Lesion growth rate reduction tops retina specialists' geographic atrophy treatment priorities

With two complement inhibitors approved in the US for geographic atrophy (GA) and additional therapies including ocular gene therapies in development, what factors do retina specialists weigh when choosing a treatment for their patients?¹ GA is an advanced form of dry age-related macular degeneration (AMD) marked by the development of atrophic macular lesions and progressive retinal cell loss; lesions often originate in the perifoveal region and may extend to the fovea, resulting in central vision loss.² Dysregulation of the complement cascade is a leading contributor to GA pathogenesis and has been the primary therapeutic target for approved treatments.³ The condition is associated with disease burden, with lesion progression and vision loss affecting patients' ability to perform daily activities.⁴

Despite the availability of approved treatments, not all patients are offered therapy, and the characteristics that drive retina specialists' prescribing decisions had not been previously quantified.¹ Csaky and colleagues conducted a preference study to quantitatively assess US retina specialists’ treatment preferences for GA using a structured experimental design.¹

Building the experiment

Csaky and colleagues recruited US-based retina specialists with at least 7 years of clinical experience and at least 50 patients with GA in the prior year to complete a best-best discrete choice experiment (BB-DCE)—a methodology designed to elicit both a first- and second-best treatment choice from among multiple options, generating trade-off insights even in scenarios where clinicians decline to recommend active treatment. A total of 166 retina specialists were included in the final analysis after pre-specified data quality assessments; most were male (78.9%), and participants had managed a median of 300 patients with GA in the prior year. The majority reported prescribing experience with pegcetacoplan (Syfovre; Apellis Pharmaceuticals; 76.5%) or avacincaptad pegol (Izervay; Astellas Pharma; 58.4%).¹

Treatment characteristics evaluated in the BB-DCE included lesion growth rate reduction (10%, 25%, 35%, or 50% at 18 months), three treatment risks—mild-to-moderate uveitis, progression to neovascular (wet) AMD, and retinal vasculitis—and intravitreal injection frequency (every month, every other month, or one-time via gene therapy). Patient profiles were defined by GA lesion location—foveal threatening (FT), non-foveal threatening (NFT), or extrafoveal (EF)—and visual acuity in the untreated eye, yielding 6 distinct profiles across which retina specialists made their recommendations. Preferences were analyzed using a mixed-logit model, and relative attribute importance (RAI) was calculated to quantify each characteristic's contribution to treatment decision-making.¹

What drove treatment decisions

Across all patient profiles, improving lesion growth rate reduction from 10% to 50% had the greatest impact on retina specialist treatment preferences, accounting for 40.9% to 52.1% of decision-making depending on patient profile. Among the three risks evaluated, progression to wet AMD carried the most weight (RAI 17.6%–21.6%), followed by mild-to-moderate uveitis (RAI 12.4%–15.3%) and retinal vasculitis (RAI 10.7%–13.1%). Although retina specialists preferred to avoid retinal vasculitis, they did not significantly differentiate between a 0.02% and a 0.1% risk. Injection frequency was the least influential characteristic regardless of patient profile (RAI 7.2%–10.7%), though retina specialists preferred a one-time injection over monthly injections when lesion growth rate reduction was comparable.¹

Patient profile also shaped preferences. Lesion growth rate reduction carried the greatest weight—and retina specialists were most willing to tolerate risk—when considering patients with FT lesions and poor visual acuity (20/200) in the other eye. Conversely, retina specialists were more risk-averse when treating patients with EF or NFT lesions and good visual acuity (20/20) in the other eye, and were more likely in those cases to select no treatment.¹

Trade-offs and risk tolerance

Csaky and colleagues found that retina specialists were willing to accept higher adverse reaction risks in exchange for greater lesion growth rate reduction. At a 10% lesion growth rate reduction with a one-time injection, the maximum acceptable wet AMD risk averaged approximately 9.4% and the maximum acceptable mild-to-moderate uveitis risk averaged approximately 12.8%. For a 35% reduction with a one-time injection, those thresholds rose to 30.2% and 42.2%, respectively. Retina specialists also tolerated modestly higher risks for less frequent injections, though the magnitude of this effect was substantially smaller than that driven by lesion growth rate reduction. Preference patterns did not differ significantly across retina specialist subgroups defined by gender, years of experience, practice location or setting, or participation in GA clinical trials.¹

Limitations and future directions

The authors acknowledged several constraints. As with all stated-preference methods, retina specialist responses to hypothetical scenarios may not fully reflect real-world prescribing behavior. The BB-DCE used lesion growth rate reduction—the primary structural end point in current GA trials—as the efficacy measure, which does not capture functional vision outcomes; the authors noted that the field is evolving toward functional measures. The study enrolled retina specialists from physician panels and databases, and preferences among participants may differ from those of the broader retina specialist population. Cost and insurance coverage were intentionally excluded from the experimental design.¹

Csaky and colleagues concluded that retina specialists prioritized lesion growth rate reduction above all other treatment characteristics and were more risk-tolerant for patients with FT lesions. They noted that when gene therapy data become available, this study may help contextualize whether retina specialists consider observed lesion growth rate reductions sufficient to offset the risks associated with novel delivery modalities.¹

Karl Csaky, MD, PhD

E: [email protected]

Csaky is affiliated with the Ophthalmology Department at the Retina Foundation of the Southwest in Dallas, Texas. This study was funded by Janssen Research & Development, LLC, which participated in study design, data interpretation, and manuscript preparation. Several authors are employees or stockholders of Johnson & Johnson.

References

1. Csaky K, Pepio AM, Thomas C, et al. US retina specialists' preferences for geographic atrophy treatment. Clin Ophthalmol. 2026;20:594882. Published 2026 Jun 9. doi:10.2147/OPTH.S594882

2. Fleckenstein M, Mitchell P, Freund KB, et al. The progression of geographic atrophy secondary to age-related macular degeneration. Ophthalmology. 2018;125(3):369-390. doi:10.1016/j.ophtha.2017.08.038

3. Bakri SJ, Bektas M, Sharp D, Luo R, Sarda SP, Khan S. Geographic atrophy: mechanism of disease, pathophysiology, and role of the complement system. J Manag Care Spec Pharm. 2023;29(5-a Suppl):S2-S11. doi:10.18553/jmcp.2023.29.5-a.s2

4. Chakravarthy U, Bailey CC, Johnston RL, et al. Characterizing disease burden and progression of geographic atrophy secondary to age-related macular degeneration. Ophthalmology. 2018;125(6):842-849. doi:10.1016/j.ophtha.2017.11.036