Atlas of Glaucoma Surgery 8180616517

Table of contents :
Prelims
Chapter-01_Reducing Intraocular Pressure Is Surgery Better than Drugs
Chapter-02_Trabeculectomy
Chapter-03_Trabeculectomy with a Scleral Tunnel Technique Combined with Mitomycin-C
Chapter-04_Cyclodestruction in Glaucoma
Chapter-05_Resurrecting the Failing Filtering Bleb
Chapter-06_The Ahmed Valve
Chapter-07_The Use of Molteno Implants to Treat Complex Cases of Glaucoma
Chapter-08_Nonpenetrating Surgery
Chapter-09_Nonpenetrating Deep Sclerectomy (Npds) Anatomic Landmarks
Chapter-10_Shortening the Learning Curve of Deep Sclerectomy
Chapter-11_Postoperative Management of Nonpenetrating Glaucoma Surgery
Chapter-12_Trabeculotomy Ab Externo
Chapter-13_Selective Laser Trabeculoplasty
Chapter-14_Combined Cataract Glaucoma Surgery
Chapter-15_Management of Angle-closure
Chapter-16_Modulation of Wound Healing
Chapter-17_Glaucomatous Complications of Refractive Surgery
Index_2

Citation preview

Atlas of Glaucoma Surgery

Atlas of Glaucoma Surgery Editors

Tarek Shaarawy MD Consultant and Head, Glaucoma Sector Department of Ophthalmology Geneva University Hospitals University of Geneva Geneva, Switzerland

André Mermoud MD Professor and Head Glaucoma Unit Department of Ophthalmology Jules Gonin Eye Hospital University of Lausanne Lausanne, Switzerland Foreword

Peter G Watson

JAYPEE BROTHERS MEDICAL PUBLISHERS (P) LTD New Delhi

Published by Jitendar P Vij Jaypee Brothers Medical Publishers (P) Ltd EMCA House, 23/23B Ansari Road, Daryaganj New Delhi 110 002, India Phones: +91-11-23272143, +91-11-23272703, +91-11-23282021, +91-1123245672 Fax: +91-11-23276490, +91-11-23245683 e-mail: [email protected] Visit our website: www.jaypeebrothers.com Branches • 202 Batavia Chambers, 8 Kumara Krupa Road, Kumara Park East, Bangalore 560 001 Phones: +91-80-22285971, +91-80-22382956, +91-80-30614073 Tele Fax: +91-80-22281761 e-mail: [email protected] • 282 IIIrd Floor, Khaleel Shirazi Estate, Fountain Plaza, Pantheon Road, Chennai 600 008 Phones: +91-44-28262665, +91-44-28269897 Fax: +91-44-28262331 e-mail: [email protected] • 4-2-1067/1-3, Ist Floor, Balaji Building, Ramkote, Cross Road, Hyderabad 500 095 Phones: +91-40-55610020, +91-40-24758498 Fax: +91-40-24758499 e-mail: [email protected] • 1A Indian Mirror Street, Wellington Square Kolkata 700 013 Phones: +91-33-22456075 , +91-33-22451926 Fax: +91-33-22456075 e-mail: [email protected] • 106 Amit Industrial Estate, 61 Dr SS Rao Road, Near MGM Hospital Parel, Mumbai 400 012 Phones: +91-22-24124863, +91-22-24104532, +91-22-30926896 Fax: +91-22-24160828 e-mail: [email protected] • “Kamalpushpa” 38, Reshimbag, Opp. Mohota Science College, Umred Road Nagpur 440 009, Phone: +91-0712-3945220 e-mail: [email protected] Atlas of Glaucoma Surgery © 2006, Tarek Shaarawy, André Mermoud All rights reserved. No part of this publication and Photo CD 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 : 2006 ISBN 81-8061-651-7 Typeset at JPBMP typesetting unit Printed at Replika Press Pvt. Ltd.

To Mohamed Abd El-Samad Nada, Pierre Mermoud, Mounir Shaarawy, Alex Mermoud, and Hussein Shaarawy. (A grand father, two fathers, and two sons) Acknowledging that from the more distinguished gentlemen we have learned that real excellence and humility are not incompatible. We in turn will always strive to pass this on to the two young gentlemen.

Contributors

Ahmad K Khalil MD PhD Research Institute of Ophthalmology Cairo, Egypt Ahti Tarkkanen MD Professor Emeritus of Ophthalmology University of Helsinki Former Director, Helsinki University Eye Hospital Helsinki, Finland André Mermoud MD Professor, Department of Ophthalmology Jules Gonin Hospital University of Lausanne, Switzerland Anthony CB Molteno FRCS Professor, Section of Ophthalmology Department of Medical and Surgical Sciences University of Otago, Dunedin School of Medicine Dunedin, New Zealand Christian Prünte MD Professor University Eye Clinic, Basel, Switzerland Daniel Elies MD PhD Refractive Surgery Department Instituto Oftalmológico de Barcelona, Spain Dilani Siriwardena FRCOphth Glaucoma Fellow Moorfields Eye Hospital London, UK Doina Gherghel MD University Eye Clinic Basel, Switzerland

Francesca Cordeiro PhD MRCP FRCOphth Wellcome Trust Lecturer Glaucoma and Optic Nerve Head Research Group Institute of Ophthalmology (assoc. with Moorfields Eye Hospital), London, UK Frank Howes MBChB MMed FCS FRCS FRCOphth Consultant Ophthalmologist Clayton Eye Centre, Wakefield West Yorkshire, UK Gonzalo Munoz MD PhD FEBO Glaucoma and Refractive Surgery Department Instituto Oftalmológico de Alicante, Spain Harry Roux Ophthalmology Resident Department of Ophthalmology University of Geneva, Switzerland Hazem R El-Kholefy FRCS Maghrabi Eye Hospital Cairo, Egypt Ivan O Haefliger MD Professor University Eye Clinic, Basel, Switzerland Jeffrey M Liebmann MD Professor of Ophthalmology, Manhattan Eye, Ear and Throat Hospital, New York New York University Medical Center, New York Jorge Zarate MD Department of Pathology University of Buenos Aires, Argentina Jose I Belda-Sanchis MD PhD FEBO Glaucoma and Refractive Surgery Department Instituto Oftalmológico de Alicante, Spain

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Josef Flammer MD Professor and Head University Eye Clinic, Basel, Switzerland Juan Jose Perez-Santonja MD PhD FEBO Glaucoma and Refractive Surgery Department Instituto Oftalmológico de Alicante, Spain Juan Roberto Sampaolesi MD Department of Ophthalmology School of Medicine, University of Beuenos Aires Argentina Kaweh Mansouri MD Glaucoma Fellow University Eye Clinic Basel, Switzerland Madhu Nagar MS Ophth FRCS Ophth Consultant Ophthalmologist Clayton Eye Centre Wakefield, West Yorkshire, UK Oscar Albis-Donado MD Glaucoma Specialist from the Association Para Evitar la Ceguera en México Assistant Professor, Universidad Del Norte Chief, Glaucoma Service Unidad Láser del Atlántico, Barranquilla, Colombia Hospital Universidad del Norte, Barranquilla Colombia Päivi Puska MD Docent of Ophthalmology, University of Helsinki Head, Glaucoma Service Helsinki University Eye Hospital Helsinki, Finland Paul J Foster PhD FRCS (Ed) Clinical Senior Lecturer Department of Epidemiology Institute of Ophthalmology University College London and Honorary Consultant Moonfields Eye Hospital, London

Peng Tee Khaw

PhD FRCS FRCOphth FRCP FRCPath FIBiol FMedSci

Professor of Glaucoma and Ocular Healing Moorfields Eye Hospital and Institute of Ophthalmology, London Peter Shah BSc (Hons) MB ChB FRCS FRCOphth Consultant Ophthalmic Surgeon Birmingham and Midland Eye Hospital and Good Hope Hospital NHS Trust, Birmingham Robert Ritch MD Professor of Clinical Ophthalmology Chief, Glaucoma Service, Surgeon Director The New York Eye and Ear Infirmary, New York New York Medical College, Valhalla, New York Roberto Sampaolesi MD Professor Emeritus, Department of Ophthalmology School of Medicine, University of Buenos Aires Argentina Selim Orgül MD Professor University Eye Clinic, Basel, Switzerland Tarek Shaarawy MD Head, Glaucoma Sector University of Geneva Geneva, Switzerland Tero Kivelä MD Docent of Ophthalmology, University of Helsinki Director; Helsinki University Eye Hospital Helsinki, Finland Tui H Bevin MPH Section of Ophthalmology, Department of Medical and Surgical Sciences University of Otago, Dunedin School of Medicine Dunedin, New Zealand Wisam A Shihadeh MD Clinical Glaucoma Fellow Department of Ophthalmology The New York Eye and Ear Infirmary, New York

Foreword

‘Glaucoma does not constitute a disease entirely but embraces congeries of pathological conditions which have the common feature that their clinical manifestations are to a greater or lesser extent dominated by an increase in intraocular pressure’.1 The concept of angle closure dates back to 1876 when two investigators, Max Knies2 and Adolf Weber,3 working independently noted the obstruction of the angle of the anterior chamber. Priestly Smith4 used this information to develop the theory of peripheral angle closure and changed the emphasis from over-production of aqueous to a failure of outflow from the eye as the cause of the raised pressure. He also noted that the change in size of the lens with age contributed to acute glaucoma. It remained then, for Otto Barkan5 in the late 1903’s to further define the diseases of the angle and to reclassify the glaucomas into open and closed angles. It was then that Curran’s6 suggestion of the mechanism of angle closure through pupil block became accepted and formed the basis of modern approaches to treating acute angle closure which are almost universally successful. Von Graefe’s7 amaurosis with excavation of the disc without inflammation (what was subsequently called simple glaucoma) is far from simple. The cause and effect of primary open angle glaucoma have been the subject of circular arguments for several decades which are still not close to resolution. So far the only intervention known to reduce the chances of progression of this condition is the reduction of intraocular pressure. Almost every pharmacological mechanism known to be involved in the circulation of aqueous by either the conventional trabecular or uveo-scleral pathways has been manipulated to provide drugs to maintain a low intraocular pressure with minimal side effects. In this medical therapy has been largely successful but the pressure of advertising has, perhaps deliberately, obscured the value of early surgical intervention in chronic open angle glaucoma. There are some patients, particularly those who present with advanced disease and/or high initial intraocular pressures, who all agree require early surgery but many have developed advanced visual field loss through procrastination and reluctance to undertake the necessary surgery. One of the worst phrases ever coined was “maximum tolerated medical therapy” which implies that surgery is a course of last resort rather than a highly successful sight saving procedure performed early in the disease. Having to use these criteria certainly biased the results of the Advanced Glaucoma Intervention Study.8 Surgery had, and to an extent still has, a degree of morbidity which, to those used to the almost complication-free operation of cataract, is unacceptable. An eye left inadequately treated results in eventual blindness. This means that a certain degree of risk must be accepted. McKenzie9 rightly associated the high intraocular pressure with the march to blindness but thought that this pressure was caused by liquid vitreous and therefore advocated the broad iris knife be driven into the vitreous and rotated to release the fluid! It is not surprising to us now that this did not work for long and was associated with many problems. In 1857 Critchett,10 incorporated an iris wick into the wound so first establishing the ‘filtering cicatrix’, a term coined by de Wecker.11 This is still the principle of all successful modern surgical, and some 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11.

Duke Elder WS. Textbook of Ophthalmol, 3 Kimpton 1940;3280-85. Knies MV. Graefe’s Arch. Ophthalmol. 1876;22 (3) 163. Weber AV. Graefe’s Arch Ophthalmol. 1877;23 (1) 1. Priestly Smith T. Glaucoma, its causes, symptoms, pathology and treatment 1879. Barkan O. Glaucoma:- Classification, causes and surgical control. Amer J Ophthalmol 1099;21 1099. Curran. Trans Ophthalmol. Soc. 1931; 51:520 Von Graefe A. Von Graefe’s Arch. Ophthalmol. 1857;32: 456. The AGIS Investigators. The advanced glaucoma intervention study 4: comparison process V. Graefe’s Arch Clin Exp Ophthalmol 1998;3(2): 456. McKenzie W. A practical treatise on diseases of the eye. 703, 706 Longman Rees, Orme, Brown and Green, London. Critchett G. Royal London Hosp. Report 1857;1, 57. De Wecker. Ann Oculist, Paris 1896;116: 249

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laser, therapies. Since the 1860’s history has repeated itself. The wheel has continued to turn with different groups developing different ways of either retracting the iris root to allow more fluid to flow through or making a hole large enough in the eye for the fluid to drain from it. This must be achieved without permitting too much fluid to escape under the conjunctiva so that it becomes so thin that it is liable to infection. That so many have tried to achieve this goal means that none has entirely filled the requirements of a completely satisfactory operation. In the last 50 years we have had anterior lip sclerectomy12, 13 iridencleisis of Holth,14 Elliott trephination,15 and Scheie’s operation,16 Stallard’s single pillar iris inclusion,17 trabeculotomy,18 trabeculectomy19, 20 and multiple laser procedures. Many attempts were made during the 1960’s by Remond Smith.21 Cairns22 and others to isolate Schlemm’s canal, allowing fluid to drain through the trabecular meshwork without opening the eye. None of these was successful over the long-term and modern attempts to do the same thing seem to have a poor record so far. So it is that one of the many modifications of trabeculectomy remains the current preferred option because so far this is the only procedure in which the flow of fluid from the eye can move into the sub-Tenon’s space at a slow enough pace. The underlying reason for this is that the sclera heals slowly if at all. The layer of excised sclera is covered by a second scleral flap which is capable of moving slightly in the early postoperative stages. This not only allows the aqueous to flow through the operated region into the subepiscleral and subconjunctival space, but also responds to the pressure variations which occur postoperatively. The aqueous itself partly controls the healing reaction of the episclera and conjunctiva. When normal, and not affected by either long-term topical medicaments or locally applied anti-metabolites, the conjunctiva and episclera will allow diffusion of aqueous through them. Furthermore the aqueous itself inhibits the scarring process so that a cavity is formed in which there is an equilibrium between the intraocular pressure, the subepiscleral tissue pressure or the episcleral venous pressure if the aqueous drains into these vessels. Surgery and laser therapy have been accepted completely for the treatment of angle closure glaucoma and it still remains true that early aggressive treatment of chronic open angle glaucoma in an otherwise normal eye has the greatest possibility of success. Unfortunately if fewer and fewer surgical procedures are being undertaken the experience and confidence of the surgeon must diminish. This makes it essential that a text such as this is available for all to refresh their memories and to ensure that the techniques of the masters of the subject can be followed completely. Even though we still do not fully understand the mechanisms and genetic background to the conditions known as glaucoma, we are able to offer palliative and sometimes curable therapies. This will continue until we can target each individual type of the multitude of conditions which we now call glaucoma.

Peter G Watson MA MB BChir FRCS FRCOphth DO Boerhaave Professor, University of Leiden, Honorary Consultant, Addenbroke’s Hospital, Cambridge Honorary Consultant, Moonfield Eye Hospital, London, UK

12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22.

Herbert H. Subconjuncival fistula formation in the treatment of primary chronic glaucoma. Trans Ophthalmol Soc UK 1903;23: 324. La Grange F. Production of a cicatrix in chronic glaucoma. Ophthalmoscope 1907;5: 467. Holth S. Iridencleisis cum iridotomia meridionali. Arch Ophthalmol 1930;4: 803. Elliot RH. A preliminary note on a new operative procedure for the establishment of a filtering cicatrix in the treatment of glaucoma. Ophthalmoscope 1909;7: 804. Scheie HG. Peripheral iridectomy with scleral cautery for glaucoma. Arch Ophthalmol 1959;61: 291. Stallard HB.Anterior flap sclerectomy with basal iridencleisis. Eye Surgery John Wright, Bristol 4th Edition., 1965;53-665. Burian HM, Allen L. Trabeculotomy ab externo, a new glaucoma operation Am J Ophthalmol 1962;53: 19. Cairns JE. Trabeculectomy. Preliminary report of a new method. Am J Ophthalmol 1968;66: 673. Watson PG. Effectiveness of trabeculectomy in glaucoma. 1975;79, 5, 831-845. Smith R. A new technique for opening the canal of Schlemm. Preliminary report. Br J Ophthalmol 1960;44: 370. Cairns JE. Goniospasis. Eine Methode, die zur Entlastung der Kanalblockade bei Primarem Weitwinkelglaukom Entwickelt Wurde, Klin.Monatsbl. Augenheilkd. 1974;165: 549.

Acknowledgements

We would like to express our utmost appreciation to our co-authors who showed a sincere willingness to contribute to this scientific endeavor. Sincere thanks are also due to Mr PG Watson for accepting to write the Foreword. Our heartfelt gratitude to Professor AB Safran, Head, Department of Ophthalmology, University of Geneva and Professor L Zografos, Head, Department of Ophthalmology, University of Lausanne, for their continued support of our clinical and academic activities. We would like to graciously acknowledge Dr K Mansouri for his efforts in the coordination of this extensive undertaking. We also find it important to mention that were it not for the patience and understanding of our Publisher Mr JP Vij, CMD of M/s Jaypee Brothers Medical Publishers, this piece of work would not have come to see the light. Last but not least we would like to offer our sincere thanks to Mrs G Ibrahim for her meticulous revision of the manuscript and for offering valuable suggestions and criticism.

Tarek Shaarawy André Mermoud

MD MD

Contents

1. Reducing Intraocular Pressure: Is Surgery Better than Drugs? ............................................... 1 T Shaarawy, J Flammer, IO Haefliger 2. Trabeculectomy .................................................................................................................. 11 PT Khaw, P Shah 3. Trabeculectomy with a Scleral Tunnel Technique Combined with Mitomycin-C ................... 32 D Gherghel, S Orgüel, Ch Prünte, J Flammer 4. Cyclodestruction in Glaucoma ............................................................................................ 37 A Tarkkanen, P Puska, T Kivelä 5. Resurrecting the Failing Filtering Bleb ............................................................................... 45 WA Shihadeh, R Ritch, JM Liebmann 6. The Ahmed Valve ................................................................................................................ 58 O Albis-Donado 7. The Use of Molteno Implants to Treat Complex Cases of Glaucoma ..................................... 77 ACB Molteno, TH Bevin 8. Nonpenetrating Surgery .................................................................................................... 102 A Mermoud 9. Nonpenetrating Deep Sclerectomy (NPDS): Anatomic Landmarks ..................................... 112 R Sampaolesi, JR Sampaolesi, J Zarate 10. Shortening the Learning Curve of Deep Sclerectomy ......................................................... 131 H Roux, T Shaarawy 11. Postoperative Management of Nonpenetrating Glaucoma Surgery ..................................... 140 K Mansouri, T Shaarawy 12. Trabeculotomy Ab Externo ................................................................................................ 150 AK Khalil 13. Selective Laser Trabeculoplasty ....................................................................................... 161 F Howes, M Nagar 14. Combined Cataract Glaucoma Surgery ............................................................................. 170 H Kholefy 15. Management of Angle-closure ........................................................................................... 182 P Foster

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16. Modulation of Wound Healing ........................................................................................... 188 D Siriwardena, MF Cordeiro 17. Glaucomatous Complications of Refractive Surgery .......................................................... 197 G Muñoz, JI Belda-Sanchís, J Pérez-Santonja, D Elíes Index .................................................................................................................................................... 203

Tarek Shaarawy, Josef Flammer, Ivan O Haefliger

1 Reducing Intraocular Pressure: Is Surgery Better than Drugs?

INTRODUCTION Glaucoma is a progressive optic neuropathy involving characteristic structural-pathological changes in the optic nerve head. 1-3 Estimate of the number of patients bilaterally blind because of glaucoma ranges between 7 and 8 million people.4-6 Glaucoma is an increasingly important public health concern due to our aging population demographics, and has been identified as the second leading cause of blindness world-wide and the first cause of irreversible blindness. It is irreversible because it results from the degeneration of retinal ganglion cells, and to date there is no cure for neuronal central nervous system degeneration, or means of regenerating lost neurons. After more than a century of active research in the management of glaucoma, the Holy Grail of glaucoma treatment is still elusive and we have to be pragmatically content with our attempts to prevent further progression of glaucomatous damage, rather than curing the disease. Glaucoma progression is strongly associated with a number of risk factors.7-14 Some of these factors are unmanageable like ethnicity and age, while others can be manipulated, with varying degrees of success, in an attempt to slow or arrest progression, like IOP and possibly vascular dysregulation. Reducing IOP is presently the evidence based, most accepted, and most practised therapeutical approach of glaucoma patients. 12,15 Currently topical ocular hypotensive medications, with its different classes, as well as filtering surgery (trabeculectomy and non-penetrating surgery) are in the forefront of therapeutic modalities to reduce IOP.15, 16-22 This review article looks at the potential advantages and disadvantages of topical medications versus filtering

surgery and vice versa. It does not directly address the question of initial treatment of glaucoma,19, 20, 23-28 or what is the better treatment29 of glaucoma, as other review articles had, but rather looks in a more specific fashion on the pros and cons of each in relation to IOP reduction. In other words this review article deals with the situation once the decision has been made to reduce IOP.

WHAT IS THE IDEAL TREATMENT TO REDUCE IOP? Based on available knowledge12,15,17,22,23,27,29 an ideal treatment to reduce IOP should achieve different objectives. It should offer sufficient reduction in IOP, possibly in the low teens. It should provide this reduction on a long-term basis and not just momentarily or sporadically. It should be associated with minimal IOP fluctuation, IOP fluctuation being identified as a significant and independent risk factor. It should, if possible, encourage patient compliance or better still, be totally independent from the compliance factor. On top of all that the ideal treatment should offer tolerable systemic and local side effects, or again better still be devoid of side effects. Last but by any means not least, in a world exceedingly aware of the heavy medical care expenses30 an ideal treatment to reduce IOP should be economically sound.

SUFFICIENT REDUCTION OF IOP Although it has been suggested that IOP reduction should be individualized to specific target pressure31 for each specific patient, in the majority of our patients we are mostly aiming at pressures in the low teens.32

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In the Advanced Glaucoma Intervention Study (AGIS),32 eyes were randomized to laser trabeculoplasty or filtering surgery when medical therapy failed. In the roughly one quarter of eyes in the study in which the IOP was always lower than 18 mm Hg (mean IOP, 12.3 mm Hg) during 6 years of follow-up, there was no net change in the mean visual field score. While 15 percent of such eyes were said to have worsened by 4 AGIS visual field units, an equal percentage “improved” by the same criterion, perhaps providing an estimate of the false-positive rate of progression. In contrast, in those eyes in which the IOP was greater than 17 mm Hg more than half the time (average IOP, 20.2 mm Hg), eyes lost an average of approximately 3 AGIS units during 8 years of follow-up. A clear dose-response relationship between IOP and risk of progressive field loss was evidenced for intermediate categories. With surgery levels of IOP in the low teens, or even lower, are technically achievable,19,20,33-36 and that is independent of the IOP values prior to surgery. What determines IOP levels postoperatively are mainly the degree of surgical precision intraoperatively, the resistance to outflow posed by the scleral flap in trabeculectomy, at least initially. On the long run the degree of wound scarring29 postoperatively and whether this has been manipulated by antimetabolites,20,34 plays a role of paramount importance. In topical medications IOP in the low teens is less likely to be achieved37 but never the less possible specially with newer classes of medications18 and with the use of combination topical medical therapies, while the level of IOP is largely dependent on IOP values before commencing therapy. Topical medications depending on their mechanisms of action, whether reducing production or increasing outflow, tend to knock down percentages of prior levels. It is fair though to acknowledge that not every patient requires an IOP in the low teens in order to halt his glaucoma progression. In the collaborative initial glaucoma treatment study23 it would seem that patients with mild, initial damage can do well at pressures in the mid-to-upper teens, while those with more advanced damage indeed do better when pressure is reduced to the lower teens.

LONG-TERM IOP REDUCTION In spite initial IOP reduction of some medications, the effect seems to ware off in many cases. Watson and coworkers 38 examined the long-term efficacy of monotherapy with topically applied beta-blocking agents. Analysis showed that less than half the eyes initially treated with topical beta-blockers might be expected to still be being treated with their original medication after 5 years. The rest required either additional medication or trabeculectomy. Long-term IOP reduction capabilities of other newer classes of medications are still not fully determined.39, 40 One study 18 with a two-year follow-up found that latanoprost significantly reduced IOP from pretreatment values, and this reduction was maintained over the 24month treatment period with no sign of upward drift. Surgery also shows deterioration of its results with time. Chen and coworkers 41 studied the long-term outcomes of primary trabeculectomies that were successful at 1 year. This was retrospective study of patients with various types of glaucoma who had trabeculectomies that were successful at 1 year and who had a follow-up of at least 10 years. Forty patients (40 eyes) were enrolled, who had primary trabeculectomies that were successful at 1 year and who had a follow-up range of 10 to 21 years. Control of IOP was evaluated at 5, 10 and 15 years and at the last obtainable followup. Successful control of IOP was defined as IOP less than 21 mm Hg or a reduction of 33 percent if preoperative IOP was less than 21 mm Hg. These results show that if an eye was considered successful by IOP at 1 year, the probability of successful control of IOP was 82 percent at 5 years and 67 percent at 10 and 15 years. If an eye did not require further glaucoma surgery at 1 year, the probability that it still would not need further surgery at 5 years was 90 percent, at 10 years 75 percent, and at 15 years 67 percent. They concluded that loss of IOP control and progression of glaucomatous damage occurs over time despite initial success at 1 year. Another study42 examined the long-term results (1 to 14 years) of trabeculectomies with 5-fluorouracil injections that were successful at 1 year. In a retrospective non-comparative case series the authors identified 87

Reducing Intraocular Pressure: Is Surgery Better than Drugs? patients (87 eyes) who had trabeculectomies with 5fluorouracil injections that were successful at 1 year and had a follow-up range of 1.0 to 14.7 years (mean, 8.1, standard deviation of 4.4 years). All patients had previously failed glaucoma surgery (66.7%), cataract surgery (47.1%), or other diagnoses making them at high risk for failure. Successful control of IOP was defined as IOP less than 21 mm Hg or a reduction of 33 percent if preoperative pressure was less than 21 mm Hg. Statistical analysis was performed using Kaplan-Meier life table analysis. If an eye is considered successful by IOP at 1 year, the probability of successful control is 61 percent at 5 years, 44 percent at 10 years, and 41 percent at 14 years. They concluded that despite successful IOP control at 1 year, trabeculectomies with 5-fluorouracil injections show a continual loss of IOP control over time.

MINIMAL IOP DIURNAL FLUCTUATIONS Large diurnal fluctuations in intraocular pressure have been identified as an independent risk factor in patients with glaucoma. In a retrospective study of 114 patients under treatment for POAG and OHT over an 11-year period of observation. Niesel and Flammer43 described, more than a quarter of a century ago, a highly significant correlation between IOP and progression of visual field defects. This correlation could be shown for the visual field outer boundary in 81 eyes with ocular hypertension and for typical visual field defects in 33 eyes with chronic glaucoma. The relationship was, however, only significant when both the standard deviation of the annual intraocular pressure and the influence of cataract development upon visual acuity were considered. If only the mean IOP, not considering the standard deviation, is considered, this correlation is rendered insignificant. In another retrospective study44 by the same group they described clearly a significant correlation between concentric constriction during 11 years of observation and the IOP fluctuation. Asrani and coworkers45 have demonstrated that the diurnal IOP range and the IOP range over multiple days were significant risk factors for glaucomatous progression, even after adjusting for office IOP, age, race, gender, and visual field damage at baseline. This implies that we can no longer rely on an IOP in the statistically normal

3

levels under treatment in office visits. Patients could still suffer from glaucomatous progression because of high fluctuations. What remains to be identified is the risk of this progression in large “within statistically normal” fluctuations compared to fluctuations outside of what is statistically normal. Migdal and coworkers37 compared the long-term functional outcome in POAG in medically treated patients versus surgically treated patients. Among many results from this study they observed that patients in the surgery treated group had the lowest mean IOPs and with fewer peaks and troughs. The maximum mean IOP was 15.5 mm Hg and the minimum mean IOP was 13.1 mm Hg for surgery compared with 22.1 mm Hg and 15.9 mm Hg for medicine. Another study46 was designed specifically to compare the IOP fluctuations in glaucoma patients under ocular hypotensive therapy with those of patients previously submitted to trabeculectomy. The IOP peaks and fluctuations for the same patients in response to the water-drinking test (WDT) were also examined. The study included 30 primary open-angle glaucoma (POAG) patients using ocular hypotensive medications and with no history of previous intraocular surgery (medical group), and 30 POAG patients previously submitted to one or more trabeculectomies though taking no medication at the time of the study (surgical group). All patients were submitted to a diurnal tension curve (DTC) followed by the WDT. The IOP peak and IOP fluctuation during the diurnal tension curve were significantly greater in the medical group than in the surgical group. The same was observed following the WDT. From an overall baseline IOP of 10.6 mm Hg, the mean IOP change following the WDT was 13 percent in the surgical group and 40 percent in the medical group. The study concluded that patients submitted to trabeculectomy have less IOP fluctuations during the diurnal tension curve and following a water-drinking provocative test. This observation does constitute a definite advantage of surgery over medical treatment in that respect, thus potentially offering better potential chance of stabilization or retardation of the glaucomatous disease process. One criticism to these two studies though, was the inclusion of patients under different classes of ocular hypotensive

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medications under the medical group. Different classes have different effects on IOP diurnal curves as has been demonstrated by Orzalesi and coworkers. 47 They compared the round-the-clock intraocular pressure (IOP) reduction induced by timolol (0.5%), latanoprost (0.005%), and dorzolamide in patients with primary open-angle glaucoma (POAG) or ocular hypertension (OHT). This was a crossover trial, 20 patients with POAG or OHT were treated with timolol, latanoprost, and dorzolamide for 1 month. The treatment sequence was randomized. All patients underwent measurements for four 24-hour tonometric curves: at baseline and after each 1-month period of treatment. The between-group differences were tested for significance by means of parametric analysis of variance. To compare the circadian IOP rhythms in the POAG-OHT and control groups, the acrophases for each subject were calculated. All the drugs significantly reduced IOP in comparison with baseline at all times, except for timolol at 3 AM. Latanoprost was more effective in lowering IOP than timolol at 3, 6, and 9 AM (P = 0.03), noon (P = 0.01), 9 PM, and midnight (P = 0.05) and was more effective than dorzolamide at 9 AM, noon (P = 0.03), and 3 and 6 PM (P = 0.04). Timolol was more effective than dorzolamide at 3 PM (P = 0.05), whereas dorzolamide performed better than timolol at midnight and 3 AM (P = 0.05). In this study latanoprost seemed to lead to a fairly uniform circadian reduction in IOP, whereas timolol seemed to be less effective during the night-time hours. Dorzolamide was less effective than latanoprost but led to a significant reduction in nocturnal IOP. Although the study compares IOP lowering effect of the medications over a diurnal curve, the study lacks, or does not report, information on the differences in fluctuations in the diurnal curve between the different medications. In fact if one compares different diurnal curves of different medications, latanaprost seems to have its curve in the lowest level, but if one examines the IOP diurnal curves presented in this study, it appears that latanaprost provides similar range of fluctuations to timolol. Another concern in that we are judging mean IOPs and not individual curves, theoretically single individuals might be at higher risk of glaucomatous progression due to

high fluctuations, which would not be apparent from mean IOP curves, this is of special concern in an era where individualized therapeutic decisions are stressed. Medication class specific or even medication specific studies comparing IOP fluctuations in surgically versus medically controlled glaucomatous patients are in dire need, if this point is to be resolved. Though the bulk of evidence, for the time being, seems to point to a relative advantage of surgery over medications in that respect.

ISSUE OF COMPLIANCE AND PERSISTENCE Though compliance is not a real issue in surgically treated patients, it does pose a serious challenge to the efficiency of medical treatment.48-54 Clinically significant non-compliance with glaucoma medications has been well documented. One study55 documented the prevalence of non-compliance in a Greek cohort. Clinically significant non-compliance (more than two doses missed per week) was established in 44 percent of patients examined. Men and those using eyedrops more than 4 times a day were more likely to default. Non-compliant patients exhibited higher mean IOP (22.9 vs. 18.5 mm Hg; p > 0.001) and worse visual field loss (10.8 vs. 7.0 dB; p = 0.008) compared with compliant patients. Involuntary non-compliance was also common in this group, with only 53 percent instilling their eyedrops accurately. Another study51 was designed to assess levels of compliance in elderly glaucoma patients on timolol eyedrops. Twenty-four percent of patients admitted to omitting eyedrops either occasionally or frequently. Fiftyone percent were found to have had insufficient drops dispensed to comply with treatment as prescribed. In non-complaint patients the mean period without drops was 85 days of the year, with a maximum of 165 days. Compliance could theoretically, but safely be assumed to be much worse in developing countries compared to developed ones, for obvious reasons. It could be assumed to improve with fewer medications and fewer doses per day, more easily tolerated side effects, as well as with better understanding of the nature and gravity of the disease process.

Reducing Intraocular Pressure: Is Surgery Better than Drugs? One study56 examined the causes of non-compliance with drug regimens in glaucoma patients. The results showed that forgetfulness was the number one reported reason for non-compliance. In the literature48-56 rates of non-compliance range between 23 percent and 51 percent, whatever the rate may be in different communities and age groups surgery has a clear advantage over medications in this respect. One useful way in assessing compliance with eyedrop medications is the miniature compliance monitor as purposed by Kass and coworkers.57 The medication monitor resembles commercially available 30 ml eyedrop bottles in size, shape and weight. It electronically records the date and time of each medication administration over a six-week period. Glaucoma patients’ persistence with long-term pharamcotherapy is also an issue of concern when discussing ocular hypotensive medications. Two studies58,59 have identified persistency as a significant factor that may influence not only health outcomes, but also long-term costs and health planning. One study compared persistency (time on initial therapy) of latanoprost versus beta-blocker monotherapy. The authors reported that patients receiving a beta-blocker as initial therapy were 3.8 times more likely to change therapy than those initially treated with latanoprost.

OCULAR SIDE EFFECTS AND COMPLICATIONS Surgery carries with it a set of serious ocular side effects and complications, most notably endophthalmitis.60-63 The use of antimetabolites34, 35, 42, 63-65 with trabeculectomy ups the stakes, on one hand better success rates are achieved, on the other higher complication rates are usually reported. Incidence of endophthalmitis is 0.2 to 1.5 percent66,67 in trabeculectomies without antimetabolites (this should be compared to incidence of endophthalmitis after cataract extraction which ranges between 0.07% and 0.12%),68 in trabeculectomies with 5-FU it is 3.0 percent69 and in trabeculectomies with MMC it is 2.1 percent.70 Another much dreaded, but fortunately a rare complication is expulsive hemorrhage. One study71 reported an incidence of 0.57 percent after

5

trabeculectomy. Another study 72examined delayed suprachoroidal hemorrhage (DSCH) after glaucoma filtration procedures. Of a total of 1863 trabeculectomy procedures, DSCH developed in 9 of 615 (1.5%) trabeculectomies without antimetabolite, 30 of 1248 (2.4%) trabeculectomies with antimetabolite. Other complications that do occur more commonly include hypotonic maculopathy (8.9%), bleb leaks (8 14.6%), hyphema (24.6%), and choroidal detachment (14.1%).73 Of special interest is cataract incidence after trabeculectomy. This complication, apart from its deleterious effect on vision, often necessitates another intraoperative surgery, which could adversely affect the initial trabeculectomy results. The cataractogenic effect of surgery has been well documented. 23,74 Cataract incidence post-trabeculectomy has been reported to be as high as 20.2 percent in a follow-up of 12 months.73 It is worth mentioning that such complication rates are not reported with non-penetrating surgery. 75-82 The vast majority of studies in the literature report significantly lower early postoperative complications compared to trabeculectomy. It also reports lower incidence of postoperative cataract formation. It is necessary though to acknowledge that the randomized controlled trials reporting on cataract incidence after non-penetrating surgery do not have the same long-term follow-ups as in the case of trabeculectomy. Ocular hypotensive medications are not devoid of ocular side effects and complications. For one, the early manifest glaucoma trial15 reported increases in clinical nuclear lens opacity gradings with medical treatment (P =0.002). Similar observation, but not statistically significant was observed in the ocular hypertensive treatment study,83 where 6.4 percent of the treatment group had cataract surgeries compared to 4.3 percent of the observation group (p=0.06). It is worth mentioning that the last two studies medication groups were under different medications. We have no information about which ocular hypotensive medication would put a patient under a higher risk of cataract occurrence. The noxious effect of ocular hypotensive medications on the ocular surface has been long identified. One study84 reported that administration of a single topical medication

6

Atlas of Glaucoma Surgery

preserved with benzalkonium chloride, irrespective of type, for 3 months or more induced a significant degree of subclinical inflammation detected as increased expression of HLA-DR on conjunctival epithelial cells. Another study85 reported that latanoprost treatment induces ocular surface changes which are more evident in POAG patients who are also affected by allergic conjunctivitis. The authors hypothesized that these findings are probably related to the very high latanoprost concentration of benzalkonium chloride and to its bedtime administration, which further amplifies the toxicity. An increasing number of studies 23,37,86,87 both experimental and epidemiological, have provided evidence that filtering glaucoma surgery maybe less effective than initially described. Of a number of risk factors for failure, duration and number of antiglaucoma drugs prior to surgery seem to play a critical role and highly accumulated antiglaucoma topical treatments significantly reduce success rates. 88 Inversely trabeculectomies performed as a primary procedure do offer higher success rates than trabeculctomies performed after a history of ocular hypotensive medications. Again very little is known about which medication, in which patient is associated with which adverse effects, and if that is clinically relevant.

SYSTEMIC SIDE EFFECTS AND COMPLICATIONS Apart from systemic side effects of general anesthesia, which is rarely resorted to in glaucoma surgery89-91

nowadays, surgery appears to be at a clear advantage in this respect. Ocular hypotensive medications have a long list of potential systemic side effects (Table 1.1).92-95 Among others, pulmonary effects of beta-blockers are exceptionally worrisome. Two drops of 0.5 percent timolol equates to a 10 mg oral dose. This is not enough to cause symptoms in many patients, but unfortunately glaucoma and airways disease frequently coexist. Glaucoma affects 5 percent of people over 65 years96 and incidence97 of asthma in elderly patients (above 65 years old) is 4 percent in males and 7 percent in females. This should not be understood in the sense that betablockers are contraindicated in patients above 65 years, only patients with a clinically relevant bronchial asthma does run a risk with beta-blockers. Attempts have been made though to offer better safety profile ocular hypotensive medications. Betaxolol [Betoptic] is cardioselective beta-blocker but is associated with poorer IOP control. 98 Carbonic anhydrase inhibitors30,47,99-105 applied topically are associated with less serious systemic side effects, but are also less potent than if orally administered. Prostaglandins18,40,47,95 are however very effective at lowering intraocular pressure with, as far as we know, minimal systemic side effects and have become the treatment of first choice in many cases. The advantage of beta-blockers still is that it has been tried and tested, we know a lot about beta-blockers and we probably do not know the same amount of information about newer classes of ocular hypotensive medications. This makes beta-blockers still a very valid option.

Table 1.1: Ocular hypotensive medications and their potential systemic side effects Medication

B Blockers

Carbonic anhydrase inhibitors (oral and topical)

Alpha agonists

Parasympathomimetics

Prostaglandin analogues

Side effects

Dyspnea, bradycardia, impotence, confusion, depression, hypotension, worsening of peripheral vascular disease

Parasthesiae (systemic) Renal stones (systemic) Blood dyscrasias (systemic and ? topical) Rashes (either) Hypokalemia (systemic) Polyuria (systemic) Metallic taste (topical and systemic)

Dry mouth GI upset palpitations fatigue decreased libido, hypotension respiratory arrest in infants

Nausea Vomiting Headache Confusion

Minimal systemic side effects caution in asthma? contraindicated in pregnancy

Reducing Intraocular Pressure: Is Surgery Better than Drugs? ECONOMICAL BURDEN OF IOP LOWERING STRATEGIES The cost of surgical reduction of IOP decreases with time, where the cost of surgery can be divided by the number of years of life expectancy. The opposite is true for ocular hypotensive medications where the cost increases with time and could be multiplied by the number of years of life expectancy. The cost of medication106,107 for a latanaprost treated patient per year is $ 337, while it is $ 336 and $ 288 for betaxolol and dorzolamide, respectively. The daily cost of latanaprost is $ 0.87, this should be put in context with the fact that according to the United Nations and the World Bank, more than one billion to 1.3 billion people live on a daily income of less than $ 1 (one dollar) a day. This makes glaucoma a surgical disease in most of the developing countries. Developing countries have the majority of glaucoma patents, and thus surgery is the treatment of choice to the majority of glaucoma patients. Unfortunately very little industry research funding is being allocated for research in glaucoma surgery, which the majority of glaucoma patients are poised to benefit from. There is evident lack of studies related to economic evaluation in glaucoma. Kobelt108 states that the genuine lack of a useful outcome measure, and the impossibility to calculate the absolute annual risk of vision loss at given levels of the one parameter that is being treated, IOP, has essentially limited the research to resource utilization. One other limitation is that economical studies usually take in consideration data from industrialized countries which could be misleading if applied to developing countries circumstances.

CONCLUSIONS In essence, surgery has over drugs the potential to fulfill many features of an ideal approach to reduce IOP. It can lower IOP to low teens, achieve long-term IOP reduction, minimize IOP fluctuations, lower cost, and minimal systemic side effects. The major drawback though, is the potentially devastating, but rare, ocular side effects. Although surgery is usually the first line treatment in developing countries, it is still resorted to as a final attempt

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to reduce IOP in developed countries. The possibility of employing surgery as a first line treatment is limited by the high incidence of potential ocular complications. Beta-blockers are effective and relatively safe ocular hypotensive medications, but have a well established list of side effects, it has been tried and tested over longterm follow-ups. The real advantage lies in the fact that the amount of information that we possess about betablockers is relatively large. Prostaglandins may offer certain advantages of limited side effects and effective IOP reduction, but longer follow-ups are in dire need to provide evidence of efficacy and safety. There is evidence that non-penetrating surgery could offer a safer option to trabeculectomy, but the widespread practice is hindered by its surgical complexity, which results in long learning curves. Being technically demanding, it is very difficult to employ in mass surgical treatment, specially in developing countries. The use of implants with non-penetrating surgery is an extraconsiderable cost. Another disadvantage is that nonpenetrating surgery does not seem to achieve its previously defined target IOP, in a significant percentage, without the postoperative use of goniopuncturing, which necessitates the access to laser equipment.109 There is an urgent need to improve our surgical options in order to reduce related ocular complications. If possible safer and simpler surgical procedures should be developed to tackle the bulk of our glaucoma problem in developing countries. Reducing IOP, is surgery better than drugs? As is the case in many aspects of glaucoma, indeed as in life itself, there are no easy answers to such questions. What could be at a clear advantage for one patient could be an absolute contraindication for another. In fact many patients, specially in the developing world, do not have the luxury of an option. We look forward to the day when effectively reducing IOP would not be such an important matter. When we can manipulate other risk factors, as vascular autoregulation, and neuronal damage, to the advantage of our glaucoma patients.

8

Atlas of Glaucoma Surgery

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68. Kresloff MS, Castellarin AA, Zarbin MA. Endophthalmitis. Surv Ophthalmol 1998;43:193-224. 69. Wolner B, Liebmann JM, Sassani JW, Ritch R, Speaker M, Marmor M. Late bleb-related endophthalmitis after trabeculectomy with adjunctive 5-fluorouracil. Ophthalmology 1991;98:1053-60. 70. Greenfield DS, Suner IJ, Miller MP, Kangas TA, Palmberg PF, Flynn HW, Jr. Endophthalmitis after filtering surgery with mitomycin. Arch Ophthalmol 1996;114:943-9. 71. Ishida M, Takeuchi S. Vitrectomy for the treatment of expulsive hemorrhage. Jpn J Ophthalmol 2000;44:571. 72. Tuli SS, WuDunn D, Ciulla TA, Cantor LB. Delayed suprachoroidal hemorrhage after glaucoma filtration procedures. Ophthalmology 2001;108:1808-11. 73. Edmunds B, Thompson JR, Salmon JF, Wormald RP. The National Survey of Trabeculectomy. III. Early and late complications. Eye 2002;16:297-303. 74. Anderson D, Normal Tension Glaucoma Study. Collaborative normal tension glaucoma study. Curr Opin Ophthalmol 2003;14:86-90. 75. Shaarawy T, Karlen M, Schnyder C, Achache F, Sanchez E, Mermoud A. Five-year results of deep sclerectomy with collagen implant. J Cataract Refract Surg 2001;27:1770-8. 76. Ambresin A, Borruat FX, Mermoud A. Recurrent transient visual loss after deep sclerectomy. Arch Ophthalmol 2001;119:1213-5. 77. Chiselita D. Non-penetrating deep sclerectomy versus trabeculectomy in primary open-angle glaucoma surgery. Eye 2001;15:197-201. 78. El Sayyad F, Helal M, El-Kholify H, Khalil M, El-Maghraby A. Nonpenetrating deep sclerectomy versus trabeculectomy in bilateral primary open-angle glaucoma. Ophthalmology 2000; 107:1671-4. 79. Gandolfi S, Cimino L. Deep sclerectomy without absorbable implants and with unsutured scleral flap: prospective, randomized 2-year clinical trial vs trabeculectomy with releasable sutures. 2000. Fort Lauderdale, USA. Ref Type: Conference Proceeding. 80. Mermoud A, Schnyder CC, Sickenberg M, Chiou AG, Hediguer SE, Faggioni R. Comparison of deep sclerectomy with collagen implant and trabeculectomy in open-angle glaucoma. J Cataract Refract Surg 1999;25:323-31. 81. Carassa, R. Viscocanalostomy versus trabeculectomy: a 12 months prospective randomized study. 2000. Boston, USA. 2000. Ref Type: Conference Proceeding 82. O’Brart DP, Rowlands E, Islam N, Noury AM. A randomised, prospective study comparing trabeculectomy augmented with antimetabolites with a viscocanalostomy technique for the management of open angle glaucoma uncontrolled by medical therapy. Br J Ophthalmol 2002;86:748-54. 83. Gordon MO, Beiser JA, Brandt JD, Heuer DK, Higginbotham EJ, Johnson CA, et al. The Ocular Hypertension Treatment Study: baseline factors that predict the onset of primary open-angle glaucoma. Arch Ophthalmol 2002;120:714-20. 84. Cvenkel B, Ihan A. Ocular surface changes induced by topical antiglaucoma monotherapy. Ophthalmologica 2002;216:175-9. 85. Costagliola C, Prete AD, Incorvaia C, Fusco R, Parmeggiani F, Di Giovanni A. Ocular surface changes induced by topical application of latanoprost and timolol: a short-term study in glaucomatous patients with and without allergic conjunctivitis. Graefes Arch Clin Exp Ophthalmol 2001;239:809-14. 86. Watson PG, Jakeman C, Ozturk M. The complications of trabeculectomy (a 20-year follow-up). Eye 1990;4:425-38. 87. Molteno A, Bosma N, Kittelson J. Otago glaucoma surgery outcome study: long-term results of trabeculectomy—1976 to 1995. Ophthalmology 2003;106:1742-50. 88. Broadway D, Grierson I, O’Brien C, Hitchings R. Adverse effects of topical antiglaucoma medications.II. The outcome of filtration surgery. Arch Ophthalmol 1994;112:1446-54. 89. Kansal S, Moster MR, Gomes MC, Schmidt CM Jr, Wilson RP. Patient comfort with combined anterior sub-Tenon’s, topical, and

10 90. 91. 92. 93. 94. 95. 96.

97. 98. 99.

Atlas of Glaucoma Surgery

intracameral anesthesia versus retrobulbar anesthesia in trabeculectomy, phacotrabeculectomy, and aqueous shunt surgery. Ophthalmic Surg Lasers 2002;33:456-62. Sauder G, Jonas JB. Topical anesthesia for penetrating trabeculectomy. Graefes Arch Clin Exp Ophthalmol 2002;240:73942. Vicary D, McLennan S, Sun XY. Topical plus subconjunctival anesthesia for phacotrabeculectomy: one year follow-up. J Cataract Refract Surg 1998;24:1247-51. Farrell TA. Minimizing the systemic effects of glaucoma medications. Geriatrics 1991;46:61-4, 73. Fraunfelder FT, Meyer SM. Systemic side effects from ophthalmic timolol and their prevention. J Ocul.Pharmacol. 1987;3:177-84. Bourgeois JA. Depression and topical ophthalmic beta adrenergic blockade. J Am Optom Assoc 1991;62:403-6. Waldock A, Snape J, Graham CM. Effects of glaucoma medications on the cardiorespiratory and intraocular pressure status of newly diagnosed glaucoma patients. Br J Ophthalmol 2000;84:710-3. Leibowitz HM, Krueger DE, Maunder LR, Milton RC, Kini MM, Kahn HA, et al. The Framingham Eye Study monograph: an ophthalmological and epidemiological study of cataract, glaucoma, diabetic retinopathy, macular degeneration, and visual acuity in a general population of 2631 adults, 1973-1975. Surv Ophthalmol 1980;24:335-610. Burrows B, Barbee RA, Cline MG, Knudson RJ, Lebowitz MD. Characteristics of asthma among elderly adults in a sample of the general population. Chest 1991;100:935-42. Kaiser HJ, Flammer J, Stumpfig D, Hendrickson P. Long-term visual field follow-up of glaucoma patients treated with beta-blockers. Surv Ophthalmol 1994;38 Suppl:S156-9. Orzalesi N, Rossetti I, Bottoli A, Invernizzi T, Fumagalli E, Fogagnolo P. Comparison of latanoprost, brimonidine and a fixed combination of timolol and dorzolamide on circadian intraocular pressure in patients with primary open-angle glaucoma and ocular hypertension. Acta Ophthalmol Scand Suppl 2002;236:55.

100. Arieta C, Amaral M, Matuda E, Crosta C, Carvalho Moreira FD, Jose N. Dorzolamide Apraclonidine in the prevention of the intraocular pressure spike after Nd : YAG laser posterior capsulotomy. Curr Eye Res 2002;25:237-41. 101. Day DG, Schacknow PN, Wand M, Sharpe ED, Stewart JA, Leech J, et al. Timolol 0.5 percent/dorzolamide 2 percent fixed combination vs timolol maleate 0.5 percent and unoprostone 0.15 percent given twice daily to patients with primary open-angle glaucoma or ocular hypertension. Am J Ophthalmol 2003;135:138-43. 102. Honrubia FM, Larsson LI, Spiegel D. A comparison of the effects on intraocular pressure of latanoprost 0.005 percent and the fixed combination of dorzolamide 2 percent and timolol 0.5 percent in patients with open-angle glaucoma. Acta Ophthalmol Scand. 2002;80:635-41. 103. Simmons ST. Efficacy of brimonidine 0.2 percent and dorzolamide 2 percent as adjunctive therapy to beta-blockers in adult patients with glaucoma or ocular hypertension. Clin Ther. 2001;23:604-19. 104. Strohmaier K, Snyder E, DuBiner H, Adamsons I. The efficacy and safety of the dorzolamide-timolol combination versus the concomitant administration of its components. Dorzolamide-Timolol Study Group. Ophthalmology 1998;105:1936-44. 105. Strahlman E, Tipping R, Vogel R. A six-week dose-response study of the ocular hypotensive effect of dorzolamide with a one-year extension. Dorzolamide Dose-Response Study Group. 106. Vold SD, Riggs WL, Jackimiec J. Cost analysis of glaucoma medications: a 3-year review. J Glaucoma. 2002;11:354-8. 107. Vold SD, Wiggins DA, Jackimiec J. Cost analysis of glaucoma medications. J Glaucoma. 2000;9:150-3. 108. Kobelt G. Health economics, economic evaluation, and glaucoma. J Glaucoma. 2003;11:531-9. 109. Gandolfi S, Quaranta L, Cimino L, Bettelli S. Deep sclerectomy versus trabeculectomy. Prospective Randomized Clinical trial. 4year interim analysis. 2003. Luxor, Egypt. Proceedings of the Second International Congress on Glaucoma Surgery. Ref Type: Conference Proceeding.

Peng Tee Khaw, Peter Shah

2 Trabeculectomy

INTRODUCTION This chapter addresses the current techniques used in glaucoma filtration surgery, in particular a guarded sclerostomy procedure best known as trabeculectomy. The decision to perform glaucoma surgery represents a key point in the long-term management of the patient’s disease, and should only be made after detailed consultation with the patient. The timing of surgery and selection of appropriate procedure need careful consideration and consultation. It is important to remember that the preoperative and postoperative management are critical determinants of the outcome of glaucoma surgery. The field of glaucoma surgery is undergoing a period of revolution with many new approaches to the traditional methods of surgery. Like all surgery, it is essential that surgeons have a sound understanding of the principles involved in the modern range of surgical procedures, and keep up to date with new procedures so that technique can be varied depending on the surgical circumstances. An example of new techniques that have revolutionized glaucoma surgery and are still changing is the use of adjuvant therapies to modify postoperative wound healing. The identification of relative risk factors for failure of glaucoma surgery enables the surgeon to vary the adjuvant therapy as appropriate while minimizing the risk. Glaucoma filtration surgery was previously performed when patients had uncontrolled intraocular pressures on maximally tolerated medical treatment, or after failed laser trabeculoplasty. The main reasons for delaying surgery were the risk of postoperative complications associated with standard trabeculectomy procedures and

high failure rates for operations in certain subgroups of glaucoma patients. Technical modifications to the trabeculectomy procedure including adjustable stitch techniques combined with the use and techniques of application of these powerful antimetabolites now enable the surgeon to have much greater control of both the operation and postoperative scarring. The identification of patients at risk of developing postoperative hypotony and the continuing development of surgical measures to reduce this risk have been important advances. The risks of surgery in each individual patient should be balanced against the projected visual loss which will occur from glaucomatous damage if the intraocular pressures are not adequately controlled. The techniques described in the following sections are continuously changing with the aim of making glaucoma surgery as safe and successful as possible.

ANESTHESIA The various operations described in this chapter can be carried out under local or general anesthetics. The methods of anesthesia are covered in another chapter in this book. However, there are specific points in terms of anesthesia in glaucoma.

General Anesthesia The lowering of intraocular pressure with anesthesia can be used to advantage by the ophthalmic surgeon if intraoperative pressure lowering is required. Blood pressure and to some extent choroidal volume can be reduced, if necessary, by varying the anesthetic in patients at risk of choroidal hemorrhage.

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Atlas of Glaucoma Surgery

Local Anesthesia When performing glaucoma surgery under local anesthesia it is important to try and avoid unnecessary elevation of IOP. It is advisable to use a technique that paralyzes orbicularis oculi to prevent eyelid squeezing and increased pressure on the globe. Patients with preexisting glaucoma may have a marked elevation in their IOP during peribulbar or retrobulbar anesthesia. This may be particularly important in patients who have advanced visual field loss. Reduced volumes of local anesthetic agents with hyaluronidase should be used in these patients if necessary, and orbital compressive devices (e.g. mercury balloons) should be avoided, if possible. Buphthalmic or myopic eyes often have extremely long axial lengths and may have large posterior staphylomas with the attendant risks of inadvertent ocular perforation during retrobulbar or peribulbar anesthesia. Patients occasionally notice an enlargement of their scotoma as a retrobulbar anesthetic takes effect, this is reversible but patients need to be warned of this. In an only eye, this may render the patient effectively blind for many hours. General anesthesia may be preferable in these patients as it avoids this problem and allows increased control of the operative conditions. Filtration surgery can also be carried out using only subconjunctival anesthesia. However, the patient may experience pain when the iris is handled particularly when an iridotomy is performed. Intracameral anesthetic may potentially be useful in this context.

FILTRATION SURGERY— PREOPERATIVE DETAILS The risks of any form of surgery should be explained to the patient in advance. In particular it is vital to explain that surgery for glaucoma is usually done to preserve vision not to improve it. Patients should be warned that their vision may well be blurred in the weeks after surgery before approaching preoperative levels. Several studies have demonstrated a loss of best-corrected visual acuity (of about 1 line) in postoperative patients, and it is essential that patients are aware of this. Patients with advanced field loss should be told of the risks of loss of their remaining field, the so called “wipe out” event,

although this is extremely rare. Patients who wear contact lenses should be advised that this may not be possible after filtration surgery.

PRE- AND INTRAOPERATIVE DROPS Parasympathetic Agonists Pilocarpine eyedrops are sometimes used preoperatively to miose the pupils. In theory, this protects the cornea from lens-corneal touch, and may reduce the chance of inadvertently cutting an excessively large iridectomy. The disadvantages include shallowing of the anterior chamber, and a theoretical possibility that the blood-aqueous barrier may be further compromised. Long-acting anticholinesterase agents should be discontinued if possible to reduce blood vessel congestion and leakage.

Sympathetic Agonists Topical adrenaline can be used at the beginning of the operation. Solutions of 0.01 percent or 0.1 percent can be dropped on the field of surgery. This produces conjunctival vasoconstriction and a reduction in bleeding during the course of the procedure. Blood contains many growth factors that promote wound healing and increase the chance of filtration surgery failure. The disadvantage of using adrenaline, is that it does cause some pupillary dilatation. However, this is not usually a problem, particularly if the operation is carried out relatively rapidly.

Povidone-iodine It has a broad spectrum of antimicrobial action. It can be used to prepare the skin, and drops can be applied to the superior and inferior fornices, to kill any bacteria. This is particularly important if the patient has pre-existing conjunctival or lid disease, which predisposes them to bacterial colonization.

Steroids It has been shown that chronic preoperative topical treatment jeopardizes filtration surgery by increasing the number of fibroblasts and inflammatory cells in the conjunctiva. This is particularly marked in association with the long-term use of adrenergic agents such as adrenaline and dipivefrin. Topical steroids such as fluoromethalone

Trabeculectomy reverse the histological change in the conjunctiva, although whether this conclusively increases the success rate has not been proven.

Nonsteroidal Anti-inflammatory Drugs The use of preoperative nonsteroidal anti-inflammatory drugs such as indomethacin or flurbiprofen has not been proven to alter the long-term results of glaucoma filtration surgery. However, in patients who may require iris manipulation and who in addition have a risk of fibrinous uveitis (especially dark irides) our impression is that preoperative topical steroids and nonsteroidal drops may be useful, even for a period as short as 24 hours before surgery.

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increasingly popular. This is because there is no chance of creating a superior rectus hematoma. Such a hematoma results in the release of growth factors that trigger wound healing. The vector force of the corneal suture is superior to that achieved with a superior rectus suture. The disadvantages of the corneal traction suture include the small risk of placing the suture too deeply and penetrating the anterior chamber (great care in buphthalmic eyes), and the chance of placing the suture too superficially with subsequent “cheese-wiring” and loss of traction. A variety of sutures can be used, but we use a 7-0 black silk suture on a semicircular needle (Fig. 2.1).

Hypotensive Agents If possible aqueous suppressants particularly those that have long-acting effects such as beta-blockers should be stopped several days in advance with outpatient monitoring. This will optimize aqueous flow postoperatively, encouraging aqueous flow through the new channel and help to prevent hypotony.

SURGICAL TECHNIQUE FOR TRABECULECTOMY Position of Filtration Area Filtration surgery is most commonly performed in the superior half of the globe. This is because the upper lid protects the drainage area. A peripheral iridectomy placed at 12 o’clock is covered by the lid, and does not give rise to diplopia. Drainage blebs that are not covered by the upper lid, particularly those in the interpalpebral fissure or the lower fornix, have a high incidence of inflammation and endophthalmitis especially when antimetabolites have been used. Scleritis may also be more common, particularly with the use of antimetabolites. It is important to avoid positioning the bleb anywhere other than the superior limbus, and other procedures should be used if this is not possible.

Traction Suture Superior rectus traction sutures are still commonly used. However, the use of a corneal traction suture is becoming

Fig. 2.1: Corneal traction suture

Conjunctival Incision The conjunctiva can be incised at the limbus (fornixbased flap) or deep in the fornix (limbus-based flap). The advantages and disadvantages of either approach are summarized in Table 2.1. The conjunctiva should be handled very gently to avoid buttonholing, particularly if antimetabolites are used. If a limbus-based flap is used, the incision should be made far into the fornix. The conjunctiva and Tenon’s should be entered in separate layers to minimize the chance of damaging the superior rectus muscle. An incision length of at least 10 mm is usually necessary to provide adequate exposure. For a fornix-based flap an incision of about 5 to 10 mm is necessary. A relieving incision is used by many surgeons but is not necessary and increases the trauma and risk of wound leakage.

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Atlas of Glaucoma Surgery Table 2.1: Fornix versus limbal based flap Fornix

Length of operation

Faster than limbus based Sclerostomy exposure Good Large eye/small Technically easier eyelid fissure Area dissected/ Smaller damaged Releasable suture Simple placement through cornea Conjunctival Increased incidence wound leaks Rare if buried corneal mattress sutures used Antimetabolite Need multiple small application sponges. Great care needed to insert Post operative appearance Reoperation

More diffuse (esp with MMC) Technically easier

Limbus

aqueous flow. Even cystic blebs from pre-antimetabolite days have these features.

Slower than fornix based Reasonable Difficult Larger More difficult Less common if deep in fornix Fewer sponges needed Easy to insert sponge without touching wound edge More focal (esp with MMC) More difficult

We dissect backwards with Westcott scissors to make a pocket of approximately 10 to 15 mm posteriorly and wide for the antimetabolite sponges. When dissecting over the superior rectus tendon we lift the conjunctiva to cut attachments avoiding the tendon itself (Fig. 2.2).

Fig. 2.3: Ring of steel and anterior aqueous flow

The restricted flow from the posterior incision resulting in more focal cystic blebs led us to change. The effects of treatment were very focal and the cells at the edge of the treatment area although growth arrested and can make scar tissue and encapsulate the area resulting in thinning and a cystic bleb. A fornix-based incision allowed a larger area of antimetabolite treatment, without a posteriorly placed restricting scar. Similar blebs can be achieved with a limbus-based flap but the incision has to be very posteriorly placed and this result is not as consistent. This does make the subsequent scleral flap and sutures more difficult.

Scleral Flap

Fig. 2.2: Dissection over rectus lifting conjunctiva

We always previously used a limbus-based incision with antimetabolite as we were worried about postoperative leaks. However, my clinical observation of cystic blebs led me to the hypothesis that they had two things in common. The first was restricted posterior flow “the ring of steel” (Fig. 2.3). The second was anterior

There are several types of scleral flap. The two most common types being rectangular and triangular in shape. There is no evidence that one is superior to the other. The scleral flap is usually outlined, and a lamellar dissection is carried out with a blade or scleral pocket knife. Alternatively, with a rectangular flap an incision can be made, and a scleral pocket made (like a phaco emulsification pocket) (Fig. 2.4) and then the two side incisions cut at the end (Fig. 2.5). The side incisions are not cut right to the limbus as this encourages posterior flow reducing the incidence of cystic blebs. We now cut the scleral flap before applying antimetabolite. There is also evidence that treatment under the flap increases the success rate and experimental

Trabeculectomy

Fig. 2.4: Scleral pocket being cut

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formation of holes in the flap and cheese-wiring of the flap sutures. All these complications allow increased aqueous leakage and reduce flap resistance. This is particularly important with the use of antimetabolites, because the conjunctival resistance to outflow may not rise for several weeks or even months after surgery. This is also very important in eyes with thin, less rigid sclera such as buphthalmos and myopia. If the scleral flap does not provide adequate resistance, the eye will be hypotonous. It is important to remember that the limbus may be thinned after multiple surgery or cryotherapy. If there is a large aqueous vein running through the site of the potential scleral flap, this vein should be avoided, as when the flap is cut, the vein will end up as a perforating hole in the scleral flap. Scleral flap sutures are preplaced at this stage whilst the eye is still firm. Scleral flap sutures are more difficult to place once the eye has been entered and is hypotonous.

Intraoperative Antimetabolite Use

Fig. 2.5: Limited side cuts to scleral flap to encourage posterior flow

and clinical evidence to suggest this is safe. We try to cut the largest flap possible and leave the side cuts at the limbus incomplete (1-2 mm from limbus). This forces the aqueous backwards over a wider area to get a diffuse bleb. An aqueous jet at the limbus predisposes to an anterior focal cystic bleb, whereas posteriorly directed diffuse flow of aqueous from incompletely cut sides of a large scleral flap results in a more diffuse noncystic bleb. The main function of the scleral flap is to provide resistance to aqueous outflow and prevent hypotony. To perform these functions the flap must be sufficiently large to cover the sclerostomy. It is important that the scleral flap is not too thin, since this increases the chance of flap dehiscence. Additional problems include

The full details of all antiscarring agents are too extensive for this chapter and are covered elsewhere. However the many potential agents are summarized in Table 2.2 and the risk factors, risks of antimetabolite complications and regimen we use in Tables 2.3 to 2.6. If intraoperative antimetabolites are indicated we now use them after the half thickness scleral flap has been cut but before the eye is entered, as there is reasonable pharmacokinetic and clinical data to suggest this is safe. If there is any problem with the scleral flap or scleral integrity or any sign of aqueous leak the use of antimetabolites can be withheld safely. The variations in the technique used to deliver intraoperative antimetabolites may account for some of the variations in efficacy and complications seen in the literature. It is very important for individual users to maintain a consistent technique and to build up experience with one technique. Changes in area of treatment, conjunctival and scleral flap construction, and adjustable sutures have led to a dramatic difference in terms of reducing short and longterm complications (Fig. 2.6). This has led to a reduction in cystic areas within the bleb from 90 to 29 percent. The blebitis and endophthalmitis rate over 3 to 5 years

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Atlas of Glaucoma Surgery

Table 2.2: Sequence of events in tissue repair and possible types of modulation after glaucoma filtering surgery (events and agents have overlapping time duration and action) Modified from Khaw et al {Khaw, 1994 5819 /id} Events

Possible modulations

Activated conjunctiva “pre-activated” cells Conjunctival/episcleral/scleral incisions. Damage to connective tissue Release of plasma proteins and blood cells Activation of clotting and complement. Fibrin/ fibronectin/blood cell clot Release of growth factors from blood

Stop medical therapy (espdrops causing red eye). Preoperative steroids Minimal trauma Less invasive surgical techniques

Aqueous released from eye Breakdown of blood aqueous barrier Release of growth factors into aqueous Aqueous begins to flow through wound Migration and proliferation of polymorphonuclear neutrophil cells, macrophages and lymphocytes.

Activation, migration and proliferation of fibroblasts

Wound contraction Fibroblast synthesis of tropocollagen glycosaminoglycans and fibronectin Collagen cross-linking and modification Blood vessel endothelial migration and proliferation Resolution of healing, apoptosis Disappearance of fibroblasts Fibrous subconjunctival scar

Hemostasis (Blood can reverse MMC) Agents preventing/removing fibrin, e.g. heparin, tissue plasminogen activator, hirudin Antagonists to growth factor production, e.g. antibodies to growth factors humanized anti-TGF-beta2 antibody (CAT 152 TrabioR) or receptors Anti-sense oligonucleotides, ribozymes Less specific antagonists, e.g. tranilast, genistein, suramin Blood aqueous barrier stabilizing agents, e.g. steroids Non-steroidal anti-inflammatory agents

Anti-inflammatory agents, e.g. steroids/ cyclosporine Anti-metabolites, e.g. 5-FU/MMC, Antibodies to inflammatory mediators Angiotensin converting enzyme or chymase inhibitors Preoperative steroids to reduce activation Antimetabolites MMC 5-FU Methylxanthine derivatives, mushroom lectins Antiproliferative gene p21(WAF-1/Cip1) Photodynamic therapy Anticontraction agents, e.g. colchicine, taxol lectins, MMP inhibitors Interferon alpha, MMP inhibitors, fibrostatin-c

Table 2.3: Risk factors for failure due to scarring after glaucoma filtration surgery Risk factors 1 Ocular Neovascular glaucoma (active) Previous failed filtration surgery Previous conjunctival surgery Chronic conjunctival inflammation Previous cataract extraction (conjunctival incision) Aphakia (intracapsular extraction) Previous intraocular surgery Uveitis (active, persistent) A red, injected eye Previous topical medications (beta-blockers + pilocarpine) (beta-blockers+pilocarpine +adrenaline) New topical medications High preoperative intraocular pressure (higher with each 10 mm Hg rise) Time since last surgery (especially if within last 30 days) Inferiorly located trabeculectomy 2 Patient Afro-Caribbean origin May vary, e.g. West vs East Africans Indian subcontinent origin Hispanic origin Japanese origin Elderly (+) vs Young + (+) (particularly children) + +

Risk 1- 3+ Comments +++ + + (+) ++ + + (+) + + (+) +++ ++ ++ ++

Uncertain

Depends on type of surgery

+ (+) +++ + (+) + (+)

Particularly if they cause a red eye

+ + + (+) + ++ + + (+) + + (+) (+)

Table 2.4: Possible risk factors for antimetabolite related complications • Elderly patient • Primary surgery no previous medications • Poorly supportive scleral tissue prone to collapse, e.g. Myopia/ buphthalmos/Ehlers-Danlos • Thin conjunctiva or sclera • Bleb placed in interpalpebral or inferior position

Anti-cross linking agents, e.g. betaaminopropionitrile/penicillamine Inhibitors of angiogenesis, e.g. fumagillin analogs, heparin analogs MMC 5-FU Death receptor ligands Stimulants of apoptosis pathways

Fig. 2.6: Showing diffuse bleb in patients right eye using large area of treatment vs a smaller area of treatment with mitomycin-C

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Trabeculectomy Table 2.5: Moorfields Eye Hospital (More flow) intraoperative single dose antiscarring regimen v2004 (Continuously evolving). Lower target pressures would suggest a stronger agent was required

Table 2.6: Various intraoperative antiscarring agents applied directly to the bleb site

Low risk patients (Nothing or intraoperative 5FU 50 mg/ml*)# No risk factors Topical medications (beta-blockers/pilocarpine) Afro-Caribbean (Elderly) Youth 10%) • Mild to moderate iritis (38-100%) • Loss of > 1 to 2 lines of Snellen visual acuity or a change in low vision category (12-38%) 2. Varying frequency • Pop effects (tissue disruption; 0-70%) • Postoperative pain (0-37%) • Conjunctival burns (0-26%) • Conjunctival chemosis (2-30%) • Conjunctival hyperemia (7-100%) • Severe iritis (4-15%) • Hyphema (0.5-17%) • Cells in anterior vitreous (0-15%) 3. Infrequent ( 1 to 2 lines of Snellen visual acuity or a change in low vision category (9.6-31%) • Progression of pre-existing cataract (14%) 2. Infrequent (15 mm Hg. The IOP remains low for 1 to 3 weeks before the distended bleb shows signs of vascular congestion and in the absence of treatment the IOP rises over 3 to 4 weeks to 25 to 35 mm Hg before the vascular congestion ceases and the IOP falls back towards normal levels. The intensity of inflammation and the amount of connective tissue laid down during this “hypertensive stage” of bleb formation are reduced by appropriate use of hypotensive medication over this period. Appropriate medication includes topical beta blockers, and topical or systemic carbonic anhydrase inhibitors. Miotics, prostaglandin analogues and adrenergic agents that may be proinflammatory should not be used during this period.

Indirect Control of Bleb Fibrosis by Hypotensive Agents At the first signs of bleb inflammation or if the IOP rises to >20 mm Hg timolol or an equivalent beta blocker is prescribed. If necessary a carbonic anhydrase inhibitor is added and the dosage adjusted to keep the IOP from rising to >30 mm Hg. Once the vascular congestion of the hypertensive stage has passed (6 to 7 weeks after the onset of drainage) the IOP falls back to normal. Very occasionally it does not do so in patients who are steroid responders. In these cases topical steroids should be discontinued and the IOP will fall to normal within 1 to 2 weeks.

Direct Control of Bleb Fibrosis by Systemic Anti-inflammatory Agents Occasionally, in the most severe cases, e.g. where active inflammation is present in the eye, it may be advantageous to administer a combination of systemic prednisone, a non-steroidal anti-inflammatory agent and colchicine as an additional measure to suppress bleb inflammation for 6 weeks after the beginning of drainage of aqueous.3-5 NB When using implants this regime should

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not be given before the onset of drainage of aqueous as it will prevent the formation of a preformed bleb lining, delay the opening of the tube and increase the incidence of hypotony after the tube opens!

Cytostatic Agents The perioperative or postoperative use of mitomycin-C or 5-fluorouracil with implants does not improve control of IOP. Both agents inhibit wound healing and may cause exposure of implants due to breakdown of the overlying tissues, therefore they should not be used.17

Postoperative Management of Cases with Immediate Drainage of Aqueous (A Vicryl Tie is Not Used on the Drainage Tube) The majority of eyes drained using this technique are cases of neovascular glaucoma or rare cases of active uveitis with secondary glaucoma whose postoperative management consists of topical steroids and cycloplegic agents which are continued for several weeks until the eye is quiet. In cases of neovascular glaucoma early photocoagulation of the underlying retinal lesions should be combined with optimal management of the underlying general vascular disease in order to minimize the vasoformative activity of the draining aqueous. Bleb inflammation and fibrosis may be limited in less severe cases by prescribing hypotensive agents while more severe cases with potential for useful vision should receive oral prednisone, a non-steroidal anti-inflammatory agent and colchicine during this period.3-5

Long-term Management (All Cases) It is important that the surgeon should appreciate how the fibrovascular capsule which regulates the IOP after the insertion of implants responds to different groups of hypotensive agents. Timolol, other beta blockers and topical or systemic carbonic anhydrase inhibitors are highly effective in reducing IOP, show marked synergism and have a favorable long-term effect on bleb permeability. Miotics and prostaglandin analogues are variable in their action and may be ineffective or even raise the IOP due to their proinflammatory side effects. Adrenergic agents are sometimes useful but rebound vasodilatation makes their action less certain. The need

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for hypotensive medication decreases slowly with time. Severely damaged eyes in which a single topical medication produces hypotony while the IOP is too high without medication can be managed by adjusting the dose of oral acetazolemide to produce the IOP required.

Early Complications The postoperative complications after insertion of implants are very similar to those that occur after conventional drainage surgery and their management is broadly the same. 1. Hyphema: Hyphemas are common given the type of case being drained by implant and require no special treatment. 2. Choroidal detachment: Choroidal detachments are uncommon and tend to occur in terminally advanced cases where thin sclera prevents watertight insertion of the tube into the AC. They are managed conservatively. 3. Leakage through tube: This should be prevented by careful surgical technique but when it does occur the eye is managed conservatively using topical steroids and cycloplegic agents and relying on the biological valve formed by the pressure ridge to prevent hypotony. 4. Hypotony: Despite good surgical technique hypotony may occur in terminal eyes as a result of temporary suppression of aqueous secretion by the ciliary body. These cases are best managed conservatively. Very occasionally hypotony occurs when a double plate implant is inserted in a case where, in retrospect, a single plate implant should have been used. These cases are initially managed conservatively, however if the IOP does not rise sufficiently within 2 to 3 weeks the second plate should be removed. This is easily done as an outpatient procedure. Using topical anesthesia the conjunctiva is incised over the anterior edge of the second episcleral plate. The plate is then grasped with a pair of toothed forceps and pulled forwards out of the bleb cavity. The connecting tube is stretched and cut as short as possible so that it retracts into the tissues. After this procedure connective tissue

encloses the cut end of the connecting tube and the IOP rises to normal levels within 3 to 4 days.

Late Complications 1. Raised intraocular pressure: In cases where a single plate has not given adequate control of IOP a second plate can be added without direct intraocular intervention. A single plate implant is placed in an adjacent quadrant to the existing bleb. After suturing the plate in position on the sclera and occluding its drainage tube by a 5.0 vicryl ligature the tube is trimmed to a length where it extends to the centre of the existing first plate. The end of the tube is beveled with the bevel facing down towards the surface of the plate to prevent the end of the tube from being occluded by contact with the inner surface of the bleb capsule. A 22 gauge needle is used to form a microkeratome as previously described and a tapered incision made in the fibrovascular bleb capsule to allow the tube to be pushed into the cavity. Following this procedure a preformed bleb lining forms around the second plate and additional drainage of aqueous starts automatically when the vicryl suture dissolves. 2. Thinning of the tissues over the tube: Late thinning of the conjunctival tissues covering the drainage tube is managed by raising a flap of conjunctiva and placing a piece of donor sclera over the tube. 3. Late migration of the tube in the anterior chamber: The tissues of growing eyes of young infants and eyes with chronic uveitis are unusually soft and may allow slow displacement of the tube from its original position in the AC. The tube’s position should be routinely noted and any slow displacement in a direction that threatens contact between the free end of the tube and the cornea should be addressed. The technique for re-siting the tube consists of raising a fornix based flap of conjunctiva and Tenon’s tissue to give access to the tube between the episcleral plate and the limbus. A careful longitudinal incision of the connective tissue sheath around the tube is made. This allows the tube to be grasped by a fine pair of forceps and withdrawn from the AC. A

The Use of Molteno Implants to Treat Complex Cases of Glaucoma mattress suture of 7.0 silk is placed and tied tightly to occlude the tube track into the AC. After reforming the AC a suitable lamellar scleral flap is raised and the tube re-inserted into the AC via an appropriately placed self-sealing incision. The tube is then covered with donor sclera and the conjunctival flap replaced.

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postoperative course was uneventful and all hypotensive medication discontinued within 6 months of operation. During the 10 years since operation the IOP has remained within normal limits and the visual acuity has recovered to 6/6 (Figs 7.44 to 7.46).

ILLUSTRATIVE CASES Special Considerations for Certain Groups of Cases Buphthalmos Implants give outstanding results when used as a primary procedure in cases of buphthalmos associated with Sturge-Weber syndrome, neurofibromatosis, congenital cataract surgery and severe cases of primary hydrophthalmia.10 Similar short-term results can be obtained in cases that have undergone many previous procedures however, the long-term consequences of multiple operations such as low grade inflammation, retinal detachment, band keratopathy and corneal decompensation sooner or later destroy the patient’s vision despite adequate control of IOP. Thus implants should be used where alternative procedures do not carry a good long-term prognosis. With children donor sclera is used to provide long-term cover for the tube and constant vigilance is required to prevent the development of amblyopia in otherwise successful cases. When implants are used in cases of Sturge-Weber syndrome the aqueous is absorbed into abnormal angiomatous vessels that have a higher intravascular pressure than normal capillaries causing the IOP to stabilize at 20 mm Hg. Attempts to lower this pressure by adrenergic agents give erratic results and such cases are best managed by accepting an IOP at the upper limit of the normal range. • Illustrative case of simple buphthalmos: Case 1: An 11-year-old girl with simple buphthalmos, presented with an IOP of 60 mm Hg, advanced cupping and a visual acuity of 6/60! She was commenced on 3 hypotensive medications which reduced the IOP to 30 mm Hg. Eleven weeks later a double plate Molteno implant was inserted using the vicryl tie technique and donor sclera. The

Fig. 7.44: Right eye of case 1 showing blebs over double plate Molteno implant and donor sclera 9 years after insertion

Fig. 7.45: Right eye of case 1 showing increased size of draining bleb 9 years after insertion

• Illustrative case of buphthalmos associated with Sturge-Weber syndrome: Case 2: An 8-month-old infant, presented with bilateral buphthalmos associated with bilateral Sturge-Weber syndrome and cerebral involvement causing epilepsy. Preoperatively the IOPs were 32 and 37 mm Hg and the horizontal corneal diameters 14 and 13 mm respectively. Single plate Molteno implants were inserted using the vicryl tie technique and donor sclera. The postoperative courses were smooth although examination under

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Atlas of Glaucoma Surgery The visual function of Case 2 is limited as a result of cerebral involvement by the hemangiomas. Interestingly both eyes, 8 diopters myopic at the time of operation, had become emmetropic by the time he was 2.5 years old (Figs 7.47 and 7.48A and B).

Fig. 7.46: Graph of IOP of case 1 over 10 years since insertion of double plate Molteno implant

anesthetic showed diffuse peripheral choroidal detachments in both eyes. These resolved spontaneously and the IOPs remained in the normal range without medication, although rising slowly for the next 7 years until recorded at 27 and 24 mm Hg after hospitalization for control of epileptic seizures. Over the next 3 months the IOPs varied between 18 and 25 mm Hg on topical adrenaline. Additional single plate Molteno implants were added to the existing plates using a vicryl tie to occlude the tube and delay drainage of aqueous from the existing bleb into the preformed bleb around the additional plates as previously described. These operations were uncomplicated and the IOPs returned to 16 to 19 mm Hg where they have remained on no treatment. After this episode his mother mentioned that he was being treated for sinusitis during the time he was hospitalized for control of his epilepsy when the IOP was raised. The possible significance of this only became apparent when a similar history of increase in IOP associated with sinusitis was later obtained from another case of buphthalmos associated with Sturge-Weber syndrome. These histories suggest that before treating any elevation of IOP in patients with Sturge-Weber syndrome after drainage by implant it is prudent to investigate the presence of any local process that might be causing elevation of the venous pressure in the angiomatous tissue.

Fig. 7.47: Case 2-6 months after insertion of single plate Molteno implants for bilateral Sturge- Weber syndrome

A

B Figs 7.48A and B: IOP curves of case 2 (A) right (b) left

Combined Cataract and Glaucoma Surgery It is very important to perform this operation in the correct sequence, which is:

The Use of Molteno Implants to Treat Complex Cases of Glaucoma a. The Molteno implant is sutured to the sclera, the tube occluded, trimmed and tucked away under the lamellar scleral flap. b. The cataract is extracted and the intraocular lens placed. c. When the cataract operation is complete the tube is inserted into the AC and the scleral and conjunctival flaps replaced. • Illustrative case of combined cataract and glaucoma surgery: Case 3: A 72-year-old male, had primary open angle glaucoma in his right only eye (the left eye having been lost to neovascular glaucoma) with preoperative IOPs of 20 to 31 mm Hg on 2 hypotensive medications, a cup-disk ratio of 0.9 and a superior arcuate scotoma extending to within 3o of fixation. His visual acuity was reduced to 6/18 due to lens opacities. A double plate Molteno implant was inserted using the vicryl tie technique combined with an extracapsular cataract extraction with posterior chamber intraocular lens. The postoperative course was smooth. He received reducing doses of acetazolamide and timolol for the first year after which the acetazolamide was continued until the IOP stabilized at 10 to 12 mm Hg 7 years after the operation. Fifteen years after operation he has an IOP of 12 mm Hg on no treatment, a visual acuity of 6/12 and his visual field shows no significant deterioration since operation (Figs 7.49 and 7.50).

Fig. 7.49: Right eye of case 3—15 years after combined operation for cataract extraction and insertion of Molteno implant when the IOP was 12 mm Hg on no treatment

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Fig. 7.50: IOP curve of case 3

Neovascular Glaucoma It is possible to salvage useful vision in cases of acute neovascular glaucoma by immediate reduction of IOP. This involves the insertion of an implant with immediate drainage of aqueous to reduce the IOP to normal levels to clear the ocular media and restore circulation through the diseased retinal vessels. The operation is followed by urgent photocoagulation of the underlying retinal disease combined with active treatment of the underlying vascular and general disease states. In cases where a double plate implant is used the connecting tube between the plates is occluded by a 5.0 vicryl ligature. • Illustrative case of neovascular glaucoma: Case 4: A 59-year-old male with type 2 diabetes treated by diet and glibenclamide who had recently undergone cataract extraction in both eyes, presented with an elevated IOP in his right eye due to iris neovascularization. This was treated by argon laser photocoagulation and trabeculectomy. His left eye was treated by argon laser photocoagulation at the same time. Two months later his IOPs were 46 and 34 mm Hg respectively with iris new vessels bilaterally. Both eyes were treated by insertion of single plate Molteno implants with immediate drainage of aqueous. The postoperative courses were uneventful. The left visual acuity was 6/24. He was prescribed oral prednisone, flufenamic acid 200 mg*** and colchicine for 6 weeks after operation to reduce intraocular inflammation and bleb fibrosis. These procedures were followed by photocoagulation to the left eye. The IOP was well ***Flufenamic acid 200 mg tds is equivalent to diclofenac 50 mg tds

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controlled in the right eye but the eye had only light perception, remained uncomfortable and became phthisical 15 months after operation. The vision in the left eye gradually improved to reach 6/ 18 2 years after operation. His IOP was controlled with timolol and a small dose (125 mg bd) of acetazolamide for 3 years until a spontaneous vitreous hemorrhage occurred. This was associated with elevation of the IOP to 25 mm Hg which fell again to 16 to 17 mm Hg with further photocoagulation and clearing of the vitreous hemorrhage. The vision was maintained at 6/18 with good control of IOP until he suffered a cerebrovascular accident which produced a right sided hemianopia and reduced his vision to 3/60 six weeks before death. This case demonstrates that immediate drainage of cases of neovascular glaucoma, combined with photocoagulation and general medical measures, can give surprisingly good visual results (Figs 7.51 to 7.54).

Fig. 7.52: Left eye of case 4 showing white quiet eye 6.5 years after insertion of implant

Fig. 7.53: Fundus of left eye of case 4 showing temporal half of the pale optic disk and extensive photocoagulation 6 years after insertion of implant

Fig. 7.51: Operative view of insertion of single plate Molteno implant into a case of acute neovascular glaucoma

• Illustrative case of uveitic glaucoma: Case 5: A 27year-old pregnant woman with Still’s disease, presented with an elevated IOP in her right aphakic only eye. She had developed uveitis in both eyes at 5 years of age and had lost her left eye. Although the uveitis was only minimally active her right eye had been treated by three drainage operations, two cataract extractions and one 180o cyclocryotherapy. Preoperatively her IOP varied between 24 and 50

Fig. 7.54: Phthisical right eye of case 4—15 months after trabeculectomy 2 months later followed by implant and left eye treated by primary implant

mm Hg on 3 medications and oral glycerol and the cup-disk ratio was 0.9. She was treated by insertion of a double plate Molteno implant without

The Use of Molteno Implants to Treat Complex Cases of Glaucoma connecting the tube to the AC combined with temporary control of IOP by reopening one of the old trabeculectomy sites (This was before the introduction of the vicryl tie/Sherwood slit technique). Four months later the IOP was 29 mm Hg on full treatment and the drainage tube was inserted into the AC. The postoperative course was uncomplicated and she was treated by systemic prednisone, a non-steroidal anti-inflammatory agent and colchicine for 4 weeks to reduce intraocular inflammation and bleb fibrosis. Her IOP on acetazolamide 125 mg bd was 10 mm Hg, and 24 mm Hg on no treatment. She has been maintained on 30 to 60 mg bd acetazolamide for the last 23 years. The tendency to intraocular inflammation has decreased over this period. Her visual acuity at operation was 6/9, falling to 6/18 shortly after operation and then gradually declined to 6/36 at 23 years. Her visual field has shown no change over this time (Figs 7.55 and 7.56). • Illustrative case of traumatic glaucoma: Case 6: A 57-year-old man, presented after being hit in the left eye by a cricket ball. Examination revealed a posteriorly dislocated lens, edematous cornea and an IOP of 33 mm Hg. He refused admission for a week. After admission a double plate Molteno implant was inserted, his lens extracted, a vitrectomy performed and the tube inserted into the posterior chamber. Postoperatively he developed a 1/4 hyphema which resolved spontaneously but otherwise the course was smooth. His cornea remained opaque, eventually calcified, became uncomfortable 15 years later and was treated by a penetrating keratoplasty. The subsequent course was smooth and 23 years after operation; he has an IOP of 8 mm Hg on no treatment with a normal disk and retina but reduced visual acuity of 2/60 as a result of traumatic macular scarring (Fig. 7.57).

RESULTS Primary Open Angle Glaucoma The introduction of the delayed drainage technique for inserting Molteno implants has led to their being used in less severe cases of primary open angle glaucoma where there are additional local and general risk factors. It is of

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Fig. 7.55: Aphakic right eye of case 5—23 years after insertion of double plate Molteno implant in a case uveitis associated with juvenile rheumatoid arthritis

Fig. 7.56: IOP curve of case 5

Fig. 7.57: Left eye of case 6—23 years after insertion of double plate Molteno implant showing clear corneal graft and end of tube visible at 11 o’clock. This tube was inserted via the pars plana

interest to compare the results obtained from cases drained by Molteno implants with those of similar cases (but fewer risk factors) drained by trabeculectomy over the same period at Dunedin Hospital.

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Control of Intraocular Pressure Overall results of trabeculectomy compared to implants for primary glaucoma are as follows: 1. All trabeculectomies compared with all implant operations: Between 1986 and 2003 754 drainage operations were carried out on cases of primary glaucoma at Dunedin Hospital. Five hundred and thirty-one were trabeculectomies carried out on relatively uncomplicated cases and 223 were insertion of Molteno implants in eyes with additional risk factors. The two groups were comparable with regard to preoperative IOP and hypotensive medication use. The mean postoperative IOP was slightly lower in the implant group throughout follow-up compared with the trabeculectomy group. The proportion on hypotensive medication was higher 1 year after operation in the implant group but this fell progressively with increasing follow-up. In the case of trabeculectomies the proportion on hypotensive medication was low 1 year after operation but increased progressively to approach that of the implants at 5 and 10 years after operation. The IOP of all cases in the implant group remains controlled whereas 40 (8%) of trabeculectomy cases have failed so far. It is informative to consider the results of trabeculectomy and Molteno implants in selected subgroups of primary glaucoma (Tables 7.1 and 7.2). 2. Trabeculectomy as first operation compared to implant as first operation: The mean postoperative IOP was slightly lower in the case of Molteno implants at 1 year after operation while the proportion of cases on hypotensive medication was slightly higher in the case of implants. However, with ongoing follow-up the mean IOP of the implant group remained slightly below that of the trabeculectomies and the proportion of cases on hypotensive medication equalized by 5 years after operation and was slightly lower in the case of implants at 10 years. The IOP of all cases of the implant group remains controlled whereas 32/510 (6%) of the trabeculectomy group failed (Tables 7.1 and 7.2).

3. Trabeculectomy af ter failed trabeculectomy compared to implant after failed trabeculectomy: The mean postoperative IOP after Molteno implants was substantially lower than that after trabeculectomy and this difference was maintained. There were no failures in the implant group compared with 8/21 (38%) of the trabeculectomy group (Tables 7.1 and 7.2). 4. Phacotrabeculectomy compared with implant combined with cataract extraction: The mean postoperative IOP after Molteno implants was substantially lower and this difference was maintained. There were no failures in the implant group compared with 7/109 (6%) of the trabeculectomy group (Tables 7.1 and 7.2). 5. Trabeculectomy and later cataract extraction compared with implant and later cataract extraction: The mean postoperative IOP was similar in the two groups. There were no failures in the implant group compared with 22/122 (18%) of the trabeculectomy group (Tables 7.1 and 7.2). Overall the long-term results of Molteno implants in these cases with primary glaucoma are superior to those of trabeculectomy. The differences are particularly marked where previous trabeculectomies have failed, in combined operations and after subsequent cataract extraction.

Secondary Glaucomas In all groups the overall prognosis for control of IOP in visually useful eyes is generally good with failure occurring in terminal eyes, eyes that have undergone multiple previous operations and cases of uveitis in which the underlying disease cannot be controlled. The outcomes of cases of buphthalmos, juvenile glaucoma, traumatic glaucoma, uveitic glaucoma, secondary glaucoma following previous intraocular surgery and neovascular glaucoma treated by insertion of Molteno implants with respect to IOP control and hypotensive medication use are presented in Tables 7.3 and 7.4.

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Table 7.1: Status of cases of primary open angle glaucoma treated by a trabeculectomy or Molteno implant at Dunedin Hospital between 1986 and 2003 as of January 2004 Number

IOP control (IOP = 5 - 21 mm Hg) No medication

Trabeculectomy as first or subsequent operation* Implant as first operation or following trabeculectomy* Trabeculectomy as first operation Implant as first operation Trabeculectomy after failed trabeculectomy Implant after failed trabeculectomy Phacotrabeculectomy Phaco/implant Trabeculectomy and later cataract extraction Implant and later cataract extraction

531 223 510 182 21 41 109 51 122 48

366 (69%) 153 (69%) 357 (70%) 135 (74%) 10 (48%) 20 (49%) 64 (59%) 39 (77%) 74 (61%) 34 (71%)

Fail

With medication 125 (24%) 70 (31%) 122 (24%) 47 (26%) 3 (14%) 21 (51%) 38 (35%) 12 (24%) 26 (21%) (%)

40 (8%) 0 32 (6%) 0 8 (38%) 0 7 (6%) 0 22 (18%) 0

* Includes cases in the respective subsets below

Table 7.2: Mean IOP and hypotensive medication use of cases of primary open angle glaucoma treated by trabeculectomy or Molteno implant at Dunedin Hospital between 1986 and 2003 Number Mean IOP (standard deviation) in mm Hg Mean number of Hypotensive Medications Preoperative Trabeculectomy as first or subsequent operation* Implant as first operation or following trabeculectomy* Trabeculectomy as first operation Implant as first operation Trabeculectomy after trabeculectomy failure Implant after failed trabeculectomy Phacotrabeculectomy Phaco/implant Trabeculectomy and later cataract extraction Implant and later cataract extraction

* Includes cases in the respective subsets below

N=531 23.7 (6.6) 1.90 N=223 24.0 (6.5) 1.98 N=510 23.7 (6.5) 1.89 N= 182 23.9 (6.6) 1.96 N= 21 25.9 (8.7) 2.10 N= 41 24.6 (6.0) 2.07 N = 109 21.0 (6.0) 1.66 N= 51 21.7 (6.2) 1.87 N = 122 24.9 (5.6) 1.95 N = 48 23.8 (7.2) 1.75

Years postoperatively 1

2

5

10

15

N=445 15.0 (3.5) 0.23 N=182 14.4 (2.9) 0.59 N=431 15.0 (3.5) 0.21 N= 147 14.4 (2.8) 0.57 N=14 18.4 (4.7) 0.72 N= 35 14.7 (3.3) 0.73 N= 89 16.2 (3.2) 0.3 N= 47 14.0 (2.3) 0.51 N= 117 14.5 (3.7) 0.21 N= 46 14.8 (2.7) 0.48

N=377 15.0 (3.4) 0.29 N=160 14.2 (3.2) 0.54 N=365 15.0 (3.3) 0.27 N= 126 14.0 (2.8) 0.49 N=11 16.2 (5.4) 0.97 N= 34 14.8 (4.3) 0.72 N= 64 16.2 (3.6) 0.42 N= 38 13.5 (2.6) 0.48 N= 115 14.9 (3.8) 0.24 N= 43 14.6 (3.0) 0.39

N=224 14.9 (3.2) 0.42 N=87 14.2 (3.1) 0.48 N=216 14.8 (3.1) 0.38 N= 63 14.2 (2.9) 0.35 N= 9 16.7 (4.7) 1.22 N= 24 14.4 (3.7) 0.81 N= 28 15.2 (3.6) 0.57 N= 21 13.1 (2.9) 0.52 N= 86 15.3 (3.11) 0.43 N= 27 14.6 (3.6) 0.52

N=90 15.4 (4.2) 0.45 N=27 13.1 (3.3) 0.50 N=87 15.3 (4.3) 0.45 N=16 12.2 (2.5) 0.40 N= 5 15.7 (1.0) 0.80 N=11 14.3 (4.0) 0.66 N= 6 19.5 (7.0) 0.85 N=11 12.0 (2.3) 0.36 N= 47 14.8 (3.4) 0.30 N= 8 14.9 (4.6) 0.68

N=14 14.5 (4.1) 0.96 N=2 10.3 (0.4) 1.00 N=12 14.1 (4.3) 0.87 — N=5 16.1 (2.4) 0.80 N=2 10.3 (0.4) 1.00 — — N=18 14.2 (3.2) 0.37 —

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Table 7.3: Status of cases of buphthalmos, juvenile glaucoma, traumatic glaucoma, uveitic glaucoma, secondary glaucoma and neovascular glaucoma treated by Molteno implant at Dunedin Hospital between 1977 and 2003 as of January 2004 Number

Buphthalmos Juvenile glaucoma Traumatic glaucoma Uveitic glaucoma Secondary glaucoma Neovascular glaucoma

IOP control (IOP = 5-21 mm Hg)

49 24 43 49 74 148

Fail

No medication

With medication

26 (53%) 9 (38%) 31 (72%) 33 (67%) 44 (60%) 40 (27%)

16 (33%) 11 (46%) 7 (16%) 11 (23%) 21 (28%) 39 (26%)

7 (14%) 4 (17%) 5 (12%) 5 (10%) 9 (12%) 69 (47%)

Table 7.4: Mean IOP and hypotensive medication use of cases of buphthalmos, juvenile glaucoma, traumatic glaucoma, uveitic glaucoma, secondary glaucoma and neovascular glaucoma treated by Molteno implant at Dunedin Hospital between 1977 and 2003 Number Mean IOP (standard deviation) in mm Hg Mean number of Hypotensive Medications Preoperative Buphthalmos Juvenile glaucoma Traumatic glaucoma Uveitic glaucoma Secondary glaucoma Neovascular glaucoma

N=49 32.9 (12.5) 1.67 N=24 27.8 (9.7) 2.00 N=43 32.7 (13.6) 1.86 N=49 31.4 (13.4) 1.87 N=74 31.2 (10.9) 2.02 N=148 40.0 (12.8) 1.30

Years postoperatively 1

2

5

10

15

20

N=43 15.0 (4.3) 0.40 N=20 17.1 (4.8) 0.81 N=35 15.9 (3.3) 0.44 N=43 15.9 (5.2) 0.58 N=65 16.4 (5.5) 0.68 N=100 19.6 (9.3) 0.77

N=42 15.2 (4.4) 0.38 N=19 17.1 (4.7) 0.58 N=34 15.4 (3.9) 0.31 N=39 15.5 (6.1) 0.46 N=60 15.9 (5.5) 0.53 N=75 19.1 (10.0) 0.72

N=36 15.5 (4.1) 0.39 N=18 16.3 (4.3) 0.77 N=29 15.5 (3.5) 0.36 N=29 14.8 (4.4) 0.52 N=37 17.4 (7.6) 0.65 N= 29 21.9 (11.0) 0.78

N=27 16.6 (3.5) 0.68 N=13 16.2 (2.6) 0.99 N=19 15.0 (4.4) 0.14 N=17 15.4 (4.6) 0.47 N=21 16.5 (4.1) 0.50 N=9 26.8 (10.7) 0.52

N=19 17.3 (3.7) 0.76 N=9 18.4 (8.8) 1.11 N=12 15.4 (3.8) 0.08 N=7 13.4 (5.5) 0.14 N=13 18.6 (6.9) 0.98 N=2 12.0 (5.7) 0.25

N=8 16.7 (3.0) 0.87 N=4 N=4 1.07 N=9 13.8 (4.4) 0.33 N=3 10.5 (4.9) 0.33 N=3 18.8 (13.3) 0.16 —

CONCLUSIONS The current surgical techniques for inserting Molteno implants provide very safe and highly effective ways of preventing postoperative hypotony and reducing the IOP to normal levels in most types of glaucoma. The only groups in which results are uncertain are very advanced cases that have undergone many previous operations, cases of chronic uveitis that remain active despite treatment and cases of neovascular glaucoma in which the underlying vascular disease is not amenable to treatment.

REFERENCES 1. Molteno ACB, Fucik M, Dempster AG, Bevin TH. Otago glaucoma surgery outcome study. Factors controlling capsule fibrosis around Molteno implants with histopathological correlation. Ophthalmology 2003;110:2196-2210. 2. Molteno ACB. New implant for drainage in glaucoma. Clinical trial. Br J Ophthalmol 1969;53:606-15. 3. Molteno ACB, Dempster AG. Methods of controlling bleb fibrosis around draining implants. In. Mills KB (Ed): Fourth International Symposium of the Northern Eye Institute. Manchester: Pergammon Press, 1988. 4. Vote B, Fuller JR, Bevin TH, Molteno ACB. Systemic antiinflammatory fibrosis suppression in threatened trabeculectomy failure. Clin Exp Ophthalmol 2004;32:81-6. 5. Fuller JR, Bevin TH, Molteno ACB, et al. Anti-inflammatory fibrosis suppression in threatened trabeculectomy bleb failure produces good

The Use of Molteno Implants to Treat Complex Cases of Glaucoma 6. 7. 8. 9. 10. 11.

long-term control of intraocular pressure without risk of sight threatening complications. Br J Ophthalmol 2002;86:1352-5. Molteno ACB, van Biljon G, Ancker E. Two-stage insertion of glaucoma drainage implants. Trans Ophthalmol Soc N Z 1979;31:1726. Molteno ACB, Polkinghorne PJ, Bowbyes JA. The vicryl tie technique for inserting a draining implant in the treatment of secondary glaucoma. Aust NZJ Ophthalmol 1986;14:343-54. Sherwood MB, Smith MF. Prevention of early hypotony associated with Molteno implants by a new occluding stent technique. Ophthalmology 1993;100:85-90. Molteno ACB, Ancker E, Van Biljon G. Surgical technique for advanced juvenile glaucoma. Arch Ophthalmol 1984;102:51-7. Cunliffe IA, Molteno ACB. Long-term follow-up of Molteno drains used in the treatment of glaucoma presenting in childhood. Eye 1998;12:379-85. Molteno ACB, Whittaker KW, Bevin TH, Herbison P. Otago glaucoma surgery outcome study. Long-term results of cataract extraction

12. 13. 14.

15. 16. 17.

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combined with Molteno implant insertion or trabeculectomy in primary glaucoma. Br J Ophthalmol 2004;88:32-5. Fuller JR, Bevin TH, Molteno ACB. Long-term follow-up of traumatic glaucoma treated with Molteno implants. Ophthalmology 2001;108:1796-1800. Molteno ACB, Sayawat N, Herbison P. Otago glaucoma surgery outcome study. Long-term results of uveitis with secondary glaucoma drained by Molteno implants. Ophthalmology 2001;108:605-13. Molteno ACB, Bevin TH, Herbison P, Houliston MJ. Otago glaucoma surgery outcome study. Long-term follow-up of cases of primary glaucoma with additional risk factors drained by Molteno implants. Ophthalmology 2001;108:2193-2200. Molteno ACB. The dual chamber single plate implant—its use in neovascular glaucoma. Aust NZJ Ophthmol 1990;18:431-6. Molteno ACB, Haddad PJ. The visual outcome in cases of neovascular glaucoma. Aust NZJ Ophthalmol 1985;13:329-35. Parrish R, Minckler D. “Late endophthalmitis”—filtering surgery time bomb? Ophthalmology 1986;103:1167-8.

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Atlas of Glaucoma Surgery André Mermoud

8 Nonpenetrating Surgery

INTRODUCTION In order to obtain a physiological per- and postoperative IOP, the idea of nonpenetrating glaucoma surgery (NPGS) was to create a reproducible postoperative outflow resistance with the trabeculo-Descemet’s membrane. Several techniques of nonpenetrating filtering surgeries based on the pioneer work of Krasnov’s sinusotomy have been described (Figs 8.1 and 8.2). In primary and most cases of secondary open-angle glaucoma, the main aqueous outflow resistance is thought to be located at the level of the juxtacanalicular trabeculum and the inner wall of Schlemm’s canal. These two anatomical structures can be removed. This technique has been called ab externo trabeculectomy. It was first proposed by Delage in 1978, and later by Zimmermann in 1984 and Arenas in 1991 (Fig. 8.3). Another way to increase the aqueous outflow in a patient with restricted posterior trabeculum outflow is to remove the corneal stroma behind the anterior trabeculum and Descemet’s membrane (Fig. 8.4). This has been called deep sclerectomy and was first described by Fyodorov and Kozlov and later by Stegmann (viscocanalostomy). The most common techniques used today are deep sclerectomy and viscocanalostomy. This chapter will describe these two techniques.

DEEP SCLERECTOMY In deep sclerectomy, the main aqueous outflow occurs at the level of the anterior trabeculum and the Descemet’s membrane (Fig. 8.4). This has been shown by Vaudaux et al in an ex vivo model of deep sclerectomy (Vaudaux). They have also reported that the outflow facility increased from 0.19 ± 0.03 to 24.5 ± 12.6 μl/min/mm Hg. To

enhance further the filtration after a deep sclerectomy, the removal of the inner wall of the Schlemm’s canal can be performed to increase the filtration through the posterior trabeculum. To keep the intrascleral space created patent, an implant may be used. Kozlov proposed a collagen implant which resorbs itself within 6 to 9 months (Chiou). Stegmann uses high viscosity hyaluronic acid; Sourdille and Dahan are using reticulated hyaluronic acid and Hema implants respectively. Kozlov et al have reported an 85 percent success rate, but no information regarding success criteria or follow-up is available (Kozlov). Long-term results of deep sclerectomy with collagen implant are encouraging. With a mean follow up of 64 ± 20 months, Shaarawy et al reported a mean IOP of 11 ± mm Hg with a complete success rate of 57 percent and a qualified success rate of 91 percent (Shaarawy).

VISCOCANALOSTOMY The hypothetic mechanism of filtration in viscocanalostomy is different from those described in other nonpenetrating filtering surgeries. Stegmann thinks that the aqueous humor filters trough the trabeculo-Descemet’s membrane to the scleral space like in deep sclerectomy, but that it does not form a subconjunctival filtering bleb since the superficial scleral flap is tightly closed with numerous nylon 10/0 sutures. From the scleral space, the aqueous humor is supposed to reach the Schlemm’s canal which is opened on either side of the deep sclerectomy, and then flows into the aqueous episcleral veins. Until now no scientific study has been able to confirm this hypothesis, and in our hands, patients who underwent viscocanalostomy presented in 50 percent of the cases a subconjunctival filtering bleb. The long-

Nonpenetrating Surgery

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Fig. 8.3: Schematic representation of abexterno trabeculectomy. A deep sclerectomy unroofing Schlemm’s canal is covered by a superficial scleral flap. The Schlemm’s canal inner wall and juxtacanalicular trabeculum are removed

Fig. 8.4: Schematic representation of deep sclerectomy. Under a superficial scleral flap, a deep corneosclerectomy unroofing Schlemm’s canal is performed. Corneal tissues behind the anterior trabeculum and Descemet’s membrane are removed. Removing of the inner wall of the Schlemm’s canal can also be performed, but is not represented on the Figure

Figs 8.1 and 8.2: Schematic representations of sinusotomy. Schlemm’s canal is unroofed. There is no superficial scleral flap to cover the sclerectomy. Inner wall of Schlemm’s canal is untouched

term follow-up study of viscocanalostomy is reported to be satisfactory (Stegmann). All types of nonpenetrating glaucoma surgeries present in common a more predictable postoperative IOP (between 5 and 10 mm Hg on the first postoperative

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day). This is due to the outflow resistance membrane left in situ peroperatively (posterior trabeculum after ab externo trabeculectomy, trabeculo-Descemet’s membrane after deep sclerectomy and viscocanalostomy). The nonperforation of the globe offers several advantages which are enlisted in Table 8.1. The mechanisms of aqueous resorption are probably multiple. Table 8.1: Advantages and disadvantages of nonpenetrating glaucoma surgeries Advantages

Disadvantages

Predictable postoperative IOP More difficult surgery Low rate of postoperative Prolonged surgery time during complications learning phase Easy ambulatory care Need Nd-Yag goniopuncture Rapid visual acuity recovery Increased cost (implant) No postoperative inflammation Not applicable in closed angle No cataract induced Glaucoma More diffused and shallow filtering blebs Limited risk for secondary endophthalmitis Safe surgery for end-stage glaucoma Easy postoperative follow-up Closed globe surgery Decreased risk for malignant glaucoma

1. There is in 50 percent of cases a subconjunctival filtering bleb which appears usually more diffuse and shallower than after trabeculectomy. 2. There is probably an increased uveoscleral outflow through the thin remaining scleral layer in the bed of the deep sclerectomy (Kazakova). 3. Stegmann believes that the aqueous humor reaches from the scleral space the Schlemm’s canal and subsequently the aqueous veins. 4. There are evidence in animal models that there is a production of new aqueous drainage veins in the scleral space months after deep sclerectomy (Delarive). This intrascleral filtering bleb has also been showed by Kazakova using an UBM in successful human deep sclerectomy (Kazakova).

SURGICAL TECHNIQUE When performing nonpenetrating glaucoma surgery the surgeon looks at two aims: one to create the trabeculoDescemet’s membrane which will allow a reproducible postoperative outflow resistance, thus decreasing the immediate postoperative complication rate, and two, to

create an intrascleral filtering bleb to decrease the amount of subconjunctival bleb and therefore the potential risk of late hypotony and bleb-related endophthalmitis. According to medium and long-term studies of NPGS, more than 50 percent of patients need a Nd-Yag laser goniopuncture, it is therefore of paramount importance to create a thin and large Descemet’s window. To create a functional intrascleral filtering bleb, a large and deep sclerectomy should be perfomed. Furthermore, to enable the maintenance of the intrascleral space, several implants have been proposed to avoid the collapse of the created space. This chapter will help the reader to understand how to dissect the different tissues in order to create a big intrascleral filtering bleb, to find Schlemm’s canal, to dissect a correct trabeculo-Descemet’s window, to place an intrascleral space maintainer using an implant and to use antimetabilites when needed. All types of anesthesia have been used successfully for NPGS. We recommend injecting the smallest amount of peri-or retrobulbar anesthesia in order to adequately rotate the glob for the deep sclerectomy dissection. Three to 4 ml of a solution of bupivacaine 0.75 percent, xilocaine 4 percent and hyaluronidase 50 U are usually sufficient for a successful local anesthesia. Topical and subconjunctival anesthesia are also possible and have been performed successfully in selected cases. A superior rectus muscle or an intracorneal traction suture is placed and the eyeball is rotated to expose the site of the deep sclerectomy (usually the superior quadrant). The conjunctiva is opened either at the limbus or in the fornix. The sclera is exposed and moderate hemostasis is performed using a wet field electrocoagulation cautery. A superficial scleral flap measuring 5 by 5 mm is dissected including 1/3rd of the sclera thickness (about 300 mm) (Fig. 8.5). This scleral flap is dissected 1 to 1.5 mm into clear cornea (Fig. 8.6). In patients with high risk of scleroconjonctival scar formation, a sponge soaked in mitomycin-C 0.2 percent is placed for 45 to 60 seconds in the scleral bed and subconjunctival space (Fig. 8.7). After removal of the sponge, the site is washed with balanced salt solution (20 to 30 ml).

Nonpenetrating Surgery

Fig. 8.5: Creation of a superficial 5 × 5 mm scleral flap

Fig. 8.6: The superficial scleral flap is 1/3rd of the scleral thickness and is prolonged 1 to 1.5 mm into clear cornea

Fig. 8.7: In patients at risk for post-operative fibrosis, a sponge soked in mitomycin-C is placed in the surgical site and then washed with balanced salt solution

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At that stage of the operation, the microscope magnification is increased. Simultaneously, the microscope light is switch on maximum illumination which is essential for the fine dissection. The two lateral and the posterior deep scleral incisions are made using a diamond blade (0.5 × 3 mm, Huco vision, St-Blaise, Switzerland). The sclera is cut almost 95 percent of his thickness (Fig. 8.8). Complete perforation of sclera in some part of the incision offers the view of the ciliary body in the anterior part, or the choroid in the posterior part of the scleral dissection (Fig. 8.9). This is a good landmark to assess the total scleral thickness. This maneuver has never been followed by any complication in our experience. The deep scleral flap is then horizontally dissected using a crescent ruby blade (2 mm bevelled up angled, Huco vision, St-Blaise, Switzerland) (Fig. 8.10). The remaining scleral layer should be as thin as possible (Fig. 8.11). Deep sclerectomy is preferably started in the posterior part of the deep scleral flap. This helps avoiding anterior chamber perforation. In the posterior part of the deep flap, the scleral fibers are layed in multiple directions. More anteriorly, the scleral fibers are more regular forming a ligament parallel to the limbus, corresponding to the scleral spur. Schlemm’s canal is then just anterior to this structure. The scleral spur is an excellent landmark for Schlemm’s canal identification (Fig. 8.12). Schlemm’s canal is opened (Fig. 8.13) and the sclerocorneal dissection is prolonged anteriorly for 1 to 1.5 mm in order to remove the sclerocorneal tissue behind anterior trabeculum and Descemet’s membrane. This part of the surgery is difficult because there is a high risk of anterior chamber perforation. To avoid a perforation, the anterior tabeculum and Descemet’s membrane can be gently detached using a sponge, a spatula or a blunt metallic blade (Fig. 8.14). Once the Descemet’s membrane detached, two lateral radial cut are made to expose the Descemet’s window (Fig. 8.15). When the anterior dissection is completed, the deep scleral flap is removed by cutting anteriorly first with the diamond blade (Fig. 8.16) and then using a Galan scissor (Fig. 8.17) (length 55 mm, curved and blunt blade). At that stage of the procedure, there should be a nice percolation of aqueous through the remaining trabeculo-Descemet’s membrane.

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Fig. 8.8: The deep sclerctomy is delineated with a diamon blade. The deep sclerectomy measures 4 × 4 mm and the sclera is dissected leaving about 5 percent of sclera over the chorriod and ciliary body

Fig. 8.10: The horizontal dissection is performed using a ruby blade

Fig. 8.11: The remaining scleral layer is very thin Fig. 8.9: Choroid or ciliary body view is a good landmark for the total scleral thickness and allow the surgeon to start the horizontal cut at he correct site

Since the main site of aqueous outflow resistance, in primary and probably other type of secondary openangle glaucoma, is thought to be at the juxtacanalicular trabeculum and Schlemm’s endothelium level this structure should be removed using a small blunt forceps (Fig. 8.18)(deep sclerectomy forceps 13,0 mm gaws, Huco vision SA, St-Blaise, Switzerland). This additional procedure has been called ab externo trabeculectomy. To peel the thin Schlemm’s endothelium and

juxtacanalicular trabeculum membrane, it is crucial to dry the exposed inner wall of Schlemm’s canal. When dried, the inner wall of Schlemm’s canal can be grabbed with the forceps (Fig. 8.19) and peeled easily by pulling on it. This maneuver is followed by another important percolation of aqueous through the posterior trabeculum. To avoid secondary collapse of the superficial flap, a space maintainer implant is placed in the scleral bed and secured with a single 10/0 nylon suture (Fig. 8.20). The superficial scleral flap is then closed and secured with two untied 10/0 nylon sutures (Fig. 8.21).

Nonpenetrating Surgery

Fig. 8.12: In the anterior part of the scleral bed, the scleral fibers are parralel to the limbus and represent the scleral spure. This is an excellent landmark to find Schlemm’s canal which is located just anterior to the scleral spure

Fig. 8.13: Opening of Schlemm’s canal. The canal is dark and contrast with the white scleral spure

The conjunctiva and Tenon’s capsule are closed with running 8/0 vicryl sutures (Fig. 8.22). The space maintainer implant may be in collagen and is processed from porcine scleral collagen as shown on Figure 8.20. It is increasing in volume after contact with aqueous and is slowly resorbed within 6 to 9 months leaving a scleral space for aqueous filtration (Chiou). The implant may also be done with high viscosity hyaluronic acid (Healon GV, Pharmacia, Upsalla,

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Fig. 8.14: Detachment of the anterior trabeculum and Descemet’s membrane using a sponge, a spatula or a blunt metalic blade

Fig. 8.15: Radial anterior deep sclerocorneal cut. This is performed either with a diamond blade or with the 11metalic blade turned upside-down to avoid a perforation of the Descemet’s membrane

Sweeden, corresponding to Stegmann’s technique also called viscocanalostomy). Reticulated hyaluronic acid may also be used (SK-gel implant, Corneal, Paris, France. This material will stay longer in the scleral dissection and may provide a better space formation. More recently, a Hema, nonresorbable implant is available (T-flux, IOLtech, La Rochelle, France) (Dahan).

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Fig. 8.16: The deep sclerocorneal flap is removed by first delineating the anterior cut with the diamond blade. This cut is performed as anterior as possible to create the bigest Descemet’s window as possible

Fig. 8.17: The flap is finally removed using Galan scissors

Fig. 8.18: Pealing off the inner endothelium of Schlemm’s canal and the juxtacanalicular trabeculum

Fig. 8.19: To better view the inner wall of Schlemm’s canal, a sponge is used to dry the site and to expose the anterior edge of the endothelium

Trabeculo-Descemet’s Perforation In the learning phase of NPGS, the surgeon may perforate quite often the thin membrane. It is important when the iris prolapsed through the perforation, to perform a peripheral iridectomy, followed by a tight superficial scleral flap closure with 6 to 8 nylon 10/0 suture (Fig. 8.23) the scleral space should be filled with high viscosity hyaluronic acid in order to reduce the aqueous humor outflow (Fig. 8.24). When the anterior chamber is shallow, viscoelastic may also be injected into the anterior chamber through a paracentesis. This

Fig. 8.20: A collagen implant is sutured in the scleral bed. This implant will serve as a space maintainer to create an intrascleral space for aqueous humor to filter

Nonpenetrating Surgery

Fig. 8.21: The superficial scleral flap is repositioned and sutured with two untied 10/0 nylon sutures

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Fig. 8.23: Tight superficial scleral flap closure with 8 nylon 10/ 0 sutures to increase the aqueous humor outflow resistance

Fig. 8.24: High viscosity hyaluronic acid may be injected into the scleral space to increase the aqueous humor outflow resistance Fig. 8.22: Closure of the Thenon’s capsule and the conjunctiva with a running 8/0 vicryl suture

injection should however be done carefully to avoid postoperative ocular hypertension. Combined surgery including phacoemulsification and NPGS are possible and are usually performed in two different sites. The deep sclerectomy is usually performed at the 12 o’clock position and the lens extraction is performed through a clear corneal temporal incision

POSTOPERATIVE MEDICATIONS Patients are treated first with topical corticosteroid and antibiotic for 2 to 3 weeks using 3 to 5 drops a day. This

is followed by nonsteroidal anti-inflammatory drugs for up to three months postoperatively using 3 drops a day. Goniopuncture with the Nd:YAG laser may be performed when there is an insufficient percolation of aqueous humor through the trabeculo-Descemet’s membrane. This is probably due to the lack of surgical dissection when the IOP rises early after the surgery. When goniopuncture is required at a later time (more than 9 months after initial surgery), low filtration is probably the result of fibrosis of the trabeculo-Descemet’s membrane, since goniopuncture resulted in increased filtration of aqueous humor and decreased IOP. The success rate of Nd: YAG laser goniopuncture is

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satisfactory, with an immediate reduction in mean IOP of 43.7 percent (from 22.2 ± 7.0 to 12.5 ± 5.8 mm Hg) (Mermoud). By opening the trabeculo-Descemet’s membrane, however, goniopuncture transformed a nonperforating filtration procedure into a perforating one.

BIBLIOGRAPHY 1. Ahmed II, Crandall AS. Viscocanalostomy vs trabeculetomy. Ophthalmology 2002; 109(3):411-2. 2. Ambresin A, Borruat FX, Mermoud A. Recurrent transient visual loss after deep sclerectomy. Arch Ophthalmol 2001;119(8):1213-5. 3. Ambresin A, Shaarawy T, Mermoud A. Deep sclerectomy with collagen implant in one eye compared with trabeculectomy in the other eye of the same patient. J Glaucoma 2002;11(3):214-20. 4. Arenas E. Trabeculectomy ab-externo. Highlights of Ophtalmology. 1991;19:59-66. 5. Argento C, Sanseau AC, Badoza D, Casiraghi J. Deep sclerectomy with a collagen implant using the excimer laser. J Cataract Refract Surg 2001; 27(4): 504-6. 6. Ates H, Andac K, Uretmen O. Non-penetrating deep sclerectomy and collagen implant surgery in glaucoma patients with advanced field loss. Int Ophthalmol 1999;23(3):123-8. 7. Ates H, Uretmen O, Andac K, et al. Deep sclerectomy with a nonabsorbable implant (T-Flux): preliminary results. Can J Ophthalmol 2003; 38(6):482-8. 8. Bauchiero L, Demarie A, Belli L, et al. Deep sclerectomy and viscocanalostomy: critical revision of the results obtained during the learning curve. Acta Ophthalmol Scand Suppl 2002;236:64-6. 9. Bylsma S. Nonpenetrating deep sclerectomy: collagen implant and viscocanalostomy procedures. Int Ophthalmol Clin 1999 Summer;39(3):103-19. 10. Carassa RG, Bettin P, Fiori M, et al. Viscocanalostomy versus trabeculectomy in white adults affected by open-angle glaucoma: a 2-year randomized, controlled trial. Ophthalmology. 2003;110(5):882-7. 11. Chiou AGY, Mermoud A, Hédiguer SEA, et al. Ultrasound biomicroscopy of eyes undergoing deep sclerectomy with collagen implant. Br J Ophthalmol 1997; 80:541-4. 12. Chiou AGY, Mermoud A, JP Underdahl, et al. An ultrasound biomicroscopic study of eyes after deep sclerectomy with collagen implant. Ophthalmology, 1998; 105:746-50. 13. Chiou AGY, Mermoud A, Jewelewicz D. Post-operative inflammation following deep sclerectomy with collagen implant versus standard trabeculectomy. Graefe’s Arch 1998; 236:539-96. 14. Chiou AGY, Mermoud A, Hédiguer SEA. Glaucome malin par blocage ciliare après sclérectomie profonde—Imagerie par biomicroscopie à ultrasons. Klin Monatsbl Augenheikld 1996;208:279-81. 15. Chiselita D. Non-penetrating deep sclerectomy versus trabeculectomy in primary open-angle glaucoma surgery. Eye. 2001;15 (Pt 2):197201. 16. Dahan E, Drusedau MU. Nonpenetrating filtration surgery for glaucoma: control by surgery only. J Cataract Refract Surg 2000; 26(5):695-70 17. Dahan E, Ravinet E, Ben-Simon GJ, et al. Comparison of the efficacy and longevity of nonpenetrating glaucoma surgery with and without a new, nonabsorbable hydrophilic implant. Ophthalmic Surg Lasers Imaging 2003;34(6):457-63. 18. Delarive T, Rossier A, Rossier S, et al. Aqueous dynamic and histological findings after deep sclerectomy with collagen implant in an animal model. Br J Ophthalmol 2003;87(11):1340-4.

19. Demailly P, Jeanteur-Lunel MN,Berkani M, et al. Non-penetrating deep sclerectomy associated with collagen device in primary open angle glaucoma. Middle term retrospective study. J Fr Ophtalmol 1996;19(11):659-66. 20. Detry-Morel M, De Temmerman S. Assessment of nonpenetrating deep sclerectomy with reticulated hyaluronic acid implant SKGEL and/or preoperative application of 5-fluorouracil: results of 2 and a half years. Bull Soc Belge Ophtalmol 2003;287:53-62. 21. Detry-Morel M. Nonpenetrating deep sclerectomy (NPDS) with SKGEL implant and/or 5-fluorouracile (5-FU). Bull Soc Belge Ophtalmol 2001;280:23-32. 22. Dietlein TS, Jacobi PC, Luke C, et al. Morphological variability of the trabecular meshwork in glaucoma patients: implications for non-perforating glaucoma surgery. Br J Ophthalmol 2000;84(12):1354-9. 23. Dietlein TS, Luke C, Jacobi PC, et al. Variability of dissection depth in deep sclerectomy: morphological analysis of the deep scleral flap. Graefes Arch Clin Exp Ophthalmol 2000;238(5):405-9. 24. Drolsum L. Deep sclerectomy in patients with capsular glaucoma. Acta Ophthalmol Scand 2003;81(6):567-72. 25. Drolsum L. Conversion from trabeculectomy to deep sclerectomy prospective study of the first 44 cases. J Cataract Refract Surg 2003;29(7):1378-84. 26. El Sayyad F, Helal M, El-Kholify H, et al. Nonpenetrating deep sclerectomy versus trabeculectomy in bilateral primary open-angle glaucoma. Ophthalmology 2000;107(9):1671-4. 27. Galassi F, Sodi A, Ucci F, et al. Deep sclerectomy in primary open angle glaucoma: comparison among different implants. Acta Ophthalmol Scand Suppl 2002;236:63-4. 28. Gianoli F, Mermoud A. Combined Surgery: comparaison between phacoemulsification associated with deep sclerectomy or with trabeculectomy. Klin Monatsbl Augenheilkd 1997; 210:256-60. 29. Guven D, Karakurt A, Ziraman I, et al. Non-penetrating deep sclerectomy in unilateral open-angle glaucoma secondary to idiopathic dilated episcleral veins. Eur J Ophthalmol 2002;12(1):668. 30. Hamard P. Management of non-penetrating surgery failure. J Fr Ophtalmol. 2003;26(Spec No. 2):S18-22. 31. Hamard P, Lachkar Y. Non-penetrating filtering surgery, evolution and results. J Fr Ophtalmol 2002;25(5):527-36. 32. Hamard P, Sourdille P, Valtot F, et al. Evaluation of confocal microscopy in the analysis of the external trabecular membrane during deep nonpenetrating sclerectomy. J Fr Ophtalmol. 2001;24(1):29-35. 33. Hamel M, Shaarawy T, Mermoud A. Deep sclerectomy with collagen implant in patients with glaucoma and high myopia. J Cataract Refract Surg 2001;27(9):1410-7. 34. Hyams M, Geyer O. Iris prolapse at the surgical site: a late complication of non-penetrating deep sclerectomy. Ophthalmic Surg Lasers Imaging 2003;34(2):132-5. 35. Jehn AB, Bohnke M, Mojon DS. Deep sclerectomy with collagen implant: Initial experience. Ophthalmologica 2002;216(4):235-8. 36. Johnson DH, Johnson M. How does non-penetrating glaucoma surgery work? Aqueous outflow resistance and glaucoma surgery. J Glaucoma 2001;10(1):55-67. 37. Jonescu-Cuypers C, Jacobi P, Konen W, et al. Primary viscocanalostomy versus trabeculectomy in white patients with openangle glaucoma: a randomized clinical trial. Ophthalmology 2001;108(2):254-8. 38. Karlen M, Sanchez E, Schnyder CC, et al. Deep sclerectomy with collagen implant: medium term results. Br J Ophtalmol 1999;83(1):611 39. Kazakova D, Roters S, Schnyder CC, et al. Ultrasound biomicroscopy images: long-term results after deep sclerectomy with collagen implant.

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Graefes Arch Clin Exp Ophthalmol. 2002; 240(11):918-23. Epub 2002 Oct 08. Kim CY, Hong YJ, Seong GJ, et al. Iris synechia after laser goniopuncture in a patient having deep sclerectomy with a collagen implant. J Cataract Refract Surg. 2002; 28(5):900-2. Kim CY, Chang HR, Lee JH, et al. Surgical outcomes of deep sclerectomy with collagen implant. Korean J Ophthalmol 2001; 15(2):107-12. Klink T, Lieb W, Grehn F. Erbium-YAG laser-assisted preparation of deep sclerectomy. Graefes Arch Clin Exp Ophthalmol 2000; 238(9):792-6. Kobayashi H, Kobayashi K, Okinami S. A comparison of the intraocular pressure-lowering effect and safety of viscocanalostomy and trabeculectomy with mitomycin C in bilateral open-angle glaucoma. Graefes Arch Clin Exp Ophthalmol 2003; 241(5):35966. Kozlov VI, Bagrov SN, Anisimova SY, et al. Non-penetrating deep sclerectomy with collagen. Ophthalmosurgery 1990; 3:44-46. Kozobolis VP, Christodoulakis EV, Tzanakis N, et al. Primary deep sclerectomy versus primary deep sclerectomy with the use of mitomycin C in primary open-angle glaucoma. J Glaucoma. 2002; 11(4):287-93. Kozobolis VP, Christodoulakis EV, Siganos CS, et al. Hemorrhagic Descemet’s membrane detachment as a complication of deep sclerectomy: a case report. J Glaucoma. 2001;10(6):497-500. Lin SC. Physiology and histology of deep sclerectomy. Br J Ophthalmol. 2003; 87(11):1310. Luke C, Dietlein TS, Jacobi PC, et al. Risk profile of deep sclerectomy for treatment of refractory congenital glaucomas. Ophthalmology. 2002; 109(6):1066-71. Marchini G, Marraffa M, Brunelli C, et al. Ultrasound biomicroscopy and intraocular-pressure-lowering mechanisms of deep sclerectomy with reticulated hyaluronic acid implant. J Cataract Refract Surg 2001; 27(4):507-17. Mermoud A, Schnyder C.C, Sickenberg M, et al. Comparison of deep sclerectomy with collagen implant and trabeculectomy in openangle glaucoma. J Cataract Refract Surg 1999, 25:323-31 Mermoud A. Sinusotomy and deep sclerectomy. Eye. 2000;14 (Pt 3B):531-5. Mermoud A, Karlen ME, Schnyder CC, et al. Nd:YAG goniopuncture after deep sclerectomy with collagen implant. Ophthalmic Surg Laser 1999;30(2):120-5. Milazzo S, Turut P, Malthieu D, et al. Scleral ectasia as a complication of deep sclerectomy. J Cataract Refract Surg 2000; 26(5):785-7. Moreno-Montanes J, Rodriguez-Conde R. Bleeding during gonioscopy after deep sclerectomy. J Glaucoma 2003;12(5):427-9 Munoz Negrete FJ, Rebolleda G, Noval S. Non-penetrating deep sclerectomy combined with phacoemulsification. Results and complications. Arch Soc Esp Oftalmol 2003;78(9):499-506. Netland PA. Ophthalmic Technology Assessment Committee Glaucoma Panel, American Academy of Ophthalmology. Nonpenetrating glaucoma surgery. Ophthalmology 2001;108(2):41621. Nozaki M, Kimura H, Kojima M, et al. Optical coherence tomographic findings of the anterior segment after non-penetrating deep sclerectomy. Am J Ophthalmol. 2002;133(6):837-9. Pallikaris IG, Kozobolis VP, Christodoulakis EV. Erbium:YAG laser deep sclerectomy: an alternative approach to glaucoma surgery.Ophthalmic Surg Lasers Imaging 2003;34(5):375-80. Price FW Jr, Ziemba SL. Placement of a collagen glaucoma drainage device to control intraocular pressure and chronic iritis secondary

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to juvenile rheumatoid arthritis. Ophthalmic Surg Lasers 2002; 33(3):233-6. Ravinet E, Mermoud A. Deep sclerectomy in refractory congenital glaucoma. Ophthalmology 2003;110(9):1859-60. Ravinet E, Tritten JJ, Roy S, et al. Descemet membrane detachment after nonpenetrating filtering surgery. J Glaucoma 2002;11(3):24452. Rebolleda G, Munoz-Negrete FJ. Non-penetrating deep sclerectomy for Sturge-Weber syndrome. Ophthalmology 2001;108(12):21523. Roy S, Boldea R, Nguyen C, et al. Analysis of filtration according to implant type after deep sclerectomy in the rabbit. Klin Monatsbl Augenheilkd 2001;218(5):354-9. Sanchez E, Schnyder C, Sickenberg M, et al. Deep sclerectomy: results with and without collagen implant. Int Ophthalmol 1997; 20:157-62. Sanchez E, Schnyder C, Mermoud A. Comparative results of deep sclerectomy transformed in trabeculectomy and those of standard trabeculectomy. Klin Monatsbl für Augenheilkd 1997; 210: 261264. Schuster B. Viscocanalostomy versus trabeculectomy. Ophthalmology 2003;110(11):2259-60. Schnyder CC, Shaarawy T, Ravinet E, et al. Free conjunctival autologous graft for bleb repair and bleb reduction after trabeculectomy and non-penetrating filtering surgery. J Glaucoma 2002;11(1):10-6. Shaarawy T, Karlen M, Schnyder C, et al. Five-year results of deep sclerectomy with collagen implant. J Cataract Refract Surg 2001; 27(11):1770-8. Shaarawy T, Nguyen C, Schnyder C, et al. Five year results of viscocanalostomy. Br J Ophthalmol 2003; 87(4):441-5. Smit BA, Johnstone MA. Effects of viscoelastic injection into Schlemm’s canal in primate and human eyes: potential relevance to viscocanalostomy. Ophthalmology 2002;109(4):786-92. Spiegel D, Schefthaler M, Kobuch K. Outflow facilities through Descemet’s membrane in rabbits. Graefes Arch Clin Exp Ophthalmol. 2002;240(2):111-3. Stegmann RC. Viscocanalostomy: a new surgical technique for open angle glaucoma. An Inst Barraquer, Spain 1995;25:229-32. Stegmann R, Pienaar A, Miller D. Viscocanalostomy for open-angle glaucoma in black African patients. J Cataract Refract Surg 1999;25(3):316-22. Sunaric-Megevand G, Leuenberger PM. Results of viscocanalostomy for primary open-angle glaucoma. Am J Ophthalmol 2001;132(2):221-8. 1998; vol. 38, No 4: S1064. Verges C, Llevat E, Bardavio J. Laser-assisted deep sclerectomy. J Cataract Refract Surg 2002; 28(5):758-65. Vuori ML. Complications of neodymium: YAG laser goniopuncture after deep sclerectomy. Acta Ophthalmol Scand. 2003; 81(6):5736. Vuori ML. Deep sclerectomy in patients with capsular glaucoma. Acta Ophthalmol Scand 2003; 81(6):567-72. Wishart PK, Wishart MS, Porooshani H. Viscocanalostomy and deep sclerectomy for the surgical treatment of glaucoma: a longterm follow-up. Acta Ophthalmol Scand. 2003;81(4):343-8. Wishart PK, Wishart MS, Porooshani H. Viscocanalostomy and deep sclerectomy for the surgical treatment of glaucoma: a longterm follow-up. Acta Ophthalmol Scand. 2003;81(4):343-8. Yalvac IS, Sahin M, Eksioglu U, et al. Hemorrhagic Descemet’s membrane detachment after viscocanalostomy. J Cataract Refract Surg 2003;29(7):1440-2.

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Atlas of Glaucoma Surgery Roberto Sampaolesi, Juan Roberto Sampaolesi, Jorge Zarate

9 Nonpenetrating Deep Sclerectomy (NPDS): Anatomic Landmarks

INTRODUCTION It was Krasnov, in 1966,1,2 who originally proposed the removal of the external wall of the Schlemm’s canal and coined the word sinusotomy for the procedure by which he removed the external wall of Schlemm’s canal from 10 to 20 o’clock over 120°; the inner wall of Schlemm’s canal was left untouched and then the conjunctiva was closed. Alkseev, in 1978,3 proposed the removal of the endothelium of the inner wall of Schlemm’s canal and of the juxtacanalicular tissue in sinusotomy in order to increase the permeability of the inner wall of the chamber angle. Zimmerman et al (1984)4 introduced nonpenetrating trabeculectomy; Fyodorov et al (1984)5-6 proposed deep sclerectomy and later, and together with Kozlov and others (1989), nonpenetrating deep sclerectomy; Kozlov et al (1990)7 perfected the method with the addition of a cylindric collagen implant and later developed laser goniopuncture, methods which were further developed by Kozlov and Kozlova (1996)8 and by Kozlova (19962000).9-10 According to Kozlov’s technique, in addition to the resection of the external wall of Schlemm’s canal, the inner wall of Schlemm’s canal with the endothelium, together with the juxtacanalicular tissue and external corneoscleral trabecular meshwork are removed. In (1991), Arenas Archila11 proposed trabeculotomy ab externo, by which the same tissues were removed, after removal of the external wall of Schlemm’s canal, but using a microtrephine working at a speed of 800 rpm. In 1999 Stegman 12 reported his results with viscocanalostomy in black African patients. Sourdille et al. (1999)13 used a triangular reticulated hyaluronic acid implant of the same size as that of the second triangular

scleral flap. We have successfully tested this technique, which, as it is currently known, is also successfully used by Demailly (1996).14 Moreover, a very complete book has been edited recently by Andre Mermoud,15 who has extensive experience in nonpenetrating surgery. The main advantage of nonpenetrating deep sclerectomy (NPDS) lies with the high percentage of cases in which it prevents the three most severe complications of trabeculectomy: flat chamber, hyphema and choroidal detachment. Furthermore, since neither anterior chamber opening nor iridectomy nor atropine instillation into the anterior chamber is required, the postoperative period is good, with the patient preserving the preoperative visual acuity, in contrast to our experience with trabeculectomy, which has a difficult postoperative course, independently of the success of the procedure. Moreover, the mild postoperative period, as well as the low percentage of complications has encouraged surgeons to safely recommend this technique as early as in the preperimetric period, when damage to the optic nerve has already occurred and pharmacotherapy has failed to regulate IOP, though visual acuity and visual field are still normal. This technique is thus pretty close to the ideal therapy for the prevention of serious anatomic and functional damage caused by the disease.

EARLY INDICATION OF NPDS IN OPENANGLE GLAUCOMAS Effective detection by non-conventional perimetry, i.e. by Frequency Doubling Technology (FDT), of visual field defects correlated with optic nerve damage revealed by confocal tomography, which in almost 50 percent of cases go undetected by conventional perimetry (SAP), has

Nonpenetrating Deep Sclerectomy (NPDS): Anatomic Landmarks shortened the preperimetric period of glaucoma thereby enabling earlier detection of visual field loss in ocular hypertension. This is vital for the indication of surgical therapy in patients under these conditions failing to control their intraocular pressure with maximum medical therapy. Very favorable results can therefore be achieved with novel less invasive surgical techniques, such as nonpenetrating deep sclerectomy. Frequency Doubling Technology (FDT) thus enables the detection of glaucomatous visual field changes earlier than SAP. Therefore, it is a valuable tool for patients who used to be considered as ocular hypertensives and who can now be correctly diagnosed with glaucoma.16 We will now describe some examples (Figs 9.1 to 9.3).

CONTRAINDICATION The NPDS is contraindicated in narrow-angle or angleclosure glaucoma, congenital glaucoma and late congenital glaucoma when the mesodermal remnants reach Schwalbe’s line.

NPDS: ANATOMIC LANDMARKS Anatomic landmarks of NPDs are being expressed in Figures 9.4 to 9.7.

NPDS: SURGICAL TECHNIQUE After retrobulbar anesthesia with 2 to 4 ml of a solution of xylocaine 4 percent, the conjunctiva and Tenon’s capsule are opened at the upper fornix or at the limbus. With the sclera thus exposed careful hemostasis is performed with the use of a bipolar cautery manufactured by “Mira.” A nylon suture is placed on the cornea 1 mm away from the limbus, at 12 hours, to move the eye. • Step 1: A rectangular one-third scleral thickness limbal-based scleral flap, the same as that created for trabeculectomy is dissected. One side of this rectangle, of 5 mm, is parallel to the limbus, while another one is perpendicular to it and 6 mm in length. Anteriorly, the scleral flap is dissected closer to the cornea than usual in trabeculectomy procedures. Corneal lamellae are dissected along 1.5 mm (Fig. 9.8).

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• Step 2: A second limbal-based triangular scleral flap is then created by penetrating 1. 5 mm along the corneal tissue. A useful landmark for this dissection, which must be performed carefully, is the orientation of the scleral fibers, which though arranged in multiple directions at the scleral level, behind this flap, they become neatly parallel and circular at the level of the scleral spur, thus adopting a more whitish and nacreous appearance. Aqueous humor percolation at this stage, with the anterior chamber closed, when the dissection goes from the scleral spur towards the cornea, is indicative of placement of the incision at the proper plane. The triangular flap, containing the external wall of the Schlemm’s canal, including its endothelium, is then resected. Anteriorly, the dissection should be made down to the deep corneal lamellae so that only the corneal endothelium remains. Descemet’s membrane and a small layer of corneal lamellae are left. The dissection plane can generally be easily created at this final stage by pulling the vertex of the triangular flap towards the cornea with a clamp (Figs 9.8 and 9.9). Figures 9.10A to C show the pathological anatomy of the external wall of Schlemms canal. • Step 3: The most important step of NPDS involves the removal of the internal elements of resistance. If this membrane is not removed the intraocular pressure will fail to be regulated (Fig. 9.11). • Step 4: At this step the implant is secured to the sclera with a nylon 10-0 suture. Implants may be made of different materials. In our first 60 patients we used the implant manufactured by Staar Surgical AG (Nidau, Switzerland). It is a cylindrical collagen implant measuring 2.5 mm in length and 1 mm in diameter processed from lyophilized American porcine scleral collagen, which is sterilized by a radiation procedure. The water content of the hydrated device is 99 percent. This implant, is resorbed within 6 to 9 months after surgery, as demonstrated by UBM (ultrasound biomicroscopy) (Fig. 9.12). In the last 22 cases we used the “corneal implant” (France). This implant is triangular and it is made of sodium hyaluronate.

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Fig. 9.1: Optic nerve fiber defect at the inferotemporal quadrant with rim notch. Visual field: normal according to SAP and Bebie curve while Frequency Doubling Technology reveals a visual field defect topographically correlated with optic nerve and fiber layer defects. It is not a hypertension, it is really a glaucoma. The intraocular pressure fails to be regulated with maximum therapy. We indicated NPDS

Fig. 9.2: Damage at the inferotemporal quadrant of the optic nerve (rim volume: 0.14 mm3: phase IV). For conventional perimetry (SAP), the visual field is normal. FDT: Visual field defect correlated topographically with the optic nerve damage. Since it is not hypertension but a glaucoma in which the IOP is not regulated with maximum therapy, the indication is NPDS.

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Fig . 9.3: Advanced optic nerve damage with a rim volume of 0.17 mm3 (phase IV). Moorfield regression analysis shows a marked optic nerve damage at the superotemporal quadrant (in red) and a smaller defect at the temporal, inferotemporal, superonasal and nasal quadrants (in yellow). SAP: normal, FDT: visual field defect correlated topographically with the damage of the optic nerve. Brusini’s GSS for SAP (bottom) and normal visual field on the left. On the right, FDT revealed that the visual field is in stage 1. Intraocular pressure was not regulated with maximum therapy and NPDS was therefore indicated.

COMPLICATIONS OF SURGERY Triangular Flap Dissected too Superficially The dissection of the triangular flap is not deep enough for the resection of the external wall of the Schlemm’s canal. The graphic at the center of the figure shows the key element for the surgeon to find the Schlemm’s canal. The most posterior darker blue sector (between 3 and 4 of the blue area) indicates the location of the Schlemm’s canal (Fig. 9.13). The external wall of Schlemm’s canal must be dissected with a cutting round spatula specially designed for this purpose by Grieshaber (Fig. 9.14). This dissection can be made with direct illumination or under transillumination (Fig. 9.15A and B). For the finding of the Schlemm’s canal it is very important to view the surgical area with direct illumination and with transillumination (Minsky’s

maneuver). The area is transilluminated by means of the optical fiber of the microscope supported by the cornea, and separated from it by one of the white triangles used for drying, but embedded in physiological solution to prevent the cornea from overheating (Figs 9.16A and B). (In Figure 9.16A under direct illumination and in Figure 9.16B, under transillumination). Transillumination (Fig. 9.16B) clearly reveals the location of the Schlemm’s canal (white arrows). In Figs 9.17A to C the external wall of the Schlemm’s canal of the same case has been completely removed.

Triangular Flap Dissected too Deeply In this case when the surgeon tries to remove part of the second flap, the iris prolapses because a perforation of the internal wall has been made (Figs 9.18A to C). If this happens, the surgical procedure should invariably be turned into a trabeculectomy (Figs 9.19A to C).

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Fig. 9.4: Resistance on the conventional outflow pathway, which was removed by trabeculectomy (vertical red line). With NPDS (vertical green line) we removed the external wall of Schlemm’s canal with collectors upon removing the triangular flap. Removal of the internal tissues includes: internal wall of Schlemm’s canal, the juxtacanalicular tissue, the external part of the corneoscleral trabecular meshwork. The internal part of the corneoscleral trabecular meshwork and the uveal trabecular meshwork, which, together with Descemet’s membrane form the trabeculo-Descemet’s membrane, remain unmoved.

Fig. 9.5: Trabeculectomy: All tissues of the internal and external places of resistance are removed when the deep scleral flap is created

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Fig. 9.6: In NPDS, the external wall of the Schlemm’s canal is removed with the second triangular scleral flap and with Mermoud’s forceps, a membrane made up by the inner wall of the Schlemm’s canal, the juxtacanalicular tissue and the external part of the corneoscleral trabecular meshwork are also removed. The tissues which are left in their place are: trabeculoDescemet’s membrane, made up by the internal part of the corneoscleral meshwork and the uveal meshwork. As stated by Dr Mermoud, this membrane is strong enough to support the anterior chamber and also permeable enough to improve aqueous humor outflow with the consequent intraocular pressure reduction.

Fig. 9.7: Chamber angle: Section of the chamber angle 5: Ciliary muscle, 6: Ciliary body, 7: Sclera, 8: Limbus, 9: Scleral septum and Schwalbe’s line, 11: Iris, 12: Cornea, 13: Schlemm’s canal, 14: Lens. Gonioscopic image S. SPUR: Scleral spur, TR: Trabecular meshwork, TRSHL: Trabecular meshwork of Schlemm’s canal, LSCHW: Schwalbe’s line, CB: Ciliary body band, LRI: Last fold of the iris, I. PR: Iris process. Optical cut 1: Profile line at the posterior corneal surface, 2: Profile line at the anterior corneal surface, 3: Profile line at the anterior iris surface

Fig. 9.8: The dissection has been correctly performed if three clear areas are visualized. Dark area (limbal area). Blue area 2 (more posterior), with its anterior limit corresponding to Schwalbe’s line, and its posterior limit, to the scleral spur and the open Schlemm’s canal. White-grayish area 3 (behind the blue area), triangular, made up of scleral tissue and covering the external surface of the ciliary muscle. On the right side of this Figure the correspondence of the surgical appearance of the three areas with the anatomic elements of the chamber angle can be seen

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Fig. 9.9: Removal of the second triangular scleral flap (Left), on which the external wall of Schlemm’s canal, identified by its hazel- or brown-colored granulous appearance, can be seen. Center and right: Correlation of this photograph with the landmarks

Figs 9.10A to C: A: Anatomopathologic examination of the triangular flap showing some corneal lamellae and the endothelium of the external wall of Schlemm’s canal. B: Endothelial nuclei of the external wall of Schlemm’s canal (flat preparation) C: Collector of the external wall of Schlemm’s canal

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Fig. 9.11: Dissection of the inner wall of Schlemm’s canal with its endothelium, juxtacanalicular tissue and the external corneoscleral trabecular meshwork (Left). Schematic representation of the tissue removed and of its previous locations (Center), where only the internal corneoscleral trabecular meshwork and the uveal trabecular meshwork, which, together with Descemet’s membrane form the trabeculo-Descemet’s membrane, are left (Bottom-right).

Fig. 9.12: Correctly placed implant (Staar). After the placement the implant which is secured with a nylon suture, the scleral flap is closed with two nylon sutures. The photograph shows the implant manufactured by Staar (Switzerland). In our last 22 cases, we have used the “Corneal” implant (France), a triangular implant made of sodium hyaluronate

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Fig. 9.13: Image visualized if the dissection has failed to be done at the correct plane and it is not deep enough for the resection of the external wall of the Schlemm’s canal by means of the triangular flap. All three areas are visible but the open Schlemm’s canal is not (Left). The schematic representation at the center shows the key element for the surgeon to find the Schlemm’s canal: the most posterior darker blue sector (between 3 and 4) of the blue area corresponds to the Schlemm’s canal

Fig. 9.14: The most important surgical step is to open the Schlemm’s canal, located at the posterior part of the blue area, adjacent to the scleral spur

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Figs 9.15A and B: Dissection of the external wall of the Schlemm’s canal (A) under direct illumination and (B) under transillumination, done with an instrument specially designed for this purpose by Grieshaber

Figs 9.16A and B: Minsky’s maneuver (see text). In (A) under direct illumination of the Schlemm’s canal area, the location of the Schlemm’s canal cannot be seen, which under transillumination (B) this can be seen very clearly (white arrows)

NPDS PEARLS The goal of step number 1 (unroofing of the Schlemm’s canal) is to remove the external wall in order to achieve a good exposure of the canal. This step is perfectly shown in Figure 9.20. The second critical step is number 2, in which the surgeon removes the external elements with Mermoud’s

forceps, as shown in Figure 9.21A. When this step is perfectly done, the space between the scleral spur and the Schwalbe’s line is enlarged, and aqueous humor percolation is observed (Figs 9.21B and C).

LEARNING CURVE See Figures 9.22A to H and 9.23A to C.

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A

B

C

Figs 9.17A to C: The dissection of the external wall of the same case is shown in A, B and C. The external wall of Schlemm’s canal is completely removed

A B C Figs 9.18A to C: In this case when the surgeon tried to remove part of the second flap, the iris prolapsed because a perforation of the internal wall had taken place (A, B and C). When this happens, the surgical procedure must invariably be turned into a trabeculectomy

GONIOSCOPY AFTER NPDS Figures 11.24A to C illustrate the typical appearance of the chamber angle after NPDS. The dark area (A) on the external wall of the chamber angle is the scleral lake (1 in the figure), which can be clearly seen full of liquid with a fine slit cut (B).

Both Figures 9.24A and B show Schlemm’s canal and the trabecular meshwork which have become convex, raised towards the interior of the anterior chamber, because they have been displaced, and therefore, deformed by the cylindrical implant.

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Figs 9.19A to C: The triangle flap whit the external wall of Schlemm‘s canal and the internal wall in place

Fig. 9.20: The goal of step 1 (unroofing of the Schlemm’s canal) is to remove the external wall of Schlemm’s canal

Figures 9.25A and B show another appearance of the chamber angle after this procedure. In (A) it looks as if the procedure has been penetrating, however, if viewed in a fine slit cut (B), a very thin trabeculo-Descemet’s membrane is seen.

ND: YAG LASER GONIOPUNCTURE17 In 20 percent of cases, YAG goniopuncture was required between months 1 to 5 postoperatively for IOP

regulation in cases reaching as high as 20 mm Hg or more according to a single-spot check, or in the presence of pathologic results revealed by a daily pressure curve. The lens designed by Rousell and Fankhauser and manufactured by Haag Streit was used for this procedure, with an aim to perforate the resistance zone if surgery had failed to remove part of the corresponding tissue, and thereby communicate the anterior chamber with the scleral lake or the subconjunctival space. The aiming beam is focused on the trabeculo-Descemet’s membrane with a power of 2 to 3.5 mJ; however, sometimes, higher power, 4 to 5 mJ is required, but it should be kept in mind that a power above 4 mJ may cause small hemorrhages which can be stopped by strongly pressing the lens against the eye. A total of 5 to 20 shots should be made at the level of Schwalbe’s line, as well as above and below it. Digital massage, which is usually indicated after trabeculectomy, is wholly contraindicated in these cases. However, more experienced surgeons have now concluded this YAG goniopuncture to be necessary in 48 percent of cases (Mermoud 2001) (Figs 9.26 and 9.27A to C).

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A

B

C

Figs 9.21A to C: The second critical step is number 2. It is necessary to remove the internal elements, internal wall of Schlemm’s canal, juxtacanalicular tissue and external part of the corneoscleral trabecular meshwork in order to regulate the intraocular pressure. It should be kept in mind that between the internal and external part of the corneoscleral trabecular meshwork there is a natural cleavage pane

In our experience of 375 NPDS Yag goniopuncture was required in 20 percent of cases. Yag laser also becomes useful in the postoperative period, when there are microperforations during the surgical procedure, and these are no noticed by the surgeon. After surgery, the signs of iris incarceration are dyscoria with ocular hypertension (Fig. 9.28). Iris incarceration must be treated first with pilocarpine, and then with laser goniosynechialysis, as shown in Figures 9.29A and B. In Figure 9.30, the UBM shows the collagen device after surgery and seven months later the device has been resorbed and there is a good scleral lake and a thin trabeculo-Descemet’s membrane.

Follow-up All patients were examined at six-month intervals: 1. With a single IOP spot check. 2. With a diurnal curve. The IOP was measured at 6 am, 9 am, noon, 3 pm, 6 pm and 9 pm always with applanation tonometry: at 6 am with the patient in bed using a hand applanation tonometer,

the other measurements are made with the patient seating at the slit lamp. In other to estimate de DPC we used the following method:18 in each curve two factors were analyzed: a. Diurnal average: Arithmetic mean of the readings obtained during the course of the curve. b. Diurnal variability: The standard deviation of those pressures. With a mean over 19 mm Hg or a variability over a 2.1 mm Hg, the DPC is considered pathological. 3. Visual field: evaluated with conventional perimetry (Octopus 101 program G2) and with nonconventional perimetry (Frequency Doubling Technology, threshold program). 4. With confocal tomography of the optic nerve (HRT). 5. With confocal flowmeter (HRF) for the measurement of the retinal and optic nerve flow. 6. Gonioscopy. 7. Ophthalmoscopy. Surgery was considered a complete success when IOP was ≤ 21 mm Hg under no antiglaucomatous medication, qualified success when IOP was ≤ 21 mm Hg under

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B

C

D

E

F

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H

Figs 9.22A to H: Step of the surgery when the triangle flap is remove and UBM of the same cases a different stage of the learning curve, in the first 100 eyes, made in one year, in the first 3 months (A, B), at the 6 months (C, D) at the 9 months (E, F) and at 1 year (G, H).

antiglaucomatous therapy associated with a regulated diurnal pressure curve (mean below 19 mm Hg and variability below 2.1 mm Hg) and visual field and optic disk with now evidences of damage progression.

1. Results of NPDS with an implant after 7 years of follow up in 60 eyes. (40 with the Staar implant, 20 with the “Corneal implant”) 60 eyes, 50 glaucomas, 10 glaucomas with cataract (combined surgery)

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Figs 9.23A to C: Typical appearance of the chamber angle after NPDS. The Schlemm’s canal and the trabecular meshwork have become convex, raised towards the interior of the anterior chamber, because they have been displaced by the cylindrical implant, which deforms them. In (A) the dark area seen by diffuse illumination on the external wall of the chamber angle is the scleral lake, which, in (B), is seen full of liquid with a fine slit cut. (C) UBM of the same case

Figs 9.24A to C: Another appearance of the chamber angle after this procedure. In (A) it looks as if the procedure has been penetrating, however, if viewed in a fine slit cut (B), a very thin trabeculoDescemet’s membrane is seen. (C) the UBM does not have enough resolution and it seems as if the trabeculoDescemet’s membrane has been broken down

IOP< 17 mm Hg: 86 percent (10 with Yag-laser goniopuncture): complete success IOP< 20 mm Hg: 10 percent with antiglaucomatous medication: qualified success (when IOP was regulated with glaucoma medication) 4 percent failure (reoperation)

Single IOP spot check before surgery (Mean): 29.8 mm Hg; after surgery: 14.7 mm Hg. Diurnal pressure curve before surgery: Mean 24.4 mm Hg, Standard deviation: 4.6 mm Hg, after surgery: Mean 15.3 mm Hg, Standard deviation: 2.1 mm Hg

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Figs 9.25A and B: (A) chamber angle before NPDS; (B) chamber angle after NPDS. The chamber angle studied with an optical cut made by the slit lamp, shows that after NPDS that half of the Schwalbe’s line and scleral spur where removed, and the optical cut between this two element is concave because this is the place of the scleral lake filled with humor aqueous

Fig. 9.26: Nd: Yag laser goniopuncture: at the left the right place to performed goniopuncture: at the Schwalbe’s line, at the posterior corneal surface and in the trabecular meshwork. At the right there is a goniophotograph showing Schwalbe’s line, the scleral spur and blood coming of the Schlemm’s canal, after goniopuncture

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Figs 9.27A to C: (A) Microperforation during surgery, (B) Ocular hypertension due to dyscoria, (C) Iris incarceration

Fig. 9.28: Goniosynechialysis with Yag laser after iris incarceration

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Figs 9.29A and B: (A) Ultrasound biomicroscopy showing, from left to right: conjunctival tissue whit aqueous humor, separating it from the cuadrangular scleral flap and two parallel lines behind it corresponding to the implant, where the nylon suture securing it can be seen. The implant is surrounded by aqueous humor and the scleral lake is seen behind it. (B) The intraescleral lake and the trabeculo-Descemet’s membrane, 8 months later. The implant is reabsorbed

Fig. 9.30: Results: 112 consecutive cases with NPDS without collagen implant: 1. IOP red points at Maximal Medical therapy (MTMT), 2. IOP orange and green points after NPDS, 3. IOP yellow and green points after Yag laser, 4. IOP green points after Medical therapy

2. Results of NPDS without an implant in 315 eyes after 2 years of follow up: IOP 10 mm Hg) was reported in 30 percent. Hemorrhage from the iridotomy and transient blurring of vision occurring in about 20 percent. Patients taking warfarin should have had a recent coagulation test (within 1 week) confirming INR< 3.0. Iritis (11%), posterior synechiae (7%) and corneal changes (4%) are also recorded complications. 4 Cataract is considered a potential long-term complication although one study found visual acuity was the same or improved in 85 percent of eyes at an average of 1.8 years after treatment. Cataract progression was responsible for eyes with decreased acuity; the rate of progression was the same as that in similarly aged persons treated by surgical iridectomy.5 Anecdotally, a small numbers of patients notice a change in their vision related to glare. Symptoms

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are most common and pronounced if the iridotomy is positioned at the level of the lid margin, probably because of the prismatic effect of the marginal tear strip. PI’s should be positioned underneath the upper lid, and never at the level of the lid margin. In all patients with thick brown irides (where the radial fibers of the peripheral iris cannot be seen because of a thick iris stroma), continuous wave laser (CWL) (i.e. the “argon” class of lasers) should be used to pretreat at the site of the iridotomy. However, retinal burns have been reported following iridotomy by argon laser alone, and macular burns are possible. 6,7 People having CWL pretreatment should be warned of this, although they can be reassured that the combined argon-YAG approach minimizes the possibility of this occurrence. 8 The sequential argon-YAG approach is the technique of choice in thick brown irides.

Preparation and Premedication Topical alpha adrenoceptor agonist (apraclonidine or brimonidine) and pilocarpine (blue eyes: 2%, brown eyes: 4%) should be used at least 30 minutes before, with a second dose immediately before starting treatment. The alpha agonists should be used with caution if there is history of ischemic heart disease.

Procedure Anesthetize the eye with amethocaine and apply a Wise or Abraham’s iridotomy contact lens. Check the defocus is set to zero. Look for iris crypts or thin areas, and treat an area as peripheral as possible between 11 and 1 o’clock. Blue eyes usually require single 1 to 2 mJ shots. Total power consumption should be less than 30 mJ. For green and brown eyes where radial fibers are visible (i.e. thin iris) use single 2 to 3 mJ shots, expecting a maximum total power of around 50 mJ. For thick brown irides that have had CWL pretreatment, settings and power consumption should be similar. If any hemorrhage is encountered, gentle pressure will help this to stop. Enlarge the iridotomy circumferentially up to 200 microns diameter.9 Verify by direct inspection that the iridotomy extends through the iris-pigment epithelium.

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CWL Pretreatment for Thick Brown Irides

Laser Iridoplasty

This is mandatory for all Chinese and African. It is very useful in other Asian and Caucasians with a thick iris. All classes of continuous wave laser used for retinal photocoagulation can be used—argon, diode or frequency doubled YAG lasers for this. Again use a Wise or Abraham’s contact lens. The treatment is given in two phases, starting with low power shots (80 to 130 mW, 0.05s, 50 microns) to treat a rosette area on the iris stoma, to produce a soft pitting or a tiny adherent bubble. About 15 to 20 shots should be needed to do this. The aim is to prevent large, adherent bubbles forming in the next phase when the power is increased (700 to 750 mW, 0.1s, 50 microns), and another 10 to 20 shots are applied to produce a punched out crater down to the radial muscle fibers and vasculature. If there is any charring or popping, reduce the power. Complete the iridotomy with a few shots of YAG. In difficult cases (typically African patients, and those who need more than 50 shots) consider aborting the procedure and opting for a surgical iridectomy.

The aim of iridoplasty is to induce contraction and compaction of the peripheral iris, drawing the iris away from the trabecular meshwork, and creating more space in the peripheral anterior chamber. Iridoplasty can be used in the management of symptomatic and asymptomatic cases (i.e. acute and chronic angleclosure). 11,12 Generally iridoplasty is a very low-risk procedure, with a lower side effect profile than PI. Transient pressure rises occur occasionally, as does a dullache which may persist for up to one week. A small number of patients notice a subjective change in their vision. Corneal burns are possible, and more often occur when treating “acute,” symptomatic cases. They are very rare in elective treatment.

Aftercare Intraocular pressure should be measured at one to two hours after treatment. If the IOP is high, oral acetazolamide plus or minus additional topical agents should be used as required. All patients should receive a strong topical steroid (prednisolone 1% or dexamethasone 0.1%) hourly for 24 hours (taking a break through the night), and then 4 times a day. All patients should be seen 1 week later in clinic and regonioscoped. Stop steroid unless there is evidence of continued inflammation. If the IOP is raised and there is anterior segment inflammation, swap to a topical NSAID.

Surgical Iridectomy A randomized clinical trial of surgical iridectomy versus laser iridotomy identified no difference in IOP control and visual acuity at 3 years post-treatment.10 Surgical iridectomy should be performed in African and AfroCaribbean patients in whom a laser iridotomy has been difficult.

Preparation and Premedication This is performed in exactly the same manner as for iridotomy. Ensure that patients do not have high or extensive low PAS. The inflammation induced by iridoplasty will, in some cases, cause an extension of PAS. People with low, early (sawtooth) PAS can be treated, provided they are given pilocarpine qid post-laser, to splint the angle open for 1 week.

Procedure Anesthetize the eye with amethocaine, apply a Wise or Abraham’s iridotomy contact lens. Any continuous wave laser used in pan-retinal photocoagulation may be used to perform iridoplasty. Different classes of lasers vary somewhat in their efficacy relative to power, and there is substantial variation in power uptake between eyes. As a general rule, you should start with a low power and increase until the desired effect is achieved. Starting from 100 mW, the desired response is usually achieved at between 180 mW and 300 mW: Pulse duration 0.5 to 0.7s, and spot size 500 microns. Burns should be applied as peripherally as possible, throughout 360°. A “full” treatment requires about 25 to 35 shots, each burn being placed about 2 aiming beam widths from the area of discoloration marking the previous shot. The ideal endpoint is a brisk contraction of the iris stroma, without

Management of Angle-closure charring or a pop (if these occur, turn the power down). The aiming beam should be crisply focused in a regular circle. Varying the direction of gaze of the subject often helps clear visualization of the area to be treated. Most often, directing gaze away from the quadrant being treated improves the view. The procedure is the identical for treatment of “acute” cases. The view may be improved a little using topical glycerine to clear a steamy cornea. The AC should be examined carefully to determine where the cornea and iris are in contact. These areas should not be treated unless no alternative exists. If there is 360° peripheral iridocorneal apposition, start the treatment more centrally, and as the burns pull open the angle, rapidly spiral the treatment into the extreme periphery.

Aftercare This is exactly the same as for cases having laser PI. In addition, any cases with PAS should be given pilocarpine (blue eyes: 2%, brown eyes: 4%) to use qid for 1 week. All patients are seen 1 week later in clinic and regonioscoped. Stop steroid unless there is evidence of continued inflammation. If the IOP is raised and there is anterior segment inflammation, swap to a topical NSAID. Pilocarpine should be discontinued at 1 week, and the gonioscopy repeated 3 to 4 weeks later to assess the effect of iridoplasty on angle configuration. In selected cases of pure plateau iris syndrome, laser iridoplasty appears to be highly effective, changing angle width from 0 to 20° in all cases in a reported series (often to 30°). The changing in angle width is relatively longlasting, with 20/23 eyes retaining open angles throughout the follow-up period of at least 6 years. The other three in whom the effect wore off were retreated with a further change in angle width, suggesting that retreatment is appropriate in certain selected cases.12

Cataract Surgery and Lens Extraction Providing trabecular function is reasonably intact (less than 180° of high PAS), any patient with angle-closure and a visually significant cataract can be very effectively managed by cataract extraction and IOL implantation.13- 15 In people

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with more than 180° PAS and uncontrolled IOP who underwent phacoemulsification cataract surgery combined with goniosynechialysis within 6 months of an episode of symptomatic angle-closure (i.e. an acute attack), IOP was controlled postoperatively without medication for at least 3 months (and in some cases up to 6 years). All patients retained the same or better visual acuity than preoperatively.16 Lens extraction remains the definitive method of managing cases of lens induced angle-closure. These cases either have very advanced (typically hypermature) lens opacities or dislocated/subluxated lenses.

Medical Management of Angle-closure Topical pilocarpine remains an effective medical method of reversing appositional angle-closure, but has attendant complications of brow-ache, induced myopia, dimming of vision and probably accelerated formation of lens opacities. Long-acting pilocarpine gel is better tolerated, and has the advantage of a single, night-time dosage regime. Previous pilocarpine treatment is believed to prejudice the outcome of trabeculectomy.17 Pilocarpine use should be carefully considered in patients with pseudoexfoliation and angle-closure because of the potential for rupture of zonules.18 Topical atropine is extremely effective in some cases of secondary angle-closure caused by retrolenticular forces. Aqueous misdirection (ciliolenticular block/ malignant glaucoma) is one example of the role for atropine. The key diagnostic features in these cases are an atypical history or a marked asymmetry in the appearance of the anterior chamber. For example, angleclosure in a myopic subject who has undergone retinal detachment surgery, either recently with a gas or oil posterior tamponade, or in the past and has a very high indent from an explant are likely to improve with atropine (and dramatically deteriorate with pilocarpine). If the central anterior chamber depth is asymmetrical (> 0.6 mm) a secondary cause should be sought, and atropine considered as a possible treatment. Atropine, however, is a temporizing measure, and the definitive management is aimed at the cause of the retrolenticular force.

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DETECTION AND CONTROL OF CONTINUING OPTIC DISK AND VISUAL FIELD DAMAGE The natural history of glaucomatous optic neuropathy accompanying angle-closure is not fully understood. It is more pressure dependent disease than open-angle glaucoma. 19 Data from studies of white-on-white automated perimetry suggest the pattern of field loss in cases in the more common, asymptomatic from of angleclosure glaucoma is similar to that seen primary open angle glaucoma, with the exception that field loss in PACG does not exhibit the same predilection for the superior hemifield as is characteristic in early to moderate cases of POAG. Consequently, after any symptomatic episodes have been dealt with, and all appropriate steps have been taken to open the drainage angle, the management of cases of PAC and PACG is broadly analogous to that of OHT and POAG. Regular examination should assess the intraocular pressure, the optic disk and visual field, as well as regular assessment of the angle, ideally by gonioscopy and either ultrasound biomicroscopy or optical coherence tomography. In patients with raised IOP in chronic angle-closure following a laser iridotomy, prostaglandin analogues have been shown to outperform beta-blockers in IOP control.20

PREVENTION IS BETTER THAN CURE The majority of cases of angle-closure glaucoma occur in the densely populated, relatively poor countries of Asia. In China alone, it is estimated that some 1.7 million people are blind in both eyes from PACG. As PACG exists in an early/latent form (anatomically narrowangles) prior to the onset of severe, visually destructive disease, and there exist tests which show reasonable performance in detecting early cases,21,22 it is justifiable to examine whether population screening and prophylactic treatment is ethically, scientifically and economically justifiable.23 Trials to address this issue are underway.24

REFERENCES 1. Anderson DR, Davis EB. Sensitivities of ocular tissues to acute pressure-induced ischaemia. Arch Ophthalmol 1975;93:267-74.

2. Moses RA. The Goldmann applanation tonometer. Am J Ophthalmol 1958;46:865-9. 3. Kobayashi H, Kobayashi K, Kiryu J, Kondo T. Pilocarpine induces an increase in the anterior chamber angular width in eyes with narrow angles. Br J Ophthalmol 1999;83:553-8. 4. Schwartz LW, Moster MR, Spaeth GL, Wilson RP, Poryzees EM. Neodymium-YAG laser iridectomy in glaucoma associated with closed or occludable angles. Am J Ophthalmol 1986;102:41-4. 5. Quigley HA. Long-term follow-up of laser iridotomy. Ophthalmology 1981;88:218-24. 6. Berger BB. Foveal photocoagulation from laser iridotomy. Ophthalmology 1984;91:1029-33. 7. Karmon G, Savir H. Retinal damage after argon laser iridotomy. Am J Ophthalmol 1986;101:554-60. 8. Ho T, Fan R. Sequential argon-YAG laser iridotomies in dark irides. Br J Ophthalmol 1992;76:329-31. 9. Fleck BW. How large must an iridotomy be? Br J Ophthalmol 1990;74:583-8. 10. Fleck BW, Wright E, Fairley EA. A randomised prospective comparison of operative peripheral iridectomy and Nd:YAG laser iridotomy treatment of acute angle closure glaucoma: 3-year visual acuity and intraocular pressure control outcome. Br J Ophthalmol 1997;81:884-8. 11. Lam DS, Lai JS, Tham CC, Chua JK. Argon laser peripheral iridoplasty versus conventional systemic medical therapy in treatment of acute primary angle-closure glaucoma: a prospective, randomized, controlled trial. Ophthalmology 2002;109:1591-6. 12. Ritch R, Tham CC, Lam DS. Long-term success of argon laser peripheral iridoplasty in the management of plateau iris syndrome. Ophthalmology 2004;111:104-8. 13. Greve EL. Primary angle-closure glaucoma: extracapsular cataract extraction or filtering procedure? Int Ophthalmol 1988;12:157-62. 14. Acton J, Salmon JF, Scholtz R. Extracapsular cataract extraction with posterior chamber lens implantation in primary angle-closure glaucoma. Journal of Cataract & Refractive Surgery 1997;23:9304. 15. Jacobi PC, Dietlein TS, Luke C, Engels B, Krieglstein GK. Primary phacoemulsification and intraocular lens implantation for acute angle-closure glaucoma. Ophthalmology 2002;109:1579-1603. 16. Teekhasaenee C, Ritch R. Combined phacoemulsification and goniosynechialysis for uncontrolled chronic angle-closure glaucoma after acute angle-closure glaucoma. Ophthalmology 1999;106:66974. 17. Broadway DC, Grierson I, O’Brien C, Hitchings RA. Adverse effects of topical antiglaucoma medication. II. The outcome of filtration surgery [see comments]. Arch Ophthalmol 1994;112:1446-54. 18. von der Lippe I, Kuchle M, Naumann GO. Pseudoexfoliation syndrome as a risk factor for acute ciliary block angle closure glaucoma. Acta Ophthalmol. 1993;71:277-9. 19. Gazzard G, Foster PJ, Devereux JG, et al. Intraocular pressure and visual field loss in primary angle closure and primary open angle glaucomas. Br J Ophthalmol 2003;87:720-5. 20. Aung T, Wong HT, Yip CC, Leong JYN, et al. Comparison of the intraocular pressure-lowering effect of latanoprost and timolol in patients with chronic angle closure glaucoma. A preliminary study. Ophthalmology 2000;107:1178-83.

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Management of Angle-closure 21. Foster PJ, Devereux JG, Alsbirk PH, et al. Detection of gonioscopically occludable angles and primary angle closure glaucoma by estimation of limbal chamber depth in Asians: modified grading scheme. Br J Ophthalmol 2000;84:186-92. 22. Devereux JG, Foster PJ, Baasanhu J, Uranchimeg D, et al. Anterior chamber depth measurement as a screening tool for primary angleclosure glaucoma in an east Asian population. Arch Ophthalmol 2000;118:257-63.

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23. Wilson JMG, Jungner G. Criteria for assessing the viability, effectiveness & appropriateness of a screening programme. 1968;34. Geneva: World Health Organization. Public Health paper. 24. Nolan WP, Baasanhu J, Undraa A, et al. Screening for primary angle closure in Mongolia: a randomised controlled trial to determine whether screening and prophylactic treatment will reduce the incidence of primary angle closure glaucoma in an east Asian population. Br J Ophthalmol 2003;87:271-4.

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16 Modulation of Wound Healing

Table 16.1: Strategies for modulating wound healing

INTRODUCTION The wound healing response is the single most important determinant of the final intraocular pressure after trabeculectomy, with excessive postoperative scarring significantly reducing success.1,2 Over the last 20 years there has been increasing use of agents to modulate this response and produce an improved outcome from filtration surgery. Recent advances in molecular and cell biology have made a major impact on our understanding of the wound healing process and its modification. This is leading to the advent of new agents as modulators of the scarring response following glaucoma surgery. The glaucoma surgeon has the opportunity to assess and modulate the wound healing response before, during and after surgery. In this chapter we look at these three stages in turn and review the spectrum of antiscarring therapies that are either currently available or in development for use in each situation. Finally, since the wound healing response is involved in the pathogenesis of glaucoma by several different mechanisms, we briefly comment on the potential of modulating other important sites implicated in this disease, such as modifying the growth factor, TGF-β in the trabecular meshwork and optic nerve head (Table 16.1).

PREOPERATIVE STRATEGIES Careful preoperative assessment of the patient allows the glaucoma surgeon to estimate the risk of failure of drainage surgery. A number of factors are known to increase the chance of scarring, as summarized in Table 16.2. This knowledge can then be applied to the individual patient, taking into account their particular

Preoperative strategies

Topical steroid Oral steroid

Intraoperative strategies

5-Fluorouracil Mitomycin-C Beta irradiation Photodynamic therapy BCECF-AM TGF β antibody Suramin

Postoperative strategies

Topical steroid 5-Fluorouracil Tranilast Interferon alpha 2β

Future strategies

Modulate TGF β in trabecular meshwork Modulate TGF β in optic nerve head

Table 16.2: Risk factors for scarring and failure after glaucoma filtration surgery Risk factor

Comment

Age

Higher risk if younger, especially under 40

Race

Higher risk if African – Caribbean, less if Caucasian

Previous topical medication

Higher risk with epinephrine or allergy

Uveitis

Higher risk if chronic or active at time of surgery

Chronic conjunctival inflammation Previous failed glaucoma surgery Previous conjunctival surgery Recent cataract surgery

May be risk factor for up to 6 months

Neovascular glaucoma Aphakia

characteristics and resulting in a personalized risk assessment for that patient. Many of the risk factors, such

Modulation of Wound Healing as previous surgery, inflammation and use of topical medications are associated with the prior activation of fibroblasts. This may prime the postsurgical fibroblastic response causing increased fibrosis and a greater risk of bleb failure.

Preoperative Topical Steroid The effect of preoperative topical steroid treatment on conjunctival histology and trabeculectomy outcome was prospectively studied by Broadway et al. 3 They investigated a group of 30 patients who were on topical glaucoma medications and who were due to undergo trabeculectomy. They performed conjunctival biopsy one month prior to surgery and then commenced pretreatment with topical fluoromethalone 1 percent four times daily. Two further biopsies were taken at the time of surgery and all specimens were examined histologically. They found that pretreatment with topical steroid reduced the number of inflammatory cells and fibroblasts. They also looked at the clinical outcome from trabeculectomy in 16 of these patients, comparing them to 16 matched control patients who had not received steroid pretreatment. Success was defined as an intraocular pressure (IOP) of less than 21 mm Hg without medication. The pretreated group had an 81 percent success rate at 12 months compared to a 50 percent success rate in the control group. This suggested that pretreatment with topical steroid modulated the early wound healing response and improved the outcome from trabeculectomy in this group of patients. All the patients in this study were at relatively high risk of failure because although they had not had previous filtration surgery, they were all on multiple topical glaucoma medications including topical adrenergic agonists. Previous work from the same group had shown that patients in this situation have an increased number of conjunctival inflammatory cells and fibroblasts and a reduced trabeculectomy success rate of 45 percent.4-6 Pretreatment with topical steroid has not, however, become standard practice, but it is used in selected cases by some clinicians, for example in the uveitic eye in combination with oral steroid. Preoperative Oral Steroid The use of oral prednisolone as an adjunct to trabeculectomy was investigated in a prospective

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randomized double-masked placebo controlled trial by Azuara-Blanco et al.7 They gave patients either 50 mg of oral prednisone or placebo twice daily for 3 days in the perioperative period. Success of surgery was defined as an IOP < 15 mm Hg with no more than one topical antiglaucoma medication. At 9 months, 63.0 percent of the steroid group and 65.6 percent of the control group had achieved this successful outcome, suggesting that the use of oral prednisone in had no beneficial effect. However, the patients in this study were not selected for preoperative risk factors for surgery failure. Many clinicians will use oral prednisolone pretreatment in situations where there is a high risk of inflammation and scarring, such as a uveitic patient or before complex tube surgery.

INTRAOPERATIVE STRATEGIES The most common stage to begin modulating the wound healing response is during surgery. Any preplanned strategies based on known risk factors may be altered at this stage by the flexible glaucoma surgeon, who will be aware of intraoperative findings such as unexpectedly thin conjunctiva. The introduction of the antiproliferative agents mitomycin-C and 5-fluorouracil has greatly improved the outcome from glaucoma filtration surgery, particularly in patients known to be at high risk of scarring.8-10 These adjuncts are now in widespread use, but their toxic cellular effects have been associated with severe complications, such as hypotony, bleb leaks and infections.11-14 This has led to the continued search for alternative intraoperative antiscarring treatments, which are also discussed below.

5-Fluorouracil 5-Fluorouracil (5-FU) is a cytotoxic agent that antagonizes pyrimidine metabolism, causing inhibition of DNA synthesis. In the context of glaucoma surgery, 5-FU has the role of inhibiting proliferation of conjunctival and Tenon’s capsule fibroblasts. Surgery is seen by the body as an injury and immediately stimulates the start of a cascade of events that are the wound healing response. A key step in this chain of events is the proliferation of fibroblasts as these cells synthesize collagen to form a scar, are responsible for wound contraction

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and produce matrix metalloproteases (MMPs) to allow wound remodelling. As 5-FU influences this important series of events it is an effective agent in the modulation of wound healing. The use of 5-FU in glaucoma surgery started in the early 1980s, but its intraoperative use did not become more widespread until there was a greater understanding of its effects on cell biology and the wound healing response.15,16 Early animal studies had showed that adjunctive injection of 5-FU following trabeculectomy decreased fibroblast proliferation and scarring with prolonged bleb survival compared to no 5-FU.17 Khaw and co-workers showed in vitro and in vivo that a 5minute exposure of 5-FU clearly caused growth arrest and a long lasting effect on cultured human Tenon’s fibroblasts.18 His group also demonstrated that a single exposure of 5-FU interferes with ocular fibroblastmediated collagen.19 This added to the developing concept of using a single intraoperative application of 5FU as a targeted, focal antiscarring treatment to improve trabeculectomy survival.20-24 The early clinical studies in America and England of intraoperative 5-FU, both as a sole treatment and as a supplement to postoperative injections, suggested a beneficial effect on filtration surgery survival and enhanced intraocular pressure lowering, with minimal side effects.25-27 Randomised trials have shown that intraoperative 5-FU is effective in trabeculectomy surgery in East and West Africa, a population group who have a higher risk of scarring and trabeculectomy failure.28, 29 Interestingly, in this population MMC and 5-FU may have similar efficacy in primary surgery.30 There are a number of clinical trials about to report their results on the effect of a single intraoperative application of 5-FU in low risk patients undergoing first-time surgery. These include a large randomised, controlled study based at Moorfields Eye Hospital (MRC 5FU trial) comparing 5FU to placebo and a similar study in Singapore. Results from these studies will also provide the clinician with detailed Long-term follow up of the outcome from trabeculectomy with intraoperative 5-FU, including visual field and optic disc changes.

Mitomycin-C The first antiproliferative agent to be used successfully to enhance the outcome from trabeculectomy was mitomycin-C.9 Mitomycin-C is an antibiotic agent that is activated by reduction into an alkylating agent. It has potent effects on cellular function, inhibiting DNA replication, mitosis and protein synthesis. In the context of glaucoma surgery it acts to modulate the wound healing response at a similar stage to 5-FU, inhibiting fibroblast proliferation. It is, however, both stronger in its effect and potentially more toxic than 5-FU. Khaw and co-workers showed that at clinical concentrations mitomycin caused cell death and permanent inhibition, whereas there is only temporary inhibition of proliferation with late recovery occurred with 5-FU.20-22 The use of a single five-minute exposure to mitomycin-C provides a superior surgical success rate compared to 5-FU injections in many high risk patients but unfortunately can also result in a greater chance of bleb leaks and possible infection.14, 31-33 The use of intraoperative MMC has, however, dramatically improved the outcome from surgery in patients who previously had a low chance of successful filtration surgery, such as people with cicatricial conjunctiva and young patients with congenital glaucoma.34-36 Adjunctive MMC usage in tube (glaucoma drainage device) surgery is also now increasingly common. Although there is relatively little evidence for this practice, MMC use in this clinical situation could be expected to be beneficial as tube surgery is most commonly performed in eyes with complex glaucoma and multiple risk factors for trabeculectomy failure. Perkins et al studied the effect of MMC in patients undergoing Molteno tube surgery and found that it increased the chance of good IOP control without medications compared to placebo.37 There is no standardised method for the intraoperative application of MMC and there is great variation between clinicians in the dose used. Many will also alter the dose depending on the case and risk factors for scarring, tailoring the antiproliferative effect to fit an individual patients’ requirements. Use of a concentration between 0.2 mg/ml and 0.5 mg/ml, applied for 2 to 5 minutes is most usual.38 The size of the MMC treatment

Modulation of Wound Healing area is an important parameter that has been demonstrated to influence bleb morphology: small treatment areas give rise to thin-walled, cystic blebs whereas large treatment areas are associated with more diffuse-looking, thicker walled blebs.39 Altering clinical practice in this way with the use of larger treatment areas to improve the bleb appearance should reduce the incidence of bleb-related complications after glaucoma surgery.

Beta Irradiation Beta radiation was proposed for use as an adjunct to glaucoma surgery in the late 1960s to early 1970s, long before modern chemical antiproliferatives.40, 41 It is simple to use in practice and became established in certain centres for intraoperative use in the treatment of complex cases, such as congenital glaucoma. 42 More recent scientific study has shown in vitro and in vivo that a single application of beta radiation inhibits proliferation of human Tenon’s fibroblasts, causing growth arrest but not cell death.43 This has led to a renewed interest in the use of intraoperative beta irradiation in trabeculectomy, although it has not yet convincingly been proven to be effective in a randomised controlled trial of routine glaucoma patients.44-46 The simplicity of its application and the suggestion that it may avoid some of the side effects of other chemical antimetabolites, has caused some clinicians to believe that beta radiation may be particularly appropriate for use in developing countries. A study in South Africa has recently been completed and is due to report on the effect of a single intraoperative application of β-irradiation.

Photodynamic Therapy with BCECF-AM This technique to modulate wound healing involves the intraoperative application of BCECF-AM (2,7,-bis-(2carboxyethyl)-5-(and-6)-carboxyfluorescein acetoxymethyl-ester and subsequent photodynamic therapy during the surgical procedure. BCECF-AM is an intracellularly acting photosensitiser, which is applied directly by subconjunctival injection to the site where it is needed at the start of surgery. When it diffuses into cells it is altered and becomes fluorescent. After the formation of the conjunctival flap a focused area of the

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sclera is illuminated with blue light of the wavelength 450 to 490 nm for 8 minutes. Under these conditions BCECF-AM produces a photo-oxidative effect that results in cell destruction of targeted cells. This effect is strictly limited to the illuminated area.47 A scleral flap is then dissected in the illumination zone and trabeculectomy surgery is completed as normal. Carboxyfluorescein has been demonstrated in vitro to exer t a phototoxic effect on human Tenon’s fibroblasts.47 Grisanti et al showed that, in a rabbit model of filtration surgery, this form of photodynamic therapy has the ability to modify postoperative fibrosis.48 Early clinical studies in Germany from the group of Diestelhorst and Krieglstein have assessed the effect of photodynamic therapy in consecutive patient series.49,50 They have indicated that this technique has potential to improve bleb survival and provide reasonable IOP reduction. These studies have also tried to assess the clinical safety and tolerability of this new treatment and so far there do not appear to be any significant problems with local toxicity, intraocular inflammation or patient discomfort. A multicentre randomised placebo controlled clinical trial to investigate the efficacy of BCECF-AM based photodynamic therapy compared to standard trabeculectomy is now planned.

TGF β2 Antibody (CAT-152) Transforming growth factor beta (TGFβ) is a multifunctional cytokine, which is implicated as the key growth factor in the process of wound healing and tissue repair, with its sustained overproduction resulting in tissue fibrosis. 51 TGFβ regulates the coordinated sequence of events involved it the wound healing process, acting as a macrophage chemoattractant, stimulating fibroblast migration, proliferation and collagen synthesis, and also enhancing angiogenesis.51, 52 There are three isoforms of TGFβ in mammals: TGFβ1, TGFβ2 and TGFβ3, with TGFβ2 being the predominant isoform in the eye.53-55 Glaucoma patients have been found to higher levels of TGFβ2 in their aqueous humor than normal subjects.56 CAT-152 is a fully human monoclonal antibody, which specifically and potently neutralizes the active form of human TGF-β2. Laboratory studies have shown its ability to modulate the wound healing process in vitro

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and in vivo. In an animal model of glaucoma filtration surgery it significantly improved outcome compared to control (p10 mm Hg) during the first postoperative days after phakic IOL surgery and is the most common cause of postoperative IOP increase (Fig. 17.1). Incidence of 7.2 to 20.8 percent for angle-supported phakic IOLs,1-4 4.5 to 15.6 percent for iris-fixated phakic IOLs5-11 and 5.8 to 23.2 percent for posterior chamber phakic IOLs12-16 have been reported. Pain and some degree of vision loss may be present, but the eye shows normal reactive pupil, deep anterior chamber, permeable iridotomies and no corneal edema. Very rarely, viscoelastic can be the cause of a pupillary block.13 Once the cause is clear and pupillary block is rulled out, decompressing the eye using the port incision or through a new paracentesis can be done. Topical beta-blocker, alpha-2 agonist or oral acetazolamide up to 1.0g a day can be used to control IOP. Prevention includes complete intraoperative removal of viscoelastic and IOP reducing therapy with oral acetazolamide during the first two days after phakic IOL implantation on a routine basis. The use of cohesive viscoelastics is preferable for phakic IOL surgery, since this

kind of viscoelastics can be removed from the anterior chamber more easily than the dispersive ones.

Pupillary Block Situation arising from an obstruction of aqueous humor circulation from the posterior to the anterior chamber caused by touch between the phakic IOL and the pupillary border (Fig. 17.2). Typically the patient presents with intense pain and photophobia, and examination shows a narrow angle, with forward displacement of the iris, crystalline lens and phakic IOL in the absence of a patent iridotomy. This can be caused by any kind of phakic IOL but is more likely after posterior chamber phakic IOLs. Reported incidences are 0 to 11.5 percent for angle-supported phakic IOLs,1-4 0 to 0.8 percent for iris-fixated phakic IOLs5-11 and 0 to 12.5 percent for posterior chamber phakic IOLs.12-16 Pupillary block is avoided by making permeable iridotomies with the Nd:Yag laser preoperatively or by performing a surgical intraoperative iridotomy or iridectomy. It is important to make sure that both layers of the iris are perforated by observing the anterior capsule of the crystalline lens or the zonular fibers through the iridotomy. In the presence of a pupillary block after anterior chamber phakic IOL implantation, miosis with pilocarpine may help to unblock the pupil separating it from the IOL before iridotomies are enlarged surgically or with the Nd:Yag laser. In the presence of pupillary block after posterior chamber phakic IOL implantation, the chamber is very flat, the IOL looks overvaulted, and the treatment implies dilating the pupil with phenylephrine 10 percent and atropine 1 percent, and performing a new peripheral iridotomy or enlarging

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Fig. 17.1: Trabecular block by viscoelastic is the most common cause of elevated IOP after phakic IOL implantation. Anterior chamber depth is normal and iris plane is in a physiological position (Courtesy of Highlights of Ophthalmology)

Fig. 17.2: Pupillary block after posterior chamber phakic IOL implantation. The anterior chamber is flat and the IOL and iris are forwarded, but the position of the crystalline lens is normal (Courtesy of Highlights of Ophthalmology).

the previous ones. If this is not effective a surgical iridectomy or lens removal may be necessary.

Malignant Glaucoma This situation implies a peripheral block at the trabeculum and reversed aqueous flow towards the vitreous. It can follow pupillary block when aqueous accumulates in the posterior chamber and pushes the iris forward (Figs 17.3A and B). The incidence of malignant glaucoma after phakic IOL implantation is very rare, but seems to be more common after posterior chamber phakic IOL, ranging from 0.1 to 1.4 percent.12-16 Typically intense pain, vomiting, photophobia and very high IOP are present, and the slit-lamp exam shows corneal edema, a non-reactive pupil with mydriasis, and a narrow

Figs 17.3A and B: Malignant glaucoma after posterior chamber phakic IOL implantation. Atalamy with forwarded crystallineIOL-iris and misdirection of the aqueous humor to the vitreous cavity (Courtesy of Highlights of Ophthalmology)

anterior chamber, situation which is not reversed by enlarging the iridotomy. Initial treatment includes inducing mydriasis to unblock the pupil and intravenous mannitol to dehydrate the vitreous. If there is no progress, explantation of the phakic IOL must be done, but

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sometimes it is necessary to perform phacoemulsification and posterior vitrectomy via pars plana to solve the problem.

Angle Closure In larger than needed posterior chamber phakic IOLs, the angle can be closed by excessive pushing of the peripheral iris forward. This is called excessive vault (Figs 17.4 and 17.5). Angle closure is more frequent in hyperopic patients because the anterior chamber angle is usually narrower. On average, a properly sized posterior chamber phakic IOL reduces the iridocorneal angle width by 15 to 20 percent. Changing the lens for a smaller one with smaller vault, or extracting the PIOL can solve the situation. In the presence of an angle-supported phakic IOL, angle closure can be caused by anterior synechiae, but this is an extremely infrequent situation (Fig. 17.6).

Fig. 17.4: Adequate vaulting of a posterior chamber phakic IOL

Pigment Dispersion Excluding the cases produced by excessive surgical trauma, this is a very rare complication after phakic IOL surgery. It has been reported after the use of posterior chamber phakic IOLs with excessive vault and IOLperipheral iris touch, together with the development of cataract (Figs 17.7A and B).

Steroid-induced Glaucoma It has been reported in 13 to 30 percent of patients after phakic IOL implantation for high myopia.1-3 The IOP raises between the second and the fourth week after surgery while topical steroids are used. Recently marketed topical steroids such as rimexolone can help to decrease the incidence of steroid glaucoma. In the presence of steroid glaucoma after phakic IOL implantation, topical steroids should be discontinued and non-steroidal antiinflammatory drugs together with antiglaucomatous agents should be used until the IOP normalizes. Phakic IOLs do not seem to produce IOP elevation in the long-term.1,3,15 In summary, in the presence of IOP increase in the first few days after phakic IOL implantation: • Check the patency of the iridotomy and if in doubt enlarge it with the Nd:Yag laser. Sometimes the haptic of the IOL may be closing the iridotomy

Fig. 17.5: Excessive vaulting of a posterior chamber phakic IOL, with pushing of the peripheral iris and angle narrowing

Fig. 17.6: The haptic of an angle supported phakic IOL can produce anterior synechiae and rarely a chronic elevation of the IOP

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Figs 17.7A and B: Pigment dispersion after posterior chamber phakic IOL implantation with excessive vault and IOL-peripheral iris touch

• Treat IOP increase with oral acetazolamide 250 mg every 6 hours and topical beta-blocker or topical alpha-2 agonist twice a day, and stop the topical steroid as soon as possible • In the presence of a posterior chamber phakic IOLs, check the gap between the lens and anterior capsule to look for signs of excessive vault which may be closing the anterior chamber angle.

GLAUCOMA AFTER LASER ASSISTED IN SITU KERATOMILEUSIS Patients undergoing laser assisted in situ keratomileusis (LASIK) may present glaucomatous complications in the postoperative period, which include the following.

Topical steroids are part of the normal postoperative regimen following LASIK. Myopic patients undergoing refractive corneal procedures are at higher risk of developing steroid-induced glaucoma. The rise of intraocular pressure due to topical steroids can cause fluid collection in the potential space between the flap and the stromal bed, leading to erroneous low applanation tonometry readings. This fluid results from transudation of aqueous humor across the stromal bed due to increased IOP. The clinical picture of steroid-induced glaucoma after LASIK is similar to that of diffuse lamellar keratitis (DLK) (Fig. 17.8).17-18 If a patient presenting fluid collection in the interface after LASIK due to increased IOP is misdiagnosed as having an inflammatory or an infectious process, higher doses of topical steroids will be used, thus producing a worsening of the induced glaucoma. Slitlamp examination of these patients show an optically clear fluid-filled space confined to the interface. Elevated IOP is often misdiagnosed, because the standard central measurement of intraocular pressure by Goldmann tonometry is erroneously very low. 19 This low IOP is caused by the “airbag” effect of the interface fluid, together with the LASIK reduction of corneal thickness, which also underestimate Goldmann applanation tonometry.20 Diffuse lamellar keratitis typically appears 1 to 3 days after LASIK, and lasts no more than 10 days with appropriate treatment. A patient who has been on topical steroids for DLK and does not improve should be carefully evaluated for steroid-induced glaucoma associated with interface fluid. In addition, a diagnosis of late DLK made more than 10 days after LASIK should make us think of this syndrome and look for the fluid in the interface.18 If interface fluid develops, IOP should be measured on the peripheral cornea or with other methods such as the Tono-pen. Topical steroids should be tapered or discontinued if possible, and medications to lower IOP should be initiated. With proper diagnosis and management, profound glaucomatous optic neuropathy can be avoided.18

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Fig. 17.8: Clinical picture of steroid-induced glaucoma after LASIK. Diffuse lamellar keratitis-like reaction, with collection of fluid at the interface level and paradoxically low IOP readings

Acute Optic Neuropathy after LASIK A positive scotoma and profound loss of vision immediately after uneventful LASIK is a rare complication of the technique.21 A relative afferent pupillary defect is normally present. Anterior segment is unremarkable, and posterior segment examination may show a normal optic disk or signs of papiledema. The visual field shows altitudinal defects or scotoma corresponding to focal defect in the retinal nerve fiber layer. This scotoma does not usually progress but rarely disappears (Figs 17.9A to C). Barotrauma and ischemia have been implicated in the development of acute optic neuritis after LASIK. Intraocular pressure reaches 80 to 230 mm Hg during the application of suction and 140 to 300 mm Hg during the microkeratome pass. This may compress the ganglion cells, the retinal nerve fiber layer and the lamina cribosa. Ischemia of the optic nerve and retina may be due to temporal closure of the short posterior cilliary arteries and central retinal artery when IOP exceeds 45 mm Hg. Risk factors for developing acute optic neuropathy after LASIK include age over 35 years, cardiovascular disease, diabetes and systemic hypertension.21 Local factors include tilted optic nerve, palor of the optic nerve, drusen of the optic disk, small optic disk with no cup and previous glaucoma or ischemic neuropathy.21 To minimize the incidence of LASIK induced optic neuritis, it is important to reduce the time of IOP rise at maximum,

Figs 17.9A to C: Altitudinal visual field defect as a result of acute optic neuropathy after LASIK. Visual field one week (A), one month (B) and six months (C) after uneventful LASIK

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especially in patients with the above mentioned systemic or local risk factors.

REFERENCES 1. Muñoz G, Alió JL, Montés-Micó R, et al. Angle-supported phakic intraocular lenses followed by lasik for the correction of high myopia. Am J Ophthalmol 2003;136:490-9. 2. Baikoff G, Arne JL, Bokobza Y, et al. Angle-fixated anterior chamber phakic intraocular lens for myopia of -7 to -19 diopters. J Refract Surg 1998;14:282-93. 3. Alió JL, de la Hoz F, Perez-Santonja JJ, et al. Phakic anterior chamber lenses for the correction of myopia: A 7-year cumulative analysis of complications in 263 cases. Ophthalmology 1999;106:458-66. 4. de Souza RF, Forseto A, Nose K, et al. Anterior chamber intraocular lens for high myopia. J Cataract Refract Surg 2001;27:1248-53. 5. Guell JL, Vazquez M, Gris O. Adjustable refractive surgery: 6-mm Artisan lens plus laser in situ keratomileusis for the correction of high myopia. Ophthalmology 2001;108:945-52. 6. Alió JL, Mulet ME, Shalaby AMM. Artisan phakic iris claw intraocular lens for high primary and secondary hyperopia. J Refract Surg 2002;18:697-707. 7. Pérez-Santonja JJ, Bueno JL, Zato MA. Surgical correction of high myopia in phakic eyes with Worst-Fechner myopia intraocular lenses. J Refract Surg 1997;13:268-81. 8. Menezo JL, Cisneros AL, Rodriguez-Salvador V. Endothelial study of iris-claw phakic lens: four year follow-up. J Cataract Refract Surg 1998;24:1039-49. 9. Dick HB, Alió J, Bianchetti M, et al. Toric phakic intraocular lens: European multicenter study. Ophthalmology 2003;110:150-62.

10. Budo C, Hessloehl J, Izak M, et al. Multicenter study of the Artisan phakic intraocular lens. J Cataract Refract Surg 2000;26:1163-71. 11. Maloney RK, Nguyen LH, John ME. The Artisan Lens Study Group. Artisan phakic intraocular lens for myopia: short-term results of a prospective multicenter study. Ophthalmology 2002;109:1631-41. 12. Zaldivar R, Davidorf JM, Oscherow S, et al. Combined posterior chamber phakic intraocular lens and laser in situ keratomileusis: Bioptics for extreme myopia. J Refract Surg 1999;15:299-308. 13. Jiménez-Alfaro I, Benítez del Castillo JM, García-Feijoo J, et al. Safety of posterior chamber phakic intraocular lenses for the correction of myopia. Ophthalmology 2001;108:90-9. 14. Sanders DR, Martin RG, Brown DC, et al. Posterior chamber phakic intraocular lens for hyperopia. J Refract Surg 1999;15:309-15. 15. Uusitalo RJ, Aine E, Sen NH, et al. Implantable contact lens for high myopia. J Cataract Refract Surg 2002;28:29-36. 16. Davidorf JM, Zaldivar R, Oscherow S. Posterior chamber phakic intraocular lens for hyperopia of +4 to +11 diopters. J Refract Surg 1998;14:306-11. 17. Lyle WA, Jin GJC. Interface fluid associated with diffuse lamellar keratitis and epithelial ingrowth after laser in situ keratomileusis. J Cataract Refract Surg 1999;25:1009–12. 18. Hamilton DR, Manche EE, Rich LF, et al. Steroid-induced glaucoma after laser in situ keratomileusis associated with interface fluid. Ophthalmology 2002;109:659-65. 19. Najman-Vainer J, Smith RJ, Maloney RK. Interface fluid after LASIK: Misleading tonometry can lead to end-stage glaucoma. J Cataract Refract Surg 2000; 26:471–2. 20. Rehany U, Bersudsky V, Rumelt S. Paradoxical hypotony after laser in situ keratomileusis. J Cataract Refract Surg 2000; 26:1823–6. 21. Cameron BD, Saffra NA, Strominger MB. Laser in situ keratomileusis-induced optic neuropathy. Ophthalmology 2001;108:660–5.

Index

203

Index

type 1 45 type 2 45 type 3 45

A Abexterno trabeculectomy 103 Ahmed valve 58 Ahmed valve combined with secondary and sutured intraocular lens implantation 69 Ahmed valve implantation and vitreoretinal surgical procedures 70 Ahmed valve in combined procedures 68 cataract extraction and Ahmed valve implantation 68 complications and their management 71 early postoperative complications 73 intraoperative complications 71 late postoperative complications 74 indications 59 models for implantation 58 AGV-B1 58 AGV-FP7 58 AGV-S2 58 AGV-S3 58 penetrating keratoplasty and Ahmed valve implantation 67 surgical technique 59 technique for double plate Ahmed 66 Anesthesia 11 general 11 local 12 Antimetabolite related complications 16 Antimetabolites 141 Antiscarring agents 17 Argon and Nd:YAG lasers 49 Argon lasers traculoplasty 161

B Bleb 45, 141 encapsulated 45

C Cairns technique 36 Capsulorrhexis 177 Closure of the scleral flap 179 Combined cataract glaucoma surgery 170 choice of the procedure 172 special considerations 170 surgical options 171 cataract surgery alone 171 combined cataract and glaucoma procedure 171 glaucoma surgery first 172 surgical procedure 173 closure of the conjunctiva 179 conjunctival flap 174 hemostasis 174 mitomycin-C 175 phacoemulsification 175 postoperative care 180 scleral flap 175 traction suture 174 Complications of transscleral Nd:YAG cyclophotocoagulation 38 Control of bleb fibrosis by antiinflammatory agents 80 Control of bleb fibrosis by delayed drainage of aqueous 81 Control of intraocular pressure 98 Cyclocryocoagulation 38 Cyclodestruction in glaucoma 37 current cyclodestructive procedures 38 infrared 810 nm diode laser cyclophotocoagulation 38 red 647 nm krypton and 670 nm diode laser cyclophotocoagulation 41 early cyclodestructive procedures 37 cyclodiathermy 37

Nd:YAG cyclophotocoagulation 38 indications for partial cyclodestruction 42 mechanism of intraocular pressure reduction 42 Cyclodiathermy 38

D Deep sclerectomy 102, 131 management 137 Nd:YAG goniopuncture after NPGS 138 perforation of trabeculo-Descemet’s membrane 137 results of NPGS 138 surgical steps 131 Diffuse lamellar keratitis-like reaction 200 Digital ocular massage 141 Diurnal pressure curve 126

E Extracapsular method for combined surgery 179

F 5-Fluorouracil 142 Failing filtering bleb 45 Filtering surgery 46 Filtration surgery-preoperative details 12 Fornix-based flap 179 Frequency doubling technology 112

G Glaucoma 1 Glaucoma filtration surgery 23 intraoperative complications 24 conjunctional, scleral and iris bleeding 25 conjunctival tear 24

204

Atlas of Glaucoma Surgery

scleral flap damage 24 suprachoroidal hemorrhage 25 vitreous loss 25 wound leak 25 postoperative complications 26 “wipe out” of remaining field/ vision 26 astigmatism 31 blebitis and endophthalmitis 30 cataract 30 choroidal effusion 26 fistula blockage 28 hypotony: due to aqueous overdrainage 26 late bleb leak focal or diffuse 29 posterior division of aqueous (malignant glaucoma) 27 ptosis and strabismus 31 pupil block 28 raised intraocular pressure 27 shallow/flat anterior chamber 26 subconjunctival fibrosis 28 postoperative management of 23 Glaucomatous complications of refractive surgery 197 glaucoma after laser assisted in situ keratomileusis 200 acute optic neuropathy after LASIK 201 angle closure 199 glaucoma associated with phakic intraocular lens implantation 197 malignant glaucoma 198 pigment dispersion 199 pupillary block 197 steroid-induced glaucoma 199 steroid-induced glaucoma after Lasik associated with interface fluid 200 trabecular block by viscoelastic 197 Guarded sclerostomy procedure 11

H Haemophilus 30 Holy Grail of glaucoma treatment 1

I Intraocular pressure 1 economical burden of IOP lowering strategies 7 ideal treatment to reduce IOP 1 in surgery better than drugs 1 issue of compliance and persistence 4 long-term IOP reduction 2

minimal IOP diurnal fluctuations 3 ocular side effects and complications 5 sufficient reduction of IOP 1 systemic side effects and complications 6 IOL insertion 177 Iridectomy 179

K Kelly-Descemet’s punch 178

L Laser trabeculoplasty 2, 161 Limbus-based flap 179

M Management of angle-closure 182 change angle configuration and prevent further closure 183 cataract surgery and lens extraction 185 laser iridoplasty 184 laser iridotomy 183 medical management of angleclosure 185 surgical iridectomy 184 detection and control of continuing optic disk and visual field damage 186 immediate control of symptoms and raised IOP 182 prevention 186 Management of filtration failure 50 bleb needling 52 bleb reconstruction 54 digital compression 50 laser cautery of bleb vessels 54 laser suturelysis 50 complications 51 historical aspects 50 indications 50 technique 50 trephination 52 technique 53 Minsky’s maneuver 121 Mitomycin-C 32, 142

N Nd:YAG goniopuncture 141 Nd:YAG laser 27 Nd:YAG laser cyclophotocoagulation 37 Neovascular glaucoma 95 New technique versus classic trabeculectomy 36

Nonpenetrating deep sclerectomy (NPDS) 112 anatomic landmarks 113 complications of surgery 115 triangular flap dissected too deeply 115 triangular flap dissected too superficially 115 contraindication 113 early indication of NPDS in open-angle glaucomas 112 gonioscopy after NPDS 122 learning curve 121 ND:YAG laser goniopuncture 123 follow-up 124 NPDS pearls 121 surgical technique 113 Nonpenetrating glaucoma surgery 102, 104, 140 complications and management 142 early postoperative complications 142 bleb leak 143 bleeding during gonioscopy 145 cataract formation 145 choroidal detachment 143 hyphema 143 hypotony 143 inflammation 143 malignant glaucoma 145 ocular hypertension 143 shallow anterior chamber 143 suprachoroidal hemorrhage 144 TDM rupture 145 late postoperative complications 145 bleb fibrosis 146 cataract progression 146 Descemet’s membrane detachment 146 encapsulated bleb 146 iris prolapse 145 peripheral anterior synechiae 146 scleral ectasis 147 postoperative medication 140 routine evaluation regimen and management 140 Nonpenetrating surgery 102 postoperative medications 109 surgical technique 104 trabeculo-Descemet’s perforation 108 Normal bleb maturation and function 45

O Ocular hypotensive medications 6 One-stitch technique 61

Index P Pars plana tunnel 64 Peripheral iridectomy 35 Phaco and Ahmed valve combined procedure 68 Phacoemulsification 177 Phacotrabeculectomy 98, 150 Pilocarpine 182 Pre-and intraoperative drops 12 hypotensive agents 13 nonsteroidal anti-inflammatory drugs 13 parasympathetic agonists 12 povidone-iodine 12 steroids 12 sympathetic agonists 12 Primary open-angle glaucoma 4, 97, 182

R Risk factors for filtration failure 46 Risk factors for scarring and failure after glaucoma filtration surgery 188

S Schlemm’s canal 102, 103, 122 Schwalbe’s line 137 Scleral-tunnel technique 36 Sclerectomy 178 Secondary glaucomas 98 Selective laser trabeculoplasty 161 complications of SLT 167 delivery of SLT 166 effectivity of SLT 164 place of SLT in relation of ALT 161 SLT laser 162 Severity of glaucoma 84 Signs of filtration failure 47 bleb encapsulation 49 due to blockage external to the ostium 49 due to blockage of the internal ostium 48 Sinusotomy 103 Stegmann’s technique 107 Streptococcus 30 Sub-Tenon’s space 33

T TDM holes 137 Tenon’s capsule 45 Trabeculectomy 1,11, 32, 98 surgical modifications 32 surgical technique for 13 antimetabolite treatment duration and washout 18

block removal (sclerostomy) 19 conjunctival clamp 17 conjunctival closure 21 conjunctival incision 13 infusion 18 intraoperative antimetabolite use 15 paracentesis 18 peripheral iridectomy 20 position of filtration area 13 postoperative antimetabolite injections 22 postoperative medications 22 scleral flap 14 scleral flap sutures 20 traction suture 13 type of sponge 18 with a scleral tunnel technique combined with mitomycin-C 32 Trabeculotomy ab externo 150 techniques 150 Transscleral contact cyclophotocoagulation 37 Transverse tear 131

205

double plate Molteno implant 78 historical background 77 process of bleb formation (immediate drainage of aqueous) 77 illustrative cases 93 case of buphthalmos associated with Sturge-Weber syndrome 93 case of combined cataract and glaucoma surgery 95 case of neovascular glaucoma 95 case of simple buphthalmos 93 case of traumatic glaucoma 97 case of uveitic glaucoma 96 results 97 single plate Molteno implant 78 to treat complex cases of glaucoma 77

V Vicryl tie technique 81 Viscocanalostomy 102

W U Use of Molteno implants 77 current surgical technique 83 choice of surgical technique 84 cytostatic agents 91 direct control of bleb fibrosis by systemic anti-inflammatory agents 91 early complications 92 indications 83 indirect control of bleb fibrosis by hypotensive agents 91 late complications 92 long-term management (all cases) 91 postoperative management in eyes drained by delayed drainage of aqueous (vicryl tie technique) 90 postoperative management of cases with immediate drainage of aqueous 91 preoperative management 84 selection of implant area 83 surgical technique for delayed drainage of aqueous 84 surgical technique for immediate drainage of aqueous 88 surgical technique for neovascular glaucoma 89

Wound healing 188 future strategies 193 modulation of TGF-α in the optic nerve head 193 modulation of TGF-β in the trabecular meshwork 193 intraoperative strategies 189 5-fluorouracil 189 beta irradiation 191 mitomycin-C 190 photodynamic therapy with BCECF-AM 191 suramin 192 TGF β2 antibody (CAT-152) 191 postoperative strategies 192 interferon alpha 2β 193 postoperative 5-fluorouracil injection 192 postoperative topical steroid 192 tranilast 193 preoperative strategies 188 preoperative oral steroid 189 preoperative topical steroid 189 strategies for nodulating wound healing 188

Y YAG laser capsulotomy and hyaloidotomy 74