Therapeutic Selection and Standards of Care in DME and AMD

Carl D. Regillo, MD, FACS: Mike, what factors do you consider in selecting treatments for patients with these conditions?

Michael A. Klufas, MD: Great question. We’ve seen a paradigm shift over the past 10 to 15 years. The focus in the past was lasers. There was some gain of vision, mostly prevention of vision loss. Then we had intravitreal anti-VEGF, which has set a high bar and has been an effective treatment for neovascular age-related macular degeneration [AMD] and diabetic macular edema. We have several agents out there in diabetic macular edema [DME]. Especially with worse presenting visual acuities, certain ages tend to do better with off-label compounded bevacizumab. In neovascular AMD, all the agents we have worked pretty well. There may be differences in durability or visual acuity gains with some, but we have to balance all those different things when selecting an agent.

In terms of switch study, switching patients, we don’t have a lot of good switch studies out there, but as clinicians day to day in the clinic, we often see a patient who may have a suboptimal response, either in terms of visual acuity or on the optical coherence tomography with swelling of the retina. In those cases,we’ve all seen where a switch maybe beneficial to the patient. We use our best clinical intuition to initiate that switch. A more interesting question is how many times will you inject the same agent before considering a switch or considering a treatment? We have all seen, especially with DME, if you continue with injections either 4, 6, or 8 weeks, the retina often dries out with the same agent over time. It can be a time-dependent thing as well, not necessarily a treatment failure of that particular agent.

Carl D. Regillo, MD, FACS: We are fortunate to have highly effective treatments, and they are probably more alike than they are different, at least for the first generation of anti-VEFG agents that we use for both conditions. But there are some nuances as you point out—some differences in patient characteristics that might lead you to choose one over the other.

Michael A. Klufas, MD: Another interesting aspect we don’t often comment about, but we have these very busy injection clinics and this therapy is very safe. Yes, we have to use proper techniques to limit adverse effects such as endophthalmitis, but all these agents are safe in large population studies. It’s nice to be able to tell your patient that you have great confidence in using that agent when initiating therapy, based on several randomized, large clinical trials and database-based populations as well.

Carl D. Regillo, MD, FACS: Dave, what is the standard of care for patients with DME and neovascular AMD?

David R. Lally, MD: Starting with neovascular AMD, the current standard of care is to initiate treatment with intravitreal anti-VEGF therapy at a monthly interval until we can determine that the retina is without fluid or that we have reduced the fluid to the level that we think is the best that we can do at reducing that level of fluid. Once we get to that point and whatever point it may be—and it’s different for many different patients and depending on their disease state and severity of their disease—we then have options....We can either extend treatment, we can maintain the interval, or we can stop treating but check these patients frequently in the office—typically with monthly checks looking for any signs of recurrent exudation. If we see that we treat, let’s consider the as-needed treatment dosing regimen. In most studies, we find that the more we inject patients, the better their final visual outcome, so I always error on the side of trying to do more injections than trying to undertreat my patients in the clinic. And we are fortunate that we now have 4 FDA-approved anti-VEGF therapies as well as 1 off-label anti-VEGF therapy, and they are all outstanding at reducing the fluid in the retina to help our patients.

If we look at the disease of diabetic macular edema, the standard of care for subfoveal center–involved diabetic macular edema would be similar to neovascular AMD, where we initiate monthly intravitreal anti-VEGF therapies until we can get the fluid resolved as best as we can. But sometimes in diabetic macular edema, we are not able to achieve that goal, and that’s because there can be other players involved besides anti-VEGF. We know that inflammation plays a role, and that’s when corticosteroids come in as second-line therapy and can be initiated at any point during that course of treatment to attempt to get a better response of reducing the fluid. For diabetic macular edema, we have our tried-and-true focal laser, where we can cauterize or heat up the leaking micro-aneurysms to make them stop leaking. Often using focal laser as an adjunct therapy can help us get to our goal.

Carl D. Regillo, MD, FACS: For both DME and neovascular AMD, it’s going to be anti-VEGF therapy as first-line treatment—intravitreal injections on a frequent and regular basis, especially at first. For wet AMD, it’s lifelong constant therapy. It may or may not be for DME, but it’s going to be a lot of treatments as you indicate. The more often you deliver treatments, usually the better your results will be, and that could be easily 8, 10-plus treatments in the first year alone and maybe a little less thereafter. Corticosteroids backup treatment for DME maybe suboptimal responders are not effective in wet AMD; in fact, wet AMD doesn’t have anything else, maybe photodynamic therapy and older treatment but in very limited fashion. As you mentioned, focal laser is probably third in line for DME, something that used to be first a long time ago but not nearly as effective as the pharmacotherapeutic approaches.

Transcript Edited for Clarity