Novel Treatment Mechanisms for Patients with DME and Wet AMD

Drs Coney, Luo, and Sheth discuss potential novel treatment mechanisms or options that we could see in the future with wet AMD and DME.

Jim Kenney, RPh, MBA: What are some potential novel treatment mechanisms or options that we could see in the future? I’ll throw this question out to the 3 of you, in both the wet AMD [age-related macular degeneration] and the DME [diabetic macular edema] space.

Joseph Coney, MD, FASRS, FACS: One other thing I’m interested in, here in Cleveland, we have about 28 offices scattered throughout northeast Ohio, and each community is really different. I learn so much from different communities and different individuals. I’ve learned a lot about the patient’s journey, particularly in my patients with diabetes. At the height of COVID-19, I wasn’t so busy, so I was able to talk to patients and learn more about their journeys. What I learned was more about their social determinants of health and what limited them from coming to the office, whether it was transportation, a lack of a car, having access to enough money for their co-pays, or paying for parking—all these things. Sometimes they wouldn’t show up. Ordinarily, we’d think that they’re a noncompliant patient, but life is complicated. Maybe they didn’t come in for a particular reason, like if they couldn’t find childcare for their grandchild who they’re taking care of.

From a diabetes standpoint, it would be nice if we had some type of therapy that we can institute that’s not very invasive. For that, a topical eyedrop is really helpful. The OTT166 drug that’s in phase 2 trials, which is looking to decrease the level of retinopathy, is really important. In some of these underserved populations, particularly in our Black and Hispanic populations, they normally present to us with a much more advanced disease state, so we’re able to institute just an eyedrop and decrease their level of retinopathy. If this medication works, this might be a great tool to decrease visually sight-threatening diseases in this population as it relates to diabetes and the complications we see from diabetic retinopathy.

Caesar Luo, MD, FASRS, FACS: I’d like to build on that. That’s a great point, Dr Coney. Something we haven’t talked about much is the difference in the patient populations with AMD and DME and their follow-up. Patients with diabetes, in general, are far more lost to follow-up for lots of reasons. In fact, most of them are out of their control. They see doctors 2 or 3 times a week. We’re just another stop on the local train for them. Unfortunately, they’re always at the physician’s office, so it’s really challenging. It’s not that they don’t want to take care of their eyes; physically, they can’t. Having something like this topical drug, this integrin inhibitor that Dr Coney is talking about, is exciting. In fact, I just had a patient with proliferative disease who, unfortunately, I had to say, “You’re too advanced for this trial, but we’re hoping you never get to this point.” It’s a very exciting thing for sure.

I’d like to add that for that population, sustained delivery therapies are extremely important. I was very excited about a port-delivery system in that patient population. Obviously, it’s on a pause, but as they work out the kinks, I think we’re going to see even more of a beneficial effect in patients with diabetes than we’re seeing with wet macular degeneration. A consistent therapy is very effective for them.

Building on that sustained delivery, a conversation I love having with our colleagues is gene delivery systems. Gene therapy has the hope of being 1 and done. It’s probably going to be 1 and less. But even if it’s 1 and less, that’s still great because you’re getting a little bio factory inside the eye, being able to produce these anti-VEGF chemicals and giving a little basal treatment all the time. That will be an exciting time. [There are] a few things to work out from a safety standpoint, but as we get there, that will be an interesting conversation. Lots of interesting things. Dr Sheth, you’re involved in a lot of these as well. Feel free to chime in.

Veeral Sheth, MD, MBA, FACS, FASRS: The general concept that both of you guys are talking about is reducing the burden on patients. Whether it’s eyedrops or gene therapy, everything we’re talking about is getting treatment into patients’ eyes without having to bring them back and forth as frequently. Along those lines, there are plenty of things being looked at. I put it into 2 buckets. It’s new therapies or mechanisms of action, and also new ways and routes of giving the drug, whether it’s suprachoroidal or subretinal. It’s an exciting time. All these things are moving us in the right direction. There are a number of trials and platforms that look promising. Over the next couple of years, we’re going to find out if some of these make it to us and ultimately help many of our patients.

Transcript edited for clarity.

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