Trabs: Still on Top

All current glaucoma treatments work via a reduction of intra-ocular pressure, a dose-related protective effect correlated to lowering not only the average pressure, but also its diurnal variation. Surgical and laser treatments may be more effective than medicines, the efficacy of which has to be reinforced daily by regular application related to a short, finite duration of action. Medicines, however, benefit from the possibility of treatment combinations using three distinct potential additive strategies – reduction in inflow and increase in either conventional (trabecular) outflow or non-conventional outflow.

Trabeculectomy has long been our default surgical glaucoma solution as it simply creates a semi-permanent, biological valve; much evidence supports it as a cheap, enduringly effective, and acceptably safe incisional treatment that is moderately independent of individual skill and technique. There is an attrition rate, however; complications are not infrequent and the results of the procedure can be frustratingly variable despite standardized surgical techniques. Dissatisfaction with side effects and complications of trabeculectomy led to the advent of glaucoma drainage devices and non-penetrating surgery; clearly these were not the answer as their routine use in the surgical control of glaucoma did not become widespread.

The advent of a variety of new surgical options represents a further attempt to refine the safety and efficacy of surgical intervention. The term MIGS refers to a number of ab interno glaucoma drainage procedures that do not require conjunctival incision and includes (amongst others) Goniosynechialysis, Endoscopic Cyclo-Photocoagulation (ECP), Trabectome, iStent, Cypass (now withdrawn), Hydrus, Kahook Dual Blade (KDB), ab interno Canaloplasty and Xen.

The wide range of options allows for a more logical and step-wise approach to surgery, and for a combination of treatments based on the mechanism of action. A further advantage of MIGS is the ability to combine surgery with phacoemulsification; phaco-trabeculectomy is no longer widely performed. For MIGS procedures performed in combination with cataract surgery, it is always challenging to isolate the effect of the procedure from that of cataract surgery alone. MIGS shows promise, but is as yet unproven and of uncertain longevity.

Some MIGS procedures offer the prospect of restoration of physiological trabecular outflow. But this potentially limits clinical efficacy because, in the presence of normal aqueous inflow, Schlemm’s canal drainage routes seem to have a physiological “floor” of around 16 mmHg due to downstream resistance to flow. Further lowering would require additional aqueous suppression treatment, a real disadvantage if low IOP is needed or medication use is to be avoided. By contrast, both conventional and non-conventional outflow procedures potentially bypass this “choke-point,” leading to lower IOPs but also raising the possibility of hypotony from over-drainage.

MIGS devices are unarguably expensive, largely due to development costs. Proponents argue that the extra cost is defrayed by reduced need for intensive follow ups and better quality of life, but this is yet to be proven. Though this may be the case for a device such as the iStent, successful use of other devices, such as Xen, still requires extra follow up due to the common need for post-operative manipulations. Furthermore, devices that have a small unit effect may need to be implanted in costly multiples. If the effect is sub-optimal or if the device later fails, the health economics alter and may well ultimately favor conventional drainage surgery; at that point, the true price comparator is not drainage surgery but only the relatively cheap medications that MIGS spares.

Ultimately, the widespread adoption of MIGS will probably come down to an individualized assessment of safety versus efficacy. MIGS procedures that are inferior to trabeculectomy in efficacy will only be widely adopted if they have significant safety benefits. In early disease, there are many options and there is often time to try a variety of treatment options. In a patient with advanced glaucoma, it cannot be appropriate to offer a treatment of unproven efficacy or longevity.

I agree with Ike Ahmed, who has stated: “A common misperception of MIGS is that it needs to be compared with the gold standard of MMC-trabeculectomy to show its effectiveness. This inappropriate interpretation is based on the idea that MIGS procedures are designed to replace conventional filtering surgery. In fact, MIGS devices are designed to address the treatment gap that exists between medical therapy and more aggressive traditional surgical options.”

It is apparent from the foregoing that the existence of MIGS raises the level of sophistication and complexity in glaucoma surgical management, making it more “granular,” titratable and refined. Nonetheless, trabeculectomy continues to be our best single “fit and forget” option. The natural comparators for trabeculectomy are still other forms of “conventional” drainage, such as glaucoma drainage tubes, and maybe the recently released MicroShunt device, but to date trabeculectomy has yet to be bettered; 21st century trabeculectomy is an increasingly safe and effective procedure.