New Retina Radio

07.08.26

Evolving Practice Patterns and Dosing Strategies in Geographic Atrophy

How have 3 years of real-world experience with complement inhibition changed when and how retina specialists treat GA? In episode 2 of the GA in Practice miniseries on New Retina Radio, moderator Geeta Lalwani, MD, and panelists Murtaza Adam, MD, and Carl Danzig, MD, examine how referral patterns, safety data, and extension study findings have shifted their approach to early treatment. The group then works through a hypothetical case of an active 73-year-old patient with extrafoveal GA and intermediate AMD in the fellow eye, exploring how lesion characteristics, CNV risk counseling, and months-long travel schedules factor into the treatment decision.

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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 (00:20): Thanks for having me, Geeta.

Geeta Lalwani, MD (00:22):

And Dr. Carl Danzig from the Advanced Retina Institute in Bonita Springs, Florida.

Carl Danzig, MD (00:26): Thank you.

Geeta Lalwani, MD (00:27):

So in episode one, we discuss clinical biomarkers and how they guide our discussion. In this miniseries, in episode two, we're going to 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 the series under the same title GA in Practice. So the tide may be turning for GA treatment in that some doctors are treating earlier than they used to. Tell me about your own personal experiences. Anti-complement therapy was first approved in 2023 and here we are in 2026. How has your practice pattern changed, Carl?

Carl Danzig, MD (01:06):

Well, I think that my practice pattern and others are going towards earlier treatment. What we have now is almost three, well, three years with one product being FDA approved and almost three years with the other product ACP being approved. And real world data has been very helpful in seeing safety and the open label extensions for both products show increased efficacy over time. What I also find is that some patients are coming to me earlier now still. I want that to be better. I'm sure you experienced it also is that we're getting referrals too late, too often. But I think with the advent and the incorporation of Valeda therapy into some practices, referring doctors are looking at disease upstream. And that's really good because sometimes I'll get referrals for photobiomodulation and the patient is GA. So they're thinking they're referring for intermediate and they never would've referred that patient otherwise.

(02:06): So when I get that patient, you don't need this, what you need is anti-complement therapy and this is why. And then we look at the OCT and the FAF and we go over the safety and we go over the brochures and what it means to have GA.

Murtaza Adam, MD (02:20):

It's such a good point. So much of what we see on a daily basis is dependent 100% on a referring optometrist and ophthalmologist. And early on when the drug was approved, the conception of both ACP and pegcetacoplan was that in the general community, not so much the retina community, was that we have a new drug for GA. Maybe we can cure it. Maybe people can get better. And so we were getting referrals for center-involving GA patients with 20 / 200 or worse vision. And there was a lot of confusion about should we start treatment? Should we not? And you really had to set the stage and reset expectations for these patients and say, listen, we can do something if you have already lost vision, but it's not going to be as profound as an impact as if we had started the treatment much, much earlier.

(03:03): But now the referring community and the education on this disease state has gotten so much better. So we're seeing patients just like you described in an earlier series we discussed where you have extrafoveal lesions that are far and away from the fovea. And these patients are at risk of losing vision within on average two and a half years. So for me, like you, Carl, I'm a clinical trialist. I love that we are always evolving and iterating. And so I view these therapies as not just something that gives patients hope and reduces their risk of vision loss, but as a bridge to future therapies. The more patients that I start earlier now, the more patients are going to be eligible for future therapies.

Geeta Lalwani, MD (03:40):

I think the other point that both of you have alluded to is that this compounding effect of therapy. We know from extension label studies in both different drugs that the more we use these drugs, the more we can reduce the rate of progression, the longer we can actually preserve vision. I think that as we understand that we are actually trying to preserve vision, that subfoveal lesions are actually very late. The farther out you start, the longer we can maintain these patients. I think we've all gotten a lot more comfortable. What about safety data, Carl? How has that helped you become more comfortable with time?

Carl Danzig, MD (04:17):

So the safety data for both products is quite robust. And in the extension trials for pegcetacoplan, there were no cases of retina vasculitis or occlusive vasculitis in their extension trial. There is an FDA warning on their label for it, but the real world cases have not increased in incidents and it's still very low risk. And when we start looking at safety, even during that medication, and we harken back to those times where we were injecting brolucizumab five, six years ago, and the incidence of that was way higher, but still it scarred us internally and we remember that. ACP has had no cases in the clinical trial. And in the real world, there's no safety label for that. There's no safety label for IOI. Patients still are worried about anything you put in their eye, especially given that they're not going acutely blind if you don't treat them today.

(05:14): It's not like wet AMD that next month they could come back with a massive hemorrhage. Here, I commonly will treat with their worst seeing eye first if they have bilateral GA. If they don't, we can't really have that conversation. But I think that the safety data has been more comforting over the years and helped guide us at earlier treatment.

Geeta Lalwani, MD (05:32):

So what dosing regimen mood do you employ for early treatment? Do you do anything different amongst patients or do you have a standard dosing regimen that you use for either pegcetacoplan or ACP?

Murtaza Adam, MD (05:44): Avacincaptad pegol. Say that three times fast.

Geeta Lalwani, MD (05:47): Thank you for saying that for me.

Murtaza Adam, MD (05:49):

For me, for most patients, I tend to treat on an average every six to eight weeks. I think that gives them flexibility. It also meets somewhere in the middle where both trials for ACP and for pegacetacoplan tested Q4 week and Q8 week treatment. And on average, if you really look at the data, if you splice it, there might be some differences in those dosing regimens in terms of efficacy, but the differences are minimal. And so I think realistically treatment fatigue is something we have to look out for for patients. And although I appreciate a patient that's self-motivated or someone that's high risk for sooner vision loss, that's someone I will treat probably every four to five weeks. But for most patients that come in the door, six to eight weeks works for them. It also kind of works for my schedule. We're all busy retina specialists and it's hard to squeeze in a patient every four weeks. We've got a whole deluge of what AMD patients treat as well.

Geeta Lalwani, MD (06:39):

Sure. The burden of treatment for these patients is real. It makes me think about, especially when we first started my ideal first patient or my ideal patient for early treatment was one that had already lost vision in one eye. And now we're treating the fellow eye that had GA present because the patient knew what was coming, we knew what was coming. And so it was easy to motivate these patients. I have since moved on to treating patients that have bilateral disease but with good vision centrally and on some occasions unilateral disease with no GA in the fellow eye. What about you both?

Carl Danzig, MD (07:10):

So I will treat patients with extrafoveal lesions and good vision commonly. If it's bilateral, I try to start with the worst eye first. If they have the same vision as bilateral, I ask them to choose one eye first. I never start with bilateral injections on the same day. But if everything goes according to plan, everything's okay and the patient's comfortable with it, I will do bilateral injections in my office two different eyes. I try to also space out when they have their wet AMD treatment because some of these patients have both. Let's be honest. We're dealing with it and these patients are not asking for extra needles in their eye, but they are scared of losing their vision. So that patient that lost vision in one eye, they've seen that movie in one eye. They don't want it to happen to their other eye that is their lifeline for driving, for reading menus, for seeing faces, all of that.

(08:01): So I am motivated and those patients are motivated. I do start monthly if possible. And then if they can't do it, I throw them a bone. Well, let's extend it to six weeks or something. Let's make it eight weeks. But it's hard to go backwards.

Geeta Lalwani, MD (08:15):

No, it makes a lot of sense. I think we've all learned to treat that treating patients earlier is better and that we can maintain their vision for much longer. So let's take a quick break and when we get back, we'll continue our discussion. Stay tuned. All right. Thanks for sticking with us. We're going to discuss a hypothetical patient now. Carla Mu. I have a 73-year-old man referred for premium cataract surgery with suspected AMD. He gets sent over to us prior to surgery to have us evaluate his retina. His OCT and fundus photos show advanced macular degeneration with a small GA lesion in the right eye and intermediate AMD in the left eye. This is a very active man. He enjoys RV trips during the summer. He's often gone for three to four months. And right now it's January and he's coming back from his trips. He's otherwise healthy, enjoys bird watching, hiking and woodworking. How are you going to talk to this gentleman about the value proposition of GA treatment in his right eye?

Murtaza Adam, MD (09:30):

So very, very active patient, someone who values obviously independence visual function. And obviously they're motivated enough to seek your opinion. So they're already in the door. I think that speaks volumes about -

Geeta Lalwani, MD (09:43): And wanted premium IOL.

Murtaza Adam, MD (09:47):

So I guess the first conversation is like, yeah, should we permit or at least recommend the patient get a premium IOL? I think in any AMD patient, especially one that has intermediate to advanced changes, the answer for that for me is no. I don't know how you guys feel about that, Carl and Geeta.

Carl Danzig, MD (10:03):

So I think that's a fantastic point and it does not make a referring ophthalmologist very happy. I'm in your boat. So when you say premium IOL, I'm thinking multifocal, not a toilet. Correct. Yeah, multifocal. Yeah. The multifocal, I would steer this patient far away from that. I will tell them that they will not be happy with their long-term result or potentially not happy. I don't want to say definitive. Some people are always happy and glass half full and I want more of those patients in my practice who doesn't. But this patient who's traveling three, four months a year, just stay active. We know that consistent treatment is important. So if we're not doing monthly, we at least want to get in their eye every six to eight weeks.

Geeta Lalwani, MD (10:46):

So let's back up here though. So are you recommending treatment for this patient? Geographic atrophy, extrafoveal in the right eye.

Murtaza Adam, MD (10:53):

So there's some important details we need to know. What's the status of their intermediate AMD in their fellow eye? Do they have large PEDs that are hollow? Do they have RPE migration that's starting to happen? Are they high risk for GA in their other eye? The other question is how far from the fovea is that extrafoveal lesion and what are the characteristics of that extrafoveal lesion? Is it very round and regular? And does it have any hyperautofluorescence around it? So if the fellow eye with intermediate AMD is high risk for GA development and the GAI has a proximity to the fovea that makes me think they are at risk of losing vision within the next few years, I'm stronger in my consultation and recommending treatment. I don't necessarily start treatment the first time, but I do tell the patient consistent treatment once you start is really important. So if you miss one injection through the summer, maybe not the end of the world, but I have patients that travel and they snowbird or they travel for the summer and they do get treatments out of town when I'm not able to treat them.

Geeta Lalwani, MD (11:48):

So those are really very good points you bring up, not only evaluating the risk factors for GA progression, but the risk factors for developing GA. And there's a lot of talk about that whether you're looking at hyperreflective foci above drusen or hyporeflective foci within drusen. And that's a good point you bring up to look at that. What about you, Carl?

Carl Danzig, MD (12:09):

So you have excellent points here. And what I'm used to in Florida specifically, and you see this in Colorado too, I'm used to setting up treatment with doctors around the country. Using -

Geeta Lalwani, MD (12:20): Our network of friends as I call it.

Carl Danzig, MD (12:21):

I know. And it's great. I mean, we even share a patient. So a patient that's on an RV trip is incredibly challenging. So I would take that patient, treat them monthly while they're in my clinic and in town, and then try to get them one therapy between those three and four months while they're traveling. Set them up with a friend and maybe they're doing an RV trip through Colorado and I know some great people. But it is a challenge, but I don't think it's insurmountable in that case. The challenges become when someone goes, "Oh, I have a summer home in Europe and I go there for the... " Or Canadians that come to see me in Florida.

Murtaza Adam, MD (13:03):

I have a patient that visits her family in Denmark on a yearly basis and she's been getting inconsistent treatment. She developed a CNV while she was away, didn't even know it, subretinal fibrosis in one eye, and then ultimately has developed progressive GA in her other eye despite me doing injections when she's home. It's very challenging.

Geeta Lalwani, MD (13:20):

I want to go back. So say this patient did not have risk factors in the fellow eye for GA, but in the right eye has a lesion within 1500 microns of the fovea. It does have some hyperautofluorescence. This patient's 73, which honestly makes me lean towards treating this patient more. Not that I would exclude older patients, but this gentleman is healthy. He's going to live a very long time. Do you take those kinds of things into consideration?

Murtaza Adam, MD (13:49):

100%. Yeah. Your point about long-term, this is a chronic condition. This is not like a wet AMD where it is chronic, but it's the here and now. And once you get it under control, generally, as long as the disease is controlled, it's not going to progress too much unless you have fluctuations. But with GA, with treatment, without treatment, progression will happen. And if this person wants to feel comfortable driving across the country in their RV, they're going to want depth perception. And that's what we're trying to give them by doing these therapies.

Geeta Lalwani, MD (14:18):

And what about the risk of CNV? How do you talk to that about this patient? This patient has good vision right now and you may give them a therapy that will cause them to have a more immediate devastating disease. How do you have that discussion?

Murtaza Adam, MD (14:31):

There's absolute risk and there's relative risk, right Carl? So what do you think about that?

Carl Danzig, MD (14:36):

So I tell patients that we have 20 years plus of great treatment for wet AMD or patients have gained good vision from treatment before 20 years ago. They just lost vision. With patients that are developing wet AMD while on anti-complement therapy, lots of times those lesions are small and have a good response to anti - VEGF therapy. I tell these patients that the risk is not small. I mean, it's relatively small compared to, but it's 3%, 10% with treatment. But there's a baseline risk of 3% without treatment. So it's a doubling of the risk with treatment. But in the end, before 2023, we had nothing for these patients. And now we have something to hopefully slow the progression and preserve what they have longer, give them that depth reception that you talk about while driving an RV around the mountains.

Murtaza Adam, MD (15:31): I want them to see well while they’re driving -

Carl Danzig, MD (15:33):

Look, I want to see them while they're driving around Florida too.

Geeta Lalwani, MD (15:36):

When you're on the road next to him, right? Yeah. So I have to say that this is probably a patient that I would really push to watch initially to demonstrate the rate of progression so that they could actually see what was happening. Not because I want to let time go by, but because I think there are certain risks inherent in treatment and this patient being off grid perhaps for three or four months. Obviously different. As you mentioned, Carl, we have a wonderful network of friends in the retina world, but you're taking a gentleman otherwise who has good vision, putting him in a risk where things can change and we need to have some sort of safety net for those kinds of patients.

Carl Danzig, MD (16:12):

I agree completely, Geeta. And you mentioned off the grid. Well, maybe you put an Amsler grid in his RV and tape it there because they need to know what to look out for and counseling them for the risk and what to know. Keep them in the grid.

Geeta Lalwani, MD (16:24):

Education, education, education. Wonderful. Well, that's a wrap for our discussion today. We have one more episode coming so stick to your podcast feed and go back to your feed to hear our first episode on early biomarkers. 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.