb failure, such as closure of the internal aspect of the fi ltering fistula and subconjunctival scarring.
COMMENTS Many corticosteroid-induced glaucomas result from the inappropriate use of corticosteroids for minor conditions, such as eye irritation or contact lens discomfort. Also, it is not uncommon for patients who have been treated with oral steroids to have pressure elevations. The failure of a physician to recognize corticosteroid-induced glaucoma may lead to needless visual loss and difficult medicolegal problems.
CHAPTER 260 • Angle Recession Glaucoma
TREATMENT
REFERENCES Agrawal S, Agrawal J, Agrawal TP: Management of intractable glaucoma following intravitreal triamcinolone acetonide.[comment]. [Comment. Letter] Am J Ophthalmol 139(3):575–576, author reply 576, 2005. Armaly MF: Effect of corticosteroids on intraocular pressure and fluid dynamics. I. The effect of dexamethasone in the normal eye. Arch Ophthalmol 70:482, 1963. Armaly MF: Effect of corticosteroids on intraocular pressure and fluid dynamics. II. The effect of dexamethasone in the glaucomatous eye. Arch Ophthalmol 70:492, 1963. Armaly MF: Statistical attributes of steroid hypertensive response in the clinically normal eye. Invest Ophthalmol Vis Sci 4:187, 1965. Jampol LM. Yannuzzi LA. Weinreb RN. Glaucoma and intravitreal steroids. [Editorial] Ophthalmology 112(8):1325–1326, 2005.
260 EXFOLIATION SYNDROME 365.52 (Pseudoexfoliation Syndrome, Pseudoexfoliation Glaucoma, Exfoliative Glaucoma, Capsular Glaucoma) Andrew G. Iwach, MD San Francisco, California Ümit Aykan, MD Istanbul, Turkey H. Dunbar Hoskins, Jr., MD San Francisco, California
ETIOLOGY/INCIDENCE The exfoliation syndrome occurs when ocular tissues synthesize an abnormal protein, which may obstruct the trabecular
481
SECTION 23 • Intraocular Pressure
meshwork. Exfoliation syndrome with glaucoma appears to be a secondary glaucoma in which exfoliation material and pigment obstruct the trabecular meshwork, with an associated elevation in intraocular pressure ● Once thought to occur primarily in Scandinavia, exfoliation syndrome is now known to occur throughout the world. ● There is a higher prevalence in certain areas of the world. ● Prevalence increases with age. ● Exfoliation syndrome occurs equally in both sexes. ● This syndrome presents unilaterally in one-third to one half of cases; however, as many as 43% of cases become bilateral in 5 to 10 years. ● As many as 7% of patients with exfoliation syndrome are initially diagnosed with glaucoma, but an additional 15% are found to have only elevated IOPs without optic nerve damage. ● Causes are related to mechanical obstruction by exfoliative material of exotrabecular origin, apparent production of exfoliative material by trabecular cells, and abnormal regulation of elastin synthesis, degradation, or both in the optic nerve. ● The main risk factor for glaucoma is the degree of chamber angle pigmentation rather than the amount of exfoliation. ● Exfoliation may be a risk factor for angle-closure glaucoma. ● Exfoliation syndrome is a risk factor in the evolution and treatment of exfoliative glaucoma and cataract. ● A poorer functional outcome and an increased incidence of preoperative and postoperative complications and senile cataract should be anticipated after surgery. ● The severity of glaucoma is related to the amount of exfoliative material present in the cribriform region.
DIAGNOSIS Clinical signs and symptoms ●
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482
Patients with exfoliation syndrome present with a pattern on the anterior lenticular surface consisting of a central translucent disk surrounded by a clear zone, which in turn is surrounded by a granular gray-white area with scalloped edges that is best seen after pupillary dilation. Dandruff-like flakes of exfoliative material are deposited on the conjunctiva, corneal endothelium, trabecular meshwork, iris, pupillary margin, ciliary processes, zonules, and anterior hyaloid face in aphakic eyes. The amount of angle pigmentation is moderate, and distribution is patchy. Transillumination defects of the iris and reduced response to mydriatics are associated with exfoliation syndrome. The amount of exfoliative material correlates with the IOP and is inversely correlated with the number of axons in the optic nerve. Quantification may be achieved with flare measurement and biochemical protein determination, which affect pharmacologic and surgical treatment. Expect greater visual field loss and more difficulty in gaining control of IOP on presentation than with primary openangle glaucoma. Expect a higher mean range of IOP, a higher maximum IOP, and a higher minimum IOP.
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In eyes with exfoliation syndrome, a small optic disk does not predispose to glaucoma. The optic disk does not show pathognomonic features for exfoliation. Fluorescein angiography of the iris reveals a decreased number of vessels, neovascularization, and leakage from the vessels. The extensive blood-aqueous barrier breakdown in eyes with exfoliation syndrome after intraocular surgery is a risk factor for early or late postoperative complications. Resulting alterations in the blood-aqueous barrier should be considered in the medical and surgical treatment.
Differential diagnosis Significant fluctuation in the diurnal curve of the IOP distinguishes exfoliative glaucoma from primary open-angle glaucoma and may be an important factor in predicting any subsequent poor response to medical therapy.
TREATMENT The treatment of glaucoma associated with exfoliation syndrome is similar to that for primary open-angle glaucoma. More aggressive management is warranted. ● IOP is typically high in exfoliative glaucoma, so the response to medical treatment is less favorable. ● The glaucoma in exfoliation syndrome tends to be less responsive to medical therapy than in primary open-angle glaucoma, and a higher percentage of exfoliative glaucoma patients require surgical intervention. ● Laser trabeculoplasty has its highest initial success rate in exfoliative glaucoma, although the IOP may rise again within a few years. ● Filtering surgery has a high success rate. ● Expect a higher incidence of vitreous loss during cataract surgery in exfoliation syndrome. ● Patients respond well to timolol initially but then have a higher IOP and significant fluctuation in the diurnal curve. ● Latanoprost causes a marked and sustained IOP reduction in eyes also being treated with timolol. ● Although the initial response to argon laser trabeculoplasty in exfoliative patients is greater, the long-term outcome is similar to that of primary open-angle glaucoma. ● Phacoemulsification can be well tolerated if a careful preoperative protocol is followed, including pupillary dilatation, wide capsulorhexis, and total nucleus hydrodisection. ● Trabecular aspiration is a new proposed mode to treat exfoliation glaucoma.
COMPLICATIONS ●
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Exfoliation syndrome is a risk factor for retinal vein thrombosis. Exfoliative glaucoma is a risk factor for accelerated cataract progression after trabeculectomy. Abnormal extracellular matrix production and vascular abnormalities may cause degenerative tissue changes, and atrophy of muscle cells might potentiate the reduction in dilating properties of the iris. There is an increased incidence of the intraoperative and postoperative complications, including insufficient dilata-
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tion of the pupil, tearing of the posterior capsule, loss of the vitreous, modifications of the corneal endothelium, increased postoperative IOP, and more frequent opacification of the posterior capsule. Comorbidity with acute cerebrovascular disease is more common with exfoliative glaucoma than with primary open-angle glaucoma.
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The increased protein content of the aqueous humor with the inflammatory reaction can result in compromise of aqueous outflow. Damage to trabecular cells after engulfi ng inflammatory debris may reduce outflow. Corticosteroids can cause IOP elevation.
CLOSED ANGLE Glaucoma Research Foundation 490 Post Street, Suite 1427 San Francisco, CA 94102
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REFERENCES
The angle can be closed by extensive peripheral anterior synechiae or neovascularization. Posterior synechiae can lead to pupillary-block angle closure. Ciliary body swelling can cause forward rotation of the iris-lens diaphragm, leading to angle closure.
Henry JC, Krupin T, Schmitt M, et al: Long-term follow-up of pseudoexfoliation and the development of elevated intraocular pressure. Ophthalmology 94:545, 1987.
DIAGNOSIS
Jonas JB, Papastathopoulos KI: Optic disk appearance in pseudoexfoliation syndrome. Am J Ophthalmol 123:174–180, 1997.
Laboratory findings ●
Konstas AG, Stewart WC, Stroman GA, Sine CS: Clinical presentation and initial treatment patterns in patients with exfoliation glaucoma versus primary open-angle glaucoma. Ophthalmic Surg Lasers 28:111–117, 1997.
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Layden WE, Shaffer RN: Exfoliation syndrome. Am J Ophthalmol 78:835, 1974.
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Ritland JS, Egge K, Lydersen S, et al: Exfoliation glaucoma and primary open-angle glaucoma: associations with death causes and comorbidity. Acta Ophthalmol Scand 82(4):397–400, 2004.
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261 GLAUCOMA ASSOCIATED WITH ANTERIOR UVEITIS 365.62
TREATMENT Systemic ●
Leon W. Herndon, MD Durham, North Carolina
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ETIOLOGY Increased intraocular pressure (IOP) can occur with any type of ocular inflammation, and it can be acute, transient, or chronic. Anterior uveitis influences IOP through a delicate balance between aqueous humor production and resistance to aqueous outflow. Usually, the production of aqueous is diminished in anterior uveitis; if this reduction is greater than the increase in resistance to outflow, the IOP will be low. In other cases, the increased resistance to aqueous outflow may be sufficiently greater than aqueous production, leading to pressure elevation. The causes of glaucoma associated with anterior uveitis can be divided into two categories, depending on whether the angle is open or closed.
Signs of acute iridocyclitis include ciliary flush, slight miosis, varying degrees of aqueous flare and cell, and frequent keratic precipitates. Chronic anterior uveitis often produces few or no symptoms but is particularly prone to cause secondary glaucoma. The IOP may vary in uveitic glaucoma due to variations in aqueous secretion, amount of outflow obstruction, and dose of corticosteroids being used at the time. A variety of noninvasive and invasive studies can be used to determine the cause of the uveitis, including serology, skin tests, chest radiographs, conjunctival biopsy, and anterior chamber paracentesis.
CHAPTER 261 • Glaucoma Associated with Anterior Uveitis
SUPPORT GROUP
Carbonic anhydrase inhibitors can be administered orally or intravenously. Systemic hyperosmotic agents are used to rapidly lower IOP and include oral glycerin, oral isosorbide, and intravenous mannitol.
Ocular ●
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Treatment should be directed at the underlying cause of the ocular inflammation. Inflammation can be treated with topical and systemic nonsteroidal anti-inflammatory agents; topical, periocular, and systemic corticosteroids; and systemic immunosuppressive agents. Ocular hypertension and glaucoma can be treated with topical β-blockers, alpha agonists, and carbonic anhydrase inhibitors. Miotics should be avoided because they may lead to increased inflammation. Prostaglandin analogs should probably be avoided because they may have a deleterious effect on the inflammatory cascade.
OPEN ANGLE Surgical ●
Inflammatory cells (polymorphonuclear leukocytes and macrophages) can infi ltrate the trabecular meshwork, leading to IOP elevation.
Closed-angle glaucoma ●
Laser iridotomy should be performed to reestablish communication between the posterior and anterior chambers.
483
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The argon or Nd : YAG laser, or both, may be used. Transient anterior chamber inflammation is a potential complication of laser iridotomy. Surgical iridectomy should be performed when laser iridotomy is unsuccessful or contraindicated.
Open-angle glaucoma ●
SECTION 23 • Intraocular Pressure
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Trabeculodialysis: ● A modified goniotomy is used in children and young adults with uncontrolled uveitic glaucoma; ● The technique involves disinsertion of trabeculum from the scleral spur, allowing direct access into Schlemm’s canal; ● The procedure has a success rate ranging from 56% to 60% in children and young adults. Trabeculectomy: ● Postoperative cellular response in uveitic glaucoma can accelerate the wound-healing process and lead to failure of the trabeculectomy; ● Antimetabolite therapy in association with trabeculectomy has been shown to improve the outcome of trabeculectomy in uveitic glaucoma with success rates of 75% to 95%. Drainage implant: ● There are different types of implant tubes for draining the aqueous from the anterior chamber to the subconjunctival space but few published reports of using drainage implants in patients with uveitic glaucoma; ● One series reported a success rate of 95.8% at 3 months and 91.7% at 6 months, 12 months, and 24 months after Baerveldt glaucoma drainage implantation in uveitic glaucoma.
COMPLICATIONS The use of antimetabolites in glaucoma surgery is associated with an increased risk of complications, such as hypotony, bleb leaks, and endophthalmitis. Postoperative inflammation or reactivation of the uveitis has been reported to occur in 5.2% to 31.1% of patients with uveitic glaucoma. Cataract progression is very common in the patient with uveitic glaucoma due to use of topical corticosteroids and after fi ltration surgery. If possible, the surgeon should allow the anterior chamber to be free of inflammation for at least 3 months before proceeding with elective cataract surgery.
Moorthy RS, Mermoud A, Baerveldt G, et al: Glaucoma associated with uveitis. Surv Ophthalmol 41:361–394, 1997. Prata JA, Neves RA, Minkler DE, et al: Trabeculectomy with mitomycin C in glaucoma associated with uveitis. Ophthalmic Surg 24:616–620, 1994. Skuta GL, Parrish RK: Wound healing in glaucoma fi ltering surgery. Surv Ophthalmol 32:149–170, 1987. Sung VC, Barton K: Management of inflammatory glaucomas. Curr Opin Ophthalmol 15:136–140, 2004. Wright MM, McGehee RF, Pederson JE: Intraoperative mitomycin-C for glaucoma associated with ocular inflammation. Ophthalmic Surg Lasers 28:370–376, 1997.
262 GLAUCOMA ASSOCIATED WITH ELEVATED VENOUS PRESSURE 365.82 John R. Samples, MD Portland, Oregon
ETIOLOGY Systemic disorders that raise the episcleral venous pressure can cause glaucoma as the increased pressure creates resistance to outflow in Schlemm’s canal, thus raising intraocular pressure. ● Schlemm’s canal is connected to the episcleral and conjunctival veins by a complicated system of vessels. Most vessels carrying aqueous humor from Schlemm’s canal are directed posteriorly, with the majority draining into episcleral veins. ● A few vessels cross the subconjunctival tissue and drain into conjunctival veins. ● Episcleral veins drain into the cavernous sinus via the anterior ciliary and superior ophthalmic veins, whereas the conjunctival veins drain into the superior ophthalmic or facial veins via the palpebral and angular veins. ● The normal episcleral venous pressure ranges between 8 and 10 mm Hg. Patients with primary open-angle glaucoma do not appear to have episcleral venous pressure elevations; in fact, there may be a negative correlation, with ocular hypertensive patients having significantly lower episcleral venous pressure.
COMMENTS DIAGNOSIS There are a number of inflammatory disorders commonly associated with secondary glaucoma, including Fuchs’ heterochromic iridocyclitis, glaucomatocyclitic crisis, sarcoidosis, and juvenile rheumatoid arthritis. Management of these conditions, as well as of other uveitic glaucomas, may be difficult because of the numerous mechanisms involved in their pathogenesis. The goal of treatment is to minimize permanent alteration of aqueous outflow and to prevent damage to the optic nerve.
REFERENCES Ceballos EM, Parrish RK, Schiffman JC: Outcome of Baerveldt glaucoma drainage implants for the treatment of uveitic glaucoma. Ophthalmology 109:2256–2260, 2002.
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Clinical signs and symptoms Elevated venous pressure is one means by which patients with thyroid eye disease may have elevated intraocular pressure. ● Elevated venous pressure may occur in association with a carotid cavernous fistula. ● The most consistent finding in patients with an elevated episcleral venous pressure is tortuous episcleral and bulbar conjunctival vessels. ● When the meshwork is open, there may be blood reflux into Schlemm’s canal. An experienced ultrasonographer may be able to detect a dilated superior ophthalmic view in some of these patients.
Categories Venous obstruction
Carotid cavernous fistula The typical carotid cavernous fistula occurs as a result of severe head injury; a large fistula is created between the internal carotid artery and the surrounding cavernous sinus venous plexus. The condition is characterized by pulsating exophthalmos, a bruit over the globe, conjunctival chemosis, engorgement of episcleral venous veins, and restriction of motility with evidence of ocular ischemia. The shunting of the internal carotid cavernous fistula causes high flow and high pressure. A more recently appreciated form of carotid cavernous fistula is the ‘low-flow’ shunt. These small fistulas may occur without a history of trauma. In these cases, the shunt is fed by a meningeal branch of the intracavernous internal carotid artery or external carotid artery that empties directly into the cavernous sinus or adjacent dural vein that connects with the cavernous sinus. Whether the patient has a high- or low-flow shunt, elevated pressure occurs. Venous backpressure may increase the episcleral venous pressure, which is the most common cause of intraocular pressure rise with the fistula. Angle-closure glaucoma has also been reported in association with carotid cavernous fistula.
Sturge–Weber syndrome In this syndrome, a hamartoma arises from the vascular tissue and produces a characteristic port-wine stain hemangioma of the skin in a trigeminal distribution. Several mechanisms of glaucoma are possible in these patients, but at least some patients seem to have an open anterior chamber angle with low arteriovenous pressure, usually associated with stooping over or a Valsalva maneuver.
Idiopathic These patients are elderly with no family history of the condition. The cause of the elevated venous pressure is unknown, and the associated glaucoma may be severe.
TREATMENT ●
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The treatment for glaucoma associated with elevated venous pressure is the same as that for other forms of glaucoma. In cases in which a carotid cavernous fistula or low-flow shunt is present, pharmacologic glaucoma control should be considered before surgical intervention is contemplated when the glaucoma is the only condition prompting consideration of surgery. In some instances, angiography alone is sufficient to prompt low-flow fistulas to close spontaneously.
Surgical ●
If surgical intervention is necessary, a fi ltering procedure should be used.
●
There is no doubt that these patients are at substantially increased risk for uveal effusion and expulsive hemorrhage. This should be included in the consent process. It has been recommended that drainage of the suprachoroid be routinely performed at the time of surgery. Prophylactic sclerotomy should routinely be performed at the same time as the filtering procedure.
PRECAUTIONS Repair of carotid cavernous fistulas may be hazardous and is a controversial area in neurosurgery. If glaucoma is the sole cause for intervention, one should be certain that it is significant and difficult to treat, and that visual field progression is present. Elevated episcleral venous pressure as a cause of glaucoma is often overlooked. Because these patients do have increased complications at the time of fi ltering surgery, careful consideration of episcleral and conjunctival vessels before fi ltration is always indicated. The consenting process should inform the patient that there is increased risk of choroidal hemorrhage when trabeculectomy is performed. Alternative, non-penetration surgeries for glaucoma may be useful in these cases.
REFERENCES Bellows AR, Chylach LT, Jr, Epstein DL, et al: Choroidal effusion during glaucoma surgery in patients with prominent episcleral vessels. Arch Ophthalmol 97:493–497, 1979. Harris GJ, Rice PR: Angle closure and carotid cavernous fistula in a series of 17 cases. Am J Ophthalmol 48:585–597, 1959.
CHAPTER 263 • Glaucoma Associated with Intraocular Tumors
In patients with thyroid eye disease, contracture of extraocular muscles and infi ltration of the plasma cells and lymphocytes into the orbit may lead to an elevated venous pressure. It must be kept in mind that thyroid dysfunction may lead to an elevated venous pressure as well as abnormal scleral rigidity. Retro-orbital tumors, cavernous sinus thrombosis, and lesions that obstruct venous return from the head also may cause venous obstruction and elevated venous pressure.
●
Palestine AG, Young BR, Pipegras DG: Visual prognosis and carotid cavernous fistula. Arch Ophthalmol 99:1600–1603, 1981. Podos SM, Minas TF, MacRif J: A new instrument to measure episcleral venous pressure: Comparison of normal eyes and eyes with primary open angle glaucoma. Arch Ophthalmol 80:209–213, 1968. Radius RL, Maumenee AE: Dilated episcleral venous vessels and openangle glaucoma. Am J Ophthalmol 86:31–35, 1978.
263 GLAUCOMA ASSOCIATED WITH INTRAOCULAR TUMORS 365.64 (Tumor Related Glaucoma, Melanomalytic Glaucoma, Melanocytomalytic Glaucoma, Neovascular Glaucoma, Angle Closure Glaucoma) Carol L. Shields, MD Philadelphia, Pennsylvania Jerry A. Shields, MD Philadelphia, Pennsylvania
ETIOLOGY/INCIDENCE A number of intraocular tumors can produce ipsilateral elevation of the intraocular pressure. In such instances, there may be a delay in clinical recognition of the underlying neoplasm while the patient is treated for the secondary glaucoma. In cases
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SECTION 23 • Intraocular Pressure
of malignant tumors, this delay in diagnosis can have serious consequences. In contrast to the primary glaucomas, which are generally bilateral, tumor-induced secondary glaucomas are almost always unilateral. The mechanism of the secondary glaucomas varies with the location, size, and type of tumor. Malignant tumors in the iris and ciliary body are more likely to obstruct aqueous outflow by directly infiltrating the trabecular meshwork. More posteriorly located intraocular neoplasms can produce anterior displacement of the lens-iris diaphragm causing angle closure, they can induce iris and angle neovascularization causing neovascular glaucoma, or they can liberate tumor cells in the anterior chamber angle, blocking aqueous outflow.
Primary tumors of the uvea Nevus Uveal nevi are benign lesions which rarely produce secondary glaucoma. Occasionally, however, localized or diffuse uveal nevi can lead to secondary glaucoma. This most often occurs with a melanocytoma or with a diffuse nevus of the iris. Melanocytoma is a specific variant of nevus which usually occurs in the optic disc, but which can arise anywhere in the uveal tract. Those located in the optic disc or choroid rarely produce secondary glaucoma whereas those which occur in the ciliary body or iris are more likely to produce secondary glaucoma by anterior chamber angle infi ltration with discohesive tumor or necrotic cells, often engulfed by macrophages (melanocytomalytic glaucoma).
Melanoma Of all patients with uveal melanoma, secondary glaucoma is found in approximately 3%. Iris melanoma is associated with secondary glaucoma in 7 % of cases and the most common mechanism of glaucoma is direct invasion of the trabecular meshwork by tumor tissue. Occasionally spontaneous hyphema is the cause of increased intraocular pressure. The diffuse iris melanoma produces a classic syndrome of acquired hyperchromic heterochromia and ipsilateral glaucoma. Iris melanoma invasion into the angle and secondary glaucoma are the two most important risk factors for metastases. In contrast to iris melanoma, ciliary body melanoma tends to attain a fairly large size prior to diagnosis. Ciliary body melanomas cause secondary glaucoma in 17% of cases and the mechanisms include anterior displacement of the iris with secondary angle closure or direct invasion of the trabecular meshwork. Less commonly, hyphema, necrosis, or iris neovascularization, are found as the cause of secondary glaucoma. Published studies show that only 2% of patients with choroidal melanoma have secondary glaucoma. When secondary glaucoma occurs due to a choroidal melanoma it is from iris and angle neovascularization (56%) or anterior displacement of the lens-iris diaphragm and secondary angle closure (44%). Large necrotic choroidal melanomas can occasionally produce intraocular inflammation or hemorrhage, which can further contribute to secondary glaucoma.
Others Other rare uveal tumors such as neurilemomas, leiomyomas, neurofibromas can produce secondary glaucoma by the same mechanisms.
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Metastatic tumors to the uvea Malignant tumors from distant primary sites metastasize via hematogenous routes to the uveal tract and rarely to the retina or optic nerve. Choroidal metastases only produce secondary glaucoma when they attain a large size, whereas iris and ciliary body metastases frequently produce secondary glaucoma because of their tendency to be friable and also involve the angle structures. In our series of patients with uveal metastases, secondary glaucoma was found in 64% of iris metastasis, 67% of ciliary body metastasis, and 2% of choroidal metastasis. Iris and ciliary body metastases usually produce secondary glaucoma by seeding into the anterior chamber angle and trabecular meshwork, mechanically blocking aqueous outflow. In some cases, a solid growth of tumor cells can assume a ring type infi ltration of the trabecular meshwork resulting in intractable glaucoma. Metastatic tumors to the choroid appear as single or multiple elevated or diffuse lesions often associated with a secondary nonrhegmatogenous retinal detachment. The most common mechanism of glaucoma with choroidal metastases is angle closure due to anterior displacement of the lens-iris diaphragm secondary to total retinal detachment. Neovascular glaucoma can occur in advanced cases with total retinal detachment.
Primary tumors of the retina Tumors of the sensory retina include retinoblastoma, vascular tumors, glial tumors, and others. Retinoblastoma, the most important retinal tumor, frequently produces secondary glaucoma. In rare instances, advanced retinal capillary hemangiomas can produce secondary glaucoma in association with a total retinal detachment. In our series of 248 patients with retinoblastoma, 17% of 303 affected eyes had secondary glaucoma. The secondary glaucoma was due to iris neovascularization in 72%, angle closure secondary to anterior displacement of the lens-iris diaphragm in 26%, and tumor seeding into the anterior chamber in 2%. In cases with iris neovascularization, secondary hyphema sometimes contributed to the mechanism of glaucoma. The presence of iris neovascularization and secondary glaucoma in an eye with retinoblastoma is a statistical risk for optic nerve invasion, choroidal invasion, and eventual metastases.
Tumors of the nonpigmented and pigmented epithelium Tumors of the nonpigmented epithelium of the ciliary body include medulloepithelioma, adenoma, and adenocarcinoma. The medulloepithelioma (previously called diktyoma) is an embryonic ciliary body tumor which becomes clinically apparent in the first few years of life. In two large series of medulloepithelioma, secondary glaucoma occurred in approximately 50% of cases. In these cases, glaucoma occurred secondary to iris neovascularization or from direct invasion of the anterior chamber angle structures by the tumor. In some instances, hyphema or cysts in the anterior chamber also contributed to obstruction of aqueous outflow. Acquired tumors of the nonpigmented ciliary epithelium are rare, slow growing benign or lowly malignant lesions and they rarely produce secondary glaucoma. Primary tumors of the pigmented epithelium (adenoma and adenocarcinoma) of the iris, ciliary body, and retina are rare. The mechanisms of glaucoma are the same as those of malignant melanoma.
Lymphoid tumors and leukemias
with retinoblastoma, cautious ocular and systemic care by an ocular oncologist and pediatric oncologist is warranted. For patients with leukemia and lymphoma, systemic evaluation by the oncologist is recommended. Ocular involvement with leukemia carries an extremely poor systemic prognosis. Retinovitreal lymphoma tends to be associated with central nervous system lymphoma while uveal lymphoma is associated with systemic lymphoma. For patients with phakomatoses, a multidisciplinary approach with neurologist, dermatologist, pediatrician, and ophthalmologist is recommended.
Differential diagnosis Systemic hamartomatoses (phakomatoses)
●
The classic phakomatoses include encephalofacial hemangiomatosis (Sturge–Weber syndrome) neurofibromatosis (von Recklinghausen’s syndrome), retinocerebellar capillary hemangiomatosis (von Hippel–Lindau syndrome) and tuberous sclerosis (Bourneville’s syndrome). The two which are more likely to be associated with either infantile or juvenile glaucoma include encephalofacial hemangiomatosis and neurofibromatosis.
●
COURSE/PROGNOSIS The course and prognosis of the patient depends on the primary tumor type, location, size, and other features. Glaucoma associated with iris melanoma is associated with a worse ocular and systemic prognosis compared to iris melanoma without glaucoma. Glaucoma associated with retinoblastoma is associated with a greater risk for optic nerve and choroidal invasion of the tumor, imparting a greater risk for metastatic disease.
DIAGNOSIS/LABORATORY FINDINGS Clinical ● ●
●
●
Examination may show an intraocular mass. Slit lamp biomicroscopy may reveal neovascularization of the iris. Gonioscopy may reveal angle invasion by tumor or angle vessels. Transillumination may show a ciliary body or choroidal shadow.
● ● ●
Uveitic glaucoma. Neovascular glaucoma from other causes. Hemolytic glaucoma. Iridocorneal endothelial syndrome. Endophthalmitis.
PROPHYLAXIS Treatment of the tumor at an early stage is a good measure to prevent glaucoma. However, some treatments, especially charged particle radiotherapy and plaque radiotherapy, can eventually lead to glaucoma.
TREATMENT Medical The management of glaucoma secondary to intraocular tumors should depend upon the type of tumor. In cases of benign tumors, it is often appropriate to first treat the glaucoma medically. In cases of malignant tumors, it may be appropriate to first treat the tumor in hopes of relieving the glaucoma. In cases of uveal melanoma, melanocytoma, metastasis, and lymphoid infi ltration, the glaucoma may resolve with the primary treatment of the tumor either by surgical resection, radiotherapy, or chemotherapy. If the glaucoma persists despite effective therapy, then medical management of the secondary glaucoma is warranted. Generally, antiglaucoma eyedrops and systemic carbonic anhydrase inhibitors are instituted as necessary.
CHAPTER 263 • Glaucoma Associated with Intraocular Tumors
Lymphoid tumors and leukemias can produce a similar infi ltration of the uveal tract and retina. The most important lymphoid tumors of the intraocular structures include benign reactive lymphoid hyperplasia (BRLH) of the uvea and malignant lymphoma, particularly large cell lymphoma (histiocytic lymphoma, reticulum cell sarcoma). Secondary glaucoma most often occurs from direct infi ltration of the anterior chamber angle and thickening of the iris and ciliary body by tumor cells. This results in blockage of aqueous outflow and secondary elevation of intraocular pressure.
Surgical Ocular tests ● ●
●
●
Ultrasonography may demonstrate an intraocular mass. Ultrasound biomicroscopy can show anterior chamber angle invasion or ciliary body tumor. Fluorescein angiography or indocyanine green angiography may demonstrate an intraocular mass or show iris neovascularization. Magnetic resonance imaging or computed tomography may reveal an intraocular mass with characteristics suggestive of a specific tumor type.
Systemic tests For patients with uveal melanoma, a complete physical examination, liver function tests, liver imaging test (ultrasound or magnetic resonance imaging), and chest x-ray is recommended and should be repeated on a six month basis by the patient’s oncologist. For patients with uveal metastases, a complete oncologic evaluation by the general oncologist is warranted. Breast cancer is the most common uveal metastasis. For patients
Most melanocytic iris tumors should be managed initially by periodic observation and any associated glaucoma should be managed medically. If the tumor shows evidence of growth or if the secondary glaucoma cannot be controlled, then surgical intervention should be considered. In cases of circumscribed tumors, excision of the tumor by a partial iridectomy or iridocyclectomy may improve the glaucoma but further medical treatment of the glaucoma may be necessary. Trabeculectomy should be avoided until all conservative methods, including argon laser trabeculoplasty and ciliary body destructive procedures are attempted. In the case of a diffuse iris melanoma with secondary glaucoma, enucleation is generally necessary. Fine needle aspiration biopsy is indicated to differentiate melanoma from melanocytoma or nevus. We have found that open biopsy of an iris tumor or filtering surgery to control glaucoma in cases of diffuse iris melanoma can predispose to extrascleral extension of the tumor. In the case of iris melanocytoma, the liberated pigment in the trabecular meshwork may gradually disappear following complete excision of the main tumor.
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SECTION 23 • Intraocular Pressure
Small ciliary body melanomas can be managed by periodic observation until growth is documented before initiating treatment. Somewhat larger tumors can be managed by local resection or episcleral plaque radiotherapy. Most tumors which are large or infi ltrative enough to produce secondary glaucoma are generally best managed by enucleation of the affected eye. Careful medical evaluation and follow-up is warranted because of the relatively high risk of metastatic disease in cases of ciliary body melanoma with secondary glaucoma. In our series of patients with ciliary body melanoma, 50% of patients with secondary glaucoma died from metastatic melanoma within two years of the diagnosis. The options in management of choroidal melanomas are well outlined in the literature and include serial observation, photocoagulation, transpupillary thermotherapy, radiotherapy, local resection, enucleation and even orbital exenteration. Unfortunately, choroidal melanomas that have produced secondary glaucoma are generally so large that enucleation is necessary. In some cases of uveal metastases associated with secondary glaucoma, the glaucoma may ultimately require laser or surgical trabeculectomy, cyclocryotherapy, retrobulbar alcohol injection, or even enucleation. Since most affected patients have a poor systemic prognosis, enucleation should be avoided if possible and the goal should be to make the patient comfortable. The management of retinoblastoma should depend upon the overall clinical findings and can include enucleation, chemotherapy, radiotherapy, cryotherapy, thermotherapy, and photocoagulation. In cases with secondary glaucoma, the tumor is usually quite advanced and enucleation is considered the treatment of choice. In most cases of retinoblastoma associated with secondary glaucoma, the optic disc cannot be visualized ophthalmoscopically because of the large tumor within the eye. Therefore, it is particularly important in these cases to obtain a long section of optic nerve stump along with the globe at the time of enucleation, since the most important route of extraocular extension of this tumor is through the optic nerve to the central nervous system. Management of small intraocular medulloepitheliomas consists of an attempt at local resection by a cyclectomy. Unfortunately, it is extremely difficult to completely remove such tumors and recurrence is common, eventually requiring enucleation. In cases with glaucoma, enucleation is usually necessary because of pain or suspected malignancy.
IRRADIATION AND CHEMOTHERAPY The management of iris and ciliary body metastases should be systemic chemotherapy or other management which the patient is receiving for the systemic cancer. If the ocular tumor continues to proliferate, then external beam radiotherapy to the eye, giving 3500–4000 cGy (Rad) to the affected eye in divided doses over a four week period should be initiated. If the uveal metastasis is the patient’s only active metastatic focus then local plaque radiotherapy is certainly justified. Plaque radiotherapy takes approximately 4 days and minimizes radiation to the uninvolved remainder of the eye and orbit. If any associated secondary glaucoma does not resolve following chemotherapy and radiotherapy, acetozolamide, timolol or other medications should be continued to control the intraocular pressure and to keep the patient comfortable. In many instances, the glaucoma will progress relentlessly and laser or fi ltering
488
surgery can be attempted. This decision should be made in light of the patient’s prognosis and enucleation should be avoided if the systemic prognosis is dismal. In some instances, enucleation is warranted for pain relief. The appropriate management of intraocular lymphoid tumors and leukemias is ocular radiotherapy combined with the chemotherapy that the patient may be receiving for the systemic disease. In the case of BRLH, about 2000 cGy (rad) is generally sufficient, whereas in the case of malignant lymphoma about 3000–4000 cGy may be necessary to bring about good resolution of the tumor. In some cases, the glaucoma resolves with the radiotherapy or chemotherapy, but in cases with severe glaucoma, this treatment may not help and enucleation of the eye, if it is blind and painful, may be necessary.
COMPLICATIONS A patient who presents unexplained unilateral glaucoma could be harboring an unsuspected intraocular malignant tumor. It is usually contraindicated to perform laser surgery or fi ltering procedures until a complete ophthalmologic examination including careful indirect ophthalmoscopy is performed to exclude the possibility of tumor. In cases where the posterior pole or ciliary body cannot be viewed because of opaque media, ultrasonography, transillumination or other procedures are necessary to rule out a tumor. It is particularly important not to perform glaucoma surgery or vitrectomy on a child with vitreous cells and unilateral glaucoma until the possibility of retinoblastoma is excluded.
COMMENTS Management of tumor-induced glaucoma usually consists of enucleation because most cases are due to advanced uveal melanoma or retinoblastoma. In cases of benign tumors, medical therapy can be attempted fi rst followed by laser or surgical therapy. It should be emphasized that the management of glaucoma secondary to iris tumors is a very difficult problem, because many such tumors are relatively benign histopathologically and all efforts are made to control the glaucoma by medical or laser treatment prior to surgical intervention. Trabeculectomy is controversial in the management of iris melanomas because of the possibility of tumor spread into the filtering bleb and episcleral tissues.
REFERENCES Char DH, Quivey JM, Castro J, et al: Helium ions versus iodine 125 brachytherapy in the management of uveal melanoma: a prospective randomized dynamically balanced trial. Ophthalmology 100:1547–1554, 1993. Girkin CA, Goldberg I, Mansberger SL, et al: Management of iris melanoma with secondary glaucoma. J Glaucoma 11:71–74, 2002. Shields CL, Materin MA, Shields JA, et al: Factors associated with elevated intraocular pressure in eyes with iris melanoma. Br J Ophthalmol 85:666–669, 2001. Shields CL, Shields JA, Gross N, et al: Survey of 520 eyes with uveal metastases. Ophthalmology 104:1265–1276, 1997. Shields CL, Shields JA, Shields MB, Augsburger JJ: Prevalence and mechanisms of secondary intraocular pressure elevation in eyes with intraocular tumors. Ophthalmology 94:839–846, 1987. Shields JA, Annesley WH, Spaeth GL: Necrotic melanocytoma of iris with secondary glaucoma. Am J Ophthalmol 84:826–829, 1977.
264 GLAUCOMATOCYCLITIC CRISIS 364.22 (Posner–Schlossman Syndrome) Abraham Schlossman, MD, FACS New York, New York
Glaucomatocyclitic crisis is unilateral glaucoma characterized by recurrent attacks of glaucoma that are usually associated with signs of mild cyclitis. The condition generally occurs in patients between 20 and 50 years old, with individual attacks of ocular hypertension lasting from a few hours to 1 month but very rarely more than 2 weeks. Multifactorial causes have been postulated for this syndrome; the condition has been reported in association with: ● Allergies; ● Herpes simplex virus infection (but not herpes zoster); ● Immunogenetic disorders; ● Stress-related disorders such as peptic ulcer; ● Primary vascular abnormality.
Ocular Treatment of the ocular hypertension should be limited to the attack and should consist of the use of mild miotics such as: ● Prostaglandin analogues; ● Ophthalmic beta blockers. Topical ocular corticosteroids (one to four times daily) are used to control inflammation and are especially helpful during the acute phase. Occasional pupillary dilation with: ● Phenylephrine 2.5% usually permits confi rmation that no synechiae are forming. Surgery is contraindicated; iridectomy and filtering operations do not prevent recurrences.
Supportive To control the patient’s pain and apprehension during attacks, analgesics, tranquilizers, or both may be helpful. Follow-up examinations are important to monitor pressure elevation and inflammation.
CHAPTER 264 • Glaucomatocyclitic Crisis
ETIOLOGY/INCIDENCE
TREATMENT
COMPLICATIONS The mean incidence and prevalence rates of the condition reported in one study were 0.4 and 1.9, respectively, in 100,000 population.
PROGNOSIS The prognosis is excellent with prompt treatment, with no permanent changes detectable in the visual fields after an attack.
Strong miotics, and perhaps strong mydriatics, are contraindicated in the treatment of glaucomatocyclitic crises because they tend to aggravate the symptoms by producing pain, congestion, and spasm of the ciliary muscle. In view of the ineffectiveness of surgical measures and the benign and self-limited nature of the disease, there exists no indication for any surgical intervention in this syndrome; medical therapy between attacks is not indicated. Topical corticosteroids give good results by allaying ciliary irritability; however, if such treatment is prolonged, steroidinduced glaucoma may occur.
DIAGNOSIS ● ●
● ● ●
●
●
● ●
● ● ●
Sudden onset. Mildly blurred vision, diminished visual acuity (temporary). Colored haloes around lights. Mild ocular discomfort. Unilateral; recurrences always in same eye (very rarely bilateral). Slight mydriasis (pupil of affected eye larger than that in the other eye and reactive). Intraocular pressure of affected eye between 40 and 60 mm Hg (fluctuates). Anterior chamber cells and minimal flare. Corneal epithelial edema, keratic precipitates (few, 25 or less; unpigmented); persist as long as 1 month after intraocular pressure has returned to normal. Ciliary flush. No posterior synechiae or iris atrophy. Rare glaucomatous cupping of optic nerve, after many attacks.
COMMENTS The value of recognizing this syndrome lies in the fact that surgical procedures not only are unnecessary but also are definitely contraindicated in this condition. Glaucomatocyclitic crises differ from acute narrow-angle glaucoma and glaucoma secondary to uveitis in that the angle of the anterior chamber is open, even at the height of an attack, and the eye is white with minimal pain during attacks. Also, facility of outflow is normal between attacks, and provocative tests give normal responses.
REFERENCES De Roetth A, Jr: Glaucomatocyclitic crisis. Am J Ophthalmol 69:370–371, 1970. Knox DL: Glaucomatocyclitic crises and systemic disease: Peptic ulcer, other gastrointestinal disorders, allergy and stress. Trans Am Ophthalmol Soc 86:473–495, 1988. Posner A, Schlossman A: Syndrome of unilateral attacks of glaucoma with cyclitic symptoms. Arch Ophthalmol 39:517–535, 1948. Posner A, Schlossman A: Further observations on the syndrome of glaucomatocyclitic crises. Trans Am Acad Ophthalmol Otolaryngol 57:531– 536, 1953.
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Yamamoto S, Pavan-Langston D, Tada R, et al: Possible role of herpes simplex virus in the origin of Posner-Schlossman syndrome. Am J Ophthalmol 119:796–798, 1995.
SECTION 23 • Intraocular Pressure
265 PRIMARY CONGENITAL GLAUCOMA 743.20 (Primary Infantile Glaucoma, Buphthalmos) Maria Papadopoulos MBBS, FRACO London, England Peng Tee Khaw PhD, FRCP, FRCS, FRCOphth, FIBiol, FRCPath, FMedSci London, England
FIGURE 265.1. Corneal clouding in pediatric glaucoma.
ETIOLOGY/INCIDENCE ●
Primary congenital glaucoma (PCG) is a rare condition characterized by isolated trabeculodysgenesis causing aqueous outflow obstruction. Developmental arrest of tissue in the anterior chamber angle leads to the characteristic appearance of an immature angle on gonioscopy. This is the most common cause of glaucoma in infancy. Most cases are idiopathic, but autosomal recessive inheritance with variable penetrance is reported in familial cases. GCL3A is the major locus for PCG, accounting for 85–90% of familial and 27% of sporadic cases. Mutations of the CYP1B1 gene, which encodes for enzyme cytochrome P4501B1, are the primary molecular defects in the majority of cases.
●
●
Corneal enlargement (megalocornea, congenital high myopia): PCG is distinguishable primarily by corneal signs (Haab’s striae) and elevated IOP with optic disc cupping. Corneal clouding (obstetric trauma, congenital corneal dystrophies, metabolic disorders, inflammatory / infectious diseases): The IOP, corneal diameters and optic disc are normal. Epiphora and photophobia (nasolacrimal duct obstruction): PCG is distinguishable by the absence of discharge with epiphora.
TREATMENT COURSE/PROGNOSIS It is a blinding condition if untreated or poorly treated. Visual prognosis depends on: ● Early diagnosis; ● Prompt surgical intervention for successful intraocular pressure (IOP) control; ● Correction of ametropia; ● Rigorous amblyopia treatment.
Medical ● ●
●
●
Medical therapy plays a temporizing role only. Preoperatively, pilocarpine 0.5–1% every 6–8 hours may lead to an improvement in symptoms, suggesting a favorable response to angle surgery. The beta blockers of choice are betaxolol, or timolol 0.1%. If necessary, oral acetazolamide should be cautiously administered in a dosage of 5–10mg/kg every six hours just prior to surgery.
DIAGNOSIS This condition occurs more frequently in male children and is typically bilateral. It usually manifests in the neonatal or infantile period (75%), retinal detachment (3%), endophthalmitis (
