ID Subconjunctival Filtration Glaucoma surgery has been the concern of ophthalmologists for over a century. It is widely recognized that glaucoma surgery is imperfect, and as glaucoma surgeons we strive to improve it. Existing techniques are refined in new versions of the surgery (e.g., “trabeculectomy 9.15”), as new approaches and devices become available. But new approaches and devices need a context. The current standards of modern trabeculectomy are adjunctive antimetabolite surgery and glaucoma drainage device (GDD) surgery. Both types of surgery entail drainage of the aqueous humor to the sub-Tenon’s space or subconjunctival space as their chief function. Both types of surgery entail drainage of the aqueous humor to the sub-Tenon’s space or subconjunctival space as their chief function. Both types have been well studied and their advantages and disadvantages described. New approaches seek to address the acknowledged deficiencies in existing strategies, often with sophisticated work-arounds. New approaches to glaucoma surgery are judged by whether they have improved efficacy without increasing the financial costs. As described in the next section, glaucoma filtration to the subconjunctival space initially had some disadvantages, but it has been refined over the years so that the risks and complications have been minimized. New approaches must prove themselves to be at least as good as established surgeries. Trabeculectomy, which is now widely acknowledged to be superior to full-thickness surgery, took more than 15 years to become a standard of care. There are many challenges in developing new approaches to glaucoma surgery, such as the considerable financial costs of procedures, the high learning curves for new procedures, and the smaller numbers of procedures performed as more patients are treated with the improving nonsurgical options. An effect of fewer glaucoma patients needing surgery is that surgeons will have less experience, which is further diluted if each surgeon performs multiple techniques. As each procedure is performed less frequently, it also becomes increasingly difficult to acquire enough data to meaningfully assess the surgical outcomes. If a surgeon is performing a particular procedure fewer than 30 times a year, an 80% success rate is practically indistinguishable from a 90% success rate. Surgeons will then be guided by a perception that a certain procedure generally has a good outcome but that in some patients the procedure fails or causes problems. Intraocular pressure (IOP) rises because the resistance to aqueous outflow rises. Increasing outflow from the eye either by restoring trabecular function or by bypassing the meshwork has been the aim of glaucoma surgeons for over 150 years. The first effective glaucoma surgery is attributed to Albrecht von Graefe, who in 1857 reported curing acute glaucoma with an iridectomy. He went on to report that one in five eyes developed a cyst or a scar at the site of the incision; he considered such a cyst to be of little consequence other than a cause of irritation and possible infection. Von Graefe generally recommended excising blebs if they formed. Only a decade later, Louis de Wecker took an opposite view, and reported that blebs had value in lowering the IOP; he recommended performing a formal sclerostomy (with iridectomy) to increase the likelihood of a bleb forming. It is worth noting that these procedures were done before topical anesthesia or tonometry was available. It was not until the early 20th century that better surgical strategies, techniques, facilities, and instrumentation led to refinements in the surgical principles and approaches. In the early 20th century, iridencleisis was widely performed. The iris incarceration in the sclerostomy increased the likelihood of continued patency, and prevented the iris from obstructing the sclerostomy. The importance of a patent sclerostomy was understood by the midpoint of the 20th century, but all the operations at that time were full-thickness procedures, culminating in Harold Scheie’s procedure (Fig. 17.1), which was routinely performed from the late 1950s until the late 1960s, when trabeculectomy with a guarding flap was described by Sugar in 1961 and later by Cairns in 1968. Cairns originally proposed that a trabeculectomy would enable aqueous humor to enter the exposed end of Schlemm’s canal. Soon after his original description, it was deduced that the dominant mechanism of pressure lowering was actually external filtration. In spite of this, the term trabeculectomy persisted, and the operation proved safer and more predictable than full-thickness procedures, but it entailed a higher failure rate due to scarring of the trapdoor and subconjunctival space. Both trabeculectomy and nonpenetrating glaucoma surgery (e.g., deep sclerectomy) were developed to eliminate the filtration bleb. But it has been demonstrated that both are best at controlling IOP when subconjunctival drainage is present. The current state-of-the-art glaucoma surgery still requires glaucoma surgeons to be “blebologists.” Seminal trials in the use of 5-fluorouracil (5-FU) and later mitomycin C (MMC) as wound-modulating agents improved the success rate of trabeculectomy and enabled surgeons to improve the postoperative healing. Although implants to shunt aqueous subconjunctivally were trialed as far back as 1912 with Emil Zorab’s silk seton,1 the first modern glaucoma drainage device was developed by Tony Molteno, then in South Africa, which he reported in the British Journal of Ophthalmology in 1969 and in simultaneous papers showing animal experimentation and the first human results.2,3 The original Molteno implant was the first to have a tube and plate design, with the plate acting as a spacer to enable fluid to percolate into the subconjunctival tissue and be absorbed. Subsequent iterations and changes in the design of tubes have led to some improvements, but the basic design of a channel for egress and a plate for distribution and absorption remains unchanged. More recently, the focus has returned to the trabecular space and Schlemm’s canal, with the development of so-called minimally invasive glaucoma surgery with its range of procedures and implants, which offer bypasses or manipulations of portions of the outflow pathway. Significant challenges exist if manipulation of the existing pathways is to result in resuscitation of normal outflow. Although the principal pathology appears to be in the trabecular meshwork or juxtacanalicular tissue, downstream collapse of Schlemm’s canal and collecting ducts frustrates our attempt to perform what Cairns envisaged in his original paper in the late 1960s. Subconjunctival filtration is still the method with the longest track record of use and of proven success in achieving sustained and significant IOP lowering. It is a clinically versatile procedure by the surgeon even in the postoperative phase. In the 1990s, two major randomized controlled trials, the Collaborative Initial Glaucoma Treatment Study (CIGTS)4 and the Advanced Glaucoma Intervention Study (AGIS),5 included surgical treatment arms involving trabeculectomy. Although surgical techniques have since evolved to improve success and decrease adverse outcomes, these studies are still considered the benchmark data from that era. Trabeculectomy precipitated cataract formation in many patients, but it offered an unqualified (no adjunctive medications or further surgery) IOP control success rate of ~ 80%. Although postsurgery complication rates were up to 50%, almost all complications resolved without intervention and seemed not to compromise the outcome. The decades of refinement in both GDD and trabeculectomy surgery have delivered progressive improvements in outcomes. A patient who undergoes one of these procedures has a very good chance, after a couple of months of intensive management, of long-term controlled IOP on fewer or no glaucoma medications (Fig. 17.2). Landers et al6 published 20-year trabeculectomy follow-up data in 2012 that demonstrated that 60% of trabeculectomy eyes maintained IOP control with no topical medication. Several older studies also show good success rates at 10 years, on the order of ~ 70%.7–10 Yet in the Tube Versus Trabeculectomy (TVT) study,11 trabeculectomy had a 5-year success rate of only 50%, reflecting about a 10% failure rate per year. The GDD failure rate was about half of that, 5% per year. The reason for the discrepancy in trabeculectomy success rates is not clear, but possible explanations include the following: (1) newer medications, in particular prostaglandin analogues, are successfully treating less recalcitrant eyes without the need for surgery, so that surgeons are operating on only severe cases; (2) newer medications are delaying surgery in all eyes, so that the cumulative dosage of medications and conjunctival propensity to scar is greater; (3) newer medications may change conjunctival physiology or fibroblast activation, predisposing patients to more aggressive scaring. Fig. 17.2 Bilateral trabeculectomy procedures performed 37 years ago. Currently, IOP is 10 mm Hg in the right eye and 11 mm Hg in the left eye. A trabeculectomy’s effects are maintained for many years in some eyes. These blebs have good morphology and function. The TVT11 was a high-quality randomized controlled trial (RCT) that provided some of our best information on success rates for alternative procedures for subconjunctival drainage. There has been criticism that the reported complication rates are higher than previous rates; this may in part reflect the better documentation of issues in a competitive RCT that might not otherwise be recorded in routine clinical practice and therefore missed in retrospective studies. With more recent advances in surgical techniques and postoperative care, for example via the Moorfields Safer Surgery System,12 more current studies may start to report improved outcomes. Recently, Kirwan et al13 published a series of 428 procedures with more than 2 years of follow-up. This was a multicenter study pooling data from nine glaucoma units with fellowship-trained glaucoma specialists who followed a broadly similar surgical approach, including fornix-based conjunctival flap, adjustable or releasable sutures, and antimetabolite use. A subgroup analysis used inclusion and assessment criteria based on the TVT study; the unqualified success rate (without IOP-lowering medications) was 85%, with qualified success rates (including use of IOP-lowering medications) of 92%. In three patients, vision decreased by three or more Snellen lines (one of these patients had declined treatment for hypotony maculopathy); 31% had cataract surgery subsequently; bleb leaks were identified in 13.6%, with 95% of these in the first weeks after surgery; 7.2% of cases had an IOP reading of less than 5 mm Hg between 6 months and the final postsurgery visit. These results depended on relatively intensive postsurgical management, with 27% having subconjunctival 5-FU injections, 16% requiring bleb needling, and 5% receiving additional sutures. Perhaps the most interesting aspect of the study was the low rate of postoperative complications related to scleral flap construction and suturing. Shallow anterior chamber was seen in 0.9%, with none flat, and choroidal detachment was seen in 5%. By comparison, CIGTS and AGIS reported shallow anterior chambers in 13 to 15% of patients after trabeculectomy. Introduction of the Ex-Press glaucoma implant (Alcon Laboratories, Fort Worth, TX) without flow restriction faced the same difficulties as early glaucoma implants and unguarded full-thickness surgery. It was intended to drain directly under the conjunctiva, but it had a high incidence of hypotony14,15 (see discussion of cystic blebs and full-thickness drainage, below), which is expected of shunts that freely drain aqueous to the subconjunctival space without any flow restriction. The obvious modification to the Ex-Press implantation, placing it under a scleral flap, was quickly adopted. Comparative studies between trabeculectomy and trabeculectomy with an Ex-Press implant placed beneath the scleral flap have shown short-term advantages, especially better early anterior chamber (AC) and IOP control, but no benefit in long-term outcomes. Kirwan et al’s13 results suggest that with due care to flap construction and adjustable/releasable suture use, addition of an expensive implant may not bring enough additional value, although we may yet see further technique refinement, just as we have with trabeculectomy and GDD surgery. Established GDD implants such as the Baerveldt, Molteno, and Ahmed implants were thought to entail higher risks of complications than trabeculectomy, but this has been challenged by the TVT study. At 3 years the serious complication rate was very similar, and GDDs narrowly outperformed trabeculectomy at 5 years.11 An issue that has yet to be fully explored is the possibility of late corneal decompensation from GDD-induced endothelial trauma. Another issue is that the implants may be less cost-effective than trabeculectomy.16 Direct comparisons between IOP outcomes of different GDD implants and comparisons of GDD with trabeculectomy are challenging. Plate size is a major determinant of IOP control after tube implant surgery, but the relationship is not consistent, and it is not clear how it translates to subconjunctival filtration without a plate, except perhaps for the commonly held notion that the larger the area of filtration, the lower the IOP. Despite the TVT results, many surgeons expect IOP after trabeculectomy to be lower than after tube surgery. An IOP in the single digits is relatively uncommon after GDD implantation, but it is not uncommon after successful trabeculectomy. The effect of bleb management in the early months after trabeculectomy is relatively undocumented. There is likely to be enormous variability in the surgical approach among glaucoma surgeons and little information on outcomes arising from such variations. Subconjunctival filtration with or without a GDD makes for quite different blebs due to several factors: shifting of the region of subconjunctival filtration away from the limbus, fibrosis due to a foreign body response or implant micromovements, and a plate that sets bleb space dimensions that may limit the area of aqueous absorption into the periocular tissues and orbital lymphatic drainage. Some glaucoma surgeons prefer to avoid IOP-lowering medications with a functioning trabeculectomy bleb because reducing flow and collapsing the bleb may decrease its drainage function and compromise the long-term outcomes. Blebs around GDDs are easiest to delineate, as the plate determines the bleb area. A fibrous capsule determines resistance to flow, and typically little subconjunctival flow occurs outside this area once the bleb is established. These are the easiest blebs to study from a biomechanical perspective because variability is small and zones are typically well defined. There is consensus that increasing plate (bleb) size leads to a lower IOP,17 but the relationship is not always observed.18 Trabeculectomy blebs are much more variable, but are described parsimoniously as one of only a few variants—diffuse, cystic, and encapsulated—with the latter often being an indication for postsurgical management. The range of possible appearances and implications are far wider than this coarse grading would suggest. For example, a significant prognostic factor for long-term bleb and trabeculectomy survival is the conjunctival vascularity surrounding the central elevated area, which is not even addressed in the classic variants above.19 Bleb grading systems, such as the Moorfields Bleb Grading System (www.blebs.net) can capture these systems for advanced clinical or research use. Diffuse blebs are the most desirable (Fig. 17.3). They are usually associated with good IOP control and a low risk of bleb-related infection, discomfort, or failure. It is thought that such blebs facilitate fluid drainage by having a sufficiently large although relatively unscarred area by which aqueous may escape the bleb. Possible routes of aqueous drainage from the subconjunctival space are the vascular or lymphatic systems of the conjunctiva–Tenon’s complex or a transconjunctival route into the tears. The exact mechanisms and destination(s) of subconjunctival aqueous drainage remain unclear and warrant further study.
17 Structure and Mechanisms of Subconjunctival Outflow
Why Include Subconjunctival Filtration in a Book About Alternative Glaucoma Surgery Approaches?
A Brief History of Approaches to Subconjunctival Filtration
How Successful Is Modern Subconjunctival-Drainage Glaucoma Surgery?
Conjunctival Bleb Morphology
Bleb Types and Implications for Subconjunctival Drainage and IOP
Ento Key
Fastest Otolaryngology & Ophthalmology Insight Engine
