New Retina Radio

07.08.26

Biomarkers, Imaging, and Early Treatment Decisions in Geographic Atrophy

Which imaging biomarkers matter most at diagnosis of GA, and how should they shape the decision to treat? In episode 1 of the GA in Practice miniseries on New Retina Radio, moderator Geeta Lalwani, MD, and panelists Murtaza Adam, MD, and Carl Danzig, MD, review the practical role of fundus autofluorescence and OCT in identifying high-risk GA, discuss ellipsoid zone integrity as an emerging endpoint, and work through a hypothetical case of an active, motivated patient with bilateral extrafoveal GA and good vision to explore how lifestyle, lesion characteristics, and patient education factor into early treatment decisions.

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Geeta Lalwani, MD (00:11):

Welcome to this three-part miniseries on New Retina Radio called GA in Practice. I have two guests with me here today, really two good friends. First, Dr. Moo Adam from Colorado Retina Associates.

Murtaza Adam, MD (00:21): Thanks for having me, Geeta.

Geeta Lalwani, MD (00:22):

And also we have here Dr. Carl Danzig from the Advanced Retina Institute in Bonita Springs, Florida.

Carl Danzig, MD (00:28): Thanks for having me.

Geeta Lalwani, MD (00:28):

In this miniseries, we discuss how data and personal experience have helped us evolve our understanding of treating geographic atrophy. A housekeeping note, if you haven't done so already, go check out our case presentations on Eyetube. You can find this series under the same title GA in Practice. So first we're going to talk about clinical biomarkers. So what clinical biomarkers are easiest to capture in the real world setting at diagnosis in your office? What's practical? Carl.

Carl Danzig, MD (00:56):

Great question, Geeta. And what's practical has to do with what we're doing with our patients when they come in. All my patients are getting an OCT at every visit and on presentation they're getting fundus autofluorescence images. I use both. The biomarkers I'm looking for on those FAF images are extrafoveal lesions, bilaterality, hyperautofluorescence, and multifocality. So if they meet any of those or all of those, that could be a risk factor for more rapid progression. Now, OCT, I'm looking for hypertransmission defects. I'm also making sure they don't have wet AMD as well.

Geeta Lalwani, MD (01:34):

So I do the same as you, Carl. I really like fundus autofluorescence as a teaching tool for the patients. If they have good vision in both eyes, it is sometimes challenging to help them have a better understanding of their disease and the progression of the disease. If you have two time points, it's so easy for patients to see how things have changed in terms of the size of geographic atrophy on the FAF, on the fundus autofluorescence. Moo, is anything different when you start treating patients? Do you do anything different?

Murtaza Adam, MD (02:05):

Similarly, I get monthly OCTs or every month OCTs depending on my treatment interval for those patients. And I try to repeat autofluorescence every six months so that we have a sort of a topographical view, a bird's eye of the macula. One of the challenges about autofluorescence is that the exact location of the fovea is a little ambiguous in these images and the fovea tends to be darker, so it sometimes can be confused for GA. So that's where multimodal imaging's really helpful because you can get that bird's eye view with the autofluorescence and then you can really nail in how far is the lesion from the central of the fovea on OCT.

Geeta Lalwani, MD (02:38):

Sure. So one of recently the EZ integrity has come into conversation about as a really natural endpoint for clinical trials. Tell me, Carl, what do you think about the EZ integrity in clinical practice and long-term as an endpoint for clinical trials?

Carl Danzig, MD (02:55):

So I think this is another biomarker and another thing we can look at. In the clinic, it's a little challenging. Not every office always has the same cameras or the imaging modalities. As a clinical trial endpoint, I know that's being looked at and it can correlate sometimes with microperimetry, which we're generally not doing in our clinical practice for patients. We know patients have a hard time with that lengthy test, but I do feel that this could be a biomarker of the future.

Murtaza Adam, MD (03:25):

Carl, you brought up a really excellent point earlier in our conversations about how on an FAF, the autofluorescence that is around the leading edge of a GA lesion where it's hyperautofluorescent is like a burning edge of the bush. That's where you have accumulation of lipofusion and other waste products in the RPE. And that actually correlates to where the EZ integrity tends to be lost. We've learned from the clinical trials not only that the treatments work, but in the natural history of the disease, the photoreceptors perish before the RPE atrophies.

Geeta Lalwani, MD (04:00):

Yeah, it gives us a good sense of directionality in what's to come. I think there are other aspects of visual acuity that we don't check that we don't have time to check such as low luminescence reading. And so we're getting better at this disease. I feel like we're still trying to understand geographic atrophy and these tools definitely make it... We're catching up to it. We're getting better

Carl Danzig, MD (04:20):

One thing that you just mentioned there, Geeta, and I really like that you talked about other things we're not testing because when we have patients that have good vision but they have GA, sometimes we're missing out on their symptoms. If we're not asking the right questions, whether they have trouble reading or they have trouble in dim lighting.

Geeta Lalwani, MD (04:38):

I think that's a very good point to bring it back to the patient and what their experience is. I find this especially important when there are other caregivers in the room because you know we'll have patients who check their vision and they're 20 / 30 and on paper that looks like a very good vision, but they're really struggling with, as you said, contrast sensitivity and whatnot. And it's very good for caregivers to hear in the room that this is all as a cause of dry macular degeneration in early onset geographic atrophy. Do you rely on anything different when you're tracking the disease or what do you do differently?

Murtaza Adam, MD (05:10):

Well, I think it's really important to be cognizant of a slightly increased risk of neovascular AMD when treating patients with complement inhibitors. So making sure that you scan through every line of your RAST or B scan on the OCT to detect neovascular AMD is important. A lot of these lesions tend to be minimally leaking and they tend to be away from the fovea. But nonetheless, if they bleed or cause secondary atrophy or fibrosis, the patient's scotoma can increase. So that's kind of the main thing that I look for when I'm monitoring these patients kind of in the short term. Obviously long term, it's about measuring GA progression.

Geeta Lalwani, MD (05:42):

All right, let's take a quick break and when we get back, we'll continue our discussion. Stay tuned.

Geeta Lalwani, MD (05:55):

So we're going to discuss a hypothetical patient here, and I'd love to hear how you both would manage him. This is an 80-year-old white man who had premium cataract surgery about five years ago and he was referred from his optometrist for suspected geographic atrophy in both eyes. The fundus autofluorescence shows a small unifocal banded lesion in the periphery of both eyes. The OCT shows a small area of slight hypertransmission temporal to the fovea in both eyes. The lesion's not picked up on color fundus photos and as you would imagine, his vision's very good. He's twenty twenty. But this gentleman lives alone, but he's very active. He's got a big social life. He plays golf. He drives to vit his family and he, in his own words, is open to aggressive therapy.

Moo, tell me, how do you talk to this patient about treatment for geographic atrophy?

Murtaza Adam, MD (06:46):

A conversation for a patient that hasn't yet to really lose significant vision on the Snellen is really different than one patient who's lost vision in one eye or is starting to lose vision in both eyes. And so for me, I try to set the stage for understanding their day-to-day life. I think you've really highlighted a lot of the things that make me more motivated to treat a patient. So it's someone who's active, someone who's really motivated, self-motivated to treat. But I also ask them, have you noticed any changes in your vision over the years? Because outside of Snellen acuity, you're going to notice difficulty with dark adaptation, you're going to notice difficulty with reading speed. Driving at dusk at nighttime might be harder. And so if they start to complain about these symptoms, that sets the stage for me to highlight the fact that even though they're twenty twenty, they have the advanced form of macular degeneration. They have geographic atrophy, the last stage that is associated with the most degree of vision loss in this disease class. So for me, it's really about that initial education and looking at so many of the factors, whether it's self-motivation or lifestyle to help decide when to treat.

Geeta Lalwani, MD (07:53):

So what about you, Carl? Do you change the way you bring this patient in or are you going to start treating him the first day? Or what's your conversation with this patient look like?

Carl Danzig, MD (08:03):

Great question because I generally like to try to treat patients earlier in the disease process here. And having someone with extrafoveal atrophy, generally it's an ideal candidate to start treatment. You want to preserve the vision they have. You don't want to wait for them to lose it and then preserve the lost vision, right? Makes sense. Now I would look at this patient and I try to measure how far outside the FAZ it would be. If it's a small lesion, and I can sometimes go back to the clinical trial inclusion criteria. It's not really exact on how I practice, but if someone has a lesion that's 0.25 millimeters squared in size and 2000 microns outside the foveal center, I might just say, "Here's some brochures. Let's talk about this in the future. There's no emergency today." As opposed to a patient that has maybe a monocular patient that has banded GA multifocal with a ring around the fovea. Totally different. But here's a patient that sounds motivated, open to education, potentially open to treatment. So I would bring him back in three to four months after giving a brochure and say, "Look, if you really want treatment, call my office and come back in sooner."

Geeta Lalwani, MD (09:13):

Yeah. I do similar to what you do. I bring them back in a shorter period. It gives me the ability to educate them further. It also gives me time. I can show them the change on the fundus autofluorescence or even on the OCT and also for them to understand what may or may not actually be progressing. Do you bring in family members? Do you ask patients to do that? I mean, this is a pretty independent gentleman. How would you discuss this with him?

Murtaza Adam, MD (09:39):

It's a good question. Family members are important I think when a patient lacks motivation and you think they need treatment or they're just really not understanding what you're telling them. They're not picking up what you're putting down. The average patient takes three to seven visits to repeat accurately the medical information that you've relayed to them. And so I love that Carl, even though this patient's low risk, you're telling them that you have this disease and that we're going to continue to talk about this over and over again. Because even after starting treatment on patients that are low risk, they'll sometimes say, "Doc, when do we stop these?" And we've had that conversation a few times already about, "Okay, this is something we're doing until either it's not useful to you or there's something better." But you'll find over the years of seeing patients that repeating the message over and over again is very, very important.

Geeta Lalwani, MD (10:28):

Yeah. I think it's super important to be able to give patients agency in their own decision as long as you feel like they're educated. And to your point, you talk about patients who are maybe less educated about their disease. And then this is a gentleman who is very agressive about his disease and you want to make sure that he understands exactly what is going to happen, that we are trying to preserve his vision and not in fact make it better. And I think that for him and his lifestyle is very important, but he has to understand timelines too.

Carl Danzig, MD (10:57):

One thing that you guys both mentioned is with family. So Moo and Geeta, great points here. And the other thing that I've learned the hard way is I'll talk to a patient and they're like, "Well, my spouse is in the waiting room. Can I bring them in now?" And I'm like, "I just spent all this chair time talking about your GA and now I've got to repeat it." So I've had my staff now ask the patient when they bring them into the room like, "Are you here with anybody? Let's bring them in."

Murtaza Adam, MD (11:22):

I find it so funny that they thought they needed to bring their family member with them, but they didn't like them enough to sit in the room to wait with them while they're waiting for you. It's just so funny.

Geeta Lalwani, MD (11:33):

It's a great, great observation. I think we've all had it and realize now the importance of bringing that family member in.

Murtaza Adam, MD (11:39): I might start asking it proactively with you.

Geeta Lalwani, MD (11:42):

That's a good idea. It's a good idea. I agree. Well, that's a wrap for our discussion today. We have two more episodes coming, so stick to your podcast feed and be sure to watch our case series on Eyetube under the series titled GA In Practice. I want to thank my colleagues, Carl and Moo, for joining me in the discussion. I'm Geeta Lalwani. Thanks for listening.