The Role of Anti-VEGF/Angiopoiten-2 Inhibition for the Treatment of AMD and DME - Episode 1

Overview of nAMD and DME

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Diana Do, MD, provides an overview of neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME).


Diana Do, MD: We're going to discuss a lot of clinically relevant material for both age-related macular degeneration (AMD) and diabetic macular edema (DME). Let me first talk about some of the important facets that we're facing in our clinical practice today. We know that both neovascular AMD and DME are extremely prevalent in our communities and there are vision-threatening complications with these diseases if they are not treated in a timely fashion. The standard treatment for both of these diseases is intravitreal VEGF inhibitors, and these have been the standard of care for over a decade. But do our patients who we see every day in our clinics achieve the same excellent visual acuity outcomes as those seen with clinical trials? Let's look at some of the data we have from our medical records, and Dr. Tom Ciulla and colleagues looked at a retrospective study of an EMR database from 2012 to 2016, and they tried to look at how many injections patients with neovascular AMD receive in clinical practice. And surprisingly, there's a large spectrum, but the vast majority receive about 7 injections over the first year, which is very different than what we expect with outstanding data from clinical trials, such as MARINA or ANCHOR, where patients were receiving monthly ranibizumab to treat their active wet AMD. Matt, in your clinical practice, do you think you're treating patients with the maximum number of injections to help them achieve the excellent visual acuity outcomes we see in clinical trials?

Matthew Cunningham, MD: That's an excellent question, Diane. And I do think as a whole, treatment burden is a big issue, not only for the patients, but also for us as the retina physicians. I would like to think that I get my patients in as frequently as in a clinical trial, but be it work issues, be it the patient rescheduling, I do think that my patients absolutely end up coming in less than an ideal time point. Patients tend to bargain with us as their retina physicians, and they keep saying, “How about 6 weeks? How about 8 weeks?” And that all we know leads to a less than ideal visual acuity outcome for our patients. I do agree with this slide that, unfortunately, in the real world we are not treating as we do in clinical trials.

Diana Do, MD: Thanks for sharing that. When we look closer at these large medical databases, we see that the vision outcomes in our clinics correlates with the number of injections these patients receive. And if you receive on average, let's say 8 to 12 injections over the first year, we expect in the real-world database to gain about 6 to 7 letters. But if you receive fewer injections, we can see that patients actually can lose vision over the first year. When we look at how many injections are necessary to achieve better visual acuity outcomes, we see that more injections with this first generation of anti-VEGF agents, either ranibizumab, bevacizumab, or even aflibercept, more treatment likely results in better vision. And if patients receive 6 or fewer injections during the first year to treat their neovascular AMD, they're more likely to actually lose vision over time. But clearly there's an area of unmet need in both neovascular AMD and diabetic macular edema, because patients in our clinics are not having the optimal outcomes that we see in clinical trials. And novel therapies are needed to help address this unmet need. Fortunately, there have been new FDA approved therapies that target not only VEGF-A, but also a new pathway, angiopoietin 2, which is also implicated in vascular permeability and angiogenesis. We're hoping that these new agents are more durable, that they can provide disease control through longer periods of time, while also providing the safety that we as physicians expect and patients also deserve.

Transcript is AI-generated and edited for clarity and readability.