Navigating treatment decisions in geographic atrophy: What three complex cases reveal

Not every patient with geographic atrophy (GA) fits neatly into the criteria used in the pivotal clinical trials that led to the FDA approval of pegcetacoplan and avacincaptad pegol. That gap shaped a recent Ophthalmology Times Case‑Based Roundtable, where Deepak Sambhara, MD, FASRS—medical director of research at the Eye Clinic of Wisconsin in Wausau—served as both moderator and case presenter, walking through three patient cases to frame a discussion on when and how to initiate GA treatment.

A lesion too small for the trials that defined treatment

The first case involved a 79-year-old woman working as a clinical psychologist who noticed a decline in vision. “I’m struggling looking at the DSM, and I find myself using magnifiers,” she told Sambhara. Her GA lesion fell below the 2.5-mm² lower size threshold used in the OAKS (NCT03525613), DERBY (NCT03525600), and GATHER1 (NCT02686658) trial programs that supported approval of pegcetacoplan and avacincaptad pegol. “The FDA label doesn’t specify sizes of GA,” Sambhara said. “The FDA label specifies GA in general.”

Participants worked through how to weigh the patient’s symptoms and motivation against those narrower trial criteria, Sambhara said. The case also raised questions about treating incomplete retinal pigment epithelial and outer retinal atrophy in the absence of complete atrophy. The patient was ultimately treated with pegcetacoplan.

A monocular patient with diminishing visual reserve

The second case centered on an 82-year-old monocular patient who had lost vision in her fellow eye to endophthalmitis following a minimally invasive glaucoma surgery procedure and was now facing GA progression in her only seeing eye. Participants were split, Sambhara said, between delaying treatment given its limited proven benefit and treating sooner given the patient’s diminishing reserve. “Having access to historical imaging can often guide how aggressive you want to be when you’re dealing with these patients,” he said.

He added that the patient’s own sense of declining vision carried the most weight. “We’re treating the patient in our chair, and sometimes the patient in our chair is going to be the biggest motivator as to how you make your judgment,” Sambhara said. The patient chose to begin treatment with avacincaptad pegol.

Managing CNV that develops during complement therapy

The third case, an 87-year-old man, addressed a patient who developed choroidal neovascularization (CNV) while on complement inhibitor therapy, a scenario several participants said they had personally encountered. Most de novo CNV cases discussed were small, type 1 lesions easily missed without a full B-scan review and highly responsive to anti-VEGF therapy, though 1 participant described a more aggressive case that presented as a subretinal hemorrhage.

Participants agreed on one point without exception, according to Sambhara: “If you see a CNV and there’s leakage, you are going to call an audible and treat with anti-VEGF that day.” What happened afterward varied. Some participants paused the complement inhibitor to stabilize the neovascular component first, others continued both therapies on separate visit schedules, and none reported administering both agents to the same eye on the same day. Sambhara said that separation protects a clinician’s ability to identify what caused an adverse event. “There is a clear delineation between visits that are specifically for anti-VEGF and visits that are for complement,” he said.

Long-term extension data and real-world registries

Discussion also turned to newer long-term and real-world data. Five-year GALE (NCT04770545) extension data for pegcetacoplan and 42-month GATHER2 (NCT04435366) open-label extension data for avacincaptad pegol were reviewed as evidence supporting sustained therapy. Participants also discussed 2 real-world registry analyses presented at the American Society of Retina Specialists 2026 annual meeting: a podium presentation by Nimesh (Nemo) Patel, MD, of Massachusetts Eye and Ear, using the Vestrum Health database, and an on-demand presentation by Sambhara using the IRIS Registry.

Both analyses examined outcomes in patients who have both GA and previously treated wet age-related macular degeneration, a population the pivotal GA trials did not study. According to Sambhara, the analyses independently found comparable outcomes between patients treated with a complement inhibitor alone and those also receiving concurrent anti-VEGF therapy, addressing whether GA arising alongside neovascular disease behaves differently than GA occurring on its own.

The value of case-based discussion

Sambhara said the roundtable format offers something didactic lectures do not. “The beauty of case-based discussions is we all come from diverse backgrounds, diverse practice settings, and diverse geographical areas,” he said, adding that varied perspectives give physicians tools they can apply to their own patients. Even as the session’s moderator, he said, “I take away information every time I moderate it or participate in a case-based roundtable to apply to my own personal practice.”