Because glaucoma is an irreversible disease that can progress to blindness, staying one step ahead of its challenges is critical. It is widely understood that early diagnosis and treatment are crucial to preventing advanced disease—but just how early?

Glaucoma begins with damage to the trabecular meshwork (TM) tissue.¹ Since half of the optic nerve fibers will typically be lost prior to the appearance of visual field damage,² it would stand to reason that half of the effort put toward controlling the disease should occur prior to the appearance of a visual field defect. 

It could also be argued that our current staging of glaucoma as mild, moderate, or severe is suboptimal, as that system describes the accumulation of visual field loss, not the severity of optic nerve damage. In mild disease, up to half of the nerve fibers have already been lost; moderate glaucoma is likely to account for 50% to 85% of nerve death. In the past, when trabeculectomy carried a significant amount of risk, it was reasonable to intervene in the last stages of the disease; however, we have safer options today and should be intervening earlier. 

Let’s consider glaucoma treatment an investment in the patient’s future vision. As any good financial advisor knows, making small investments early in life is far likelier to yield profound benefits at retirement age than making a series of larger investments later on. The same can be said of glaucoma treatment: early interventional treatments that decrease the rate of disease progression will have compounding benefits as a function of time, yielding better vision for a longer period. 

Drop the Drops?

The new era of interventional glaucoma offers several safe and efficacious therapies that seem ideal for employment early in the course of the disease. Selective laser trabeculoplasty (SLT) and drug delivery interventions are great examples, and as we think about data, SLT has an excellent foundation with the LiGHT trial supporting its use early in the patient journey.^3-4 

In the trial, SLT easily bested eye drop therapy for ocular hypertension and early glaucoma in terms of avoiding trabeculectomy and preventing visual field progression. Additionally, SLT seems to work better the earlier it is employed, with its top efficacy achieved when used as a primary therapy.^4-5 This means we are making a great tool less effective by applying it too late in the patient’s treatment. 

It seems unlikely to me that SLT is the only therapy in glaucoma that is less effective the later it is introduced, and I wonder if this property extends to the entire class of TM and canal treatments. These include micro-invasive techniques that address trabecular meshwork pathology directly. In a study of 1,115 eyes that was published early this year, stent technologies achieved a mean rate of progression of −0.024 dBs/year with serial standard automated perimetry, which is similar to that reported in non-glaucomatous eyes and slower than that reported in medically treated glaucoma.⁶ 

There are a few possible explanations for this observation: One is that procedures simply work better than eye drops due to their day-to-day consistency and 24-hour IOP control. Eye drops, as we know, are plagued with diurnal fluctuations, lack of nocturnal control, and meaningful compliance and tolerability limitations. Another possibility is that by targeting the meshwork and the primary site of glaucoma’s origin, we are addressing the fundamental pathology of glaucoma and modifying the disease trajectory on that basis.

Seize the Opportunities

My belief is that addressing the meshwork with a procedure early on is critical, but we could argue about whether that has been fully proven. If compliance with topical eye drop therapy is thought to be the main limitation of these poorly performing control arms, then the procedural pharmaceutical options now available for glaucoma and ocular hypertension are sure to be a major step forward. 

The two therapies currently available consist of a depot injection of bimatoprost,⁷ which may be administered in the office setting; and a significantly longer duration implant (up to 3 years).⁸ Given that compliance with topical therapy may be even more lackluster in the asymptomatic/earlier stages of the disease, should pharmacotherapy begin with procedural pharmaceuticals rather than self-administered drop therapy in early glaucoma patients?

Consider a typical patient presentation that should illustrate the limitations of our current paradigm. I am often referred patients for new interventional glaucoma techniques. However, upon examining the patient, I find the following history: more than a decade of topical eye drop use; out-of-control pressures; difficulty tolerating topical therapy; severe optic nerve damage; and considerable visual field loss. In most cases, I feel that these patients would be better suited for aggressive incisional glaucoma surgical techniques that will help them play catch-up and achieve dramatic IOP-lowering, allowing them to retain the small amount of visual function they currently have. 

But what if these patients had been referred sooner? Ten or 15 years earlier would have typically been the optimum time, in my opinion. It’s possible that the patient, asymptomatic at that stage, would be hesitant to undergo a procedure. But it is our job to educate those patients about the data we have and what likely lies ahead. Glaucoma care providers know what happens over time: The disease progresses, tolerability of topical therapies worsens, and damage accumulates. We need to work with our patients to seize the opportunity for interventional glaucoma. It is earlier in the disease than we recognize, and often, the time is now. 

Nathan M. Radcliffe, MD, is a  clinical associate professor of ophthalmology at New York Eye and Ear Infirmary of Mount Sinai and a surgeon at the New York Eye Surgery Center. He has been compensated by Glaukos for his participation.

References

1. Stamer WD, Acott TS. Curr Opin Ophthalmol. 2012;23(2):135-143.

2. Quigley HA, Addicks EM, Green WR. Optic nerve damage in human glaucoma III. Quantitative correlation of nerve fibre loss and visual field defect in glaucoma, ischemic neuropathy, papillodema and toxic neuropathy. Arch Ophthalmol. 1982;100:135–146.

3. Gazzard G, Konstantakopoulou E, Garway-Heath D, et al. Laser in Glaucoma and Ocular Hypertension (LiGHT) Trial: Six-Year Results of Primary Selective Laser Trabeculoplasty versus Eye Drops for the Treatment of Glaucoma and Ocular Hypertension. Ophthalmology. 2023;130(2):139-151.

4. Gazzard G, Konstantakopoulou E, Garway-Heath D, et al. Selective laser trabeculoplasty versus drops for newly diagnosed ocular hypertension and glaucoma: the LiGHT RCT. Health Technol Assess. 2019;23(31):1-102. 

5. Mcllraith, Strasfeld M, Colev G, et al. Selective laser trabeculoplasty as initial and adjunctive treatment for open-angle glaucoma. Journal of Glaucoma, 2006 Apr; 15, 124-130.

6. Gillmann K, Hornbeak DM. Rates of visual field change and functional progression in glaucoma following trabecular microbypass implantation of iStent technologies: a meta-analysis. BMJ Open Ophthalmol. 2024;9(1):e001575. Published 2024 Feb 15. doi:10.1136/bmjophth-2023-001575.

7. Craven ER, et al. Bimatoprost SR Study Group. 24-Month Phase I/II Clinical Trial of Bimatoprost Sustained-Release Implant (Bimatoprost SR) in Glaucoma Patients. Drugs. 2020 Feb;80(2):167-179. 

8. Berdahl JP, et al. Efficacy and Safety of the Travoprost Intraocular Implant in Reducing Topical IOP-Lowering Medication Burden in Patients with Open-Angle Glaucoma or Ocular Hypertension. Drugs. 2024 Jan;84(1):83-97. 

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