Geographic Atrophy Treatment Landscape: Insights From Mitul Mehta, MD

Mitul Mehta, MD, MS:

Hello, my name is Mitul Mehta. I’m an Associate Clinic Professor at the University of California, Irvine and a Retina Specialist and the Fellowship Director of Vitreoretinal Surgery.

Question:

What is your take on treating geographic atrophy as a retina specialist, given the complexities of patient selection based on genotypic and phenotypic characteristics? How do you see AI and genetic research improving satisfaction and personalized treatments?

Mitul Mehta, MD, MS:

I give these current drugs all the time; literally every day I do an injection of one of the medications for geographic atrophy. In addition to the standard, having patients wear blue blocking sunglasses, drinking enough water, having enough cardiovascular exercise, taking their AREDS vitamins, the complement inhibition pathway seems to be what we have right now for geographic atrophy.

Do I wish it was better? Yes, I absolutely do wish it was a more effective treatment, but it is not not effective. It’s just not as effective as we wish it was. Because this is what we have right now, this is what we’re giving to patients to hopefully bide them time. Part of the situation is that these patients are older, so if we can keep them seeing into their old age, then that’s the point of the treatment. We’re always going to be running up against the life expectancy of the patient as going to be the end point of treatments for chronic diseases.

Same goes for diabetes or heart disease or any other disease of the body is that we know that at some point the patient is going to pass. The goal is to maintain their ability to function to the best possibility throughout that time. With these current treatments, we’re able to do that. We’re able to buy them more time to see their family and their loved ones. Because of that, we’re doing it as retina specialists, I believe that they’re important treatments to offer to patients.

In terms of patient selection, there’s a couple things we like to be aware of. Because the first rule of medicine is do no harm. We want to make sure these patients are not ones who are going to have any of the side effects. The most common side effect that is visually threatening is actually infection. We haven’t talked about that much in geographic atrophy treatments because the issue is that a lot of these patients who were in the clinical trial, they did as per the expected results of the trial.

But outside of the trial, since the drugs have become FDA approved and they’ve been able to be given for normal protocol treatments, we’ve discovered new side effects and new issues that are more severe in terms of their effect on the patient’s vision. Because that didn’t even happen a single time in any of the clinical trials, that threw us all for a loop. But it seems to be that the risk of those things is less than for endoptimitis, which is one of the most significant side effects that we’re worried about as retina specialists whenever we give people injections in the eye because that risk happens every time we do the injection.

For a patient who’s getting 10 injections in a year, their risk factor is 10 times what it is for somebody who’s getting a single injection. It seems to be, as best we know, that in these patients who have these rare side effects of retinovascularitis, if it happens once, it’s going to happen to that patient. If it doesn’t happen on the first time, it doesn’t seem like it’s going to happen to that patient. There have been very few actual incidences of these rare complications, but enough people have heard about it because retina specialists do like to talk about their complications in their patients. We all know about these risks, so it’s definitely a risk to consider.

There are other risks like damage to the optic nerve and intraocular inflammation that seem to be controlled with topical steroids. But the more severe ones tend to be the retinovascularitis and endophthalmitis, and some patients do get reactivation or activation of exudative macular degeneration as well. But we know how to treat that. I had one patient recently who had that, and I gave her an injection of an anti-VEGF and it completely resolved, and we continued the complement inhibition injection. We see these things all the time and most of the complications we see we can manage and as long as we can manage it, and the goal is to keep the patient’s vision as stable as possible for as long as we can, as long as we can do that, then we’re doing okay. That’s pretty much the way I think about this.

One thing that I do, which is not at all on label for these drugs is I give them all a fluorescein angiogram, which used to be the standard of care for every macular degeneration patient. But since we got overwhelmed with macular degeneration patients, since we’ve had a treatment for wet macular degeneration, we really don’t have time to do a fluorescein angiogram on every single patient. Now that we have OCTs that are such amazing quality now, we don’t even need a fluorescein angiogram on every single patient. Because we weren’t doing as many fluorescein angiograms as before, it’s now a diversion of what our routine is, but it’s not different than what the routine was when I was in training.

When I was in training, every retina patient got a fluorescein angiogram, at least when they were new, when they had a retina problem, because that was the modality of diagnosis that we actually had. We had our exam and we had fundus photos and fluorescein angiograms. Then when OCT came around, we started getting OCTs on every patient, and that was in the time domain OCT. Those OCTs were nowhere near as good quality as the ones we have today. Having the more advanced imaging has kind of pushed aside fluorescein angiogram, but I’m doing them on all of these patients just to see if there’s any underlying inflammation and if I see any underlying inflammation, I don’t use these complement inhibitors.

Question:

How does ethnicity influence disease progression and treatment response in geographic atrophy? How should these insights shape clinical practice, especially in patient assessment and treatment decisions? What factors should ophthalmologists consider when managing geographic atrophy in patients from diverse ethnic backgrounds?

Mitul Mehta, MD, MS:

One of the things we need to think about is who was in the clinical trial, and the phase 3 clinical trials are the larger trials that kind of guide our thought process for treating these patients. In a lot of these macular degeneration trials, almost all patients were just Caucasian or the vast majority of patients were Caucasian. Some of them [had] diabetic retinopathy; you’ll have a much more diverse patient set because that’s kind of what we see in the clinic. Different backgrounds are going to respond differently to different treatments, and we have to take that into account and you have to look at what the patients in your specific practice are doing and how they’re responding. Evaluate your treatments and your own patients as distinct from what the clinical trials are showing because the clinical trials might not be completely applicable to your own patients.

In my specific practice, we have 2 offices. In one office, we have a large number of Caucasian patients and Asian patients, specifically Chinese and Korean. In another one of my offices, we have a very large Vietnamese population and Hispanic population. Those 2 groups of patients or those 4 groups of patients respond relatively differently to different types of medications. It’s interesting how different their diseases are between those two. Some of them are much, much worse than others, and some of them just are very recalcitrant to treatment. We have to look into that and to make our own assessments of our own patients.

Question:

What are the current best practices for managing geographic atrophy with newly approved complement inhibitors like avacincaptad pegol and pegcetacoplan? How do you discuss long-term commitment and potential risks with patients and their families regarding these injectable medications?

Mitul Mehta, MD, MS:

As I mentioned before, these are drugs that are available and I use both of them, and different patients have different mindsets as to what they’re looking for in terms of treatments. Neither of these treatments actually improve vision, and that’s a very important thing for patients to understand, and it is important enough for them to understand that I never give patients an injection of these medications the first time I meet them because they need to understand that this is a chronic disease that they have, and these medications will not make their vision better. What it can do is slow down the progression of the disease.

Because we don’t have a very good metric to determine whether or not it’s even working for them, we can’t compare an eye that’s being treated to that same eye not being treated. We don’t know what the drug is actually doing for them. We don’t know if their progression is a slower progression than it would’ve been otherwise. We don’t have a very good idea for an individual patient. We have an idea for a population of patients, but not for an individual patient.

I tell all of them, this is a disease that is unrelenting. It will continue to get worse. This much we know. If we had prior imaging from them, we can at least say, “Over the last X many times we’ve seen you, this is the disease; this is how it has progressed. That gives us an idea of how it’s progressing in you. But things don’t typically happen in a straight line in humans. They don’t actually follow specific rules per se, but they do get worse. Our goal is to slow the curve down such that you lose vision the day after you die. That’s my goal is to keep you functioning as long as is possible. If we can slow this down enough that it never affects you, that’s the goal. But the downside to that is you have to come in every so often, and we make a decision based on the actual life of the patient because ultimately, patients who are in the real world don’t actually follow the clinical trials.”

My schedule is not completely exact every single time. Sometimes I might be out of town, sometimes the patient might be out of town. Sometimes they may not be able to get a ride. There’s all these different things that happen in the real world that make it so that the patients can actually match an exact clinical trial protocol. But that’s the advantage of the drugs being approved. We have a little bit of flexibility in that regard.

We do that and we tell the patients, “This is going to be our best guess as best we know from the clinical trials, and based on that, this seems to be a reasonable way for us to proceed with this trial or with this drug. If we don’t think that you feel like there’s not enough benefit from the drug, then we can stop. We haven’t lost much by stopping it. But I would prefer that if we can maintain this treatment, as long as we find it to be effective, then we’ll keep on doing it.” But it requires buy-in, not from just the patient, but from their family members as well, because they need a ride.

This content is independent editorial sponsored by Astellas. Astellas had no input in the development of this content.