Non-Penetrating Glaucoma Surgery
Dedication To the women in our lives: Loty Mermoud, Samia Nada, Marianne Mermoud, Ghada Ibrahim, Sophie Mermoud, and Heba Shaarawy. In recognition of their undivided love, their unlimited tenderness, and their uncompromising strength. We salute and thank you. André and Tarek
Non-Penetrating Glaucoma Surgery Edited by
André Mermoud
MD, PD
Head Glaucoma Unit Hôpital Ophtalmique Jules Gonin University of Lausanne Lausanne Switzerland
Tarek Shaarawy
MD
Head Glaucoma Unit Memorial Research Institute of Ophthalmology Giza Egypt Foreword by
Robert Ritch
MD
Chief Glaucoma Service The New York Eye and Ear Infirmary New York USA
Martin Dunitz
© 2001 Martin Dunitz Ltd, a member of the Taylor & Francis Group First published in the United Kingdom in 2001 by Martin Dunitz Ltd, The Livery House, 7–9 Pratt Street, London NW1 0AE This edition published in the Taylor & Francis e-Library, 2003. Tel.: +44 (0) 20 7482-2202 Fax.: +44 (0) 20 7267-0159 E-mail:
[email protected] Website: http://www.dunitz.co.uk All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without the prior permission of the publisher or in accordance with the provisions of the Copyright, Designs and Patents Act 1988 or under the terms of any licence permitting limited copying issued by the Copyright Licensing Agency, 90 Tottenham Court Road, London W1P 0LP. A CIP record for this book is available from the British Library. ISBN 0-203-21537-0 Master e-book ISBN Distributed in the United States by: ISBN 0-203-27180-7 (Adobe eReader Format) ISBN 1 84184 042 4 (Print Edition) Tel.: 1-800-215-1000 Distributed in Brazil by: Ernesto Reichmann Distribuidora de Livros, Ltda Tatuape 03440-000, São Paulo
Composition by Scribe Design, Gillingham, Kent, UK
Contents
1
2
3
4
5
Contributors
vii
Foreword
ix
Acknowledgements
xi
The history of filtering surgery Howard C Cohn
1
6
Experimental studies in non-penetrating glaucoma surgery 67 Christophe Nguyen and Tarek Shaarawy
7
Indications and contraindications for non-penetrating glaucoma surgery 87 Elie Dahan
8
Surgical technique 97 André Mermoud and Emilie Ravinet
9
Viscocanalostomy Robert Stegmann and Roberto G Carassa
Evolution of non-penetrating glaucoma surgery 13 André Mermoud Anatomical features of outflow pathway Farid Achache
21
How does non-penetrating glaucoma surgery work? 33 Douglas H Johnson and Mark Johnson Mechanisms of filtration in non-penetrating filtering surgeries 57 André Mermoud and Emilie Ravinet
10 Modulation of wound healing Tarek Shaarawy
109
117
11 Postoperative management of non-penetrating filtering surgery 125 Tarek Shaarawy
vi
Contents
12 Complications and reoperations 139 André Mermoud and Emilie Ravinet
15 Implants in non-penetrating filtering surgery 177 Corinne C Schnyder and Emilie Ravinet
13 Results of non-penetrating glaucoma surgery 161 Tarek Shaarawy
16 Erbium:YAG laser-assisted deep sclerectomy 185 Wolfgang E Lieb
14 Phacoemulsification combined with viscocanalostomy and deep sclerectomy 169 Fathi El-Sayyad
Index
195
Contributors Farid Achache, MD Hôpital Ophtalmique Jules Gonin, University of Lausanne, Lausanne, Switzerland.
André Mermoud, MD, PD Hôpital Ophtalmique Jules Gonin, University of Lausanne, Lausanne, Switzerland
Roberto G Carassa, MD Department of Ophtalmology and Visual Sciences, University S. Raffaele, Milano, Italy.
Christophe Nguyen, MD Hôpital Ophtalmique Jules Gonin, University of Lausanne, Lausanne, Switzerland.
Howard C Cohn, MD 45 Rue Vineuse, Paris 75016, France.
Emilie C M Ravinet, MD Hôpital Ophtalmique Jules Gonin, University of Lausanne, Lausanne, Switzerland.
Elie Dahan, MD University of the Witwatersrand and Oxford Eye Center, Johannesburg, South Africa. Fathi El-Sayyad, FRCS Magrabi Eye Hospital, Cairo, Egypt. Douglas H Johnson, MD Professor of Ophtalmology, Mayo Clinic, Rochester MN, USA. Mark Johnson, MD Biomedical Engineering Department, Northwestern University, Evanston, IL, USA. Wolfgang E Lieb, MD Professor of Ophthalmology, Julius-Maximilians-University, Würzburg, Germany.
Robert Ritch, MD Chief, Glaucoma Service, The New York Eye and Ear Infirmary, New York, USA. Corinne C Schnyder, MD Hôpital Ophtalmique Jules Gonin. University of Lausanne. Lausanne, Switzerland Tarek Shaarawy Hôpital Ophtalmique Jules Gonin, University of Lausanne, Lausanne, Switzerland Robert Stegmann, MBChB, Mmed Medical University of Southern Africa
Foreword Surgical procedures to lower intraocular pressure in glaucoma were first developed in the middle of the 19th century, although the role of a filtration bleb in successful surgery for open-angle glaucoma was not recognized initially. In 1869, DeWecker was the first to consider an anterior sclerotomy successful only if filtration continued postoperatively. Over the next half century, a number of procedures were described. Limbal trephination, introduced by Elliot in 1909, became the most popular operation until the 1940s, when it fell out of favor because the very thin conjunctival bleb predisposed to late endophthalmitis. Thermal cautery of the scleral wound edges with entry into the anterior chamber was described by Preziosi in 1924. Scheie’s modification, thermal sclerostomy, and posterior lip sclerectomy became the most widely used operations. These full thickness procedures were complicated by frequent flat anterior chambers, choroidal detachments, subsequent cataract formation, and late bleb leaks and endophthalmitis. Guarded filtration procedures were developed in the hope of avoiding these complications. In 1968, Cairns reported good success using microsurgical techniques to perform a trabeculectomy under a scleral flap, which was hinged either posteriorly in the sclera or anteriorly at the limbus. Although the incidence of late endophthalmitis was significantly reduced, the intraocular pressure was not lowered to as great an extent and certain subsets of patients, such as those with neovascular glaucoma, uveitis, and previous surgery had high rates of failure. Nevertheless, trabeculectomy rapidly became the procedure
of choice and has remained so for the past 30 years. The antifibrosis agents 5-fluorouracil and mitomycin C were introduced in an attempt to provide the pressure-lowering effect of fullthickness surgery with the safety of trabeculectomy. Surgical success rates were notably improved, particularly for complicated glaucomas, and they have become routinely used in virtually all filtration procedures. However, the thin, avascular blebs produced, particularly with mitomycin C, have led to a resurgence of chronic hypotony, hypotony maculopathy, bleb leaks, bleb dysesthesia, bleb infections, and endophthalmitis. There is an increasing consensus that new approaches to glaucoma surgery are needed. Ideally, these approaches should achieve a more physiological means of lowering intraocular pressure, be capable of reducing pressure to the low teens necessary to prevent progression of glaucomatous damage in most patients, and be free of the complications noted above. Non-penetrating surgery, originally attempted by Krasnov and by Zimmerman, with limited success, offers the promise of successful lowering of intraocular pressure with significant reduction in the frequency of the complications of shallow anterior chamber and hypotony. Two recently developed approaches, deep sclerectomy devised by André Mermoud, and viscocanalostomy, devised by Robert Stegmann, have seen increasing popularity among glaucoma surgeons. These procedures involve excising a portion of sclera under a larger scleral flap to make a scleral lake, the maintenance of which is enhanced by collagen
x
Foreword
implants or viscoelastics. The procedure is technically more difficult to perform compared to trabeculectomy and there is a longer learning curve. Reported results vary from equivalence in effect to trabeculectomy at the hands of the most experienced surgeons to a greater failure rate than trabeculectomy in many case series. Nevertheless, the potential opportunity to create a filtering procedure which successfully controls intraocular pressure in the absence of a bleb is a driving force to modify and improve upon non-penetrating glaucoma surgery. I believe that the momentum developing will provide the impetus for innovation in
techniques and methodology, probably in conjunction with newer developments in wound healing modification, to bring about a procedure which will take the place of trabeculectomy, just as trabeculectomy took the place of full-thickness procedures. This book, edited by André Mermoud and Tarek Shaarawy, is the first, and most likely not the last, to bring together a developing field in order to provide a comprehensive overview of concepts and techniques of non-penetrating glaucoma surgery. Robert Ritch, MD The New York Eye and Ear Infirmary
Acknowledgements In the rich, intricate tapestry of life people meet. These encounters can be brief or prolonged, but sometimes an everlasting effect emerges, and a person’s life will never be the same again. Therefore, first and foremost, we wish to thank our mentors, Professor T Murray, Professor C Gailloud, Professor JB Bourke, Professor T Souidan, Professor S Galal, Professor T El-Emary, Dr R Faggioni, Dr G Baerveldt, Dr J Salmon, and Dr A Azab, for their uncompromising principles, and the way in which the professoround integrity of each one of them has inspired our careers. We would also like to acknowledge with appreciation all the contributors for their excellent contributions. We are extremely
grateful and indebted to Professor Robert Ritch for writing the foreword. Also, we wish to thank our publisher Alan Burgess, of Martin Dunitz Ltd, for his patience and understanding, as well as Charlotte Mossop, the project editor, who saw this project through to timely completion. Not far behind the authors is a dedicated clan of supporters. They include our book coordinator Dr L Bolle, our talented illustrator Miss C Darphin, Mr M Curchod, the photography department of Jules Gonin Eye hospital, and our executive secretaries. This book is the joint effort of a group of people who enjoy what they do for a living. André Mermoud Tarek Shaarawy April 2001
1 The history of filtering surgery Howard C Cohn
The ancient Greeks and Romans did not differentiate between glaucoma and cataract. The term glaucoma in Greek was used to describe a general glazed appearance of the pupil. In the time of Hippocrates (460–377 BC) all maladies of the eye were attributed to ‘disturbed or ill humors’. The two conditions were not differentiated until the time of Celsius (25 BC–AD 50) and later Galen (AD 131–210): cataract was treatable, glaucoma was not (Ref. 1, page 380). For problems involving sight or the eye, from the second century BC various ‘magic’ eye drops were concocted containing zinc, copper, mydriatics, and other substances including albumin, saliva, mother’s milk, children’s urine, crocodile and lion bile. 2 The first person to suggest an association between raised intraocular pressure (IOP) and glaucoma was At Tabari in the 10th century, followed by Sams-ad-Din of Cairo in the 14th century who described ‘a migraine of the eye or headache of the pupil, an illness associated with pain in the eye, hemicrania and dullness of the humors, followed by dilatation of the pupil and cataract. If it becomes chronic, tenseness of the eye and blindness intervene’. But it was not until 1622 that the first original description of glaucoma as distinct from cataract was described by Richard Banister: ‘The humour settled in the hollow nerves, be growne to any solid or hard substance, it is not possible to be cured. If one feele the Eye by rubbing upon the
Eie-lids, that the Eye be growne more solid and hard than naturally it should be.’ Pierre and Antoine-Pierre Demours gave an excellent description of the association of raised IOP and glaucoma. In the early 19th century Guthry, Lawrence, and Donders described two separate conditions with raised IOP: acute inflammatory syndrome and non-congestive or simple glaucoma (Ref. 1, pages 381–83). In the late 18th century and early 19th century, the cause of glaucoma was ascribed to gouty iritis (Beer, 1792), serous choroïditis (Mackenzie, 1835), thickening of the sclera (Coccius, 1867), among others (Ref. 1, page 387).
Iridectomy and acute glaucoma Von Graefe3 in 1857 described the beneficial effect of an iridectomy in treating acute glaucoma but noted no improvement in cases of chronic glaucoma treated by the same method. He did describe grossly cystoid cicatrices in about 20% of eyes undergoing iridectomy, but thought they were less desirable than a smooth well-healed, scleral incision.4 At this period in history the difference between open-angle glaucoma and angleclosure glaucoma was in the process of being
2
The history of filtering surgery
discovered. Before the difference was recognized there were various theories proposed as to how an iridectomy lowered IOP. As reviewed by Lagrange,5 Donders proposed that iridectomy reduced secretion of aqueous humor by reflex pathways, whereas Fuchs and Axenfeld thought that the liquid went under the choroid to be resorbed. Bowman and Ulrich proposed that vitreous passed through the iridectomy into the anterior chamber to ‘disappear by osmosis’. Knies in 1876 and Weber in 1877 were on the right track when they described the high frequency of anteriorchamber obstruction in acute glaucoma. After the introduction of the gonioscope by Salzmann in 1914, Seidel, Curran, and Raeder in the 1920s introduced the concept of pupillary block, and the explanation of why iridectomy cured angle-closure glaucoma but not chronic simple (open-angle) glaucoma. Curran showed that a peripheral (and not sector) iridectomy was sufficient (Ref.1, page 387). Various surgical procedures have been proposed over time for the treatment of glaucoma according to our progressive understanding of the disease process.
Simple sclerotomy Mackenzie in 1835 was the first to do an invasive procedure—sclerotomy—designed to treat serous choroiditis, the cause he proposed for simple glaucoma; he later added a paracentesis.
Iridodesis Because a paracentesis rapidly closed, Critchett6 in 1858 proposed drawing a piece of iris
into the corneal wound to facilitate drainage by ‘iris inclusion’ or iridodesis. A broad needle was used to make a corneal incision at the limbus. The iris was drawn into the wound with a blunt hook and left as is with the protruding part excised. Kronfeld7 aptly called it ‘a technically simple but otherwise horrible method to relieve pupillary block... not likely to give rise to a lasting safe outlet for aqueous’.
Anterior sclerotomy Louis de Wecker may be regarded as the father of glaucoma filtering surgery. He was the first to realize that it was the scleral incision and not the excision of iris that was responsible for the pressure lowering of von Graefe’s iridectomy in some cases of glaucoma.8 He described the filtering cicatrix9 as a desirable result, and said that it was not the nuisance with risk of complications that von Graefe thought. De Wecker in 1869–71 described the anterior sclerotomy with a Graefe type knife (Ref. 1, page 528). An incision and counter incision were made just behind the limbus with the knife drawn up toward the limbus as for a cataract incision but leaving the limbus intact. The goal was to form a filtering bleb but the incision soon closed. De Wecker added an iridectomy and Dianoux in 1905 proposed prolonged massage, neither of which were successful.10
Small-flap sclerotomy In 1903, Major Herbert proposed a small-flap sclerotomy where a small incision was made into the anterior chamber through the sclera
Small-flap sclerotomy
(a)
(b)
(c)
(d)
3
Figure 1.1 Lagrange’s sclerecto-iridectomy (1906). (a) Graefe knife incision through the limbus; (b) Incision carried superiorly and posteriorly exiting the sclera 2–3 mm behind the limbus and exiting the conjunctiva another 3 mm further on; (c) Sclerectomy; (d) Sector iridectomy; (e) Final appearance: no sutures used. (e)
behind and parallel to the limbus. A small limbus-based sclera flap was then raised and iris was incarcerated into the wound. There was no resection of scleral tissue. Herbert also
tried infolding of the conjunctiva into scleral incisions but obtained few long-term successes.7
4
The history of filtering surgery
Sclerecto-iridectomy Lagrange5 described a sclerecto-iridectomy in 1906 in which a corneoscleral conjunctival flap was created with a Graefe knife. (Fig. 1.1) A sclerectomy of the anterior lip was done with scissors, followed by a basal iridectomy. No sutures were used. Aqueous humor then had free access to the subconjunctival space. It is interesting to see that his results are reported mainly in terms of visual function: visual acuity and the visual field, besides the presence of a filtering cicatrice. (The IOP could not yet be measured accurately and was described only as normal, slightly, or greatly elevated by digital testing.) Of 15 cases followed-up for at least 6 months, visual acuity was the same in 12 and improved in 3. The visual field was stable in 13 and improved in 2. O’Brian (Ref. 1, page 534) in 1947 described 85% success with Lagrange’s sclerecto-iridectomy. Lagrange5 summarized the mainstream of thought at the turn of the century in his 1907 article quoting Priestly-Smith ‘the only effective treatment of chronic glaucoma is the creation of a sclero-corneal subconjunctival fistula’, and Critchett who said: ‘the operator who finds the means of assuring formation of this filtering cicatrice will have rendered a great service to humanity.’
Iridencleisis Holth11 reported iridencleisis in 1908, after noting that well-healed incisions for iridectomies in chronic glaucoma did not work as well as did irregular wounds where there was often a piece of iris incarcerated and a filtering cicatrice. The iridencleisis procedure begins with a triangular 6 mm lance incision made in
the conjunctiva 5 mm behind the limbus, then the lance is advanced into the anterior chamber at the limbus. A sector iridectomy is done with incarceration of one or both iris pillars into the scleral wound. Various modifications of the procedure are described; no sutures were used. Holth describes the postoperative care: ‘Of course, the patient is left in the dark for the first 4 days after the operation to avoid constriction of the pupil...’ He had 85% success in 34 cases with normal IOP re-established as measured by the new Schiotz tonometer. All successful cases had persistent ‘conjunctival edema’.
Posterior trephination Argyll-Robertson, one of the first to introduce the concept of producing a filtering scar by sclerectomy, proposed posterior trephining in 1876 at the junction of the pars plana and ciliary body. Four cases with qualified success were reported. (Ref. 1, page 529).
Limbal trephination Elliot12 in 1909 described a technique of limbal trephination as an easier operation than Herbert’s small-flap sclerotomy or Lagrange’s sclerecto-iridectomy. The operation was done under cocaine and adrenaline local anesthesia. However, if necessary a ‘hypodermic of morphine’ was used. A conjunctival flap was dissected either at the superior limbus or inferior limbus (Fig. 1.2), Elliot noted that it was often easier to approach the inferior limbus of an eye of an anxious patient who tended to stay in upgaze. A trephine of 2 mm
Posterior-lip thermal sclerotomy
5
trephine hole too far posterior and entering the suprachoroidal space. If the bulging uveal tissue is excised vitreous may present. Elliot concluded: ‘To some the publication of the present paper may seem premature, the ideas embodied in it have been so long before the writer’s mind that he has wondered that others have not anticipated him. He is convinced that it is founded on sound principles and it is obviously very easy to perform the operation. He hopes that those who have been deterred from attempting the more difficult procedures of other surgeons will try this. Its technique is within the reach of all. Operative skill can scarcely be said to be required.’
Thermal sclerostomy
Figure 1.2 Elliot’s trephination procedure (1909).
diameter was used. A strong myotic, eserine, was used at the end of each operation. In 21 of his first 50 cases, an iridectomy was done, but only if the iris presented in the trephine hole at surgery. Two cases had to be reoperated because of iris incarceration. The anterior chamber had reformed the day after surgery in 37 of 50 cases. Intraocular pressure was lowered in all cases. Subconjunctival filtration was noted to be ‘very free’. No cases of ‘septic accident’ were described. The one complication Elliot mentioned was making the
Preziosi13 in 1924 proposed doing a thermal sclerostomy under a conjunctival flap. A galvano cautery was used in the absence of any knife incision to enter the anterior chamber, thereby creating a fistula.
Posterior-lip thermal sclerostomy Scheie14 described a posterior-lip thermal sclerostomy in 1958. He had observed that application of an electric cautery for hemostasis of the posterior lip of an iridectomy incision produced inadvertent filtering blebs. The thinking of the time is illustrated in his introduction: ‘The filtering cicatrice seemed to be best explained by slight retraction of the wound edges resulting from scleral shrinkage cause by the cautery. The fact the filtration
6
The history of filtering surgery
(a)
(b)
(c)
(d)
Figure 1.3 Scheie’s procedure (1958). (a) Ab externo incision perpendicular to sclera 1 mm behind the limbus; (b) Application of cautery to lips of scleral incision with gaping wound; (c) Prolapse of iris; (d) Iris root grasped for peripheral iridectomy. Reproduced by permission of the American Journal of Ophthalmology.)
occurred was surprising because many ophthalmic surgeons have cautioned against the use of cautery even for control of bleeding when performing a filtration operation.’ The technique was done under local anesthesia, (Fig. 1.3) A limbus base conjunctival flap was raised. After initial cauterization of the sclera at the limbus a small scratch
incision is made with the blade through the cauterized area 1 mm behind the limbus. Then cautery is progressively applied to the posterior lip of the incision, which is progressively deepened until the iris prolapses. An iridectomy is done and the conjunctiva and Tenon’s capsule are closed by 6.0 catgut in separate layers. No medication was instilled.
Sinusotomy Scheie presents data on 41 eyes of 30 patients, 14 with angle-closure glaucoma. In the 14 eyes operated for angle-closure glaucoma the IOP was regarded as controlled if repeat readings were under 30 mmHg by Schiotz tonometry. In 21 of 27 eyes with openangle glaucoma the IOP was controlled, although six of these eyes had hypotony. Hypotony was defined as a tension of 10 mmHg or less, but in no instance caused diminution of vision or visual difficulty. The longest follow-up was 14 months. Apart from two small hyphemas, no operative complications were encountered in his series. He did note that the bleb was usually thick and should be much less prone to developing infection compared with the thin polycystic blebs associated with corneo-scleral trephination. Scheie15 compared his thermal sclerostomy with iridencleisis and trephination. In a larger series of 111 eyes with open-angle glaucoma, the success rate of the Scheie procedure was 86% in controlling the IOP. The most frequent complication was flat or shallow anterior chamber: only two-thirds of eyes had a reformed chamber at 3 days. Hyphema occurred in 17 eyes, and hypotony in 20 eyes, but none had disk edema or loss of visual acuity. His success rate with iridencleisis was 83% in 141 eyes, with hypotony noted in just 3.5%. Delayed anterior chamber reformation occurred in seven eyes. The success rate of trephination in achieving IOP control was 98% in 69 eyes with hypotony in 21, none with visual loss. Hyphema occurred in 20 eyes. Scheie used a 1.0 mm or a 1.5 mm trephine. In comparison to the 2 mm trephine originally used by Elliott, the surface area of a 1 mm trephine is four times smaller. Scheie’s results with trephination were better than those of others. Leydhecker16 found the success of Eliott’s operations to be only about 60%; an unfavourable comparison with the 80–90% success of the Scheie procedure. Throughout the
7
1960s and early 1970s, the Scheie procedure was one of the most frequently performed filtering procedures.
Posterior-lip sclerectomy Iliff and Haas17 described a posterior-lip sclerectomy in 1962. Under a limbus-based conjunctival flap a 5 mm incision is made into the anterior chamber and a Holth scleral punch is used to make a scleral opening of 1 mm 3 mm. An iridectomy is done. Haas18 in 1967 described an 85% success with posterior-lip sclerectomy, although complications included flat blebs, flat chambers, and choroidal detachments.
Trabeculotomy Trabeculotomy was described by Harmes and Dannheim19 in 1969 with a 60% success rate for controlling IOP. Trabeculotomy was not designed as a filtering procedure as such, but was supposed to increase outflow facility. Of 300 cases, 12% developed a filtering bleb and 8% had a gross hyphema requiring anteriorchamber washout.
Sinusotomy Krasnov20 published his sinusotomy or externalization of Schlemm’s canal in the 1960s, assuming the site of obstruction to outflow was intrascleral beyond the outer wall of Schlemm’s canal. If the outer wall is opened leaving the inner wall intact, reduction of IOP should be obtained. A resection of a narrow
8
The history of filtering surgery
1.5 mm wide lamella of sclera directly over Schlemm’s canal is made from the 10 o’clock to 2 o’clock position. Krasnov said that care should be taken not to damage the inner wall of Schlemm’s canal, which is the trabecular zone. The moment of reaching Schlemm’s canal is crucial in sinusotomy. If the diagnosis of intrascleral glaucoma should prove correct there is a constant flow of fluid through the undamaged trabecular meshwork. In cases of ‘trabecular insufficiency’ the site over Schlemm’s canal will be more or less dry and a different surgical procedure should be used. Krasnov described 340 cases with a followup of 1–5 years with normalization of IOP in 83%. A prolonged normalization of IOP is usually associated with visible subconjunctival filtration. He concludes: ‘We have now almost completely abandoned conventional fistulising surgery in glaucoma apart from exceptional cases.’
Setons and shunts Many different materials have been implanted into the anterior chamber in an attempt to facilitate filtration. Rollett and Moreau in 1907 placed horse hair through corneal punctures in two cases of absolute glaucoma. Zorab used a silk loop through a keratome incision under the conjunctiva in a procedure he called aqueoplasty. Substances including gold leaf, platinum, various plastic rods and plates were placed in limbal wounds to act as wicks to keep a sclerostomy open. Results overall were poor (Ref. 1, page 543). Since the 1970s posterior tube shunts have achieved a certain degree of success in maintaining functional blebs in eyes where standard filtration procedures are not feasible or have failed. Molteno21 was the first to
report success with his episcleral plate joined to a plastic tube coming from the anterior chamber.
Trabeculectomy Trabeculectomy was first tried under a scleral flap by Sugar22 in 1961. A 2 mm section of the trabecular meshwork and Schlemm’s canal was removed with a punch forceps, and a peripheral iridectomy was done. The scleral flap was then tightly sutured and all cases failed. Sugar proposed the reason for failure: crushing action of the punch forceps closing off the edges of Schlemm’s canal. The first successful trabeculectomy technique was described by Cairns23 in 1968. The procedure excised a length of Schlemm’s canal, adjacent trabecular meshwork, tip of the scleral spur, and deep layers of the cornea; a fornix or limbal-based scleral flap was used. An iridectomy was done, and the scleral flap was sutured firmly. Only six of 300 cases had a flat anterior chamber, one of which lasted for over 3 days. Moderate uveitis was present in five cases. There were no hyphemas. Cairns24 reviewed 80 cases in 1972. Overall IOP control was 97.5%; 30% had no obvious drainage bleb; only 2.5% of those without a bleb needed medical therapy. Cairns proposed five possible modes of action: • creation of a fistula • aqueous humor drainage through the trabecular meshwork into Schlemm’s canal • aqueous drainage directly into collector channels • possible localized cyclodialysis • possible hyposecretion
Laser sclerostomy From the 1970s guarded filtration surgery by trabeculectomy became the standard operation for uncontrolled open-angle glaucoma as well as other types. In comparison to full thickness procedures the risk of hypotony was reduced by the protective scleral flap. Modifications of the technique, including laser suture lysis and releasable flap sutures, allowed even finer control of postoperative filtration. Trabeculectomy is the standard against which non-penetrating filtering procedures can be compared. Several investigators have looked at the long-term results of trabeculectomy. In 150 eyes followed-up for an average of 10 years (range 1–20 years) Watson et al25 reported that 90% had a final IOP of less than 20 mmHg. Once drainage was established there were excellent chances that IOP would remain controlled. Only three eyes had longterm hypotony and no cases of endophthalmitis or blebitis were reported, but visual fields remained stable or improved in only 41%. The progressive visual field loss in the other 59% may have been because a low enough ‘target pressure’ could not be achieved. Wilensky and Chen 26 looked at a follow-up after 15 years of 40 eyes that had an initially successful trabeculectomy at 1 year (defined as IOP < 21 mmHg or a drop of at least 33% if initial IOP was < 21 mmHg). The success rate of IOP control was 83% at 5 years, 73% at 10 years, and only 42% at 15 years. Nouri-Mahdavi et al27 looked at the optic disc and automated visual field changes to judge long-term stability of primary openangle glaucoma after trabeculectomy. In 78 eyes followed-up for 25–112 months the probability of a single operation giving successful IOP control was only 48% at 3 years and 40% at 5 years. Khalili et al28 looked at 700 trabeculectomies followed-up for 3–12 years. Success was defined as IOP below 21 mmHg throughout the
9
entire study period, no evidence of progressive disc or visual field deterioration, no drop in visual acuity, and no additional glaucoma surgery. The success rate was only 44%. In half of the failures the IOP began to rise within the first postoperative month. Molteno et al29 looked at first-time trabeculectomies on 289 eyes with primary open-angle glaucoma. The probability of obtaining an IOP of 21 mmHg or less was 0.93 at 5 years, 0.87 at 10 years, and 0.85 at 15 years, but mean visual acuity decreased significantly over the years leading to blindness in 47 eyes. The chances of retaining visual acuity greater than 20/400 and greater than 5° radius visual field was only 0.6 at 15 years. Eyes with better preoperative visual acuity had better chances of preserving useful vision. Johnson et al30 found that the probability of blindness in 86 eyes was 46% at 10 years after filtering surgery, mostly trabeculectomy. The resultant IOP (14 mmHg) in the group that went blind was similar to that which preserved visual function (15.4 mmHg), but the group that went blind had more advanced field loss at the time of surgery (scotomas above and below the horizontal axis). A conclusion one can draw is that an IOP of even 14 mmHg is too high long-term for an eye with advanced glaucomatous loss.
Laser sclerostomy Laser sclerostomy is a filtering procedure that has not gained widespread popularity. Various techniques have been described either ab interno31–33 or ab externo, most of which were done with the THC:YAG (holmium) laser that creates a 200 micron diameter lumen (onehundredth the surface area of Elliot’s 2 mm
10
The history of filtering surgery
trephine hole). With the holmium laser, Iwach et al34 reported at 30 months in 81 eyes a probability of success of 0.72 in low-risk eyes and 0.3 in high-risk eyes. Complications of this full-thickness procedure included more hypotony and flat or shallow anterior chambers than with the guarded filtration of trabeculectomy, as well as iris incarceration in the absence of an iridectomy. An additional reason for lack of acceptance of this technique was the concomitant rise in popularity of antimetabolites, which increased the success rate of standard trabeculectomy.
Non-penetrating trabeculectomy With recognition of the juxta canalicular meshwork and inner wall of Schlemm’s canal being the site of major resistance to outflow,35 procedures were devised to selectively remove this tissue, leaving a thin trabeculo-Descemetic membrane intact. Zimmerman et al36 first described a nonpenetrating trabeculectomy in 1984, followed by Koslov et al 37 who described non-penetrating deep sclerectomy in 1989. Viscocanalostomy was described by Stegmann37 in 1995. These new operations, the subject of this book, are the most specific target oriented procedures to date to treat open-angle glaucoma. In evaluating these new procedures it is wise to keep in mind the words of Duke-Elder (Ref. 1, page 528): ‘Any operation devised for the relief of glaucoma should ideally be such as to preserve the function of the eye, maintain its tension within normal limits, and retain the integrity of the globe. The number of operations advocated from time to time is evidence that this ideal has never been attained.’
Acknowledgment I thank Dr. Ana Bassols of Chauvin Laboratories for invaluable help in tracking down original old publications.
References 1. Duke-Elder S. System of Ophthalmology (Vol XI). London: Henry Kimpton, 1969. 2. Clavel J, Chausson JD. La Perennité d’une Vocation. Lausaunne: Fondation de l’Asile des Aveugles, 1993. 3. von Graefe A. Uber die Wirkung der Iridectomie bei Glaucom und uber den glaucomatosen Prozess. Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie 1857;3:456–555. 4. von Graefe A. Weitere Zusatze uber Glaukom und die Heilwirkung der Iridectomie. Arch Ophthalmol 1861;8:243–313. 5. Lagrange F. Nouveau traitement du glaucome chronique simple: iridectomie et sclerectomie combinées. Ann Ocul 1907;137:89–103. 6. Critchett G. Cases illustrative of a new method of treating deep-seated inflammation of the globe or acute glaucoma. J R Lon Ophthalmol Hosp 1858;1:57–66. 7. Kronfeld P. The rise of the filter operations. Surv Ophthalmol 1972;17:168–79. 8. de Wecker L. Die Sklerotomie als Glaukomoperation. Ber Ophthalmol Ges 1871;8:305–10. 9. de Wecker L. La cicatrice a filtration. Ann Ocul 1882;87:133–43. 10. Dianoux C. Glaucome et sclerotomie. Ann Ocul 1905;133:81–85. 11. Holth S. Iridencleisis antiglaucomatosa. Ann Oculist 1908;137:345–75. 12. Elliot RH. A preliminary note on a new operative procedure for the establishment of a filtering cicatrix in the treatment of glaucoma. Ophthalmoscope 1909;7:804–06.
References 13. Preziosi L. The electro-cautery in the treatment of glaucoma. Brit J Ophth 1924;8: 414. 14. Scheie HG. Retraction of scleral wound edges as a fistulizing procedure for glaucoma. Am J Ophthalmol 1958;45:220–29. 15. Scheie HG. Filtering operations for glaucoma: a comparative study. Am J Ophthalmol 1962;53:571–90. 16. Leydhecker W. Comparative study of late after-effects of glaucoma operations. In Glaucoma Tutzing Symposium, Karger, Basel/New York, 1967, 224–38. 17. Iliff CE, Haas JS. Posterior lip sclerectomy. Am J Ophthalmol 1962;54:688–93. 18. Haas JS. Symposium on Glaucoma. Trans N Orleans Acad Ophthal, 1967:175. 19. Harms H, Dannheim R. Epicritical consideration of 300 cases of trabeculotomy “ab externo”. Trans Ophthal Soc UK 1969;88:491–99. 20. Krasnov MM. Externalization of Schlemm’s canal (sinusotomy) in glaucoma. Br J Ophthal 1968;52:157–61. 21. Molteno ACB. New implant for glaucoma clinical trial. Br J Ophthalmol 1971;53:606. 22. Sugar HS. Experimental trabeculectomy in glaucoma. Am J Ophthalmol 1961, 51:623–27. 23. Cairns JE. Trabeculectomy—preliminary report of a new method. Am J Ophthalmol 1968;66:673–79. 24. Cairns JE. Surgical treatment of primary open angle glaucoma. Trans Ophthalmol Soc UK 1972;92:745–56. 25. Watson PG, Jakeman C, Ozturk M et al. The complications of trabeculectomy (a 20-year follow-up). Eye 1990;4:425–38. 26. Wilensky JT, Chen TC. Long term results of trabeculectomy in eyes that were initially successful. Trans Am Ophthalmol Soc 1996;94:147–59. 27. Nouri-Mahdavi K, Brigatti L, Weitzman M, Caprioli J. Outcomes of trabeculectomy for
28.
29.
30.
31.
32.
33.
34.
35.
36.
37.
11
primary open-angle glaucoma. Ophthal mology 1995;102:1760–69. Khalili MA, Diestelhorst M, Krieglstein GK. Long-term follow-up of 700 trabeculectomies. Klin Monatasbl Augenheilkd 2000;217:1–8. Molteno AC, Bosma NJ, Kittelson JM. Otago glaucoma surgery outcome study: long-term results of trabeculectomy, 1976 to 1995. Ophthalmology 1999;106:1742–50. Johnson DH, Parc CE, Oliver J et al. The long term outcome of glaucoma filtration surgery. Invest Ophthal Vis Sci 2000;41:S518. Jaffe GJ, Mieler WF, Radius RL et al. Ab interno sclerostomy with a high powered argon endolaser. Arch Ophthalmol 1989;107:1183–85. March WF, Bernitzky D, Gherezghiher T et al. Creation of filtering blebs with the YAG laser in primates and rabbits. Glaucoma 1985;7:43–45. Melamed S, Solomon A, Neumann D et al. Internal sclerostomy using laser ablation of dyed sclera in glaucoma patients: a pilot study. Br J Ophthalmol 1993;77:139–44. Iwach AG, Hoskins HD, Drake MV, Dickens CJ. Update of the sunconjunctival THC:YAG (holmium) laser sclerostomy ab externo clinical trial: 30 month report. Ophthalmic Surg 1994;25:13–21. Bill A, Svedbergh B. Scanning electron microscopic studies of the trabecular meshwork and the canal of Schlemm—an attempt to localize the main resistance to outflow of aqueous humor in man. Acta Ophthalmol 1972;50:295. Zimmerman TJ, Kooner KS, Ford VJ et al. Effectiveness of nonpenetrating trabeculectomy in aphakic patients with glaucoma. Ophthalmic Surg 1984;15:44–50. Stegmann RC. Viscocanalostomy: a new surgical technique for open angle glaucoma. An Inst Barraquer 1995;25:225–32.
2 Evolution of non-penetrating glaucoma surgery André Mermoud
Historical review of nonpenetrating filtering surgery In 1962 Kraznov performed the first sinusotomy. This operation consisted of removing a lamellar band of the sclera and opening Schlemm’s canal over 120° from 10 to 2 o’clock (Fig. 2.1).1–4 The inner wall of Schlemm’s canal was untouched and then the conjunctiva was closed. Kraznov believed that the aqueous outflow resistance in most cases of primary open-angle glaucoma was situated at the level of scleral aqueous-drainage veins and not in the trabeculum. He therefore developed a safe non-penetrating filtering surgery, leaving in place the trabeculum and the inner wall of Schlemm’s canal. When there was no percolation of aqueous through the trabeculum and Schlemm’s canal inner wall, Kraznov entered the anterior chamber and performed a peripheral iridectomy, creating a full-thickness procedure that was the standard filtering surgery at that time. Sinusotomy was definitely safer than full thickness surgery with almost no postoperative complication, which was certainly not the case with standard fullthickness procedures frequently leading to a major hypotony, followed in many cases by a flat anterior chamber, choroidal detachments, and cataract formation. Kraznov also reported
Figure 2.1 Schematic representation 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.
14
Evolution of non-penetrating glaucoma surgery
that the filtering blebs were more diffuse after sinusotomy and that they tended to disappear with time. Sinusotomy never became popular because it was a difficult operation, it needed a surgical microscope and Schlemm’s canal had to be found, which was not easy. Moreover the surgical results were not convincing. Kraznov reported an 83% success rate but did not specify the success criteria, the number of patients followed-up or the period of followup. Postic and Stankov-Tomic4 have reported a 50% success rate in 12 glaucoma patients operated on by sinusotomy. These six successful patients had low intraocular pressure (IOP) with filtering blebs. The other 50% presented a primary drop in IOP after surgery, and then an IOP rise because of fibrosis of the filtering bleb. To my knowledge, there is no long-term report on the outcome of sinusotomy. In the late 1960s, and for the next three decades, trabeculectomy described by Sugar5 in 1961 and Cairns6 in 1968 became the standard technique for filtering surgery, providing a satisfactory IOP control with fewer postoperative complications than full-thickness filtering procedures. However, even with the many modifications proposed to the original trabeculectomy, the lack of a reproducible postoperative IOP reduction as well as the early postoperative complications led several surgeons to reconsider Kraznov’s work. Several techniques of non-penetrating filtering surgery based on sinusotomy have been described. Since the main aqueous outflow resistance may be located at the juxtacanalicular trabeculum and the inner wall of Schlemm’s canal, these two anatomical structures have to be removed. Ab externo trabeculectomy (Fig. 2.2) was first proposed by De Laage de Meux and Kantelip7 in 1976, and later by Zimmerman et al8,9 (Fig. 2.3) in 1984, by Arenas in 199110 and Tanibara et al11
Figure 2.2 Schematic representation of ab externo trabeculectomy. A deep sclerectomy unroofing Schlemm’s canal is covered by superficial scleral flap. Schlemm’s canal inner wall and juxtacanalicular trabeculum are removed.
in 1993. Another method to improve the aqueous outflow in a patient with a restricted posterior trabeculum clearance is to remove the corneal stroma behind the anterior trabeculum and the Descemet’s membrane (Fig. 2.4). This technique was first described
Ab externo trabeculectomy
15
Figure 2.3 Professor Thom J Zimmerman
by Fyodorov13 and Kozlov et al14 (Fig. 2.5) and later by Sanchez et al.15
Ab externo trabeculectomy Ab externo trabeculectomy is very similar to sinusotomy except for the presence of a superficial scleral flap and the removal of the inner wall of Schlemm’s canal and the juxtacanalicular trabeculum (Fig. 2.2).
Figure 2.4 Schematic representation of deep sclerectomy. Under superficial scleral flap, deep corneosclerectomy, unroofing Schlemm’s canal, is performed. Corneal tissue behind anterior trabeculum and Descemet’s membrane are removed.
Surgical technique The conjunctiva is opened either at the fornix or at the limbus in the superior quadrant. A 4 4 mm superficial scleral flap is created at the 12 o’clock position. The depth of this scleral flap corresponds to about one third of the full scleral thickness. A radial cut is made on the edge of the flap at the limbus to locate
the Schlemm’s canal. Once the Schlemm’s canal is found, it is unroofed in the same manner as Kraznov did in sinusotomy. At this stage, there is a 4 mm-long Schlemm’s river parallel to the limbus. Different techniques
16
Evolution of non-penetrating glaucoma surgery Figure 2.6 Professor Alain Bechtoille
Figure 2.5 Professor Valentin Kozlov Figure 2.7 Dr Elie Dahan have been proposed to remove the inner wall of Schlemm’s canal. A fine forceps with two small plates at the end may be used to grab the endothelium and to peel it off from one side to the other. Trabeculo-aspiration has been proposed by Bechtoille (Fig. 2.6) who uses a fine canula connected to a phaco infusionaspiration system (unpublished work). Dahan (Fig. 2.7) uses a fine diamond-coated spatula that allows the surgeon to scrape the endothelium (unpublished work). All of these manoeuvres have been grouped into so-called ab externo trabeculectomy because the juxtacanalicular trabeculum is removed and the corneoscleral and uveoscleral trabecula are left intact. Valtot, in an unpublished report, showed that the tissues removed corresponded to the endothelium of the Schlemm’s canal and the juxtacanalicular trabeculum; this was confirmed by Roy et al, who examined a large series of excised fragments by transmission and electronic microscopy (unpublished work). The outflow resistance of the remaining membrane formed by the posterior trabeculum has been studied by Rossier et al 16 They found that in enucleated human eyes the
mean outflow facility increased from 0.21 ± 0.6 to 2.03 ± 1.43 µL/min per mmHg after the removal of 4 mm of the Schlemm’s canal inner wall and the juxtacanalicular trabeculum.
Results Zimmerman and colleagues8,9 have reported good results of non-penetrating ab externo trabeculectomy in both phakic and aphakic patients. However, after their first two publications, they abandoned this technique because of
Deep sclerectomy surgical difficulties. Arenas currently continues to use ab externo trabeculectomy, and has reported a success rate of 88%.10 Other investigators who have been using similar techniques have reported satisfactorily controlled IOPs in 85.8% to 90% of patients.11,12 With regard to long-term results, Arenas, Valtot, and Bechtoille have all separately reported satisfactory IOP control over time, but no results have yet been published.
Deep sclerectomy Deep sclerectomy was first described by Fyodorov13 and Kozlov et al.14 The route of the aqueous outflow is different from the one described for sinusotomy and ab externo trabeculectomy where the postoperative drainage occurs through the posterior trabeculum. In deep sclerectomy, the main outflow occurs at the level of the anterior trabeculum and the Descemet’s membrane. This was shown by Vaudaux and Mermoud17 in an ex vivo model of deep sclerectomy. They reported that the mean outflow facility increased from 0.19 ± 0.03 to 24.5 ± 12.6 µL/min per mmHg after deep sclerectomy. In comparison with the same experiment performed in ex vivo ab externo trabeculectomy, the postoperative outflow facility increase is ten times higher after deep sclerectomy.16 To provide an aqueous outflow through the anterior trabeculum and the Descemet’s membrane, the corneal stroma behind these structures has to be removed (Fig. 2.4).
Surgical technique The conjunctiva may be opened either at the fornix or at the limbus. A 5 5 mm superfi -
17
cial scleral flap is made, including one third of the scleral thickness (300 µm). To be able to reach the Descemet’s membrane later in the dissection, the superficial scleral flap has to be cut 1–1.5 mm anteriorly into the clear cornea. A second deep scleral flap measuring 4 4 mm is dissected, leaving about 10% of the sclera over the choroid and the ciliary body. The second flap is usually started in its posterior part. The horizontal dissection is started posteriorly, moving anteriorly with a crescent blade. Near the limbus the Schlemm’s canal is automatically unroofed. The dissection is continued anteriorly with a blunt spatula or a sponge to find the natural cleavage plan between the Descemet’s membrane and the corneal stroma. When the Descemet’s membrane has been exposed for 1 mm, the second scleral flap is excised. At this stage, the aqueous is seen percolating through the anterior trabeculum and the Descemet’s membrane. To enhance the filtration, an ab externo trabeculectomy can be peformed as well at this stage. To keep the intrascleral space created patent, an implant may be used. Kozlov et al14 have proposed a collagen implant that resorbs itself within 6–9 months.18,19 Stegmann et al use high viscosity hyaluronic acid,20 and Sourdille and Dahan are using reticulated hyaluronic acid and Hema implants, respectively (unpublished work).
Results Kozlov et al14 have reported an 85% success rate, but no information regarding success criteria or follow-up is available. Demailly et al21 reported a mean decrease in IOP of 9.1 ± 7.1 mmHg after 219 deep sclerectomy procedures with collagen implants. They reported a success rate using Kaplan–Meier
18
Evolution of non-penetrating glaucoma surgery
survival analysis of 89% without glaucoma medication at 6 months and 75.6% at 16 months; with glaucoma medication their success rate increased to 97% at 6 months, and 79% at 16 months. Karlen et al22 have reported the mediumterm success rate (36 months) of 100 patients who underwent deep sclerectomy with collagen implant. The mean preoperative IOP was 27.8 ± 8.6 mmHg and dropped to 5.7 ± 4 mmHg on the first postoperative day and remained stable at 13 ± 3.5 mmHg during the entire follow-up period. Complete success, defined as an IOP lower than 21 mmHg without medication, was 44.6% at 36 months; qualified success, defined as an IOP lower than 21 mmHg with medication, was 97.7% at 36 months. Goniopuncture had to be performed on 41 of the patients, and 5-fluorouracil injections were given in 23 patients; cataract progression occurred in seven patients. When the different types of open-angle glaucoma were compared, no difference was found in terms of reduction in IOP, number of patients requiring antiglaucoma medication, or success rate. There was, however, a tendency for a lower success rate in patients with pseudoexfoliative or pseudophakic glaucoma. In comparison with the standard filtering trabeculectomy, deep sclerectomy offers a similar IOP drop with a lower rate of postoperative complications and a quicker recovery of visual acuity.23,24
Viscocanalostomy The assumed mechanism of filtration in viscocanalostomy is different from the one described in other non-penetrating filtering surgeries. Stegmann et al20 think that the aqueous filters through the trabeculo-
Descemet’s membrane to the scleral space as 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 humour is supposed to reach the Schlemm’s canal, which is open 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 my own hands, patients who underwent a viscocanalostomy presented in 50% of the cases a subconjunctival filtering bleb. Long-term follow-up of viscocanalostomy is reported to be satisfactory. In a prospective study involving 214 eyes of 157 patients, a postoperative IOP below 22 mmHg was observed in 82.7%. 20
Summary In comparison with full-thickness filtering procedures, sinusotomy showed an important progress in terms of postoperative complications. Unfortunately, the long-term IOP drop did not come up to expectations and trabeculectomy became the standard filtering surgery for the next three decades. Since sinusotomy has been modified over the past few years, non-penetrating filtering surgery has become of interest again, mainly because it provides a more reproducible early drop in IOP with fewer postoperative complications. The main changes made from sinusotomy in the new non-penetrating filtering surgeries are: the peeling of the inner wall of Schlemm’s canal (ab externo trabeculectomy) and the excision of the corneal stroma behind the anterior trabeculum and the Descemet’s membrane (deep sclerectomy). These new techniques compare favourably with
References trabeculectomy in terms of IOP drop. However, long-term follow-up is still needed to tell us whether this IOP control can be maintained or not.
References 1. Krasnov MM. Vestn Oftal 1964;77:37–41. 2. Krasnov MM. Externalization of Schlemm’s canal (sinusotomy) in glaucoma. Br J Ophthalmol 1968;52:157–61. 3. Krasnov MM. Symposium: microsurgery of the outflow channels–sinusotomy foundations, results, prospects. Trans Am Acad Ophthalmol Otolaryyngol 1972;76:368–74. 4. Postic S, Stankov-Tomic M. Sinusotomie d’après Krasnov dans le glaucome chronique simple. Bull Mém Soc Fr Ophtalmol 1967;80:716–26. 5. Sugar HS. Experimental trabeculectomy in glaucoma. Am J Ophthalmol 1961;51:623. 6. Cairns JE. Trabeculectomy: preliminary report of a new method. Am J Ophthalmol 1968;66:673–79. 7. de Laage de Meux M, Kantelip B. Surgical anatomy of corneoscleral limbus. Arch Ophthalmol (Paris) 1976;36:39–50. 8. Zimmerman TJ, Kooner KS, Ford VJ et al. Effectiveness of non penetrating trabeculectomy in aphakic patients with glaucoma. Ophthalmic Surg 1984;15:49–50 9. Zimmerman TJ, Kooner KS, Ford VJ et al. Trabeculectomy vs non penetrating trabeculectomy: a retrospective study of two procedures in phakic patients with glaucoma. Ophthalmic Surg 1989;15:734–40 10. Arenas E. Trabeculectomy ab-externo. Highlights Ophthalmol 1991;19:59–66 11. Tanibara H, Negi A, Akimoto M et al. Surgical effects of trabeculotomy ab externo on adults eyes with porimary open angle glaucoma and pseudoexfoliation syndrome.
19
Arch Ophthalmol 1993;111:1653–61. 12. Tavano G, Chabin T, Barrut JM. Hémitrabéculectomie non invasive. Bull Soc Ophtalmol Fr 1993;93:749–50. 13. Fyodorov SN. Non-penetrating deep sclerectomy in open-angle glaucoma. Eye Microsurg (Russian) 1989;52–5. 14. Kozlov VI, Bagrov SN, Anisimova SY et al. Deep sclerectomy with collagen. Eye Microsurg 1990;3:44–46 15. Sanchez E, Schnyder CC, Sickenberg M et al. Deep sclerectomy: results with and without collagen implant. Int Ophthalmol 1997;20:157–62. 16. Rossier A, Uffer S, Mermoud A. Aqueous dynamics in experimental ab externo trabeculectomy. Ophthalmic Res 2000 Jul–Aug;32:165–71 17. Vaudaux J, Mermoud A. Aqueous humor dynamics in non-penetrating filtering surgery. Ophthalmol Pract 1998;38:S1064. 18. Chiou AGY, Mermoud A, Hediguer S et al. Ultrasound biomicroscopy of eyes undergoing deep sclerectomy with collagen implant. Br J Ophthalmol 1996;80:541–44. 19. Chiou AGY, Mermoud A, Underdahl PJ, Schnyder CC. An ultrasound biomicroscopic study of eyes after deep sclerectomy with collagen implant. Ophthalmology 1998;105:104–08. 20. Stegmann R, Pienaar A, Miller D. Viscocanalostomy for open angle glaucoma in black African patients. J Cataract Refract Surg 1999;25:316–22. 21. 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 22. Karlen M, Sanchez E, Schnyder CC et al. Deep sclerectomy with collagen implant: medium term results. Br J Ophthalmol 1999;83:6–11 23. Mermoud A, Schnyder CC, Sickenberg M et al. Comparison of deep sclerectomy with
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Evolution of non-penetrating glaucoma surgery
collagen implant and trabeculectomy in openangle glaucoma. Cataract Refract Surg 1999;25:323–331 24. Chiou AGY, Mermoud A, Jewelewicz DA.
Comparison of post-operative inflammation following deep sclerectomy with collagen implant versus standard trabeculectomy. Clin Exp Opthalmol 1998;236:593–6
3 Anatomical features of outflow pathway Farid Achache
Intraocular pressure (IOP) is important for maintainance of ocular rigidity and hence optimization of optical function. Aqueoushumor dynamics control IOP, which depends on the rate of aqueous-humor production (inflow) and the rate at which it leaves the eye through the anterior chamber angle (outflow). The pressure gradient from anterior chamber to episcleral veins is explained by a resistance to filtration in the way of the aqueous outflow. Since Morton Grant1,2 demonstrated that this site of aqueous-outflow resistance is located between the anterior chamber and Schlemm’s canal, it has been generally accepted that the greatest resistance is found in the internal wall of Schlemm’s canal between the trabecular meshwork and the canal. It has also been shown that the resistance might also relate to canal collapse. In addition, experimental studies on monkeys show that about 30% of this resistance is located within the intraocular outflow channels. Therefore the precise location of the resistance to outflow is not completely described and is still a matter for debate. Grant has estimated this resistance to be 3 mmHg/µL per min. On the basis of these findings it has been established that IOP may be expressed by a physical factor called the ‘Facility of outflow’ (0.3 µL/min per mmHg).
Outflow pathways The standard drainage route that conveys aqueous humor from within outwards consists of trabecular meshwork, Schlemm’s canal, collector channels, intrascleral venous plexus, aqueous veins, episcleral and conjunctival veins. This outflow pathway is regarded as the conventional route and accounts for 83–96% of aqueous outflow. The uveoscleral pathway, first described in monkeys by Anders Bill3 more than 30 years ago, is an accessory system also called the unconventional outflow route, which drains 5–15% of aqueous-humor production. The uveoscleral pathway allows free access from the anterior chamber to the supraciliary and suprachoroidal spaces via the collagen-containing spaces between the ciliary-muscle-fibre bundles. From there, the fluid crosses the sclera and the uveal vascular system. This secondary drainage pathway has given rise to a new treatment strategy that reduces IOP by enhancing uveoscleral outflow. In addition, we must take into account the transscleral outflow, which is a less wellknown drainage route (Fig. 3.1).4,5
22
Anatomical features of outflow pathway Figure 3.1 Drainage pathways of the aqueous humor.
Production of aqueous humor Aqueous humor crosses posterior and anterior chambers, providing the surrounding avascular structures with oxygen and other nutrients such as glucose, aminoacids, and polypeptide growth-modulating factors. At the same time, aqueous humor disposes of metabolic wastes coming from these structures. The pathway of aqueous flow involves active production of aqueous humor by the non-pigmented ciliary epithelium of the ciliary processes. Aqueous humor consists of a dilute
solution of the constituents of the plasma, in addition to the substances specifically secreted. Three mechanisms take place in aqueous humor production. Diffusion and ultrafiltration of lipids and water substances are passive processes in response to osmotic gradient and hydrostatic pressure, and account for 15–20% of the whole aqueous humor flow. Secretion is an active process based on the active transport of sodium through the non-pigmented layer of the ciliary epithelium. The sodium leaves the capillary wall easily and then crosses the outer basal lamina and the pigmented layer. Sodium overcomes the tight junctions of the non-
The ciliary body
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Figure 3.2 The ciliary muscle with the longitudinal ciliary fibers (LCM) and the circular ciliary fibers (CCM). Vascularization of the ciliary body. MAC = major arterial circle, ACA = anterior ciliary arteries, LPCA = long posterior ciliary arteries. The ciliary epithelium (CE) with the outer pigmented and the inner non-pigmented layers.
pigmented layer by penetrating the apex of the cell under the carbonic anhydrase dependent reaction. Finally, sodium leaves the cell to reach the posterior chamber, by way of the sodium pump. This latter process needs the energy provided by Na+ K+ ATPase reaction, which transforms ATP into ADP. Secretion is an active sodium-dependent process, accounting for 95% of the whole aqueous humor production. The aqueous secretion rate is about 2.5 µL/min.5,6
The ciliary body The ciliary body is the medium part of the uvea, between iris and choroid; it extends 6 mm from the scleral spur anteriorly to the ora serrata posteriorly. The anterior 2 mm is the pars plicata or corona ciliaris, characterized by the radial ridges of the ciliary processes. The posterior 4 mm is called the pars plana or orbicularis ciliaris, because of its flat surface. On a sagittal section, the ciliary
24
Anatomical features of outflow pathway
body is three-sided and has a triangular shape; its outer side is adjacent to the supraciliaris space and the sclera. The base of the triangle is occupied by the root of the iris, which is inserted in the middle part of the anterior face of the ciliary body. The space between the root of the iris and the scleral spur is occupied by the ciliary body band, located in the apex of anterior chamber angle. On the inner surface of the ciliary processes, the zonulae fibers stretch from the top of the ciliary processes towards the equatorial area of the lens. The three components of the ciliary body are the ciliary processes, the ciliary vessels, and the ciliary muscle (Fig. 3.2). 7
The ciliary processes The 70 major and minor ciliary processes spread over 2 mm in the area called pars plicata or corona ciliaris, and extend into the posterior chamber. The minor ciliary processes are set between the major processes. Each ciliary process is limited by a two-layered ciliary epithelium that extends anteriorly to the iris. The outer layer, close to the stroma and the ciliary vessels, is a pigmented layer composed of cuboidal cells with numerous melanin granules that lies on a basement membrane. The inner layer is non-pigmented and faces the aqueous humor of the posterior chamber; it consists of columnar cells rich in mitochondria, and is limited by an internal basement membrane. The cells are linked to each other by tight junctions and interlock by interdigitations seen on their lateral and apical surfaces. The ciliary epithelium, particularly the non-pigmented layer, forms a barrier between blood and the ocular cavity, which is called the ciliary bloodaqueous barrier. The stroma occupies spaces between the epithelium and capillaries; it is sparse and composed of ground substance
consisting of mucopolysaccharides, proteins, a few collagen fibrils, and wandering cells of connective tissue and blood origin.4,7
The ciliary vessels Blood is provided by branches of the major arterial circle, resulting from the anastomoses of the anterior and posterior ciliary arteries. The anterior region of the ciliary process is irrigated by the anterior ciliary process arterioles and the posterior and central area is supplied by the posterior ciliary process arteries. The ciliary vessels branch into a dense capillary network along the base of the ciliary process. The endothelium of the capillaries is surrounded by pericytes and mural cells lying on a basement membrane and interrupted by fenestrae, which promotes a high permeability through the vascular wall. The whole capillary network joins the choroidal veins.7
The ciliary muscle The ciliary muscle is composed of two main parts: longitudinal and circular. The anterior tendons insert the ciliary body anteriorly by elastic-like tendons to the scleral spur and the corneoscleral meshwork as well as uveal trabeculae. The posterior tendons insert into Bruch’s membrane and the elastic network of the choroid. The muscle bundles of the ciliary body are meridional in the outer portion, reticular in the intermediate portion, and circular in the inner portion. The meridional fibers, also called Bruch’s muscle, stretch posteriorly to the supra choroidal lamina. The circular fibers, also known as Müller’s muscle, stand in the innermost area of the ciliary body. The spaces between the muscle bundles are occupied by sparse connective tissue made up
The scleral spur of collagen fibers and fibroblasts, and are wider in the longitudinal part. The width of the spaces depends on the state of muscular activity, enlarging during relaxation, which allows aqueous humor access, and closing during contraction. Muscle cells as well as muscle bundles are limited by a basal lamina and the capillaries have a continuous wall. The ciliary muscle is richly innervated with sensory nerve endings of trigeminal origin. The longitudinal portion is innervated by sympathetic fibers arising from the superior sympathetic ganglion and the circular portion receives parasympathetic fibers coming from the third nerve.7
Posterior and anterior chambers Posterior chamber Aqueous humor secreted by the ciliary processes pours down into the posterior chamber. The posterior chamber is a narrow space bounded posteriorly by the zonula fibers and the lens, peripherally by the ciliary processes, and anteriorly by the inner surface of the iris. The posterior chamber’s volume is about 0.06 mL.
25
lens. The volume of the anterior chamber is about 0.2 mL, and its depth ranges from 2.6 mm to 4.4 mm (average 3.15 mm), being shallower in young children, hyperopic eyes, and old people. The peripheral part of the anterior chamber is the angled recess called the drainage angle.8
Anterior chamber angle The different structures of the angle are located in a defined region of 1.5 mm diameter called the limbus, which is the transitional zone between the cornea and the sclera. The outer surface of the limbus is flat and extends 2 mm from the corneolimbal junction anteriorly to the sclerolimbal junction posteriorly. The corneoscleral junction is the apparent limbus from which we find the pars plicata, about 3 mm behind, and the pars plana, about 5 mm posteriorly. The sclerolimbal junction is the transition between white sclera and bluishgray limbus and represents the main landmark for the most conventional surgical procedures. The inner surface of the limbus is a groove called the scleral sulcus, the anterior boundary of which is Schwalbe’s line, the posterior boundary is the scleral spur. The scleral sulcus accommodates the Schlemm’s canal and the trabecular meshwork (Figs 3.3 and 3.4).
Anterior chamber
The scleral spur
Aqueous humor leaves the posterior chamber and flows through the pupil to reach the anterior chamber. The anterior chamber is limited anteriorly by the inner corneal face and posteriorly by the outer surface of the iris, and through the pupil by the anterior face of the
The scleral spur is in the deep limbus. The posterior ridge of the scleral spur, called the scleral roll, is a circular condensation made up of collagen fibers for the most part (80%) and a small amount of elastic tissue for the remainder (5%). Moses and Grodzki9 proved in 1977
26
Anatomical features of outflow pathway Figure 3.3 Structures of the anterior chamber angle; anatomical landmarks seen in gonioscopy. SL = Schwalbe’s line; TM = trabecular meshwork; SS = scleral spur; CBd = ciliary board; SC = Schlemm’s canal; I = iris; S = sclera; CB = ciliary body.
Figure 3.4 Outer projections of the deep limbus structures.
Trabecular meshwork
27
that there are myofibroblast-like cells within the scleral spur. The scleral spur is the mooring point of the anterior tendons of the longitudinal ciliary muscle. The contraction of the ciliary muscle pulls the scleral spur backwards and opens the trabecular meshwork spaces, improving the outflow.6
give contractile properties to the trabecular meshwork. The trabecular meshwork consists of three parts, from within outwards: the uveal meshwork, the corneoscleral meshwork; the juxtacanalicular meshwork, also called endothelial or cribriform meshwork (Fig. 3.4).8,10,11
Schwalbe’s line
Uveal meshwork
Schwalbe’s line is the transition area between the corneal endothelium, the end of Descemet’s membrane and the anterior part of the trabecular meshwork. This region has been called Zone S; it consists of circular arranged collagen and elastic fibers. 8
Trabecular meshwork The trabecular meshwork is a sieve-like band of connective tissue about 750 µm in width, closing the inner part of the scleral sulcus as a bridge joining Schwalbe’s ring to the scleral spur, providing a tubular duct: the Schlemm’s canal. The meshwork is made up of several sheets containing an extracellular collagen substance, elastic fibers, and mucopolysaccharides. Each trabecular beam is surrounded by a single layer of endothelial cells characterized by a strong phagocytory activity and linked by intercellular junctions; they are oriented in the long axis of the trabecular beam, with a bulging nucleus, and lie on a basement membrane. The cells produce glycoaminoglycanes as hyaluronic acid, collagen types I, III, IV, V, and VI, extracellular glycoproteins such as fibronectine and laminin, and fibrillar material. The core of the trabecular beam is made up of collagen and elastics fibrils that
The uveal meshwork is the inner portion neighbouring the aqueous humor of the anterior chamber; it consists of a superimposition of perforated sheets. The size of the apertures range from 25 µm to 75 µm. Posteriorly, the uveal meshwork is connected with the ciliary muscle whereas the anterior part joins the periphery of Descemet’s membrane, the inner part of the Schwalbe’s ring, and the corneal lamellae or the corneoscleral trabeculae. Elastic fibrils are dispersed in the center of the collagen core. 8,9
Corneoscleral meshwork The corneoscleral meshwork is the mid portion of the trabeculum; it extends from the scleral roll posteriorly close from the anterior tendons of the ciliary muscle to the anterior side of the scleral sulcus. This meshwork consists of about 15 layers, the openings of which decrease in size from within outwards with the range 5–50 µm. Elastic fibrils are dispersed around the collagen core. Each beam is surrounded by trabecular cells lying on a basal membrane. The trabecular cells are spindle-shaped and present long cytoplasmic processes; they contain numerous Golgi complexes, rough endoplasmic, ribosomes, lysosomes, and mitochondria.
28
Anatomical features of outflow pathway Figure 3.5 Schlemm’s canal and trabecular meshwork layers.
Juxtacanalicular meshwork The juxtacanalicular meshwork is involved in the increased resistance of outflow; it is adjacent to the inner wall of the Schlemm’s canal and represents the outermost portion of the trabecular meshwork. The meshwork is made up of a layer of connective tissue delineated by endothelium. The endothelial cells are spindle-shaped with long cytoplasmic processes and contain the same intracytoplasmic material. The juxtacanalicular meshwork is a band of 2–20 µm between the endothelium’s canal and the outermost sheet of the corneoscleral trabeculum. The structure of this portion is made up of two to five layers of
loosely arranged cells in a connective substance that is mostly collagen. The outer cells share a basal lamina with the inner wall of Schlemm’s canal. Some of the cells are joined by desmosomes and gap junctions whereas others are separated by pores of up to 10 mm in width through which aqueous humor can filter to reach the endothelium lining of Schlemm’s canal.8,11
Schlemm’s canal Schlemm’s canal was described by Schlemm in 1830; it drains aqueous humor from the
Schlemm’s canal
29
Figure 3.6 Schlemm’s canal: the vacuolar transcellular channels (from Tripathi, RC. Experimental Eye Research 1977;25:65–116).
trabeculum to the episcleral and conjunctival veins via the collector channels. The canal is a circular channel, single or multiple, 36–40 mm in length and 190–370 µm in diameter. The lumen is either elongated, oval, or triangular, and sometimes crossed by septa; it has a vessel-like structure limited by a layer of endothelial cells with a bulging nucleus in the lumen. The endothelial cells contain numerous Golgi complexes, lysosomes, and actine microfilaments; they are rich with hyaluronic acid synthesized by the Golgi complexes, and are dispersed on a basal lamina interrupted on the trabecular side. The inner wall of the canal is characterized by the presence of giant vacuoles in the endothelial cells; this specific feature is the result of progressive invagination of the
basal pole of the cells. The vacuoles contain aqueous humor and sometimes erythrocytes. In somes cases, vacuoles have apical openings that may connect trabeculum with the lumen of the canal, providing a transcellular channel (Figs 3.5 and 3.6). Studies have shown that the process of vacuole formation is pressure-dependent.12–19 The number and size of the vacuoles depend on IOP. There are many vacuoles at high pressure and few at low pressure. The outer wall of Schlemm’s canal consists of endothelial cells attached one to another by zonulae occludentes laying on a basal lamina more consistent than the one on the inner wall one.8,11,20 A pericanalicular connective tissue surrounds the canal.
30
Anatomical features of outflow pathway Figure 3.7 Collector channels. AC = anterior chamber; PC = posterior chamber; C = cornea; I = iris; S = sclera; CP = ciliary processes; SP = scleral spur; E = endothelium; L = Schwalbe’s line; CM = corneoscleral meshwork; UM = uveal meshwork; SC = Schlemm’s canal; ICC = interior collector channels; ECC = external collector channels; 1 = intrascleral venous plexus; 2 = deep scleral plexus; 3 = ciliary venous plexus; AV = aqueous vein; EPV = episcleral vein; CV = conjunctival vein; M1 = longitudinal fibers of ciliary muscle; M2 = circular fiber of ciliary muscle (modified from Tripathi RC. Experimental Eye Research 1977;25:65–116).
Collector channels Internal collector channels The internal collector channels are simple digitations of the inner wall of Schlemm’s canal, without connection with the anterior chamber and were first described by Sondermann in 1933.
External collector channels The external collector channels arise from the outer wall of the Schlemm’s canal and are
limited by the same endothelium lining surrounded by a fine connective tissue in a complex system of 25–35 vessels running in two directions. Those vessels that reach the episcleral plexus directly are called aqueous veins (up to eight); they were first described by Ascher in 1942 and they were linked to the Schlemm’s canal by Ashton in 1952. Aqueous veins are thick and terminate in episcleral and conjunctival veins in a laminated junction called the laminated vein of Goldman; they can be observed with a slitlamp, 2 mm from the limbus and more often in the inferonasal region. The other system consists of thinner vessels that drain indirectly
References into three staged venous plexuses; the deep and mid-scleral plexus and the episcleral plexus. The deep scleral plexus is made up of fine branches of the anterior ciliary veins and join the mid-scleral plexus to constitute the intrascleral plexus. The intrascleral plexus collects blood from the ciliary venous plexus, which flows into the episcleral plexus. The episcleral plexus receives blood from the conjunctival veins of the perilimbal conjunctiva and drains into the cavernous sinus via the anterior ciliary and superior ophthalmic veins (Fig. 3.7). The conjunctival veins join the superior ophthalmic or facial veins through the palpebral and angular veins.8
Innervation of the outflow pathway The innervation of the trabecular meshwork is provided by the supraciliary nerve plexus and the ciliary plexus, which takes place in the area of the scleral spur. Parasympathetic fibers arise from the ciliary ganglion and perhaps from the pterygopalatine ganglion and the ganglion cells of the ciliary body. Sympathetic fibers come from the superior sympathetic ganglion. Sensory nerves originate from the trigeminal ganglion.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
References 14. 1. Grant WM. Further studies on facility of flow through trabecular meshwork. Arch Ophthalmol 1958;60:324–44. 2. Grant WM. Experimental aqueous perfusion in enucleated human eyes. Arch Ophthalmol 1963;69:783–801. 3. Bill A. The routes for bulk drainage of
15.
16.
31
aqueous humour in the vervet monkey (Cercopithecus ethiops). Exp Eye Res 1966;5:55–7. Shields B. Textbook of glaucoma: aqueous humor dynamics 2nd edn. Baltimore: Kimberly Kist, 1987:5–20. Alm A, Kaufman PL, Kitazawa Y et al. Uveoscleral outflow: biology and clinical aspects. London: Mosby International Limited, 1998. Brubaker RF. The flow of aqueous humor in the human eye. Trans Am Ophthalmol Soc 1982;80:391–5. Cole DF. Aqueous and ciliary body. In: Graymore CN, ed, Biochemistry of the eye. New York: Academic Press, 1970:114–18. Bron AJ, Tripathi RC, Tripathi BJ. Anterior chamber and drainage angle. In: Wolff’s anatomy of the eye and orbit. 8th edn. London: Chapman and Hall, 1997:279–307. Moses RA, Grodzki WF Jr. The scleral spur and scleral roll. Invest Ophthalmol Vis Sci 1977; 16:925–28. Ritch R, Shields M, Krupin T. The Glaucomas. St. Louis: Mosby-Year Book Inc, 1996:71–131. Fine BS. Structure of the trabecular meshwork and the canal of Schlemm. Trans Am Acad Ophthalmol Otol 1966;70:777–83. Johnstone MA, Grant WM, Murray A. Pressure-dependent changes in structures of the aqueous outflow system of human and monkey eyes. Am J Ophthalmol 1973;75:365–82. Tripathi RC. Comparative physiology and anatomy of the aqueous outflow pathway. In: Davson H, ed., The Eye. New York and London. Academic Press. 1974;5:163–237. Tripathi RC. Pathologic anatomy of the outflow pathway of aqueous humour in chronic simple glaucoma. Exp Eye Res 1977;25:403–7. Grierson I, Lee WR. Acid mucopolysaccharides in the outflow apparatus. Exp Eye Res 1975;21:417–31. Grierson I, Lee WR. Light microscopic
32
Anatomical features of outflow pathway
quantitation of the endothelial vacuoles in Schlemm’s canal. Am J Ophthalmol 1977;84:234–45. 17. Grierson I, Lee WR. Pressure effects on flow channels in the lining endothelium of Schlemm’s canal. Acta Ophthalmol 1978;56:935–50. 18. Kayes J. Pressure gradient changes in the trabecular meshwork of monkeys. Am J Ophthalmol 1975;79:549–56.
19. Svedbergh B. Effects of artificial intraocular pressure elevation on the outflow facility and the ultrastructure of the chamber angle in the vervet monkey (Cercopithecus ethiops). Acta Ophthalmol 1974;52:829–44. 20. Speakman JS. Drainage channels in the trabecular wall of the Schlemm’s canal. Br J Ophthalmol 1960;44:513–23.
4 How does non-penetrating glaucoma surgery work?* Douglas H Johnson and Mark Johnson
The advent of a new surgical procedure for glaucoma often raises the question of how the procedure lowers intraocular pressure (IOP), especially given the conventional understandings of the site of outflow resistance in glaucoma. Trabeculectomy was introduced in 1968 as a means of bypassing the clogged trabecular meshwork, allowing aqueous to enter Schlemm’s canal directly through the cut ends of the canal.1 Later experience found trabeculectomy most successful in cases in which a filtration bleb developed, giving rise to the understanding that it functions as a “guarded” filtration procedure.2,3 IOP can be lowered in the absence of a visible filtration bleb, however, indicating that the procedure may well allow aqueous to enter Schlemm’s canal directly in some cases, or alternatively that subclinical transconjunctival filtration of aqueous can occur. Viscocanalostomy and deep sclerectomy are new operations for glaucoma that have been designed to avoid the complications of filtering blebs and also the shallow or flat anterior chambers sometimes seen after trabeculectomy.4,5 Both procedures involve fashioning a partial thickness scleral flap, removing a second layer of sclera deep to the initial flap, and exposing Descemet’s membrane. Descemet’s membrane is thought to act as a semipermeable layer of tissue, allowing aqueous to percolate through it. Schlemm’s
canal is also unroofed during the removal of the second, deep scleral layer. In viscocanalostomy, the cut ends of the canal are then expanded with a viscoelastic material such as Healon. Healon is also injected into the region of excised sclera, or “scleral lake”, to prevent healing. By never entering the anterior chamber or removing trabecular meshwork, complications such as hypotony and hyphema are said to be avoided.4 Deep sclerectomy is similar because Schlemm’s canal is unroofed and Descemet’s membrane exposed by the removal of the second, deeper layer of sclera. Variations of these procedures include removing the inner wall of Schlemm’s canal and adjacent meshwork, but leaving the inner meshwork intact, or placement of a collagen implant or drainage device in the filtration bed.5 Do these operations relieve the specific pathological problem of primary open-angle glaucoma (POAG)? Or do they function as simply another way to make a hole in the eye? This chapter is a summary of current thought on the pathophysiology of aqueous-outflow resistance in glaucoma, and in light of this provides an interpretation of the mechanism of pressure reduction created by these new surgeries. The chapter does not attempt to be comprehensive in scope, but rather to present a synopsis of current conventional wisdom regarding aqueous-outflow resistance.
*Reproduced with permission from Johnson DH, Johnson M. How does non-penetrating glaucoma surgery work? Aqueous outflow resistance and glaucoma surgery. J Glaucoma 10: 55–67 (Lippincott Williams & Wilkins)
34
How does non-penetrating glaucoma surgery work?
Aqueous-outflow resistance The increased IOP found in glaucoma is caused by an increase in aqueous-outflow resistance within the drainage pathways, and not excess secretion of aqueous humor.6,7 Thus, researchers for the past 100 years have concentrated on trying to understand the mechanism by which outflow resistance is generated in the normal eye, and how this resistance is increased in the glaucomatous eye. Aqueous humor passes from the anterior chamber through the outflow pathway as a bulk flow driven by a pressure gradient. Neither metabolic poisons8 nor temperature9 affect this bulk flow (outside of an effect on the viscosity of the fluid), and thus the outflow system does not involve active transport. There is consensus that the bulk of outflow resistance in the normal eye resides near or within the inner wall of Schlemm’s canal; however, there is no such consensus about where the increased outflow resistance characteristic of POAG is localized, although it appears not to reside in the aqueous veins. We begin by reviewing the basis for these conclusions.
Two pathways for aqueous drainage Two pathways for aqueous drainage have been found to exist. The “conventional” pathway through the trabecular meshwork was discovered first. Early experiments showed that dye injected into the anterior chamber enters the episcleral veins and can be seen exiting at the limbus. These limbal vessels on the surface of the eye, the “aqueous veins”, contain aqueous humor.10 On histological
examination, these aqueous veins originate as collector channels in the outer wall of Schlemm’s canal. Casting techniques show that the trabecular meshwork, Schlemm’s canal, the collector channels and aqueous veins, and the episcleral veins form a continuous pathway.11 The “unconventional” or uveoscleral pathway originates at the angle of the eye. Aqueous passes through the ciliary body and ciliary muscle, enters the supraciliary and suprachoroidal spaces, and finally passes through the sclera12–14 or is reabsorbed by the vortex veins.15,16 In lower animals, the origin of this pathway is the ciliary cleft. The ciliary cleft becomes progressively smaller as the ciliary muscle enlarges and accommodative ability of the animal increases. The unconventional outflow may account for 30% of aqueous outflow in young monkeys and young humans.17 With age, uveoscleral outflow becomes reduced, decreasing to perhaps 10% of the total outflow in both monkeys and humans.18 It is difficult to study the amount of aqueous drainage by this route, however, and studies must use radioactive tracers or microspheres to understand the dynamics of fluid flow within this pathway. In humans, these methods cannot be done, and studies must use tonography or aqueous-humor fluorophotometry. These methods make a number of assumptions in the calculation of uveoscleral flow, which make the interpretation of results tenuous.19
Trabecular meshwork (conventional outflow) As stated above, the conventional aqueousoutflow system in the human eye is comprised of the trabecular meshwork, Schlemm’s canal, and the aqueous veins (Fig. 4.1). The trabecu-
Aqueous-outflow resistance
35
Figure 4.1 Trabecular meshwork Schlemm’s canal (SC) appears as a large, single lumen channel in this section. Aqueous spaces between lamellae are visible. (U = uveal meshwork; C = corneoscleral meshwork; J = juxtacanalicular tissue. Light microscopy, toluidine blue stain, 400).
lar meshwork has two major regions, the uvealcorneoscleral region and the juxtacanalicular region. The resistance of the trabecular meshwork to aqueous outflow was assessed by Grant nearly half a century ago.20 In a now classic experiment, a modified scalpel was used to incise the trabecular meshwork of enucleated normal eyes, with measurements taken of outflow resistance before and after each cut. Incision of the uveal and proximal corneoscleral meshwork did not affect outflow resistance. A deeper incision through the entire meshwork and into Schlemm’s canal, however, eliminated 75% of the normal outflow resistance.20 Other investigators have confirmed the finding that an appreciable fraction of outflow resistance (25–50%) is distal to the trabecular meshwork and Schlemm’s canal.21,22 Not all studies agree, however; Mäpea and Bill, using a micropuncture technique to measure the pressure distribution in the outflow pathway,
concluded that less than 10% of the outflow resistance is distal to the inner wall. While this discrepancy has not been resolved, all studies do agree that at least half of aqueous outflow resistance is generated proximal to the aqueous veins. Grant20 also studied a series of eight enucleated glaucomatous eyes, and found that an incision through the meshwork into Schlemm’s canal eliminated all of the abnormal glaucomatous outflow resistance. The remaining scleral resistance was similar to that found in normal eyes. This finding of the abnormal outflow resistance of glaucoma residing proximal to the aqueous veins is supported by the success of trabeculotomy, goniotomy, and direct removal of the trabecular meshwork (goniocurettage) in adults with POAG.23–28 Although the success of these procedures may diminish with time, their initial success in lowering IOP shows that the meshwork is the site of the abnormally high
36
How does non-penetrating glaucoma surgery work?
Figure 4.2 Uveal meshwork as seen from anterior chamber in view similar to clinical gonioscopy. Round cords of tissue form the first layer of meshwork, nearest the anterior chamber. Deeper layers appear as wider, flatter lamellae. (C = cornea; Ir = iris. Scanning electron microscopy, 250).
Figure 4.3 Trabecular meshwork. Corneoscleral lamellae consist of broad, flat sheets of tissue with oval windows (ar rowheads) allowing aqueous to pass between layers. JCT has irregular arrangement of tissue, without organized lamellae. Two erythrocytes are present (arrow), probably displaced during tissue dissection. (CS = corneoscleral lamellae; SC = Schlemm’s canal. Scanning electron microscopy, 250).
outflow resistance in POAG. In addition, laser trabeculoplasty also reduces outflow resistance in the glaucomatous eye.29 Because no incision is made during laser trabeculoplasty, inadvertent fistula formation through the
sclera cannot occur, as could potentially happen after trabeculotomy. While it is unclear how laser trabeculoplasty actually works in the meshwork to lower this abnormal outflow resistance,30,31 its application to
Aqueous-outflow resistance
37
Figure 4.4 Juxtacanalicular tissue. Schlemm’s canal endothelial lining is a continuous sheet of cells, which contain giant vacuoles (GV). JCT appears as loose arrangement of extracellular matrix. Elastic tendons (E), which will insert into inner wall of canal, ar e visible (6 250).
the trabecular meshwork strongly suggests a local meshwork effect. Evidence exists for contraction of the meshwork around the lasered spots, stimulation of trabecular-cell replication, and induction of matrix metalloprotease enzymes that digest the extracellular matrix.32–35
Uveal and corneoscleral meshwork regions
The uveal and corneoscleral regions are composed of a series of sheets or lamellae of collagenous tissue covered by a nearly continuous lining of endothelial cells. The uveal meshwork contains small, thin, cord-like lamellae (Fig. 4.2). The corneoscleral meshwork has wider, flatter lamellae, which contain oval windows between layers (Fig. 4.3). The aqueous spaces between the uveal cords are very large and become smaller in the
subsequent layers of the corneoscleral region. The number and size of these openings are large enough that the uveal and corneoscleral meshwork can be expected to create negligible resistance to flow. Poiseuille’s law predicts that a single pore 100 µm long (the thickness of the trabecular meshwork from the anterior chamber to Schlemm’s canal) with a diameter of 20 µm can carry the entire aqueous outflow (2 µL/min) with a pressure drop of 5 mmHg. Since the uveal and corneoscleral regions of the meshwork have numerous openings this large and larger,36 we can conclude that the pressure drop through this region is negligible. Experimental support for this proposition was provided by Grant,20 who cut through the proximal regions of the meshwork and found no effect on outflow resistance. In the latter stages of open-angle glaucoma, collapse and fusion of the trabecular lamellae have been described in these
38
How does non-penetrating glaucoma surgery work?
Figure 4.5 Inner wall of Schlemm’s canal and underlying juxtacanalicular tissue. Schlemm’s canal has been unroofed by removing outer wall of canal. Inadvertent damage occurred to some inner-wall cells, removing them and exposing the elastic tendons of the JCT. Boundary of damaged cell layer indicated by arrowheads. (IW = inner-wall cells; ET = elastic tendons. Scanning electron microscopy, 1 800).
regions in some eyes, but are not generally considered a prominent feature of the glaucomatous process.37–40
Juxtacanalicular region
The second major region of the trabecular meshwork is the loose tissue near Schlemm’s canal, known as the juxtacanalicular connec-
tive tissue (JCT). This region contains fairly free cells within an extracellular matrix (Fig. 4.4). The cells are interconnected by thin arms to one another, to the cells of the inner wall of Schlemm’s canal, and to fine collagen and elastic fibrils and fibers found in this region. These cells differ from those of the endothelial lining of Schlemm’s canal, because they have a more a fibroblastic appearance and only patches of surrounding basal lamina.41 The
Aqueous-outflow resistance intervening extracellular matrix, or “ground substance”, contains basement membrane material, including collagen IV, laminin, fibronectin, proteoglycans, and glycosaminoglycans. Tendon-like extensions from the ciliary muscle pass through this region42 and insert into the wall of Schlemm’s canal (Fig. 4.5). These connections are responsible for the effects of ciliary muscle contraction on outflow resistance.43
Outflow resistance of JCT and role of extracellular matrix
With its small openings and tortuous flow pathways, the JCT is expected to be the principal site of outflow resistance.44,45 Using microcannulation techniques, Maepen and Bill found that most of the outflow resistance was localized in the JCT of living monkeys, within several µm of the inner wall endothelium.46 Although this technique is difficult and subject to artifact, the results are consistent with the expected site of outflow resistance reported by other studies.37–40,44,45 Studies are not unanimous, however, that the site of outflow resistance is in the JCT. Alternative sites have been proposed, including a layer of cells between the corneoscleral meshwork and JCT,47 fusion of the trabecular lamellae,48 or collapse of Schlemm’s canal.49 Theoretical calculations suggest the JCT contains too much optically empty space to account for the measured outflow resistance of the eye. 44,45,47,50 In addition, the configuration of the JCT changes with IOP, appearing collapsed at low pressures and expanded at higher pressures.50–52 This expansion of the JCT with higher pressures does not fit the measured increase in aqueous-outflow resistance that occurs as IOP is raised. This increase is about 1% per mmHg and is called
39
the outflow obstruction coefficient (Q).53 Conventional thought suggests that partial collapse of the canal accounts for this increase in resistance with increased pressure. Lens depression, which prevents canal collapse, eliminates Q.54 As mentioned above, theoretical calculations44,45,47,50 of the flow resistance of the JCT indicate that the aqueous channels, viewed with conventional electron microscopy, would generate an insignificant fraction of outflow resistance. If the JCT were filled with an extracellular matrix gel such as glycosaminoglycans and proteoglycans, sufficient outflow resistance would be created to match that measured in the eye.44 Glycosaminoglycans and proteoglycans are known to be present in the meshwork and JCT.55–60 Glycosaminoglycans generate flow resistance in other connective tissues,61 and they could create flow resistance in the eye. Proteoglycans consist of glycosaminoglycans attached to a core protein. They are poorly visualized with conventional histochemical techniques.62 Glycosaminoglycans are highly negatively-charged molecules that hold substantial amounts of water, and occupy large volumes of space as a consequence of their charge and hydration. Conventional histochemical preparation techniques employ cationic ions that collapse these macromolecules, and thus they are not well visualized on standard electron micrographs. The result would be large areas of empty space on electron micrographs. Large amounts (up to 40% of total area) of such empty spaces are seen in the JCT on conventional electron micrographs.44,45,47,50 Because it is not known if these empty regions were truly empty in life, before fixation and processing of the tissue, or were filled with proteoglycans that were lost in processing, the empty spaces are called “optically” empty spaces.
40
How does non-penetrating glaucoma surgery work?
Endothelial lining of Schlemm’s canal
While the JCT contains large areas of optically empty space as seen with electron microscopy, a continuous anatomic barrier to aqueous outflow does exist. This barrier is the endothelial lining of Schlemm’s canal. This endothelial lining has several unique aspects which appear to represent a specific engineering solution to a unique physiological situation: movement of fluid into the lumen of a vessel across an intact endothelium down a pressure gradient, without collapsing the lumen, rather than from the lumen into the surrounding tissue. Venous capillaries also have fluid movement into them, from the surrounding tissue, but this is because of the higher oncotic pressure within the lumen that draws the tissue fluid in. As in other endothelia, the endothelial cells that line Schlemm’s canal are attached to one another by tight junctions.41,63 One of the unique aspects of this endothelium is the appearance of out-pouchings or invaginations in the endothelial lining, called “giant vacuoles”41,64 (Figs. 4.4 and 4.6). Giant vacuoles can form within one cell or between neighboring cells. On their basal side is an opening which connects with the underlying aqueous spaces of the JCT. They are not formed by metabolic processes, and do not require energy to form.8,9 Current thought indicates that these structures form passively as a result of the pressure drop across the inner wall endothelium.64,65 Tripathi64 suggested that the giant vacuoles may be transient structures and proposed a process by which vacuolar formation could occur as a cyclic process. A second unique characteristic of the endothelium of Schlemm’s canal is the appearance of small pores passing through these cells (Fig. 4.6). The pores are predominantly intracellular, but a substantial fraction of them are also intercellular66 and may correspond to a
Figure 4.6 Inner wall of Schlemm’s canal. In contrast with figure 4.5, cellular monolayer is intact. Bulging structures are presumably giant vacuoles, although they cannot always be distinguished from prominent nuclei. Pores (arrowheads) are found in presumed giant vacuoles and also in flat areas between cells. (Scanning electron microscopy, 3 700).
paracellular pathway described by Epstein and Rohen.67 The tight junctions between the endothelial cells become less complex, with fewer junctional strands, as IOP increases.63 This “loosening” of the junctions could make the formation of intercellular pores more
Aqueous-outflow resistance
41
Table 4.1 Hydraulic conductivity (Lp) of endothelia19 Endothelium
Lp (cm2 s per g) 10
Reference
Not fenestrated Brain capillary Cornea Lung capillary Skeletal muscle capillary Aorta Mesentery, omentum Aqueous-outflow pathway
0.03 1.6 3.4 2.5–7 9 50 4 000–9 000
117 116 117 117 118 53,117 *
Fenestrated Intestinal mucosa Synovium (knee) Renal glomerulus
32–130 120 400–3 100
53,117 53 53,117
*Flow rate of 2 µL/min driven by a pressure drop of 5 mmHg through a cross-sectional area of between 0.054cm2 and 0.13 cm2 (canal width of 150–350µm; canal length around the eye of 3.6 cm3); note that this is not necessarily Lp for innerwall endothelium since this calculation is based on the entire pressure drop through the outflow pathway; Lp for inner-wall endothelium is probably higher than this value.
likely at higher pressures, and could serve as a means of “self-regulation” of IOP by the meshwork. The pores have an average diameter of about 1 µm (size range: 0.1 µm to greater than 3 µm),68 and their density in the inner wall varies between 1 000 and 2 000 pores/mm2, or roughly 0.2–1 pores/cell.68–74 Scanning electron microscopy shows that 13–29% of giant vacuoles have pores, consistent with this estimate.70,72,73 The nature of the pores is not fully understood, because the number of pores may increase if fixative is perfused through an eye, suggesting that some pores may be fixation artifacts.66,68 The finding of pores by numerous laboratories, however, using both scanning and electron microscopy, suggest they are real structures.64,66,69,71,73,74
Outflow resistance of endothelium
Another unique aspect of the endothelium of Schlemm’s canal is its “leakiness”: it has the highest hydraulic conductivity of any endothelium in the body (Table 4.1). Endothelia of high hydraulic conductivity are usually fenestrated (e.g. glomerulus), whereas the endothelium of Schlemm’s canal is not. Yet the hydraulic conductivity of the canal endothelium is almost ten times higher than that of the renal glomerulus. In addition, the intercellular spaces are composed of tight junctions, which greatly limit fluid flow through the intercellular spaces. In other endothelia, fluid passes between the cells through the cells’ junctional complexes,75 or through fenestra if the endothelia is fenes-
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How does non-penetrating glaucoma surgery work?
trated.76 Compared with other endothelia that have tight junctions, the large hydraulic conductivity of the endothelium of Schlemm’s canal is even more exceptional. From this, we can conclude that fluid probably passes through the endothelium of Schlemm’s canal by a different mechanism to that which occurs in other endothelia. The pores of the endothelium of Schlemm’s canal appear to constitute this difference. Pores are numerous enough that the outflow resistance has been calculated to be, at most, 10% of the total outflow resistance of that measured in the eye. 71 Furthermore, it has been found that an increase in the IOP increases the number of inner wall pores.73,77 This is not associated with a decrease in outflow resistance53 which provides further evidence that the inner-wall endothelium accounts for only a small part of the outflow resistance. Giant vacuoles and pores allow the endothelium of the canal to function as a one-way valve, because they decrease greatly in number when the pressure within the canal becomes higher than that in the eye;51,73 this prevents reflux of blood from the canal into the eye during periods when the episcleral venous pressure is elevated, such as with bending or Valsalva maneuvers. This unique physiological requirement is also necessary in the drainage pathways for cerebrospinal fluid where giant vacuoles and pores are also seen.78–80 Although the pores of the endothelium of Schlemm’s canal are numerous enough that the endothelium is predicted to have a low resistance to aqueous outflow, disruption of the endothelium can nonetheless greatly decrease outflow resistance. Perfusion with agents that interfere with the cytostructural protein actin (cytochalasins, latrunculins) or that interfere with cell-to-cell contacts (EDTA) cause ruptures of the inner wall that reduce
outflow resistance.81–88 This change is more than would be predicted based on the calculated resistance of the inner-wall pores.66,68,71 Removal of these agents leads to a reversal of the inner-wall ruptures and a return of resistance toward baseline. On the assumption that these agents affect the cytoskeleton as expected and as shown by histological studies,84,86,87 four explanations are possible: 1) The inner and outer walls of Schlemm’s canal may have more resistance than theorized. 2) Disruption of the endothelial cells also disrupts the underlying basement membrane and extracellular matrix. 3) Cytoskeletal agents affect other cells within the meshwork, particularly the cells of the juxtacanalicular tissue. These cells have processes that connect with each other and with the endothelium of the canal. Disruption of these connections could “relax” the juxtacanalicularSchlemm’s canal network, loosening the tethering of the inner wall, expanding the canal wall and increasing the draining surface, permitting more extensive flow through the meshwork. 89 4) The inner wall acts in conjunction with the underlying extracellular matrix to modulate outflow resistance. In this potential hydrodynamic interaction, termed “funneling”, the endothelial pores themselves contribute negligible flow resistance, but since they force the fluid to “funnel” through those regions of the JCT nearest the pores, their number and size can greatly increase the effective outflow resistance of the JCT.90 Disruption of cells, or separation of innerwall cells from their underlying attachments, would eliminate the funneling effect and decrease outflow resistance. This may
Aqueous-outflow resistance explain the results of studies reporting that disruption of the inner-wall cells decreases outflow resistance.81,84,86,89
Collapse of Schlemm’s canal
Schlemm’s canal is a continuous channel oriented in a circumferential direction. The canal is oval in shape, with dimensions of about 280 30 µm at low IOP.50,80,91,92 A lumen of this size is too large to generate an appreciable outflow resistance. As IOP increases, the trabecular meshwork expands into the lumen of the canal, causing a concomitant narrowing of the lumen,51–80 raising the possibility that this collapse may cause a significant increase in outflow resistance. However, throughout the canal, especially near the collector channels, septae are present between the inner and outer walls. The proximity of these structures to the collector channels suggests they will prevent collapse of the canal and occlusion of the collector channels as IOP is increased.80,91,93 At an IOP of 40 mmHg, the canal is predicted to be largely collapsed except at the sites of the septae.91 Nesterov postulated that canal collapse could cause the elevated outflow resistance characteristic of POAG, and designed an operation to unroof the canal to remedy this problem.49 Although outflow resistance is elevated by collapse of the canal, resistance levels at high IOPs are not as high as found in glaucoma (in normal eyes, facility changed from a baseline of 0.40 µL/min per mmHg at 10 mmHg to a facility of 0.28 µL /min per mmHg at 50 mmHg; whereas the facility of eyes with POAG is usually less than 0.13).53,91 Assuming that Q, the obstruction of outflow with increasing IOP, is caused by collapse of the canal, the underlying problem in glaucoma must therefore involve more than just the collapse of
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Schlemm’s canal. While collapse of Schlemm’s canal is not the primary cause of glaucoma, if it occurs it can make the problem of increased IOP worse. Pilocarpine, which decreases outflow resistance, increases ciliary muscle tone and acts to expand the trabecular meshwork and JCT, and may also open the canal.94
Collector channels and aqueous veins
After entering the canal, the aqueous humor travels circumferentially around the eye until it reaches one of the 30 or so collector channels that join Schlemm’s canal. Fluid flows from the collecting channels into aqueous veins that ultimately drain into the episcleral venous system. The aqueous veins have an average diameter of 50 µm and a length of about 1 mm.21 Use of Poiseuille’s law indicates that the resistance of the aqueous veins should be negligible, if the veins are neither collapsed nor compressed. Measurement of the pressure in Schlemm’s canal in live monkeys supports this conclusion.46,95 Experimental evidence in the human eye, however, indicates that some resistance does occur in the collector channels and aqueous vein system. The trabeculotomy experiments previously mentioned have shown that 25–50% of the total outflow resistance is distal to Schlemm’s canal, presumably in the aqueous veins. However, most studies suggest the abnormal increase in outflow resistance found in glaucoma is not found in the aqueous veins nor in Schlemm’s canal. 20,23,91
Abnormal outflow resistance in the glaucomatous eye Several pieces of evidence indicate the trabecular meshwork is the site of the abnormally
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How does non-penetrating glaucoma surgery work?
increased outflow resistance of POAG, as discussed above. Surprisingly, histological examination of the meshwork does not show specific abnormalities or ultrastructural changes that could account for the elevation of pressure.37–40 The few changes found appear to be an exaggeration of aging changes found in the normal eye. A small increase in the amount of tendon and tendon-sheath material in the JCT is found, increasing from 15% to 22% in POAG when compared with aged normal eyes.37,38 This increase in tendon and tendonsheath material does not occur early in the disease process: IOP can be elevated even with normal amounts of the tendon and tendonsheath material.39 The increase in the tendon and tendon-sheath material is not enough to obstruct aqueous channels. 44,45,47,50 Studies have also examined glycosaminoglycans and proteoglycans of the meshwork in POAG, phagocytosis by trabecular cells, and the size of Schlemm’s canal.59,60,92,96 Elucidation of the pathophysiologic mechanism of POAG remains an area of intense research.
Uveoscleral outflow (unconventional pathway) The uveoscleral (or uveovortex) pathway originates at the angle of the eye, passes through the ciliary body and ciliary muscle, enters the supraciliary and suprachoroidal spaces, and finally passes through the sclera.12,13 Aqueous humor and aqueous proteins seep through sclera and episclera, passing into orbit, and are absorbed there by blood vessels. Aqueous may also be absorbed osmotically by the vortex veins.15,16 The unconventional outflow is relatively insensitive to IOP, increasing only a small amount with increases of pressure.14 The ciliary muscle probably represents a major site of flow resistance along this
pathway. Pilocarpine, which causes ciliary muscle contraction and decreases the size of spaces between the muscle bundles, decreases outflow through this pathway. Atropine, which relaxes the ciliary muscle, does the converse.97 Furthermore, prostaglandin F2, shown to increase unconventional outflow,98–101 may act by decreasing the extracellular matrix between ciliary muscle bundles.102
The mechanisms of laser and glaucoma surgery Laser trabeculoplasty Since laser trabeculoplasty was first described,29 it has been recognized that this procedure decreases outflow resistance by a mechanism other than simply making holes in the trabecular meshwork. When holes are created, they quickly heal shut (even with a YAG laser).29,103 Wise and Witter29 hypothesized that laser trabeculoplasty worked mechanically, either by shrinking collagen or through the formation of scar tissue that later contracts. Such contraction or shrinkage would lead to tension on the remaining trabecular meshwork, which then would open the intertrabecular spaces,29 and/or prevent collapse of Schlemm’s canal.31 Melamed and Epstein provided support for this hypothesis by showing that the actual sites of the laser burns appeared to be non-filtering, with aqueous flow being diverted to the remaining meshwork.104 Laser-induced shrinkage of the trabecular tissues does not lead to an immediate change in outflow facility in enucleated human
The mechanisms of laser and glaucoma surgery
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Figure 4.7 Inner wall of Schlemm’s canal and ruptured septa. Canal has been unroofed by removing outer wall. One of the septae that bridge the inner and outer walls has been inadvertently damaged, revealing loose arrangement of cells within. (IW = inner wall cells; Sep = ruptured septa. Scanning electron microscopy, 3 700).
eyes.30,31 This finding is consistent with the clinical observation that it takes about 3–6 weeks after laser for outflow facility to improve.29 While it could be that scarring caused by the laser takes several weeks to occur and affect outflow facility, another mechanism of laser action could be a change in the activity of the trabecular cells.30,31,105,106 Increased phagocytic activity, activation of cells leading to altered metabolic activity, increased levels of cell division, or a tissue remodeling between the lasered spots may occur. However, no conclusive experiment has been done to elucidate the mechanism by which improvements in outflow facility occurs after laser treatment.
Schlemm’s canal. 1 Healing and fibrosis occur, however, and it is likely that the cut ends of the canal become closed with scar tissue.2,107,108 The development of a filtering bleb is strong evidence that aqueous humor bypasses both the meshwork and canal, and exits through the surgical fistula. The advantage to this procedure over a full-thickness filter is the prevention of low pressures provided by the scleral flap. Once the eye has healed, aqueous continues to seep through the fistula and enters the filtration bleb.
Non-penetrating surgery Viscocanalostomy
Trabeculectomy As mentioned above, the original concept of trabeculectomy was to bypass the trabecular meshwork and allow aqueous humor to enter
Unroofing Schlemm’s canal (removing the outer wall of the canal) can cause damage to the inner wall of the canal (Figs 4.5 and 4.7).109,110 The septae, which bridge the inner and outer walls, can easily damage the inner
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(a) (a)
(b)
(b)
Figure 4.8 Viscocanalostomy in necropsy eye. Dilated Schlemm’s canal is apparent, this region of canal had a cannula inserted. Rupture of anterior portion of canal wall apparent at low (Fig. 4.8a) and high (Fig. 4.8b) magnification. Arrow denotes ruptured anterior portion of canal wall. Note compaction of meshwork immediately underlying inner wall of canal, with loss of intertrabecular spaces. (SC = Schlemm’s canal; toluidine blue; Fig. 4.8a at 40, Fig. 4.8b at 400). AC = anterior chamber; CC = collector channel.
Figure 4.9 Viscocanalostomy showing portion of canal receiving viscoelastic material only. This portion of meshwork was distal to the end of the cannula. Note septum within lumen of canal. Dilation of canal, with rupture of anterior portion of canal wall is apparent at low (Fig. 4.9a) and high (Fig. 4.9b) magnification (long arrow). Fig. 4.9a also shows disruption of inner wall of canal (short arrow) from displacement of septum: note sharp kink in septum. Same eye as Fig. 4.8. (toluidine blue; Fig. 4.9a at 40, Fig. 4.9b at 400). AC = anterior chamber; SC = Schlemm’s canal.
The mechanisms of laser and glaucoma surgery wall when they are pulled away during the unroofing procedure. Injection of viscoelastic into the ends of Schlemm’s canal is designed to enlarge the canal,4 but it is likely that this injection ruptures both the inner and outer endothelial walls of the canal as shown in both the human eye (Figs 4.8 and 4.9) and the monkey.110 These ruptures probably extend into the JCT, and may also rupture some of the meshwork itself. The operation probably functions as a “gentle” trabeculectomy, allowing aqueous to bypass the site of abnormal outflow resistance, the JCT tissue and enter the canal through these presumed and inadvertent ruptures. In addition, excising a deep layer of sclera and exposing Descemet’s membrane may also create a route for aqueous drainage that bypasses the meshwork. Studies in the rabbit, however, indicate that Descemet’s membrane is not permeable enough to allow relief of the elevated IOP of glaucoma.111,112 If the ruptured regions of the JCT and canal heal with time, surgery may fail in those eyes that did not develop filtration blebs. There is no theoretical basis for relieving elevated IOP by expanding the lumen of Schlemm’s canal. Injection of viscoelastic will certainly dilate the canal lumen, but the viscoelastic itself will probably not remain in the canal long enough to prevent healing of the cut ends of the canal. The high-molecularweight viscoelastic used in this procedure has not been shown to retard healing. The creation of a “scleral lake” underneath the partial thickness scleral flap has no theoretical effect on the abnormal outflow resistance found in glaucoma. Ultrasonic measurements of the area of the lake found no relation to IOP in a series of human eyes.113 A small effect on pressure may occur by removing a segment of the aqueous veins in that region, eliminating some of the normal resis-
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tance created by these aqueous veins (see above). If the cut ends of the aqueous veins did not heal shut, but remained open, this might lower IOP a few millimeters. Deep sclerectomy
During conventional trabeculectomy, many surgeons do not actually remove a piece of the trabecular meshwork at all, but rather a piece of cornea anterior to the meshwork. Deep sclerectomy takes this approach, with the exception of leaving Descemet’s membrane intact.5 Descemet’s membrane is semi-permeable, and therefore creates some resistance to aqueous drainage into the surgical fistula, but as indicated above, Descemet’s membrane is not permeable enough to relieve the elevated pressure of glaucoma.111,112 Deep sclerectomy appears to be another variation of a “guarded filter”, adding a second “guard” to that of the partial thickness scleral flap, which is still used in this surgery. The operation also unroofs Schlemm’s canal, and aqueous percolates through the remaining trabeculo-Descemet’s membrane. As mentioned above, damage to the inner wall of the canal is highly likely to occur during the removal of the outer wall when unroofing the canal (Figs 4.5 and 4.7). Such damage to the inner wall and underlying juxtacanalicular tissue would allow aqueous a new route into Schlemm’s canal.
Trabecular aspiration Application of high vacuum to the meshwork region is reported to lower IOP in pseudoexfoliative glaucoma, but has little effect on POAG.114,115 If the suction were strong enough to break the endothelial lining of the canal and rupture the JCT, IOP would be lowered; this would be expected to lower pressure in both
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How does non-penetrating glaucoma surgery work?
POAG and pseudoexfoliation. If the suction were not that strong, it could function in removing the accumulations of pseudoexfoliative material that occur within the meshwork.116
Goniotomy While spectacularly successful in infant eyes with abnormally developed meshworks, goniotomy and trabeculotomy have been generally disappointing in adult eyes.3,117,118 Trabeculotomy and goniotomy make excellent theoretical sense, because the surgical incision through the trabecular meshwork and JCT into Schlemm’s canal allows aqueous to bypass the abnormal portions of the meshwork. Because the aqueous veins may have some outflow resistance, as discussed above, IOP should not drop too low. Clinical studies report that pressure stabilizes in the high teens.117,118 Blood reflux into the eye from Schlemm’s canal could occur if the episcleral venous pressure was increased during a cough or Valsalva maneuver, or if the patient were to bend over. This would probably be an acceptable, minor side-effect if the operation otherwise kept IOP normal, avoiding a filtration bleb and all of its attendant problems. Healing of the goniotomy incision has been the main problem in adult eyes.107,108,117–119 Why healing does not occur more frequently in the infant eye is unknown, but may relate to the elastic condition of infant eye tissues. Infant sclera retracts when cut, sometimes making it difficult to make a trabeculectomy scleral flap cover the surgical bed from which it was dissected. This same elastic property may be the reason that infant eyes become larger when IOP is elevated. Such buphthalmos occurs until about the age of 2 years, which is about the same age at which goniotomies are no longer
are effective in children. In the infant eye undergoing goniotomy, the cut ends of the meshwork may retract enough because of the elastic nature of the infantile tissues that the incision gapes, and does not heal together. In the adult eye, such elastic retraction would not occur, allowing the cut ends of the meshwork to lie in apposition to each other, and thus allow healing of the incision. A study of goniotomy in adults has suggested that incision of the meshwork near Schwalbe’s line, anterior to the usual site of incision in goniotomy, may overcome this problem. Success in adult eyes has been reported with this anterior incision.120
Goniocurettage Goniocurettage is an operation related to goniotomy that involves removal of the trabecular meshwork. By the use of a sharpened curette to scrape away the meshwork for about 90° of the circumference of the eye, Jacobi et al121–123 report success in lowering IOP. An ab interno incision is used, and a filtration bleb is not created. Damage to the collector channels during the removal of meshwork could limit the effectiveness of this procedure, which is the most promising of the new glaucoma surgeries. IOP is lowered into the high teens, and does not reach as low a level as after conventional filtration surgery.
Future goals Our understanding of aqueous-outflow mechanisms is incomplete, especially with regard to the pathogenesis of POAG. Although ideas abound, and a working hypothesis has been presented in this chapter,
References much remains unsolved. The ideal surgical procedure would address the as-yet-unknown site of pathology in glaucoma and leave the eye otherwise intact. In practice, however, any procedure that is effective in lowering IOP, that has minimal complications and sideeffects, and provides long-term success in pressure control would be helpful in the management of glaucoma. The current practice of filtration surgery, especially with the use of antifibrotic agents such as mitomycin C, creates eyes that can develop conjunctival leaks, infection, and problems from filtration blebs. We look forward to improvements in the surgical control of pressure in the new millennium.
Summary Histological, experimental, and theoretical studies of the aqueous-outflow pathways point toward the juxtacanalicular region and inner wall of Schlemm’s canal as the likely site of aqueous-outflow resistance in the normal eye. At least 50% of the aqueous-outflow resistance in the normal eye, and the bulk of the pathologically increased resistance in the glaucomatous eye reside in the trabecular meshwork and/or in the inner wall of Schlemm’s canal. The uveoscleral/uveovortex pathways, which account for perhaps 10% of the aqueous drainage in the normal aged human eye, can become major accessory routes for aqueous drainage after pharmacological treatment. Surgeries designed to incise or remove the abnormal trabecular meshwork of glaucoma address the pathological problem of the disease. Surgeries that unroof Schlemm’s canal or expand the canal, such as viscocanalostomy, probably cause inadvertent
49
ruptures of the inner wall and juxtacanalicular tissue, thus relieving the abnormal outflow resistance of glaucoma. This chapter is a summary of current thought on the pathophysiology of aqueous-outflow resistance in glaucoma, and in light of this provides an interpretation of the mechanism of pressure reduction created by these new surgeries.
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53. Brubaker RF. The effect of intraocular pressure on conventional outflow resistance in the enucleated human eye. Invest Ophthalmol Vis Sci 1975;14:286–92. 54. Van Buskirk EM. Changes in the facility of aqueous outflow induced by lens depression and intraocular pressure in excised human eyes. Am J Ophthalmol 1976;82:736–40. 55. Acott TS, Westcott M, Passo MS, Van Buskirk EM. Trabecular meshwork glycosaminoglycans in human and cynomolgus monkey eye. Invest Ophthalmol Vis Sci 1985;26:1320–29. 56. Tschumper RC, Johnson DH, Bradley JMB, Acott T. Glycosaminoglycans of human trabecular meshwork in perfusion organ culture. Curr Eye Res 1990;9:363–69. 57. Johnson DH, Bradley J, Acott T. The effect of dexamethasone on glycosaminoglycan of human trabecular meshwork in perfusion organ culture. Invest Ophthalmol Vis Sci 1990;31:2568–71. 58. Johnson DH, Knepper PA. Microscale analysis of the glycosaminoglycans of the human trabecular meshwork: a study in perfusion cultured eyes. J Glaucoma 1994;3:58–69. 59. Knepper PA, Goosens W, Hvizd M, Palmberg PF. Glycosaminoglycans of the human trabecular meshwork in primary open angle glaucoma. Invest Ophthalmol Vis Sci 1996;37:1360–67. 60. Knepper PA, Goosens W, Palmberg PF. Glycosaminoglycan stratification of the juxtacanalicular tissue in normal and primary open angle glaucoma. Invest Ophthalmol Vis Sci 1996;37:2414–25. 61. Levick JR. Flow through interstitium and other fibrous matrices. Quart J Exp Physiol 1987;72:409–37. 62. Hascall VC, Hascall GK. Proteoglycans. In: Hay ED, ed. Cell biology of extracellular matrix. New York, NY: Plenum Press, 1981:39–63. 63. Ye W, Gong H, Sit A et al. Interendothelial junctions in normal human Schlemms’s canal
respond to changes in pressure. Invest Ophthalmol Vis Sci 1997;38:2460–68. 64. Tripathi RC. Ultrastructure of Schlemm’s canal in relation to aqueous outflow. Exp Eye Res 1968;7:335–41. 65. Johnstone MA. Pressure-dependent changes in nuclei and the process origins of the endothelial cells lining Schlemm’s canal. Invest Ophthalmol Vis Sci 1979;18:44–51. 66. Ethier CR, Coloma FM, Sit AJ, Johnson M. Two pore types in the inner-wall endothelium of Schlemm’s canal. Invest Ophthalmol Vis Sci 1998;39:2041–48. 67. Epstein DL, Rohen JW. Morphology of the trabecular meshwork and inner-wall endothelium after cationized ferritin perfusion in the monkey eye. Invest Ophthalmol Vis Sci 1991;32:160–71. 68. Sit AJ, Coloma FM, Ethier CR, Johnson M. Factors affecting the pores of the inner wall endothelium of Schlemm’s canal. Invest Ophthalmol Vis Sci 1997;38: 1517–25. 69. Kays J. Pore structure of the inner wall of Schlemm’s canal. Invest Ophthalmol Vis Sci 1967;6:381–94. 70. Bill A. Scanning electron microscopic studies of the canal of Schlemm. Exp Eye Res 1970;10:214–18. 71. Bill A, Svedbergh B. Scanning electron microscopic studies of the trabecular meshwork and the canal of Schlemm––an attempt to localize the main resistance to outflow of aqueous humor in man. Acta Ophthamol 1972;50:295–320. 72. Segawa K. Pore structures of the endothelial cells of the aqueous outflow pathway: scanning electron microscopy. Jpn J Ophthalmol 1973;17:133–39. 73. Lee WR, Grierson L. Pressure effects on the endothelium of the trabecular wall of Schlemm’s canal: a study by scanning electron microscopy. Graefe’s Arch Clin Exp Ophthalmol 1975;196:255–65. 74. Svedbergh B. Effects of intraocular pressure on the pores of the inner wall of Schlemm’s
References canal. Jpn J Ophthalmol 1976;50:127–35. (Suppl III) 75. Curry FE, Michel CC. A fiber matrix model of capillary permeability. Microvasc Res 1980;20:96–99. 76. Levick JR, Smaje LH. An analysis of the permeability of a fenestra. Microvasc Res 1987;33:233–56. 77. Grierson I, Lee WR. Pressure effects on flow channels in the lining endothelium of Schlemm’s canal. Acta Ophthalmologica 1978;56:935–52. 78. Tripathi RC. Tracing the bulk outflow route of cerebrospinal fluid by transmission and scanning electron microscopy. Brain Res 1974;80:503–06. 79. Tripathi RC, Tripathi BJ. Bulk flow of humors of the eye and brain through vacuolar transendothelial channels. Prog Appl Microcirc 1985;5:118–34. 80. Tripathi RC. The functional morphology of the outflow systems of ocular and cerebrospinal fluids. Exp Eye Res 1977;24:65–116 (suppl). 81. Johnson DH. The effect of cytochalasin D on outflow facility and the trabecular meshwork of the human eye in perfusion organ culture. Invest Ophthalmol Vis Sci 1997;38:2790–99. 82. Kaufman PL, Bárány EH. Cytochalasin B reversibly increases outflow facility in the eye of the cynomolgus monkey. Invest Ophthalmol Vis Sci 1977;16:47–53. 83. Kaufman PL, Bill A, Bárány EH. Effect of cytochalasin B on conventional drainage of aqueous humor in the cynomolgus monkey: the ocular and cerebrospinal fluids. Exp Eye Res 1977;25:411–14. 84. Bill A, Lütjen-Drecoll E, Svedbergh B. Effects of intracameral Na 2EDTA and EGTA on aqueous outflow routes in the monkey eye. Invest Ophthalmol Vis Sci 1980;19:492–504. 85. Kaufman PL, Erickson K. Cytochalasin B and D dose-outflow facility response relationships in the cynomolgus monkey. Invest Ophthalmol Vis Sci 1982;23:646–50. 86. Hamanaka T, Bill A. Morphological and
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functional effects of Na 2EDTA on the outflow routes for aqueous humor in monkeys. Exp Eye Res 1987;44:171–90. 87. Svedbergh B, Lütjen-Drecoll E, Oberr M, Kaufman PL. Cytochalasin B-induced structural changes in the anterior ocular segment of the cynomolgus monkey. Invest Ophthalmol Vis Sci 1987;17:718–34. 88. Peterson JA, Tian B, Bershadsky AD et al. Latrunculin-A increases outflow facility in the monkey. Invest Ophthalmol Vis Sci 1999;40:931–41. 89. Sabanay I, Gabelt BT, Tian B et al. H-7 effects on the structure and fluid conductance of monkey trabecular meshwork. Arch Ophthalmol 1999;118:955–62. 90. Johnson M, Shapiro A, Ethier CR, Kamm RD. Modulation of outflow resistance by the pores of the inner wall endothelium. Invest Ophthalmol Vis Sci 1992;33:1670–75. 91. Johnson M, Kamm RD. The role of Schlemm’s canal in aqueous outflow from the human eye. Invest Ophthalmol Vis Sci 1983;24:320–25. 92. Johnson DH, Matsumoto Y. Schlemm’s canal becomes smaller after successful filtration surgery. Arch Ophthalmol 2000;118:1251–56 93. Hoffman F, Dumitrescu L. Schlemm’s canal under the scanning electron microscope. Ophthalmic Res 1971;2:37–45. 94. Van Buskirk EM. Anatomic correlates of changing aqueous outflow facility in excised human eyes. Invest Ophthalmol Vis Sci 1982;22:625–32. 95. Mäpea O, Bill A. The pressures in the episcleral veins, Schlemm’s canal and the trabecular meshwork in monkeys: effects of changes in intraocular pressure. Exp Eye Res 1989;49:645–63. 96. Matsumoto Y, Johnson DH. Trabecular meshwork phagocytosis in glaucomatous eyes. Ophthalmologica 1997;211: 147–52. 97. Bill A, Wålinder P-E. The effects of
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How does non-penetrating glaucoma surgery work?
pilocarpine on the dynamics of aqueous humor in a primate (Macaca irus). Invest Ophthalmol 1966;5:170–75. 98. Crawford K, Kaufman PL, Gabelt BT. Effect of topical PGF 2a on aqueous humor dynamics in cynomolgus monkeys. Curr Eye Res 1987;6:1035–44. 99. Camras CB, Podos SM, Rosenthal JS et al. Multiple dosing of prostaglandin F2 or epinephrine on cynomolgus monkey eyes. I. Aqueous humor dynamics. Invest Ophthalmol Vis Sci 1987;28:463–69. 100. Camras CB, Bhuyan KC, Podos SM et al. Multiple dosing of prostaglandin F2 or epinephrine on cynomolgus monkey eyes. II. Slit-lamp biomicroscopy, aqueous humor analysis, and fluorescein angiography. Invest Ophthalmol Vis Sci 1987;28:921–26. 101. Kerstetter JR, Brubaker RF, Wilson SE, Kullersrand LJ. Prostaglandin F 2-1-isopropyl ester lowers intraocular pressure without decreasing aqueous humor flow. Am J Ophthalmol 1988;105:30–34. 102. Lütjen-Drecoll E, Tamm E. Morphological study of the anterior segment of cynomolgus monkey eyes following treatment with prostaglandin F2. Exp Eye Res 1988;47:761–69. 103. Melamed S, Teehasaened C, Epstein DL. Role of fibronectin in closure of YAG trabeculopuncture. Laser Light Ophthalmol 1989;2:233–41. 104. Melamed S, Epstein DL. Alterations of aqueous humour outflow following argon laser trabeculoplasty in monkeys. Br J Ophthalmol 1987;71:776–81. 105. Bylsma SS, Samples JR, Acott TS, Van Buskirk EM. Trabecular cell division after argon laser trabeculoplasty. Arch Ophthalmol 1988;106:544–47. 106. Acott TS, Samples JR, Bradley JMB et al. Trabecular repopulation by anterior trabecular meshwork cells after laser trabeculoplasty. Am J Ophthalmol 1989;107:1–6. 107. Bárány EH, Linnér E, Lütjen-Drecoll E,
Rohen JW. Structural and functional effects of trabeculectomy in cynomolgus monkeys. Albrecht v Graefes Arch Klin Exp Ophthal 1972;184:1–28. 108. Lütjen-Drecoll E. Electron microscopic studies on reactive changes of the trabecular meshwork in human eyes after microsurgery. Albrecht v Graefes Arch Klin Exp Ophthal 1972;183:267–85. 109. Sit AJ, Coloma FM, Ethier CR, Johnson M. Factors affecting the pores of the inner wall endothelium of Schlemm’s canal. Invest Ophthalmol Vis Sci 1997;38:1517–25. 110. Smit BA, Johnstone MA. Effects of viscocanalostomy on the histology of Schlemm’s canal in primate eyes. Invest Ophthalmol Vis Sci 2000;41:S578 (abstr). 111. Speigel D, Schefthaler, Kobuch K. Outflow facilities through Descemet’s membrane in rabbits. Invest Ophthalmol Vis Sci 2000;41:S578 (abstr). 112. Fatt I. Permeability of Descemet’s membrane to water. Exp Eye Res 1969;8:340–54. 113. Sannace C, Miserocchi E, Carassa RG et al. Viscocanalostomy: an ultrasound biomicroscopic study. Invest Ophthalmol Vis Sci 2000;41:S578 (abstr). 114. Jacobi PC, Krieglstein GK. Trabecular aspiration: clinical results of a new surgical approach to improve trabecular facility in glaucoma capsulare. Ophthalmic Surg 1994;25:641–45. 115. Jacobi PC, Dietlein TS, Krieglstein GK. Bimanual trabecular aspiration in pseudoexfoliation glaucoma: an alternative in nonfiltering glaucoma surgery. Ophthalmology 1998;105:886–94. 116. Gottanka J, Martus P, Johnson DH, LütjenDrecoll E. Correlation of pseudoexfoliative material and optic nerve damage in pseudoexfoliation syndrome. Invest Ophthalmol Vis Sci 1997;38:2435–46. 117. Luntz MH, Livingston DG. Trabeculotomy ab externo and trabeculectomy in congenital and adult-onset glaucoma. Am J Ophthalmol 1977;83:174–79.
References 118. Tanihara H, Negi A, Akimoto M et al. Surgical effects of trabeculotomy ab externo on adult eyes with primary open angle glaucoma and pseudoexfoliation syndrome. Arch Ophthalmol 1993;111:1653–61. 119. Melamed S, Pei J, Puliafito CA, Epstein DL. Q-switched neodymium-YAG laser trabeculopuncture in monkeys. Arch Ophthalmol 1985;103:129–33. 120. Quaranta L, Hitchings RA, Quaranta CA. Ab-interno goniotrabeculotomy versus mitomycin C trabeculectomy for adult openangle glaucoma: a 2–year randomized clinical trial. Ophthalmology 1999;106:1357–62.
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121. Jacobi PC, Dietlein TS, Krieglstein GK. Goniocurettage for removing trabecular meshwork: clinical results of a new surgical technique in advanced chronic open-angle glaucoma. Am J Ophthalmol 1999;127:505–10. 122. Jacobi PC, Dietlein TS, Krieglstein GK. Microendoscopic trabecular surgery in glaucoma management. Ophthalmology 1999;106:538–44. 123. Jacobi PC, Dietlein TS, Krieglstein GK. Technique of goniocurettage: a potential treatment for advanced chronic open angle glaucoma. Br J Ophthalmol 1997;81:302–07.
5 Mechanisms of filtration in nonpenetrating filtering surgeries André Mermoud and Emilie Ravinet
To improve the reproducibility and safety of filtering procedures, several non-penetrating filtering surgeries have been described in the past few years.1–16 The principal common concept of non-penetration is to create filtration through a naturally occurring membrane that acts as an outflow resistance site, which allows a progressive drop in intraocular pressure (IOP) and avoids postoperative ocular hypotony. This membrane, the trabeculo-Descemet’s membrane, consists of the trabeculum and the peripheral Descemet’s membrane.1 To expose the membrane a deep sclerokeratectomy should be done, which also provides a postoperative scleral space. This space may act as an aqueous reservoir and as a filtration site, which may prevent the need for a large subconjunctival filtration bleb. In this way the risk of late bleb-related endophthalmitis can be reduced. Several studies have shown that in patients with various glaucomas such as primary openangle glaucoma, pseudoexfoliative, pigmentary, the main site of aqueous outflow resistance is located at the juxtacanalicular trabecular meshwork and the inner wall of Schlemm’s canal. By removing the internal wall of Schlemm’s canal and the juxtacanalicuar meshwork, the main outflow resistance in patients with openangle glaucoma can probably be relieved. This additional technique has been called ab
Figure 5.1 Schematic representation of the trabeculoDescemet’s membrane. (A) Posterior trabeculum, (B) anterior trabeculum and (C) Descemet’s membrane.
externo trabeculectomy and has been proposed by several investigators (Fig. 5.2).5–7 In primary and secondary closed-angle glaucoma and probably in congenital glaucoma, the outflow resistance is located before the trabecular meshwork. Thus nonperforating filtering surgery is probably not
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Mechanisms of filtration in non-penetrating filtering surgeries
(a)
(b) Figure 5.2 Schematic representation of the anatomy before (a) and after (b) ab externo trabeculectomy. The arrows represent the site of aqueous humor passage. The pealing of the membrane corresponds to the ablation of the inner endothelium of Schlemm’s canal and the juxtacanalicular trabeculum (c) scanning electron microscopic view of the peeled membrane.
(c)
indicated for the treatment of these forms of glaucoma.
and safety of non-penetrating surgeries: aqueous humor flow through the trabeculoDescemet’s membrane and aqueous resorption after its passage through the trabeculoDescemet’s membrane.
Mechanisms of filtration after non-penetrating glaucoma surgery
Flow through trabeculoDescemet’s membrane
There are two sites of interest when one studies the mechanisms involved in efficiency
The trabeculo-Descemet’s membrane offers resistance to aqueous humor outflow. This
Mechanisms of filtration after non-penetrating glaucoma surgery
59
Figure 5.3 Continuous IOP recording during a deep sclerectomy. The slope of decrease is slow and corresponds to an average of 2.7 ± 0.06 mmHg/min.
resistance allows a slow decrease in IOP during surgery and accounts for the reliable and reproducible IOP on the first postoperative day. Thus the main advantage of the trabeculo-Descemet’s membrane is to reduce immediate postoperative complications, such as hypotony, flat anterior chamber, choroidal detachments, and induced cataract. In an experimental model, the gradual decrease in IOP was studied and the resistance of the trabeculo-Descemet’s membrane calculated. Experiments were done on enucleated human eyes unsuitable for keratoplasty. The mean rate of IOP decrease was 2.7 ± 0.6 mmHg/min (Fig. 5.3). The ocular aqueous outflow resistance dropped from a mean of 5.34 ± 0.19 mmHg µL per min pre-
operatively to a mean of 0.41 ± 0.16 mmHg µL per min postoperatively.1 The resistance of the trabeculo-Descemet’s membrane thus appears low enough to ensure a low IOP and yet high enough to maintain the anterior chamber depth and avoid the postoperative complications in relation to hypotony. In the same study, Vaudaux and Mermoud,1 on histological examination looked at the surgical site by ocular perfusion with ferritine. They were able to show that the main outflow through the trabeculo-Descemet’s membrane occurred at the level of the anterior trabeculum (Fig. 5.4). There was, however, some degree of outflow through the posterior trabeculum and Descemet’s membrane.
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Mechanisms of filtration in non-penetrating filtering surgeries Aqueous humor resorption After aqueous humor passage through the trabeculo-Descemet’s membrane, four hypothetical mechanisms of aqueous resorption may occur: a subconjunctival filtering bleb; an intrascleral filtering bleb; a suprachoroidal filtration; an episcleral vein outflow via Schlemm’s canal (Fig. 5.5).
3 1
2
Subconjunctival bleb
Figure 5.4 Histology of a deep sclerectomy performed in an eye perfused with ferritine. Blue color represents the aqueous humor passage. Main aqueous humor flow takes place at the level of anterior trabeculum (1). There is also some passage through Descemet’s membrane (2) and the posterior trabeculum (3).
A
As observed after trabeculectomy almost all patients undergoing non-penetrating filtering surgeries have a diffuse conjunctival bleb on the first postoperative day. As shown by ultrasonic biomicroscopy (UBM) studies, successful cases have a low profile and diffuse subconjunctival filtering bleb even years after surgery (Fig. 5.6). However, this bleb tends to be smaller than the one seen after trabeculectomy (Fig. 5.7).
D
B
C
Figure 5.5 Schematic representation of deep sclerectomy with four hypothetical mechanisms of aqueous humor resorption after passage through the trabeculo-Descemet’s membrane. (A) the subconjunctival filtering bleb; (B) the intrascleral filtering bleb; (C) the subchoroidal passage; (D) the episcleral drainage via Schlemm’s canal ostia.
Mechanisms of filtration after non-penetrating glaucoma surgery
(a)
61
(b)
Figure 5.6 Photographic (a) and ultrasonic biomicroscopy (b) images of subconjunctival filtering bleb 5 years after deep sclerecomy with collagen implant.
(a)
(b)
Figure 5.7 Photographic (a) and ultrasonic biomicroscopy (b) images of subconjunctival filtering bleb 5 years after trabeculectomy.
Intrascleral bleb
During deep sclerectomy, a certain volume of sclera is removed ranging between 5 and
8 mm3. Provided the superficial scleral flap does not collapse, this scleral volume may be transformed into an intrascleral filtering bleb. Thus, in order to keep this intrascleral volume
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Mechanisms of filtration in non-penetrating filtering surgeries
Figure 5.8 Ultrasonic biomicroscopy image of intrascleral filtering bleb 2 years after a deep sclerectomy with collagen implant. The echogenicity of the intrascleral bleb is very similar to that of a diffuse low grade subconjunctival filtering bleb.
upright, different devices such as the collagen implant have been tried. Hyaluronic acid or non-resorbable Hema implants have also been used. On UBM, an intrascleral bleb was observed in more than 90% of patients who received a collagen implant (Fig. 5.8) and the mean volume of the intrascleral bleb was 1.8 mm3 in an unpublished study done by D Kazakova and myself. In the intrascleral filtering bleb the aqueous resorption mechanism may be different to the one occurring in the subconjunctival space. The aqueous humor is probably resorbed by new aqueous drainage vessels, as shown by Delarive et al (unpublished data). In this study on rabbits Delarive et al showed that in the scleral space created after deep sclerectomy, irrespective of whether or not a collagen implant was used, new aqueous humor drainage vessels were growing and resorbing the aqueous flowing through the trabeculo-Descemet’s membrane (Fig. 5.9). Similar results have been obtained by Nguyen
(a)
(b)
Figure 5.9 (a) Histology of intrascleral filtration site 9 months after deep sclerectomy with collagen implant done in a rabbit. There are many newly formed aqueous humor draining vessels stained in blue by ferritine, which was injected into the anterior chamber before enucleation. (b) Same preparation in an unoperated eye. There are only a few drainage vessels.
Mechanisms of filtration after non-penetrating glaucoma surgery
63
(a) Figure 5.10 (a) Anterior segment fluoresceine and indocyanine green angiography representing normal rabbit limbal area with the Schlemm’s canal and a few collector canals.
(b) Figure 5.10 (b) Same area 6 months after deep sclerectomy with collagen implant. Numerous new aqueous-humor drainage vessels are present in surgical site.
and coworkers with the same model by anterior segment fluorescein and indocyanine green angiography (Fig. 5.10) (unpublished data). Subchoroidal space
By thinning the sclera by 90%, aqueous humor outflow into the suprachoroidal space may occur; in fact on UBM, it is possible to see fluid between the ciliary body and the remaining sclera (Fig. 5.11) in 45% of the patients studied years after the deep sclerectomy (D Kazakova et al, unpublished data). However, this observation could also indicate a chronic ciliary body detachment with subsequent reduction of the aqueous production. Further studies on aqueous dynamics following nonpenetrating filtering surgery are needed to better understand the exact mechanisms of aqueous drainage and their respective importance in terms of success and complications.
Figure 5.11 Ultrasonic biomicroscopy image of a subchoroidal aqueous humor passage after deep sclerectomy.
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Mechanisms of filtration in non-penetrating filtering surgeries
Figure 5.12 Schlemm’s canal is dilated peroperatively during viscocanalostomy. The aqueous humor drainage may take this route to reach episcleal veins after operation.
Figure 5.13 The Hema implant inserted with both arms into the two ostia of Schlemm’s canal. This procedure may also promote resorption of aqueous humor through the episcleral veins via Schlemm’s canal.
Schlemm’s canal
of open-angle glaucoma. The immediate postoperative complication rate is low, and visual acuity is almost unaffected. The created trabeculo-Descemet’s membrane window allows a progressive drop in IOP while at the same time offering enough resistance to prevent the immediate postoperative complications. Downstream, there appears to be several hypothetical aqueous outflow mechanisms, namely, a subconjunctival filtering bleb, an intrascleral bleb with probable new aqueous drainage veins, a suprachoroidal passage with hypothetical increased uveoscleral outflow and/or decreased aqueous humor production by chronic ciliary body detachment, and a possible physiological route towards the episcleral veins via the two open ostia of Schlemm’s canal.
When the deep sclerectomy dissection is done, Schlemm’s canal is opened and unroofed. On either side of the deep sclerectomy the two surgically created ostia of Schlemm’s canal may drain the aqueous humor into the episcleral veins. This mechanism is probably more important after viscocanalostomy, during which the ostia and Schlemm’s canal are dilated with high viscosity hyaluronic acid (Fig. 5.12). It is probably also important with Hema implants because the two arms of the “T” are inserted into the two ostia of Schlemm’s canal, thereby preventing their collapse (Fig. 5.13). Research has still to be done to establish the importance of this mechanism.
Conclusion and summary Non-penetrating filtering surgeries as performed by several investigators offer a drop in IOP and a satisfactory long-term success rate for all types
References 1. Vaudaux J, Mermoud A. Aqueous dynamics after deep sclerectomy: ex-vivo study. Ophthalmic Pract 1998;16:204–09.
References 2. Sanchez E, Schnyder CC, Mermoud A. Résultats comparatifs de la sclérectomie profonde transformée en trabéculectomie et de la trabéculectomie classique. Klin Monatsbl Augenheilkd 1997;210:261–64. 3. Chiou AGY, Mermoud A, Jewelewicz DA. Post-operative inflammation following deep sclerectomy with collagen implant versus standard trabeculectomy. Graefe’s Arch Clin Exp Ophthalmol1998;236:593–96. 4. Sanchez E, Schnyder CC, Sickenberg M et al. Deep sclerectomy: results with and without collagen implant. Int Ophthalmol 1996–1997;20:157–62. 5. Zimmerman TJ, Kooner KS, Ford VJ. Effectiveness of non penetrating trabeculectomy in aphakic patients with glaucoma. Ophthalmic Surg 1984;15: 44–50. 6. Zimmerman TJ, Kooner KS, Ford VJ et al. Trabeculectomy vs nonpenetrating trabeculectomy: a retrospective study of two procedures in phakic patients with glaucoma. Ophthalmic Surg 1984;15:734–40. 7. Arenas E. Trabeculectomy ab-externo. Highlights Ophthalmol 1991;19:59–66. 8. Tanibara H, Negi A, Akimoto M. Surgical effects of trabeculotomy ab externo on adults eyes with primary open angle glaucoma and pseudoexfoliation syndrome. Arch Ophthalmol 1993;111:1653–61. 9. Stegmann RC. Viscocanalostomy: a new
10.
11.
12.
13.
14.
15.
16.
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surgical technique for open angle glaucoma. An Inst Barraquer Spain. 1995;25:229–32. Kozlov VI, Bagrov SN, Anisimova SY. Deep sclerectomy with collagen. Eye Microsurgery 1990;3:44–46. Demailly P, Jeanteur-Lunel MN, Berkani M. Non penetrating deep sclerectomy associated with collagen device in primary open angle glaucoma: middle term retrospective study. J Fr Ophthalmol 1996;19:659–66. Mermoud A, Schnyder CC, Sickenberg M et al. Comparison of deep sclerectomy with collagen implant and trabeculectomy in open angle glaucoma. J Cataract Refract Surg 1999;25:323–31. Karlen M, Sanchez E, Schnyder CC et al. Deep sclerectomy with collagen implant: medium term results. Br J Ophthalmol 1999;83:6–11. Shaarawy T, Karlen ME, Sanchez E et al. Long term results of deep sclerectomy with collagen implant. Acta Ophthalmol Scand 2000;78:323. Chiou AG, Mermoud A, Hediguer SE, Faggioni R. Ultrasound biomicroscopy of eyes undergoing deep sclerectomy with collagen implant. Br J Ophthalmol 1996;80:541–44. Chiou AGY, Mermoud A, Underdahl PJ, Schnyder CC. An ultrasound biomicroscopic study of eyes after deep sclerectomy with collagen implant. Ophthalmology 1998;105:104–08.
6 Experimental studies in non-penetrating glaucoma surgery Christophe Nguyen and Tarek Shaarawy
In primary open-angle glaucoma the main site of aqueous-outflow resistance is thought to be at the level of juxtacanalicular trabecular meshwork and the inner wall of Schlemm’s canal.1 In other types of secondary open-angle glaucoma—such as pseudoexfoliative glaucoma, pigmentary glaucoma, some types of
uveitic glaucoma, and traumatic glaucoma— the resistance of aqueous outflow is probably also in part located at the same site. By removing the internal wall of Schlemm’s canal and the juxtacanicular meshwork, the main outflow resistance in these patients can probably be relieved.
(b) (a) Figure 6.1a Normal anatomy of the angle. 1 = Descemet’s membrane, 2 = Anterior trabeculum, 3 = Posterior trabeculum, 4 = Schlemm’s canal.
Figure 6.1b Filtration membrane after ab externo trabeculectomy. 1= Descemet’s membrane, 2 = Anterior trabeculum, 3 = Posterior trabeculum. Inner wall of Schlemm’s canal and juxtacanalicular trabeculum have been removed.
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Experimental studies in non-penetrating glaucoma surgery
Figure 6.2 Filtration membrane after deep sclerectomy (DS). 1 = Descemet’s membrane, 2 = Anterior trabeculum, 3 = Posterior trabeculum, 4 = Inner wall of Schlemm’s canal. Corneal stroma behind the anterior trabeculum and Descemet’s membrane is removed.
To decrease the outflow resistance without penetrating the anterior chamber, different surgical techniques have been described. In ab externo trabeculectomy (Fig. 6.1)2–7 the internal wall of Schlemm’s canal and the juxtacanicular meshwork are removed, whereas in deep sclerectomy described by Fyodorov8 and Kozlov et al9 (Fig. 6.2), and viscocanalostomy described by Stegmann et al,10 the corneal stroma behind the anterior trabeculum and Descemet’s membrane is removed. The common goal of these techniques is to improve the outflow facility but retain some residual outflow resistance by maintaining a membrane between the anterior chamber and the scleral dissection.
A great deal of interest has been directed towards the properties of this membrane. Outflow resistance of the membrane before and after surgery has been calculated. Histological studies have been done to visualize the site of filtration in pig, rabbit, and human eyes. With the description by Kozlov et al9 of the use of a collagen implant placed within the scleral bed to enhance the filtration of deep sclerectomy, another direction of research was opened. Some experimental studies have been done to better understand the mechanisms of filtration involved in deep sclerectomy with an implant and also to compare deep sclerectomy with and without an implant. Investigations have been done as well on the structural aspect of the juxtacanalicular trabeculum and the inner wall of Schlemm’s canal, and the variability of depth dissection after non-penetrating glaucoma surgery.
Model for experimental non-penetrating glaucoma surgery For in vivo studies on non-penetrating glaucoma surgery, the best model is the monkey. However, the rabbit model has been extensively used in glaucoma research and is certainly more practical. Deep sclerectomy is technically possible on the rabbit’s eye. The outflow canal in rabbits is a circular draining area without endothelium located behind the limbus and measures about 200 µm in diameter. In some areas the rabbit sclera may be thin and these sites should not be used for surgery. However, in appropriate locations, there is enough sclera for a deep sclerectomy. For in vitro research, enucleated pig eyes and enucleated human eyes unsuitable for penetrating keratoplasty are generally used.
Aqueous dynamics after non-penetrating glaucoma surgery
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Figure 6.3 Schematic representation of aqueous outflow measurement. 1 = Balanced salt solution (BSS) reservoir; 2 = Manometer; 3 = Microsyringe pump; 4 = Electronic transducer; 5 = Pressure monitor; 6 = Chart recorder; 7 = 26-gauge needle.
Aqueous dynamics after non-penetrating glaucoma surgery Anterior trabeculum and Descemet’s membrane pathway after deep sclerectomy The method used in deep sclerectomy to improve aqueous outflow in a patient with
restricted posterior trabeculum clearance is to remove the corneal stroma behind the anterior trabeculum and Descemet’s membrane, creating a new pathway for aqueous drainage.8,9 The membrane made up of anterior trabeculum and Descemet’s membrane is called the trabeculo-Descemet’s membrane. The presence of this membrane offers a resistance to aqueous outflow from the anterior chamber to the subconjunctival space (Fig. 6.2) and leads to a progressive decrease in intraocular pressure (IOP) after deep sclerectomy.11,12
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Experimental studies in non-penetrating glaucoma surgery
Vaudaux et al13 first studied in vitro the aqueous dynamics through this membrane. The aims of their study were to examine the resistance of the trabeculo-Descemet’s membrane, and to show, with histological examinations, the precise site of aqueous outflow after deep sclerectomy. Twelve enucleated pig eyes and nine enucleated human eyes unsuitable for penetrating keratoplasty (from an eye bank) were cannulated in the anterior chamber. Outflow facility was measured before and after deep sclerectomy, by the infusion with constant pressure method (Fig. 6.3).14–18 The trabeculoDescemet’s membrane resistance was then calculated as the reciprocal of the outflow facility. The outflow facility of trabeculoDescemet’s membrane outflow facility was found by substracting the preoperative outflow facility from the postoperative outflow facility. The mean preoperative outflow facility was 0.22 ± 0.03 µL/min per mmHg in pig eyes and 0.19 ± 0.01 µL/min per mmHg in human eyes. The mean postoperative outflow facility was 31.9 ± 12.0 µL/min per mmHg in pig eyes and 25.5 ± 12.6 µL/min per mmHg in human eyes.
Figure 6.4 Histology of the trabeculo-Descemet’s membrane dyed with ferritin. The dye is present in the anterior part of the trabecular meshwork (human eye).
The mean value of trabeculo-Descemet’s membrane outflow facility was 31.7 ± 12.0 µL/min per mmHg in pig eyes and 24.3 ± 12.6 µL/min per mmHg in human eyes. The investigators concluded that the trabeculo-Descemet’s membrane offers a sufficient intraoperative and postoperative aqueous outflow resistance to lower most of the surgically-induced complications of filter-
Table 1 Mean values of aqueous outflow facility and resistance: before (preoperative) and after deep sclerectomy (postoperative) and of the trabeculo-Descement’s membrane (TDM), in porcine and human eyes Parameter (µL/min/mm Hg)
Porcine (± SD; N = 9)
Human (± SD; N = 5)
Preoperative facility Postoperative facility TDM facility Preoperative resistance Postoperative resistance TDM resistance
0.22 ± 0.03 31.9 ± 12.0 31.7 ± 12.0 4.61 ± 0.76 0.22 ± 0.08 0.24 ± 0.09
0.19 ± 0.01 24.5 ± 12.6 24.3 ± 12.6 5.34 ± 0.19 0.41 ± 0.13 0.43 ± 0.14
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ing surgery. However, the resistance is small enough to induce postoperative low and controlled IOP (Table 1). They also showed that after deep sclerectomy, aqueous outflow occurs mainly at the anterior trabeculum level as seen on histological specimens dyed with ferritin (Fig. 6.4). The anterior trabeculum is much thinner compared to the posterior trabeculum. Furthermore, the anterior part of the trabecular meshwork is not used in physiological conditions and may not be damaged by glaucomatous disease to the same extent. By removing the corneal stroma behind the anterior trabeculum, deep sclerectomy allows aqueous humor to filter through trabeculum that has been less used. This remaining trabeculum is so thin (10 µm) that it could be regarded as diffused perforations. Further studies are needed to establish whether there is an aqueous flow through the Descemet’s membrane.
Posterior trabeculum pathway after ab externo trabeculectomy As the likely site of main aqueous outflow resistance,1 the juxtacanalicular trabeculum and the inner wall of Schlemm’s canal are removed in ab externo trabeculectomy.2–7 In this technique the filtration membrane is smaller in surface area and is formed by the posterior trabeculum alone, because the internal wall of Schlemm’s canal and the juxtacanicular meshwork are removed (Fig. 6.1). In comparison to deep sclerectomy, ab externo trabeculectomy is an easier and safer surgical technique. Although the risk of intraoperative perforation is reduced, no clinical or experimental study has reported any advantage of ab externo trabeculectomy over deep sclerectomy or viscocanalostomy.
Figure 6.5 Electron microscopy of the peeled membrane.
Rossier et al,19 using basically the same technique as Vaudaux et al13 studied aqueous dynamics after ab externo trabeculectomy (Fig. 6.1). The purpose of their research was to assess the decrease in IOP, the residual outflow resistance of the trabeculum, and the filtration site by histological examination in enucleated pig and human eyes after ab externo trabeculectomy. Rossier et al19 did experiments in two phases: first on 16 fresh enucleated pig eyes, and then on six enucleated human eyes that were regarded as unsuitable for corneal graft. The anterior chamber of each eye was cannulated and perfused at constant pressure. Measurement of the resistance to aqueous
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(a)
(b)
Figure 6.6a Light microscopy of the corneoscleral angle after ab externo trabeculectomy. This section shows the postoperative human trabecular meshwork. 1= Cornea; 2 = residual trabecular meshwork; 3 = sclera; 4 = longitudinal ciliary muscle; 5 = iris.
Figure 6.6b Electron micrograph showing a part of a human trabeculum. Ferritin (little black dots) is visible in the trabeculular stroma (1) and lumen (2). 3 = Collagen fibrils; 4 = elastic fibers (electron-dense mass); 5 = endothelial cells. 25000.
outflow was done by the constant pressure method (Fig. 6.3), 14–18 which was done before and after external trabeculectomy. The surgery began by opening the Schlemm’s canal. At this stage, aqueous humor started to filter through
the remaining trabeculum and internal wall of Schlemm’s canal, and the first decrease in IOP was seen on the pressure monitor. The internal endothelium and juxtacanalicular trabeculum were then removed with a forceps (Fig. 6.5), at
Aqueous dynamics after non-penetrating glaucoma surgery
(a)
(b)
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(c)
Figure 6.7 Comparison between sinusotomy, deep sclerectomy and ab externo trabeculectomy in pig eyes. (a) Sinusotomy. A lamellar band of the sclera is removed and Schlemm’s canal is opened over 120° from to 10 to 2 o’clock. The inner wall of Schlemm’s canal is not touched. (b) Ab externo trabeculectomy. (c) Deep sclerectomy. Arrows = aqueous dynamics.
which point a second decrease in IOP was seen on the recording chart. The remaining trabecular resistance was calculated and eyes were then prepared in order to study the site of aqueous filtration. The investigators injected ferritin into the anterior chamber and the eyes were fixed, sectioned, and then examined histologically. In pig eyes, they reported that the average rate of IOP decrease was 35.7 ± 27.2 mmHg/min after Schlemm’s canal had been opened and 47.3 ± 25.6 mmHg/min after ab externo trabeculectomy. In human eyes, the average rate in IOP decrease was 4.71 ± 2.80 mmHg/min after Schlemm’s canal had been opened and 14.8 ± 7.15 mmHg/min after ab externo trabeculectomy. Rossier et al19 reported a mean outflow facility of 0.31 ± 0.13 µL/min per mmHg in pig eyes and 0.24 ± 0.08 µL/min per mmHg in human eyes before surgery, and 79.0 ± 47. ) µL/min per mmHg in pig eyes and 6.33 ± 6.67 µL/min per mmHg in human eyes after ab externo trabeculectomy.
In pig eyes, the mean residual membrane outflow facility was 78.7 ± 50.0 µL/min per mmHg. 5 mm of residual trabecular membrane provided 99.6% of the total postoperative outflow. Ab externo trabeculectomy allowed the preoperative outflow facility to be multiplied by 255. When compared to pig eyes, human eyes had much lower residual membrane outflow facility (mean 6.10 ± 6.63 µL/min per mmHg). The residual membrane provided 96.4% of the postoperative filtration, and ab externo trabeculectomy multiplied the preoperative outflow facility value by only 26.4. The difference between the pig and the human outflow facility may be explained by the difference between their respective angle anatomies. When studied on radial histological slides, the trabeculum of pig eyes is wider and thinner, which may explain the higher outflow facility through that area. After the filtration site had been traced by cationized ferritin, histological examination allowed Rossier et al19 to show that aqueous
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humor exited effectively through the residual posterior trabecular meshwork (Figs. 6.6a and 6.6b). They concluded that ab externo trabeculectomy significantly lowers IOP and improves outflow facility in enucleated pig and human eyes. By comparison of the two quite similar studies, deep sclerectomy seems to offer better reduction of outflow resistance than ab externo trabeculectomy in human eyes. However, in the pig eyes the results were the opposite probably because the anatomy of pig eyes is different and it is not possible to fully expose the anterior trabeculum and the Descemet’s membrane during deep sclerectomy. In the study by Vaudaux et al13 dissection of the pig eye was not really a deep sclerectomy but rather a sinusotomy (Fig. 6.7).20–23 In this operation, a lamellar band of the sclera is removed and Schlemm’s canal is opened over 120° from 10 to 2 o’clock. The inner wall of Schlemm’s canal is not touched and then the conjunctiva is closed.
Deep sclerectomy with a collagen implant Comparative study of deep sclerectomy with and without collagen implant In deep sclerectomy the simple removal of the scleral and corneal tissue overlying trabecular structures carries the risk of inducing secondary fibrosis and subsequent failure to control IOP. The sclerocorneal space created by non-penetrating glaucoma surgery acts as an aqueous decompression space that should be kept open. Kozlov et al9 first proposed the
Figure 6.8 Comparison of mean intraocular pressure (IOP) after deep sclerectomy with and without collagen implant during the 9 months of follow-up. After an initial significant decrease, the mean IOP returned to preoperative value after 2 months.
use of intrascleral collagen implant to maintain this newly created space. To better understand the usefulness and mechanisms of action of intrascleral implant, Delarive et al24 used an animal model and compared deep sclerectomy with and without a collagen implant. The issues of filtration, aqueous dynamics, evolution of the collagen implant with time, and scarring response of different adjacent tissues involved in deep sclerectomy with and without collagen implant were all addressed. Deep sclerectomy was done in both eyes on 18 pigmented rabbits, and a randomly selected eye received the collagen implant. This procedure was followed by measurements of IOP and aqueous outflow facility, together with light microscopy studies at different times after surgery. The follow-up of this study was 9 months.
Deep sclerectomy with a collagen implant
Figure 6.9 Comparison of preoperative and postoperative mean outflow facility (OF) (µL/min per mmHg) in deep sclerectomy with collagen implant (DSCI) and deep sclerectomy (DS). A significant increase in OF was observed during the entire 9 months of follow up in both DSCI and DS.
The investigators reported a significant decrease in IOP (p < 0.009) during the first 6 weeks after deep sclerectomy with collagen implant (mean IOP = 13.07 ± 2.95 mmHg preoperatively and 9.08 ± 2.25 mmHg at 6 weeks); deep sclerectomy without collagen implant showed a significant decrease in IOP at weeks 4 and 8 after surgery (mean IOP = 12.57 ± 3.52 mmHg at 8 weeks; p = 0.035; Fig. 6.8). After the initial decrease, the mean IOP returned progressively to its preoperative value in both groups. Outflow facility was significantly increased throughout the 9 months of follow-up in both deep sclerectomy with collagen implant and deep sclerectomy groups (p < 0.05; Fig. 6.9). The preoperative mean outflow facility was 0.15 ± 0.02 µL/min per mmHg. At 9 months, the mean outflow facility was 0.52 ± 0.28 µL/min per mmHg (p =
