We have many options available for the treatment of glaucoma. We have five classes of agents, with a sixth class of ocular hypotensive agents (rho kinase inhibitors) on the horizon. Considering all formulations, molecules and dosing options, we have hundreds of thousands of possible eyedrop combinations for glaucoma. We can all agree that we need not employ each formulation or all possible combinations on all medically uncontrolled patients, but where does one draw the line?
We understand that there are diminishing returns for IOP lowering when we add agents to primary therapy. We have excellent evidence that a second agent is additive.1 And, to my satisfaction, we see that adding even a third eyedrop can lower meaningfully compared to two agents.2 But, do we have evidence that a fourth or fifth agent can further lower IOP? The literature is scant.
How do we proceed? In my mind, we begin by asking how close we are to our target and how severe the consequences of falling short might be. For young patients who are far from their target IOP, it makes more sense to limit therapy at three topical agents and pursue surgical options. Eyes that need a significant amount (≥5 mmHg) of additional IOP lowering are unlikely to be helped by even a third drop, and are very unlikely to be helped by a fourth. Certainly, we can consider the patient’s risk profile (e.g., monocular) and willingness to execute futile options. But then again, with the arrival of safer glaucoma surgery, wasting time on low-yield medical options could be more harmful than surgery.
In summary, the art of glaucoma is alive and well, but maximally or rationally tolerated medical therapy is likely hovering around three molecules, two bottles for most patients.
1. Tanna AP, Lin AB. Medical therapy for glaucoma: what to add after a prostaglandin analogs? Curr Opin Ophthalmol. 2015 Mar;26(2):116-20.
2. Fechtner RD, Harasymowycz P, Nixon DR, Vold SD, Zaman F, Williams JM, Hollander DA. Twelve-week, randomized, multicenter study comparing a fixed combination of brimonidine-timolol with timolol as therapy adjunctive to latanoprost. Clin Ophthalmol. 2011;5:945-53.
Dr. Nathan M. Radcliffe is a clinical associate professor of ophthalmology at New York Eye and Ear Infirmary and is a cataract and glaucoma surgeon at the New York Eye Surgery Center.