Incomplete RPE and Outer Retinal Atrophy (iRORA) Development in Eyes With Fellow-eye Neovascular Age-related Macular Degeneration.

Background and objective: The utility of incomplete retinal pigment epithelium (RPE) and outer retinal atrophy (iRORA) in intermediate age-related macular degeneration (iAMD) as a clinical endpoint is not yet elucidated. We aim to understand the time to iRORA development in iAMD.

Patients and methods: Eyes with iAMD without iRORA of subjects with fellow-eye neovascular AMD (nAMD) were identified from visits between 2010 and 2019 at a tertiary clinic. Spectral Domain Optical Coherence Tomography 512 × 128mm macular cubes (Cirrus HD-OCT, Zeiss) were assessed for time to first detection of iRORA and complete RPE and Outer retinal atrophy (cRORA) at 24 months. Up to three iRORA lesions were followed. Univariable Cox regressions evaluated baseline OCT characteristics, age, and gender as predictors for iRORA or cRORA development. Baseline OCT characteristics included intraretinal hyperreflective foci (IHRF), subretinal drusenoid deposits (SDD), hyporeflective drusen cores (hDC), and drusen volume measured with semi-automatic segmentation of Bruch's membrane to RPE.

Results: In 101 eyes of 101 subjects (64% female; median 81 years old), 28.70% (n = 30) developed iRORA whereas 2.97% (n = 3) developed cRORA without iRORA at 24 months. Median (range) time to first iRORA or cRORA was 20 (12 to 24) months. The presence of baseline IHRF was associated with increased risk of iRORA development at month 24 (HR = 2.28, 95% CI: 1.14 to 4.56; P value = 0.019).

Conclusion: In subjects with fellow-eye nAMD, approximately one third of iAMD eyes developed iRORA at 24 months. Intraretinal hyperreflective foci was associated with a two-fold increased risk in iRORA development. [Ophthalmic Surg Lasers Imaging Retina 2025;56:274-279.].