Trabeculectomy has been used for 55 years to reduce intraocular pressure (IOP) in patients with progressive glaucoma or those with serious vision loss to prevent progression. It reduces IOP by draining aqueous humor from the eye via the creation of a small fistula, or channel, through the sclera via a scleral flap under the conjunctiva. The reduction in pressure on the optic nerve prevents or slows further damage and loss of vision.¹ Trabeculectomy has a significantly greater chance of effectively reducing IOP than any other type of glaucoma surgery in patients with primary open-angle glaucoma (POAG) who do not have complex problems, have not had previous glaucoma surgery, and who are at serious risk of blindness.

Trabeculectomy in the Paradigm

When trabeculectomy was introduced, it was heralded as safer than the procedures that preceded it, which had high risks of hypotony and infection. Although these risks decreased with trabeculectomy, the risk of scarring leading to surgical failure increased. This led to the introduction and use of the antiscarring agents mitomycin C (MMC) or 5-fluorouracil. Unfortunately, the use of these antimetabolite drugs was associated with a new set of complications and the surgical failure rate remained relatively high. There remained concerns regarding the margin between risk and benefit.

The debut of minimally invasive glaucoma surgeries (MIGS) ensured greater safety, and many surgeons and patients are now comfortable with MIGS procedures because they are less invasive. However, none of the MIGS devices or procedures currently available are as efficacious as trabeculectomy.

Indeed, the reason that trabeculectomy has been around for 55 years is its efficacy. As for many procedures, there are some rules of thumb that any surgeon needs to remember: trabeculectomy works better in patients who have no other comorbidities, have POAG, and have had no previous glaucoma surgery. In people with progressive POAG and those who have serious vision loss and need low IOP immediately, sometimes to 10 mmHg or lower, trabeculectomy has a significantly higher chance of hitting that target pressure than any other intervention.

Despite its efficacy, trabeculectomy seems to be underutilized. It is possible that the reason for this is that trabeculectomy used to be a fairly unpredictable operation. However, the introduction of MMC and 5-fluorouracil in the late 1980s and 1990s improved the success rates significantly. With appropriate case selection and technique modifications, in units where the surgical volume is high, trabeculectomy is a safe and predictable procedure. Like many types of surgery, one must perform a high volume of trabeculectomy procedures to gain proficiency, as is the case with phacoemulsification, probably the most common surgical procedure worldwide. However, most ophthalmologists are not performing trabeculectomy frequently, so they’re less comfortable performing it and are seeking safer (but often less effective) alternatives. There are many countries in Asia and Africa where MIGS devices are too expensive to be used systematically and where glaucoma surgeons still rely on trabeculectomy. These surgeons are performing many procedures, at low cost and with positive results. Consequently, in many countries, trabeculectomy is still the surgery of preference. Despite this, in developed countries, concerns remain and trabeculectomy is on the decline as it is not considered mainstream; this is potentially problematic.

The Risk of Scarring

One of the downsides of trabeculectomy is the risk of scarring. The standard method to reduce the risk of scarring includes (1) selecting patients carefully; (2) calming red, inflamed eyes before surgery; (3) administering postoperative steroids early because when initiation of the inflammatory cascade is prevented, scarring is minimized; and (4) using MMC at the time of surgery to reduce scarring and improve bleb survival. However, MMC is a toxic drug, and its use can sometimes produce avascular drainage blebs that are more prone to infection and may cause ischemic blebs, corneal epithelial damage, corneal and scleral toxicity, and wound leakage.^2,3

Furthermore, it is challenging to control precisely where the MMC goes and to predict the patient’s reaction to it. For instance, some surgeons inject MMC, but in my experience, when it is injected, there is less control over where it ends up on the ocular surface. Using sponges ensures a greater degree of control. In those cases where the risk of scarring is higher, surgeons might also add intracameral bevacizumab, which has mild antiscarring properties. Nevertheless, this is far from ideal, and more evidence is needed to support this practice.

Beta Therapy for Scar Prophylaxis

Independent of the type of surgery, scarring is the leading cause of surgical failure. When glaucoma surgeries fail, it is because scar tissue forms underneath the conjunctiva during healing and impedes drainage of excess fluid from the bleb, a small reservoir that forms under the conjunctiva and Tenon’s capsule. When the filtration bleb fails, IOP increases.

For many years, my colleagues at Moorfields Eye Hospital have been using beta therapy for scar prophylaxis. Beta therapy was pioneered more than half a century ago to manage pediatric glaucoma, and 30 years ago a retrospective cohort study of these patients was published reporting good results.⁴ Subsequently, beta therapy’s intraoperative use with trabeculectomy demonstrated effectiveness in multiple studies.^5-11 A study combining beta therapy and MMC achieved better results than the use of MMC alone.¹¹

Additionally, recent studies found that patients treated with beta therapy alone were more likely to have lower IOP after trabeculectomy than those treated with MMC^10,11 (up to 5.5 times more likely¹⁰). Also, beta therapy has proven to have a good safety profile in the very long term, as reported in a recent study by my colleagues at Moorfields, in which they audited for signs of problems associated with radiation exposure among the clinical records of 135 eyes that received trabeculectomy and beta therapy between 1992 and 1995.¹² Despite these encouraging results, beta therapy awaits translation into a commercially available device that surgeons can use on a regular basis.

Beta therapy prevents scarring by modulating fibroblast activity and causing cell cycle arrest. It can be accurately and precisely applied using a 12-mm strontium-90 plaque.¹² The applicator is placed on the intact conjunctivae over the area of the intended bleb for about 30 seconds to deliver a single dose of up to 10 Gy. Of note, the unique dose prescription convention traditionally utilized with legacy strontium-90 beta ophthalmic applicators specifies the maximum dose to the center point of the proximal surface, as is the dose reported in Murdoch et al.¹² Conversely, for other indications of ophthalmic plaque brachytherapy the standard convention for dose prescriptions is the specification of the minimum dose to the distal apex of the lesion.¹⁵

Because beta radiation attenuates rapidly over short distances,¹⁴ the dose stays where it is applied and, unlike MMC, it will not affect other areas. According to the literature, the safety profile of beta therapy is good and it is effective in reducing scarring, but it has yet to be used on a large scale outside of controlled studies.

Beta Therapy and Bleb Procedures

Subconjunctival minimally invasive procedures are more effective than angle procedures, but they are not quite as effective as trabeculectomy, largely because of scarring. With the advent of transscleral drainage MIGS devices, often termed minimally invasive bleb procedures (MIBS), it is possible to prevent the low pressures and early complications more easily than with trabeculectomy, but because there is a greater risk of scarring than with MIGS, higher doses of MMC are needed. Again, it is difficult to balance the pros and cons, but it is here that beta therapy, in which targeted radiation is delivered to the eye, has the potential to improve the outcomes of MIBS and bridge the safety profile of MIGS with the effectiveness of trabeculectomy.

The future of the most effective glaucoma surgery procedure is open to new players to improve its outcomes. Beta therapy is a promising new tool and will likely help to improve surgical outcomes as ophthalmologists gain experience with its efficacy, favorable safety profile, and ease of use. GP

Keith Barton, MD is a consultant ophthalmologist and glaucoma specialist at Moorfields Eye Hospital in London, England; professor of ophthalmology at UCL Institute of Ophthalmology; and cofounder and cochair of Ophthalmology Futures Forums and the International Glaucoma Surgery Registry. Prof. Barton reports consultancy to Alcon, AbbVie, Allergan, Ivantis, Meditec, Radiance Therapeutics, Kowa, Glaukos, iStar, EyeD, ELTSight, Sight Sciences, Alimera Sciences, and Nova Eye Inc. Reach him at keith@keithbarton.co.uk.

References

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