Diabetic Macular Edema: Limitations of Anti-VEGF Agents

Nancy Holekamp, MD: That’s a nice summary of Protocol T and of the visual acuity improvement we see. You mentioned 10 to 13 letters over the first year of treatment, and when we look at mean vision gains, it’s about 30% to 40% of patients who will have significant vision gain. A large majority will at least lose no more vision. Dr Rahimy was discussing vision preservation and why these anti-VEGF agents have become the standard of care, but there must be some limitations. Dr Rahimy, can you discuss some of the limitations of the new anti-VEGF therapy?

Ehsan Rahimy, MD: It’s been great for our field. I was in training around the time anti-VEGF was taking off, so I don’t recall what it was like before then. We used a lot of laser on the patients that I’ve had over the years, and as you know, laser comes with functional vision loss due to collateral damage of retinal tissue. So it’s been great, but it hasn’t been perfect.

A major limitation of therapy is long-term duration and treatment burden. It’s a burden on patients [and] on society in terms of cost; sometimes family members are responsible for bringing patients to and from the office, and you’re removing them from the workforce. It’s a burden to us, as clinicians, as our clinics are inundated with injections. We need something better.

We’re looking for longer-duration treatments because we recognize there’s a disconnect between what we see in clinical trials, as far as visual outcomes, and what we see in the real world. If we adhere to clinical trial protocols, patients should be getting treated monthly to receive injections every month. But we know from our real-world studies, there is one done of the IRIS Registry—the Intelligent Research in Sight—a comprehensive clinical registry of all practices across the country, and it looked at the injections patients with DME [diabetic macular edema] received in their first year.

If you go by many of our established clinical trials, patients can get upward of 12 monthly injections for that first year. [More than] 50% of patients in the real world get 3 injections or less in that first year. They’ve correlated that the number of injections received is directly tied to visual outcomes. We know that making these visits is a challenge, even if you’re dealing with the most compliant patients. We spoke often about diabetes being a disease of noncompliance, but I think that’s not entirely fair to all our patients.

Some of these patients with DME have, on average, more than 25 outpatient office visits, so sometimes you’re just forced to choose. Many people don’t have many sick days. They’re working age, they have to put food on the table, and if they’re not noticing a change in vision and they have other pressing issues, they may be forced to miss an injection appointment, I try to make it up down the line.

That’s where we are in our field. We must think creatively. Are there ways to get around this? That’s where different injection regimens have come around when it’s PRN treating as needed. That was a protocol that we saw in many of the diabetic retinopathy clinical research network studies; essentially you can have different formulas. The patients come in every so often—every month, every 2 months, every 3 months,—and based on the changes you’re seeing in their vision or in their OCT [optical coherence tomography] measurements, you are supplementing with an injection. Otherwise you must see that patients are stable and continue to follow them.

Most retina specialists do, in terms of their treatment and not just for diabetic macular edema but also other retina vascular diseases, what we call treat-and-extend. There are variations of this protocol, but the concept is that we will start monthly treatment until we can get the patient as stable as possible. That could be, at least in my clinic, until I have a stable OCT image, the patient’s objective acuity, and the patient’s subjective vision as good as it’s going to get. Often they carry different weightings. The patient’s objective vision would be the lowest of the 3 because in the real world, we can’t reliably count on the visions that are being tested [because] it’s not a clinical research setting.

If the patients forget their glasses, they’re in a bad mood, their eyes are dry, we can’t always rely on that. Once we have a patient to a point of stability, the next step is to begin stretching out their treatment at intervals. Rather than coming in at 4 weeks, we’ll try to take them out to 6 weeks, then 8 weeks, and then 10 weeks as long as we don’t see a recurrence of disease activity or a drop in the vision. This way we’re able to comfortably get a patient out only when they need to come in. With a DME, I’m curious what our colleagues do. I have some DME patients that come in every 4-6 months, and that’s a lot more palatable for their lifestyle; they only come in 3-4 times a year and sometimes only twice a year.

Nancy Holekamp, MD: Thanks to all of you for this rich and informative discussion, and thank you for watching this HCPLive® Peer Exchange. If you enjoyed the 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.