Complement inhibition in GA: Timing, safety, and follow-up

How early should clinicians refer patients with geographic atrophy (GA), and how should they weigh treatment risks, drug choice, and the burden of ongoing care? Those questions anchored a recent Modern Retina Clinical Forum in New Orleans, Louisiana, “From Detection to Decision-Making: Navigating Disease Progression and Treatment in Geographic Atrophy.”

Murtaza K. Adam, MD, a vitreoretinal surgeon and chair of clinical research committee at Colorado Retina Associates in Denver, moderated the discussion, which centered on 3 cases.

Referring before symptoms appear

The first case involved an asymptomatic phakic woman aged 70 years with intermediate age-related macular degeneration (AMD) in one eye and advanced nonfoveal GA in the other. Adam said the audience included retina specialists, other practicing physicians, and trainees who identify and refer patients with GA rather than treat them. Participants from some academic centers and trainees described a practice pattern of waiting until patients notice vision problems before referring, he said.

The patient had a multifocal, foveal-sparing GA lesion that put her worse eye at significant risk of vision loss within the next 1 to 2 years. Adam used the case to underscore the timeline of vision loss without treatment and the importance of early referral and treatment. “This is not wet AMD,” he said. “You’re not waiting until a patient starts to see vision loss and then referring them.” He compared the approach with glaucoma, in which clinicians do not wait for a cup-to-disc ratio of 0.9 before starting drops in a patient with a concerning disc or elevated IOP. The case changed the perspective of many in the room, he said.

Managing neovascularization after complement inhibition

The second case was a phakic woman aged 79 years who was functionally monocular. She had a large central GA lesion in her right eye, and her better-seeing left eye had multifocal GA at high risk for progression. She started treatment with pegcetacoplan (Syfovre; Apellis Pharmaceuticals) at an interval of approximately 6 to 8 weeks, and after her second injection, she developed juxtafoveal choroidal neovascularization (CNV). She had few symptoms, but optical coherence tomography showed macular edema and thickening associated with the CNV.

The discussion centered on treating patients with both disease states and on counseling them about the risks and benefits of starting complement inhibitors. Adam said the early perspective in the room was that complement inhibition is associated with a higher rate of CNV for both FDA-approved drugs, but that these patients also have good visual outcomes in post hoc analyses. In his experience, the CNV tends to be minimally leaking and easy to treat, allowing clinicians to extend the anti-VEGF interval without greatly increasing treatment burden.

Adam said he began treating GA in patients who already had neovascular AMD and added GA therapy in between, so the order is simply reversed. He counsels patients that they may need both wet and dry AMD medications, he said. If the CNV is caught early, before a hemorrhage occurs, clinicians can usually preserve central acuity.

Choosing a drug for a patient who travels

The third case was a pseudophakic woman aged 79 years with asymmetric GA who presented before GA treatments were available. Over approximately 18 months, vision in her right eye fell from 20/50 to counting fingers, which Adam described as very rapid progression of the lesion. Her better eye progressed more slowly. When treatment became available, she was concerned about retinal vasculitis as a complication of pegcetacoplan, so Adam treated her with avacincaptad pegol (Izervay; Astellas), for which the reported rate of vasculitis is zero or much lower.

Her lifestyle has been the main challenge. She spends 4 to 6 months of the year in Europe visiting her daughter and grandchildren, so treatment has not been consistent or persistent. Her vision has remained stable even as the GA lesion has grown, but Adam said he is starting to advise fewer, shorter trips and a focus on treatment to preserve the longevity of her fovea and central vision.

Access barriers that drive attrition

Asked whether anything new came up during the discussion, Adam said he values how these panels bring together people from many backgrounds and practice environments. A retina fellowship applicant at a university in California described how patients there often travel long distances for treatment. To keep the institution from losing money on GA therapy, those patients must be treated in the operating room with an intravenous line, a process Adam called “something I’d never heard in my entire career.”

High gasoline prices in California add transportation costs on top of co-pays, he said. The example added nuance to the conversation about attrition, loss to follow-up, and maintenance of therapy for a disease that progresses no matter what clinicians do.