Mastering Corneal Collagen Cross-linking Techniques (C3-R/CCL/CxL)
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DVD Contents 1. Limited Topoguided PRK Followed by Collagen Cross-linking for Keratoconus. A John Kanellopoulos (Greece). 2. Riboflavin UV-A Induced Collagen Cross-linking In Keratoconus. C Banu Cosar, E Coskunseven (Turkey). 3. One Shot Epithelium Rhexis. Roberto Pinelli (Italy). 4. Tunnel Creation By Femtosecond Laser and the Implantation of Ferrara Ring Segments. Carlo Lovisolo (Italy) 5. Slit Lamp Video Wood Light Fluorescein Patterns of Custom Designed Reverse-Geometry Contact Lens in Keratoconus. Carlo Lovisolo (Italy).
Mastering Corneal Collagen Cross-linking Techniques (C3-R/CCL/CxL) with Video DVD Rom Editors Ashok Garg MS PhD FIAO (Bel) FRSM, FAIMS, ADM, FICA
International and National Gold Medalist Chairman and Medical Director Garg Eye Institute and Research Centre 235-Model Town, Dabra Chowk Hisar-125005 India
Roberto Pinelli
A John Kanellopoulos
MD
MD
Director, Istituto Laser Microchirurgia Oculare Crystal Palace, Via Cefalonia 70, 25124, Brescia Italy
Director, Laservision gr. Institute Mesogeion 2 and Vasilissis Sofias Pyrgos Athinon Building B, 11527-Athens Greece
David O Brart
Carlo F Lovisolo
MD, FRCS, FRCOph
MD
Department of Ophthalmology Kings College, London The Rayne Institute St Thomas Hospital, London UK
Medical Director QuattroElle Eye Center Via Cusani, 709, 20121 Milano Italy
Foreword Eric D Donnenfeld ®
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[email protected] Mastering Corneal Collagen Cross-linking Techniques © 2009, Editors All rights reserved. No part of this publication and Video DVD Rom should be reproduced, stored in a retrieval system, or transmitted in any form or by any means: electronic, mechanical, photocopying, recording, or otherwise, without the prior written permission of the editors and the publisher. This book has been published in good faith that the material provided by contributors is original. Every effort is made to ensure accuracy of material, but the publisher, printer and editors will not be held responsible for any inadvertent error(s). In case of any dispute, all legal matters are to be settled under Delhi jurisdiction only.
First Edition: 2009 ISBN 978-81-8448-493-9 Typeset at JPBMP typesetting unit Printed at Ajanta Press
Dedicated to – My Respected Param Pujya Guru Sant Gurmeet Ram Rahim Singh Ji for his blessings and motivation. – My Respected Parents, teachers, my wife Dr. Aruna Garg, son Abhishek and daughter Anshul for their constant support and patience during all these days of hard work. – My dear friend Dr. Amar Agarwal, a renowned International Ophthalmologist for his constant support, guidance and expertise. — Ashok Garg – All patients affected by Keratoconus, in the hope that a near future will offer a solution avoiding for many of the them the corneal transplant. — Roberto Pinelli – My parents, the endless and willing teachers and my family : my wonderful wife Nathalie, and our children: Alexander, Angelina and Konstantine. — A John Kanellopoulos – My wife Elizabeth. — David O. Brart – My kids Alessandro and Luca Ghigo, the lastcomers, two potentially brilliant researchers in the field of nanotechnology. — Carlo Francesco Lovisolo
Contributors A John Kanellopoulos
Athiya Agarwal
Carina Koppen
MD
MD DO
MD
Director, Laser Vision Gr. Institute Mesogeion 2 and Vasilissis Sofias Pyrgos Athinon (B Building) Athens 11527 Greece
Agarwal’s Eye Hospital 19 Cathedral Road Chennai - 600 086 Tamilnadu India
Department of Ophthalmology University Hospital Antwerp Wilrijkstraat 10, B-2650 Edegem (Antwerp) Belgium
Amar Agarwal
Aylin Ertan
Carlo F Lovisolo
MD
MD
Kudret Goz Hastanesi Kennedy Caddesi No.71 Kavaklidere-Ankara Turkey
Medical Director QuattroElle Eye Center via Cusani, 7-9, 20121 Milano Italy
MS FRCS FRCOphth
Agarwal’s Eye Hospital 19 Cathedral Road Chennai - 600 086 Tamilnadu India Antonio Calossi OD FAILAC FBCLA Studio Optometrico Calossi Via 2 Giugno, 37 50052 Certaldo (FI) Italy
Bahri Aydin
Antonio Leccisotti
Belquiz A Nassaralla
MD
MD PhD
Istituto Laser Microchirurgia Oculare Crystal Palace, Via Cefalonia, 70 25124 Brescia Italy Arun C Gulani MD
MD
Alparslan Turkes cad. No.57 Emek 06510 Ankara Turkey
Goiania Eye Instiute Department of Cornea and Refractive Surgery, Goiania, GO Brazil Brian Boxer Wachler
Director Gulani Vision Institute 8075 Gate Parkway (W) Suite 102, Jacksonvill Florida-32216 USA
MD
Ashok Garg
Caitroina Kirwan
MS PhD FRSM
MRC Ophth
Chairman and Medical Director Garg Eye Institute and Research Centre 235-Model Town, Dabra Chowk Hisar-125005 India
Department of Refractive Surgery Mater Private Hospital Eccles Street Dublin 7 Ireland
Director Boxer Wachler Vision Institute 465 N, Roxbury, Dr. Suite 902 Los Angeles, CA 90210 USA
C Banu Cosar MD
Associate Professor of Ophthalmology Sinpas Aqua City 1. Etap H Block D:13, Cekmekoy 34773 Istanbul Turkey Chitra Ramamurthy MD
The Eye Foundation 582-A DB Road RS Puram Coimbatore-641002 Tamilnadu India CS Siganos MD
Deptt. of Ophthalmology Institute of Vision and Optics University of Crete Greece David PSO’ Brart MD FRCS FRCOphth
Department of Ophthalmology St. Thomas’ Hospital, London UK
MASTERING CORNEAL COLLAGEN CROSS-LINKING TECHNIQUES D Ramamurthy
Joao J Nassaralla
Lee T Nordan
MD
MD PhD
MD
Medical Director The Eye Foundation 582-A, DB Road R.S. Puram Coimbatore-641002 Tamilnadu India
Faculty of Health Sciences University of Brasilia, DF Goiania Eye Institute Department of Retina and Vitreosu Goiania, GO Brazil
Gulani Vision Institute 8075 Gate Parkway (W) Suite 102, Jacksonvill Florida-32216 USA
John Marshall Efekan Coskunseven MD
Dunya Eye Hospital Istanbul Turkey Francisco Sanchez Leon MD
Department of Ophthalmology St. Thomas Hospital London UK Jorge L Alió MD PhD
Director Instituto Oftalmologico Novavision Av. Lomas Verdes 464 Naucalpan, Edo.Mexico Mexico CP53120
Professor and Chairman of Ophthalmology Instituto Oftalmologic De Alicante Avda. Denia 111, 03016 Edificio Vissum, Alicante Spain
GD Kymionis
Kanxing Zhao
MD PhD
MD PhD
Deptt. of Ophthalmology, Institute of Vision and Optics University of Crete Greece
Tianjin Medical University Tianjin Eye Hospial and Eye Institute No.4, Gansu Rd, Tianjin 20020 China
Ioannis G Pallikaris
Keith M Meek
MD PhD
Director Deptt. of Ophthalmology Institute of Vision and Optics University of Crete Greece James Doutch BSc
School of Optometry andVision Sciences, Cardiff, University Cardiff UK
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PhD
PhD
Chairman and Medical Director School of Optometry andVision Sciences, Cardiff, University Cardiff UK Konstantinos Samaras MD MRCOph
Department of Ophthalmology St. Thomas Hosptial London UK
Liquing Liu MD
Tianjin Eye Hospial and Eye Institute No.4, Gansu Rd Tianjin 300020 China Marie Jose Tassignon MD PhD
Department of Ophthalmology University Hospital Antwerp Wilrijkstraat 10, B-2650 Edegem (Antwerp) Belgium Mesut Erdurmus MD
Alparslan Turkes cad. No.57 Emek 06510 Ankara Turkey Michael O’ Keeffe FRCS
Professor Department of Refractive Surgery Mater Private Hospital Eccles St, Dublin 7 Ireland Mohmed H Shabayek MD
Instituto Oftalmologico De Alicante Avde. Denia 111, 03016 Edificio Vissum, Alicante Spain MS Sridhar
Laure Gobin
MD
Jie Hou
MD
PhD
Department of Ophthalmology University Hospital Antwerp Wilrijkstraat 10, B-2650 Edegem (Antwerp) Belgium
SRIVISION Eye Hospital 225/A, Road No. Jubilee Hills Check Post Jubilee Hills Hyderabad-33 India
Tianjin Eye Hospial and Eye Institute No. 4, Gansu Rd Tianjin 300020 China
CONTRIBUTORS Nikos Tsiklis
Robert o Pinelli Roberto
Tar ak Pujara Tarak
MD
MD
MD
Deptt. of Ophthalmology Institute of Vision and Optics University of Crete Greece
Director Istituto Laser Microchirurgia Oculare Crystal Palace, Via Cefalonia, 70 25124 Brescia Italy
Clinical Affairs Manager CustomVis, 9 Esmerelda Pass Darch, Western Australia-6065 Australia
Sally Hayes
Tarek Elbeltagi
PhD
MD
School of Optometry and Vision Sciences, Cardiff, University Cardiff UK
Istituto Laser Microchirurgia Oculare Crystal Palace Via Cefalonia, 70 25124 Brescia Italy
Nilesh Kanjiani DO FER
Agarwal’s Eye Hospital 19 Cathedral Road Chennai - 600 086 Tamilnadu India Nurullah Cagil MD
Ataturk Hastanesi Egitim ve Arastirma hastanesi, Goz Hastaliklari Lodumlu Yolu, No. 3 Bilkent Ankara Turkey
Soosan Jacob MS FRCS DNB MNAMS
Agarwal’s Eye Hospital 19 Cathedral Road, Chennai - 600 086 Tamilnadu India Sunita Agarwal MS DO
Agarwal’s Eye Hospital 19 Cathedral Road, Chennai - 600 086 Tamilnadu India
Yan Wang MD
Professor, Tianjin Medical University Director Refractive Surgery Center Tianjin Eye Hospial and Eye Institute No.4, Gansu Rd Tianjin 300020 China
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Foreword This is one of the most exciting times for ophthalmology in general, and cornea and refractive surgery in particular. The breakthroughs over the last several years are changing the way we approach the cornea and offering our patients new and exciting opportunities for visual rehabilitation. At present, there is no technology with more promise than corneal collagen cross-linking. It combines two relatively mundane entities: riboflavin or vitamin B2, which is a naturally occurring photosensitizer found in all human cells, and ultraviolet light. A remarkable change occurs in the cornea stroma when riboflavin and ultraviolet light react together at the right concentrations and for the correct duration. The crosslinking of the corneal collagen fibrils strengthens the biomechanical properties of the cornea with a resultant increase in the tensile strength of the collagen fibrils. Although there may also be a slight flattening of the cornea, the most important effect of the cross-linking is that it stabilizes the corneal curvature and prevents further steepening and bulging of the corneal stroma. There is no significant change in the refractive index or the clarity of the cornea. The clinical applications of collagen cross-linking offers for the first time, a treatment for one of the most common corneal disorders, keratoconus, as well as the most dreaded complication of corneal refractive surgery, ectasia. Corneal ectasia is a rare but well-described complication of laser in-situ keratomileusis (LASIK) and an even more rare complication of photorefractive keratectomy (PRK). Over the last several years, risk factors for ectasia have been identified, which include high myopia, deep ablations, reduced residual corneal bed, young age, thin pachymetry, and most importantly, pre-operative corneal irregularity. However, ectasia may occur with no risk factors despite our best attempts to prevent it. Corneal ectasia is a condition in which the cornea is weakened by LASIK or PRK so that it protrudes irregularly and bows outward. This creates progressive steepening and thinning of the cornea, loss of uncorrected visual acuity, and loss of best spectacle-corrected visual acuity. The final results of ectasia may be as minimal as the need for the patient to return to the use of glasses. However, many patients may require a lifetime of rigid contact lenses, intracorneal ring segments, or penetrating keratoplasty for visual rehabilitation. Collagen cross-linking may arrest the progression of ectasia and when combined at the same time or subsequently with topographic or wavefront guided photoablation, may return uncorrected visual acuity. Patients at risk for ectasia may be prophylactically treated to prevent its occurrence. The elimination of corneal ectasia as a risk of LASIK and PRK has the potential to open an era of refractive surgery where the most dreaded complication has been eliminated. Keratoconus is a naturally occurring ocular condition similar to ectasia and characterized by progressive thinning and steepening of the central cornea. Keratoconus frequently affects patients in their teens and early twenties, progresses over the course of a decade, and leaves patients visually handicapped, often with high myopia, irregular astigmatism, and significant loss of best corrected visual acuity. Rigid contact lenses can be used to improve visual acuity in many patients, but keratoconus frequently progresses to the point that corneal transplantation is required to restore useful vision. It may recur following corneal transplantation and require further transplant surgery. The incidence of keratoconus in the general population is estimated to be approximately one in 2000 and in the United States, keratoconus is the third most common indication for penetrating keratoplasty. Corneal transplantation has undergone remarkable improvements, but it still has inherent risks
MASTERING CORNEAL COLLAGEN CROSS-LINKING TECHNIQUES
that can result in permanent loss of vision, it significantly impacts the patient’s quality of life during the surgical recovery phase, with lost work time, and it often requires permanent changes in lifestyle. Any modality, such as corneal collagen cross-linking that can delay or prevent corneal transplantation in patients with these conditions is of great benefit. The field of collagen cross-linking is advancing quickly. It offers for the first time a treatment for ectasia and keratoconus, two diseases that currently have no real treatment aside from corneal transplantation. There is a strong need to bring together the leading international investigators of collagen cross-linking to educate the ophthalmic community on recently published data, unpublished data, techniques, pitfalls, and personal observations. Drs. Ashok Garg, Roberto Pinelli, A. John Kanellopoulos, David Brat, and Carlo Lovisolo, the editors of Mastering Corneal Collagen Cross-linking have done exactly this. They have brought together the leading names in corneal collagen cross-linking and have created a wonderful resource for all of us to learn from their vast experience experience. The basic science of collagen cross-linking is explained, followed by chapters that expand our knowledge of ectasia and keratoconus. There are several chapters that describe the different techniques for employing corneal collagen cross-linking. There are also chapters on managing complications to help us avoid or treat untoward results. In addition, the DVD provides a visual representation of collagen cross-linking surgery which supplements the book beautifully. This book is an exceptional resource and the definitive book on corneal collagen cross-linking. Mastering Corneal Collagen Cross-linking should be required- reading for all of us with an interest in cornea and/or refractive surgery surgery.
Eric D Donnenfeld MD
Professor of Ophthalmology New York University Medical Center Trustee Dartmouth Medical School 2000 N Village Ave Rockville Centre N.Y. 11570,USA Ph. 001-516766-2519 E-mail:
[email protected] xii
Preface Corneal Collagen Cross-linking with Riboflavin and UV-A (C3-R) treatment is certainly a new and promising development in refractive surgery in recent times. The weakened cornea in form of Keratoconus or Post-Lasik/ PRK Corneal Ectasia (Keratoectasia) is one of the most challenging task for Ophthalmologists. Reduced corneal mechanical stability in Keratoconus and Corneal Ectasia can be treated by Photo-oxidative cross-linking of the Corneal Collagen. To achieve high absorption of irradiation energy in the cornea, Riboflavin at a concentration of 0.1% and UV-A light at a wavelength of 370 nm corresponding to the relative maximum of absorption of Riboflavin (Vitamin B2) is used. Therapeutic C3-R cross-linking procedure causes decrease in corneal curvature of about 2D which leads not only to stabilization but also to an increase in visual acuity and more compact and stronger corneas. This book has been written with the aim of providing complete insight into this new technique for the benefit of refractive surgeons worldwide. Its 23 chapters have been written by International Experts of this technique and they cover all aspects of C3-R technique in a comprehensive manner. It deals with all steps mainly indications, contraindications, various surgical procedures, complications and their management. Video DVD given with this book shows the surgical steps of C3-R treatment by International Masters beautifully. Our sincere gratitude to publisher Shri Jitendar P Vij (CEO), M/s Jaypee Brothers Medical Publisher Pvt. Ltd. (India), Mr Tarun Duneja (Director– Publishing) and all staff members who took active interest and done hard work in timely preparation of this book, first of its kind in the world. C3-R treatment alone or combined with INTACS provide real hope for patients with progressive Keratoconus and Keratoectasia. We expect this book shall provide the complete information on C3-R procedures to refractive surgeons who are interested to master this technique for the benefits of patients. Editors
Contents 1. Corneal Collagen Cross-linking (C3-R)—A Promising Technique. ........................................................ 1 Ashok Garg (India) 2. Corneal Biomechanical Properties ........................................................................................................ 5 Jorge L Alio, Mohamed H Shabayek (Spain) 3. Assessment and Risk Factors for Corneal Ectasia following Laser in Situ Keratomileusis and its Assessment ......................................................................................................... 9 Yan Wang, Kanxing Zhao, Liquing Liu, Jie Hou (China) 4. Avoiding Keratoconus in Patients undergoing Refractive Surgery ...................................................... 15 Michael O’ Keefe, Caitroina Kirwan (Ireland) 5. Clinical Significance of Collagen Corneal Cross-linking in PostLASIK Corneal Ectasia ..................... 21 Post-LASIK Nurullah Cagil, Bahri Aydin, Mesut Erdurmus (Turkey) 6. Biophysical Aspects of Collagen, Corneal Cross-linking Covering Details about UV-A and Riboflavin and their Mechanism of Action on the Cornea .................................................................. 25 MS Sridhar(India), Tarak Pujara (Australia) 7. The Importance of Epithelial Debridement for Riboflavin Absorption Prior to Riboflavin/Ultraviolet-A (UV-A) Corneal Collagen Cross-linkage Therapy : A Laboratory Study Using Spectrophotometry in Porcine Corneas .................................................... 29 David PS O’ Brart, Konstantinos Samaras, James Doutch, Sally Hayes, John Marshall, Keith M Meek (UK) 8. Indications and Contraindications: Traditional Techniques Vs Transepithelial Technique ............... 38 Roberto Pinelli, Antonio Leccisotti, Tarek Elbeltagi (Italy) 9. Considerations on Endothelial Safety in UV-A—Cross-linking Treatment .......................................... 44 Carina Koppen, Laure Gobin, Marie Jose Tassignon (Belgium) 10. Corneal Collagen Cross-linking with Riboflavin and Ultraviolet-A Light : Step by Step Technique ....................................................................................................................... 51 Belquiz A Nassaralla, Joao J Nassaralla (Brazil) 11. Advances in CorneoplastiqueTM: Art of Laser Vision Surgery .............................................................. 56 Arun C Gulani, Lee T Nordan (USA) 12. Applications of Collagen Corneal Cross-linking .................................................................................. 64 D Ramamurthy, Chitra Ramamurthy (India) 13. Cross-linking Plus Topography guided PRK for PostLASIK Ectasia Management .............................. 69 Post-LASIK A John Kanellopoulos (Greece) 14. INTACS and Corneal Collagen Cross-linking with Riboflavin and Ultraviolet-A as a Combined Treatment for Irregular Astigmatism .................................................... 81 Nikos Tsiklis, GD Kymionis, E Coskunseven, CS Siganos, Ioannis. G Pallikaris (Greece) 15. Transepithelial Cross-linking for the Treatment of Keratoconus : Concepts ....................................... 87 Roberto Pinelli (Italy) 16. Corneal Collagen Cross-linking in Keratoconus .................................................................................. 92 C Banu Cosar, Efekan Coskunseven (Turkey)
MASTERING CORNEAL COLLAGEN CROSS-LINKING TECHNIQUES
17. Corneal Collagen Cross-linking with Riboflavin (C3-R) Combined with Intrastromal Ring Segment Implantation and Overnight Contact Lens Molding in Keratoconus ...................................................................................................................... 98 Carlo F Lovisolo, Antonio Calossi (Italy) 18. Transepithelial Cross-linking Treatment in Eyes with INTACS .......................................................... 110 Aylin Ertan (Turkey) 19. Re-shaping Keratoconus : Laser PRK followed by Corneal Cross-linking .......................................... 120 Arun C Gulani, Brian Boxer Wachler (USA) 20. Cross-linking in Keratoconus : Advantages and Disadvantages ......................................................... 132 C Banu Cosar (Turkey) 21. Corneoplastics using Corneal Collagen Cross-linking and Intracorneal Rings of Keratoconus and Lasik Ectasia ........................................................................................................... 134 Francisco Sanchez Leon (Mexico) 22. Collagen Corneal Cross-linking Different Techniques ....................................................................... 140 Francisco Sanchez Leon (Mexico) 23. Posterior Corneal Changes in Refractive Surgery .............................................................................. 147 Amar Agarwal, Soosan Jacob, Sunita Agarwal, Athiya Agarwal, Nilesh Kanjiani (India) 24. Complications with the Use of Collagen Cross-linking ..................................................................... 156 A John Kanellopoulos (Greece)
Index ..................................................................................................................................................... 159
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CORNEAL COLLAGEN CROSS-LINKING (C3-R)–A PROMISING TECHNIQUE
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MASTERING CORNEAL COLLAGEN CROSS-LINKING TECHNIQUES
INTRODUCTION In last one decade Corneal Refractive Surgery has advanced rapidly with excellent visual results worldwide. Refractive surgeons have come across the problem of Post Refractive Keratectasia or Corneal ectasia. Due to effect of Excimer Laser photoablation on the corneal biomechanical properties a significant decrease in the bio mechanical assets was found after surgery. This implies that due to creation of flap and subsequent corneal thinning by ablation weakens the cornea and decreases its elastic properties. This leads later to corneal ectasia. This is indicator for the clinical significance of evaluating corneal biomechanical properties specifically the corneal hysteresis and resistance factor in screening refractive surgery patients. Similarly in Keratoconus (a progressive non inflammatory cone like Ectasia) the corneal hysteresis (CH) and corneal resistance factor (CRF) are significantly lower than in the normal eyes and post Lasik surgery corneas Low values of CH means that the cornea is less capable of absorbing the energy of the air pulse whereas low values of CRF indicates that corneal rigidity is lower than normal. The corneal biomechanical properties are primarily determined by the collagen fibres and the degree of interfibrillar linkage. Corneal Ectatic conditions whether inflammatory or non inflammatory have weak interfibrillar linkage strength. WHAT IS CROSS-LINKING?
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Cross-linking of human Collagen is a physiologic process. Corneal Collagen Cross-linking also known as C3-R/CCL/CxL treatment is a new approach to increase the mechanical and chemical stability of corneal tissue. The primary aim of this treatment is to create additional chemical bonds inside the corneal stroma by means of a highly localized photopolymerization while minimizing exposure to the surrounding structure of the eye. This procedure was first developed by Prof. Theo Seiler, Prof. Wollensak and Prof. Eberhard Spoerl in 1998 at the University of Dresdan, Germany. They did this procedure in cases of progressive Keratoconus and Post Refractive Corneal Ectasia. Followed this other studies undertaken by Dr A Caporossi, Dr Roberto Pinelli and their colleagues (Italy) and Dr Brian Boxer in USA.
There are several different techniques of crosslinking. The most promising technique in cornea is use of UV light and Riboflavin (Vitamin B2 solution) for inducing cross-linking to increase biomedical rigidity of the cornea. This slows down or even stops the progressive thinning of the cornea. In this Photopolymerisation is performed by means of a nontoxic and soluble photo mediator (Riboflavin) and a wavelength which was absorbed strongly enough to protect deeply layers of the eye. (Riboflavin - UVA technique). PHYSIOLOGY OF COLLAGEN CORNEAL CROSS-LINKING In this procedure custom made Riboflavin eye drops are applied to the cornea which is then activated by ultraviolet light. Using UVA at 370 nm, the photosenstizer Riboflavin is excited into its triplet state generating reactive oxygen species (ROS) which is mainly singlet oxygen and to a much less degree superoxide anion radicals. The ROS can react further with various molecules including chemical covalent bonds bridging amino groups collagen fibrils / type II photochemical reaction (Fig. 1.1 and 1.2). The wavelength of 370 mm of UVA is chosen because of an absorption peak of Riboflavin at this wavelength Biomechanical studies have shown an increase in the corneal rigidity of 328.9% in human cornea after crosslinking (Fig. 1.3). The increase on biomechanical rigidity after C3-R is probably caused by an increase
Figure 1.1: Bonding tissues and cross-linking
CORNEAL COLLAGEN CROSS-LINKING (C3-R)–A PROMISING TECHNIQUE
PARAMETERS FOR C3-R TREATMENT • • • •
Disorder should be progressive in nature Thinnest corneal pachymetry higher than 400 um No central corneal scarring Maximum corneal curvature should not exceed 60 D.
PREOPERATIVE WORK UP FOR C3-R TREATMENT
Figure 1.2: Strengthening of corneal fibres by C3-R Treatment
Figure 1.3: UV-XTM Illumination system
in the collagen fiber diameter due to interfibrillar and Intrafibrillar covalent bonds by photosensitized oxidation cross-linking. The cross-linking results in more compact stronger corneas that are more resistant to biomechanical deformation or ectasia.
• Visual acuity assessment (UCVA, BCVA, Contrast senstivitiy) • Intra ocular pressure recording • Detailed Slit Lamp Examination specially for Vogts Striae, Fleischer’s ring and corneal scarring • Slit lamp photographs of corneal changes • Pentacam evaluation for central corneal thickness and thinnest pachymetry • Corneal Topography • OCT Examination. STEPS OF C3-R TECHNIQUE (FIG. 1.4) The procedure takes place ambulatory and takes about one hour. • First eye is anesthelized with Topical proparacaine 0.5 eye drops. Then Manual debridement of corneal epithelium. (Thin surface layer) is abrased in the
INDICATIONS FOR C3-R TREATMENT • Progressive keratoconus • Iatrogenic post refractive keratectasia (Post Lasik Ectasia) • Pellucid marginal degeneration. EXCLUSION CRITERIA • Corneal thinkness less than 400 um at thinnest position • Keratometric readings above 60 Diopter • Active ocular disease • Herpes Keratitis • Diabetes • Pregnancy • Previous ocular surgery other than Laser refractive surgery • Immunocompromised Patients • Patients with known sensitivity.
Figure 1.4: Corneal collagen cross-linking (controlled UVA radiation is applied to corneal stroma to stiffen the cornea
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MASTERING CORNEAL COLLAGEN CROSS-LINKING TECHNIQUES
central 7 mm of cornea in order to allow penetration of stroma. Riboflavin solution containing 0.1% Riboflavin, 20% Dextran T 500 in isotonic sodium chloride solution (ph 7.0) is applied every 3 minute for the first 30 minutes. This is followed by irradiation of cornea with 365 nm UVA using UV-XTM for 30 minutes. Riboflavin drops are then continued for another 30 minutes at the interval of every 5 minutes as the eye is exposed to a UVA light positioned above the cornea to deliver predetermined dose of UVA light. The distance between the UV delivery system and cornea should be 5 cm (50 mm) so as to deliver a dose of 3 mw/cm2 (Total of 5.4 J/cm2 in 30 mts). As the UVA light interacts with the Riboflavin chemical bonds (cross links) form between the Corneal Collagen molecules and make the Cornea stiffer. As a result the corneal collagen tissue is stronger and can more uniformly retains its natured curved shape rather than bow forward into the cone like shape that is hallmark of Keratoconus and corneal ectasia. At the end of treatment the cornea is flushed with BSS and a bandage contact lens is placed over the cornea. POSTOPERATIVE FOLLOW-UP Patient is prescribed Topical antibiotics, nonsteroidal anti inflammatory and Lubricating eye drops in the postoperative period. Eye may be little painful after the treatment and it may take off after 48 hours. Till the closure of epithelial defect the patient is followed
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up everyday. Bandage contact lens is taken off when epithelial defect heals. Subsequent follow-up should be taken at 1 week, 4 weeks, 12 weeks, 24 weeks and 1 year. On each follow-up Refraction, Keratometry, Slit lamp and Pentacam Examination is mandatory. OCT is done at the one month visit and subsequent visits. FUTURE PROSPECTS Corneal Collagen Cross-linking with Riboflavin and UVA for the treatment of progressive keratoconus and post refractive keratectasia are relatively safe and effective treatment. The ability to permanently strengthen the inherently weakned cornea is a major advancement and achievement of this technique. C3-R treatment alone or combined with intacs implantation in Keratoconus are allowing improved vision and comfort to the patients. C3-R is a simple, safe and effective procedure in the management of progressive ectatic disorders of the cornea. C3-R treatment shall become a standard treatment in near future. A lot of clinical research works is going on for the further improvement and wider applications of this treatment, New Clinical research works have started for possible combining of C3-R treatment with topography guided advanced surface ablation, intacs, orthokeratology and conductive keratoplasty. Possible C3-R treatment applications in treating corneal edema, bullous Keratopathy are also being investigated with lot of hope and promise.
CORNEAL BIOMECHANICAL PROPERTIES
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MASTERING CORNEAL COLLAGEN CROSS-LINKING TECHNIQUES
INTRODUCTION Corneal refractive surgery advanced rapidly during the past two decades, due to the encouraging, predictable and stable results of corneal remodelling by photoablation using excimer lasers. A result of such advancement a new frontier of diagnostic equipments and tools became accessible to ophthalmic surgeon such as; corneal topographer, wavefront sensors, very high frequency optical coherence tomography (VHF OCT), and confocal microscopy. This technology aided in analysing not only the optical but also the structural properties of the cornea. Recently the biomechanical properties of the cornea have been introduced as a new parameter in corneal refractive surgery, parameter that evaluates corneal characteristics from the biomechanical perspective; such as the corneal resistance factor, and corneal hysteresis. These parameters can be helpful for diagnosing certain corneal pathologies especially corneal ectatic diseases, were the biomechanical corneal characteristics are different from normal corneas. TERMINOLOGY Corneal Hysteresis The term “Hysteresis” is derived from an ancient Greek word which means “coming behind”. It was first introduced into scientific vocabulary in 1890 by the Scottish physicist, Sir James Alfred Ewing. Hysteresis is a property of physical systems that do not instantly follow the forces applied to them, but react slowly, or do not return completely and instantaneously to their original state.
Figure 2.1: Corneal resistance factor which is the amount of pressure needed to flatten the anterior corneal surface
applanation. Pallikaris et al 6 measured the ocular rigidity in living human eyes increasing the intraocular pressure by injecting a saline solution into the anterior chamber; while, Grabner et al7 used the dynamic corneal imaging method by central indentation to assess the individual elastic properties of eyes. Where as, Luce8 determined the biomechanical properties of the cornea using the Reichert ocular response analyzer (ORA), based on a dynamic bidirectional applanation process. OCULAR RESPONSE ANALYZER ORA The Ocular Response Analyzer, (ORA Reichert Ophthalmic Instruments, Depew NY) (Fig. 2.2) measures the corneal biomechanical properties by using a dynamic bidirectional air applanation process (non invasive method). It is composed of an air pump which applies a force on the anterior corneal surface (specific point) through a pressure transducer while an infrared light emitter is focused on the same point
Corneal Resistance Factor
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The static resistance component of the cornea which indicates the overall corneal resistance or simply the pressures “force” needed to applanate “deform” the cornea, this deformation is proportional to applied force and is expressed in mmHg (Fig. 2.1). However, measuring the biomechanical properties in vivo is a challenging task, and has been approached by several methods,1-8 whether invasive as anterior Chamber saline injection and measuring ocular rigidity or non invasive as dynamic corneal imaging with central indentation and dynamic bidirectional air
Figure 2.2: Ocular response analyzer (ORA)
CORNEAL BIOMECHANICAL PROPERTIES
and the reflection of this infrared beam is monitored by a light intensity detector. This system records two applanation pressure measurements; one while the cornea is moving inward, and the other as the cornea returns. Due to its biomechanical properties, the cornea resists the dynamic air puff causing delays in the inward and outward applanation events, resulting in two different pressure values (Figs 2.3 and 2.4).
Figure 2.3: The infrared light intensity is maximally detected when the anterior corneal surface is applanated
Figure 2.4: ORA graph showing the difference in pressure between the In signal peek and the out signal peek which evaluates the viscoelastic property of the cornea (corneal hysteresis)
properties in normal non complaining individual and keratoconic eyes using the ocular response analyzer ORA. The study included a total of 250 eyes divided into three groups: 164 normal eyes, 21 keratoconic eyes and 65 eyes that had undergone a corneal refractive surgery procedure to evaluate the effect of LASIK on the corneal biomechanical properties. The author’s inclusion criteria were: for normal and post-refractive surgery groups, patients with any irregular patterns of corneal topography or history of ocular disease were not included; and for keratoconus group, only eyes with keratoconus with at least one clinical sign that was confirmed by corneal topography. Results of this study, demonstrated that in the normal group, a decrease in the corneal biomechanical properties was observed in elder patients. This implies a loss of the elastic properties of the cornea with age, which coincides with the increase of ocular rigidity found by Pallikaris et al.6 As for the post LASIK surgery group, or the effect of excimer laser photoablation on the corneal biomechanical properties, a significant decrease in the biomechanical properties was found after the surgery. This result coincides with other studies 1,7,10 and implies that the creation of the flap and the corneal thinning by ablation weaken the cornea and decreases its elastic properties. This could lead later to corneal ectasia after refractive surgery11,12. This can be an indicator for the importance of evaluating corneal biomechanical properties precisely the corneal hysteresis and resistance factor in screening refractive surgery candidates. In keratoconic eyes, the corneal hysteresis (CH) and the corneal resistance factor (CRF) were significantly lower than in normal eyes and post LASIK surgery corneas. Low values of CH imply that the cornea is less capable of absorbing the energy of the air pulse, where as, low values of CRF, indicates the cornea rigidity is lower than normal. REFERENCES
CORNEAL BIOMECHANICAL PROPERTIES IN NORMAL, KERATOCONIC EYES AND POSTLASIK EYES In Prospective, conventional, comparative, interventional study,9 that reported the corneal biomechanical
1. Jaycock PD, Lobo L, Ibrahim J, et al. Interferometric technique to measure biomechanical changes in the cornea induced by refractive surgery. J Cataract Refract Surg 2005;31:175-84. 2. Mamelok AE, Posner A. Measurements of corneal elasticity in relation to disease, using the Wiegersma elastometer. Am J Ophthalmol 1955;39:817-21.
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MASTERING CORNEAL COLLAGEN CROSS-LINKING TECHNIQUES 3. Vaughan JM, Randall JT. Brillouin scattering, density and elastic properties of the lens and cornea of the eye. Nature 1980;284:489-91. 4. Kasprzak H, Forster W, von BG. Measurement of elastic modulus of the bovine cornea by means of holographic interferometry. Part I. Method and experiment. Optom Vis Sci 1993;70:535-44. 5. Wang H, Prendiville PL, McDonnell PJ, Chang WV. An ultrasonic technique for the measurement of the elastic moduli of human cornea. J Biomech 1996;29:1633-36. 6. Pallikaris IG, Kymionis GD, Ginis HS, et al. Ocular rigidity in living human eyes. Invest Ophthalmol Vis Sci 2005;46:409-14. 7. Grabner G, Eilmsteiner R, Steindl C, et al. Dynamic corneal imaging. J Cataract Refract Surg 2005;31:163-74.
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8. Luce DA. Determining in vivo biomechanical properties of the cornea with an ocular response analyzer. J Cataract Refract Surg 2005;31:156-62. 9. Ortiz D, Piñero D, Shabayek MH, et al. Corneal biomechanical properties in normal, post-laser in situ keratomileusis, and keratoconic eyes. J Cataract Refract Surg 2007;33:1371–75. 10. Kamiya K, Miyata K, Tokunaga T, et al. Structural analysis of the cornea using scanning-slit corneal topography in eyes undergoing excimer laser refractive surgery. Cornea 2004;23:S59-S64. 11. Dupps WJ, Jr. Biomechanical modeling of corneal ectasia. J Refract Surg 2005;21:186-90. 12. Guirao A. Theoretical elastic response of the cornea to refractive surgery: Risk factors for keratectasia. J Refract Surg 2005;21:176-85.
ASSESSMENT AND RISK FACTORS FOR CORNEAL ECTASIA FOLLOWING LASER IN SITU KERATOMILEUSIS AND ITS ASSESSMENT
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MASTERING CORNEAL COLLAGEN CROSS-LINKING TECHNIQUES
INTRODUCTION Although corneal ectasia (keratectasia) after laser in situ keratomileusis (LASIK) is reported uncommon, which is estimated to be 0.1%1to 0.66%,2 it is still an enigmatic and potentially devastating complication following laser in situ keratomileusis (LASIK). 3 Abnormal collagen in addition to thin corneas may lead to progressive inferior corneal steepening, increase in myopia, irregular astigmatism, and loss of best corrected visual acuity. Unfortunately, the etiology of corneal ectasia is not fully known. When contact lenses are no longer effective in preventing ectasia progression, there are some surgical management available, such as lamellar keratoplasty and intrastromal corneal ring segments. Various medical therapies did not differ significantly in decreasing the progression of ectasia. Hence, penetrating keratoplasty is another commonly performed surgical procedure for ectatic corneas. However, it is associated with many complications.4 Recently, Crosslinking seems to be one of the more effective means in the management of mild to severe cases. It is essential that before the clinical treatment, the surgeon must correctly identify, assess, and understand the risk factors of corneal ectasia following laser in situ keratomileusis. Precise assessment is crucial in the management of corneal ectasia after laser in situ keratomileusis. ASSESSMENT
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Accurate detection of corneal ectasia is very important. A precise diagnosis of corneal ectasia may explain a patient’s symptoms postoperatively. A regression of refractive power may alter the postoperative management and treatment. Corneal ectasia is a direct contraindication for any enhancement surgeries and may detriment the cornea even further. There may be no clinical symptoms in early stages. Although in some advanced cases, astigmatism may appear which may be detected by a refractive examination. Some patients may report acute onset of blurred vision. In the postoperative period, patients may frequently notice dramatic fluctuations in their vision3 and experience regression of their refractive surgical outcome. Like early keratoconus, corneal ectasia is difficult to detect using clinical tests. A useful tool for early
detection of keratoconus or keratectasia is pachymetry, which shows the relationship of the apical, central and thinnest part of the cornea. Corneal topography provides useful and accurate information with regards to the position of the ectasia. It also allows to detect the progression, and for early cases. Corneal topography is a diagnostic tool for corneal ectasia. CORNEAL TOPOGRAPHY Corneal ectasia has a similar clinical entity and topography with keratoconus and forme fruste keratoconus. Therefore, after LASIK, corneal ectasia has been reported in patients with keratoconus,5 and forme fruste keratoconus (FFKC). 6,7 Also, the progression of ectasia can be most effectively evaluated via analysis of a series of corneal topographies. Most diagnoses and assessments for keratoconus are based on anterior corneal curvature and elevation data derived from Placido-based corneal topography. But some mild degrees of post-LASIK keratectasia may be better detected at the level of the posterior corneal surface. The posterior corneal shape is mainly used for early recognition of this pathologic condition. Thus, it is prudent to be able to accurately evaluate any changes in the posterior cornea after LASIK.8,9 ORBSCAN The Orbscan corneal topography system, which uses a placido device, can obtain the corneal curvature and has been used in refractive surgery for many years. It takes 40 slit sections of the cornea during two scans. The anterior and posterior corneal height profiles are reconstructed from these sections using threedimensional ray tracing with 9600 points. The Orbscan has been proven to provide useful and accurate information regarding the morphology and topographic changes related to keratoconus. 10 Posterior topographic changes after LASIK are obviously, which has been well investigated.11,12 The risk of ectasia, which is highly suspected as corneal ectasia or keratoconus, is suggested as follows:13 • A variance of more than 1.00D in astigmatism between the eyes. • Keratometric or corneal steepness on the mean power map.
ASSESSMENT AND RISK FACTORS FOR CORNEAL ECTASIA FOLLOWING LASER IN SITU KERATOMILEUSIS AND ITS ASSESSMENT
Figure 3.1: This Orbscan quad map shows a posterior float of approximately 0.065 mm, a strong red flag for forme fruste keratoconus
• The posterior surface float is greater than 0.05 mm (The difference between the highest and lowest spots). Near the center of the posterior elevation map appears a dark reddish color. Wang et al12 have shown that the posterior elevation increases after LASIK. The increase is correlated with residual corneal bed thickness (Figure 3.1). • Irregularity at 3 mm to 5 mm of the central cornea. • The thinnest area of corneal thickness is more than 20 μm thinner than the thickness of the central cornea. • The number of abnormal maps using the normal band scale. One abnormal map does not indicate forme fruste keratoconus or corneal ectasia. It is necessary to check after a few months. Two abnormal maps may indicate early keratoconus or corneal ectasia. Recently however, some studies showed that Orbscan fails to correctly identify the posterior corneal
surface and can give incorrect diagnosis of post LASIK ectasia. 14,15 We believe that corneal topography is an important complementary tool in the diagnosis of post LASIK ectasia. To fully evaluate these measurements, the clinician must look at the indices as a whole rather than at each individual values separately. The three components that are displayed (The elevation, curvature, and pachymetry) are designed to help in the analysis by comparing each one to another. PENTACAM Previous studies have reported that the Pentacam has a high degree of repeatability for the measurement of the posterior corneal curvature.16 The Pentacam is a rotating Scheimpflug camera with a higher depth of focus. It assesses the anterior chamber of the eye, the topographic corneal thickness,
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MASTERING CORNEAL COLLAGEN CROSS-LINKING TECHNIQUES
Figure 3.2: This Pentacam quad map shows corneal ectasia after LASIK. Each abnormal part of on the 3 maps (A, B, C) is at the same point
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corneal curvature, anterior chamber angle, and volume and height from up to 25,000 true elevation points. The system takes 50 pictures in a maximum of two seconds while rotating around a central point with a moveable eye. Scheimpflug imaging differs from the Placido-based system in that it allows for the measurement of both the anterior and posterior corneal surfaces and the computation of a complete pachymetric map. The method of depicting elevation data and the subtracted reference shapes commonly uses a best-fit-sphere (BFS) and identifies a 4 mm optical zone centered on the thinnest portion of the cornea (exclusion zone). BFS is defined by utilizing all the valid data from within the 9 mm central cornea with the exception of the exclusion zone.17 The proposed screening parameters are:18,19 • Anterior elevation differences < +12μm are normal. • Anterior elevation differences > +15μm are indicative of keratoconus.
• Anterior elevation differences + 12 ~ +15μm are suspicious. • Similar numbers (about 5μm higher) apply to posterior elevation. The confirmation can be made for forme fruste keratoconus when the hot spot on the tangential map, relative pachymetry map and back elevation map, using the toric ellipsoid, are all at the same point. By Holliday’s experience,18 exceed -3.0% are significant for relative pachymetry, also for elevations of more than 15μm above the toric ellipsoid on the back elevation map (Fig. 3.2). Other indices of the ectasia are the position of the thinnest point. At the beginning of the ectasia, the thinnest point is at central position. The thinnest point can transform from central position toward an eccentric position. Several other parameters could also be extracted from corneal tomography examination. These include a faster and a more abrupt increase of the corneal
ASSESSMENT AND RISK FACTORS FOR CORNEAL ECTASIA FOLLOWING LASER IN SITU KERATOMILEUSIS AND ITS ASSESSMENT
Figure 3.3: Pentacam map shows a steep and abrupt increase of the corneal thickness spatial profile and percentage of increase in thickness. The patient was suspected as keratoconus level 1 after LASIK
thickness spatial profile and the percentage of increase of thickness relative to normal corneas.17 Figure 3.3 shows a particular case of a patient with post-LASIK ectasia. All of these can be used in a series of follow-up exams of the posterior corneal curvature in post-LASIK eyes. This will help to identify and predict keratectasia following LASIK. However, whether these measurements are more sensitive and specific than the classic Placido-based topography needs further investigation. RISK FACTORS After LASIK, there are many risk factors that may increase the probability of corneal ectasia. None of these factors are absolute predictors of corneal ectasia, but are correlated with its occurrence. Also, LASIK is not necessarily a causative or contributing factor to corneal ectasia seen postoperatively.20 Possible risk factors analyzed by Randleman et al3 include high
myopia, and thin preoperative corneal thickness. Some possible risk factors include: • Forme fruste keratoconus (FFKC): Some ectasia after LASIK has been reported in patients with forme fruste keratoconus.6,7 One study showed 88% of affected eyes met the FFKC criteria. 3 Therefore, screening and identifying patients with FFKC preoperatively is necessary. • Keratoconus in one eye or a family history of keratoconus. Eyes with keratoconus are known to produce unpredictable refractive results and scarring after LASIK.21,22 • Residual stromal bed thickness after laser ablation was less than 250μm. Many studies have showed that the residual stromal bed thickness of more than 250μm would possibly be safe. 1 • High myopia: Patients with high myopia require more tissue ablation during LASIK. This leaves them with a lower residual stromal bed thickness than patients with low myopia, increasing the risk for developing ectasia.
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MASTERING CORNEAL COLLAGEN CROSS-LINKING TECHNIQUES
• Patients that have underwent enhancement after LASIK surgery. It has been proposed that multiple enhancements were correlated with ectasia .23 Enhancement after LASIK surgery may make residual stromal bed thinner. • Asymmetrical cornea steepening. • Asymmetrical astigmatism. • High keratometric measurements: A higher risk of keratoectasia is suggested by K readings of 46D or more at the steepest point.13 • Age: With aging, the structure and shape of the cornea changes and may attribute to the development of ectasia. • Patients who have genetic corneal dystrophies.24 Clinically, some of the patients who developed corneal ectasia may have multiple risk factors. As technology continually advancing, the knowledge for assessing corneal ectasia following laser in situ keratomileusis continues to grow and criterion may be changed. Further studies are needed to provide more accurate and predictable treatment outcomes. ACKNOWLEDGMENTS We thank John Barkley OD, Thanh Nguyen OD and Tran Nguyen OD (Nova Southeastern University, FL, USA) for providing generous assistance and attentive correction of the language. REFERENCES
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1. Kim TH, Lee D, Lee HI. The safety of 250μm residual stromal bed in preventing keratectasia. J Korean Med Sci 2007;22:142-45. 2. Pallikaris IG, Kymionis GD, Astyrakakis NI. Corneal ectasia induced by laser in situ keratomileusis. J Cataract Refract Surg 2001;27:1796-1802. 3. Randleman JB, Russell B, Ward MA, et al. Risk factors and prognosis for corneal ectasia after LASIK. Ophthalmology 2003;110(2):267-75. 4. Tan BU, Purcell TL, Torres LF, et al. New surgical approaches to the management of keratoconus and post-LASIK ectasia. Trans Am Ophthalmol Soc 2006;104:212-20. 5. Clair-Florent M, Schmitt-Bernard C, Lesage C, Arnaud B. Keratectasia induced by laser in situ keratomileusis in keratoconus. J Refract Surg 2000;16:368-70. 6. Argento C, Cosentino MJ, Tytiun A, et al. Corneal ectasia after laser in situ keratomileusis. J Cataract Refract Surg 2001;27:1440–48. 7. Lafond G, Bazin R, Lajoie C. Bilateral severe keratoconus after laser in situ keratomileusis in a patient with forme fruste keratoconus. J Cataract Refract Surg 2001;27:1115– 18.
8. Chen D, Lam AKC. Intrasession and intersession repeatability of the Pentacam system on posterior corneal assessment in the normal human eye. J Cataract Refract Surg 2007;33:448–54. 9. Ciolino JB, Belin MW. Changes in the posterior cornea after laser in situ keratomileusis and photo refractive keratectomy. J Cataract Refract Surg 2006;32:1426–31. 10. Kim H, Joo CK. Measure of keratoconus progression using Orbscan II. J Refract Surg 2008;24:600-605. 11. Nilforoushan MR, Speaker M, Marmor M, et al. Comparative evaluation of refractive surgery candidates with placido topography, Orbscan II, Pentacam, and wavefront analysis. Cataract Refract Surg 2008;34:623– 31. 12. Wang Z, Chen J, Yang B. Posterior corneal surface topographic changes after laser in situ keratomileusis are related to residual corneal bed thickness. Ophthalmology 1999;106:406-09. 13. Karpecki PM. Bausch and Lomb Orbscan anterior segment analysis system. Wang M In: (Ed) Corneal topography in the wavefront era. Thoroare, USA:SLACK;2006:192-206. 14. Prisant O, Calderon N, Chastang P, et al. Reliability of pachymetric measurements using Orbscan after excimer refractive surgery. Ophthalmology 2003;110:511–15. 15. Matsuda J, Hieda O , Kinoshita S. Comparison of central corneal thickness measurements by Orbscan II and Pentacam after corneal refractive surgery. Jpn J Ophthalmol 2008;52:245–49. 16. Jain R, Dilraj G, Grewal SPS . Repeatability of corneal parameters with Pentacam after laser in situ keratomileusis. Indian J Ophthalmol 2007;55(5):341-47. 17. Belin MW, Khachikian SS, Arósio R. Keratoconus / Ectasia detection with the Oculus Pentacam: Belin/Ambrósio enhanced ectasia display. Highlights of ophthalmology 2007;55(6):5-12. 18. Maus M, Kröber S, Swardz T. Pentacam. In: Wang M. Corneal topography in the wavefront era. Thoroare, USA:SLACK;2006:281-93. 19. Holladay JT. Detecting forme fruste keratoconus with the Pentacam. Cataract and Refractive surgery today 2008;2:11-12. 20. Binder PS, Lindstrom RL, Stulting RD, et al. Keratoconus and corneal ectasia after LASIK. J Refract Surg 2005;21(6):749-52. 21. Buzard KA, Tuengler A, Febbraro JL. Treatment of mild to moderate keratoconus with laser in situ keratomileusis. J Cataract Refract Surg 1999;25:1600–09. 22. Ellis W. Radial keratotomy in a patient with keratoconus. J Cataract Refract Surg 1992;18:406–09. 23. Holland SP, Srivannaboon S, Reinstein DZ. Avoiding serious corneal complications of laser assisted in situ keratomileusis and photorefractive keratectomy. Ophthalmology 2000;107:640–52. 24. Rabinowitz YS. The genetics of keratoconus. Ophthalmol Clin N Am 2003;16:607-20.
AVOIDING KERATOCONUS IN PATIENTS UNDERGOING REFRACTIVE SURGERY
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INTRODUCTION
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Keratoconus remains a common indication for corneal transplantation surgery. 1 Ectasia usually develops during adolescence and progresses slowly thereafter, with a minority of affected patients requiring corneal transplantation.2,3 The popularity of keratorefractive surgery and technological advances have contributed to an increased awareness of sub-clinical or forme fruste keratoconus. The fear of inducing, or of worsening pre-existing corneal ectasia by performing keratorefractive surgery has hastened our search for better diagnostic tools which detect subtle corneal abnormalities indicative of early ectasia. However, the diagnosis of forme fruste keratoconus remains particular difficulty. Corneal topography has become mandatory for all patients contemplating refractive surgery but in spite of improved software programmes it has not yet been perfected. A number of guidelines exist to help detect topographical evidence of ectasia but these alone are often insufficient to allow a definitive diagnosis to be made. Aberrometry records the higher order aberrations of the eye and has been found to have a role in the detection of corneal ectasia. 4-7 More specifically vertical coma is increased in both early (Figures 4.1A and B) and advanced (Figures 4.2A and B) ectasia.8,9 However, increased vertical coma in the presence of normal topography and low clinical suspicion is not diagnostic of ectasia and this finding should only be considered in addition to other factors and not as an isolated finding. More recently, new technology has been developed which records corneal hysteresis, a reflection of the corneal viscoelastic properties and is thought to provide an indication of its biomechanical integrity.10 The Reichert Ocular Response Analyzer (ORA; Reichert Ophthalmic Instruments, Buffalo NY, USA) can be used clinically to measure corneal hysteresis (CH) in addition to the corneal resistance factor (CRF) which reflects the overall resistance of the cornea. Kirwan et al examined both CH and CRF in normal eyes and eyes with forme fruste and advanced keratoconus.11 Both parameters were found to be significantly lower in eyes with advanced keratoconus compared with normal and forme fruste keratoconus (FFKC) eyes, while no difference was found between the latter two groups
when pachymetry matched. Due to significant overlap in both CH and CRF across all 3 groups, they concluded that this instrument was not useful as a single test in the detection of early ectasia. Laser in situ keratomileusis (LASIK) has been performed on more than 17 million people worldwide, but a dramatic increase in the reported incidence of keratoconus has not occurred.12 Binder reported 85 eyes with post LASIK ectasia.13 Faraj et al reported that 78% of patients with post LASIK have pre-existing forme fruste keratoconus, a preoperative central corneal thickness
