Roles for VEGF Inhibitors in the Management of Retinal Diseases - Episode 10

Updates in the Management of Non-Proliferative Diabetic Retinopathy

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Drs Ehsan Rahimy and Joseph M. Coney analyze the implications of clinical trial data on the management of nonproliferative diabetic retinopathy.

W. Lloyd Clark, MD: Ehsan, we’ve got a lot of data on regression, a reduction in the rates of vision-threatening complications using anti-VEGF agents infrequently as every 4 months. This is not particularly aggressive treatment. There doesn’t appear to be today widespread adoption of this type of management in patients that have the threat for vision loss in diabetes. How does this work for you in clinical practice? How do you apply this data as you see patients with diabetic eye disease?

Ehsan Rahimy, MD: There are so much great data to unpack from PANORAMA and from Protocol W. As you alluded to, there’s been slow uptake in our field. Although anytime you’re dealing with something that’s potentially paradigm shifting in terms of the way we handle or manage a condition that we used to observe, there’s going to be a gradual phase-in and phase-out to start adopting these therapies. At this point in my practice, I’m fairly comfortable offering anti-VEGF therapy to my patients with severe NPDR [nonproliferative diabetic retinopathy]. If there’s a mistake that colleagues who are a bit averse to it may be making, it’s not even having that discussion with patients. In my practice, I’m all about educating my patients, letting them know what’s available, trying to get them to engage, understanding their disease process, and letting them know that treatment options are available. Here are some studies, here’s what they showed. And I let them be an active decision maker in that process, rather than me practicing paternalistic medicine and saying, “I’m not even going to say anything to this patient other than, ‘Come back in 3 or 4 months.’”

That type of care with diabetic retinopathy potentially lends itself to increased noncompliance more than anything in the long run. I’ve been pleasantly surprised that when I share these data from Protocol W and from PANORAMA, and the findings essentially corroborate one another, that our risk of progressing to vision-threatening complications is substantially reduced. I’ve been pleasantly surprised at the number of patients who want to do therapy.

There are a couple of take-home points from that. No. 1, consistency is more important than frequency. What I mean by that is, we saw in year 2 from PANORAMA, the every-8-weeks arm that switched to as-needed treatment, their level of DRSS [Diabetic Retinopathy Severity Scale] improvement fell off a cliff. It doesn’t get talked about much because that was an as-needed treatment arm. Remember that in year 1 that you had an 80%, 2-step improvement. In year 2, that dropped all the way down to 50%. And the reason was patients were being undertreated and they got an average of 1.8 injections of the 6 eligible injections. Whereas that every-4-month arm group essentially maintained their 2-step improvement. It was 65% in year 1 and 62% in year 2 across much less injections.

The way I look at it is, consistency is more important than the frequency. If we can get a patient to a regular interval that’s comfortable for them, that they’re compliant with, whether it’s 4 months or 6 months, then that’s great. Part of this is also the psychology. I think about things as if I were that patient. I don’t have retinopathy, and I hope I never do, but I think about it in terms of going to the dentist. If I’m going to a clinical care provider, and that visit is being tied to something procedural, then I’m far more likely to be compliant with that visit, knowing that something is being proactively done for me. Rather than just showing up, somebody looking at something and saying, everything is fine.

When push comes to shove, if I have something else going on, as Joe alluded to, diabetes is not entirely a disease of noncompliance. We have patients who care very much about their visits but are forced to choose. They’re working class, so they can’t take that many days off. They may have to juggle seeing the eye care provider with the kidney doctor, with the cardiologist, maybe they’re hospitalized. Sometimes they just end up missing these appointments, not because they don’t want to be there but because they’re forced to. If I can tie in a procedure, my belief is—and we have some real-world data forthcoming that suggest that—adherence to visits ends up increasing when we’re tying that injection to it.

I’ll end with 1 anecdote of a patient I saw earlier this week. We talked about turning back the hands of time. This was probably 1 of my earlier patients who elected to want to start treating his severe NPDR. His right eye had severe NPDR, and his left eye was moderate. We said we’d just start therapy. He had no DME [diabetic macular edema], by the way; his vision was 20/20. He was an engineer, very educated, and wanted to know everything about diabetes. I remember him the first time he came to see me. He presented the PANORAMA paper printed up. He brought it to me, and he wanted to start therapy, and we did so with his right eye. I tried to do my own algorithm, where I extended his treatment. I eventually lost him for over a year.

He came back just this week. His right eye was still at about a severe NPDR state, and the FA [fluorescein angiography] looked somewhat comparable to before. But his fellow eye that was moderate had progressive proliferative diabetic retinopathy with vitreous hemorrhage during that interval period. And it’s just an N-of-1, it’s just 1 anecdote, but that’s the type of patient I’m thinking about. Because you could have the most compliant patient in the world, but diabetes is a terrible multisystem disease that will inevitably cause someone to become noncompliant and miss a visit. But by treating that patient, did we potentially lengthen the leash and help prevent a terrible outcome from coming by the time they do inevitably get back to us?

W. Lloyd Clark, MD: Joe, these are very powerful data. What do you think it’s going to take for us to change the way we think as a retina community to begin to prevent vision loss vs treating the end-stage complications? Are there data that we need? Is there just time? Are there factors you can identify that may change this line of thinking in the future?

Joseph M. Coney, MD: For 1, training younger physicians to understand the disease is important. When I was training, if it didn’t change an outcome—and at that time it was vision—then we didn’t institute that therapy. I was always trained to look at vision as an outcome. Now we’re talking about trying to change the disease process, so to speak, where vision is not effective, which is a little harder to gauge. By training younger physicians in understanding the historical standpoint of eyes, because the data are prevalent. The progression of retinopathy hasn’t changed since we had been doing the studies in the 1970s. That has been consistent. And if you have an eye that has moderate disease, we know what the rate of progression is over the next 5 years. We know what the rate of progression is—you have severe disease if it’s untreated. And when you have sight-related problems, you know what the progression is. From a historical standpoint, that needs to be told to younger physicians. That’s No. 1.

No. 2, for me, it took a patient to have that outcome where it happened on my watch, and because they missed an appointment, for whatever reason, they got worse. I don’t want that to happen again. When I talk to patients with these issues, she always comes up in my mind. The other eye we were able to save. She also has proliferative disease. She’s still 20/20 in that eye, but in the eye that developed the tractional detachment, we never gained vision better than hand motion. And she never misses an appointment now. She’s 3 years out. She’s constantly undergoing therapy, and the impact that we’ve made on her is important.

When you have personal testimonies, when you have personal patients, that’s a sounding bar that helps us to make a change. It makes the paradigm shift, which may go against what you were originally taught. For me, I’ve learned every day with my patients, and that discussion with my patients is critical; knowing more about their lifestyles, and how this disease is a little different from what we see with our patients with AMD [age-related macular degeneration] who are normally brought in by a caregiver. These are individuals, these are our colleagues, and these are people who work next to you. That’s the reason I find this disease so fascinating. There’s not 1 thing you can point to, but personal stories, and having your patients not do well, is a strong testament to changing your behavior so it won’t happen again. If you can decrease that, it’s just imperative.

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 in-box.

Transcript edited for clarity.