Small Animal Ophthalmology: A Problem-Oriented Approach

We dedicate this book to our families, our pets, and our patients. For Elsevier: Commissioning Editor Joyce Rodenhuis D...

Author: Robert L. Peiffer Jr. DVM PhD DACVO | Simon M. Petersen-Jones DVetMed PhD DVOphthal DipECVO MRCVS

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We dedicate this book to our families, our pets, and our patients.

For Elsevier: Commissioning Editor Joyce Rodenhuis Development Editor Louisa Welch Project Manager Morven Dean/Jane Dingwall Designer Erik Bigland Illustration Manager Kirsteen Wright

© 2009, Elsevier Limited. All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, without either the prior permission of the publishers or a licence permitting restricted copying in the United Kingdom issued by the Copyright Licensing Agency, 90 Tottenham Court Road, London W1T 4LP. Permissions may be sought directly from Elsevier’s Health Sciences Rights Department in Philadelphia, USA: phone: (+1) 215 238 7869, fax: (+1) 215 238 2239, e-mail: [email protected]. You may also complete your request on-line via the Elsevier homepage (http://www.elsevier.com), by selecting ‘Customer Support’ and then ‘Obtaining Permissions’. First published 1989 Second edition 1996 Third edition 2001 Fourth edition 2009 ISBN: 978-0-7020-2861-8

British Library Cataloguing in Publication Data A catalogue record for this book is available from the British Library Library of Congress Cataloging in Publication Data A catalog record for this book is available from the Library of Congress Knowledge and best practice in this field are constantly changing. As new research and experience broaden our knowledge, changes in practice, treatment and drug therapy may become necessary or appropriate. Readers are advised to check the most current information provided (i) on procedures featured or (ii) by the manufacturer of each product to be administered, to verify the recommended dose or formula, the method and duration of administration, and contraindications. It is the responsibility of the practitioner, relying on their own experience and knowledge of the patient, to make diagnoses, to determine dosages and the best treatment for each individual patient, and to take all appropriate safety precautions. To the fullest extent of the law, neither the publisher nor the author assumes any liability for any injury and/or damage. The Publisher

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Contributors

Peter GC Bedford BVetMed PhD DVOphthal DipECVO FRCVS GBDA Professor of Canine Medicine and Surgery Royal Veterinary College Hatfield, UK Ellen Bjerkås DVM PhD DipECVO Professor Department of Companion Animal Clinical Sciences Norwegian School of Veterinary Sciences Oslo, Norway Cynthia S Cook DVM PhD DipACVO Veterinary Vision San Carlos, CA, USA Björn Ekesten DVM PhD Professor of Clinical Neurophysiology Department of Clinical Sciences Swedish University of Agricultural Sciences Uppsala, Sweden Bruce H Grahn DVM Diplomate ABVP ACVO Professor of Veterinary Ophthalmology Department of Small Animal Clinical Sciences Western College of Veterinary Medicine University of Saskatchewan Saskatoon, Saskatchewan, Canada R Gareth Jones BVSc CertVOphthal MRCVS The Park Veterinary Group Leicester, UK Olivier Jongh DMV Clinique Vétérinaire du Val de Saône Neuville sur Saône, France

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CONTRIBUTORS

Mary L Landis MS VMD Resident in Ophthalmology Bucks County Animal Ophthalmology Doylestown, PA, USA Sebastien Monclin DVM Resident of Ophthalmology University of Liège Belgium Domenico Multari DVM SCMPA PhD Centro Veterinario Oculisto ‘Fontane’ Treviso, Italy Kristina Narfström DVM PhD DipECVO Professor of Veterinary Ophthalmology Department of Veterinary Medicine & Surgery University of Missouri Columbia, MO, USA Robert L Peiffer Jr DVM PhD DipACVO Bucks County Animal Ophthalmology Doylestown, PA, USA Simon M Petersen-Jones DVetMed PhD DVOphthal DipECVO MRCVS Assistant Professor of Comparative Ophthalmology Department of Small Animal Clinical Sciences Veterinary Medical Center Michigan State University East Lansing, MI, USA Peter W Renwick MA VetMB DVOphthal MRCVS Willows Referral Service Shirley, Solihull, UK Serge G Rosolen DVM PhD Eye Veterinary Clinic Asnières, France Robin Stanley BVSc(Hons) FACVSc Animal Eye Care East Malvern, Victoria, Australia

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Wendy M Townsend DVM MS DipACVO Assistant Professor of Comparative Ophthalmology Small Animal Clinical Sciences Veterinary Teaching Hospital Michigan State University East Lansing, MI, USA

Mike Woods MVB CertVOphthal MRCVS Practice Principal & Ophthalmologist Primrose Hill Veterinary Hospital Dun Laoghaire, Co Dublin, Ireland

CONTRIBUTORS

Joe Wolfer DVM DipACVO Veterinary Ophthalmologist Animal Eye Clinic Toronto, Ontario, Canada

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Preface to First Edition

Ophthalmology has blossomed and matured as a recognized, valued specialty of veterinary medicine and surgery; ophthalmic exposure is generally emphasized in the professional curriculum; the competency and sophistication of the general practitioner is continually improving; and several excellent contemporary comprehensive textbooks are available on the subject. Then why this text? We have recognized a need by the general practitioner for an informative source that he or she can turn to as a guide to the management of a particular problem. Appropriate management implies two inseparable principles – accurate diagnosis and adequate therapy. We have attempted to address each with equal emphasis. We perceive a need by the student for a text that condenses a large amount of information into a ‘friendly’ manual that emphasizes problem solving rather than memorization and that provides more usable information than lecture notes without the depth of a reference text. We hope this manual meets these needs. Why these authors? The profession and the specialty are evolving and changing. Although I am somewhat reluctant to classify myself as ‘mature’ as a clinical ophthalmologist, I cannot help but be impressed by the energy, enthusiasm, and ideas of a younger generation of amazingly well-trained ophthalmologists. All of the contributors fit this mold, and I hope that they and their colleagues who follow will continue to probingly question the established as well as addressing unsolved problems. Experience is almost always tainted by dogmatism, which in turn can cloud truth; I have encouraged Drs Cook, Leon, Cottrell, and Petersen-Jones to express their ideas and philosophies without unwarranted respect for sacred cows. The product is exciting. We have attempted not to reproduce a comprehensive text but to produce a clinical manual; references are not included. As conditions may present with more than one presenting sign, there is some repetition; conditions are discussed in detail under their most obvious or significant sign. We have discussed in detail only those surgical procedures that are likely to be routinely performed by the practitioner, and details of these procedures are described with their pictorial presentation rather than in the text. Emphasis is placed on techniques that have proven to be most valuable and effective for the authors, and readers should recognize that there may indeed be quite acceptable alternative approaches to clinical problems. We do hope that this

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PREFACE TO FIRST EDITION

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handbook will prove a ready and valuable reference to the general practitioner presenting with a challenging ophthalmic case and when reviewed in its entirety will provide a practical overall approach to small animal ophthalmology. Bob Peiffer Chapel Hill 1989

Preface to Fourth Edition

When the first edition of Small Animal Ophthalmology: a Problem-Oriented Approach was published in 1989 I would not have foreseen struggling with the Preface to the Fourth Edition almost two decades later. The children have grown and moved away, and a German Shorthair and Redbone Coon Hound have been replaced by a pair of Labrador Retrievers. The cat, I suspect, is reincarnate of his predecessors, and the Pennsylvania winters are a bit longer and colder than those in the South. I have been fortunate to have Simon Petersen-Jones to share the labor from the second edition onward and both myself and the text have benefited from his diligence and insight. While the world has changed, the scope and intent of the text remain constant – to provide the student or general practitioner with a practical reference that condenses an ever-expanding base of knowledge in small animal ophthalmology into an affordable user-friendly clinical manual that emphasizes problem-solving in dealing with patients that present with ophthalmic signs. This was a novel approach at the time, and the fact that the book has been translated into Japanese, Spanish, and French, and oft mimicked since, speaks to its utility. We have maintained the theme of recruiting accomplished contributors who provide broad, contemporary, and international perspectives. All share a commitment to excellence in the management of their patients that is reflected in the quality of their work. As I compare their contributions to those in the first edition I realize that progress is made in small steps; successful management of canine glaucoma is still largely an exercise in frustration in spite of new potent drugs and the contemporary technologies of laser and implants. Treatment of tear film deficiencies still requires long-term management and a motivated and educated pet owner, although the lacrimostimulants have obviated the necessity of parotid duct transposition in many. Technologies and methodologies in imaging, cataract surgery, and retinal detachment repair have remarkably enhanced outcomes for many of our patients. The potential of molecular medicine beckons from a seemingly distant horizon. Practicing ophthalmology during these times has been an adventure and a privilege indeed. We are grateful for the competence and professionalism of the Elsevier staff who have provided encouragement, guidance, and the occasional nudge that

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PREFACE VERSO TO FOURTH RUNNING EDITION HEAD

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these projects seem to require. The opportunity to include a CD-Rom allows us to expand the visual impact of observation to formulate differential diagnoses. We will be content with our labors if readers emerge from their study more proficient in the management of their ophthalmic cases. Bob Peiffer Doylestown, Pennsylvania. 2008

I am delighted to join with Bob again to help edit another edition of Small Animal Ophthalmology: a Problem-Oriented Approach. I well remember over 20 years ago writing a chapter for the first edition. I was an ophthalmology resident visiting Dr Peiffer (as have many aspiring young ophthalmologists before and after me) when he asked if I would be interested to write a chapter for the book he was developing. I jumped at the opportunity, never suspecting that I would join Bob to edit the subsequent editions. Veterinary ophthalmology has a rapidly expanding knowledge base but the problem-oriented approach still works well. Our patients present to us with certain clinical signs that fall into the broad categories of the chapters in the book, rather than with a diagnosis of, for example, retinal detachment or distichiasis. It is our job to identify the clinical signs and through a systematic and thorough eye examination reach a diagnosis. The aim of the book is to help practitioners achieve this goal. In this latest edition we have added a CD-Rom that allows for case presentations – we hope that this will be useful and educational for our readers. Simon Petersen-Jones East Lansing, Michigan. 2008

Clinical basic science Cynthia S. Cook, Robert L. Peiffer, Jr and Mary L. Landis

OCULAR EMBRYOLOGY

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The ocular primordia appear during the first weeks of gestation as bilateral evaginations of the neural ectoderm of the forebrain. These optic sulci gradually enlarge and approach the surface ectoderm as optic vesicles connected to the forebrain by the optic stalks. Thickening of the overlying surface ectoderm to form the lens placode (Fig. 1.1A,B) occurs as a result of inductive influences by the optic vesicle. Invagination of the lens placode occurs concurrently with that of the optic vesicle to form a hollow lens vesicle within a bilayered optic cup (Fig. 1.1C,D), the inner layer of which will form the stratified layers of the neural retina and the inner epithelial layer of the iris and ciliary body; the outer layer becomes the cuboidal monolayered retinal pigment epithelium, the outer pigmented epithelial layer of the iris and ciliary body, and, in the dog and cat, the pupillary sphincter and dilator muscles (the only muscles in the body of neural ectodermal origin). The potential space between the two apposed layers becomes formed and fluid-filled in retinal detachment and uveal cysts. The stalk attaching the lens vesicle to the surface ectoderm atrophies through a combination of cell death and active migration of cells out of the stalk (Fig. 1.1E,F). Invagination to form the optic cup occurs eccentrically, with formation of a slit-like opening called the optic (choroid) fissure located inferiorly (Fig. 1.1F). The vascular supply to the embryonic eye, the hyaloid artery (or primary vitreous), enters the optic cup through this opening and arborizes extensively around the lens to form the tunica vasculosa lentis. Embryonic remnants of this vascular structure may persist as insignificant posterior capsular opacities (including Mittendorf’s dot, located inferior to the suture junction), persistent tunica vasculosa lentis, or, more significant clinically, persistent hyperplastic primary vitreous (PHPV). The term persistent embryonic vasculature, or PEV, encompasses the entire spectrum. Failure of the optic fissure to close normally may result in congenital defects anteriorly (iridial coloboma) or posteriorly (chorioretinal or optic nerve coloboma). Microphthalmos or anophthalmos may occur as a result of deficiencies in the early formation of the optic sulcus or vesicle, or from incomplete closure of the optic fissure with failure to establish early intraocular pressure (Fig. 1.2).

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SMALL ANIMAL OPHTHALMOLOGY

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A

B

C

D

E

F

The posterior lens epithelial cells elongate, forming primary lens fibers that obliterate the space within the lens vesicle. Secondary lens fibers are formed by elongation of cells at the equator (lens bow); these fibers pass circumferentially around the embryonal lens nucleus. Note that the sutures are associated only with the fetal and adult lens fibers. This marvellous differentiaton of the young posterior epithelial cells accounts for the unchanging 3–6 μm thick posterior capsule (the bane of the cataract surgeon) compared to the more robust anterior capsule, which progressively thickens with age as basement membrane produced by the lens epithelial cells accumulates. Thickening of the future neural retina occurs with segregation into inner and outer neuroblastic layers. Cellular proliferation takes place in the outer neuroblastic layer, with migration to form the inner layer. The ganglion cells are the first to achieve final differentiation, extending axons that form the nerve fiber layer and collectively form the optic nerve. The horizontal, amacrine, and

Fig. 1.2 Microphthalmia in a merle Australian Shepherd pup. This genetic syndrome (merle ocular dysgenesis) occurs in dogs with a predominantly white coat color. Microphthalmia occurs through multiple mechanisms including hypoplasia of the optic vesicle.

CLINICAL BASIC SCIENCE

Fig. 1.1 Sequential development of ocular structures. These scanning electron micrographs are of mouse embryos on days 10 and 11 of gestation, corresponding to days 17–24 of gestation in the dog. The sequence in most mammals is quite similar. (A) On external examination the invaginating lens placode can be seen (arrow). Note its position relative to the maxillary (Mx) and mandibular (Mn) prominences of the first visceral arch. (B) Embryo of the same age as that in (A). Frontal fracture through the lens placode (arrow) illustrates the associated thickening of the surface ectoderm (E). Mesenchyme (M) of neural crest origin is present adjacent to the lens placode. The distal portion of the optic vesicle concurrently thickens as the precursor of the neural retina (NR), while the proximal optic vesicle becomes a shorter, cuboidal layer which is the anlage of the retinal pigment epithelium (PE). The cavity of the optic vesicle (V) becomes progressively smaller. (C) The epithelium of the lens placode continues to invaginate (L). There is an abrupt transition between the thicker epithelium of the placode and the adjacent surface ectoderm, which is not unlike the transition between the future neural retina (NR) and the future pigmented epithelium (PE) (periodic acid–Schiff). (D) As the lens vesicle enlarges, the external opening, or lens pore (arrow), becomes progressively smaller. The lens epithelial cells at the posterior pole of the lens elongate to form the primary lens fibers (L). NR = anlage of the neural retina; PE = anlage of the pigmented epithelium (now a very short cuboidal layer) (magnification ×221). (E) External view of the lens pore (arrowhead) and its relationship to the maxillary prominence (Mx). (F) Frontal fracture reveals the optic fissure (*) where the two sides of the invaginating optic cup meet. This forms an opening in the cup allowing access to the hyaloid artery (H), which ramifies around the invaginating lens vesicle (L). The former cavity of the optic vesicle is obliterated except in the marginal sinus (S), at the transition between the neural retina (NR) and the pigmented epithelium. E = surface ectoderm. Arrowhead = stalk of separating lens vesicle. (Reprinted with permission from Vet. Comp. Ophthalmol. (1995) 5: 109–123.)

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Müller cells also differentiate in the inner neuroblastic layer. The bipolar cells and photoreceptors develop in the outer neuroblastic layer and form the inner and outer nuclear layers in the adult. Retinal dysplasia may result from disorganized development of the neural retina, with formation of rosettes. The retinal pigment epithelium is the determining factor for the differentiation of the layers on each side, namely the retina and the choroid and sclera. Following detachment of the lens vesicle from the surface ectoderm, development of the anterior chamber structures progresses. A specialized population of the neural ectoderm called the neural crest cells migrate between the surface ectoderm and lens vesicle to form the corneal endothelium, which secretes its basement membrane, Descemet’s membrane. Additional neural crest cells form the corneal stroma between the surface epithelium and endothelium. The pupillary membrane and anterior iris stroma develop from neural crest cells migrating onto the anterior surface of the optic cup; persistence or dysplasia of the pupillary membrane results in uveal attachments between the iris and lens and/or cornea (Figs 1.3 & 1.4). Neural crest cells also form the outer two coats of the posterior globe, the choroid (including the tapetum) and sclera.

OCULAR ANATOMY, PHYSIOLOGY, AND BIOCHEMISTRY Orbit The orbit in the cat and dog is formed by contributions of the frontal, palatine, lacrimal, maxillary, zygomatic, and presphenoid bones. The bony orbit is incomplete superotemporally, where it is bridged by the dense orbital ligament spanning the frontal process of the zygomatic bone and the zygomatic process of the frontal bone. The lacrimal gland lies superiorly, under this orbital ligament. The orbital contents are covered by a connective tissue layer, the periorbita, which is firmly attached to the orbital margins rostrally. Seven extraocular muscles innervated by the third, fourth, and sixth cranial nerves

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Fig. 1.3 Peter’s anomaly in a cat. Note the persistent pupillary membranes attached to the anterior lens capsule with associated anterior subcapsular opacity.

A C D


B

Fig. 1.4 Schematic of components of Peter’s anomaly (anterior segment dysgenesis) which result from incomplete or delayed separation of the lens vesicle from the surface ectoderm. (A) Persistent pupillary membranes; (B) corneal opacity with absence of endothelium and Descemet’s membrane; (C) iris hypoplasia; (D) anterior lenticonus and anterior polar cataract associated with anterior capsular defects. (Courtesy of Farid Mogannam.)

control movement of the globe. There is a variable amount of fat between the periorbita and the bony wall and surrounding the extraocular muscles. The zygomatic salivary gland is located inferotemporally, deep to the zygomatic arch, and may be a site of infection or mucocele formation. The wall of the bony orbital wall is thinner medially and may allow extension of infectious or neoplastic processes originating in the nasal cavity or periorbital sinuses. Infectious processes involving the roots of the molar teeth may also extend to involve the orbit. Space-occupying orbital lesions include both inflammatory and neoplastic etiologies. Due to the incomplete nature of the bony orbit, both inferiorly and superotemporally, a space-occupying process may become quite advanced before exophthalmos and/or deviation of the globe is noted. Diagnosis and management of such conditions are discussed in subsequent chapters.

Eyelids The eyelids form the initial barrier to mechanical damage to the eye. They also serve to distribute the tear film and, through the meibomian glands, provide an oily secretion to slow tear evaporation. The eyelids consist of: 1. An outer layer of thin, pliable skin 2. A small amount of loose connective tissue containing modified sweat glands and the circumferential fibers of the orbicularis oculi muscle (innervated by branches of the facial nerve) 3. The more rigid fibrous connective tissue of the tarsal plate 4. The radial fibers of the levator palpebrae superioris (innervated by the oculomotor nerve) and Müller’s (sympathetic innervation via branches of the trigeminal nerve) muscles 5. The palpebral conjunctiva containing goblet cells.

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Cilia are found on the margin of the upper lid; posterior to these follicles are the openings of the sebaceous (meibomian) glands; these gland orifices are found along the eyelid margin (Figs 1.5 & 1.6). Dysplasia or metaplasia of these glands results in formation of aberrant hair follicles (distichia or ectopic cilia), which may contact the cornea and result in epiphora and, rarely, keratitis. Surgical manipulations of the eyelids require delicate handling to minimize swelling and careful apposition of surgical or traumatic wound margins. Particular attention should be paid to maintenance of a smooth eyelid margin. Closure of full-thickness defects should utilize a two-layer pattern; the tarsal plate has the greatest strength and should be included in the subcutaneous layer.

Lacrimal system The precorneal tear film consists of three distinct layers: 1. A mucous layer located closest to the cornea and produced by the conjunctival goblet cells 2. A thick aqueous layer 3. An outer oily layer produced by the meibomian glands of the eyelids. The aqueous portion of the tear film is the combined product of the orbital lacrimal gland and a gland located at the base of the third eyelid. The major lacrimal gland is located in the superotemporal area of the orbit beneath the orbital ligament and supraorbital process of the frontal bone; its secretions gain access to the conjunctival sac from numerous small ducts in the superior fornix. The tears are distributed over the surface of the cornea through the action of the eyelids and exit through the nasolacrimal puncta. These two openings are located nasally, superior, and inferior to the medial canthus, just inside the eyelid margin (see Fig. 1.5). The puncta open into two canaliculi joining to form the nasolacrimal duct, which passes through a bony canal in the maxilla to open ventrolaterally in the nasal cavity.

Pupil Dorsal (superior) punctum Medial (nasal) canthus Ventral (inferior) punctum Third eyelid

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Cilium Limbus Lateral (temporal) canthus Conjunctiva

Iris

Fig. 1.5 External appearance of the canine eye depicting the adnexal structures. With the exception of the pupillary shape, the feline eye is identical.


Orbicularis oculi m.

Levator palpebrae superioris m.

Palpebral conjunctiva

Müller’s m. Fornix

Bulbar conjunctiva Tarsal plate Gland of Zeis and Moll

Zonules

Cilium A

Retinal vessels

Meibomian gland

Tapetum Lens

Pupil Optic nerve

Anterior chamber Iris

Myelinated fibers

Iridocorneal angle Ciliary body

Optic disk

B

A Stroma

Endothelium

Epithelium

Descemet’s membrane

B Nerve fiber layer Ganglion cell layer Inner plexiform layer Inner nuclei layer Outer plexiform layer Outer nuclei layer Rods and cones Pigment epithelium Choroid Sclera Fig. 1.6

Inner limiting membrane Ganglion cell Ganglion cell axons forming optic nerve Bipolar cell Outer limiting membrane Nuclei of photoreceptors

Schematic anatomy of the canine and feline eye.

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Conjunctiva and third eyelid The conjunctiva is a mucous membrane that covers the globe between the fornix and the cornea, the third eyelid, and the inner surface of the eyelids (see Fig. 1.6). Over the surface of the globe, the conjunctiva blends with Tenon’s capsule, which attaches firmly to the limbus. The conjunctiva is a highly vascular, delicate tissue containing many mucus-secreting goblet cells. The vascularity and mobility of the conjunctiva can be used to the surgeon’s advantage to act as a graft for corneal defects. The stroma is rich in lymphatics and the conjunctiva is a site of localization of lymphocytes, and provides a reservoir of immunocompetent cells for the globe, playing an important role in the inflammatory responses of the avascular cornea. The third eyelid is a mobile, semi-rigid structure located inferonasal to the globe (see Fig. 1.5). It is covered on both palpebral and bulbar surfaces by conjunctiva. The third eyelid owes its rigidity to a T-shaped piece of hyaline cartilage located within its substantia propria. At the base of the cartilage is a seromucoid lacrimal gland that produces approximately one third of the precorneal tear film. Poorly defined connective tissue attaches the gland and base of the cartilage to the sclera and periorbita inferiorly. Inadequacy of these attachments with prolapse of the gland occurs not uncommonly, particularly in the American Cocker Spaniel and English Bulldog breeds. Removal of the gland in such cases is contraindicated as it may predispose to future development of keratoconjunctivitis sicca; the gland should be repositioned and fixated as described in Chapter 4 (pp. 88–90).

Cornea

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The cornea is the transparent, avascular, anterior portion of the outer fibrous coat of the eye (see Fig. 1.6A). The cornea consists of surface epithelium, collagenous stroma, and Descemet’s membrane, which is the basement membrane produced by the inner endothelial monolayer. As the cornea is avascular, its oxygen and nutritional needs are met by diffusion externally from the precorneal tear film and internally from the aqueous humor; the peripheral cornea is also oxygenated by the limbal capillary plexus. Corneal transparency is a product of several factors unique to corneal physiology. Relative dehydration of the cornea is maintained by an active Na+-K+ ATPase-associated pump mechanism within the endothelial monolayer. The regular arrangement of the collagen fibrils in the corneal stroma minimizes scattered light and thus enhances transparency. The normal absence of pigment and blood vessels in the stroma is also a requirement for optical transparency. The cornea has remarkable healing capabilities. Simple epithelial defects are covered by a combination of sliding of adjacent cells and mitosis to restore normal architecture. Wounds that extend into the stroma heal first by reepithelialization, with a longer period of time required to fill the stromal defect. Corneal scarring is a result of the irregular pattern created by replacement collagen fibrils. Vascularization is expected to accompany any corneal injury or inflammatory condition that persists longer than 7–10 days and contributes to the granulation tissue that initially fills a deep corneal wound. Descemet’s membrane is elastic and tends to resist tearing during an injury. Wounds extending to Descemet’s membrane (descemetocele) and full-thickness lacerations are indications for immediate surgical management. Some regen-

Iris and ciliary body The iris and ciliary body comprise the anterior portion of the middle, vascular coat of the eye, called the uvea (see Fig. 1.6). The iris creates a pupillary opening of variable diameter to adjust the quantity of light that is able to pass through the lens to reach the photosensitive retina. This variable aperture is maintained by the sympathetically supplied radial dilator muscle and the parasympathetically supplied circumferential sphincter muscle. Both muscles are located on the posterior side of the iris, adjacent to the pigmented epithelial layer. The iris anterior to these muscles consists of a loose, vascular connective tissue that is variably pigmented. Full-thickness corneal wounds often seal with prolapsed iris tissue, which must be replaced into the anterior chamber (if viable) or excised. Surgical manipulations of the iris are frequently accompanied by hemorrhage that may complicate postoperative healing. The ciliary body is the posterior continuation of the iris and consists of an anterior portion called the pars plicata (with the ciliary processes) and a posterior portion called the pars plana. The ciliary body is lined by a bilayered epithelium of which only the inner layer is pigmented. Aqueous humor is produced by the ciliary epithelium through a combination of passive ultrafiltration and active secretion involving carbonic anhydrase. The passive production of aqueous humor is influenced by mean arterial blood pressure. Inflammation of the anterior uvea will result in reduced active aqueous secretion and thus lowered intraocular pressure. The stroma of the ciliary body contains the smooth fibers of the parasympathetically innervated ciliary muscle, which is important in accommodation of the lens for near vision. Aqueous humor circulates from the ciliary processes into the posterior chamber of the eye, through the pupil, to exit via the trabecular meshwork within the iridocorneal angle. During this process, metabolites are exchanged with the avascular lens and cornea. Morphologic or physiologic barriers to aqueous circulation and outflow are responsible for elevations in intraocular pressure (glaucoma).


erative properties are attributed to the canine endothelium, fewer to the feline.

Lens The lens is a transparent, biconvex structure anchored equatorially to the ciliary body by collagenous zonular fibers (see Fig. 1.6). Contraction of the ciliary muscle alters the degree of curvature of the lens, thereby changing its optical power. The lens is surrounded by an outer capsule; deep to the anterior portion of the capsule is a monolayer of cuboidal epithelium. These epithelial cells are metabolically active and undergo mitosis throughout life. As the cells multiply they migrate to the equator of the lens where they elongate and gradually lose their nucleus and other organelles to form the lens fibers. These fibers are added in a circumferential arrangement so that older fibers are within the deeper portion of the lens. The fiber ends meet anteriorly at the upright Y suture and posteriorly at the inverted Y suture. The anterior epithelial cells utilize glucose, which diffuses into the lens from the circulating aqueous humor and is broken down anaerobically to lactic acid.

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Saturation of the normal pathways for glucose metabolism occurs in diabetes mellitus and results in accumulation of sorbitol within the lens. Sorbitol accumulation causes the lens to imbibe water by osmosis, which leads to the formation of a clinically observable cataract that usually progresses rapidly.

Retina The retina (see Fig. 1.6) is a complex photosensory structure consisting of ten layers: 1. 2. 3. 4. 5. 6. 7. 8. 9. 10.

Pigment epithelium Photoreceptors (rod and cone outer segments) External limiting membrane (Müller cell processes) Outer nuclear layer (photoreceptor nuclei) Outer plexiform layer Inner nuclear layer (nuclei of Müller; amacrine, horizontal, and bipolar cells) Inner plexiform layer Ganglion cell layer Nerve fiber layer (axons of ganglion cells) Inner limiting membrane (Müller cell processes).

The principal neuronal connections of the retina involve the photoreceptors, which synapse with the bipolar cells that then synapse with the ganglion cells in the inner plexiform layer. The axons of the ganglion cells form the nerve fiber layer and join to make up the optic nerve at the posterior pole. The amacrine and horizontal cells form internal connections between bipolar cells and may thus exert a regulatory influence. Müller cells are a non-neuronal constituent that forms a supporting matrix and the barriers of the inner and outer limiting membranes. Inherited retinal degenerative processes and sudden acquired retinal degeneration (SARD) initially involve the photoreceptors, either rods or cones, or both. With time the condition usually progresses to involve the other retinal layers, and diffuse thinning and blindness results.

Tapetum The tapetum is a modification of the choroid located deep to the pigment epithelium and choriocapillaris. It is composed of a highly organized arrangement of cells containing zinc and riboflavin, which results in a reflective appearance. The color of the tapetum ranges from green to blue to yellow and varies with the species, breed, and age. Thinning of the overlying retina (as occurs in retinal degeneration) results in a hyper-reflective appearance of the tapetum.

Optic nerve and central visual pathways

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The optic nerve consists of combined axons of the ganglion cells and is surrounded by all three meningeal layers of the central nervous system. The optic disk is the origin of the optic nerve within the globe; its irregular triangular appearance in the dog is a result of the variable quantity of myelin surrounding the nerve fibers of the optic disk (see Fig. 1.6). The optic nerve exits the orbit at the optic foramen. The right and left optic nerves meet at the optic chiasm, located rostral to the pituitary gland. In cats and dogs, the majority (65–75%)

Visual fields:

L

R

L


of nerve fibers cross in the chiasm to travel as the optic tracts to the contralateral lateral geniculate nucleus. This decussation is responsible for coordinated bilateral vision as well as the occurrence of a consensual pupillary light reflex (Fig. 1.7). The majority of axons in the optic tracts terminate in the lateral geniculate nucleus, synapsing on neurons whose axons form the optic radiations and terminate in the occipital cortex. This pathway is responsible for conscious visual perception. The remaining optic tract axons bypass the lateral geniculate nucleus and terminate in the rostral colliculus of the pretectal area. Parasympathetic axons originating here synapse in the oculomotor nucleus of the midbrain, origin of the oculomotor nerves, whose axons synapse in the ciliary ganglion prior to entering the globe as the short ciliary nerves to the pupillary sphincter muscles. This pathway is responsible for the direct and consensual pupillary light responses. The cat has two short ciliary nerves whereas the dog has several.

R Constrictor

Retina

Dilator Optic nn.

Ciliary ganglion Optic tract Oculomotor nerve Lateral geniculate nucleus

Chiasm Forebrain

Midbrain Oculomotor nucleus

Cervical spinal cord

Optic tract

Middle ear

Cranial cervical ganglion

Cervical sympathetic trunk

Thoracic spinal cord T1–T3

Fig. 1.7

Pupillary reflex pathways.

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Sympathetic control of the pupillary dilator muscle originates in the hypothalamus, the axons from which synapse with preganglionic neurons in the first three or four segments of the thoracic spinal cord. These axons join the sympathetic trunk terminating in the cranial cervical ganglion. Postganglionic fibers travel to the eye after crossing the roof of the middle ear cavity and are distributed to the ciliary muscle, pupillary dilator, third eyelid, and the Müller’s muscle of the upper lid. Compromise of sympathetic innervation to the globe and adnexa results in the classic signs of Horner’s syndrome: ptosis (drooping of the upper lid), miosis (pupillary constriction), and protrusion of the third eyelid.

OCULAR PATHOLOGY The systematic examination of surgical and necropsy-obtained ocular tissue is essential for optimal patient management, the career-long educational process, and enhancing understanding of ocular disease in animals. Maximal benefit is obtained from optimally fixed tissues; in almost all cases, immersion fixation in 10% formalin is adequate. Fixation should be expedient as the retina, especially, undergoes rapid autolysis; trimming of periocular tissues enhances penetration of fixatives, and injection of 0.5 ml of the fixative into the vitreous cavity with a 27-gauge needle at the equator will minimize neurosensory retinal separation artifact. Otherwise, submit globes intact so that the pathologist can appreciate the intertissue relationships. Use adequate volumes of fixative (at least 100 ml for dog and cat eyes), and allow 72 h for fixation to occur.

Ocular response to disease A detailed discussion of ocular pathology would fill a text of its own; principles and concepts of importance to clinicians are discussed with particular disease processes throughout the following chapters. Three related features warrant note: 1. The propensity of the ocular tissues (especially the epithelium of lens, uvea, and retina, but also the corneal endothelium and uveal vasculature) to undergo reactive changes of hypertrophy, hyperplasia, and metaplasia (in the case of feline ocular sarcomas, perhaps neoplasia as well) 2. In contrast to the above, the fact that many of the specialized ocular tissues are post-mitotic, with limited regenerative potential 3. Because of the dependence of the ocular tissues on tissue transparency and intertissue relationships for normal function, the devastating effect that these changes can have on vision. A focus of hepatitis may resolve with scarring and minimal, if any, functional significance, while a comparable process in the eye may lead to blindness.

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Fibroplasia in the cornea, for example, will result in scarring and opacification. In the anterior chamber, peripheral anterior and posterior synechia and membranes are associated with secondary glaucoma. Iris neovascularization, also known as rubeosis irides or pre-iridal fibrovascular membrane, is a common cause of intraocular hemorrhage and secondary angle closure glaucoma.


Hypertrophy, hyperplasia, and metaplasia of lens epithelium are an integral part of cataractogenesis, and the bane of the cataract surgeon who has to deal with postoperative capsular fibrosis. Vitreous detachment, fibrosis, and neovascularization lead to cyclitic membranes and their dire consequences of retinal detachment and phthisis bulbi. The clinical ophthalmologist wages a relentless pharmacologic battle against these processes with anti-inflammatories and antimetabolites, and new approaches will likely play an important role in the future management of ocular disease.

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Diagnostics Serge G. Rosolen, Domenico Multari, Mike Woods and Olivier Jongh

INTRODUCTION

2

The ophthalmic examination, combined with history and signalment, provides the foundation for obtaining an accurate diagnosis. Ophthalmic diagnosis is achieved by a combination of basic knowledge, the mastering of simple instrumentation, and critical observation. The former includes an understanding of anatomy, physiology, and disease mechanisms. Instrumentation facilitates critical observation. Basic equipment and simple techniques, including a magnifying loupe, bright focal illumination, Schirmer tear test strips, diagnostic dyes, cytology, direct ophthalmoscopy, and Schiøtz tonometry should be readily available in any practice, and in experienced hands will be adequate to manage the great majority of ophthalmic cases. More expensive and sophisticated instrumentation and technologies, including the slit-lamp biomicroscope, indirect ophthalmoscope, applanation tonometry, electrophysiology, gonioscopy, ultrasonography, and other imaging modalities, fluorescein angiography, keratoscopy, and retinoscopy represent the next level of diagnostics and are available to specialists or to those with a particular interest in the field. A systematic approach to examination should be followed and modified for each individual case based upon the history and signs. Technical competency in diagnostics is achieved simply by practice; making an ophthalmic examination a part of every routine physical examination will hone skills for the occasion upon which they are more urgently required.

INSTRUMENTS AND BASIC DIAGNOSTIC TECHNIQUES Magnifying loupe A binocular magnifying loupe of ×2 to ×4 magnification and a focal length of 15–25 cm is useful not only for diagnostics but also for surgery; it allows freedom of both hands for manipulation and a loupe-mounted diffuse illuminator facilitates observation.

Focal illumination 14

A transilluminator provides an excellent light source for external eye examination and to evaluate the pupillary light reflexes (PLRs). For the latter, it is

Schirmer tear test (STT)

DIAGNOSTICS

important to use a narrow beam of bright light with a constant source of energy (such as a rechargeable handle) directed toward the posterior pole. One of the most common causes of abnormal PLRs is a dim light source.

This test is used quantitatively to evaluate the aqueous component of the tear film and thus aid in the diagnosis of keratoconjunctivitis sicca (KCS). The STT is indicated in all patients with external ocular disease. Individually wrapped sterile filter paper test strips may be dye impregnated to facilitate reading; these strips are typically 5 mm wide and 50 mm in length. If performing a STT, it should be undertaken before any other procedures or tests; if there is discharge in or around the eye, dry cotton swabs should be used gently to clean the area, avoiding irritation and reflex lacrimation. The strips have a notch near one end where they are folded prior to use; fold the strip without touching it with fingers while it is still in the overwrap. Then open the package and, grasping the strip from the end opposite the notch with fingers or forceps, place it into the lower conjunctival sac approximately midway between the medial and lateral canthus with the short folded end in the fornix and the notch on the eyelid margin (Fig. 2.1). The lower lid can be rolled outward with the thumb to facilitate insertion, but care should be applied not to compress the eye, which may likewise elicit reflex lacrimation. The lids may be maintained in an open position, or closed by gentle pressure on the upper lid if blinking and retention of the strip becomes a problem. After 1 min, the moistened distance from the notch in the longer part is measured. Normal values in the dog are 15–25 mm/min; values lower than 10 mm/min are suggestive of a deficit in aqueous tear production. Most clinical cases of KCS have a wetting of less than 5 mm; cats have slightly lower and more variable normal values. There is a wide range of normal readings, and results should be interpreted in association with clinical signs. Increased aqueous tear production may occur if conditions causing ocular irritation are present.

Fig. 2.1

Schirmer tear test being performed in a feline patient.

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Diagnostic stains Fluorescein stain Fluorescein is a water-soluble dye; owing to its lipid insolubility, it does not penetrate intact corneal epithelium. Epithelial erosions or ulcers, which expose the hydrophilic stroma, allow penetration and retention of the dye. The barrier to penetration in the healthy eye resides in the outermost cells of the corneal epithelium. As Descemet’s membrane does not retain fluorescein, descemetoceles will not stain. Fluorescein is available as impregnated paper strips or as a solution; the solution may become contaminated with multiple usage, and individually wrapped strips are preferred. Fluorescein staining is indicated in all patients with ocular pain or observable corneal lesions. The tip of the fluorescein-impregnated strip is moistened with a drop of sterile saline and gently applied to the superior bulbar conjunctiva. If the patient exhibits severe blepharospasm, local anesthetic can be instilled but may result in a mild diffuse positivity that is usually readily discernible from significant retention. Blinking will distribute the dye over the corneal surface. The excess dye is immediately flushed with a sterile saline rinse and the eye is then examined with a focal light and magnification (Fig. 2.2). A cobalt blue filter will facilitate detection of subtle lesions. To evaluate nasolacrimal patency, apply the fluorescein as described above, but do not rinse the eye. If the ipsilateral nostril shows dye within 5 to 10 min, the nasolacrimal drainage system on that side is patent; the absence of dye passage, however, does not necessarily mean the contrary, and negative passage is followed by cannulation and irrigation. Dye may be seen in the nasopharynx related to alternative duct openings. Biomicroscopic observation of the fluorescein-stained tear film while holding the lids open enables evaluation of the tear break-up time (BUT) as an indirect method of evaluating the non-aqueous components of the tear film; mucus deficiency will result in shortening of the BUT from the 20–30 s normally encountered.

Rose bengal and lissamine green These dyes stain cells of the cornea and conjunctiva that are not covered by mucin; usually these are degenerating cells. The stains are taken up by neoplastic cells as well and may be useful in defining the extent of epithelial neo-

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Fig. 2.2 Fluorescein uptake by the corneal stroma associated with a boxer ulcer.

DIAGNOSTICS

plasia of the cornea and conjunctiva. The dyes are available as solutions or impregnated strips; as with fluorescein, the latter are preferred. Rose bengal may cause irritation upon instillation and persists somewhat longer than fluorescein. It is useful in highlighting dendritic intraepithelial erosions caused by herpesvirus, which may be difficult to detect with fluorescein, and in the diagnosis of tear film abnormalities involving the lipid or mucin components of the tear film (Fig. 2.3). Application techniques are identical to those described for fluorescein.

Cytology, culture, and additional diagnostic procedures Cytologic examination is increasingly utilized in small animal ophthalmology; over the last decades, it has emerged as a reliable tool in facilitating diagnosis in a minimally invasive way. Techniques of sampling of a smear are outlined for each of the ocular structures. On the other hand, the microscopic interpretation of a smear is beyond the scope of this chapter. Routine dermatologic techniques can be utilized to obtain scrapings from the eyelid skin for parasitic and fungal detection. Fine needle aspiration may prove useful for characterizing proliferative lesions (by using a 23-G needle and a 5 ml syringe). Impression smears can be obtained from ulcerated lesions (Figs 2.4 & 2.5), notably in cats with suspected squamous cell carcinoma. If necessary, biopsy of skin lesions is performed to evaluate tissue architecture with histopathology. Conjunctival cytologic evaluation is useful: 1. In the differential diagnosis of acute conjunctivitis (the cellular response associated with specific conjunctivitis is helpful when performed early in inflamed conjunctivas, and Gram stain can provide guidelines for antibiotic selection) 2. In the identification of inclusion bodies (chlamydial, mycoplasma, canine distemper, and leishmania inclusions) 3. To facilitate the diagnosis of conjunctival tumors including lymphosarcoma, mast cell tumor, melanoma, and squamous cell carcinoma.

Fig. 2.3 Rose bengal positivity in a punctate pattern was evident in this 6-year-old Shih Tzu with a vascularized cornea due to keratoconjunctivitis sicca.

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SMALL ANIMAL OPHTHALMOLOGY Fig. 2.4 A middle-aged mixed breed presented with ulcerated lesions of both eyelids.

Fig. 2.5 Impression smears obtained from these ulcerated lesions revealed a neoplastic population formed by lymphoid cells (Giemsa, original magnification ×400). Mycosis fungoides was confirmed with partial-thickness biopsy of the eyelid lesions.

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Cells from the conjunctival surface may be harvested using a sterilized spatula (i.e. Kimura spatula), the blunt end of a sterile surgical blade, or a small nylon cytology brush; moist sterile cotton swabs are less likely to capture as many cells. Sterile swabs may be utilized for culture of potentially pathogenic microorganisms (bacterial and fungal), and a cytology brush is preferred for the detection of the presence of herpesvirus, calicivirus, or Chlamydia (Chlamydophila) by polymerase chain reaction (PCR). Unfixed and unstained slides may be submitted for immunofluorescent antibody (IFA) studies. The scraping should be made from the area most severely involved. A topical anesthetic may not be necessary in most cases if the animal’s head is firmly restrained, but greatly facilitates the procedure and is unlikely to affect culture results. Mucus and exudate are removed prior to scraping. It requires gentle but firm manipulation to collect an adequate sample (the conjunctiva should blanch but should not bleed). Collected cells are immediately transferred to a glass microscope slide; gentle spreading will avoid fracturing nuclear

Fig. 2.6 Aspiration of aqueous humor with a 25-G hypodermic needle in a cat.

DIAGNOSTICS

membranes. The material is air dried and fixed and can be stained with the routine stains of value such as Giemsa, Gram, or Wright’s. Corneal cytology is often a rewarding diagnostic method for characterization of exudative lesions (keratomalacia, keratomycosis) and may aid in the differentiation of proliferative lesions (eosinophilic keratitis or nodular episclerokeratitis). Topical anesthesia is usually applied prior to obtaining the sample. Care must be taken not to rupture deep ulcers with pressure. Special stains for fungi (periodic acid–Schiff) may be useful. Cells can also be harvested by using a cellulose strip that is gently applied on the corneal surface (‘impression cytology’). Aspiration of aqueous humor may be undertaken with topical or general anesthesia, with a 25–27-G hypodermic needle, inserted just anterior to the limbus, bevel up and parallel to the iris surface (Fig. 2.6). Approximately 0.1–0.2 ml of fluid can be collected and is generally safe; remove the barrel from the tuberculin syringe and allow the fluid to collect by pressure differential rather than aspiration. Centrifugal cytology (‘cytospin’) is particularly well suited for the preparation of small sample volumes and dilute cell suspensions. Aqueous humor cytology may allow distinction between nongranulomatous and granulomatous uveitis, and protein-laden macrophages are encountered with phacolytic or phacoclastic uveitis. Lymphosarcoma and feline melanoma cells may exfoliate into the aqueous; if cells are seen with the biomicroscope, aqueocentesis with cytology may confirm the diagnosis. Aqueous humor samples can also be collected for culture, PCR, and antibody level determination. Tumors of the anterior uvea are candidates for trans-corneal fine needle aspiration, best performed by those familiar with the technique. Aspiration is accomplished as described above for aqueous humor as a microsurgical procedure with the needle positioned over the tumor and an attempt made to aspirate surface cells. Alternatively the needle may be directed into the tumor. Technical challenges include obtaining an adequate sample and interpretation may be problematic. Potential complications of hemorrhage, lens trauma, and tumor seeding temper the decision to pursue this modality.

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Cytology of vitreous or sub-retinal fluid is indicated for both diagnostic and therapeutic reasons, the former where other diagnostic options have been exhausted, the latter for intravitreal pharmacologic cycloablation or in the management of retinal detachments by pneumatic retinopexy. The procedure is performed transsclerally, usually with general anesthesia and a 25-G needle. For vitreous aspiration, the needle penetrates the eye 5–6 mm posterior to the limbus (entering through the pars plana but avoiding the lens) and is directed toward the posterior pole; a volume of 0.5 ml liquefied vitreous can be aspirated. For withdrawal of subretinal fluid, the needle is gently introduced through the sclera overlying the bullous retinal detachment. Assessment of orbital disorders using fine needle (23 or 24 G) aspiration remains a reliable method that can facilitate diagnosis for the clinician, provided that localization of the lesion allows for accurate sampling. Exophthalmos results from a space-occupying lesion in the orbit (benign or malignant neoplasm, orbital inflammation, cystic disease). Palpation, imaging, and the direction of globe displacement may be used to determine the site of the orbital lesion. Ultrasound guidance provides optimal assurance of a representative sample. Several routes for fine needle aspiration biopsy are available, dependent upon location: through the eyelids, conjunctiva, the mucosa caudal to the last upper molar, or, in the case of posterior orbital lesions, transdermally at the posterior junction of the orbital ligament and zygomatic arch (Fig. 2.7).

Fig. 2.7 Fine needle aspiration biopsy through the mucosa caudal to the last upper molar in a dog.

To evaluate the structure and function of the lacrimal puncta, lacrimal canaliculi, lacrimal sac, and nasolacrimal duct, topical anesthesia, sedation, or general anesthesia may be required in dogs, dependent on the nature of the patient. In cats, general anesthesia is usually required; the lacrimal puncta are smaller and less accessible. A curved stainless steel lacrimal cannula may be utilized; 22–23 G works well in dogs, 26 G in cats. Its rigidity allows the operator easily to identify and enter the opening of the nasolacrimal duct in the lacrimal bone after having entered the lower punctum and nasolacrimal sac. The disadvantage of a rigid cannula is that of possible damage to the mucous membranes if the animal is not adequately restrained and anesthetized, or if the procedure is not performed gently; alternatively a Teflon intravenous catheter works almost as well. The cannula should be mounted on a 2.5–3.0 ml syringe filled with sterile saline, or a small saline-filled compressible bottle. The cannula is inserted into the upper punctum, located 4–5 mm from the medial canthus, stretching the upper lid superiorly with the index finger to immobilize and straighten the canaliculus and facilitate cannula penetration. After the lacrimal punctum is entered, the system is flushed; saline will exit from the lower punctum. Smooth movements are then used to pass through the lacrimal sac and locate and enter the opening of the nasolacrimal duct. At this point, the lower punctum is closed with finger pressure on the adjacent lid. The nasolacrimal duct is flushed and keeping the nose of the animal angled downward, the fluid should flow from the ipsilateral nostril. Cannulation with monofilament nylon suture can be used to localize and attempt to dislodge obstructions. Radiographs can be helpful in diagnosing nasolacrimal cysts or obstructions occurring secondary to sinus disorders. Contrast media may be injected through the upper puncta (dacryocystorhinography) to localize obstructive lesions.

DIAGNOSTICS

Evaluation of the lacrimal drainage system

Direct ophthalmoscopy The ophthalmoscope has a light source which is directed into the patient’s eye so that the beam is nearly parallel with the line of sight of the examiner. A rheostat controls the light intensity while the dimension and the characteristics of the beam may be varied with a series of colored filters (blue to excite fluorescein, green to help differentiate pigment from retinal hemorrhage), a slit (to help evaluate the elevation of lesions), and a grid (to project onto the fundus in order to measure lesions). A selection of lenses ranging from + (black) 40 D to – (red) 25 D (diopters) is assembled on a rotating wheel which adjusts the depth of focus into the eye (Table 2.1). Thorough examination of the fundus of the eye can be performed only in a dark room through a well-dilated pupil; 1–2 drops of 1% tropicamide should be applied 15–20 min prior to examination. Observation with a setting of around 0 to +1 or +2 D and the instrument held 30–60 cm from the eye allows critical evaluation of the fundus reflex. The fundus is then observed from a distance of 2–5 cm and starting with a setting of 0, altered to achieve optimal focus. Direct ophthalmoscopy provides magnification of fundic features by 14 to 15 times. The disk is located and evaluated initially, the major vessels are traced to the periphery, and each quadrant is evaluated systematically to obtain a mental panorama. The main disadvantages of direct compared with indirect

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examination are the small field of vision, limited to about 4–5 mm of the fundus, and the risks due to the close proximity to the muzzle of uncooperative patients! There are notable intra- and inter-species differences in the ophthalmoscopic anatomy of the fundus including color and extent of the tapetum, intensity of retinal pigment epithelium (RPE) pigment in the non-tapetum, degree of myelination of the optic disk, location of the disk in relation to the tapetal/nontapetal junction, and vascular patterns (Fig. 2.8).

Hand lens monocular indirect ophthalmoscopy The most economical way to perform indirect ophthalmoscopy is by using a 14–30 D hand-held lens and a focal light source such as the Finoff transillumiTable 2.1 Ophthalmoscope settings for examination of normal canine eyes.

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Structure

Ophthalmoscope settings (diopters)

Cornea

+15 to +20

Iris

+12 to +15

Anterior capsule of lens

+12 to +15

Posterior capsule of lens

+8 to +12

Vitreous

+2 to +8

Optic disk and fundus

+2 to −2

A

Fig. 2.8 Variations in normal fundus appearance. (A) The fundus of a sandcoated retriever with a richly myelinated optic disk.

DIAGNOSTICS

B

C

Fig. 2.8 Variations in normal fundus appearance. (B) An Australian Shepherd fundus: the tapetum is aplastic, which allows visualization of the underlying choroidal vessels and sclera. (C) This Siamese cat fundus exemplifies the non-myelinated optic disk characteristic of felines. There is absence of pigment in the non-tapetal retinal pigment epithelium and choroid to reveal the radial choroidal vasculature.

nator. Relatively inexpensive glass Nikon or Volk lenses or even less inexpensive +10 to +20 magnifying lenses, 30–55 mm in diameter, can be utilized. After dilatation of the pupil and in a dark room, the observer should stand in front of the animal at arm’s length, holding the transilluminator in front of the observer’s own nose and the lens 5–6 cm in front of the patient’s cornea (an assistant is required to restrain the patient’s head and retract the lids). The fundus image is made to fill the entire lens by moving the lens toward or away from the cornea.

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Indentation tonometry Tonometry is the assessment of intraocular pressure (IOP). Digital tonometry is a very crude technique; two-finger ballottement of the globe through the upper lids can detect a discrepancy between the two eyes, but should not be used without additional objective measurement. Instrumental tonometry may be performed by indentation or applanation methods. Indentation tonometry is based on the measurement of the extent of indentation of the cornea obtained with a Schiøtz tonometer. It is a relatively inexpensive instrument which consists of a plunger that glides through a cylindrical chamber stabilized by a bracket handle, and a footplate that conforms with and is placed on the anesthetized corneal surface. The plunger can be charged with different weights (5.5 g, 7.5 g, 10.0 g). The depth of indentation is reflected by movement of a lever, which allows a scale reading to be converted to an estimation of IOP. Theoretically, the curvature and rigidity of the human cornea differ from those of the small animal cornea, so species-specific conversion tables are required for optimal quantitative accuracy; practically, indentation tonometry only estimates IOP and it is not critical whether the table with human data that comes with the instrument or a veterinary scale is used. Normal values should be less than 25 mmHg. As a rule of thumb, with the 5.5 g weight, scale values between 3 and 7 on the Schiøtz scale represent normal pressure in the dog; normal values in the cat are 2–6. Readings of less than 2–3 suggest an elevated IOP and those greater than 7 a hypotensive eye. Size of the eye (smaller eyes give values higher than actual IOP), age-related differences in scleral rigidity (young eyes are more elastic and give higher values as well), and corneal lesions (edematous corneas will indent more, scarred corneas less) can affect accuracy of results. Before each patient evaluation, the instrument should be calibrated on the convex steel test block; the indicator should read 0. The patient is given a few drops of topical anesthetic and the instrument is applied to the eye. Because the plunger is gravity driven, it is essential that the tonometer be held as close to perpendicular as possible and that its components are well cleaned and free moving. The footplate is applied to the cornea, positioning the head of the dog by elevating the nose toward the ceiling. It is important not to occlude the jugular veins in order not to artifactually increase the IOP, or to compress the globe while retracting the eyelids, for the same reason. Occasionally it is easier to restrain the dog on its back, with the head held perpendicular to the body axis with the cornea in the horizontal plane. The measurement should be repeated several times in order to obtain three readings within 1–2 scale units of each other. The instrument should be placed as centrally as possible on the corneal surface, as the sclera has a different rigidity. The curved surface of the footplate should be in perfect and complete contact with the cornea. No force should be applied on the handle, which should be held gently to allow the instrument to rest freely on the corneal surface. Readings should be regarded as estimations of IOP rather than precise determinations. The main disadvantage is that the technique is demanding and requires practice to master. Suggestions for reliable use include: • Calibrate the tonometer before each use • Ensure that the cornea is well anesthetized; most systemic anesthetics and sedatives alter blood pressure and thus IOP, and are ideally avoided

DIAGNOSTICS

• Do not compress the jugular veins or the globe • Keep the cornea horizontal, the tonometer vertical and in the center of the cornea; avoid the limbus and the sclera as well as the third eyelid (you can slip the footplate beneath the third eyelid if it protrudes) • Make several measurements (3–5) • Always evaluate both eyes • Interpret readings in conjunction with other clinical signs • After each use, disassemble and clean the instrument • Make tonometry a part of your routine physical/ophthalmic examination to build confidence in your technique.

ADVANCED DIAGNOSTICS To appreciate fully the anatomic details and pathologic changes of the eye, special examination techniques and more sophisticated equipment may be necessary to refine preliminary observation and pursue differential diagnoses.

Slit-lamp biomicroscope The slit-lamp biomicroscope allows definition and precise localization of lesions within the adnexa, cornea, anterior chamber, lens, anterior vitreous and, using an interposed biconvex lens, the posterior segment. These structures can be examined with high magnification; the beam of light can be controlled to appear diffuse, pinpoint (to detect subtle flare and cells), or a slit, and may be colored by inserting various filters. Observations of reflected and/or transmitted light provide a magnified three-dimensional view of the various ocular structures.

Indirect ophthalmoscope The monocular hand lens method, already described, can be replaced by a more sophisticated and expensive instrument, the binocular indirect ophthalmoscope, which emits a bright light from a unit on the examiner’s head that is directed into the eye of the animal; the emergent rays are converged by a 14– 30 D biconvex condensing lens placed in the same fashion as described for monocular indirect ophthalmoscopy. The image is inverted and magnified less than with direct ophthalmoscopy, dependent upon the dioptric power of the lens utilized. The indirect ophthalmoscope has three major advantages: both hands can be used to manipulate the patient’s head and eyelids while the examiner is at arm’s length from the animal; it is possible to obtain a panoramic (although inverted) view of the ocular fundus; and bright illumination can penetrate translucent ocular media. The technique is easily mastered with practice.

Applanation tonometry In contrast to Schiøtz indentation tonometry, applanation tonometry enables measurement of the variable force necessary to flatten a constant small area of the cornea. The ‘Tono Pen’® and the ‘Tono Vet’® are hand-held tonometers with several advantages over the Schiøtz tonometer, but are much more expensive. Readings are not as subject to the influences of rigidity and other tissue characteristics as with indentation tonometry although readings are sensitive

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to artifacts induced by manual lid retraction, which yields spuriously high measurements.With the ‘Tono Pen’®, the stainless probe contains a solid-state strain gauge which converts intraocular pressure to an electrical signal. Every touch on the anesthetized cornea produces a waveform that is translated into a number on the digital display indicating the IOP expressed in mmHg. Every four valid readings the device sounds a prolonged beep and the mean IOP is displayed. The tip of the instrument has to be covered with a disposable latex protective membrane to ensure sterility and prevent exposure to the preocular fluids. The device is light and fits comfortably in the user’s hand and can be used regardless of the position of the animal’s cornea, so minimal restraint is needed.

Gonioscopy The iridocorneal angle and outflow pathways are not directly visible without using a refractory lens placed on the corneal surface. In most cases, gonioscopy can be performed with topical anesthesia. Many different lenses are used in small animal ophthalmology, with the Franklin, Barkan, and Koeppe lenses the most popular direct goniolenses; an indirect (mirror) lens facilitates 360° examination simply by rotation of the lens. The interface between lens and cornea is maintained with saline or 1.0% methylcellulose solutions. A coaxial light source and some magnification are needed for optimal observation (the biomicroscope is ideal); an otoscope can be satisfactorily used. The technique is indicated to evaluate glaucoma patients; when the glaucoma is unilateral, the presence of goniodysgenesis in the contralateral eye is an important risk factor, as well as suggesting the pathogenesis of the glaucoma in the involved eye. Cross-sectional and gonioscopic anatomy of the outflow pathway is depicted in Figure 2.9. Parameters of interpretation are summarized in Table 2.2.

Retinoscopy Retinoscopy, also called skiascopy, is a technique by which the refractive state of the eye can be determined objectively by observing characteristic light reflections that are created by illuminating the retina with a band or circular beam of light emitted from the retinoscope. The nature of these reflexes and how they are influenced both by the properties of incoming light and by refractive lenses placed between the eye and the retinoscope indicates the refractive power of the eye. This technique has been used to define the normal, pathologic, and surgically induced refractive state of the eye in dogs. It is necessary to provide basic definitions of refractive properties of the eye and refraction.

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• Emmetropia is an eye without refractive error where the plus power of the cornea and lens refracts light to a point source on the plane of the retina. • Ametropia is an eye with a refractive error, generally from variations in axial length of the eye, astigmatism, or a shift in position or absence of the crystalline lens. • Myopia is ametropia due to relatively excessive refractive power, generally due to a longer than normal axial length; images are formed in front of the plane of the retina.

DIAGNOSTICS

A

c svp pl

tm

cc

i

cbol

cbil

B

a b c d

e

f

g

a. Corneal dome b. Superficial band of pigment zone – varies in density c. Deep band of pigment zone d. Individual fibers of the pectinate ligament e. Ciliary cleft (space of Fontana) containing the uveal trabecular meshwork f. Iris g. Pupil

Fig. 2.9 Anatomy of the outflow pathways is depicted schematically in cross-section in (A) and gonioscopically in (B). The normal gonioscopic appearance of the canine (C) and feline (D) outflow pathway is shown. Key for (A): c: cornea; i: iris; pl: pectinate ligment; cc: ciliary cleft containing uveal trabecular meshwork; cbil: inner leaflet of ciliary body; cbol: outer leaflet of ciliary body; tm: scleral trabecular meshwork; svp: scleral venous plexus. (Courtesy of R.L. Peiffer.)

• Hyperopia is a refractive error caused by relatively inadequate refractive power, generally due to a shorter than normal axial length; images are formed behind the plane of the retina. • Astigmatism is an eye with aspherical ametropia caused when the refractive surfaces of the eye have different radii of curvature in different meridians, generally caused by differences in corneal curvature, such that an eye has two focal points. • A meridian is an imaginary line on the surface of a spherical body; a corneal meridian is a line formed by the intersection with the corneal surface of an anteroposterior plane passing through the apex of the cornea and can be horizontal or vertical.

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SMALL ANIMAL OPHTHALMOLOGY C

D

Fig. 2.9 For caption see previous.

• Refraction is the bending of light rays; minus lenses (concave) diverge light rays and plus lenses (convex) converge light rays. • Diopters are a measure of lens power, defined by the inverse of the focal length in meters. • Optical infinity is any distance greater than 6 m.

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A retinoscope is characterized by a light projection system and an examiner observation system. The projection system has a bulb that projects a linear band or streak of light into the patient’s eye. The observation system is an aperture that allows the examiner to view emergent light rays from the eye. When performing retinoscopy, refracting lenses from a trial lens may be used;

Scheme for classification of gonioscopic observations.

Iridocorneal angle • Open (approximately 2 mm)

DIAGNOSTICS

Table 2.2

• Narrow • Closed (pectinate ligament, ciliary cleft, inner and outer pigment zones not visible with iris root in contact with peripheral cornea) Pectinate ligament • Normal • Goniodysgenesis (pectinate fibers shortened/thickened to imperforate; flow holes reduced in number and size; anterior insertion displaced axially) Ciliary cleft and trabecular meshwork • Normal • Compressed • Collapsed (iris root apposed to inner pigment zone; pectinate ligament not visible) • Obstructed (with inflammatory or neoplastic infiltrates)

veterinary patients are generally refracted with a skiascopy bar or rack, which contains a series of spherical plus and minus lenses in increments of 0.5 D to 1.0 D. The optimal distance to perform retinoscopy is 66 cm between the patient’s and observer’s eyes; at this distance it is necessary to use a (+)1.5 D working lens to optimize neutralization of the emergent light rays. Emerging light rays reflecting from an illuminated retina leave an emmetropic eye as parallel rays, from a myopic eye as converging rays with a reflex moving opposite to or against the motion of the streak, and from a hyperopic eye as diverging rays with a reflex moving with the motion of the streak. Some reports have documented a tendency for the canine population mean toward a slight hyperopia, especially for large breeds, while other reports suggest a tendency toward slight myopia, especially for small- and medium-size dogs.1,2

Computerized topography of the cornea (keratoscopy) This examination of the curvature of the corneal surface involves projecting onto it concentric rings of light (Placido’s rings), the reflected image of which is analyzed by a computer which measures the distance between these rings. Optical measurement of corneal curvature is termed keratometry. The results are reported in millimeters or diopters; for the dog eye mean corneal curvature in diopters is 39.94 ± 2.61; mean radius of curvature in mm is 8.46 ± 0.55.3 Mean curvature for large breed dogs is less than that for dogs of medium size or small breeds, indicating a flatter cornea in larger dogs. This technique allows evaluation of astigmatism and is requisite for refractive procedures on the cornea.3

29


Specular microscopy The specular microscope allows in vivo observation of the corneal endothelium; endothelial cells of the dog and cat form a regular monolayered mosaic of hexagonal cells at a normal density of about 2000 cells/mm2 (Fig. 2.10).4,5

Ultrasonography Ocular ultrasonography in two-dimensional B-mode with a 10 MHz probe is ideal but very adequate studies can be performed with a 7.5 MHz probe, which is generally more readily available to practitioners (Fig. 2.11A). The technique

Fig. 2.10 Specular microscopic appearance of the normal canine corneal endothelium demonstrates a monolayer of regular hexagonal cells.

A

30

Fig. 2.11 Ultrasonography. (A) Normal eye (7.5 MHz probe). (B) Pathology. I Exophthalmos/orbital abscess/cellulitis (10 MHz probe). II Orbital abscess/cellulitis (7.5 MHz probe) (Courtesy of Dr A. Bertoldi.)

DIAGNOSTICS

BI

BII Fig. 2.11 For caption see opposite.

31

SMALL ANIMAL OPHTHALMOLOGY CI

CII Fig. 2.11 Ultrasonography. (C) Persian cat, iris melanoma: the iris is completely pigmented, irregular, and thicker than normal (20 MHz probe).

32

provides the ability to image the inner structures of the eye if alterations (corneal edema, intraocular hemorrhage, cataract) of the normally transparent tissues prevent direct intraocular observation. It also allows an evaluation of the soft and bony tissues of the orbit, making it of particular value in cases of exophthalmos (Fig. 2.11B). Suspected intraocular disease in the presence of opaque media, uveal neoplasia, orbital diseases, and retinal detachment are the major indications for ultrasonography (Fig. 2.11C,D,E). One-dimensional (A-mode) ultrasonography can be used to determine biometric parameters of corneal thickness, anterior chamber depth, lens thickness, and axial length

DIAGNOSTICS

(20.43 ± 0.48 mm), which are useful in the study of the physiologic optics of the eye (Fig. 2.11F). Most dogs and cats tolerate ultrasound examination very well with only topical anesthesia (e.g. proparacaine hydrochloride 0.05%); in some uncooperative patients sedation is necessary. Recently, very high frequency ultrasound with probes ranging from 20 MHz to 60 MHz has enabled images of very high detail and resolution to be obtained (Fig. 2.11G).

Radiology Radiology is used in small animal ophthalmology as a preliminary for other imaging techniques (ultrasound, CT scan, MRI), which generally provide more sensitive information. Orbital bone, sinus, and skull evaluation are the main indications. Dacryocystorhinography allows evaluation of the nasolacrimal duct.

Computed tomography (CT) A CT scan is recommended when critical evaluation of the orbit is required. Detailed imaging of the orbital contents, including globe, extraocular muscles, and optic nerve, as well as the adjacent bony skull and sinuses, is invaluable in the diagnosis and localization of orbital neoplastic, inflammatory, or traumatic disease.

Magnetic resonance imaging (MRI) This technology magnetizes and determines the concentration of protons in tissues and offers enhanced projection and resolution of soft tissues compared with a CT scan. It is of particular value in neurophthalmology.

Electroretinography (ERG) and visual evoked response (VER) (Fig. 2.12) The ERG records the total response of the retina to a short light stimulus by measuring the difference in potential between the retina and cornea through surface electrodes at the cornea and the lateral canthus. The VER simultaneously records the activity of the visual cortex and reflects the integrity of the entire afferent visual pathway. Two major waves characterize the ERG: 1. The initial negative a-wave reflects the activity of the photoreceptors (rods and cones) 2. The following b-wave reflects the activity of the Müller cells/ON bipolar cells complex. Other minor waves are elicited, depending upon the conditions of stimulation and recording. The oscillatory potentials (OPs) are a component of the b-wave that reflect the activity of the amacrine cells in the inner nuclear layer. The i-wave,6 a positive deflection following the b-wave, likely reflects the activity of ganglion cell and/or optic nerve activity. Furthermore, in specific experimental conditions, in addition to the a-, b-, and i-waves, there is a slower second positive deflection, the c-wave, which is more prolonged and probably arises from the RPE. ERG must be conducted under general anesthesia and care must be taken in electrode positioning to avoid third eyelid protrusion.7 ERG protocols can be designed to evaluate the individual photoreceptor populations (rods or

33

SMALL ANIMAL OPHTHALMOLOGY DI

DII

34

Fig. 2.11 Ultrasonography. (D) Mixed breed dog, iris melanoma: the iris is pigmented, irregular, and thicker than normal (20 MHz probe).

cones) by manipulating the parameters of stimulus and patient status in regard to dark or light adaptation, stimulus spectral composition, stimulus intensity, and stimulus frequency.8 Patterned stimuli can be projected onto the retina to assess ganglion cell activity or localized retinal activity (multifocal ERG) if prior refraction has been performed and corrected. This ensures that the stimulus is projected onto the retina.9 Waveforms are evaluated by amplitude and temporal relationship to the stimulus; anesthesia may affect both of these parameters. The electro-oculogram (EOG) measures the standing potential of the RPE and to date has not proven to be of great value in veterinary ophthalmology because verbal cooperation of the patient is not possible with animals! Record-

DIAGNOSTICS

E Fig. 2.11 Ultrasonography. (E) Dog: retinal detachment and vitreous hemorrhage are visible (10 MHz probe).

F Fig. 2.11 Ultrasonography. (F) Normal biometry using a 10 MHz probe.

ing of ERGs during dark adaptation can provide insights into functional alterations of the RPE. The VER is in essence a localized electroencephalogram (EEG) that utilizes active scalp electrodes placed over the occipital lobe and signal averaging to evaluate the conduction of impulses from the ganglion cells of the retina to the visual cortex along the optic nerve, optic chiasm, optic tract, lateral geniculate body, and the optic radiation. Flash or pattern stimuli (evoked in the same conditions that were previously described for ERGs) can be used to differentiate between peripheral (retinal) and central processes that cause visual dysfunction. It is important to note that the amplitude of the VER signal ranges from 5 to 10 microvolts while the amplitude of the ERG signal is generally greater than 100 microvolts. The VER responses are challenging to record and results may be difficult to interpret.

35

SMALL ANIMAL OPHTHALMOLOGY G Fig. 2.11 Ultrasonography. (G) Dog: glaucoma, goniodysplasia (GD). Note increased contact of the iris with the anterior lens capsule (35–50 MHz probe). (Courtesy of Dr J. Sapienza.)

Electrophysiology is indicated when critical assessment of the retinal components and pathways is required and may be a more sensitive indicator of retinal health than ophthalmoscopy. Differentiation between peripheral and more central causes of visual impairment may also be accomplished. ERG is useful in the detection of inherited retinal degenerations, to evaluate retinal function in the presence of opaque media that precludes critical direct evaluation, and to study drug effects on retinal function.

Fluorescein angiography (Fig. 2.13) The ocular vascular system and the integrity of the blood–ocular barriers can be observed by direct ophthalmoscopy using an exciting wavelength of light (blue) and the appropriate barrier filters (yellow) following the intravenous injection of fluorescein dye (0.1 ml/kg of a 10% solution). The technique is useful to evaluate neovascular or inflammatory changes. Serial photography provides the ability to observe sequentially the choroidal and retinal arteriovenous filling. Hypofluorescence can result from a masking defect (hemorrhage, exudate, or pigment) or a filling defect (vascular occlusion). Hyperfluorescence can develop because of a window defect of the tapetum or RPE, or result from incompetency of the blood–ocular barriers due to inflammation or neovascularization.10 Scanning laser ophthalmoscopy (SLO) 36

This contemporary technology utilizes illumination with two laser beams (red and argon) which facilitate detailed and dynamic image recording of the fundus;

B

M

R

H

C

As

G

Am

Conduction (VEPs)

Post-receptoral (ERG)

Receptoral (ERG)

Pre-receptoral (EOG: basal membrane)

a

OP2

OP3

b OP4

i

Fig. 2.12 Electroretinography. (A) On left, retinal histologic section; on right, retinal functional aspect. Electroretinogram (ERG) reflects the activity of photoreceptors (a-wave) and the bipolar cell/Müller cell complex (b-wave). Visual evoked cortical potentials (VEPs) reflect the activity of the visual pathways from the ganglion cells to the primary visual cortex.

A

Nerve fiber layer

Ganglion cell layer

Inner plexiform layer

Inner nuclear layer

Outer plexiform layer

Photoreceptor cell bodies

Photoreceptor outer segments

Retinal pigment epithelium

DIAGNOSTICS

37


α : a-wave implicit time

Flash onset

Amplitude (microvolts)

OP3 200

OP4

b

β : b-wave implicit time γ : Photopic Negative Response

OP2

100 0

i

a α

0

β

Bandpass 0.1-70 Hz Baseline

γ

50 Time (milliseconds)

100

B Fig. 2.12 Electroretinography. (B) The parameters and measurements of the flash ERG in diurnal species. The first negative deflection following the flash onset (flash onset is represented by the red arrow) is the a-wave. It corresponds to the hyperpolarization of the photoreceptors due to the closing of the sodium channels. This negative deflection is followed by a positive wave known as the b-wave (corresponding to the activity of the bipolar and Müller cells). Oscillatory potentials (OPs) are found on the ascending limb of the b-wave; the exact origin of these OPs remains unclear and their number can vary between one and three depending on the intensity of the stimulation used. Approximately 20 milliseconds later, a second positive wave appears which is known as the i-wave (corresponding to the function of the ganglion cells and/or of the prechiasmatic optic nerve). Each wave is characterized by amplitude (in microvolts), peak latency, and implicit time, calculated from the flash onset. The amplitude of the a-wave is calculated from the baseline to the peak of the a-wave, whereas the b-wave is calculated from the peak of the a-wave to the positive peak of the b-wave. The distance that separates the baseline from the negative peak of the b-wave is known as the photopic negative response. It corresponds to the response of ganglion cells and to the parts of their axons that are still unmyelinated.

it can be performed through a small pupil or when media opacities obscure ophthalmoscopic detail. Digital image analysis is utilized to study vascular, inflammatory, or degenerative disorders of the retina and optic nerve.11

Ocular coherence tomography (Fig. 2.14) Ocular coherence tomography (OCT) is a contemporary high-resolution (10 μm) non-invasive imaging technique12 that produces cross-sectional images without the use of any radiation or contact. The precision of images obtained by this device is ‘histologic’. This technique is useful to evaluate the junction of the vitreous and the retina and to characterize intraretinal changes.

EXAMINATION OF THE EYE 38

The first step in ophthalmic diagnosis is to collect a thorough history; while doing this, the animal should be observed so that an impression of alertness,

DIAGNOSTICS

-3.39 log cd.s.m-2 -3.09 log cd.s.m-2

b i

0.81 log cd.s.m-2

a 50 μV 25 ms -3.39 log cd.s.m-2

0 min of dark adaptation 2 min of dark adaptation 5 min of dark adaptation 10 min of dark adaptation 15 min of dark adaptation

100 μV

30 min of dark adaptation

25 ms C

Fig. 2.12 Electroretinography. (C) On left: representative ERG obtained in photopic conditions in dogs. The averaged responses to 15 flashes at progressively increasing intensities (from −4.89 log cd.s/m2 to 0.81 log cd.s/m2) delivered at 1.3 Hz were taken at the onset (vertical arrow) in photopic constant background. On right: representative ERG obtained in scotopic conditions in dogs. The averaged responses to three standard flashes (intensity: −3.39 log cd.s/m2) delivered at 0.1 Hz were taken at the onset (vertical arrow) of the dark adaptation process (t0) and at regular time intervals thereafter (t2, t5, t10, t15, and t30 minutes). Note the gradual gain in amplitude and in lengthening in the timing of the b-wave of the ERG. The progressive increase in the amplitude of the b-wave during dark adaptation is supposed to reflect the function of the neural–retinal pigment epithelium junction.

39


1

2 3

4

AI

1 3 2

AII

40

Fig. 2.13 Angiography. (A) Normal angiogram of a dog. I Fundus photography. 1: Tapetal fundus; 2: arteriole; 3: venule; 4: non-tapetal fundus. II Arterial phase. 1: Retinal arteriole filled with fluorescein; 2: venule; 3: choroidal fluorescence.

DIAGNOSTICS

2

1 3

AIII

1

4

2

3

AIV Fig. 2.13 Angiography. III Arteriovenous phase. 1: Laminar filling; 2: choroidal fluorescence; 3: intervascular area. IV Venous phase. 1: Retinal arteriole; 2: venule totally fluorescent; 3: intervascular area; 4: choroidal fluorescence.

41


2

1

BI

2

1

BII

42

Fig. 2.13 Angiography. (B) Pre-retinal masking of hypofluorescence by hemorrhage (arrow). I Fundus photography. 1: A hemorrhage is visible; 2: venule in proximity to hemorrhage. II Arterial phase. 1: A non-perfused retinal vessel emerging over choroidal hypofluorescent area (2).

DIAGNOSTICS

BIII

BIV Fig. 2.13 Angiography. III Arteriovenous phase. IV Venous phase.

43

SMALL ANIMAL OPHTHALMOLOGY CI

CII Fig. 2.13 Angiography. (C) Hyperfluorescence by window effect and leakage into a tissue (staining). I Fundus photography. Retinal pigment epithelium dystrophy. Note abnormal pigment in tapetum lucidum (arrow). II Arterial phase. Window effect with visualization of choroidal vessels (arrow).

44

DIAGNOSTICS

CIII

CIV Fig. 2.13 Angiography. III Arteriovenous phase. Note leakage from a retinal vessel (arrow). IV Venous phase. Leakage into retina (arrows).

45


V

A

a Cc

NR b Sc

B Fig. 2.14 Ocular coherence tomography. Vitreo-retinal junction in cat: fundus photography reveals a vitreo-retinal junction abnormality (A). OCT examination (B): between the sclera (Sc) and the vitreous (V), the neuroretina (NR) is detached from chorio-capillaris (Cc). Two spaces (a & b) are visible and arrows show vitreo-retinal connections.

visual acuity, and behavior is registered. Ocular examination should be conducted routinely as a part of the general physical examination. A systematic standard approach is suggested for a quick but complete eye examination, first in ambient light, then in a dark room.

Examination with ambient illumination

46

• The gross appearance of the eye and surrounding structures is observed to determine the presence of periorbital swelling, lacrimation, abnormal discharge, and the size and position of the eye. Examination of the anterior segment of the eye follows. Both eyes must always be considered, even if only one is obviously affected. In such instances it is preferable to examine the normal (or less obviously affected) eye first. A magnifying loupe and focal illumination are used to assess the adnexa and anterior segment structures. The STT, if indicated, is performed before additional manipulations or applications are performed. • Pupil light reflex (PLR), menace response, blinking, and ocular and periocular sensation should then be evaluated. PLR can be tested in ambient light; repeat the procedure in a darkened room prior to the instillation of dilating agents if abnormalities are noted. First each eye is

•

•

•

•

•

DIAGNOSTICS

•

directly stimulated with a bright focal light and the completeness and briskness of PLR is noted. This is the direct reflex, while the pupil of the opposite eye constricts due to the consensual reflex. For anatomic reasons in non-primates, the consensual pupil may not constrict to exactly the same size as the pupil of the stimulated eye. The menace response should be tested next, paying attention not to cause air movement toward the patient’s eye and a consequent blink (mediated by the trigeminal nerve). Bear in mind that absence of the menace response is normal in very young animals and problematic to interpret in cats. Manipulate the head and neck to evaluate ocular motility. Critically evaluate globe size and position, observe the symmetry of the globes from above, palpate around the orbital rim and the orbital fossa, and retropulse both globes simultaneously. Distinction between exophthalmos and globe enlargement is critical. Then consider the eyelids, third eyelid, conjunctiva, sclera, and cornea, and anterior chamber, iris, lens, and anterior vitreous, using the magnifying loupe and the focal light. If the adnexa is inflamed and there is discharge, STT is indicated, and cytology and culture should be considered. If a serous discharge is bilateral without evidence of inflammation, or the discharge is concentrated on the medial aspect and the hyperemia is particularly evident in the medial canthus, the lacrimal drainage system should be investigated, with a suspicion of obstruction and/or dacryocystitis. In these cases palpation over the lacrimal sac may be painful and induce the expression of exudates through the punctae. If the patient exhibits blepharospasm, look for corneal ulcers, a foreign body, entropion, or ectopic cilia, and stain with fluorescein. Chronic disorders of the cornea manifested by neovascularization and melanosis may be associated with trichiasis, distichiasis, lagophthalmos, lacrimal secretory disorders, or immune-mediated disease. If intraocular disease is suspected, based on the presence of episcleral/ scleral injection, corneal edema, aqueous cells or flare, or abnormal PLRs, tonometry is a requisite. Congestion of episcleral vessels may be differentiated from conjunctival injection by applying one drop of phenylephrine; in cases of conjunctivitis the hyperemic pattern will almost completely disappear. Episcleral injection is an indication of episcleritis, glaucoma, or uveitis. Because pupillary dilatation is necessary for the remainder of the ophthalmic exam, one drop of 1.0% tropicamide should be applied to each eye at this point; perform the rest of the general physical examination in the interim. Gonioscopy is optimally performed prior to mydriasis.

Dark room examination • When the pupils are completely dilated as an effect of the previously instilled mydriatic, the lens, vitreous, and the ocular fundus may be carefully examined. The lens can be examined by moving the transilluminator to the right and to the left from the frontal position in

47


such a way as to shift the incident light and better visualize any opacity with the magnification loupe. • Using the direct ophthalmoscope with a lens setting between 0 and +2 D and the eye examined from arm’s length it is possible to evaluate the fundus reflex as a relatively sensitive indicator of opacities within the media, which appear as a dark shadow when using this technique of distant direct ophthalmoscopy. The fundus should then be examined using the indirect or direct ophthalmoscope. During all steps of the examination, all data should be recorded in the patient’s permanent record and, in case of consultation, transmitted to the veterinary ophthalmologist. Most importantly, ocular disease should always be approached from the ‘whole animal’ perspective. Detecting unsuspected ocular conditions in their early stages during the course of a routine examination, or simply reassuring a client of the inevitability and insignificance of nuclear sclerosis, will elevate the quality of your service. Ocular signs such as cataracts of rapid onset in an unlikely breed or vitreous hemorrhage should alert the astute clinician to rule out diabetes mellitus or systemic hypertension, respectively. Only in the eye can one directly observe the central nervous system (optic nerve) and the peripheral vasculature (retinal arterioles and venules). Ocular function draws from a significant component of the nervous system and this association should be kept in mind.

REFERENCES

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1. Gaiddon, J., Bouhana, N. and Lallement, P.E. (1996) Refraction by retinoscopy of normal, aphakic and pseudophakic canine eyes: advantage of a 41 diopters intraocular lens? Vet. Comp. Ophthalmol. 2: 121– 124. 2. Davidson, M.G. (1997) Clinical retinoscopy for the veterinary ophthalmologist. Vet. Comp. Ophthalmol. 2: 128–137. 3. Rosolen, S.G., Ganem, S., Gross, M. et al. (1995) Refractive corneal surgery on dogs: preliminary results of keratomileusis using a 193 nanometer excimer laser. Vet. Comp. Ophthalmol. 5: 18– 24. 4. Stapleton, S. and Peiffer, R.L. (1980) Specular microscopic observations of the clinically normal canine endothelium. J. Am. Vet. Med. Assoc. 176: 249–251. 5. Peiffer, R.L., DeVanzo, R. and Cohen, K.L. (1981) Specular

microscopic appearance of the normal feline endothelium. Am. J. Vet. Res. 42: 854–855. 6. Rosolen, S.G., Rigaudière F., Le Gargasson, J.-F. et al. (2004) Comparing the photopic ERG i-wave in different species. Vet. Opthalmol. 7(3):189–192. 7. Rosolen, S.G., Rigaudière, F., Lachapelle, P. (2002) A practical method to obtain reproducible binocular electroretinograms in dogs. Doc. Ophthalmol. 105: 93– 103. 8. Narfström, K., Ekesten, B., Rosolen, S.G. et al. (2002) Guidelines for clinical electroretinography in the dog. Doc. Ophthalmol. 105: 83– 92. 9. Lescure, F. (1998) Evaluation of the angiograms – semeiology. In: Fluorescein Angiographic Atlas of the Small Animal Ocular Fundus. Pratique Médicale et Chirurgicale des Animaux de Compagnie, Paris, pp. 75–105.

angiography for clinical and toxicological studies on animals. Invest. Ophthalmol. Vis. Sci. 40: 1461 [ARVO abstract]. 12. Puliafito, C.A., Hee, R.H., Schuman, J.S. and Fujimoto, J.G. (1996) Optical Coherence Tomography of Ocular Diseases. Slack Inc., Thorofare.

DIAGNOSTICS

10. Rosolen, S.G., Gautier, V., SaintMacary, G. et al. (2000) Eye fundus images with confocal scanning laser ophthalmoscope on dog, monkey and minipig. Vet. Ophthalmol. 4: 41–45. 11. Rosolen, S.G., LeGargasson, J.-F. and Saint-Macary, G. (1999) SLO

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Therapeutics Bruce H. Grahn and Joe Wolfer

INTRODUCTION

50

3

The eye is a delicate and complex organ which is affected by a variety of diseases; successful medical management of ocular disease is based not only on an accurate diagnosis but also on in-depth knowledge of pharmacology and therapeutics. The purpose of this chapter is to enhance the veterinarian’s understanding of ocular therapeutics by reviewing the pharmacokinetics and indications for medications that are commonly prescribed for ocular disorders by topical, subconjunctival, and/or systemic routes. The eye may be medicated topically, systemically, or by injection into the subconjunctival, intraocular, or orbital tissues. There are several compartments in the eye, separated by semi-permeable barriers. Delivery of systemic medications to the cornea via the circulatory system is limited to diffusion from the perilimbal vasculature, and those agents secreted in the tears or that penetrate the blood–ocular barriers enter the anterior chamber and pass through the corneal endothelium; topical or subconjunctival medications are appropriate for most corneal diseases. Diseases of the anterior segment may be medicated topically, subconjunctivally, or systemically, while most posterior segment, orbital, and eyelid diseases require systemic medications. Intraocular and intraorbital injections have inherent risks, are indicated in specific ophthalmic diseases, and should be performed by an ophthalmologist; these injections will not be discussed in detail in this chapter. When an animal is to be medicated at home, owner compliance is an important and often forgotten factor. The owner must have the time and ability to medicate the eye during the specified treatment period and a sense of what to expect in terms of improvement or deterioration in the condition. Treatment instructions should be given to the owner verbally and in written form. Consider the following with regard to owner compliance: topical solutions are usually easier to apply than ointments but they require more frequent application. Is the animal manageable by the owner alone and, if not, will an assistant be available to restrain the animal during medication? Will painful orbital or ocular inflammation preclude or reduce the frequency of administration of medications? If the medications are used for an extended period of time, has the most economical formulation been selected? Are systemic side effects going

PHARMACOKINETICS OF OPHTHALMIC MEDICATIONS

THERAPEUTICS

The most commonly used route for ocular therapy is topical. The ocular penetration of a topical medication is dependent on the concentration and kinetics within the conjunctival cul-de-sac, corneal permeability, and the rate of elimination of the medication from the conjunctival sac.1 Tear flow and space within the conjunctival fornix have a dynamic effect on topical ophthalmic medications. Commercial droppers deliver 25–50 μl/drop of solution or suspension and immediate reflex tearing occurs after a drop of medication is placed on the eye. The non-blinking eye will retain approximately 10–25 μl (varies with species) of additional fluid in the conjunctival fornix and tear film, after which immediate overflow occurs.2 Application of more than one drop at a time will not increase the amount of available medication because this volume will overflow into the nasolacrimal duct or onto the eyelid.3 It is important to wait at least 5 min between the applications of consecutive topical medications. Only 20% of topically applied medications will remain on the ocular surface after 5 min.2 This rapid reduction is the result of drainage through the nasolacrimal system and absorption of the medication through the cornea and conjunctiva. Therefore, if increased concentrations of topically applied medication within the cornea and the anterior chamber are desired, an increased frequency of application is useful provided the applications are at least 10 min apart. Most of the intraocular penetration of topically applied medications occurs via the cornea.4 The cornea has a thick hydrophilic stroma which is enveloped by two thin lipophilic structures: the epithelium and the endothelium. Factors such as solubility, ionization, and molecular size affect absorption of all pharmaceuticals. Membrane factors including weakness or absence of portions of the cornea (the epithelial barrier is not present in corneal ulcers, enhancing permeability) are also important.5 The intact epithelium is a significant barrier for hydrophilic medications, while the underlying stroma is a significant barrier for lipophilic agents, which consequently accumulate in the epithelium. In order to penetrate the intact cornea adequately, topical medications require both hydrophilic and lipophilic characteristics. Protein binding of pharmaceuticals in the tear film, aqueous humor, and vitreous also influence the availability of medications.6 The protein concentrations in these fluids will increase during inflammation due to disruption of the blood–ocular barriers and significant protein binding may occur.7 Topical ophthalmic pharmaceuticals are available as solutions, emulsions or suspensions, and ointments. Emulsions and ointments have slightly prolonged contact times compared to solutions and therefore require less frequent administration to achieve therapeutic concentrations. However, emulsions have the disadvantage of being less stable and ointments are more difficult to apply, result in blurred vision, and may elicit rubbing and self-induced trauma. For a more complete review of pharmacokinetics and corneal penetration of topically applied ophthalmic pharmaceuticals, the reader is referred to reports by Shell8 and Burstein and Anderson.9

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to be induced by the long-term topical ophthalmic medications and is the owner adequately informed and prepared for these effects?


52

Treatment compliance is dependent on provision of accurate and thorough instructions to the owner, and a demonstration is worth a thousand words. Bottles of ophthalmic solutions and suspensions should be kept at a safe distance from the eye during medicating in order to avoid contamination of the bottle and injury to the eye. Instruct the owner to rest their hand holding the medication on the animal’s forehead, use the other hand to stablilize head and retract the eyelids, and to come from behind and above to place one drop onto the ocular surface at a safe distance. Gentle occlusion of the lower puncta for a few minutes after medications are applied will increase the total available medication by decreasing drainage into the nasolacrimal duct. When ointments are being applied, it is preferable to place a 5 mm strip on a clean fingertip, and then use the lid margin to scrape the medication onto the lower palpebral conjunctival surface. This prevents contact and contamination of the ointment tube and corneal and conjunctival injury. Alternately, the upper or lower lid can be retracted and the medication applied directly to the conjunctival surface. Subconjunctival injection of medications can be a valuable adjunct to topical therapy. It is important that the practitioner understands the indications and limitations of their use. Medications, including some of the antibiotics, enjoy enhanced ocular penetration with bulbar subconjunctival injections.10 Depot formulations provide prolonged therapy, and in fractious or aggressive patients subconjunctival injection under sedation may be the only means of therapy. The pharmacokinetics of subconjunctival injections are not well understood and likely vary considerably between classes of pharmaceuticals and their formulations. Medications injected into the subconjunctival space are thought to enter the ciliary circulation, thereby gaining access to the anterior segment. However, some of the injected medication simply leaks through the puncture site in the conjunctiva and is absorbed directly through the cornea.11 In the case of subconjunctival corticosteroids, transscleral penetration has also been reported.12 Direct absorption of medication from the subconjunctival injection site bypasses the epithelial barrier and increases intraocular drug availability by avoiding tear dilution.13 The use of subconjunctival medications at surgery minimizes the need for some of the topical medications during the immediate postoperative period. Other advantages include increased intraocular concentration of medications that penetrate the cornea poorly, and ensured presence of the therapeutic agent when owner compliance is poor.14 Subconjunctival injections require the utmost care. Topical anesthesia is required and occasionally sedation or general anesthesia is necessary to ensure accurate bulbar subconjunctival injection. A subconjunctival injection is performed by manually retracting the upper eyelid and gently grasping the superior bulbar conjunctiva with small tissue forceps (i.e. Bishop Harmon). A 25 G needle (attached to a 1 ml syringe) is inserted bevel up through the tented bulbar conjunctiva. Up to 0.5 ml of medication may be slowly injected to form a subconjunctival bleb. The dosage will vary with the ocular condition and medication but the total volume per injection site should not exceed 0.5 ml. Long-lasting (depot) medications should be avoided unless they are required as they are irritating and may predispose to granuloma formation.15 Subconjunctival injections of solutions including antibiotics and atropine need to be repeated every 24 h; the repetition rate will vary depending on the response to therapy and the frequency of topical and systemic medications. Subconjunctival injections of long-lasting steroids, e.g. betamethasone valerate, need to be

THERAPEUTICS

repeated every 7–10 days. There are inherent risks associated with the use of subconjunctival injections; complications include irritation at the injection site, granuloma formation, an inability to withdraw medications if necessary, and rarely inadvertent intraocular injections. Many medications are irritating and should not be administered subconjunctivally, especially when similar approved topical medications are available. Systemic medications may be administered orally, intramuscularly, intravenously, or subcutaneously for therapy of glaucoma, and eyelid, orbital, posterior segment, and optic nerve diseases. Systemic anti-microbials, corticosteroids, non-steroidal anti-inflammatory drugs (NSAIDs), hypotensive agents, and carbonic anhydrase inhibitors are commonly so administered for these conditions. The blood–ocular barriers are composed of tight junctions of the endothelium of the iris and retinal blood vessels and the ciliary and retinal pigment epithelium. These barriers are only penetrated by a few lipophilic medications of low molecular weight (e.g. chloramphenicol). However, with inflammatory eye conditions the blood–ocular barriers are compromised, which allows most systemic medications to reach the anterior and posterior segments. Antibiotics should be selected initially on the basis of cytologic evaluation of scrapings or fine needle aspirates from the eye, eyelid, or orbit and re-evaluated when bacterial cultures and sensitivities are available. Systemic corticosteroids are indicated in most inflammatory conditions of the posterior segment. Prednisone, prednisolone, dexamethasone, and flumethasone are common choices for severe posterior segment, optic nerve, or orbital inflammation. Systemic NSAIDs are frequently administered to control inflammation of the posterior segment or orbit. Examples include flunixin, carprofen, aspirin, ketoprofen, and indometacin. Contraindications for NSAIDs include platelet disorders, coagulopathies, some hepatic and renal insufficiencies, and specific hypersensitivities to these drugs. Systemic carbonic anhydrase inhibitors decrease the production of aqueous humor by the non-pigmented ciliary epithelium and are indicated for treatment of acute glaucoma and prophylactic treatment of primary glaucoma; examples of these agents include methazolamide, dichlorphenamide, and acetazolamide. These medications are contraindicated when acidosis or hypokalemia is present as they will aggravate these conditions. Clinical manifestations of acidosis and hypokalemia include panting, vomiting, diarrhea, and collapse. Because of these adverse effects, the availability of topical carbonic anhydrase inhibitors has largely obviated their use. Numerous fixed ratio topical ophthalmic medications are available and frequently prescribed by veterinarians. It is our opinion that many of these medications (usually an antibiotic and steroid combination) are overused, often because of a lack of a specific diagnosis. Topical or systemic corticosteroid therapy does not require the addition of antibiotics, and vice versa. If both are required for separate purposes then separate formulations are usually more appropriate to deliver adequate concentrations of each.

Antimicrobials Topical antimicrobials (antibiotics, antifungals, and antivirals) (see Appendix, Tables 1 & 2) Topical antibiotics may be categorized, based on their intended use, into primary, secondary, and tertiary types. Primary antibiotics are used to treat bacterial conjunctivitis and simple corneal ulcers. The bacterial flora of the

53


54

normal surface of dogs and cats are a mixed population of predominantly Gram-positive organisms.16,17 Therefore, broad-spectrum antibiotics including triple antibiotics (neomycin, polymyxin B, bacitracin), gentamicin, or chloramphenicol are appropriate for bacterial conjunctivitis or simple corneal ulcers. Triple antibiotics and gentamicin are bactericidal. Chloramphenicol is bacteriostatic but penetrates the eye rapidly and achieves high intraocular concentrations. Secondary categories of topical ophthalmic antibiotics are indicated for specific anterior segment conditions. An example is tetracycline, which is the topical antibiotic of choice for feline Chlamydia or Mycoplasma conjunctivitis. It is bacteriostatic and achieves an adequate concentration in the cornea and conjunctiva. The tertiary category of antibiotics should be reserved for septic conditions including melting corneal ulcers and panophthalmitis. Examples include some fluoquinolones and aminoglycosides which are bactericidal and effective against most antibiotic-resistant Gram-negative bacteria including Pseudomonas. Prudent selection of tertiary antibiotics is encouraged and should be based on culture and sensitivities. Indiscriminate usage of any antibiotic is discouraged as development of bacterial resistance is common. Bacterial infections of the conjunctiva, cornea, or anterior segment require a minimum of one drop QID with antibiotic solutions or emulsions for 7 days or until the infection is resolved. When ointments are prescribed, a 5 mm strip is applied to the conjunctiva a minimum of three times per day until the infection is resolved. Fusidic acid, a viscid topical antibiotic drop, is now available in North America; this slow-release viscid suspension may be applied only twice a day and still produce inhibitory antibacterial drug levels.18 Ointments are contraindicated when the cornea is perforated because they are irritating to the uvea.3 Topical gentamicin and tobramycin should be avoided when the cornea is perforated as toxic effects on the corneal endothelium and the retina and ciliary epithelium were found when those tissues were exposed to high concentrations of aminoglycosides.19,20 Most antivirals are nucleoside analogs that are similar in structure to nucleosides and when they are incorporated into viral DNA or RNA they alter or disrupt the viral replication. Idoxuridine, adenine arabinoside, and trifluridine are topical antivirals that have been used to treat feline herpetic keratitis and conjunctivitis. Idoxuridine mimics thymidine, thereby altering virus metabolism. It is available as a solution or ointment and should be applied frequently (q2 h for 2 weeks) and q6 h for 4 weeks. Adenine arabinoside inhibits virus DNA polymerase. It is available as an ointment and should be applied q4 h for several weeks to be effective. Trifluridine inhibits viral DNA synthesis and is available as a solution which is applied q4 h for at least 3 weeks. Trifluridine has the highest in vitro activity against feline herpesvirus. Bromovinyldeoxyuridine is a pyrimidine analog of nucleoside thymidine and, although it is selective for human herpes simplex 1, it is ineffective against feline herpes virus 1 (FHV-1).21 Vidarabine is a nucleoside analog of adenosine and has been used topically to treat FHV-1; however, it is no longer available commercially. Ganciclovir is an acyclic analog of guanosine and in vitro potency studies have suggested it may be useful in treating FHV-1 infections.22 Valganciclovir is a prodrug of ganciclovir. Penciclovir is similar to aciclovir structurally and a moderately high anti-feline herpesvirus 1 activity has been demonstrated in

THERAPEUTICS

vitro; and further in vitro studies are required.22 Famciclovir is a prodrug of penciclovir. Cidofovir is an acyclic analog of cytosine and its in vitro efficacy suggests that it may be as potent as idoxuridine; however in vivo efficacy has not been established and topical usage resulted in stenosis of the nasolacrimal duct in rabbits and humans.22,23 Foscarnet is a non-nucleoside replication inhibitor of herpesviruses that has been investigated for in vitro anti-feline herpesvirus activity, and unfortunately is not effective.22 Fungal infections of the dog and cat eye are uncommon and are usually limited to the cornea (with the exception of systemic mycotic disease with ocular involvement). Topical antifungal ophthalmic medications including amphotericin B, natamycin, miconazole, clotrimazole, silver sulfadiazine, ketaconazole, itraconazole, fluconazole, econazole, thiabendazole, flucytosine, or povidone–iodine may be required. Natamycin is the only available commercial topical ophthalmic antifungal and is administered as a solution q6 h until the corneal fungal infection is eliminated. Miconazole solutions may be administered topically or subconjunctivally. Clotrimazole and silver sulfadiazine are available as dermatologic ointments which may be applied topically onto the eye.24 Dilute (1 : 25) povidone–iodine solution has also been reported as a useful and readily available topical ophthalmic antifungal agent.24 There are many complexities that affect the development of ocular mycoses, accurate diagnosis, and the management of effective fungal therapy. Therefore referral of affected animals and consultation with a veterinary ophthalmologist is strongly encouraged.

Subconjunctival antimicrobials Antibiotic or antifungal solutions may be injected under the bulbar conjunctiva as adjunct therapy for bacterial or fungal infections of the anterior segment. Medications inadvertently placed under the palpebral conjunctiva are not considered as useful since the blood circulation is away from the eye in this location. Gentamicin, penicillin, or cephalosporins are appropriate antibiotics for subconjunctival injections. Miconazole solution can be administered as an antifungal agent. These injections increase the anterior segment concentration of the drug by absorption into the anterior ciliary circulation and across the cornea from the injection site. The contraindications for these forms of therapy include known hypersensitivities. Conjunctival and episcleral irritation are commonly observed with this form of therapy.

Systemic antimicrobials Bacterial infections of the eyelid, orbit, anterior and posterior uvea require systemic antibiotic therapy. Ideally these antibiotics are chosen on the basis of culture and sensitivity results; however these are seldom available at the critical stage of early infection. Cytologic evaluations of fine needle aspirates from the infected intraocular or orbital tissues should be performed and aerobic and anaerobic cultures collected as early as possible in the course of disease. Thorough examination of cytologic specimens from the ocular surface may aid the clinician in identification of the potential bacteria and assist in the selection of an appropriate antibiotic. Bactericidal antibiotics that are effective against aerobic and anaerobic bacteria are appropriate for most of these infections. Beta-lactams including ampicillin, amoxicillin, or cephalosporins are

55


recommended and they may be administered via oral, intravenous, intramuscular, or subcutaneous routes. The antibiotic initially selected should be reconsidered after cultures and sensitivities are available. The prognosis for maintenance of vision is dependent on prompt control of intraocular or orbital infections. Intravenous therapy is recommended to establish immediate tissue concentrations. Intramuscular or oral therapy should be continued until the clinical signs of the infection are gone. It is worth repeating that most systemic antibiotics will penetrate inflamed intraocular tissues well. Systemic antifungals (including amphotericin B, ketoconazole, flucytosine, itraconazole, thiabendazole) have been reported in the therapy of blastomycosis, coccidioidomycosis, cryptococcosis, candidiasis, aspergillosis, and histoplasmosis. For a review of the systemic antifungal therapy of ocular and systemic mycosis, the reader is referred to Noxon et al.25 and Ford.26 Aciclovir is a systemic antiviral drug that has been administered to cats with FHV-1 conjunctivitis and keratitis. Aciclovir is a thymidine kinase substrate which interferes with viral DNA synthesis. This medication is administered orally at a dose of 2 mg/kg for 21 days. The effectiveness of this medication against feline herpes is controversial.27,28 Interferon α may be effective in controlling feline herpesvirus infection and has synergistic activities in vitro with aciclovir.29,30 However, clinical trials have not been reported to date. L-lysine has also recently been recommended as an oral supplement, 250 mg orally every 12 h. This amino acid has been reported to reduce the severity of recrudescent FHV-1 infection and virus shedding in experimental cats;31,32 however, its clinical efficacy has not been demonstrated. Valaciclovir is the L-valy ester of aciclovir. Although it is more readily absorbed, it induces bone marrow suppression and hepatic necrosis in cats and has no treatment value in cats.33 Famciclovir at a dosage of 31.25–62.5 mg twice daily for 7–14 days has been reported empirically to be safe and effective, but scientific clinical studies have not been performed. Systemic antivirals theoretically might be advantageous in minimizing recurrences. Nonetheless feline herpetic ocular disorders are difficult to treat and veterinarians are encouraged to consult with veterinary ophthalmologists regarding effective systemic and topical FHV-1 therapy.

Anti-inflammatory medications Topical anti-inflammatories Topical corticosteroids and NSAIDs are commonly used to control anterior segment inflammation and are often used in combination for severe intraocular inflammation. However, indiscriminate use of these potent anti-inflammatories is discouraged.

Topical ophthalmic corticosteroids (see Appendix, Tables 3 & 4)

56

Corticosteroids inhibit phospholipase which alters the arachidonic acid metabolic pathway and minimizes inflammation. Corticosteroids decrease vasodilatation, capillary permeability, leukocyte infiltration, and release of inflammatory mediators from cells. They also inhibit fibroblasts and collagen formation. Corticosteroids are derived from cholesterol and are available in several forms. The acetate forms are generally more lipophilic which allows for better corneal penetration when compared to succinates or phosphates. Dexamethasone and

THERAPEUTICS

prednisone are excellent selections for control of anterior segment inflammation and are available as suspensions, solutions, or ointments. Less potent corticosteroids are also available, the most common of which is hydrocortisone which is often combined with an antibiotic in a solution or ointment form. Topical corticosteroids are contraindicated when corneal ulceration is present. Local immunosuppression predisposes to or exacerbates infectious disease, notably fungal and viral infections. Continuous topical corticosteroid therapy may induce adrenal gland suppression via conjunctival absorption, and continuous use is recommended only if other options are not available for preservation of vision.

Topical NSAIDs (see Appendix, Table 5) These medications inhibit the cyclo-oxygenase pathway and reduce intraocular inflammation. Their inhibition of cyclo-oxygenase and endoperoxide isomerase decreases the production of prostaglandins, which cause miosis, altered blood– aqueous barrier, vasodilatation, and increased vascular permeability. NSAIDs also inhibit leukocyte chemotaxis and movement,34 and are commonly used to treat ocular inflammation today. Topical ophthalmic NSAIDs are indicated to control most anterior segment inflammation; there are several preparations available including flurbiprofen, ketorolac, diclofenac, and suprofen. They should be used with caution when corneal ulceration is present as delayed epithelial healing, stromal infiltrates, punctate keratitis, and collagenolysis may develop concurrent to their usage.35–37 Topical NSAIDs may be contraindicated in animals with some forms of glaucoma as they may increase the intraocular pressure. They should be avoided or used with caution in animals with platelet dyscrasias, as they may decrease platelet aggregation and promote intraocular hemorrhage. However, despite these cautions, topical NSAIDs remain an important class of pharmaceuticals that the veterinarian should consider to control anterior segment inflammation. Topical mast cell stabilizers and antihistamines Cromolyn sodium solution is a topical mast cell stabilizer which prevents the release of inflammatory mediators from mast cells. It is useful in the treatment of inflammatory conjunctival diseases where mast cells predominate, such as allergic conjunctivitis. However, conjunctivitis associated with inhalant or food allergies are very uncommon in the dog and cat. When allergic conjunctivitis is confirmed with cytology or biopsy it may be controlled in the acute stages with any one of several topical human antihistamines that are available commercially including antazoline, pheniramine maleate, and pyrilamine, as well as cromolyn sodium.

Subconjunctival anti-inflammatory drugs Subconjunctival corticosteroids are indicated to control progressive, poorly responsive, anterior segment inflammation. They provide anti-inflammatory effects to the anterior segment via the ciliary circulation, and by seepage of the medication onto the cornea through the bulbar conjunctival injection site. Subconjunctival corticosteroid injections are contraindicated when corneal ulceration is present. Conjunctival and episcleral inflammation and granulomas occur frequently after long-acting corticosteroid injections and their usage

57


should be discouraged. Prednisone, dexamethasone, or betamethasone sodium phosphate may be recommended as adjunctive therapy for non-responsive immune-mediated anterior segment inflammation.

Systemic anti-inflammatories Systemic corticosteroids may be required to control severe anterior and posterior segment inflammation. Similar to antibiotics they readily concentrate intraocularly when the blood–ocular barrier has been compromised. They are contraindicated when corneal ulcers are present as they delay epithelialization and healing. Prednisone and dexamethasone are the most frequently prescribed. They may be administered orally, subcutaneously, intramuscularly, or intravenously at immune suppressive doses for prednisone (2 mg/kg) and dexamethasone (0.5 mg/kg) or anti-inflammatory doses for prednisone (1 mg/kg) and dexamethasone (0.125 mg/kg) in the dog and cat. The commonly used systemic NSAIDs include flunixin meglumine, aspirin, carprofen, meloxicam, phenylbutazone, aspirin, ketorolac, etodolac, deracoxib, and ketoprofen. They may be administered intravenously (carprofen, flunixin meglumine, meloxicam, ketoprofen, ketorolac) or orally (aspirin, etodolac, deracoxib, carprofen, meloxicam, phenylbutazone, ketoprofen). Flunixin meglumine is often administered to dogs prior to intraocular surgery. It should not be administered for longer than 3 days.38 Aspirin, carprofen, ketorolac, etodolac, deracoxib, or ketoprofen may also be administered to control intraocular inflammation. The recommended dosage for aspirin is 10 mg/kg BID in the dog and 10 mg/kg q72–96 h in the cat. The recommended dosage for carprofen in the dog is 2 mg/kg q12 h and 4 mg/kg SQ in cats. The recommended dosages for ketorolac in dogs is 0.5 mg/kg IV, and for cats is 0.25 mg/kg IM, etodolac 15 mg/kg orally, and deracoxib 4 mg/kg orally in dogs. The recommended dosage for ketoprofen in the dog and cat is 1 mg/kg q24 h. Systemic NSAIDs are contraindicated in patients with bleeding disorders, impaired renal function, or pre-existing hypersensitivities and they predispose the animal to gastrointestinal ulceration.39 Systemic steroids and NSAIDs are commonly used and provide excellent anti-inflammatoriy activity. They deserve consideration in most severe ocular inflammations when contraindications are not present.

Ocular hypotensive medications These medications lower the intraocular pressure by reducing the rate of production of aqueous humor, by increasing the rate of outflow of aqueous humor by conventional (trans-trabecular) or uveoscleral pathways, or via a combination of these actions. They are useful in the emergency management of acute glaucoma, as adjunctive medical therapy to surgical procedures, and as prophylactic medications to slow the onset of primary glaucoma. They are available in topical and systemic formulations, and as intravitreal injections.

Topical ocular hypotensives (see Appendix, Table 6) Parasympathomimetics

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Parasympathomimetics may be direct acting (i.e. have their effect directly on cholinergic receptors) or be indirect acting and inhibit acetylcholinesterase. These medications lower the intraocular pressure by altering the filtration angle which increases the outflow of aqueous humor.

THERAPEUTICS

Direct acting parasympathomimetics Pilocarpine has been commonly used in the past to lower the intraocular pressure. Pilocarpine is a potent miotic and is available as a solution or gel. Pilocarpine should be administered 3–4 times/ day and is usually used in combination with other antiglaucoma drugs including beta-adrenergic blockers, adrenergics, and systemic carbonic anhydrase inhibitors. Pilocarpine is seldom used today as an ocular hypotensive agent because it irritates the ocular surface and induces uveitis, and more effective medications are readily available. Pilocarpine is also contraindicated in uveitis and secondary glaucoma because its miotic effect may predispose to posterior synechiae and pupillary occlusion. A frequently observed side effect after prolonged use is conjunctival hypersensitivity which warrants dilution of the pilocarpine or discontinuance of this drug. Despite its diminished usage in the therapy of glaucoma in the dog and cat, topical pilocarpine is still used occasionally in the therapy of neurogenic keratoconjunctivitis sicca, and in the pharmacologic diagnosis of some parasympathetic ocular neuropathies. Indirect acting parasympathomimetics Cholinesterase inhibitors are categorized into reversible and irreversible agents. Physostigmine salicylate is a reversible cholinesterase inhibitor with a short duration of activity which limits its use to a diagnostic agent for parasympathetic disorders. Demecarium bromide is an irreversible carbamate inhibitor that is available as a topical solution. It is a potent cholinesterase inhibitor that lowers the intraocular pressure and has a duration of action of approximately 12–48 h. Isoflurophate and echothiophate iodide are irreversible cholinesterase inhibitors. They are also longacting, potent organophosphates that lower the intraocular pressure and are only occasionally administered today on a q12–48 h basis in the dog. In general, most parasympathomimetics are irritating to the eye and may produce painful spasms of the ciliary and iridial muscles. Systemic toxicity may also develop and the clinical signs include salivation, vomiting, diarrhea, and abdominal cramps. These drugs should be used with caution and avoided when systemic anticholinesterases are being administered.

Adrenergics Epinephrine and dipivefrin are adrenergic agents that lower the intraocular pressure in the dog and cat. Their mechanism of action is not completely understood. However, the outflow facility has been shown to increase and the aqueous humor formation may decrease.40 Epinephrine and dipivefrin solutions are administered q8 h. Contraindications include known sensitivities to adrenergic medications and predisposition to arrhythmias. Alpha-adrenergic agonists Alpha-adrenergic agonists, notably apraclonidine hydrochloride and brimonidine, lower IOP by decreasing aqueous production in humans and rabbits; the effect is transient and a 1.0% solution may be of value in the dog in managing the IOP elevations that may occur following surgical procedures, including cataract extraction and cyclocryosurgery.

Adrenergic antagonists Numerous topical adrenergic antagonists are available for treating glaucoma, and betaxalol and timolol maleate are the most commonly used in veterinary medicine. Limited studies are available regarding their therapeutic efficacy in the dog or cat. The beta-blocker timolol maleate has been shown to reduce aqueous humor production in the dog significantly,41 and more so in the cat,

59


by up to 71%.42 Timolol decreases the rate of aqueous humor production by reduction of blood flow through the ciliary processes. It is available as a solution and may be administered topically, one drop q12 h in dogs and cats. Betaxalol is a selective β-1 blocker and has been used as a prophylactic to delay the onset of primary glaucoma in the contralateral eye.43 These drugs are contraindicated in animals with known sensitivities to beta-blockers, including some cardiovascular and respiratory diseases.

Prostaglandin analogs Several prostaglandin pro-ester topical anti-glaucoma medications are available. Latanaprost, unoprostone, and travoprost are currently popular examples of these prostaglandin analogs. They exert potent and relatively long-lasting hypotensive effects after topical ocular application in the dog. Latanaprost is available as a 0.005% solution, travoprost is available as a 0.004% solution, and unoprostone as a 0.12% solution. These may be applied q12–24 h. These prostaglandin analogs induce miosis and increase uveoscleral outflow of aqueous humor, and may decrease aqueous humor production. Long-term clinical studies are not yet available in dogs. These medications are not as effective in cats.44,45

Carbonic anhydrase inhibitors Topical carbonic anhydrase inhibitors include dorzolamide hydrochloride, a 2% solution that should be applied q8 h, brinzolamide, a 1% solution that may be administered q8 h, and a dorzolamide (2%)–timolol (0.5%) solution that may be administered q8–12 h. Topical application avoids the potential acidotic side effects associated with systemic carbonic anhydrase medications and their use is encouraged over oral agents. These medications decrease the intraocular pressure by reducing production of aqueous humor and, aside from topical hypersensivity which is uncommon, there are no other contraindications in dogs.

Systemic ocular hypotensive medications

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Systemic medications that reduce intraocular pressure include carbonic anhydrase inhibitors, mannitol, and glycerine. Carbonic anhydrase inhibitors reduce the intraocular pressure by decreasing the rate of aqueous humor production. Examples of carbonic anhydrase inhibitors include dichlorphenamide, acetazolamide, and methazolamide. Dichlorphenamide is currently the carbonic anhydrase of choice as it effectively lowers the intraocular pressure and has the fewest side effects. Carbonic anhydrase inhibitors are contraindicated in dogs or cats with a predisposition to or concurrent acidosis. Topical carbonic anhydrase inhibitors are now available and are aimed at avoiding the systemic side effects of these drugs. Intravenous mannitol solution and oral glycerine paste reduce the vitreous volume by osmosis and lower the intraocular pressure. They are indicated in the emergency management of some cases of canine glaucoma. Water should be restricted for 1 h after administration to attain maximum effect. Glycerine is contraindicated in the vomiting patient and both are contraindicated in patients with congestive heart failure, hypertension, or renal failure.46 Their use in the diabetic patient is controversial.3,46,47 Since the emergence and success of topical prostaglandins in the emergency management of primary

Intravitreal hypotensive injections Intravitreal injections of cyclotoxic agents have been utilized as a last resort therapy for blind glaucomatous eyes where other forms of therapy have failed and surgical therapy (enucleation or evisceration and intraocular silicone prosthesis) are not applicable due to significant anesthetic risk or financial considerations. Gentamicin when injected into the vitreous at a dose of 10–25 mg is toxic to the ciliary epithelium and decreases aqueous humor production;48,49 cataract and phthisis are frequent sequelae. More recently, intravitreal injections of the antiviral agent cidofovir (350–500 μg) have been used in dogs with more predictable cosmetic results.50 However, intravitreal injections for the treatment of glaucoma in the dog or cat carry significant risk to the eye and therefore should be used only when all other alternative therapies have been considered.

THERAPEUTICS

glaucoma in dogs, oral glycerine and intravenous mannitol are seldom required today.

Mydriatics and cycloplegics Mydriasis is dilatation of the pupil, and cycloplegia is paralysis of the ciliary muscle which results in a loss of accommodative function. Parasympatholytics paralyze the iris sphincter muscle and cause mydriasis. Cycloplegia may develop depending on the type of parasympatholytic administered. Sympathomimetics stimulate the adrenergic receptors of the dilator muscle and may cause mydriasis.

Parasympatholytics Tropicamide is available as a topical ophthalmic solution. Tropicamide has minimal effect on the ciliary muscles, has a rapid onset of action (20 min), is short acting (2–4 h) and is the mydriatic of choice for intraocular examinations. Atropine has a slow onset of action (45 min) and the pupillary dilatation is accompanied by cycloplegia. Atropine is available as a topical ophthalmic solution or ointment and as a systemic medication which can be administered subconjunctivally. Topical or subconjunctival atropine is recommended for mydriasis and cycloplegia when uveitis is diagnosed in the dog and cat. Atropine may be required as often as every 6 h to maintain comfort by control of the ciliary spasm or as needed on a daily basis when the uveitis is mild. Salivation is a common side effect of these drugs as they are bitter tasting, reaching the mouth via drainage through the nasolacrimal duct; this may be a significant problem in cats that is minimized by the use of ointments rather than solutions. Systemic side effects of atropine include tachycardia, decreased gastrointestinal motility, and reduced tear production.

Sympathomimetics Phenylephrine and epinephrine are examples of sympathomimetics. They are available as topical ophthalmic solutions which have a synergistic effect with parasympatholytics. This synergistic activity is useful in cases of resistant miosis associated with severe uveitis. Dilute solutions of epinephrine and phenylephrine are useful for differentiation of pre- and post-ganglionic Horner’s syndrome. Intracameral injections of sterile dilute solutions of epinephrine or phenylephrine are also administered during intraocular surgery to maintain

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mydriasis and control capillary bleeding. Adrenergics are contraindicated in patients with a predisposition to cardiac arrhythmias or known sensitivities to these drugs.

Indirect acting sympathomimetics Cocaine and hydroxyamfetamine are indirect acting sympathomimetics which may be administered topically to diagnose Horner’s syndrome. These medications are the drugs of choice for confirming the diagnosis of Horner’s syndrome and differentiating central and pre-ganglionic from post-ganglionic lesions.51 However, the availability and need for strict control of these potentially addictive drugs has limited their use in veterinary medicine.

Lacrimomimetic drugs and artificial tears Ciclosporin is a potent immunosuppressive drug that is very useful in the treatment of immune-mediated keratoconjunctivitis sicca (KCS) in the dog. It is a T-cell suppressor which decreases lacrimal gland inflammation. In addition this drug has a direct lacrimomimetic effect and it also reduces corneal inflammation. It is available commercially as a 0.2% ophthalmic ointment and has been compounded as a 1% and 2% solution and as a 1% emulsion. A quarter of an inch strip of the ointment or one drop of the solution or emulsion is applied to the cornea every 12 h and, if instituted early in the course of immune-mediated keratoconjunctivitis sicca, will reverse the low tear production in the majority of patients with restoration of normal Schirner values in 6 weeks. Topical ciclosporin is poorly absorbed through the cornea and has minimal systemic effects. It may be used when corneal ulcers are present and it remains the drug of choice for dry eye in the dog.52 In addition it has been reported as an effective agent in the control of chronic superficial keratitis in the dog.53 The contraindications for topical ophthalmic ciclosporin include keratomycosis and known hypersensitivities to ciclosporin or its carriers. Recently, other calcineurin inhibitors similar to ciclosporin have been utilized to treat KCS in dogs. These include tacrolimus and sirolimus. However, most of the information reported at this time regarding these potentially carcinogenic topical medications is anecdotal and only two conflicting studies are reported.54,55 Before these medications are utilized further, placebocontrolled pharmaceutic studies need to be completed and their safety thoroughly assessed. Pilocarpine has been reported to be an effective lacrimomimetic drug in the treatment of neurogenic KCS.56 Oral pilocarpine can be toxic and should be administered with caution to dogs. Signs of toxicity include vomiting and diarrhea. These clinical signs are often used to ensure an adequate dosing and, if the tear production is not increased at that time, the pilocarpine is discontinued.

Tear replacements

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Numerous tear supplements are available. These include hypertonic, isotonic, and hypotonic tear solutions. In addition, tear replacements are available as ointments which provide a longer duration of effect compared to the solutions. Artificial tears, hydroxymethylcellulose, and polyvinyl alcohols should be administered frequently and are usually required in excess of q4 h to prevent corneal dehydration. Hyaluronic acid solutions increase the duration of tear

MISCELLANEOUS TOPICAL DRUGS

THERAPEUTICS

contact and stabilize the tear film, and they are useful adjunctive agents in the treatment of qualitative and quantitative tear film abnormalities in the dog and cat.

(see Appendix, Table 7) Proparacaine and tetracaine are topical anesthetics that are required prior to tonometry and to facilitate the ocular examination. Topical anesthetics are toxic to the corneal epithelium and repetitive or prolonged use is strongly discouraged as it may lead to severe corneal ulceration, or even perforation. The preservatives that are present are reported to interfere with bacterial cultures.57 Ideally laboratory submissions including bacterial, fungal, and viral cultures, and cytologic samples should be collected prior to application of any topical solutions, emulsions, or ointments. Fluorescein and Rose bengal are stains which are routinely used in ocular examinations. Fluorescein is a water-soluble dye which readily penetrates the conjunctival submucosa or the corneal stroma when the lipophilic epithelium has been disrupted. It is applied topically during the ophthalmic examination to confirm corneal ulceration. It is available as an impregnated strip or solution. Rose bengal is available as an impregnated strip. It is a supravital dye that is used to detect devitalized epithelium. These stains will interfere with bacterial and viral cultures and immunocytology, and therefore those laboratory submissions should be completed before these stains are applied.58,59

REFERENCES 1. Mishima, S. (1981) Clinical pharmacokinetics of the eye. Invest. Ophthalmol. Vis. Sci. 21: 504–541. 2. Peiffer, R.L. and Stowe, C.M. (1981) Veterinary ophthalmic pharmacology. In: Gelatt, K.N. (ed) Veterinary Ophthalmology. Philadelphia: Lea & Febiger, pp. 160–205. 3. Regnier, A. and Toutain, P.L. (1991) Ocular pharmacology and therapeutic modalities. In: Gelatt, K.N. (ed) Veterinary Ophthalmology, 2nd edn. Philadelphia: Lea & Febiger, pp. 162–194. 4. Doane, M.G., Jensen, A.D. and Dohlman, C.H. (1978) Penetration routes of topically applied eye medications. Am. J. Ophthalmol. 85: 383. 5. Schoenwald, R.D. (1990) Ocular drug delivery. Pharmacokinetic

considerations. Clin. Pharmacokinet. 18: 255–269. 6. Mikkelson, T.J., Chrai, S.S. and Robinson, J.R. (1973) Competitive inhibition of drug–protein interaction in eye fluids and tissues. J. Pharm. Sci. 62: 1942–1945. 7. Mikkelson, T.J., Chrai, S.S. and Robinson, J.R. (1973) Altered bioavailability of drugs in the eye due to drug–protein interaction. J. Pharm. Sci. 62: 1648–1653. 8. Shell, J.W. (1982) Pharmacokinetics of topically applied ophthalmic drugs. Surv. Ophthalmol. 26: 207–218. 9. Burstein, N.L. and Anderson, J.A. (1985) Review: Corneal penetration and ocular bioavailability of drugs. J. Ocular Pharmacol. 1: 309–326. 10. Bartlett, J.D. and Cullen, A.P. (1989) Clinical administration of ocular

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drugs. In: Bartlett, J.D. and Jaanus, S.D. (eds) Clinical Ocular Pharmacology. Toronto: ButterworthHeinemann, pp. 29–66. 11. Wine, N.A., Gonall, A.G. and Basu, P.K. (1964) The ocular uptake of subconjunctivally injected C14 hydrocortisone. I. Time and major route of penetration in a normal eye. Am. J. Ophthalmol. 58: 362–366. 12. McCartney, H.J., Drysdale, I.O., Gornall, A.G. et al. (1965) An autoradiographic study of the penetration of subconjunctivally injected hydrocortisone into the normal and inflamed rabbit eye. Invest. Ophthalmol. Vis. Sci. 4: 297–302. 13. Lapalus, P. and Garraffo, R.G. Ocular pharmacokinetics. In: Hockwin, O., Green, K.G. and Rubin, L.F. (eds) Manual of Oculotoxicity Testing. New York: Gustav Fischer, pp. 119–136. 14. Fraunfelder, F.T. and Hanna, C. (1974) Ophthalmic drug delivery systems. Surv. Ophthalmol. 18: 292–298. 15. Fisher, C.A. (1979) Granuloma formation associated with subconjunctival injection of a corticosteroid in dogs. J. Am. Vet. Med. Ass. 174: 1086–1088. 16. Murphy, C.M., Lavach, J.D. and Severin, G.A. (1978) Survey of conjunctival flora in dogs with clinical signs of external eye disease. J. Am. Vet. Med. Ass. 172: 66–68. 17. Gerding, P.A., McLaughlin, S.A. and Troop, M. (1988) Pathogenic bacteria and fungi associated with external ocular diseases in dogs: 131 cases (1981–1986). J. Am. Vet. Med. Ass. 193: 242–244. 18. Van Bijsterveld, O.P., Andriesse, H., Nielsen, B.H. (1987) Fusidic acid in tear film: pharmokinetic study of fusidic acid viscous eye drops. Eur. J. Drug Metab. Pharmokinet. 12: 215–218. 19. Petroutsos, G., Savoldelli, M. and Pauliquen, Y. (1990) The effect of gentamicin on the corneal endothelium. Cornea 9: 62–65.

20. Moller, I., Cook, C., Peiffer, R.L. et al. (1986) Indications for and complications of the pharmacological ablation of the ciliary body for the treatment of chronic glaucoma in the dog. J. Am. Anim. Hosp. Ass. 22: 319–326. 21. Nasisse, M.P., Guy, J.S., Davidson, M.G. et al. (1989) In vitro susceptibility of feline herpesvirus-1 to vidarabine, idoxuridine, tridfluridine, acyclovir, or bromovinlydeoxyuridine. Am. J. Vet. Res. 50: 58–60. 22. Maggs, D.J. and Clark, H.E. (2004) In-vitro efficacy of ganciclovir, cidofovir, pencyclovir, foscarnet, idoxuridine, and acyclovir against feline herpesvirus 1. Am. J. Vet. Res. 65: 399–403. 23. Sandmeyer, L.S., Keller, C.B. and Bienzle, D. (2005) Effects of cidofovir on cell death and replication of feline herpesvirus-1 in cultured feline corneal epithelial cells. Am. J. Res. 66: 217–222. 24. Severin, G.A. (1995) Severin’s Veterinary Ophthalmology Notes, 3rd edn. Fort Collins: Design Pointe Communications, pp. 88–89. 25. Noxon, J.O., Monroe, W.E. and Chinn, D.R. (1986) Ketaconazole therapy in canine and feline cryptococcosis. J. Am. Anim. Hosp. Ass. 22: 179. 26. Ford, M.M. (2004) Antifungals and their use in veterinary ophthalmology. In: Moore, C.P. (ed) Ocular Therapeutics. Vet. Clin. North Am. 34: 669–691. 27. Nasisse, M.P. (1991) Feline Ophthalmology. In: Gelatt, K.N. (ed) Veterinary Ophthalmology, 2nd edn. Philadelphia: Lea & Febiger, pp. 539–541. 28. Weiss, R.C. (1989) Synergistic antiviral activities of acyclovir and recombinant human leukocyte (alpha) interferon on feline herpes virus replication. Am. J. Vet. Res. 50: 1672– 1677. 29. Weiss, R.C. (1989) Synergistic antiviral activities of acyclovir and recombinant human leukocyte (alpha)

tracts of dogs. Am. J. Vet. Res. 51: 1131–1138. 39. Giuliano, E.A. (2004) Nonsteroidal anti-inflammatory drugs in veterinary ophthalmology. In: Moore, C.P. (ed) Ocular Therapeutics. Vet. Clin. North Am. 34: 707–723. 40. Gwin, R.M., Gelatt, K.N., Gum, G.G. et al. (1978) Effects of topical epinephrine and dipivalyl epinephrine on intraocular pressure and pupil size in the normotensive and glaucomatous beagle. Am. J. Vet. Res. 39: 83–86. 41. Gumm, G.G., Larocca, R.D., Gelatt, K.N. et al. (1991) The effect of topical timolol maleate on intraocular pressure in normal beagles and beagles with inherited glaucoma. Prog. Vet. Comp. Ophthalmol. 1: 141–149. 42. Lui, H.K., Chiou, G.C.Y. and Gorg, L.L. (1980) Ocular hypotensive effects of timolol in cat eyes. Arch. Ophthalmol. 98: 1467–1469. 43. Miller, P.E., Schmidt, G.M., Vainisi, S.J. et al. (2000) The efficacy of topical prophylactic antiglaucoma therapy in primary closed angle glaucoma in dogs: a multicenter clinical trial. J. Am. Anim. Hosp. Assoc. 36: 431–438. 44. Studer, M.E., Martin, C.L. and Stiles, M.J. (1998) The effect of latanaprost 0.005% on intraocular pressure in normal feline and canine eyes. Proc. Am. Coll. Vet. Ophthalmol. 29: 45. 45. Willis, A.M. (2004) Ocular hypotensive drugs. In: Moore, C.P. (ed) Ocular Therapeutics. Vet. Clin. North Am. 34: 755–776. 46. Dugan, S.J., Roberts, S.M. and Severin, G.A. (1989) Systemic osmotherapy for ophthalmic disease in dogs and cats. J. Am. Vet. Med. Ass. 194: 115–118. 47. Adams, R.E., Kirschner, R.J. and Leopold, I.H. (1963) Ocular hypotensive effect of intravenously administered mannitol. Arch. Ophthalmol. 69: 55–58. 48. Moller, I., Cook, C.S., Peiffer, R.L. et al. (1986) Indications for and complications of pharmacological

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interferon on feline herpesvirus replication. Am. J. Vet. Res. 50: 1672–1677. 30. Sandmeyer, L.S., Keller, C.B. and Bienzle, D. (2005) Effects of interferon-α on cytopathic changes and titers for feline herpesvirus-1 in primary cultures of feline corneal epithelial cells. Am. J. Res. 66: 210–216. 31. Collins, B.K., Nasisse, M.P. and Moore, C.P. (1995) In vitro efficacy of L-lysine supplementation on ocular shedding rate of feline herpesvirus type 1. Proc. Am. Coll. Vet. Ophthalmol. 26: 141. 32. Maggs, D.J. and Nasisse, M.P. (1997) Effects of L-lysine supplementation on ocular shedding rate of herpesvirus (FHV-1) in cats. Proc. Am. Coll. Vet. Ophthalmol. 28: 101. 33. Nasisse, M.P., Dorman, D.C., Jamison, K.C. et al. (1997) Effects of valcyclovir in cats infected with feline herpesvirus 1. Am. J. Vet. Res. 58: 1141–1144. 34. Gayles, B.I. and Fiscella, R. (2002) Topical non-steroidal antiinflammatory drugs for ophthalmic use: a safety review. Drug Saf. 25: 233–250. 35. Hendrix, D.V.H., Ward, D.A. and Barnhill, M.A. (2002) Effects of antiinflammatory drugs and preservatives on morphologic characteristics and migration of canine corneal epithelial cells in tissue culture. Vet. Ophthalmol. 5: 127–135. 36. Lin, J.C., Rapuano, C.J., Laibson, P.R. et al. (2000) Corneal melting associated with use of topical nonsteroidal anti-inflammatory drugs after ocular surgery. Arch. Ophthalmol. 118: 1129–1132. 37. Flach, A.J. (2001) Corneal melts associated with topically applied nonsteroidal anti-inflammatory drugs. Trans. Am. Ophthalmol. Soc. 99: 205–212. 38. Dow, S.W., Rosychuk, R.A., McChesney, A.E. et al. (1990) Effects of flunixin and flunixin plus prednisone on the gastrointestinal

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ablation of the ciliary body for the treatment of chronic glaucoma in the dog. J. Am. Anim. Hosp. Assoc. 1986; 22: 319–326. 49. Bingaman, D.P., Lindley, D.M., Glickman, N.W. et al. (1994) Intraocular gentamicin and glaucoma: a retrospective study of 60 dog and cat eyes (1985–1993). Vet. Comp. Ophthalmol. 4: 113–119. 50. Peiffer, R.L. and Harling, D.E. (1998) Intravitreal cidofovir (Vistide) in the management of glaucoma in the dog and cat. Proc. Am. Coll. Vet. Ophthalmol. 29: 29. 51. Scagliotti, R.H. (1998) Neuroophthalmology. In: Gelatt, K.N. (ed) Veterinary Ophthalmology, 3rd edn. Philadelphia: Lea & Febiger, pp. 1307–1400. 52. Kaswan, R.L., Salisbury, M.A. and Ward, D.A. (1989) Spontaneous canine keratoconjunctivitis: a model for human keratoconjunctivitis sicca – treatment with cyclosporine eye drops. Arch. Ophthalmol. 107: 1210. 53. Jackson, P.A., Kaswan, R.L., Meredith, R.E. et al. (1991) Chronic superficial keratitis in dogs: a placebo controlled trial of topical cyclosporine treatment. Prog. Vet. Comp. Ophthalmol. 1: 269–275.

54. Berdoulay, A., English, R.V., Nadelstein, B. et al. (2003) The effect of 0.02% tacrolimus aqueous suspension on the tear film in dogs with keratoconjunctivitis sicca. Proc. Am. Coll. Vet. Ophthalmol. 34: 33. 55. Adkins, E.A., Hendrix, D.V.H., Stuffle, J.L. et al. (2003) An investigation of the safety and efficacy of topical ophthalmic application of tacrolimus in dogs. Proc. Am. Coll. Vet. Ophthalmol. 34: 39. 56. Rubin, L.F. and Aguirre, G.D. (1969) Clinical use of pilocarpine for keratoconjunctivitis in dogs and cats. J. Am. Vet. Med. Ass. 151: 313. 57. Kleinfeld, J. and Ellis, P.P. (1966) Effects of topical anesthetics on growth of microorganisms. Arch. Ophthalmol. 76: 712–715. 58. Roat, M.E., Romanowski, E., Araullo-Cruz, T. et al. (1987) The antiviral effect of rose bengal and fluorescein. Arch. Ophthalmol. 105: 1415–1417. 59. da Silva Curiel, J.M.A., Nasisse, M.P., Hook, R. et al. (1991) Topical fluorescein dye: effects on immunofluorescent antibody tests for feline herpesvirus keratoconjunctivitis. Prog. Vet. Comp. Ophthalmol. 1: 99–104.

Abnormal appearance Wendy Townsend, Peter Bedford, and Gareth Jones

4

The conditions discussed in this chapter are those in which an alteration in the gross appearance of the eye is the primary presenting clinical feature. Other signs of disease may also be present and the reader should refer to other chapters in this book in cases where visual impairment, ocular pain, or ocular discharge is the most significant presenting sign. The first part of this chapter describes the normal appearance of the eye and adnexa (Figs 4.1 & 4.2). Abnormal appearance is discussed in the second part of the chapter.

NORMAL APPEARANCE Selective breeding, particularly in dogs, has resulted in a wide variation in skull shape, globe position, and adnexal conformation. Many of these traits may be considered ‘normal’ for a particular breed. Examples include the exophthalmos (globe prominence) and lagophthalmos (failure to blink completely) noted frequently in brachycephalic animals. In all cases the clinician must decide if the noted attribute is an incidental finding or associated with ocular disease.

The globe The size of the globe, shape and length of the palpebral fissure, and depth of the orbit all contribute to the external appearance of the eye. Brachycephalic animals have shallow orbits and large palpebral fissures resulting in a very prominent globe. In contrast, dolicocephalic dogs have the globe positioned deeper within the orbit resulting in a much less prominent globe. In all animals the globe should be centrally positioned within the orbit and freely mobile. The extraocular muscles provide globe movement and maintain a centrally directed gaze. Sympathetic innervation of the orbital smooth muscle (muscularis orbitalis) maintains positive tone within the orbit and thereby an anterior position of the globe. The retractor bulbi muscles function to retract the globe.

The eyelids The appearance and position of the eyelids are determined by a number of factors including the length of the palpebral fissure, physical support by the

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SMALL ANIMAL OPHTHALMOLOGY Fig. 4.1 The normal appearance of the eye and adnexa in the dog. Right eye.

Fig. 4.2 The normal appearance of the eye and adnexa in the cat. Right eye.

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presence of the globe, and tension at the medial and lateral canthi. The shape of the cranium and mass of facial skin can alter this relationship, leading to conformational differences between the breeds. An example of an abnormality required by breed standards is the ‘diamond eye’ conformation in breeds like the St Bernard and the Bloodhound, where central lower ectropion and third eyelid exposure can be responsible for chronic conjunctivitis. Similarly Shar Peis have excess facial skin that frequently contributes to entropion. In normal animals the eyelids rest on the globe and follow its contour. The eyelid margins are hairless and distinct. In dogs two to four rows of cilia are present along the upper eyelid. Varying amounts of sclera are exposed depending upon breed and facial conformation. Cats have little exposed sclera and no true cilia.

ABNORMAL APPEARANCE

The eyelids protect the globe, remove debris from the ocular surface, and distribute the tear film. The eyelids should move freely and fully across the corneal surface. The superior eyelid is the most mobile. Regular blinking is an essential feature. Dogs blink three to five times per minute; cats one to five times per minute. Brachycephalic animals blink less frequently and less completely (lagophthalmos) due to their exophthalmos and decreased corneal sensitivity. Cats normally demonstrate complete and incomplete blinks. Elevation of the upper eyelid occurs primarily through the action of the levator palpebrae superioris muscle that is innervated by cranial nerve III, assisted by the smooth muscle fibers of Müller’s muscle. The orbicularis oculi muscle innervated by cranial nerve VII is responsible for closure of the eyelids.

The third eyelid The third eyelid (membrana nictitans) arises as a fold of ventromedial conjunctiva and lies against the anteromedial aspect of the globe. A T-shaped cartilage stabilizes the third eyelid. The top of the T runs across the free edge and the base runs through the center to end in the gland of the third eyelid. The leading edge of the third eyelid may or may not be pigmented (Figs 4.3 & 4.4). When lacking pigment, the third eyelid appears more prominent. The position of the third eyelid is influenced by globe size, position of the globe within the orbit, orbital depth and contents, and length of the palpebral fissure. Movement of the third eyelid is passive in dogs. Retraction of the globe will result in protrusion of the third eyelid. In cats, smooth muscle contributes to movement of the third eyelid and sympathetic stimulation can cause the third eyelid to move slightly.

The conjunctiva/sclera The conjunctiva is the transparent mucous membrane that lines the eyelids (palpebral conjunctiva) and covers the membrana nictitans and the anterior sclera (bulbar conjunctiva). There is little variation between species and breeds.

Fig. 4.3 The normally pigmented leading edge of the membrana nictitans in a 2-yearold German Shepherd Dog. Left eye.

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SMALL ANIMAL OPHTHALMOLOGY Fig. 4.4

Left eye of a dog with a non-pigmented leading edge to the third eyelid.

Fig. 4.5 eye.

Comparison of the bulbar, palpebral, and membrana conjunctival surfaces. Left

Pigmentation may be normal, especially within the palpebral fissure, and is usually diffuse and irregular. It is important to appreciate the differences in normal appearance across the conjunctival sac. The bulbar conjunctiva is loosely bound to the globe and it appears mainly white due to the color of the sclera beneath. Blood-filled capillaries impart a salmon pink color. Elements of the underlying episcleral vasculature are not very prominent in the normal dog but are more readily seen in the cat. In contrast, the palpebral conjunctiva is firmly attached and its deep pink appearance is that of the underlying tarsal tissues (Fig. 4.5). The conjunctiva within the fornix has a similar coloration but is loosely attached.

The cornea 70

The normal cornea is transparent with a glossy and smooth anterior surface. The junction between the cornea and sclera is the limbus. The corneal diameter

ABNORMAL APPEARANCE

varies from 12.5 mm in the dog to 18.0 mm in the cat. The radius of curvature is approximately 8 mm. Multiple layers comprise the cornea. The tear film is the outermost later which overlies a multilayered epithelium and creates a smooth optical surface. The thickest corneal layer, the stroma, is predominantly collagen fibrils in regularly arranged lamellae that provide optical clarity. Descemet’s membrane is the basement membrane of the innermost layer, a single layer of endothelium. In order to allow transparency, the cornea is avascular; nutrition is supplied via the aqueous and to a lesser extent by the precorneal tear film, limbal scleral circulation, and conjunctival vasculature. The stroma must be maintained in a relative state of dehydration for transparency and both the epithelium and endothelium are involved in this process. The epithelium presents a barrier to water in the tear film while an active endothelial pump mechanism regulates fluid exchange with the aqueous. In puppies and kittens, it is common for the cornea to appear cloudy immediately after the palpebral fissure first opens and before the endothelial ‘pump’ becomes fully functional.

The aqueous and the anterior chamber The aqueous is a modified ultrafiltrate of blood and is normally transparent due to a low protein and cell content. It is produced by the ciliary processes, released into the posterior chamber, and flows forward between the iris and lens through the pupil into the anterior chamber. The aqueous circulates thermodynamically within the anterior chamber and drains into the scleral vasculature through the 360° of the iridocorneal angle. In domestic species, the angle extends into the ciliary body as the ciliary cleft. The entrance to the cleft is spanned by fibers of the pectinate ligament and the cleft contains the trabecular meshwork. The pectinate ligament may be visualized with the naked eye in the cat because of the considerable depth of the anterior chamber. In the dog, the use of a goniolens is required to examine the iridocorneal angle (see Fig. 2.9). Individual variation exists in both the amount of pigmentation in the scleral shelf and the physical structure of the pectinate ligament. Those individuals with a wider pigmentary zone are more difficult to examine. The pectinate ligament should always be visible. Intraocular pressure (IOP) is maintained by homeostatic mechanisms resulting in equilibrium between the rates of aqueous production and outflow. The normal IOP ranges from 13 to 24 mmHg.1 In the dog this value can fall to below 10 mmHg with age.

The iris The iris rests on the anterior surface of the lens, imparting an anterior bow to the iris. Loss of this lenticular support results in flattening of the iridal surface, a deepened anterior chamber, and iridodonesis (trembling of the iris) with ocular movement. The iris is divided into two areas by the collarette (the area where the iris changes from a lighter to a darker color): the ciliary zone (peripherally) and the pupillary zone (centrally). The pupillary ruff is the edge of the iris that forms the pupil. The major arterial circle is the prominent circular vessel within the ciliary zone; this vessel is especially easy to visualize in cats with blue irides. The anterior iris is defined by a condensation of melanocytes and a pigmented epithelium lines its posterior surface. The stroma of the iris

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contains two muscles: the iris dilator (longitudinal muscle) and the iris constrictor (circular muscle located in the pupillary zone). The iris regulates the amount of light entering the eye via the constrictor and dilator muscles. Iris coloration is related to the density of coat and skin pigmentation and consequently demonstrates considerable variation between both species and breeds. Darker coated breeds of dog will have a dark brown iris while in the subalbinotic breeds the iris is often blue (Fig. 4.6). Yellow, green, and blue iris coloration can all be seen in cats (Fig. 4.7). Heterochromia iridis describes a difference in color within the same iris and heterochromia irides describes a difference in color between the two irides of the same individual.

Fig. 4.6 A blue iris demonstrating the difference in color density between the ciliary and pupillary zones in a 4year-old Siberian Husky. Left eye.

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Fig. 4.7

Blue iris color in a 2-year-old cat.

The pupil The pupil is round in the dog and a vertical ellipse when constricted in the cat. A slight exposure of the darkly colored iris pigment epithelium may occur at the pupillary rim. Abnormal prominence of the iris pigment epithelium may occur with cystic hypertrophy due to chronic uveitis. Eversion of the pupillary margin (ectropion uveae) may occur secondary to formation of pre-iridal fibrovascular membranes (rubeosis iridis). The pupil should move freely with maximal dilatation in the dark and brisk constriction in bright light; this movement is observed when assessing the direct and consensual pupillary light responses. Senile iris atrophy may cause an irregular scalloped pupillary margin and incomplete constriction in bright light. Posterior synechia (adhesions between the iris and anterior lens capsule) may also distort the pupillary margin and prevent free pupillary movement.

ABNORMAL APPEARANCE

Senile iris atrophy can result in a lace-like appearance demonstrable by transillumination or retroillumination using reflection of light from the fundus to highlight the thinned iris. Atrophy of the sphincter muscle results in pupil irregularities and reduced pupillary constriction.

The lens The lens is a transparent biconvex structure enclosed within its own capsule. Nutrition is via fluid exchange with the aqueous across the lens capsule. The lens is normally positioned between the posterior iridal surface and the vitreous body. Without the use of mydriatic drugs to dilate the pupil, only the axial portion of the lens is visible. With mydriasis a complete examination of the lens including the equatorial regions can be performed. Lens transparency is attributed to the absence of blood vessels and the precise arrangement of the proteins within the lens fibers. New cortical fibers are formed throughout life by the equatorially positioned lens epithelial cells. The anterior Y and posterior inverted Y suture lines mark the meeting of the ends of lens fibers. In young animals increased prominence of the tips of these suture lines may be present. The continuous cortical lens fiber formation causes compression of the central nuclear material which results in altered refraction through the nuclear region noted clinically as nuclear sclerosis. Nuclear sclerosis is a normal aging change which can be differentiated from a true cataract using indirect ophthalmoscopy, distant direct ophthalmoscopy, or distant examination with a transilluminator. The tapetal reflex and detail of the fundus can be observed through a sclerotic nucleus.

The posterior segment The fundus is divided into tapetal and non-tapetal areas. The non-tapetal area occupies the greater part of the fundus and this area is usually darkly colored due to pigment within the retinal pigment epithelium and the underlying choroid. The retinal pigment epithelium, which overlies the reflective brightly colored tapetum, is non-pigmented. Tapetal color varies, but most commonly is yellow, orange, green, or blue (Fig. 4.8). The tapetum may be small or completely absent, particularly in the toy breeds. A ‘red’ reflex is normal in subalbinotic breeds which may lack a tapetum in addition to having reduced or absent pigment within the retinal pigment epithelium and choroids (Fig. 4.9). Edema and/or infiltrates within the vitreous, retina, or sub-retinal space will

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Fig. 4.8 A yellow-green tapetal reflex in a 4-yearold crossbred dog.

Fig. 4.9 The red tapetal reflex due to subalbinism in a 2-year-old Old English Sheepdog.

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reduce the intensity of the tapetal reflex. Where the retina is degenerate or absent due to complete detachment, tapetal reflectivity will be considerably increased. In the presence of extensive retinal degeneration there will be a loss of the pupillary light reflex, which enhances the appearance of the increased reflection from the affected eye. In dogs the optic disk is circular to triangular in shape, the variation due to varying degrees of myelination. The disk may reside in the tapetal or nontapetal fundus as the size of the tapetum varies greatly between individuals.

ABNORMAL APPEARANCE

The dark gray spot in the center of the disk represents the physiologic pit. Three to four large retinal venules anastomose in an incomplete venous circle over the optic disk. Fifteen to 20 arterioles, lighter in color and more tortuous than the venules, radiate away from the periphery of the optic disk. In cats the optic disk is unmyelinated which accounts for its perfectly circular and dark salmon to grey coloration. The disk is always located in the tapetal fundus. The feline tapetum is more brightly reflective than that of the dog. Three to five main pairs of retinal arterioles and venules are present. The venules do not traverse the surface of the optic disk.

ABNORMAL APPEARANCE The eye should never be examined in isolation. The ocular examination should be systematic. The most significant changes in appearance are listed in Table 4.1. Each clinical sign listed in Table 4.1 will be discussed in terms of investigation, diagnosis, and treatment.

The globe Changes in globe size Abnormally small globe Microphthalmos is the presence of a congenitally small globe. Microphthalmos may be seen alone or in association with multiple ocular anomalies including nystagmus, persistent pupillary membranes, colobomata, cataract, and retinal dysplasia. Associated cataracts are usually non-progressive. The degree of visual impairment depends upon the extent of the abnormalities. Penetrating sharp trauma or perforation of a corneal ulcer through Descemet’s membrane may lead to collapse of the globe. A careful ophthalmic examination should be performed to assess damage while preventing further trauma to the globe. Prompt repair can be successful depending upon the extent of intraocular damage. The prognosis for vision following globe rupture from blunt trauma is usually poor due to more pronounced intraocular damage. Phthisis bulbi is a previously normal globe that has become irreversibly damaged, hypotensive, and shrunken. Phthisis bulbi is a common sequela to severe injury, chronic uveitis, or long-standing glaucoma. Phthisical eyes are non-visual. If the eye is a chronic source of discomfort, enucleation is indicated. In phthisical feline globes, post-traumatic sarcomas have developed. These sarcomas are very aggressive and often metastasize.2 Therefore enucleation of blind traumatized feline globes is recommended.

Enlarged globe Buphthalmos is the acquired enlargement of a globe, typically associated with glaucoma. Buphthalmos must be differentiated from exophthalmos (rostral displacement of the globe within the orbit). The cardinal signs of glaucoma are a dilated non-responsive pupil, episcleral congestion, corneal edema, and an elevated IOP. Degenerative corneal changes may occur with chronic glaucoma. Linear breaks in Descemet’s membrane (Haab’s striae) also indicate increased globe size (Fig. 4.10). Buphthalmic globes are usually blind due to the associated ganglion cell degeneration and optic nerve atrophy; exceptions include the

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Table 4.1 Abnormal appearance. Globe Small globe

Globe rupture, microphthalmos, phthisis bulbi

Enlarged globe

Glaucoma, neoplasia

Exophthalmos

Arteriovenous fistula (rare), orbital fracture, retrobulbar space-occupying lesion (e.g. masticatory myositis, extraocular polymyositis, neoplasia, retrobulbar abscess/cellulites, zygomatic mucocele), temporomandibular osteopathy, traumatic proptosis

Enophthalmos

Horner’s syndrome, loss of retrobulbar fat (debility, senility), orbital fracture, severe ocular pain, temporal muscle atrophy, contracture of extraocular muscles

Eyelids Alopecia

Bacterial pyoderma, immune-mediated disease, mycoses, nutritional disease, parasitic infestation, seborrhea

Swellings/masses

Abscess, allergy, epibulbar dermoid, neoplasia, ophthalmia neonatorum, trauma

Shape of palpebral fissure

Coloboma, ectropion, entropion, combined entropion/ectropion (diamond eye), laceration, symblepharon, dermoid, ankyloblepharon, Horner’s syndrome

Membrana nictitans Prominence

Anterior segment pain, dysautonomia, Horner’s syndrome, retrobulbar lesion, sedation, ‘Haw’s syndrome’, symblepharon, systemic disease (e.g. tetanus)

Distortion

Prolapse of the nictitans gland, scrolling of the cartilage

Masses

Lymphoid follicles, neoplasia, plasma cell infiltration

Conjunctiva/sclera

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Redness

Conjunctivitis (superficial), ciliary flush/episcleral congestion, episcleritis (deep), subconjunctival hemorrhage

Swelling

Allergy, conjunctivitis, diffuse neoplasia

Masses

Cyst, neoplasia, nodular episcleritis

Cornea Opacity

Cellular infiltration (white/gray), edema (white/ blue), pigmentation (black), scarring (blue/gray), vascularization (red)

Masses

Dermoid, granulation tissue, inclusion cysts, abscess, infiltrative neoplasia

Vascularization

Superficial and deep keratitis, corneal infiltration and degeneration, eosinophilic keratitis, healing ulcer, herpes keratitis, immune-mediated disease, sequestrum, trauma

Infiltration

Calcareous degeneration, corneal ‘melting’ ulcer, lipidosis (dystrophy, degeneration, and infiltration), neoplasia

Change in contour

Bullous keratopathy, corneal abscess, corneal laceration, descemetocele, inclusion cyst, iris prolapse

Loss of tissue

Laceration, ulceration, post-corneal nigrum slough

ABNORMAL APPEARANCE

Table 4.1 continued

Anterior chamber Turbidity

Lipid-laden aqueous, uveitis (flare/hypopyon, keratic precipitates, hyphema)

Masses

Foreign body, lens luxation, neoplasia, uveal cyst

Hyphema

Blood dyscrasias, chronic glaucoma, congenital lesions, hypertension, neoplasia, retinal detachment, trauma, uveitis

Iris Discoloration

Chronic uveitis (pigmentation), rubeosis iridis (vascularization)

Masses

Neoplasia, uveal cysts

‘Strands’

Persistent pupillary membrane, synechiae

Pupil Dilated

Coloboma, dysautonomia, glaucoma, iris atrophy, oculomotor nerve lesion, optic neuropathy, retinopathy, pharmacologic agents, fear

Constricted

Uveitis, Horner’s syndrome, pharmacologic agents

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Table 4.1 continued Distorted

Synechiae, coloboma, iridodonesis, ‘D’-shaped pupil, iris atrophy

Lens Opacification

Cataract, uveitis (anterior capsular pigment), nuclear sclerosis, persistent pupillary membrane, persistent hyperplastic primary vitreous

Shape

Lenticonus, coloboma

Position

Luxation, subluxation

Posterior segment

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Leukocoria (white pupil)

Cataract, intraocular foreign body, neoplasia, persistent hyperplastic primary vitreous, retinal detachment, vitreous abscess

Increased reflectivity (+ dilated pupil)

Retinal degeneration, retinal detachment with disinsertion

Decreased reflectivity

Posterior uveitis (vitreal haze), bullous retinal detachment

Fig. 4.10 Haab’s striae in chronic glaucoma. Right eye, 6-year-old Norwegian Elkhound.

ABNORMAL APPEARANCE

globes of young animals where the elastic sclera can allow for globe enlargement with some degree of vision remaining. A similar finding is occasionally found in dogs where the IOP is only moderately elevated. For permanently blind eyes options to improve patient comfort include enucleation or evisceration and implantation of an intrascleral silicone prosthesis. An alternative approach is to destroy part of the ciliary body to reduce IOP. Techniques include cyclocryotherapy, cyclophotocoagulation, and pharmacologic ablation using intravitreal gentamicin or cidofovir.3 In every instance the etiology of the glaucoma should be determined in order to rule out the presence of an intraocular tumor resulting in secondary glaucoma.

Changes in globe position Exophthalmos (globe protrusion) Exophthalmos is the rostral displacement of a normal sized globe within the orbit (Fig. 4.11). This displacement will cause widening of the palpebral fissure and may prevent complete eyelid closure. The induced lagophthalmos may result in exposure keratitis (drying and ulceration of the central cornea) to develop. A comparison of the position of each globe, particularly when viewed from above, helps to distinguish exophthalmos from buphthalmos. Resistance of the globe to retropulsion is also helpful to confirm exophthalmos. The direction of displacement of the globe can be helpful in localizing the site of the mass lesion. The third eyelid is often passively elevated due to displacement by a spaceoccupying lesion. Intraconal lesions (within the endorbital muscle cone) often have minimal protrusion of the nictitating membrane as compared to extra-

Fig. 4.11 A retrobulbar neoplasm causing exophthalmos in a 1-year-old Springer Spaniel.

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conal lesions (outside the endorbital muscle cone but within the soft tissue confines of the orbit).4 Historical information concerning chronicity, progression, and association with trauma may assist in ranking differential diagnoses. The presence of pain, particularly upon opening the mouth, is highly suggestive of a retrobulbar abscess, orbital fracture, or masticatory muscle myositis. One must perform a careful oral examination with particular attention paid to the area caudal to the last upper molar where extension of retrobulbar neoplasia, the draining sinus of a retrobulbar abscess, or distension due to zygomatic mucocele formation may be observed. Radiography may only reveal non-specific soft tissue swelling although an occlusal view of the nasal cavity is important in the investigation of nasal tumors, which can erode through the orbital wall. Periosteal changes may be seen in craniomandibular osteopathy. Dental radiographs may reveal fractured tooth roots and lytic areas along the maxilla. Ultrasonographic examination can confirm the presence as well as the location of a retrobulbar mass and may give some indication of the tissue type based on the echo texture.5 Imaging techniques such as computed tomography (CT) and magnetic resonance imaging (MRI) can be invaluable.6 A fine needle aspirate may allow for a cytologic diagnosis.7 An exploratory orbitotomy may be necessary to confirm the exact nature and extent of the orbital pathology. Orbital abscesses or cellulitis are common, especially in young dogs that chew on sticks. The lesions are typically acute and unilateral. Marked pain is often present upon opening the mouth. Upon oral examination a fluctuant swelling and/or mucosal hyperemia are often noted caudal to the ipsilateral last molar (see Ch. 6). Extraocular polymyositis typically occurs in young Golden Retrievers and causes a bilateral, non-painful exophthalmos with reduced ocular movement (Fig. 4.12). Minimal spongy resistance to retropulsion is detected. Ultrasonographic examination or CT will demonstrate the swollen extraocular muscles. The inflammation must be suppressed with systemic corticosteroids and, if

Fig. 4.12 Extraocular polymyositis in a Golden Retriever. Note the marked exophthalmos but no third eyelid protrusion. (Courtesy of Dr D. Ramsey.)

ABNORMAL APPEARANCE

required, azathioprine. If untreated, fibrosis and contracture of the muscles may cause the development of strabismus and enophthalmos.8 The prognosis for orbital neoplasia is dependent on the nature of the tumor; the majority of these lesions are primary and malignant. Animals are usually older with a slowly progressive, non-painful exophthalmos. Only rarely can a tumor be removed via an orbitotomy without an enucleation. Usually exenteration (removal of the globe and orbital contents) is required and in many patients even this is not curative. Lateral orbitotomy enables extirpation of the zygomatic salivary gland when mucocele formation is the cause of the exophthalmos.

Enophthalmos (globe recession) Enophthalmos is the recession of a normal sized globe into the orbit. There is associated elevation of the third eyelid and variable narrowing of the palpebral fissure. Retraction of the globe as a result of pain is a common cause. If enophthalmos follows trauma, the clinician should check to see if the globe has been perforated or ruptured, or if there are periorbital fractures. A ruptured globe will be hypotensive. Ultrasonographic examination may be required to demonstrate the presence of a posterior scleral rupture. Enophthalmos may also result from loss of retrobulbar fat in cachexic states, the presence of retrobulbar scar tissue, post-inflammatory contracture of the extraocular muscles or chronic, post-masticatory muscle myositis muscle wasting. The history and clinical signs should make the diagnosis obvious and the treatment is addressed to the cause. Horner’s syndrome is a common cause of enophthalmos. The other cardinal signs of Horner’s syndrome are ptosis, relative miosis, and elevation of the third eyelid (Fig. 4.13). As the pain associated with a corneal ulcer or anterior uveitis can cause similar clinical signs, staining with fluorescein dye and a complete ocular examination are indicated. Pharmacologic testing with phenylephrine

Fig. 4.13 Third order Horner’s syndrome following bullous osteotomy in a 4-year-old domestic short-haired (DSH) cat. The signs of ptosis, miosis, enophthalmos, and membrana nictitans protrusion are present in the right eye.

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can confirm the presence of Horner’s syndrome and give an indication as to whether the lesion is central (first order), preganglionic (second order), or postganglionic (third order).9 Pupillary dilatation and third eyelid retraction within 20 min following topical application of 10% phenylephrine is suggestive of third order Horner’s syndrome; responses greater than 20 min suggest first or second order lesions. Common causes of Horner’s syndrome include middle ear disease, iatrogenic damage sustained during total ear canal ablations, and trauma to the neck. Less common causes include polyneuropathy, neoplasia, and brachial plexus avulsion. A complete physical examination focusing upon the tympanic membrane, middle ear, cervical, and thoracic regions is indicated. In many instances the etiology remains obscure and clinical signs resolve after 60–90 days. The incidence of idiopathic Horner’s syndrome appears to be increased in the Golden Retriever.10

Proptosis Traumatic proptosis occurs when a sudden forward displacement of the globe traps the eyelid margins behind the globe’s equator (Fig. 4.14). Minor trauma such as scruffing or dog fights may result in proptosis in the brachycephalic breeds. Proptosis in the dolicocephalic breeds or cats requires considerable trauma. Various criteria including the absence of the pupillary light reflex and the degree of ocular damage are used to determine the prognosis for vision.11 Often the eye is blind due to the accompanying optic neuropraxia or damage. If three or more rectus muscles are torn, the optic nerve has been transected; if the cornea or sclera is ruptured, the globe should be enucleated. In those eyes deemed salvageable, the cornea must be kept moist until the animal is stable for general anesthesia. Under anesthesia a lateral canthotomy to enlarge the palpebral fissure will facilitate globe replacement. A temporary tarsorrhaphy is then performed to maintain the globe in situ. The tarsorrhaphy is maintained until the orbital swelling subsides and lid movement is noted; the sutures are then removed in a staggered fashion. Lateral (divergent) strabismus is a

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Fig. 4.14 Traumatic proptosis of the right eye in a 5-year-old Cavalier King Charles Spaniel. Complete avulsion of the optic nerve has occurred.

Changes in primary gaze Strabismus Strabismus is a deviation in the position of the globe that can be due to a congenital anomaly, a neurologic lesion, or abnormality of the extraocular muscles. Congenital esotropia (bilateral medial strabismus) is seen in Siamese cats. Acquired strabismus may result from traumatic proptosis or retrobulbar lesions. Lesions of cranial nerves III, IV, and VI will produce specific deviations. A progressive, restrictive ventromedial strabismus has been reported in young dogs, particularly Shar Peis, that appears to result from post-inflammatory changes to the extraocular muscles (Fig. 4.16).12

ABNORMAL APPEARANCE

common sequela due to oculomotor nerve damage or avulsion of the medial rectus muscle (Fig. 4.15).

Fig. 4.15 Acquired strabismus following traumatic proptosis in a 3-year-old Tibetan Spaniel. Rupture of the medial rectus muscle has occurred. Left eye.

Fig. 4.16 Ventromedial strabismus due to progressive extraocular muscle fibrosis in a 2year-old Chow Chow dog.

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Nystagmus Nystagmus is an involuntary oscillatory movement of the eyes that consists of alternating slow and fast phases. During the slow phase the eyes move away from the primary gaze position (straight ahead), followed by the fast phase which recenters the eyes. Normal nystagmus can be induced as a response to movement of the head, for example in the oculocephalic reflex. Abnormal nystagmus is associated with central or peripheral vestibular disease and in some cases only occurs when the animal’s head is moved to a particular position (positional nystagmus). It may be present without changing head position (spontaneous nystagmus). Animals with multiple congenital ocular abnormalities (e.g. microphthalmos, persistent pupillary membranes, and cataract), or conditions resulting in a very early onset of blindness, often show abnormal eye movements of an oscillatory or wandering nature which are described as a searching nystagmus. Cerebellar disease can also result in oscillatory eye movements.

The eyelids Congenital/neonatal eyelid conditions A coloboma is a congenital absence of tissue within the eye or its adnexa. In the cat, colobomas usually involve the lateral part of the upper eyelid and are bilateral. The absence of the eyelid margin is obvious and haired skin will be seen fused to the bulbar conjunctiva obliterating most of the dorsal conjunctival fornix. Eyelid closure is not complete and exposure keratitis results. The associated trichiasis also results in keratitis and discomfort (Fig. 4.17). Blepharoplastic techniques are necessary to correct the deformity, but success in producing an adequate blink response depends on the amount of normal eyelid present. An epibulbar dermoid (choristoma) is a congenital mass of haired skin in an abnormal location. The dermoid may involve the eyelid, the conjunctiva, the cornea, or all three. The temporal limbus is the most common site of involvement (Fig. 4.18). Treatment is by resection, keratectomy, or blepharoplastic repair depending upon the location.

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Fig. 4.17 A lateral upper eyelid coloboma (eyelid agenesis) in a 2year-old DSH causing trichiasis, corneal vascularization, and elevation of the third eyelid. Right eye.

ABNORMAL APPEARANCE Fig. 4.18 Temporal limbal dermoid in a 6month-old Shih Tzu dog. Left eye.

Fusion of the eyelids (ankyloblepharon) is normal in kittens and puppies up to 10–14 days of age. On occasion it may persist beyond this time, necessitating surgical separation of the fused lids. Ophthalmia neonatorum is the development of a purulent conjunctivitis prior to eyelid opening which results in a swelling of the fused lids. Early intervention is required to avoid corneal damage and loss of the eye. The eyelids must be opened, the material collected for culture, and the conjunctival sac irrigated. Broad-spectrum topical antibiotics are then applied to control bacterial infection and keep the ocular surface moist until tear production is established. Abnormalities of eyelid conformation are common and often breed related. An inward rolling of the eyelid margin is called entropion while an eversion is termed ectropion. In entropion the resultant trichiasis can result in superficial keratitis and corneal ulceration. Surgical intervention is required to correct the eyelid deformity (see Ch. 6). Ectropion causes chronic exposure of the ventral conjunctival sac which may lead to permanent conjunctival changes. Several techniques involving eyelid shortening and lateral canthoplasty are available for the correction of ectropion should this prove to be necessary.13 Many patients can be managed using daily irrigation with sterile saline and periodic use of lubricating ointments. A combination of ectropion and entropion associated with overly long eyelids and a weak lateral canthal ligament is seen in breeds that select for a diamond-shaped palpebral fissure. Surgical correction is challenging and several procedures have been devised to shorten and lift the palpebral fissure.14

Acquired eyelid lesions Traumatic eyelid lacerations require careful surgical repair with minimal debridement and treatment of any secondary infection. In particular accurate apposition of the eyelid margin is required for a satisfactory result. Blepharitis has a number of possible causes including bacterial pyoderma, immune-mediated disease, mycotic infection, parasitic infestation, and sebor-

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rhea. Obtaining a specific diagnosis depends on skin scrapings, bacteriologic culture, and/or biopsy. Treatment is with systemic antibiotics, antifungals, corticosteroids, and antiparasitic drugs as indicated. The initial blepharitis is often exacerbated by self-trauma. Measures should be taken to control selftrauma as part of managing this condition. Swellings or masses of the eyelids may be due to abscess formation (stye or hordeolum), chalazion, allergy, epibulbar dermoid, neoplasia, ophthalmia neonatorum, and trauma. Hordeola (styes) result from bacterial abscesses involving the meibomian gland or the glands of Zeiss or Moll. Treatment requires the use of systemic antibiotics, hot compresses, and surgical drainage. A chalazion results from the retention or blockage of the oily secretions within a meibomian gland, which ruptures into the surrounding eyelid tissue inciting an inflammatory response; in dogs they are most commonly encountered associated with meibomian adenomas. Chalazia are firm, nodular, non-painful, yellow-gray masses when viewed on the conjunctival surface. Treatment requires curettage and application of a topical antibiotic and corticosteroid solution. Eyelid tumors in the dog are usually benign. The most common tumor is the meibomian gland adenoma. Benign tumors involving up to approximately one-fourth of the eyelid length can be treated successfully by wedge resection and direct two-layer closure. Removal of larger tumors often requires more elaborate reconstructive procedures. Eyelid tumors in cats are more commonly malignant and include squamous cell carcinoma and fibrosarcoma (Fig. 4.19). Facial paralysis results in a loss of the palpebral reflex and thereby possible exposure-induced damage to the ocular surface. If the initial portion of the facial nerve is affected, the parasympathetic innervation to the lacrimal gland and gland of the third eyelid may be disrupted, resulting in reduced tear production. Unilateral facial nerve paralysis may be idiopathic or associated with erosive middle ear disease. Bilateral lesions may be idiopathic although systemic endocrinopathies, such as hypothyroidism, which may be associated with

Fig. 4.19 Upper eyelid mast cell tumor with a small central area of erosion in a 4-year-old DSH. Left eye.

ABNORMAL APPEARANCE

neuropathies, should be considered. Brachycephalic dogs with their prominent globes and shallow orbits are most likely to develop severe exposure keratopathy as a result of facial paralysis. In all cases topical tear replacement should be applied frequently. If the third eyelid does not adequately spread the tear film during attempted blinks, a temporary tarsorrhaphy can be performed until normal eyelid movement is restored. If the condition cannot be corrected, a permanent canthoplasty may be required to provide adequate corneal coverage. The epiphora-induced staining of facial hair at the medial canthus indicates excessive lacrimation, poor tear drainage, or both (Fig. 4.20). Excessive lacrimation is suggested by Schirmer tear test values greater than 25 mm of wetting per minute. The clinician must determine the cause of excessive lacrimation to correct the overflow of tears. Entropion, distichiasis, and trichiasis are all irritating and can thereby induce excessive lacrimation. Epiphora due to an inability to drain the normal tear film volume may involve a congenital lesion or acquired blockage or occlusion of the nasolacrimal system. Management of epiphora is discussed in Chapter 7.

The third eyelid Prominence of the third eyelid Prominence of the third eyelid is commonly caused by anterior segment pain. Treatment is thus directed towards the cause (see Ch. 6). Other causes of protrusion include sedation, dehydration, ‘Haw’s’ syndrome in cats (often associated with diarrhea), retrobulbar lesions, symblepharon, Horner’s syndrome (see above), dysautonomia, and systemic disease (e.g. tetanus).

Scrolling of the third eyelid The third eyelid may be distorted by a scrolling of its cartilage resulting in the free margin of the membrane rolling outwards (Fig. 4.21). There may be epiphora due to an inability to pool tears in the medial lacrimal lake and to

Fig. 4.20

Marked facial hair staining due to epiphora in a 2-year-old Burmese cat.

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Fig. 4.21 Scrolling of the third eyelid cartilage in a 1-year-old Bernese Mountain Dog. Left eye.

complete the blink. Correction requires resection of the scrolled portion of the cartilage while leaving the cross-bar of the T-shaped structure intact.

Prolapse of the nictitans gland The base of the third eyelid is enveloped by the nictitans gland which produces up to 50% of the aqueous portion of the precorneal tear film. In dogs with a genetic predisposition (Beagle, American Cocker Spaniel, English Bulldog, Boston Terrier) and rarely in cats (Burmese), the nictitans gland can prolapse subconjunctivally between the posterior surface of the third eyelid and the cornea. The gland appears as a smooth, ellipsoidal mass at the medial canthus (Fig. 4.22). Diagnosis is straightforward. Treatment requires surgical repositioning of the gland either by anchoring it to the ventromedial orbital rim or by performing a ‘pocketing’ procedure (Fig. 4.23).15 Gland excision should be avoided as this may adversely affect the precorneal tear film.

Other third eyelid conditions

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Other conditions altering the appearance of the third eyelid include lymphoid follicle hyperplasia, plasmacytic conjunctivitis, and neoplasia. It is normal for the bulbar surface of the third eyelid to have a roughened appearance due to the conjunctival lymphoid tissue overlying the nictitans gland. Proliferation of lymphoid follicles tends to occur in young dogs, apparently as a non-specific immune response, and is often accompanied by mild irritation and a mucoid discharge. If the irritation does not improve after a course of topical antibiotics and corticosteroids, careful debridement of the hyperplastic lymphoid follicles with dry gauze placed over a cotton-tipped applicator may relieve the irritation. Plasmacytic conjunctivitis (plasmoma) is most common in the German Shepherd Dog and may present as the solitary component of the disease complex or accompany chronic superficial keratitis. Plasma cells and lymphocytes infiltrate the nictitating membrane. The third eyelid becomes thickened, develops

ABNORMAL APPEARANCE

Fig. 4.22

Prolapse of the nictitans gland in a 4-month-old Bulldog. Left eye.

an irregular border, and may become depigmented. A seromucoid discharge may be present. Topical corticosteroids or ciclosporin effectively control this immune-mediated condition. Tumors involving the nictitating membrane include squamous cell carcinoma, fibrosarcoma, adenomas or adenocarcinomas, and hemangiomas or hemangiosarcomas. Treatment often requires surgical excision of the third eyelid and associated nictitans gland in their entirety.

The conjunctiva/sclera Conjunctivitis is specifically inflammation of the conjunctiva. Causes of conjunctivitis include allergy, eyelid lesions, foreign bodies, immune-mediated disease, infection, irritation, precorneal tear film deficiencies, and trauma (see Ch. 7). Conjunctival tissues may become edematous. Marked chemosis (swelling) may obscure visualization of the cornea (Fig. 4.24). Differential diagnoses for a ‘red eye’ include conjunctivitis, uveitis, glaucoma, episcleritis, and neoplasia. Conjunctivitis is a common misdiagnosis. A complete ophthalmic examination is indicated in every animal with a ‘red eye’. Differentiation between conjunctival hyperemia and episcleral hyperemia/ injection is of tremendous importance as episcleral injection is often associated with serious intraocular disease. Several key features assist in differentiation. The conjunctival vasculature is bright red in color, branches extensively, is freely mobile as it moves with the conjunctiva over the surface of the globe, and readily blanches with the application of topical phenylephrine. The episcleral vasculature in contrast is dark red in color, straight, runs at 90° to the limbus, is not mobile, and does not blanch when phenylephrine is applied topically (Fig. 4.25). Episcleritis is an immune-mediated inflammatory disease of the episclera that occurs most commonly in dogs. Episcleritis may be a distinct raised pink lesion (nodular form) or more diffuse (Fig. 4.26). The lesion often involves the adjacent cornea. Episcleritis is usually treated with corticosteroids, systemic tetra-

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A

B

C

D

Fig. 4.23 Diagram showing correction of prolapse of the nictitans gland by suturing the orbital rim. (A) An Allis tissue forceps is gently applied to the periphery of the free margin of the third eyelid, which is pulled across the eye. An incision is made in the medioventral conjunctival fornix (at the base of the third eyelid) using scissors. Blunt dissection allows access to the periosteum of the medioventral orbital rim. A firm bite of periosteum along the orbital rim is taken using 3/0 polydioxanone swaged (PDS, Ethicon) or monofilament nylon suture with a swaged-on needle introduced through the previously made incision. It can be difficult to obtain a bite of periosteum and bring the needle out through the incision, because access to the area is limited. (B) The needle is then passed through the original incision dorsally towards the prolapsed gland so as to emerge from the gland at its most prominent point of prolapse. (C) With the third eyelid everted, the needle is passed back through the exit hole in the gland to take a horizontal bite from the most prominent part of the gland. (D) Finally the needle is passed back through the last exit hole to emerge through the original incision in the conjunctival fornix, thus encircling a large portion of the gland. The suture ends are tied. This creates a suture loop through the gland which anchors it to the periosteum of the orbital rim, preventing it from re-prolapsing. The conjunctival incision can now be repaired using 6/0 polyglactin (Vicryl, Ethicon) or it may be left unsutured. Postoperatively, topical antibiotic cover is given. Redrawn with permission from BSAVA: Petersen-Jones, S.M. (1993) Conditions of the eyelid and nictating membrane. In: Petersen-Jones, S.M. and Crispin, S.M. (eds) BSAVA Manual of Small Animal Ophthalmology. Quedgeley: BSAVA Publications, pp. 65–90.

ABNORMAL APPEARANCE

Fig. 4.24 Marked chemosis of the palpebral conjunctiva of the upper eyelid in a 5year-old Beagle. Right eye.

Fig. 4.25 Acute glaucoma demonstrating episcleral congestion in a 4-year-old Welsh Springer Spaniel. Right eye.

Fig. 4.26 Raised area of episclera at the lateral limbus with associated lipid deposition in the adjacent cornea in a 2-year-old mixed breed dog.

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cycline and niacinamide, or, if necessary, immunosuppressive drugs such as azathioprine. An uncommon conjunctival disease, membranous or ligneous conjunctivitis, has been seen in Dobermann Pinschers and Golden Retrievers.16 The ocular lesion appears as a bilateral yellow-green membrane lining any or all of the conjunctival surfaces. Removal of the membrane leaves a roughened and ulcerated epithelial surface. Exfoliative cytology reveals inflammatory cells with a prominent eosinophilic component. The membrane is composed of epithelial cells and a proteinaceous exudate. Variably associated systemic signs include proteinuria and ulcerative lesions of the skin and other mucous membranes, particularly within the oral cavity. The condition can be controlled in most cases with topical corticosteroids in conjunction with systemic corticosteroids and/or azathioprine. Conjunctival adhesions (symblepharon) are a sequela of severe conjunctivitis. In cats the most common cause is infection with feline herpesvirus-1 (FHV1). The chemotic, ulcerated conjunctiva may adhere to itself, the third eyelid, or the cornea, and may obliterate the conjunctival fornices, interfere with tear drainage, or obscure vision (Fig. 4.27). Recurrent bouts of inflammation due to recurrences of the herpesvirus infection are possible. Surgery to break down the adhesions and reconstruction of fornix and limbus is best reserved for the most severely affected animals (e.g. those with visual impairment) as adhesions will often reform after surgery. This tendency to reform adhesions can be decreased by the postoperative application of a bandage contact lens for 3–4 weeks. The most common congenital conjunctival mass is the dermoid. Acquired masses include neoplasia (squamous cell carcinoma, limbal melanocytoma, conjunctival malignant melanoma, and hemangioma), conjunctival cysts, and nodular episcleritis. Ocular melanosis, a familial condition in Cairn Terriers, is characterized by the development of darkly pigmented scleral/episcleral patches, diffuse proliferation of pigmented cells, and pronounced thickening of the anterior uvea leading to secondary (melanocytic) glaucoma (Fig. 4.28).

Fig. 4.27 Extensive symblepharon obscuring the cornea and causing functional blindness of the affected eye in a 1year-old DSH cat. Right eye.

ABNORMAL APPEARANCE Fig. 4.28 The development of darkly pigmented scleral and episcleral patches in melanocytosis. Nineyear-old Cairn Terrier. Left eye. (Courtesy of Dr S. Petersen-Jones.)

Limbal melanocytomas and staphylomas may affect the sclera as well as the cornea and are discussed within the corneal pigmentation section of this chapter.

The cornea Loss of corneal transparency is readily diagnosed and may result from fluid accumulation, pigmentation, vascularization, symblepharon, endothelial deposits, or stromal lipid deposition.

Congenital corneal opacities When puppies’ eyelids open there is usually some degree of corneal opacity that normally clears over the subsequent few weeks. Sometimes there is delayed corneal clearing usually resulting in a central geographic gray appearance to the superficial stroma. This will usually clear with time. With some congenital ocular malformations corneal opacities may be present and persist; examples include anterior segment dysgenesis and the insertion of persistent pupillary membrane on the corneal endothelial surface.

Corneal edema Corneal edema occurs if there is a break in the anatomic or functional integrity of the corneal epithelium or endothelium. It is commonly seen within an area of corneal ulceration as the loss of epithelium allows the exposed stroma to imbibe fluid from the tear film (Fig. 4.29). Canine adenovirus I infection (or, historically, use of live CAV I vaccine) can result in corneal edema due to immune complex deposition (a type III hypersensitivity reaction) along the corneal endothelium (Fig. 4.30). The immune complexes prevent normal functioning of the corneal endothelial pumps that maintain dehydration of the corneal stroma. Corneal edema may also be seen in association with anterior uveitis or glaucoma. Therefore, when evaluating a patient with corneal edema,

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Fig. 4.29 Ulcerative keratitis and corneal edema due to epithelial dystrophy in a 4-year-old Boxer. Left eye.

Fig. 4.30 Blue eye. Dense corneal edema due to CAV I infection. Right eye.

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a complete intraocular assessment including tonometry and gonioscopy should be performed. Severe corneal edema may limit one’s ability to visualize intraocular structures and ultrasonography may be helpful to assess intraocular changes. The treatment of corneal edema is directed toward resolution of the underlying cause. The edema may be transient and resolve completely if the underlying cause is successfully treated, but with severe damage the edema can be permanent as endothelial cells have minimal regenerative capabilities, especially in older animals. Corneal edema may also result from inherited endothelial dystrophy. This condition occurs in Boston Terriers, Chihuahuas, Dachshunds, English Springer

ABNORMAL APPEARANCE

Spaniels, Miniature Poodles, and occasionally other breeds. Usually middleaged or older animals are affected. The condition is typically bilateral and begins in the dorsotemporal or central regions of the cornea. The progressive edema eventually involves the entire cornea (Fig. 4.31). In severely affected patients, fluid-filled bullae may form and rupture to form superficial corneal ulcers that are painful and often slow to heal. Topical hyperosmotic agents such as 5% sodium chloride ointment or solution may decrease bullae formation although they will not completely resolve the corneal edema. The results of penetrating keratoplasty for this condition may be disappointing due to the lack of a suitable pool of corneal donors or rejection. The use of a thin conjunctival flap or thermokeratoplasty may be palliative in selected cases. In the cat an idiopathic severe focal edema with formation of large bullae has been described and is termed ‘bullous keratopathy’. Some cases have been associated with a congenital endothelial dysplasia, while others have been associated with anterior uveitis. Third eyelid flaps are often beneficial in treating cats with acute bullous keratopathy.

Corneal pigmentation Acquired pigmentation is often common in dogs and results from the migration of melanocytes from the limbus; it is often accompanied by superficial vascularization. The pigment typically arises in response to chronic corneal irritation or inflammation (Fig. 4.32). Common causes include chronic superficial keratitis (pannus), deficiencies in the precorneal tear film, lagophthalmos, and trichiasis from entropion or corneal contact with the nasal folds. Brachycephalic breeds are commonly affected. Therapy is directed at correction of the underlying cause. Corneal sequestrum is a disease peculiar to cats and is the cause of the majority of cases of brown or black corneal lesions in cats. The characteristic lesions range from faint brown discoloration of the central cornea to the formation of a variably sized, dense black plaque (Fig. 4.33). The sequestrum consists of necrotic corneal stroma and is often surrounded by a ring of inflammatory cells. The condition may be unilateral or bilateral. The amount of pain associated

Fig. 4.31 Diffuse corneal edema due to corneal endothelial dystrophy in a 9-yearold Dachshund. Right eye.

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SMALL ANIMAL OPHTHALMOLOGY Fig. 4.32 Extensive corneal pigmentation and fibrosis secondary to trichiasis, medial canthal entropion, and lagophthalmos in a 3-year-old Shih Tzu.

Fig. 4.33 Corneal sequestrum in a 4-yearold Burmese cat. Right eye.

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with the condition varies with the intensity of the inflammatory response. Very dense plaques will often slough which may leave a full-thickness corneal defect. The etiopathogenesis remains open to speculation, but infection with feline herpesvirus may play a role.17 Sequestra frequently form in areas of longstanding corneal ulceration. Performing a grid keratotomy in cats has also been shown to induce sequestrum formation.18 In Persians and Himalayans, corneal exposure due to lagophthalmos is likely a contributing factor; therefore the likelihood of the condition developing bilaterally is greatly increased. While faint sequestra may respond to therapy with topical lubricating ointments,

ABNORMAL APPEARANCE

dense sequestra are often removed by keratectomy and, if the lesion is deep, repaired with a conjunctival pedicle flap or lamellar corneal graft. Limbal melanocytomas may infiltrate the cornea as well as the sclera and appear as raised black lesions which tend to be slow growing (Fig. 4.34). They must be differentiated from intraocular melanomas that have extended through the sclera. Their behavior is usually benign. Progressive lesions usually respond to treatment by excision with or without a graft, laser excision, or cryosurgery. Staphylomas are the protrusion of uveal tissue through thinned cornea or sclera. Staphylomas may initially appear black or slightly brown due to a covering of fibrin. Subsequent granulation and scar formation mutes the color to a vascular gray. Staphylomas may be congenital, traumatic, or secondary to severe scleritis or chronic glaucoma.

Corneal vascularization Corneal vascularization is a common feature of corneal disease. Whenever corneal vascularization is present, the possibility of precorneal tear film deficiency or concurrent corneal ulceration should be considered. Therefore a Schirmer tear test and staining the cornea with fluorescein dye are essential parts of the complete ophthalmic examination. It should be remembered that vascularization will occur as a normal component of stromal healing and should not be inappropriately suppressed. Once the stimulus for vascularization is resolved, the corneal vessels will narrow and no longer transmit blood, and are observed as faint gray lines (‘ghost vessels’) upon close examination of the cornea. Corneal vascularization is a common pathologic reaction to a number of different insults. These include precorneal tear film deficiency, eyelid abnormalities, trauma, infection, chemical irritants, immune-mediated disease, and diseases involving adjacent structures such as episcleritis, scleritis, anterior uveitis, and glaucoma. Differentiation between superficial and deep corneal vascularization is helpful to determine the underlying cause for the vascularization. The presence of deep vessels typically indicates intraocular involvement. Deeper vessels tend to branch less, are darker in color, and their origins from scleral vessels are obscured by the scleral overhang at the limbus. In

Fig. 4.34 Limbal melanoma and associated lipid keratopathy in a mixed breed dog.

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contrast, superficial vessels branch frequently, are lighter red in color, and can be seen crossing the limbus as they arise from the conjunctival vessels. Chronic superficial keratitis (CSK, pannus) is an immune-mediated condition characterized by progressive, superficial, densely vascularized corneal inflammatory lesions. CSK occurs bilaterally with the lesions first developing in the ventrolateral quadrant of the cornea. Lymphocytes and plasma cells infiltrate the superficial stroma accompanied by vascularization. The lesions progress at a variable rate to produce a thick, superficial, corneal granulation tissue which may eventually involve the entire cornea resulting in severe visual impairment or blindness. There is a variable degree of pigmentation of the lesions and in long-standing cases corneal fibrosis (scar tissue) and/or corneal lipid degeneration is present (Fig. 4.35). Exposure to ultraviolet light is a known predisposing factor for CSK. Therefore dogs that reside at high elevations are often more difficult to treat. Treatment consists of topical immunosuppression with corticosteroids and/ or topical ciclosporin.19,20 Subconjunctival depot corticosteroids are useful in more severe cases or those in which the owners have difficulty applying medication. Owners should be aware of the need for lifelong treatment and the likelihood of periods of exacerbation. Treatment with beta radiation may be useful in severe cases. Limiting exposure to ultraviolet light, either by keeping the dog indoors during peak ultraviolet light levels or using sunglasses (Doggles®), can be of benefit as well. Performing a superficial keratectomy may reduce extensive irreversible corneal changes that limit vision. As the cornea vascularizes quite rapidly following keratectomy, topical ciclosporin should be continued during the healing phase. Eosinophilic keratitis, a condition unique to the cat, is a progressive, superficial, corneal inflammatory lesion with a surface deposit of a white ‘cottage cheese-like’ material (Fig. 4.36). While any part of the cornea may be involved, the lesions are often noted dorsotemporally. Exfoliative cytology of the lesion

Fig. 4.35 Chronic superficial keratitis in an 8-year-old German Shepherd Dog. The marked corneal vascularization and pigmentation indicate chronicity. Left eye.

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Fig. 4.36

Eosinophilic keratoconjunctivitis in a 4-year-old cat.

typically reveals multiple eosinophils as well as mast cells, neutrophils, lymphocytes, and plasma cells. The etiopathogenesis remains unknown, but infection with feline herpesvirus-1 has been implicated.17 The disease is controlled by administration of topical mast cell stabilizers, topical corticosteroids, or topical ciclosporin. As FHV-1 may be involved, the possibility of causing reactivation of latent herpetic infections should be discussed with the owners when employing topical corticosteroids in the treatment regimen. Occasionally systemic megestrol acetate therapy is utilized, but the clinician must be aware of the potential side effects, including inducing diabetes mellitus, when using this drug in the cat. Lesions often resolve completely with treatment, although recurrence is common. Symblepharon is another cause of corneal opacity in which a vascularized whitish/gray membrane of conjunctival origin is adherent to the corneal surface. It has been discussed above with conditions causing abnormal appearance of the conjunctiva.

Corneal lipid and calcium deposition Lipid keratopathy is the deposition of lipid within the corneal stroma. The lipid deposition may be due to corneal dystrophy or degeneration or systemic hyperlipidemia (hyperlipoproteinemia, dyslipoproteinemia).21 If the deposition is marked or progressive, the animal should be investigated for hyperlipoproteinemia and/or endocrinopathy. Crystalline stromal dystrophy is a genetic, bilateral (although not always comcurrent or symmetric) condition characterized by discrete subepithelial crystalline refractile opacities, usually in an oval or circular pattern, imparting a ‘ground glass’ appearance, in an otherwise normal cornea (Fig. 4.37). Lesions may slowly alter in size, but generally have no effect on vision and require no

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Fig. 4.37 Crystalline stromal dystrophy in a 3-year-old Miniature Dachshund.

Fig. 4.38 Lipid keratopathy in a Shetland Sheepdog. The lesion developed 6 months following cataract extraction. (Courtesy of Dr S.M. Petersen-Jones.)

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treatment. A number of dog breeds are affected and the condition has been shown to be familial in some breeds. Siberian Huskies suffer from a more severe manifestation of the condition with lipid deposition also occurring deeper in the cornea.22 In Shelties corneal dystrophy may be associated with focal thinning of corneal stroma and overlying recurrent erosions. Corneal lipid deposition can occur as a degenerative process secondary to corneoscleral diseases such as keratitis, episcleritis, and limbal melanocytoma. Lipid leakage from blood vessels causes the lipid deposition (Fig. 4.38). The appearance of the lipid deposit is more variable than with dystrophies; it may be a diffuse white color or appear as a granular deposit or refractile ‘flakes’.

ABNORMAL APPEARANCE

Lipid deposition as a circumferential ring in the perilimbal cornea is known as arcus lipoides and in such cases the possibility of a predisposing systemic condition should be investigated. Lipid crystals may occasionally erode through the corneal epithelium causing ulceration and pain (Fig. 4.39). Management of lipid keratopathy involves treatment for a possible underlying hyperlipidemia. If the lesion is extensive, progressive, or painful, a keratectomy may be required. Calcareous degeneration is characterized by the presence of dense white, often needle-shaped, chalky, stromal deposits (Fig. 4.40). These lesions frequently will ulcerate causing discomfort and may become vascularized. This condition often affects older dogs. Cushing’s disease or uremia may be predisposing factors. Topical 1–5% disodium ethylenediamine tetra-acetic acid (EDTA) may assist in resolution of the lesions by chelating the calcium present within the corneal stroma. Keratectomy may be indicated if the lesion causes discomfort or is extensive, but healing may be complicated.

Corneal endothelial deposits Roundish, usually yellow to gray foci on the corneal endothelial surface are known as keratic precipitates (KPs) (Fig. 4.41). The keratic precipitates form as a result of anterior uveitis and represent the deposition of inflammatory cells on the endothelial surface. The KPs tend to be deposited inferiorly and may be concealed by an elevated third eyelid. Keratic precipitates are seen more commonly in cats with chronic anterior uveitis than in dogs, where they most commonly accompany lens-induced uveitis. The KPs will slowly resolve as the underlying uveitis is treated but may leave a focal endothelial scar.

Fig. 4.39 Crystalline stromal dystrophy and associated vascularization in a 6-year-old Shetland Sheepdog. Left eye.

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Fig. 4.40 Calcareous degeneration of the cornea in an elderly crossbred dog. (Courtesy of Dr S.M. Petersen-Jones.)

Fig. 4.41 Keratic precipitates associated with toxoplasmosis in a 2-yearold DSH cat. Right eye.

A slowly progressive thin pigment deposit involving the corneal endothelium and originating from the limbal region is sometimes observed. The pigment is presumed to be due to migration or slow proliferation of limbal pigment. No therapy is required. Occasionally iris cysts (see below) rupture against the corneal endothelium leaving an adherent donut-shaped deposit of pigmented tissue.

Alteration of corneal contour 102

A profound accumulation of fluid in the cornea may cause distortion of the corneal profile, the appearance of which is referred to as keratoconus. Other

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possible causes of a misshapen corneal contour include corneal abscesses and inclusion cysts. Both of these conditions are rare and necessitate keratectomy. Corneal abscesses are typically painful and consist of a usually central yellowish stroma opacity with indistinct borders and associated focal edema. They are typically accompanied by vascularization and conjunctival inflammation. Corneal inclusion cysts are typically non-painful and are filled with a thick, cream or tan colored material composed of desquamated epithelial cells; they occur as a sequel to ulceration or trauma, which may be surgical as well as accidental (Fig. 4.42). Minimal inflammation is present although a few superficial corneal blood vessels may be present. A deep corneal ulceration will often cause an obvious concavity within the corneal contour. If such a lesion does not retain fluorescein dye at the base, this indicates the presence of a descemetocele (see pp. 221–223). A corneal ulceration that involved the loss of corneal stroma can heal leaving an epithelialized indentation (corneal facet). A corneal laceration usually causes an obvious alteration in the corneal contour. Corneal laceration, with or without iris prolapse, requires surgical repair of the wound, reformation of the anterior chamber, and medical treatment to control possible infection and anterior uveitis.

The anterior chamber and anterior uvea Congenital lesions of the iris include colobomas, persistent pupillary membranes, and iris cysts. Colobomas of the iris are rare. Their presence may create an irregular or false pupil (Fig. 4.43). In older individuals, colobomas must be distinguished from senile iris atrophy (discussed in the normal iris section of this chapter). Persistent pupillary membranes (PPMs) are single or multiple strands of iris tissue that arise from the iris collarette. The strands may be free floating, insert onto the corneal endothelium (iris to cornea PPM) (Fig. 4.44), span the iris (iris to iris PPM) (Fig. 4.45), or attach to the anterior lens capsule (iris to lens PPM). Non-progressive focal opacities of varying extent are associated with the corneal attachments. The lenticular attachments often result in focal cataract formation (see pp. 127–128).

Fig. 4.42 Epithelial inclusion cyst in a 12year-old Yorkshire Terrier.

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Fig. 4.43 Appearance of polycoria due to an iridal coloboma in a 1-year-old Siberian Husky. Note that an iris to iris persistent pupillary membrane is present as well.

Fig. 4.44 Persistent pupillary membrane (PPM) with corneal attachment in a 12week-old Afghan Hound.

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Fig. 4.45 Iris to iris persistent pupillary membranes (PPM) in a 2year-old Labrador Retriever.

Anterior uveitis is inflammation of the iris and ciliary body (see Ch. 6). Acute anterior uveitis is typically painful. Animals with a low-grade, chronic uveitis are often less noticeably painful and may present because the owner has noticed a change in the appearance of the eye. Clinical signs can include episcleral congestion; corneal changes such as edema, vascularization, and keratic precipitates; hypopyon (white blood cells) or fibrin within the anterior chamber, iris color changes, pupillary abnormalities, and lens changes such as posterior synechia and cataract formation. The potential etiologies of chronic uveitis are similar to those described for acute uveitis (see Table 6.5 and pp. 245–247).23 Typically, the iris color change consists of darkening with a loss of normal surface detail, although animals with a blue iris may develop a yellow hue to the iridal stroma. In some forms of uveitis, predominantly uveodermatologic syndrome, iris depigmentation occurs. A reddening of the iris (rubeosis iridis) may develop and is most easily noted in animals with a light-colored iris, typically cats. Rubeosis iridis is due to neovascularization of the iridal surface. The inflammation may result in adhesions between the iris and the anterior lens capsule (posterior synechiae). These adhesions limit pupillary movement and often distort the pupillary shape. Extensive posterior synechiae will block aqueous passage through the pupil causing the iris to bulge anteriorly (iris bombé) and leads to secondary glaucoma as a result of iridocorneal angle collapse. Lenticular changes include pigment deposits on the anterior capsule due to transient adhesion of the iris to the lens capsule or adherent pigment containing macrophages, and cataract formation. Secondary lens luxation may occur, particularly in cats with chronic uveitis. Uveodermatologic syndrome is a specific form of immune-mediated uveitis seen in dogs, most commonly Akitas and the Arctic breeds. Melanocytes are the immune system’s target in uveodermatologic syndrome. Therefore severe anterior and posterior uveitis and a characteristic poliosis (whitening of the hair) and vitiligo (depigmentation of the skin) around the eyes and muzzle are seen. Control of the uveitis is challenging; retinal detachment and degeneration and secondary glaucoma are common sequelae.

ABNORMAL APPEARANCE

Anterior uveitis

Blood-filled anterior chamber (hyphema) Hyphema may result from inflammatory disease, systemic disease such as clotting disorders or hypertension, or ocular disease such as persistence of embryonic blood vessels, neoplasia, retinal detachment, and trauma. Investigation of hyphema requires a thorough ocular and systemic examination, ultrasonography (to investigate the possible presence of intraocular neoplasia or retinal detachment), hematology, biochemistry, clotting profiles, and blood pressure measurement. Spontaneous hyphema is often associated with preiridal fibrovascular membrane formation (rubeosis iridis) as the new vessels on the iris surface are very fragile and hemorrhage easily. Chronic uveitis, long-standing retinal detachment, intraocular neoplasia, and chronic glaucoma can all incite formation of pre-iridal fibrovascular membranes. In older animals for which no other ocular or systemic cause of hyphema can be identified, retinal detachment should be strongly considered.24 Non-specific therapy for hyphema includes decreased activity to discourage re-bleeding, the use of topical corticosteroids to control any concurrent uveitis, and topical atropine

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to prevent significant adhesions. Intraocular pressure should be monitored and increased pressure treated as necessary. Uncomplicated hyphemas will usually resorb over several weeks; those associated with intraocular disease may persist indefinitely.

Mass lesions in the anterior chamber Mass lesions are readily visualized within the anterior chamber given adequate corneal transparency. In patients with uveitis, organized fibrin, hypopyon, and other inflammatory products may be seen as strands or masses adherent to the corneal endothelium, anterior lens capsule, or iris. Anterior chamber foreign bodies are usually accompanied by corneal or scleral damage and a uveitic response (Fig. 4.46). The iris cyst is typically a spherical, often free-floating, structure of variable size in the anterior chamber (Fig. 4.47). On occasion its origin from the iridal pigment epithelium or ciliary epithelium is indicated by a connecting strand.25 The thin walls typically transilluminate, but occasionally the pigment density renders the cyst totally opaque. Iridal cysts are usually of no clinical significance although on occasion their size and/or number are such that vision may be obscured. In such cases deflation by needle aspiration or laser puncture is indicated. The presence of a luxated lens anterior to the iris is usually heralded by the sudden onset of corneal edema and glaucoma, particularly in the dog (see Ch. 6). Occasionally in the dog and routinely in the cat, the presence of the lens in the anterior chamber does not cause glaucoma. However, contact of the lens with the corneal endothelium can still incite corneal edema. Lens luxation is discussed further within this chapter under the abnormal appearance of the lens. Uveal tumors may be primary or secondary (Fig. 4.48). The primary tumors include melanoma, adenoma, adenocarcinoma, and medulloepithelioma. The diagnosis of uveal neoplasia depends on the demonstration of a solid mass

Fig. 4.46 A linear foreign body (a thorn) and attendant anterior uveitis in a 4-year-old crossbred dog. Left eye.

ABNORMAL APPEARANCE Fig. 4.47 Multiple anterior uveal cysts demonstrating their appearance on transillumination in a 10year-old Dobermann. Right eye.

Fig. 4.48 Posterior iridal and ciliary body mass extending through the pupil into the anterior chamber in a 5-year-old Newfoundland dog. Right eye.

involving the iris or ciliary body. Histopathologic confirmation is often not performed until the eye has been enucleated.26 Most primary ocular tumors in the dog are benign, but ultimately the eye will be destroyed by the resultant glaucoma. In an eye that is otherwise normal, owners may request local resection, although this is a skilled procedure and in many cases enucleation is eventually performed. Laser photocoagulation has been used to treat uveal tumors with some success.27 In cats primary tumors are more often malignant. A cat with diffuse iris melanoma may present due to iridal pigmentation changes as opposed to the observation of a distinct mass within the anterior chamber. Metastasis of diffuse iris melanoma is not infrequent.28 Although any metastatic tumor embolus may locate in the eye, the most common secondary uveal tumor is lymphoma. The ocular manifestations of lymphoma vary considerably and may not be specific for neoplasia. Clinical signs such as anterior uveitis, glaucoma, and/or intraocular hemorrhage may

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be the initial presenting features.29 For the treatment of secondary tumors, palliative enucleation, chemotherapy, or euthanasia of the terminal patient represent the treatment options.

Pupillary abnormalities Ophthalmic patients may present with anisocoria, a difference in size between the two pupils (Fig. 4.49). The clinician must determine which is the abnormal pupil by comparing relative sizes in light and dark conditions, checking the direct and consensual pupillary light responses, and performing visual tests. Possible causes of an abnormally dilated pupil include unilateral iris atrophy, glaucoma, oculomotor and parasympathetic nerve lesions, mydriatic application, dysautonomia, severe unilateral retinal disease, and optic neuropathy. Causes of the unilaterally constricted pupil include anterior uveitis, synechiae formation, Horner’s syndrome, miotic usage, and organophosphate poisoning. Cranial trauma may result in anisocoria. The prognosis is poor if the anisocoria progresses to dilated non-responsive pupils. If bilateral mydriasis or miosis is present the differential diagnoses should similarly consider all those causes listed for anisocoria. A ‘D’-shaped or reverse ‘D’-shaped pupil or spastic pupil syndrome (a static anisocoria) may be seen in cats infected with feline leukemia virus.30 The prognosis for long-term survival is poor.

The lens Changes in the appearance of the lens most commonly result from a loss of transparency or because of dislocation from its normal position in the posterior chamber. Gross opacification is obvious, but magnification or the use of slitlamp biomicroscopy may be necessary to detect small lesions and identify the position of the opacity within the lens. Distant direct ophthalmoscopy makes it easy to differentiate between the opacity of cataract and the translucency of nuclear sclerosis. Cataract results in a black shadow against the reflection from the fundus whereas nuclear sclerosis presents no barrier to the fundus reflection. Nuclear sclerosis is a normal aging feature due to the compaction of the nuclear region of the lens. It has little or no effect on vision, but the blue-gray appearance of the lens often prompts a misdiagnosis of cataract. Cataract is simply defined as opacity of the lens and/or its lens capsule (Figs 4.50 & 4.51). There are a number of possible causes including genetic defects, congenital anomalies, diabetes mellitus, trauma, and accompanying other ocular conditions (e.g. uveitis, glaucoma, lens luxation, and retinal degeneration). With inherited cataract, the predominant reason for cataract formation in dogs, the age of onset and the appearance of the opacity are often specific

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Fig. 4.49 Anisocoria in a 4year-old Persian cat.

ABNORMAL APPEARANCE Fig. 4.50 Posterior polar and equatorial cataract in a 7-year-old Labrador Retriever. Left eye.

Fig. 4.51 Cortical ‘spoke wheel’ cataract in a 9-yearold Boston Terrier. Left eye.

for the breed. Lens opacity may also be due to the attachment of posterior synechiae and any associated pigment migration, the presence of pupillary membranes, or the persistence of elements of the primary vitreous. The reason for presentation of the cataract patient may be the abnormal appearance of the eye as the owner may be unaware of the degree of visual impairment. If the cataract is progressive or has a significant effect on vision then the patient should be assessed for possible surgery. This assessment should involve a complete systemic and ophthalmic examination together with electroretinography and ocular ultrasonography to determine if other ocular disease if present and to assess the integrity and functionality of the retina.

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There is no medical treatment for cataract. Surgical extraction can successfully restore sight. Phacoemulsification is the most commonly performed procedure with a success rate for vision of 90–95%.31 Primary lens luxation most commonly occurs in the terrier breeds. The lens may move posteriorly into the vitreous cavity if vitreal liquefaction is present or, more commonly, anteriorly into or through the pupil into the anterior chamber (Fig. 4.52). Its position within the pupil or the anterior chamber together with adherent vitreous produces interference with the transpupillary flow of aqueous, and acute secondary glaucoma is the usual presenting feature in the dog; the cat’s deeper anterior chamber is somewhat protective against pupillary block and acute IOP elevation (see Ch. 6). Diagnosis is usually straightforward as one visualizes the lens in the anterior chamber. The elevated IOP should be relieved followed by emergency lens extraction.32 A posteriorly luxated lens does not necessarily require removal, although in some patients the lens repeatedly moves between the anterior chamber and the vitreous, causing glaucoma each time it is in the anterior chamber. Conservative longterm management may be possible using long-acting miotics to maintain the lens within the vitreous cavity. Secondary lens luxation occurs in both dogs and cats as a result of conditions such as uveitis, hypermature cataract formation, and glaucoma. Spontaneous lens luxation occurs infrequently in aged animals, particularly Siamese cats. An anteriorly luxated lens may become cataractous. Contact between the anteriorly luxated lens and the corneal endothelial surface may result in pain and an area of corneal edema.

The posterior segment Leukocoria is defined as white appearance to the pupil. The differential diagnoses include cataract, neoplasia, persistent hyperplastic primary vitreous, vitreous abscess, posterior uveitis, and retinal detachment. Persistent hyperplastic primary vitreous is a congenital cause of leukocoria in which stromal fibrovascular and posterior capsular plaques render the pos-

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Fig. 4.52 Primary anterior lens luxation in a 5-year-old Jack Russell Terrier. Left eye.

ABNORMAL APPEARANCE

terior lens opaque.33,34 The lesions may range from small fibrovascular dots that minimally impair vision to severe retrolental and lenticular changes that markedly impair vision. Cortical cataract may also be present. The problem may be sporadic although it is inherited in some breeds, notably the Dobermann and Staffordshire Bull Terrier. The presence of retrolenticular vasculature is diagnostic, although ocular ultrasonography may be needed to demonstrate the full extent of the involvement, particularly when cortical and capsular cataract is extensively present. In visually impaired individuals, treatment is difficult because it involves the removal of the lens and the anterior vitreous. Hemorrhage can be a severe complication. Animals with this condition should not be used for breeding. Severe retinal dysplasia with retinal non-attachment or detachment may result in congenital leukocoria due to contact of the retina with the posterior surface of the lens. Cataract formation may also be present. This condition is discussed further on pages 136–141. Labrador Retrievers and Samoyeds are affected by another inherited condition, oculoskeletal dysplasia. The condition is inherited as an autosomal recessive trait.35 Homozygotes demonstrate skeletal and ocular abnormalities including cataracts and complete retinal detachment in association with retarded growth of the radius, ulna, and tibia resulting in a chondrodysplastic appearance. Heterozygotes do not develop the skeletal abnormalities and the ocular lesions are less severe, manifesting often as multiple retinal folds. Animals with bilateral retinal detachment will often present with blindness, but if the condition is unilateral and the retina is occupying the anterior vitreous or there is vitreal hemorrhage, the resulting abnormal appearance or anisocoria may be the reason for presentation.36 Generally, the prognosis for vision in retinal detachment is poor due to the late presentation of many of these cases. The treatment is discussed on pages 155–160. Hypertensive retinopathy is now recognized commonly in older animals, particularly cats. Hypertensive retinopathy may cause retinal detachment and intraocular hemorrhage (Figs 4.53 & 4.54). The retinal vasculature may appear tortuous. Feline patients presenting with this problem should be investigated for underlying cardiac, renal, and thyroid disease. Treatment with a calcium channel blocker such as amlodipine besylate can offer rapid and effective hypotensive therapy preventing the development of further retinal pathology and allowing retinal reattachment. If the detachment occurred recently, then at least partial restoration of vision is possible.37 As hypertensive retinopathy is fairly common, the systolic blood pressure should be evaluated in all cases of serous retinal detachment. Alterations in the quality of the tapetal reflex may be the reason for presentation. A ‘glassy’ appearance or ‘glare’ may be the layperson’s description of the pupil due to tapetal hyperreflectivity following retinal degeneration or retinal detachment with disinsertion. The loss of the pupillary light response exacerbates the appearance. The funduscopic changes resulting from retinal degeneration are described on pages 144–147 and 182–186. Alterations noted upon examination of the posterior segment may include asteroid hyalosis, tapetal hyporeflectivity, tapetal hyperreflectivity, retinal vascular tortuosity or attenuation, retinal hemorrhage, and optic neuritis. Asteroid hyalosis is an innocuous degenerative change of the vitreous. Minute,

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SMALL ANIMAL OPHTHALMOLOGY Fig. 4.53 Complete retinal detachment resulting from hypertensive retinopathy associated with hyperthyroidism in a 13-year-old DSH cat. Left eye.

Fig. 4.54 Multiple preretinal, intraretinal, and subretinal hemorrhages due to hypertensive retinopathy in an 8-yearold DSH cat.

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spherical, lipid opacities are suspended throughout the vitreous. The condition is frequently noted in geriatric animals, but may also occur in association with ciliary body epithelial tumors and previous episodes of inflammation. Areas of tapetal hyporeflectivity indicate areas of thickened neural retina or subretinal infiltrates. Causes of tapetal hyporeflectivity include retinal edema, retinal dysplasia, retinitis, and separation of the sensory retina from the retinal pigment epithelium by subretinal fluid or a cellular infiltrate. Areas of tapetal hyperreflectivity indicate thinning or absence of the neural retina. Causes include retinal atrophy, retinal degeneration, and dysinsertion retinal detachment. The retinal vasculature may appear tortuous due to systemic hypertension, hyperviscosity syndrome, polycythemia, and inflammation. The retinal vasculature may appear thin or attenuated with anemia, progressive retinal atrophy, chronic sudden acquired retinal degeneration, and chronic glaucoma. Retinal hemorrhages may occur at different levels in the sensory retina. The hemorrhages may be pre-retinal (between the sensory retina and vitreous),

ABNORMAL APPEARANCE

within the nerve fiber layer, intraretinal, or subretinal. Causes of retinal hemorrhage include vasculitis, thrombocytopenia, thrombocytopathy, coagulopathy, hypertension, anemia, and polycythemia. Optic neuritis causes the optic nerve head to appear swollen with indistinct margins. Peripapillary hemorrhage is often present. Causes include inflammation and neoplasia. For further discussion of the differential diagnoses and treatment options for the above findings, see Chapter 5.

REFERENCES 1. Gelatt, K. and Mackay, E. (1997) Distribution of intraocular pressure in dogs. Trans. Am. Coll. Vet. Ophthalmol. 28: 13. 2. Dubielzig, R.R. (2002) Feline ocular sarcomas. In: Peiffer, R. and Simons, K. (eds) Ocular Tumors in Animals and Humans. Ames: Iowa State Press, pp. 283–288. 3. Bingaman, D., Lindley, D., Glickman, N. et al. (1994) Intraocular gentamicin and glaucoma: a retrospective study in 60 dog and cat eyes (1985–1993). Vet. Comp. Ophthalmol. 4: 113–119. 4. Ramsey, D.T. and Fox, D.B. (1997) Surgery of the orbit. Vet. Clin. North Am. Small Anim. Pract. 27(5): 1215–1264. 5. Dziezyc, J., Hager, D.A. and Millichamp, N.J. (1987) Twodimensional real-time ocular ultrasonography in the diagnosis of ocular lesions in dogs. J. Am. Anim. Hosp. Assoc. 23(5): 501–508. 6. Morgan, R.V., Ring, R.D., Ward, D.A. et al. (1996) Magnetic resonance imaging of ocular and orbital disease in 5 dogs and a cat. Vet. Radiol. Ultrasound 37(3): 185–192. 7. Boydell, P. (1991) Fine needle aspiration biopsy in the diagnosis of exophthalmos. J. Small Anim. Pract. 32(11): 542–546. 8. Ramsey, D., Hamor, R., Gerding, P. et al. (1995) Clinical and immunohistochemical characteristics of bilateral polymyositis of dogs. Proc. Am. Coll. Vet. Ophthalmol. 26: 130–132.

9. Kern, T.J., Aromando, M.C. and Erb, H.N. (1989) Horner’s syndrome in dogs and cats: 100 cases (1975– 1985). J. Am. Vet. Med. Assoc. 195(3): 369–373. 10. Boydell, P. (1995) Idiopathic Horner’s syndrome in the Golden Retriever. J. Small Anim. Pract. 36(9): 382– 384. 11. Gilger, B.C., Hamilton, H.L., Wilkie, D.A. et al. (1995) Traumatic ocular proptoses in dogs and cats: 84 cases (1980–1993). J. Am. Vet. Med. Assoc. 206(8): 1186–1190. 12. Allgoewer, I., Blair, M., Basher, T. et al. (2000) Extraocular muscle myositis and restrictive strabismus in 10 dogs. Vet. Ophthalmol. 3(1): 21–26. 13. Gelatt, K. and Gelatt, J. (2001) Small animal ophthalmic surgery: practical techniques for the veterinarian. New York: Butterworth Heinemann, pp. 74–123. 14. Bedford, P.G.C. (1998) Technique of lateral canthoplasty for the correction of macropalpebral fissure in the dog. J. Small Anim. Pract. 39(3): 117–120. 15. Morgan, R.V., Duddy, J.M. and McClurg, K. (1993) Prolapse of the gland of the third eyelid in dogs: a retrospective study of 89 cases (1980 to 1990). J. Am. Anim. Hosp. Assoc. 29(1): 56–60. 16. Ramsey, D.T., Ketring, K.L., Glaze, M.B. et al. (1996) Ligneous conjunctivitis in four Doberman Pinschers. J. Am. Anim. Hosp. Assoc. 32(5): 439–447. 17. Nasisse, M.P., Glover, T.L., Moore, C.P. et al. (1998) Detection of feline

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herpesvirus 1 DNA in corneas of cats with eosinophilic keratitis or corneal sequestration. Am. J. Vet. Res. 59(7): 856–858. 18. La Croix, N.C., van der Woerdt, A. and Olivero, D.K. (2001) Nonhealing corneal ulcers in cats: 29 cases (1991– 1999). J. Am. Vet. Med. Assoc. 218(5): 733–735. 19. Jackson, P.A., Kaswan, R.L., Merideth, R.E. et al. (1991) Chronic superficial keratitis in dogs: a placebo controlled trial of topical cyclosporine treatment. Prog. Vet. Comp. Ophthalmol. 1(4): 269–275. 20. Clerc, B. (1996) The treatment of immune-mediated and auto-immune ocular diseases in dogs and cats using cyclosporine A ointment. (A literature review and personal experience). Pratique Médicale et Chirurgicale de l’Animal de Compagnie 31(1): 73–81. 21. Crispin, S. and Barnett, K.C. (1983) Dystrophy, degeneration, and infiltration of the canine cornea. J. Small Anim. Pract. 24: 63–83. 22. MacMillan, A., Waring, G., Spangler, W. et al. (1979) Crystalline corneal opacities in the Siberian Husky. J. Am. Vet. Med. Assoc. 175: 829– 832. 23. Crispin, S. (1988) Uveitis in the dog and cat. J. Small Anim. Pract. 29: 429–447. 24. Nelms, S.R., Nasisse, M.P., Davidson, M.G. et al. (1993) Hyphema associated with retinal disease in dogs: 17 cases (1986–1991). J. Am. Vet. Med. Assoc. 202(8): 1289–1292. 25. Spiess, B.M., Bolliger, J.O., Guscetti, F. et al. (1998) Multiple ciliary body cysts and secondary glaucoma in the Great Dane: a report of nine cases. Vet. Ophthalmol. 1(1): 41–45. 26. Dubielzig, R.R., Steinberg, H., Garvin, H. et al. (1998) Iridociliary epithelial tumors in 100 dogs and 17 cats: a morphological study. Vet. Ophthalmol. 1(4): 223–231. 27. Nasisse, M.P., Davidson, M.G., Olivero, D.K. et al. (1993) Neodymium : YAG laser treatment of

primary canine intraocular tumors. Prog. Vet. Comp. Ophthalmol. 3(4): 152–157. 28. Kalishman, J.B., Chappell, R., Flood, L.A. et al. (1998) A matched observational study of survival in cats with enucleation due to diffuse iris melanoma. Vet. Ophthalmol. 1(1): 25–29. 29. Krohne, S.G., Henderson, N.M., Richardson, R.C. et al. (1994) Prevalence of ocular involvement in dogs with multicentric lymphoma: prospective evaluation of 94 cases. Vet. Comp. Ophthalmol. 4(3): 127–135. 30. Nell, B. and Suchy, A. (1998) ‘Dshaped’ and ‘reverse-D-shaped’ pupil in a cat with lymphosarcoma. Vet. Ophthalmol. 1(1): 53–56. 31. Sigle, K.J. and Nasisse, M.P. (2006) Long-term complications after phacoemulsification for cataract removal in dogs: 172 cases (1995– 2002). J. Am. Vet. Med. Assoc. 228(1): 74–79. 32. Glover, T.L., Davidson, M.G., Nasisse, M.P. et al. (1995) The intracapsular extraction of displaced lenses in dogs: a retrospective study of 57 cases (1984–1990). J. Am. Anim. Hosp. Assoc. 31(1): 77–81. 33. Boeve, M.H., Stades, F.C., van der Linde-Sipman, J.S. et al. (1992) Persistent hyperplastic tunica vasculosa lentis and primary vitreous (PHTVL/PHPV) in the dog: a comparative review. Prog. Vet. Comp. Ophthalmol. 2(4): 163–172. 34. Gemensky-Metzler, A.J. and Wilkie, D.A. (2004) Surgical management and histologic and immunohistochemical features of a cataract and retrolental plaque secondary to persistent hyperplastic tunica vasculosa lentis/persistent hyperplastic primary vitreous (PHTVL/PHPV) in a Bloodhound puppy. Vet. Ophthalmol. 7(5): 369–375. 35. Pellegrini, B., Acland, G.M. and Ray, J. (2002) Cloning and characterization of opticin cDNA: evaluation as a candidate for canine oculo-skeletal

37. Van de Sandt, RROM, Stades, F.C., Boeve, M.H. et al. (2004) Arterial hypertension in the cat: a pathophysiological and clinical overview with the emphasis on ophthalmic aspects. Eur. J. Comp. Anim. Pract. 14(1): 47– 55.

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dysplasia. Gene 282(1/2): 121– 131. 36. Hendrix, D.V., Nasisse, M.P., Cowen, P. et al. (1993) Clinical signs, concurrent diseases and risk factors associated with retinal detachment in dogs. Prog. Vet. Comp. Ophthalmol. 3(3): 87–91.

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Visual impairment Ellen Bjerkås, Björn Ekesten, Kristina Narfström, and Bruce Grahn

EVALUATION OF VISUAL FUNCTION

5

This chapter deals with visual impairment and concerns both diseases primarily related to the eyes as well as eye diseases occurring secondary to systemic conditions. When an animal is examined because of visual impairment, careful questioning of the owner is of utmost importance and may often give an indication as to the nature of the disease. Essential information to be obtained from the owner is listed in Table 5.1.

Ophthalmic history Age Congenital conditions or malformation are more likely to be diagnosed in younger animals than in older ones. Puppies and kittens may also be prone to general infection, which may include ophthalmia neonatorum with accumulation of exudate underneath the fused eyelids in puppies, and upper respiratory and ocular infection caused by feline herpesvirus-1 in kittens. Both of these conditions may have deleterious effects on vision if concurrent keratitis is severe. Degenerative diseases, like hereditary rod–cone degeneration (generalized progressive retinal atrophy, PRA) and primary glaucoma show breed-specific age of onset of clinical signs and most often become evident in older animals.

Breed Many diseases show a breed-related incidence, and knowledge of such diseases often makes it easier to establish a diagnosis. However, incidence of breedrelated diseases varies in different parts of the world, which makes local knowledge essential.

General health and other clinical signs

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Visual impairment may occur as part of a systemic disease, and a general physical examination should always be performed in connection with the ocular examination. Examples of systemic diseases causing visual impairment are diabetes mellitus, which causes cataract frequently in dogs, occasionally in cats; malignant lymphoma with uveal infiltration of neoplastic cells and secondary uveitis; hypertension causing retinal hemorrhage and/or detachment, especially

• Age • Breed • General health

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Table 5.1 Essential information to acquire from the owner.

• Other clinical signs • Onset (sudden or gradual) • Known etiology (e.g. injury, accident) • Initial clinical signs • Pain/no pain • Vision in daylight/poor light • Duration

in the cat; and diseases affecting the central nervous system which may impair the conduction or interpretation of the visual impulse.

Onset The onset of impaired vision may be sudden, as in injuries, acute glaucoma, hypertensive retinopathy, and certain inflammatory retinal conditions, or gradual, as in chronic keratitis, most forms of cataracts and progressive retinal degenerations (the PRAs). In congenital conditions, the animal may have been born with reduced vision, or vision loss may develop secondary to the malformation. Examples of the latter would include retinal detachment or intraocular hemorrhage caused by collie eye anomaly (CEA), glaucoma related to dysplasia of the pectinate ligament, or progression of congenital cataract caused by persistent hyperplastic tunica vasculosa lentis/persistent hyperplastic primary vitreous (PHTVL/PHPV or more readily referred to as persistent embryonic vasculature (PEV)).

Known etiologic factors The owner is usually able to provide information about the occurrence of an ocular injury. Useful information may also be vaccination status, as corneal edema (blue eye) may occur, although very rarely nowadays, after vaccination with live modified hepatitis virus (canine adenovirus-1) in dogs. In addition to the risk of direct infection, introduction of a new animal into a household or a change in environment may impair an animal’s immune balance. This is seen in cats with subclinical infection of feline herpesvirus-1 and may result in exacerbation of keratitis.

Initial clinical signs Initial signs may vary from ocular hyperemia and discomfort to acute vision loss, dependent on specific cause. Accidents and injuries most often cause uni-

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lateral problems. Early stages of keratoconjunctivitis sicca may present with only moderate signs with conjunctivitis and mucoid discharge, while in chronic cases dryness of the cornea causes chronic keratitis with neovascularization and pigment deposits. In early stages of lens subluxation, obvious clinical signs may be moderate with just some ocular hyperemia, while in acute uveitis the clinical signs may be more obvious with the animal showing severe discomfort. One should remember that animals in their usual surroundings may apparently function more or less normally even though visually impaired. Thus, the owner may not have noticed vision loss until the animal is introduced to an unfamiliar environment. A unilaterally blind animal often shows no noticeable evidence of blindness until the second eye becomes affected.

Pain Assessment of pain may sometimes be difficult for the owner. However, if a condition is painful, the animal will usually try to avoid examination and keep the eyelids partly closed. More subtle signs of pain or discomfort may be lethargy, inappetence, or otherwise altered behavior including bad temper and reluctance to play or take part in other types of activity. Most congenital conditions as well as retinal degenerations are not painful, while glaucoma, uveitis, and large corneal ulcers may cause severe pain. Cataracts are rarely painful unless secondary lens-induced uveitis is present.

Vision in daylight and in dim light This information is important when dealing with diseases of the retina. The PRAs cause initial night blindness, with a later reduction of day vision, while hemeralopia presents with day blindness. In sudden acquired retinal degeneration (SARD) both day and night vision are acutely and simultaneously impaired. Animals with axially positioned cataracts may have better vision in dim light than in daylight, due to pupil dilatation.

Examination of the patient General examination This should be an assessment of the animal’s general condition including examination of cardiovascular circulation, respiration, mucous membranes, and peripheral lymph nodes. The owner should be questioned about appetite, thirst, and changes in the animal’s behavior. Information on the diet should be obtained; for example, cats fed dog food may develop a taurine-related retinopathy. Medication may influence the clinical signs: certain sulfonamides may be responsible for the development of keratoconjunctivitis sicca, systemic treatment with high doses of enrofloxacin may cause retinal degeneration in cats, and atropine drops impair pupillary light reflexes. In many cases diagnostic work-up is required, including hematology, serum biochemistry, urine analysis, sampling (bacteriology, cytology, polymerase chain reaction, serology), blood pressure measurements, diagnostic imaging, and electroretinography.

Neurologic examination

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If a condition affecting the central nervous system (CNS) is suspected, a full neurologic examination should be performed.1,2 Common causes of blindness of CNS origin are presented in Table 5.2. The general physical examination may already have revealed CNS signs, such as reduced vision, nystagmus,

Some causes of blindness of CNS origin.

• Optic neuritis • Trauma to optic nerves • Hydrocephalus (juvenile or acute, decompensating)

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Table 5.2

• Hepatic encephalopathy • Lysosomal storage diseases and other CNS degenerative diseases • Brain tumors (meningioma, lymphoma, pituitary tumors, reticulosis) • Encephalitis (canine distemper, feline infectious peritonitis, toxoplasmosis) • Meningitis (bacterial, viral, fungal, or algal) • Cerebrosvascular accident (cats) • Brain trauma • Toxicity (lead, ivermectin, levamisole) • Parasites (migrating larvae)

hearing loss, paresis of facial muscles, head tilt, changes in behavior, or ataxia. A neurologic examination should at least include testing of the cranial nerves, the postural reactions, and the spinal reflexes. Cranial nerves II (optic) and III (oculomotor) affect the pupillary light reflexes, while III, IV (trochlear), and VI (abducens) control ocular position and movements. It should be noted that the trigeminal nerve (V) in addition to containing sensory fibers from the cornea and the skin of the face also has a motor branch to the masticatory muscles. The facial nerve (VII) is responsible for the motor function of the facial muscles including most of the muscles of the eyelids. The trigeminal and facial nerves are tested together by tapping or pricking each side of the face. The sympathetic nerve supply, which leaves the spinal cord in the T1–T3 region, is responsible for pupil dilatation and for the tone of the smooth muscles in the periorbital fasciae and eyelids (Müller muscles).

Testing vision Obstacle course The easiest way of testing an animal’s vision is to set up an obstacle course in unfamiliar surroundings and carefully observe the animal’s movements through the area. The test should be performed both in normal and in dim light to assess day (photopic) and night (scotopic) vision. An obstacle course can be set up with almost anything; a set of small buckets put upside down can be moved around to create new paths; if unaltered, an animal may learn the path after one or two attempts, which may lead the examiner to draw the wrong conclusions. An obstacle course is a very crude way of testing vision, especially in

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younger animals that are easily distracted. Most cats are reluctant to walk an obstacle course, however, and will usually choose to hide under the nearest table instead. It may be noted that dogs with reduced vision tend to use their nose more eagerly, whereas cats tend to feel with their paws.

Cotton ball An additional way of vision testing is to hold up a cotton ball, attract the animal’s attention to it, and then drop the ball. The ball may be dropped both in front of the animal and to its sides to assess central and peripheral vision. Most animals will follow the movement of the cotton ball, even if vision is reduced. However, puppies, lethargic animals, and some cats may show little interest in the procedure. These animals may be tested by dragging a noiseless object, like a cotton ball tied to a string, along the floor.

Swinging light In a darkened room the examiner watches for corresponding head or eye movements while the light beam from a penlight is swept across the visual axis. Visual field defects are difficult to assess in animals, but an attempt can be made by repeating the procedures in various planes and with one eye blindfolded.

The optic nerve The optic nerve is the afferent path for both vision and pupillary light reflexes. At the chiasm, optic nerve fibers decussate to different degrees amongst species. As a rule, the more laterally the eyes are placed in the skull, the greater the degree of decussation. In the cat about two-thirds, and in the dog about threequarters, of the optic nerve fibers cross in the optic chiasm to the opposite side of the brain. Temporal nerve fibers from the nasal visual field remain uncrossed in the optic tract on the same side, while nasal fibers from the temporal visual field cross to the opposite optic tract (i.e. the visual field from one side of the body projects to the opposite visual cortex). This knowledge is important when assessing visual field defects in humans, but of less importance in animals, where visual field defects are difficult to evaluate. In the optic tract, 80% of the nerve fibers project via the lateral geniculate nucleus to the visual cortex of the cerebrum, whereas 20% go to the midbrain. The midbrain structures handle reflex vision, like dazzle reflex and pupillary light reflexes, and also visual input for balance and gaze fixation. The function of the optic nerve can be tested in many ways. Practical testing includes: • • • •

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Menace reaction Visual placing reaction Pupillary light reflexes Dazzle reflex.

Note the difference between reactions and reflexes: a reaction involves higher (cortical) function, whereas reflexes are not dependent upon cortical function and may even be present in an animal with abnormal visual perception associated with higher lesions. The menace reaction A normal menace reaction requires a normal visual pathway – the sensory pathway – as well as normal facial innervation – the motor pathway (Fig. 5.1). The visual pathway consists of the retina, the optic

Cortex

Facial nerve

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Nucleus (thalamus)

Optic nerve Optic chiasm Fig. 5.1 The menace reaction. A sudden movement in front of the eye produces a rapid blink. The menace reaction requires normal visual pathways to the visual cortex as well as normal motor pathway to the eyelids.

nerve, the optic chiasm, the optic tract, the lateral geniculate nucleus in the thalamus, the optic radiation, and the visual cortex. The motor pathway involves the connection from the visual cortex to the facial nucleus and the facial nerve (VII). The menace reaction is a way of testing whether the animal is visual, as a positive response (usually expressed by a blink) tells that an image has been formed in the visual cortex. The animal is threatened by suddenly moving a hand into its visual field or by opening a clenched fist in front of the eye. It is, however, important to note that the menace reaction is absent in young puppies, and can also be absent in animals with cerebellar or facial nerve lesions, without the animal being blind. Seriously ill animals may also react poorly to the stimulus. The visual placing reactions Normal visual placing reactions require normal visual pathways to the cerebral cortex, communication from the visual cortex to the motor cortex, and intact motor pathways to the lower motor neurons (final common pathway) of the forelimbs. Testing in small dogs and cats can be performed by holding the animal in front of a table. The animal is allowed to see the table surface when moved towards the table edge. Normal animals reach for the surface before the carpus touches the table. Some cats and dogs that are accustomed to being carried around may ignore the table and animals with neurologic deficits may perform the test poorly. Peripheral visual fields can be tested by making a lateral approach to the table. Larger dogs can be led over a curb or a step. The dazzle reflex This is a stimulation of the optic nerve by the examiner suddenly shining a bright light into the eye of the patient. Normally, this will make the animal blink. The dazzle reflex (or the retinal light reflex) is not a reaction, i.e. it is subcortical, mediated by reflex centers in the midbrain with fibers to the facial nucleus. The pupillary light reflexes Most important in the evaluation of visual function is the assessment of the pupillary light reflexes (PLRs) (Fig. 5.2). The

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1 6

2

3

4

5

Fig. 5.2 The pupillary light reflex arc. Shining light into one eye produces constriction of the pupil in the stimulated eye (direct pupillary light reflex) as well as in the contralateral eye (indirect pupillary light reflex). 1: optic nerve (II); 2: optic chiasm; 3: lateral geniculate nucleus; 4: parasympathetic nucleus of cranial nerve III; 5: visual cortex; 6: oculomotor nerve (III).

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afferent, or sensory, pathway involves the retina, the optic nerve (II), and the optic chiasm to the optic tract, where the majority of the fibers continue the visual pathway to the lateral geniculate nucleus. However, about 20% leave the optic tract before the lateral geniculate nucleus and course towards the midbrain, where they synapse in the pretectal nuclei. From the pretectal nuclei, fibers are distributed to the parasympathetic nuclei of the oculomotor nerve (III). The efferent or motor pathway extends via the parasympathetic fibers of the third cranial nerve through the ciliary ganglion (in which the fibers synapse) to the ciliary body and iris sphincter muscle. Pupillary constriction and dilatation is essentially a balance between parasympathetic and sympathetic control. The constrictor muscle of the iris, inner-

VISUAL IMPAIRMENT

vated by the parasympathetic fibers of the oculomotor nerve (III), is a sphincter muscle located at the pupillary border and is more powerful than the dilator muscle, which runs along the peripheral iris in a radial fashion. The dilator muscle is innervated by sympathetic nerves. These nerves leave the spinal cord in the first three thoracic segments and run along the neck in the vagosympathetic trunk, through the middle ear cavity and through the superior orbital fissure before entering the eye. Before testing the pupillary light reflexes, it is important to evaluate the size of both pupils, and to note any difference in pupil size – anisocoria. A dim light is directed from below and any changes in pupil size noted. When evaluating anisocoria, it must be remembered that, because sympathetics dilate the pupils, a sympathetic lesion will be most noticeable in the dark, as a small pupil stays small. Conversely, the parasympathetics constrict the pupils. Therefore, in parasympathetic lesions, as the pupil stays dilated, the difference in pupillary size will be greater in the light. Also remember that an anxious or excited animal may have widely dilated pupils due to sympathetic stimulation, and that re-evaluation of pupil size after the animal has relaxed may be necessary. Pupillary light reflexes in very young animals may be sluggish and incomplete, probably related to the stage of maturational myelination of the optic nerve. Testing of direct and consensual pupillary light reflexes In a darkened room, a bright light is shone into one eye. Normally this causes a rapid and complete constriction of the pupil in the stimulated eye, the direct PLR. The constriction in the other eye, the consensual (or indirect) PLR, is slightly slower. The indirect PLR is produced because of the decussation of nerve fibers in the optic chiasm as well as the contralateral connections in the nuclei of the midbrain. By evaluating the direct and consensual PLRs it is possible to localize defects along the reflex arcs, as well as to evaluate the function of the retina and optic nerve in an eye where more anterior lesions do not allow inspection of intraocular structures. The PLRs are independent of cortical vision but do still provide useful information on the integrity of the components of the afferent and efferent pathways. As the pupillary light reflexes do not involve higher (cortical) structures, a positive reflex does not necessarily infer that the animal has normal vision. It may be noted that blindness with an abnormal PLR localizes the lesion rostral to the lateral geniculate body, while blindness with a normal PLR reveals the lesion to involve the lateral geniculate body, optic radiation, or visual cortex.

Refraction The optical properties of the eye probably play an important role in visual discrimination in small animals, as well as in people. Refractive errors, e.g. myopia and hyperopia, are known in dogs and may be breed related.3 Although refractive errors may be suspected from the behavior of the patient, the refractive state of the eye can be objectively determined using a retinoscope and a series of lenses. The technique is called retinoscopy or skiascopy. Retinoscopy is easily performed in most dogs and cats. Lenses that correct for the refractive error and therefore enhance visual performance of the patient can be used to verify the diagnosis, and contact lenses can be used to adjust visual acuity. Long-term use of contact lenses to correct refractive errors may be used in small

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animals and contact lenses for aphakic (with no lens) dogs are now commercially available.

Electrophysiology Electrophysiologic testing becomes invaluable in animals with visual dysfunction.4 Different procedures can be performed depending on the site of a suspected lesion, such as the retina, optic nerve, or the visual cortex. To examine visual function clinically, the recording of two types of response is recommended. The electroretinogram (ERG) allows a rapid and objective examination of the outer and inner retina while the visual evoked potential (VEP) depends on normal optic nerve function and therefore reflects the conduction of the retinal signal all the way to the brain. Because the area centralis region is magnified in the optic nerve and brain response, the VEP also provides some insight into potential visual acuity. ERG The ERG is a technique for observing the changes of electrical potential that occur when the eye is stimulated by light. These voltage changes, generated in the retina, reflect the responses of several types of neuron summed across the retina. They are critically dependent on the function of the retinal photoreceptors, i.e. the rods and cones. The ERG is usually recorded by means of a corneal contact lens electrode in response to a defined flash of light or repeated flashes (flicker) and displayed on an oscilloscope or on a computer screen. General anesthesia, intubation, and continuous monitoring of the patient are recommended during the procedure. In veterinary ophthalmology the ERG mainly has two broad applications: the easiest and most straightforward simply tests whether or not a standard stimulus elicits an ERG response. An example of this application is in an animal with complete cataracts. An ERG is indicated before proceeding to cataract surgery in order to ascertain that the retina is functional and not affected by PRA. The second and more sophisticated application is the study of rod and cone function as a part of research projects or in the early diagnosis of hereditary retinal dystrophies. A complex set of processes, PI, PII, and PIII, first described by Granit,5 collectively comprise the ERG response, with its a-, b-, and, in some types of recording, c-waves. Grossly, the a-wave reflects the membrane current of photoreceptors and thus reflects their activity directly. The b-wave is generated as a complicated interaction, involving potassium movement between the bipolar and Müller cells, in response to input from the photoreceptors. The cwave is generated mainly through hyperpolarization of the apical membrane of the pigment epithelium and thus reflects retinal pigment epithelial cell function. The rod photoreceptors mainly function under scotopic conditions, and the cones mainly under photopic conditions. ERG recordings thus represent various combinations of rod and cone responses depending on the specific lighting used as background and/or stimulus. Therefore, it is important that a fixed protocol is used to obtain meaningful ERGs. In order to interpret the ERG responses successfully it is, moreover, recommended that a technique be used that allows for the direct separation of rod and cone contributions to the ERG. Recommendations regarding how to perform diagnostic ERGs in dogs have recently been published.6

VISUAL IMPAIRMENT

The waveform of the ERG together with the amplitude and implicit times of the a- and b-waves is most often used when evaluating ERGs in a clinical situation. Comparisons are made of the observed responses with those of normals or controls. It should be noted that there are species, breed, and age-related variations in ERG parameters, so comparisons have always to be made with breed and age-matched animals. VEP Using active scalp electrodes, VEPs can be recorded in anesthetized animals using stroboscopic flashes of light and averaging techniques.7 VEPs are cone dominated and reflect activity in a small part of the central area of the retina. Fibers from the central area of the retina are projected onto the surface of the occipital cortex, whereas fibers from the peripheral areas are projected to deeper parts of the cortex and are not readily recorded. Apart from the central area of the retina, VEP mainly tests function of the post-retinal structures such as the optic nerve and the visual cortex. The waveform of the VEP consists of three major positive waves, the P1, P2, and P3. The characteristics of the VEP recording depend on a complex array of spatial and temporal conditions of light stimulation including luminance, contrast, and rate of stimulation. Depth of consciousness, age, visual acuity, and degree of light adaptation also influence the VEP. The VEP is currently used most often for research purposes, but the technique certainly has evolving clinical applications in the assessment of disease affecting the optic nerve and central visual systems. VEPs and ERGs can, moreover, be recorded simultaneously in the anesthetized animal, which makes it possible to evaluate visual function electrophysiologically in a more complete fashion.

Other Ultrasonography indicated to define space-occupying lesions, foreign bodies, scleral tears, and retinal detachment, especially in cases where the fundus cannot be visualized. Fluorescein angiography is a specialized technique used to assess the retinal and choroidal vasculature. It requires a fluorescein fundus camera with filters that are placed in both the illuminating beam and the observing beam. The exciter filter in the illuminating beam transmits blue-green light at the peak excitation wavelength for fluorescein, thus making it fluoresce. The barrier filter (in the pathway for the observing beam) transmits yellow light at fluorescein’s peak emission range. Fluorescein is delivered by an intravenous bolus and serial photographs are taken of the various stages of filling and emptying of retinal and choroidal vessels.

CONGENITAL DISEASE AND MALFORMATIONS Anophthalmia, nanophthalmia, and microphthalmia In anophthalmia, the globe is not present. This is a rare condition caused by a defect in the formation of the optic vesicle from the neuroectoderm, and may be unilateral or bilateral. Histologic examination of tissue from the orbital region may often reveal traces of rudimentary optic structures. Microphthalmia is relatively common in the dog, and may present as a small but otherwise normal globe; this form of microphthalmia is termed nanophthalmia. The term microphthalmia, however, is usually used to describe a small

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and abnormal globe, the result of retarded or aberrant development of the optic vesicle with associated ocular anomalies that may include cataract, persistent pupillary membrane, retinal dysplasia, and colobomas. Microphthalmia is seen more frequently in certain breeds, including the Collie breeds, English Cocker Spaniel, Saint Bernard, and Dobermann Pinscher, but may occur spontaneously in dogs of any breed. Teratogenic agents as well as hereditary factors may cause malformations of the eyes. Microphthalmia may occur unilaterally or bilaterally, and one or more littermates may be affected.

Clinical findings Anophthalmic or grossly microphthalmic eyes should not be difficult to recognize. Mild cases of microphthalmia or nanophthalmia may cause diagnostic problems, however, especially if the condition occurs bilaterally. In certain breeds, like the Collie and the Shetland Sheepdog, the breed standard demands small eyes, making differentiation between normal and microphthalmic eyes difficult. The following features may be of help when comparing a unilaterally microphthalmic eye to its fellow normal eye. • Compare both eyes by inspection from above and in front of the animal and observe differences in the palpebral fissure, recession of the microphthalmic eye into the orbit (enophthalmia), and protrusion of the third eyelid. • Note the exposure of the sclera and the diameter of the cornea. • Closer examination may reveal abnormalities including persistent pupillary membranes, abnormal pupil shape (dyscoria), cataracts, and multifocal retinal dysplasia or retinal detachment. • Colobomas may be present, but are more rarely diagnosed. • There are often abnormal eye movements such as a ‘searching’ nystagmus or a fine oscillatory nystagmus, which indicates that the visual pathways are not fully developed.

Differential diagnoses Difference in iris pigmentation between two otherwise normal eyes (heterochromia irides) is not uncommon and should not be confused with abnormalities of the eyes. Phthisis bulbi (shrinkage of the eye) occurs as a result of severe trauma or as an end-stage of intraocular inflammation. This condition is commonly preceded by a history of red eye and ocular pain, whereas microphthalmia is painless. Microphthalmia as a congenital condition is usually detected in the young animal, while phthisis bulbi may occur in animals of any age.

Prognosis and treatment

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Abnormal development of the eye cannot be treated and the prognosis depends on the degree of visual impairment and whether the condition is unilateral or bilateral. Secondary cataracts may develop as may chronic conjunctivitis due to poor configuration of eyelids and globe. The conjunctivitis may need daily cleansing to remove accumulated discharges. Cataract surgery in microphthalmic eyes may be rewarding if no other malformations are present. Enucleation may be recommended if the microphthalmic eye is blind and causes discomfort

Persistent pupillary membrane (PPM) During the embryonal phase before the pupil is formed, the area is covered by a vascular membrane, the pupillary membrane. The membrane is formed during development of the eye by anastomoses between the tunica vasculosa lentis, which branches from the hyaloid artery and forms a meshwork around the lens, and vascular loops from the annular vessel in front of the lens. Normally, regression of the pupillary membrane starts about 2 weeks before birth, with the membrane no longer present by 2–4 weeks after birth. Minute remnants of the membrane are frequent in animals and are usually of no significance. These remnants may be seen as tissue strands originating from the collarette of the iris. The strands may extend from iris to iris across the pupil, from iris to lens or to cornea or to both, or there may be sheets of tissue in the anterior chamber extending between iris, lens, and cornea. Where attached to the lens, there may be concurrent cataract formation, and attachment to the inside of the cornea may cause focal corneal opacities and edema. A variant of PPM may be seen as an area of pigmented flecks on the anterior lens capsule.

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to the animal. The use of the animal for future breeding is not advised, particularly in those breeds where the condition is suspected to be inherited.

Clinical findings PPM is congenital and may therefore be diagnosed in the young animal. The condition is not painful and there is no history of previous injury to the eye. With corneal involvement the opacity does not stain with fluorescein, as it affects the endothelium and the stroma. A genetic disposition has been described in the Basenji8 and has been suggested in the English Cocker Spaniel and the Collie.9 More than one puppy in a litter is often affected.

Treatment and prognosis There is no effective treatment for this congenital condition, but, unless the changes are extensive, vision is not impaired. Severely affected dogs from breeds where a hereditary disposition is suspected should not be used for breeding.

Congenital lens disorders These disorders are usually part of other developmental abnormalities of the eye and may be due to a chance error in embryogenesis. In some cases, however, the abnormalities have a hereditary background. Congenital developmental abnormalities of the lens, which often occur in combination with other malformations of the eye, such as persistence of the hyaloid vessels or microphthalmia, include: • Aphakia – the total absence of the lens or the presence of only rudimentary lens tissue. This is a rare condition. • Microphakia – smaller than normal lens equatorial diameter. Elongated ciliary processes can be seen surrounding the lens, and the lens borders are clearly visible when the pupil is dilated. The condition may be breed related, as in the Miniature Schnauzer, where it is associated with congenital cataract.

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• Spherophakia – an abnormal spherical shape to the lens which is usually microphakic as well. • Coloboma – where the lens has an equatorial notching (Fig. 5.3). The zonular fibers are either deficient or absent in the affected area. This condition may be associated with congenital cataract and colobomas of the iris and ciliary body. • Lenticonus/lentiglobus – a thinning of the lens capsule permitting the cortex to bulge. This causes a conical malformation, most commonly at the posterior pole. Lentiglobus is more severe than lenticonus. The capsule in the affected area may show dysplastic or degenerative changes that influence lens metabolism and result in cataract development. Spontaneous rupture of the posterior capsule may occur. The abnormality is most often diagnosed in connection with abnormalities of the posterior hyaloid system, as described in persistent hyperplastic tunica vasculosa lentis/persistent hyperplastic Primary vitreous (PHTVL/PHPV) in the Dobermann Pinscher,10 or in connection with microphthalmia and cataract. A congenital defect of the lens including cataract, posterior lenticonus, and sometimes also microphthalmia has been described in the Cavalier King Charles Spaniel (Fig. 5.4).11 • Cataracts – nuclear and sometimes posterior and/or anterior cortical opacification with or without capsular involvement is observed in litters of several breeds. This type of congenital cataract has been described specifically in the English Cocker Spaniel.9 In the West Highland White Terrier a specific type of posterior suture line cataract has been described, as well as congenital complete cataracts.12

Persistent hyaloid artery (PHA) The hyaloid artery is present in fetal life, but will normally undergo regression during the first postnatal weeks. Remnants of the obliterated hyaloid artery

128

Fig. 5.3 Congenital malformations of the lens in a 1-year-old Samoyed dog: unilateral lens coloboma and cataract.

VISUAL IMPAIRMENT

Fig. 5.4 Posterior lenticonus, with rupture of the posterior lens capsule, and bilateral congenital cataract in the eye of a 12-week-old Cavalier King Charles Spaniel.

which persist without any other abnormalities are referred to as PHA.13 The artery can remain as a curvilinear structure, still containing blood, between the optic disk and the lens. Usually, however, only a small connective tissue strand remains.

Clinical findings The persistent hyaloid artery can be seen as a white strand adherent to the posterior lens capsule, below the posterior pole. The vessel remnants extend back into the vitreous body and move with the eye movements. Occasionally, the hyaloid vessel arises from an anomalous superficial retinal vessel. Small vessel remnants do not affect vision, but at the site of adherence to the lens there may be a focal opacity (Mittendorf’s dot). Secondary cataracts may develop in this area. The condition may occur unilaterally or bilaterally and is occasionally seen in the dog. A familial disposition has been suspected in the Sussex Spaniel.

Persistent hyperplastic tunica vasculosa lentis/persistent hyperplastic primary vitreous (PHTVL/PHPV) or persistent embryonic vasculature (PEV) In this disorder, parts of the hyaloid system and primitive vitreous become hyperplastic and remain postnatally instead of undergoing normal regression.10,14 Embryologic alterations occur in the eye cup, the primary vitreous, the hyaloid artery, and the tunica vasculosa lentis. The hyperplasia and lack of normal regression are considered to be caused by a disharmony between growth factors and inhibitors within the eye. In severe cases, secondary cataracts develop. The condition may be unilateral or bilateral and may occur sporadically in any animal. In the Dobermann Pinscher primarily, but also in other

129


breeds such as the Staffordshire Bull Terrier and Standard Pinscher,15,16 the disorder occurs bilaterally, and appears to be inherited by an incomplete dominant mode of inheritance in the Dobermann Pinscher.

Clinical findings In the mildest form of PEV, tiny punctuate opacities, residual tissue from the vascular network, are found on the axial posterior lens capsule. These lesions do not progress and do not detectably affect vision. They are only seen by use of a slit-lamp biomicroscope, and may be difficult to diagnose in puppies because of small eye size. The severe forms occur bilaterally and often lead to visual impairment. A plaque of white fibrovascular tissue may be identified on the posterior capsule. In addition, large remnants of the hyaloid system can persist and may be accompanied by pigment or blood in and around the lens, lenticonus, or other lens malformations (Figs 5.5 & 5.6). PHTVL may also be seen as vascular loops anterior to the lens. In the most severe forms, secondary cataracts are either present at birth or develop early in life.

Diagnosis and differential diagnosis Since the condition is congenital and can be diagnosed in the puppy, a scoring system depending on the severity of the disorder has been suggested. The disease does not include persistent pupillary membranes as described earlier, but small loops of the tunica vasculosa lentis system may be seen adjacent to the anterior capsule of the lens. Differential diagnoses include congenital cataract and retinal detachment.

Therapy and prognosis In severely abnormal eyes, lens extraction (see cataract therapy) can be performed together with posterior capsulorhexis and vitrectomy. The prognosis

130

Fig. 5.5 PHTVL/PHPV in a 9-month-old Dobermann Pinscher. Fibrovascular tissue and pigmentation are seen on the posterior lens capsule as well as posterior lenticonus.

VISUAL IMPAIRMENT

Fig. 5.6 Intralenticular bleeding and low-grade uveitis is seen in conjunction with PHTVL/ PHPV in this 1-year-old Dobermann Pinscher.

for the operation is less favorable than in uncomplicated lens extraction, because of the increased incidence of intraoperative and postoperative complications. Dobermann Pinscher puppies can be screened for PHTVL/PHPV at about 7–8 weeks of age. Severely affected animals should not be used for breeding, while dogs expressing only multifocal pin-point posterior capsular opacities may be bred to normal-eyed animals.

Congenital vitreous opacification Vitreous opacification is uncommon and is usually due to hemorrhage associated with congenital retinal abnormalities. These may result from rupture of blood vessels in a detached retina or from retinal neovascularization. The congenital diseases most commonly connected with blood in the vitreous are: • Collie eye anomaly (CEA) in collie breeds. The hemorrhage usually occurs sporadically in the young dog, most often before 2 years of age. • Total retinal dysplasia with non-attachment, as seen sporadically in many breeds and as an inherited condition in the Labrador Retriever, Sealyham Terrier, Bedlington Terrier, and occasionally the English Springer Spaniel. • Multiple congenital ocular anomalies may be the result of mating of two merle-colored dogs and does also occur in the Australian Shepherd Dog. • Other conditions including preretinal arteriolar loops and vascular malformations.

Clinical findings Hemorrhage in the vitreous is diagnosed unilaterally or bilaterally as blood seen behind the lens. The blood may also pass forward into the anterior segment of the eye. The condition is usually non-painful unless occurring secondary to

131


a painful ocular disease. One should remember that acquired vitreal hemorrhage is not an uncommon condition and will be discussed later in this chapter.

Diagnosis Examination of the fellow eye, if unaffected, may reveal congenital anomalies of types that may cause vitreous hemorrhage. The breed incidence is also important to consider.

Differential diagnosis Intralenticular hemorrhage may be seen in connection with PHTVL/PHPV. The hemorrhage in this disorder, however, is within the retrolental plaque of tissue and sometimes also within the lens (see Fig. 5.6). Breed incidence must be considered. Hyphema (blood in the anterior chamber) may resemble vitreous hemorrhage, and may occur from the same disorder (e.g. CEA), but will most often represent a different condition, like trauma, uveitis, or neoplasia. While hyphema is seen in front of the lens, hemorrhage from hyaloid vessel remnants is seen behind the lens. Hyperviscosity of the blood is usually associated with monoclonal gammopathies and plasma cell producing tumors, and may lead to vessel rupture and hemorrhage. A thorough clinical examination should be performed. This disease, however, is usually diagnosed in older animals.

Treatment and prognosis Surgical removal (vitrectomy) of congenital intravitreal hemorrhage is rarely indicated. The condition is serious because it usually indicates a severe disorder of the posterior segment or an underlying systemic disease. This is especially true if the blood remains unclotted, indicating continuous bleeding. The hemorrhage may seemingly clear if the dog is inactive for a period, but will return as soon as the dog is exercised. If, however, the hemorrhage should clear permanently, the vitreous may undergo degenerative changes which may lead to traction on the retina with subsequent detachment. More uncommonly, secondary glaucoma or uveitis may develop.

Congenital malformations of the retina and the optic nerve The retina can be congenitally malformed in several ways including involvement of all layers of the neuroretina, such as in retinal dysplasia, or specific cells in the retina being affected, such as rod–cone dysplasia or retinal pigment epithelial cell dystrophy. In certain defects structures posterior to the retina are malformed, as well as in posterior segment colobomata. Congenital malformations are often caused by hereditary factors but some are also induced by maternal infection or X-irradiation, such as retinal dysplasia (see below), or may occur as a spontaneous malformation. See Table 5.3 for a summary of hereditary retinal disease affecting specific cells of the neurosensory retina in the dog and cat.

General treatment 132

There is usually no effective treatment for congenital malformations of the posterior segment of the eye. If the defect is known to be hereditary, preventive

AR AR

Rod–cone dysplasia/rcd1



Rod dysplasia/rd

Early rod degeneration/erd

Photoreceptor degeneration/pd/type A PRA

Cone–rod dystrophy/crd1

Cone–rod dystrophy/crd2

Early cone–rod dystrophy

Cone–rod dystrophy

Cone–rod dystrophy

Irish Red & White Setter

Rough Collie

Cardigan Welsh Corgi

Norwegian Elkhound

Norwegian Elkhound

Miniature Schnauzer

Pit Bull Terrier

Pit Bull Terrier

Shorthaired Dachshund

Longhaired Dachshund

Wirehaired Dachshund

AR

AR

AR

AR

AR

AR

AR

AR

AR

AR


Irish Setter

Mode of inheritance

Disease/Gene symbol

1.5–3.0 y

0.5 y

1.5–3.0 y

0.4–0.5 y

0.4–0.5 y

1.5–5.0 y

0.75–1 y

0.5–1.5 y

0.3 y

0.3 y

0.3 y

0.3 y

Diagnosis by ophthalmoscopy

Summary of some clinically characterized hereditary primary photoreceptor disorders of dog and cat breeds.

Breed of dog

Table 5.3

5 wk

6 wk

5 wk

7 wk

7 wk

6 wk

5 wk

6 wk

3 wk

6 wk

6 wk

6 wk

Diagnosis by ERG

VISUAL IMPAIRMENT

133

Disease/Gene symbol

Cone degeneration/achromotopsia

Cone degeneration/achromotopsia

X-linked progressive retinal degeneration/XL PRA1



Dominant progressive retinal atrophy (rhodopsin mutant dog)

Dominant progressive retinal atrophy (rhodopsin mutant dog)

Progressive rod–cone degeneration/prcd

Breed of dog

Alaskan Malamute

German Shorthaired Pointer

Siberian Husky

Samoyed

Mixed breed

Old English Mastiff

Bull Mastiff

Toy and Miniature Poodle

Table 5.3 continued

134 0.5–1.0 y

3.0–5.0 y

AR

0.5–1.0 y

1–2 y

3.0–5.0 y

2.0 y

–

–

Diagnosis by ophthalmoscopy

AD

AD

X-linked

X-linked

X-linked

AR

AR

Mode of inheritance

9 mo

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