Geeta Lalwani, MD:

Hi there. My name is Geeta Lalwani and we'll be discussing geographic atrophy in practice. Our first case is by Dr. 'Moo' Adam.

Murtaza Adam, MD:

Thank you for having me, Geeta. Our first case here is a 79-year-old phakic female who was referred for geographic atrophy in her left eye. She was 20 / 400 in the right eye and we'll dig into why that was and 20 / 30 in the left. She's really concerned about her independence, maintaining it, driving, reading, all the things that she loves to do at her post-retirement. And so if we take a look at this fundus photo of the right eye, you can see there is a opacity that's blocking our view of the posterior pole. This is actually a dense posterior polar/PSC cataract that's obscuring our view. What's amazing is despite the cataract blocking our view on fundus autofluorescence and colored fundus photos, you can see a pretty decent view with the infrared penetration using OCT. And you can see that this is center involving geographic atrophy where the foveal umbo is exaggerated and you can see loss of the outer retina RPE and photoreceptor layers.

If you take a look at the left eye, fundus photography shows these prominent choroidal vessels in areas where there's suspected geographic atrophy. And it looks very multifocal with large soft drusen within the macula and the arcades. If we take a look at the autofluorescence, you can see now much more discreet evidence of hypoautofluorescence and multifocal hypoautofluorescence consistent with geographic atrophy, as well as some hyperautofluorescence at the edges of some of these lesions that are concerning, I think, for a high rate of progression. Using multimodal imaging is so important because using OCT helps you define exactly where the fovea is. And then autofluorescence and fundus photography, it can be difficult to know exactly how close a lesion is to the fovea. And you can see here, there's not much time if this progresses further and further. Infrared imaging is also helpful in a pinch to highlight areas of geographic atrophy.

In opposition to autofluorescence, it shows a brightness where the areas of geographic atrophy are. I use this pretty commonly when I just get an OCT on my patients to kind of illustrate exactly where their disease is at. So this case presented to me just kind of in the first few months after aproval for pegcetacoplan. And so we discussed the patient's poor prognosis in the right eye. She was count fingers 2400 with a dense cataract and central geographic atrophy, non-central GA in the left eye. And so we thought, let's start treatment in that left eye to try to save what we can, preserve vision for as long as we can and slow down the growth of her high risk geographic atrophy. In the context of this time, anytime I really see a new drug on the market, I try to either treat the worst seeing eye or exercise caution with the new molecule when there's a lack of real world data.

And so in this patient, we treated her right eye first as a trial to make sure she didn't have any inflammatory response to pegcetacoplan. She also did get cataract surgery in the right eye because although her GA seemed to be limiting her vision, I think we thought that cataract surgery would give her some gain of function. So here is her baseline image. And after starting treatment with pegcetacloplan in the right eye, we then started treatment in the left eye. And you can see at four months after one injection, actually after her first injection, she developed a CNV. You can see some macular edema here. So this case took a little bit of a turn. We see that there are increased rates of CNV formation in both clinical trials for pegcetaclopan and avastin captain pegol. And fortunately these lesions tend to be really slow leaking or minimally leaking.

And so this patient, although minimally symptomatic, we treated her same day with anti - VEGF therapy and she's done well ever since. So we extended her on a treat and extend protocol with her aflibercept and then continued pegcetacoplan in her left eye every four to six weeks in an effort to really slow that GA. Interestingly, her right eye, despite that dense cataract and pretty central geographic atrophy improved to 20 / 100 and she was pretty happy with that outcome. She's maintained 20 / 30 vision about a year and a half after starting treatment.

Geeta Lalwani, MD:

So that's a wonderful case, Moo. So tell me about the conversation that you had as you were sort of gearing up to start treating her.

Murtaza Adam, MD:

I was kind of new to the whole conversation. This drug was not around up until a few months before she presented and treatment options for GA have been lacking for most of our careers. And so this conversation's very different than a patient that has neovascular AMD where vision loss is truly imminent. And there's no question in most cases for us to initiate treatment. For her, it was a bit of an easier conversation because she had lost vision from her geographic atrophy in her fellow eye and she knew the impact that it would have if the GA progressed in her left eye. So we just discuss how this drug doesn't reverse changes, doesn't stop the disease, but does retard or slow down the progression of disease in an effort to buy time. And when first generation anti-VEGFs came out, they were a boon for patients. They transformed the lives of thousands of patients that were otherwise losing vision prior to that implementation and release of these drugs.

And we're seeing this now happen in GA. I always tell my patients, we're going to continue these medicines until your vision's maybe not good enough to justify it or there's something better that we can use. But it's great to have an option today to give these patients hope.

Geeta Lalwani, MD:

So what about you? Do you do anything different when you discuss it with patients?

Carl Danzig, MD:

I do a lot of the same things that you do, Moo, and I think that you really laid it out nicely about a monocular patient, how to manage. I'm really happy that she got cataract surgery because if we can't look in and see the details of the macula, well they're not looking out in the macular very well, but that OCT was phenomenal. They could break through that. I think you did everything that I would've done. Start with the right eye first, then proceed with the left. I always talk about expectations that we're trying to preserve their vision as long as possible, potentially preserve it and protect their retina longer. So when we talk about injections, patients come to me and say, "Well, how come I'm not getting the four month medicine that I see on commercials?" I'm like, "Well, my neighbor's getting aflibercept and she comes in every three months or faricimab and comes in every three months or whatever." And I said, "Well, that's a different disease state than what you have.

Now granted, your patient did develop neovascular membrane and you're right. I think those do regress quickly and they're generally pretty small and very manageable. But this patient, it's scary when a monocular patient develops that, but what a great success story here.