Ensuring Adherence to Geographic Atrophy Treatment

Nancy M. Holekamp, MD, FASRS: One of the biggest hurdles will be the discussion with patients to get them on treatment and then to get them to stay on treatment. Nora, how are you going to take someone who might be functioning with extrafoveal lesions, seeing well, but you know what’s in store for them? How are you going to get them to start this treatment and then remain compliant on treatment?

Eleonora M. Lad, MD, PhD: Maybe I’ll start with a patient who has an easier argument. A patient who has one eye already involved, either by neovascular disease that affected vision and they’re aware of, or geographic atrophy [GA] that affected the foveal center, or maybe another retinal condition, a vein occlusion that affected vision in the other eye. That’s a much easier conversation. The patient will be motivated to prevent an increase in geographic atrophy area and involvement of the fovea at all costs. That’s the easiest scenario. Then we come to the scenario you pose, which is bilateral geographic atrophy, extrafoveal, vision not yet affected. We have excellent imaging tools that we discussed, and hopefully they’ll become better over time. We might even add microperimetry in the mix to show them the visual consequence of geographic atrophy, which is a blind spot in the rGA [retinal vascular analysis]. Some of my patients are observant, and they can map their distortion and geographic atrophy blind spot on the Amsler grid.

Hopefully, if we have tools in our armamentarium that are functional and become better with time, such as a good microperimetry protocol that’s easy to implement, we could use this. I could use that as another motivating tool in addition to imaging, because they can realize, say they come in 1 year later and their scotoma increased, that we’re trying to prevent this from encroaching on the center. It’s similar to the conversation I have with my patients with diabetes right now who have extrafoveal DME [diabetic macular edema]. They can tell that they’re a little fuzzy in one area of the macula, and so do patients with GA. I would use that scenario to tailor it for my patients with extrafoveal GA and tell them we do not want that pathology area to encroach on the center because that’s important. With diabetics I have a different conversation about lifestyle modifications, but with GA, hopefully with the advent of new treatments, we have a way to prevent fast progression.

Jayanth Sridhar, MD: I agree 100% Nora, and I think the question we’re all thinking proactively about is, how do we keep patients on treatment with a treatment that does not improve vision but prevents progression? That’s a different conversation than what we’re used to having. We’ve been very blessed with anti-VEGF therapy to have treatment that improves vision. It makes that conversation a lot easier to make a patient stay on treatment, but we’re going to have to change that initial education about what we’re trying to achieve. This may be a case where we look to our colleagues, to our neurology colleagues who treat patients with dementia, who do treatments that reduce progression of dementia, to change that conversation about what the goals are. One of the things we will have to fight will be patients dropping off treatment because they see themselves worsening, and it’s hard for them to visualize what it would have been like. That’s where imaging, as Nora said, is important, but maybe also us doing the education, leveraging our ancillary staff and getting them involved, and being proactive in terms of having those conversations with the patient and the caregiver.

David R. Lally, MD: I think you’re right on the money. That initial counseling conversation is going to be the most important thing to get the patient to buy in or trust the therapy that’s being recommended by the physician. Specifically with the patients with bilateral nonfoveal GA, they might be seeing well in today’s world, they’re seeing and driving, their activities of daily function are right where they’ve been for a long time. I typically quote a natural history study that came out of Europe a few years ago that showed that if you had bilateral nonfoveal GA and you were driving with good vision, there was a two-thirds chance you lost your ability to drive within a median of 1 and a half years. It speaks to how you might be doing OK in today’s world, but we know that not too long from now, it may be a very different world for you, and you have to trust that we have that knowledge and the data to tell you that. If you can share that, that is impactful on them and they start to understand that, “I’m OK today, but tomorrow I might not be.”

Jayanth Sridhar, MD: Dave, you brought up safety issues. We’ve had in the past in our field, drugs that look safe in trials and have come out, and then when you start exposing it to larger amounts of people, you start to see events that weren’t as obvious when you applied it in a clinical trial population. Nora, to your point, I probably won’t start my patients in the first few months post-approval who are asymptomatic, because the one advantage we have with condition is that it’s slow moving. We have the advantage of waiting a bit and using it on the patients who may be more time sensitive, more time critical, more motivated themselves. So in case there is some sort of untoward safety [issue] that we don’t know about, then at least you can find the patients who maybe will have the highest immediate benefit. Nancy, I don’t know if you would do the same, or if you have a latency period when a drug comes on the market for the first time?

Nancy M. Holekamp, MD, FASRS: Well, I didn’t used to. After about 40,000 vials were on the market, it became clear that an anti-VEGF agent was having IOI [intraocular inflammation] problems, so we need to watch that closely. I already have patients who are very time sensitive, and it’s always relentlessly progressing, and so there are certain people I will not wait on to use this treatment.

I wanted to return to the compliance issue because it’s going to be hard because no one is getting better. I’m glad you mentioned dementia or Alzheimer disease, and I think we must change how we think about this disease. Dry macular degeneration is a neurodegeneration like dementia and Alzheimer disease. I would even think of glaucoma. Our glaucoma specialists call it an optic neuropathy, but I would call it also a neurodegeneration. When we look to glaucoma, that’s what’s closest to us, compliance is terrible, and it’s just an eye drop. When people are first diagnosed with glaucoma, the compliance rate with drops is about 10%, but the people who are most compliant with their glaucoma drops are the people losing vision. The people who can sense that they’re losing vision, or who have already lost vision in one eye and can sense that they’re losing vision in the other eye, are going to be the low hanging fruit. They’re going to be the people who want early treatment, as soon as the drugs become available. I think we will have to rely on the clinical trial data, that in general, clinical data can tell us that it’s safe enough to get approval.

Eleonora M. Lad, MD, PhD: I was going to bring up the glaucoma analogy, and we have peripheral vision fields in that condition to help guide management, but that’s a late finding. By the time you have visual field encroachment, the disease has progressed quickly. We have to think of ways to leverage other specialties or subspecialties within ophthalmology to change the education, the dynamics around the treatment of GA.

Transcript edited for clarity