Therapeutic selection and standards of care in DME and AMD

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

Michael A. Klufas, MD: Excellent question. We have seen a paradigm shift over the past 10 to 15 years. In the past, the focus was on lasers. There was some vision gain, mostly prevention of vision loss. Then we had intravitreal anti-VEGF, which set the bar high and was 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 poorer visual acuities, certain ages tend to do better with the off-label compound bevacizumab. In neovascular AMD, all the agents we used worked quite well. There may be differences in durability or visual acuity gains with some, but we need to balance all of these different things when selecting an agent.

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

Carl D. Regillo, MD, FACS: We are fortunate to have very 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 certain nuances, as you point out, certain differences in patient characteristics that might lead you to choose one over the other.

Michael A. Klufas, MD: Another interesting aspect that we don’t talk about often, but we have these very busy injection clinics and this therapy is very safe. Yes, we need to use proper techniques to limit adverse effects such as endophthalmitis, but all of 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 this agent when initiating treatment, based on several large randomized clinical trials and population-based databases.

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

David R. Lally, MD: Beginning with neovascular AMD, the current standard of care is to initiate treatment with anti-VEGF intravitreal therapy at monthly intervals until we can determine that the retina is fluid-free or that we have reduced the fluid to the level we think is the best we can do to reduce that fluid level. Once we get to that point and whatever it is — and it’s different for many different patients and depending on the condition and severity of their illness — then we have options… We can either extend the treatment, either maintain the interval, or we may stop treatment but check these patients frequently in the office, usually with monthly checks for any signs of recurrent exudation. If we see that we are treating, consider the dosage regimen of treatment as needed. In most studies we find that the more patients we inject the better their final visual outcome, so I always make the mistake of trying to do more injections than trying to outsource my patients to the clinical. And we are fortunate to now have 4 FDA-approved anti-VEGF therapies as well as one off-label anti-VEGF therapy, and they are all outstanding in reducing fluid in the retina to help our patients.

If we look at diabetic macular edema disease, the standard of care for diabetic macular edema involving the subfoveal center would be similar to neovascular AMD, where we initiate monthly intravitreal anti-VEGF therapies until we can solve the liquid as well as we can. But sometimes in diabetic macular edema we’re not able to achieve that, and that’s because there may be other players involved besides anti-VEGFs. We know that inflammation plays a role, and that’s where corticosteroids come in and can be initiated at any time during this treatment to try and get a better blood-reducing response. liquid. For diabetic macular edema, we have our proven focal laser, where we can cauterize or heat leaking micro-aneurysms to stop them leaking. Often using the focal laser as an adjunct treatment can help us achieve our goal.

Carl D. Regillo, MD, FACS: For DME and neovascular AMD, this will be anti-VEGF therapy as first line therapy – frequent and regular intravitreal injections, especially at first. For wet AMD, it’s constant therapy for life. It may or may not be for DMO, but there will be a lot of treatments as you indicate. The more often you administer treatments, the better your results will usually be, and that could easily be 8, 10 plus treatments in the first year alone and maybe a little less after that. Adjunctive treatment with corticosteroids for DME may be suboptimal responders are not effective in wet AMD; in fact, wet AMD has nothing else, maybe photodynamic therapy and older treatment, but in a very limited way. As you mentioned, focal laser is probably third in line for EMR, something that was first a long time ago, but not as effective as pharmacotherapeutic approaches.

Transcript edited for clarity

Martin E. Berry