Retina Specialists Favor Efficacy Over Risk in Geographic Atrophy Care

Growth rate reduction was the single biggest driver of treatment choice for retina specialists (RS) managing geographic atrophy (GA), according to the results of a survey published in Clinical Ophthalmology that represents the first quantitative assessment of RS treatment preferences for GA.

Pegcetacoplan (Syfovre; Appellis Pharmaceuticals) and avacincaptad pegol (Izervay; Iveric Bio) are 2 FDA-approved complement inhibitors for GA, which is an advanced form of dry age-related macular degeneration that affects roughly 5 million people globally and 1 million in the US. Both drugs carry a risk of progression to wet age-related macular degeneration (AMD). In phase 3 trials, pegcetacoplan reduced lesion growth rate by 16% to 18% with every-other-month dosing and 19% to 22% with monthly dosing at 24 months, while avacincaptad pegol reduced lesion growth rate by 14% to 27% at 12 months with monthly dosing.¹

"Geographic atrophy is a huge clinical unmet need that has had no answers in the past; we've had no previously approved options…," Eleonora Lad, MD, PhD, associate professor of ophthalmology at Duke University, said in an interview with The American Journal of Managed Care® following the FDA approval of pegcetacoplan for GA.² “Now that we have this approval, it's the beginning of a treatment of a major disease.”

Retina Specialist Treatment Preferences for GA

Researchers conducted a best-best discrete choice experiment survey of 166 US retina specialists with at least 7 years of experience and at least 50 patients with GA treated in the prior year. The survey tested 5 treatment attributes: lesion growth rate reduction (10%, 30%, or 50% over 18 months), mild-to-moderate uveitis, progression to wet age-related macular degeneration, risk of retinal vasculitis, and intravitreal injection frequency (one-time [gene therapy], every other month, or monthly). Neither pegcetacoplan nor avacincaptad pegol offers one-time dosing, with both approved options requiring ongoing monthly or every-other-month injections. The "one-time" scenario tested in the survey represents a hypothetical gene therapy still in development.

Respondents evaluated these attributes across 6 patient profiles that varied by GA lesion location and visual acuity in the unaffected eye. Preferences were analyzed using a mixed-logit model, which measured the relative attribute importance (RAI) of each treatment characteristic.¹

Lesion growth rate reduction carried the greatest decision weight overall, accounting for 40.9% to 52.1% of RAI and peaking among patients with foveal-threatening lesions and poor visual acuity in the unaffected eye. Among the 3 risk attributes, progression to wet AMD ranked as the most important, at 17.6% to 21.6% RAI, followed by mild-to-moderate uveitis risk (12.4%-15.3% RAI) and retinal vasculitis risk (10.7%-13.1% RAI). RS did not significantly differentiate between a 0.02% and 0.1% vasculitis risk. Additionally, injection frequency ranked least important overall (7.2%-10.7% RAI), though retina specialists still preferred a hypothetical one-time gene therapy when efficacy was equal.

Retina specialists tolerate higher risk when efficacy is greater. For a one-time injection, they accepted up to 9.4% wet AMD risk for a 10% lesion growth rate reduction; at 35% reduction, that threshold climbed to 30.2%. Patients with foveal-threatening lesions and poor visual acuity in the other eye were seen as the most important to treat by 80.1% of respondents, and willingness to prescribe across the 6 patient profiles ranged from 56.3% to 87.1%. These preferences held regardless of a specialist's years of experience, practice setting, or prior involvement in GA clinical trials.

What Does This Study Mean for How Doctors Treat GA?

As the study relies on stated preferences from hypothetical choice tasks, its findings may not fully reflect real-world clinical decisions. Efficacy was also measured through lesion growth rate, a structural end point rather than a functional vision outcome, and the choice tasks excluded cost, insurance coverage, and scheduling considerations. The 6 patient profiles used may not capture the full range of GA presentations, and the retina specialists who participated may differ meaningfully from those who chose not to.

Retinal specialists consistently prioritized lesion growth rate reduction over adverse-event risk and injection frequency across patient profiles, with risk tolerance increasing for patients with foveal-threatening lesions. The authors noted these findings may help inform shared decision-making when considered alongside patient preference data, and they call for further research incorporating functional vision measures as they become available in GA trials.

“When clinical trial data for gene therapies become available, this study may support assessing whether [retina specialists] consider observed reductions in the lesion growth rate to outweigh observed risks of wet AMD and uveitis and the need for a one-time intravitreal injection,” the authors concluded.

Disclosure: The study was funded by Janssen Research & Development, and several coauthors are Janssen or Johnson & Johnson employees or stockholders; medical writing support was also funded by Janssen. J&J has a one-time gene therapy for GA in development.

References

1. Csaky K, Pepio AM, Thomas C, et al. US retina specialists' preferences for geographic atrophy treatment. Clin Ophthalmol. 2026;20:594882.

2. Joszt L. Pegcetacoplan approval a "dream come true" for patients with geographic atrophy, says Dr Eleonora Lad. AJMC. March 5, 2023. Accessed August 11, 2026. https://www.ajmc.com/view/pegcetacoplan-approval-a-dream-come-true-for-patients-with-geographic-atrophy-says-dr-eleonora-lad