Prevalence of Outer Retinal Tubulation and Association with Geographic Atrophy Growth Among Patients in the OAKS and DERBY Trials

Abstract

Purpose : Outer retinal tubulation (ORT) has been identified as a biomarker for advanced Age-Related Macular Degeneration (AMD). A previous proof of concept analysis of FILLY, a Phase 2 clinical trial investigating the C3 and C3b inhibitor pegcetacoplan for Geographic Atrophy (GA) secondary to AMD, found a trend toward slower GA lesion growth in patients with fully formed ORT present. This analysis examined the prevalence of ORT and association with GA lesion growth rate among patients in the larger Phase 3 OAKS and DERBY trials.

Methods : In total, 300 patients were included in the analysis who were randomized to sham treatment in either the OAKS or DERBY trial. Key inclusion criteria were baseline Spectralis optical coherence tomography (OCT) measurement from which the presence of a fully formed ORT could be established, and at least one post-baseline GA lesion assessment via fundus autofluorescence (FAF) for which the lesion area could be measured. The analysis included calculation of the prevalence of ORT at baseline, Month 12, and Month 24 for patients that had suitable Spectralis OCT images available and descriptive summaries of the change in GA lesion size (mm²) as measured by FAF over 24 months.

Results : ORT prevalence rates were 32% (96/300) at baseline, 37.5% (106/283) at Month 12, and 43% (114/265) at Month 24. Baseline prevalence rates were higher among subfoveal lesions at 37.5% (75/200) compared to nonsubfoveal lesions at 21% (21/100). Patients with a fully formed ORT at baseline had a mean change from baseline GA lesion area (mm²) of 3.04 (95% CI [2.94, 3.87]) and a mean percentage change from baseline of 42.91% (95% CI [37.55, 48.28]) at Month 24. Patients without an ORT present at baseline had a mean change from baseline GA lesion area (mm²) of 4.26 (95% CI [3.90, 4.63]) and a mean percentage change from baseline of 63.90% (95% CI [57.79, 70.01]) at Month 24.

Conclusions : The presence of ORT was associated with slower GA lesion growth. While ORT were more likely to be present in foveal-involving lesions, similar trends in both subpopulations support the conclusion that presence of ORT is a protective risk factor, independent of lesion location. These findings have potential implications for both clinical trial design as well as real world GA management.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.