When most of us were in training, the glaucoma treatment algorithm was straightforward. We began with topical therapy, progressed to laser after maxing out meds in one way or another, and then finally moved to incisional glaucoma surgery (trabeculectomy or tube). We had plenty of data to suggest that initial surgery did just as well as medications (CIGTS),¹ and data that laser did just as well as meds (GLT),² but still, the traditional treatment progression was well established.

I can find a few early cracks in the armor of this treatment algorithm that go back many years. To begin with, there has never really been a study to suggest that selective laser trabeculoplasty (SLT) was inferior in any way to topical therapy. Laser has only taken second place to drops because of clinical inertia or doctor/patient psychology, and honestly, now even inertia and psychological excuses should not be enough to prevent laser from becoming first-line therapy given the preponderance of strong evidence in support of primary SLT.³ Keep this in mind — in the EMGT, meds did better than placebo in preventing progression.⁴ But has topical therapy ever been shown to be better at visual field preservation than another type of IOP-lowering therapy? The answer is no. 

The second crack in the armor was that cataract extraction as an IOP-lowering procedure in open-angle glaucoma patients with cataract represented a notable exception to the traditional treatment pathway. Third, the arrival of the iStent (Glaukos) and other MIGS procedures represented, in my opinion, the beginning of the end of the traditional treatment algorithm. For the first time we had a safe minimally invasive glaucoma procedure that was FDA approved for mild glaucoma/cataract patients using as little as 1 eye drop daily. And, with the Hydrus Microstent (Alcon), we have 5-year data showing that cataract plus Hydrus patients had less visual field progression and needed fewer incisional glaucoma surgeries than cataract plus drops patients.⁵ If you are keeping track, the score is eye drops 0, SLT 1 (LiGHT), and stents 1 (Horizon).

I could probably end this editorial here, and I suspect that most of us could keep busy just adhering to available data and offering the above therapies earlier. But we need to keep our eyes on a few things, namely interventional glaucoma treatments. Drug delivery has arrived in several forms, with the office-based sustained release bimatoprost (Durysta; AbbVie) and with the travoprost long-term release implant (iDose; Glaukos). Additionally, we have options for standalone trabecular MIGS, including the 510(k) cleared iStent infinite (Glaukos) for refractory glaucoma. Other unique options like micropulse transscleral laser therapy, new suprachoroidal biostenting options, and even transscleral subconjunctival microstents, are available as well.

With the arrival of these other options, the traditional treatment pattern should be essentially disassembled. Now one might say, “Wait a minute, drug delivery and standalone MIGS and the others haven’t been shown to be superior to anything; we can’t use them that early.” And I don’t know if I would be jesting or just being intellectually honest by replying, “You are right, let’s keep these therapies in the second-line bucket of other unproven therapies like eye drops.” The important caveat here is that drops have solid RCT evidence of IOP-lowering efficacy (a surrogate endpoint) and that we should ask the same of our alternative interventional therapies.

Personally, I think when it comes to these therapies where no comparative data exist, we can revert to discussions of risks and benefits with our patients, tailoring therapies to each patient’s needs, and probably the best guide: “What surgery would I pick if this were my eye or a family member’s eye?” I doubt any of us have recently written, “Meds then laser then trab” on a sticky note and given it to a family member prior to a glaucoma check-up. GP

Nathan M. Radcliffe, MD, is a clinical associate professor of ophthalmology at the New York Eye and Ear Infirmary of Mount Sinai and a surgeon at the New York Eye Surgery Center.

References

1. Lichter PR, Musch DC, Gillespie BW, et al. Interim clinical outcomes in the Collaborative Initial Glaucoma Treatment Study comparing initial treatment randomized to medications or surgery. Ophthalmology. 2001;108(11):1943-1953. doi:10.1016/s0161-6420(01)00873-9

2. The Glaucoma Laser Trial (GLT). 2. Results of argon laser trabeculoplasty versus topical medicines. The Glaucoma Laser Trial Research Group. Ophthalmology. 1990;97(11):1403-1413. 

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 vs eye drops for the treatment of glaucoma and ocular hypertension. Ophthalmology. 2023;130(2):139-151. doi:10.1016/j.ophtha.2022.09.009

4. Heijl A, Leske MC, Bengtsson B, et al. Reduction of intraocular pressure and glaucoma progression: results from the Early Manifest Glaucoma Trial. Arch Ophthalmol. 2002;120(10):1268-1279. doi:10.1001/archopht.120.10.1268

5. Ahmed IIK, De Francesco T, Rhee D, et al. Long-term outcomes from the HORIZON randomized trial for a Schlemm’s canal microstent in combination cataract and glaucoma surgery. Ophthalmology. 2022;129(7):742-751. doi:10.1016/j.ophtha.2022.02.021