Roger A. Goldberg, MD, MBA

Early Treatment Recommended for Geographic Atrophy, with Roger Goldberg, MD, MBA

Pegcetacoplan has demonstrated long-term efficacy and safety in treating patients with 

, based on the 48-month results from the GALE open-label extension of the OAKS and DERBY studies.

 Annual Scientific Meeting of the American Society of Retina Specialists

 in Long Beach, CA, by Roger Goldberg, MD, MBA, Bay Area Retina Associates, this study aimed to determine the impact of early versus delayed treatment with intravitreal (IVT) pegcetacoplan for GA secondary to AMD. Investigators collected data from both the treated and fellow eyes, as well as the location of GA lesions.

US Food and Drug Administration’s (FDA)

 approval of pegcetacoplan. A group of 1258 patients were randomized to either intravitreal pegcetacoplan 15mg or sham either monthly or every other month for 2 years. These trials initially indicated that both the monthly and EOM dosing of pegcetacoplan slowed GA lesion growth, based on FAF imaging at 24 months.

 to discuss the study and his presentation. He noted the long-lasting anatomic benefits shown by pegcetacoplan treatment, indicating both the drug’s efficacy and potential for dose extension.

“What really highlights the need for earlier intervention is that, when we look at the microperimetry data and compare the patients who have been on 4 years of therapy versus sham treatment for 2 years followed by 2 years of active treatment, we see about a 35% risk reduction in the central 4 or central 16 low sight on microperimetry progressing to an absolute scotoma,” Goldberg told 

P patients who completed OAKS and DERBY were given the option to continue to the additional 36-month GALE open-label extension. Those in the pegcetacoplan arms continued to receive pegcetacoplan monthly (PM) or pegcetacoplan every other month (PEOM); these arms made up the “Early Treatment” group. The patients from OAKS and DERBY who were receiving sham were crossed over to receive active pegcetacoplan treatment at the same interval; these patients comprised the “Delayed Treatment” group. Patients with both subfoveal (SF) and nonsubfoveal (NSF) GA lesions were enrolled.

 = 782) of patients involved in OAKS and DERBY enrolled in the GALE open-label extension. Of these, 79% (

 = 622) of patients enrolled in GALE completed the trial in the first 24 months. Between months 24 and 28, investigators noted a reduction in GA growth versus projected sham in NSF GA by 36% with PM and 30% with PEOM. The overall combined group (PM and PEOM) exhibited a 28% reduction (all 

Eyes in the Early Treatment group demonstrated consistently better outcomes, with GA lesion growth reduced by 22% to preserve 1.1 mm2 of retinal tissue. No events of retinal vasculitis were observed through month 48. Like OAKS and DERBY, reported events of retinal vasculitis in the post-marketing setting were rare (around 1 in 4000), with >510,000 injections administered across the real-world setting and phase 3 programs during 2024 alone.

Ultimately, Goldberg and colleagues determined that earlier treatment was largely more effective and beneficial to patients. Goldberg also discussed the risk-benefit ratio inherent to discussions of GA treatment, weighing the frequency of injection against the rapidity of positive outcomes.

“I think a lot of the debate that comes up around treatment of GA is frankly about this risk-benefit ratio, because it is an injection given monthly or every other month,” Goldberg said. “That being said, we now have shown anatomic and functional benefits. Although we’re seeing an increased treatment effect over time, we’re not seeing an increased risk of adverse events over time.”

Editor's Note: Goldberg reports disclosures with Annexon, Apellis, Neurotech, NovoNordisk, Roche/Genentech, Regeneron, and others.

Golberg R, Singerman L, Dhoot D, Boyer D, Maia A, et al. Early vs Delayed Pegcetacoplan Treatment for GA Secondary to AMD: 48-Month Results From OAKS, DERBY, and GALE Open-Label Extension. Abstract presented at the 43

 Annual Scientific Meeting of the American Society of Retina Specialists in Long Beach, CA, July 30-August 2.

Chiang A, Davis M, Stevens W, et al. Visual Acuity and Quality of Life Outcomes With Pegcetacoplan Treatment: A Post Hoc Analysis From the OAKS and DERBY Trials. Am J Ophthalmol. Published online May 29, 2025. 

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Based on an open-label extension of the OAKS and DERBY trials, pegcetacoplan has highlighted the superior effectiveness of early versus delayed GA treatment.

Effects of AREDS Vitamins on Geographic Atrophy Lesions with Roger Goldberg, MD, MBA

2025 Association for Research in Vision and Ophthalmology (ARVO) annual meeting

, Roger Goldberg, MD, MBA, cofounder of Emmetrope Ophthalmics and a practicing vitreoretinal surgeon at Bay Area Retina Associates, presented the results from his post hoc analysis of the OAKS and DERBY phase 3 trials testing micronutrient supplements AREDS and AREDS2 in reducing nonsubfoveal (NSF) 

A previous post hoc analysis indicated AREDS and AREDS2 could potentially slow down GA lesion progression without affecting overall GA area growth. Goldberg and colleagues analyzed whether the OAKS and DERBY trial populations exhibited similar effects.

“We actually had quite a large population of patients with untreated geographic atrophy, of whom about half were on AREDS vitamins,” Goldberg told 

. “So we had a great comparison between patients on vitamins and patients not on vitamins.”

During the study, eyes were grouped by AREDS micronutrients use (AREDS, AREDS2, or no micronutrients); sham observed NSF GA eyes and fellow eyes with NSF GA that met study inclusion criteria from subjects in the modified intent-to-treat population were pooled and included in the analysis.

Changes in GA distance to foveal centerpoint from baseline and changes in square root transformed total GA lesion size, measured by reading center assessments on fundus autofluorescence (FAF) images over 24 months. For analyses of distance to foveal centerpoint, if it was reached or an event of exudative AMD occurred, the data from subsequent timepoints were excluded.

A total of 516 eyes with NSF GA were included – 226 of these were on micronutrients and 290 were not. Participants exhibited no meaningful difference in progression towards the fovea between the sham and fellow eyes between micronutrient supplementation compared to those not (13 µm faster growth, 

 = .5). There was also no meaningful difference in area-based GA progression between eyes on and not on oral supplementation (.07 mm more progression, 

Ultimately, Goldberg and colleagues noted that this analysis found no evidence that oral micronutrient supplements slow GA progression towards the fovea or overall GA growth. Goldberg also acknowledged the limited ability of post hoc analyses to fully guide clinical practice, justifying the study’s departure from previous findings.

“I think AREDS are safe, so if patients want to take them, I think that’s fine,” Goldberg said. “Do I think it’s a substitute for either considering one of the FDA approved medicines, or that it should impact or impede our development of new agents? No. But lots of therapies are in development across all stages, some still targeting a compliment cascade, some targeting totally new pathways. I’m excited and optimistic for what the next decade or two will bring.”

Goldberg reports the following disclosures: Regeneron, Alimera, EyePoint, Cognition, 4DMT, and others

Goldberg, R, Saperstein, D, Do, D, et al. Analysis of AREDS oral micronutrients supplementation on geographic atrophy growth: Insights from the OAKS and DERBY studies. Abstract presented at Association for Research in Vision and Ophthalmology in Salt Lake City, UT, from May 3 – May 8, 2025.

Goldberg’s post hoc analysis has indicated that AREDS and AREDS2 vitamins do not slow either GA progression to the fovea or overall GA growth.

In closing, I’d like to get a thought from each of you to our primary care colleagues mainly. Dante, what would be your last parting thoughts to primary care doctors on age-related macular degeneration [AMD]?

: When I started my career 25 years ago, for the patient with AMD, the going thought was there wasn’t much you could do for them, and the patient was going to lose vision. They were not going to go totally blind but they were going to lose the center vision and probably not be able to drive or read. That’s completely different today. There’s a lot we can do for these patients. We can maintain their vision; we can improve their vision in certain circumstances. We’re doing a whole lot of work with the dry disease itself, too. I would be optimistic to those patients. I hate when I hear the patients come in and say, “Oh, I hear I’m going to go blind,” because many of them aren’t anymore. We’re going to be able to improve their vision and keep them seeing, reading, and driving. I have patients now who have been driving 15 or 20 years. They wouldn’t have been driving before the advent of these agents., So optimism would be my closing point when it comes to AMD.

: Roger, what would be your closing thoughts?

: Yes. My word was hope, not optimism, but we’ve come so far. I know everybody on this Zoom here tonight is very involved in clinical research. Generation 1.0 of the anti-VEGF agents, our ability to treat wet AMD, diabetic retinopathy and some other diseases, is incredible. The next 30 years are going to be another period of incredible innovation and growth of what we’ll be able to do for our patients. I think we’ll look back on these last 15 years and say, “Oh my gosh, you were injecting patients every month with a single class of medicine.” We’ll look back and say, “That’s barbaric,” because we’re going to have a much broader armamentarium of medicines, and diagnostics, and ways to monitor, and the introduction of artificial intelligence, and stem cells and gene therapy. As someone who’s involved in clinical research in this space, it’s an exciting time. We’ve come far in 15 years, but the next 15 and 30 years are going to be even more impressive.

: Lloyd, close us off with your parting thoughts.

: Yes. I would go back to basics a bit. The number of senior patients continues to grow dramatically. The baby boomers are coming of age, and there’s a tremendously large group of patients for whom life expectancy is much longer. As you get into your 80s and 90s, the incidence of age-related macular degeneration goes up dramatically. The incidence of diabetes is exploding, and then we have the more common senior causes of vision loss, including cataracts and glaucoma. These patients over the age of 70 need a dilated eye examination by a competent eye care provider every year. There’s a number of things that can trip them up, and their health is so good with better nutrition, better exercise, and better systemic management from you. We don’t want their vision to be their limiting factor, so make sure they get an eye exam, a dilated eye exam, every year because many of these problems if we catch them early will not impact their quality of life.

: That’s absolutely a tremendous point. I want to thank Roger, Dante, Lloyd. You guys have been fantastic, covering exudative age-related macular degeneration in such a thoughtful and in-depth way.

I want to thank everyone for watching this 

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A panel of eye care specialists share clinical advice and future directions for the treatment of wet AMD.

Clinical Pearls for the Management of Wet AMD

I’d like to move into our final topic here for the last few minutes, which is emerging treatment options. This is something that gets us all excited. Dante, I’d like to start with you on emerging treatment options and talk about one that you’ve been involved with, the port delivery system. Can you talk to us about what a port delivery system is?

: As I had mentioned before, if you ask retina specialists what do they want, do they want anti-VEGF agents that are more efficacious, or do they want ones that last longer? We’re pretty happy with the efficacy we can get out of these agents, if we can get the patient to have them on a frequent basis. What we really want are agents that last longer, so that we don’t have to do the injections as frequently and the patient isn’t burdened so much. One of the developments is essentially a reservoir, it’s about the size of a piece of rice. It’s a drug reservoir like one you might use systemically, but it’s just this tiny thing we put in, in the operating room, it’s an outpatient procedure with local anesthesia. We place this thing, similar to a cataract surgery, and we fill it up with a drug, ranibizumab, that’s the port delivery system. The drug is then delivered by simple passive diffusion over time. You can measure the drug being delivered from these devices out to a year and a half in some patients.

This provides potentially a long-term delivery device for the drug, and you can refill the device in the office. You don’t have to do an injection in the eye, you access through a septum in the device. It sits under the conjunctiva, so it’s covered, it’s behind the eye, under the eyelid. Patients don’t see it, but it can be accessed multiple times to refill the drug in these patients. This is going to provide not necessarily a more efficacious treatment, but a treatment where patients won’t need to come in as frequently. Eventually, we may be able to monitor some of these patients at home with a home OCT [optical coherence tomography]-type device. It’s going to really answer this durability, burden of therapy question. It’s a pretty exciting thing. It just got FDA approved about a month ago. Hospitals are ramping up to start providing it to patients. The data looked good. There was a big reduction in the burden of therapy, the number of treatments that were necessary. There may be a slightly increased risk—a small absolute risk, but about 3 times the risk—of infection in the eye, but the overall risk is relatively low. It’s exciting.

: It’s definitely exciting. There’s another drug, faricimab, that looks like it’s going to be approved in early 2022. This is the first bispecific antibody. Roger, talk to us a bit about what faricimab is.

: Yes. It is a full-length antibody, and for those of you who remember your immunology, that’s a little Y-shaped molecule. One arm of the Y is basically ranibizumab, an anti-VEGF agent. The other arm of the Y is an Ang2 inhibitor; angiopoietin-2 plays on this Tie2 pathway. It’s one that frankly the retina specialists are starting to learn about as we’ve seen good data emerge in inhibiting this, but it’s a good cop, bad cop. There’s a molecule that’s constitutively expressed on blood vessels, including in the retina, called Ang1, angiopoietin-1. That stimulates this receptor, the Tie2 receptor, and it leads to a whole cascade of positive effects that maintain the normal nonpathologic permeability, normal homeostasis, and desensitizes the blood vessel to the effects of free-floating vascular endothelial growth factor, or VEGF.

What happens though in situations where there’s oxidative stress or free radical formation or inflammation, you get an upregulation of the expression of Ang2. Ang2 is the bad cop, it kicks Ang1 off of that Tie2 receptor. It stimulates that whole cascade of pro-inflammatory effects, pro-permeability, pro-leakage. As Lloyd and Dante both talked about, leakage is our enemy here in treating both diabetic retinopathy and diabetic macular edema [DME], as well as wet AMD [age-related macular degeneration]. Then it also sensitizes those same blood vessels to the effect of VEGF, which we know is circulating at excess levels in wet AMD. Faricimab is a novel approach. It has this neat science where you can inhibit and target 2 pathways with 1 antibody. And unlike the port delivery, this has a conventional drug delivery system, it’s an intravitreal injection. There’s no learning curve to doing an intravitreal injection for those of us who are already performing thousands of these. We’re cautiously optimistic, the data looked good that have been shared so far both in wet AMD and in DME. We’re cautiously optimistic that we’ll get approval of that drug in the first quarter of 2022.

: Roger, Dante had mentioned the benefits of the port delivery system being extended durability. Is there better efficacy with this bispecific treatment, greater durability? What can we expect from it?

: The clinical trials were designed as what are called noninferiority trials vs aflibercept in this case. Our expectation isn’t necessarily better visual acuity outcomes, but hopefully a better drying agent, and therefore that is has better durability, can last longer, reducing that treatment burden, that injection burden.

: Lloyd, I’m going to ask you a 2-part question. Both Dante and Roger have talked about increased durability, decreased treatment burden. Have we capped out at what we can expect from a visual acuity standpoint from treating these patients with wet AMD?

: We talked about this earlier, the biggest predictor of final vision is presenting vision, so early diagnosis, early detection it appears is key. We can have unbelievable outcomes in patients if we catch them early. If you catch a new small choroidal neovascular membrane and you treat it aggressively with an effective anti-VEGF agent, we have patients who are 20/20, 20/25, and stay that way for years on end. At this point, we don’t think it’s particularly feasible or realistic that there’s a new agent on the horizon that’s going to offer better efficacy for the individual patient than what we have now. We do believe, however, that durability is definitely achievable; it’s a modest incremental goal. Down the road, I would like to believe that we can have better, more effective clinical outcomes.

The realistic goal today in terms of what we have in the pipeline, be it these drugs, these devices, and other compounds as well, is that we have a realistic shot of treating patients somewhere between 2 and 4 times a year and maintaining the same outcomes as monthly therapy. That is an improvement over what we’re doing now. Many clinicians and many patients just can’t keep up, most people can’t keep up with 12 injections a year. These interventions that both Dante and Roger have described, these are compared against aggressive therapy with on-label treatment, monthly therapy. That’s the gold standard treatment. If we can deliver that type of clinical outcome with treatments 2 or 3 times a year, that’s important to patients, and that’s the next step in delivering better care.

: You mentioned early on the ability to treat these patients earlier in the course of their disease. Is there anything that is coming that may help us diagnose these patients earlier?

: Dante mentioned home OCT, which the idea is to do non-office–based surveillance of patients. There are different ways potentially that this could be done. We could do this with Amsler grid testing at home; that’s been tried and is not particularly effective. But the OCT is this clinical tool that we use in practice that actually looks at the retinal anatomy in high magnification. It can measure the retinal thickness and find subtle changes in terms of fluid. There’s now technology that can be deployed at home so that patients can acquire these images and send them to us in clinical practice. We’re still trying to figure out how that fits into clinical medicine today. We also have a number of logistical issues to work through in terms of payers and access. But that would be a dramatic opportunity to put these devices in patients’ hands, and have highly durable agents. That would free them up for a much higher quality of life. They’d spend less time with us, and they would enjoy that tremendously.

: When you think about the advent of these amazing therapies, we’ve also had the advent of the imaging you refer to, the OCT test that we’ve talked about on multiple occasions. We’ve gone in the last 20 years from having prototypes and $100,000 scans that were very rudimentary, to now possibly being able to put that instrumentation in patients’ homes at an affordable level and allowing us to diagnose and monitor these patients on a daily basis. It’s absolutely amazing where we’ve come from and where we’ve come to.

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Dante J. Pieramici, MD; Roger A. Goldberg, MD, MBA; and Lloyd Clark, MD, review novel compounds in development for the treatment of wet AMD.

Roger A. Goldberg, MD, MBA

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