Roles for VEGF Inhibitors in the Management of Retinal Diseases - Episode 5

Making Informed Therapy Decisions for Macular Edema

November 22, 2021
W. Lloyd Clark, MD

Joseph M. Coney, MD

Diana V. Do, MD

Ehsan Rahimy, MD

Expert ophthalmologists debate the rationale behind choosing an anti-VEGF inhibitor for patients and the challenges involved in treatment management.

W. Lloyd Clark, MD: I want to ask this question carefully. In a broader sense, are there data to help make the decision about individual agents and specific indications? We all have our different practice patterns. In terms of AMD [age-related macular degeneration], Ehsan, are there specific data that we have that help inform your choice for initial therapy? And then based on a response to that, if there’s a need for switching, do you have information that you lean on? What data are important to you for making initial and then subsequent treatment decisions in AMD?

Ehsan Rahimy, MD: This is an area of active ongoing research, the search for potential biomarkers that may help predict a patient’s response, or what agent would a patient best respond to, or what type of treatment regimen would a patient best respond to. Until then, everything has been trial and error, and we adjust our patient’s particular regimen by treating and extending them. Most of us agree that there’s a wealth of clinical knowledge that tells us we can start with any of the VEGF inhibitors with AMD. For that reason, most of us do start with Avastin [bevacizumab] first. At what point do you switch is where you get a lot of different remarks and different opinions in terms of, at what point is it too early, is it too late to start switching? As I mentioned myself, I’ll give a patient 3 injections. I’m looking for their anatomic improvement on the OCT [optical coherence tomography], trying to resolve all intraretinal fluid first. Ideally both, but if after some point, they have a stable amount of subretinal fluid, I will then continue to extend that patient in 2-week increments. I will give them a trial of switching to another agent if they still have some persistent fluid after X number of monthly injections, and it doesn’t appear that they’re improving anymore.

I’m also looking at their visual acuity benefit. In the real world, we are extrapolating what the clinical trials have told us in terms of patients’ visual acuity benefits because as we know, vision is just not a reliable day-to-day indicator in our clinics. The reason is not only the acuity charts; a patient may be tested in a different room each time they come in by a different technician, at a different time of day. Sometimes they forget their glasses, sometimes they have dry eyes. We just can’t rely on visit-to-visit visual acuity testing. We’re extrapolating what we’ve seen from clinical trials and assuming patients can get that same type of benefit. The only real reproducible measure we have in our offices is the OCT. That’s why essentially, you hear colleagues comment sometimes that we’re treating the OCT first, and we’re trying to stabilize that and try to then extend treatment out, so the patient doesn’t need as much in the way of injections long term.

W. Lloyd Clark, MD: Joe, are there data that you use to make treatment decisions in diabetes? Is there specific clinical or other information that drives your treatment choice?

Joseph M. Coney, MD: No, it’s no different than what we said earlier. It all depends on how the patient responds. Sometimes, I’m limited in what I use by insurance companies, so even when patients have lower visual acuity and I want to use branded drugs, I still have a hard time. But with diabetes specifically, it’s important to determine what’s the driving force in that particular life because it’s a multifactorial disease. When it comes to AMD, it’s also inconsistent sometimes in how patients respond, and that has to do with the types of lesions that patients present with. If a patient presents, let’s say with a RAP [retinal angiomatous proliferation] lesion or with a polypoidal lesion, we know that those eyes can be more difficult to treat. Their burden of therapy may be greater, their interval may be shorter, they may need longer durations of therapy compared to other patients because their risk of recurrence is much higher. This would give us different responses, and it also depends on when a patient comes in. The most important thing across all disease states is how fast the patient comes in. Whether it’s a vein occlusion, whether it’s DME [diabetic macular edema], or whether it’s wet AMD, because we know when those eyes have damaged tissue, you can resolve the fluid, but you don’t necessarily improve the vision.

W. Lloyd Clark, MD: Diana, we have some comparative effectiveness data in AMD and DME. Do we have anything to help us in RVO [retinal vein occlusion], or is it total trial and error here?

Diana V. Do, MD: Fortunately, in retinal vein occlusion, we also have a wealth of comparative clinical trials, and specifically, the National Eye Institute funded the SCORE study. And that looked at both anti-VEGF agents and intravitreal steroids. And when we looked across different drugs, we saw that anti-VEGF agents, specifically aflibercept and ranibizumab, were effective and safe in the treatment of macular edema due to retinal vein occlusion. In addition, they had fewer adverse effects that are associated with intravitreal steroids.

W. Lloyd Clark, MD: Great. Let’s wrap up this section with a quick discussion on challenges of treating patients with VEGF inhibitors. Ehsan, what difficulties do you face daily treating patients with these drugs?

Ehsan Rahimy, MD: I’d say, Lloyd, there are 3 challenges we’re all dealing with in terms of caring for our patients on a day-to-day basis who are receiving injection therapy. No. 1 is the durability of these agents. We know we need longer-duration therapies. Those fortunately may be right around the corner. We have some potentially new entrants into the field. Some are sitting with the FDA right now, there’s the Port Delivery System, there’s faricimab, there’s KSI-301 and others that are in clinical trials. Basically, we’re looking for a “better anti-VEGF,” something that lasts much longer. Can we give injections every 4 months or every 6 months and still maintain the same degree of visual acuity gains with fewer treatments? That’s something our patients would be greatly appreciative of. That then feeds into No. 2, which is the unfortunate long-term compliance issues and the long-term essential loss of vision that we’re seeing in real-world studies that are being done that show patients are receiving fewer injections than is recommended by clinical trials. We see this with both DME and with AMD in the real world, patients are not getting as many injections and are gradually losing vision in the long run, or at least losing their visual acuity gains they gained from the earlier phases of their clinical trial enrollments.

Then the third is just the need for an alternative class of agents, so VEGF is great. Maybe our field just got really lucky and we hit the jackpot with VEGF, but ideally, we would like to have other therapeutic targets to pair with our VEGF therapy to potentially get incremental or synergistic gains. And the way a lot of us look at this is maybe we’re like the earlier days of oncology. We think about oncology, and they’re able to pair different chemotherapy regimens that target different pathways and find a perfect tailored regimen for a given patient. We ideally want that to be the case in retinal diseases. So far, we have VEGF and we have steroids, and we haven’t had anything else. Previous investigations into some of these pathways have unfortunately failed. We saw what happened with PDGF [platelet-derived growth factor], but potentially, we may be getting a new entry here with Ang-2 coming out, and there are other therapeutic targets in the pipeline.

W. Lloyd Clark, MD: To our audience, thank you very much for watching this HCPLive® Peer Exchange. If you enjoyed this content, please subscribe to our e-newsletters to receive upcoming Peer Exchanges and other great content right in your inbox.

Transcript edited for clarity.