New Parameters for Faster Geographic Atrophy Progression Established, with Srinivas Sadda, MD

A recent study presented at the 43rd Annual Scientific Meeting of the American Society of Retina Specialists in Long Beach, CA, has delineated a series of parameters associated with faster geographic atrophy (GA) growth, including nonsubfoveal GA location, multifocal lesions, better starting vision, and a higher number of intermediate or large drusen.1

Presented by Srinivas Sadda, MD, Doheny Retina Institute, the study was undertaken in response to conflicting data in existing research, which utilized older imaging modalities and smaller patient cohorts. More recent pivotal studies have provided a more robust natural history dataset based on untreated sham eyes over a long period of time.1

To that end, Sadda and colleagues investigated fundus autofluorescence (FAF), color fundus photography (CFP), and optical coherence tomography (OCT) features, as well as disease and patient characteristics, which were associated with faster GA progression during the phase 3 OAKS and DERBY trials.1

OAKS and DERBY were multicenter, randomized, double-masked, sham-controlled trials investigating pegcetacoplan for the treatment of GA secondary to age-related macular degeneration. Each one spanned 24 months, collectively investigating 1258 patients aged ≥60 years. The investigation ultimately found that pegcetacoplan slowed GA lesion growth with an acceptable safety profile.2

Investigators in this study included eyes with GA from the pooled sham arms of both OAKS and DERBY. They compared baseline and GA characteristics based on quartiles by annualized change from baseline to month 24 in GA size.1

A total of 311 sham eyes were included in the final analysis. Mean patient age was 77.7 years and 195/311 (63%) of included patients were female. Sadda and colleagues noted mean baseline GA as 8.097 mm2 (3.9891). For sham eyes, better mean best-corrected visual acuity (BCVA), BCVA ≥60 Early Treatment Diabetic Retinopathy Study (ETDRS) letters at baseline, nonsubfoveal GA, multifocal lesions, and more intermediate/large drusen (>20) were all associated with faster GA progression. Study eyes showed faster GA progression associated with worse mean low luminance visual acuity and the presence of nonsubfoveal lesions.1

Sadda sat down with HCPLive to discuss the study, highlighting the more contradictory indications, such as faster reading and better visual acuity, which are also associated with faster disease progression.

“That was probably, to me, one of the most interesting aspects of the study: the fact that we observed that patients who read faster and had better acuity at baseline actually grew faster, which is particularly concerning because those are the patients we really want to be safe,” Sadda said. “Patients who had a greater low luminance deficit also grew faster, although now that we got that result, I think we have a very good explanation, because we would expect that those patients who have a low luminance deficit probably have photoreceptors on the edge that are ready to go.”

Sadda also commented on the possibility of using these parameters to stratify patients in future GA trials.

“You could enrich for a group of patients who are going to grow faster, but any time you try to apply stratification there, it’s a double-edged sword,” Sadda warned. “On one hand, you can isolate a group that’s going to get worse faster, but it’s not necessarily going to be the group that’s going to respond best to therapy. You have to be careful, because sometimes, when you identify patients who grow faster, you’re identifying patients who are very severely advanced, and maybe nothing can save them. So that, I think, is a risk.”

Ultimately, however, Sadda expressed hope regarding these parameters, implying that they could potentially be utilized for predictive models, including AI, which could be used to patients’ benefit.

Editor's Note: Sadda reports disclosures with Roche/Genentech, Abbvie/Allergan, Apellis, Nanoscope, Astellas, IvericBio, and others.

References

1. Sadda S, Schwartz R, Tsuboi M, Yu S, et al. Baseline Characteristics Associated with Geographic Atrophy Progression in the OAKS and DERBY Trials. Abstract presented at the 43rd Annual Scientific Meeting of the American Society of Retina Specialists in Long Beach, CA, July 30-August 2, 2025.

2. Heier JS, Lad EM, Holz FG, et al. Pegcetacoplan for the treatment of geographic atrophy secondary to age-related macular degeneration (OAKS and DERBY): two multicentre, randomised, double-masked, sham-controlled, phase 3 trials. Lancet. 2023;402(10411):1434-1448. doi:10.1016/S0140-6736(23)01520-9