Incomplete Retinal Pigment Epithelium and Outer Retinal Atrophy Characterized Using Fundus Autofluorescence: An 18-Month Post Hoc Analysis of GATHER2

Purpose: To identify fundus autofluorescence (FAF) characteristics corresponding to incomplete retinal pigment epithelial and outer retina atrophy (iRORA), defined using optical coherence tomography (OCT), and progression of iRORA to complete lesions (cRORA). Methods: In this GATHER2 (NCT04435366) post hoc analysis, pooled eyes from participants assigned to avacincaptad pegol (2 mg) or sham were analyzed for baseline iRORA beyond the borders of geographic atrophy; each iRORA was assessed for progression to cRORA at months 6, 12, and 18 using OCT. For each OCT-defined lesion at baseline and at each follow-up visit, FAF patterns were defined as none (no autofluorescence abnormalities), not classifiable, increased autofluorescence (IAF), questionably decreased (QDAF), or definite decreased (DDAF). Results: Overall, 153 iRORA from 95 eyes were identified at baseline, and the majority demonstrated none (34.6%; n = 53) or QDAF (34.6%; n = 53) patterns. A smaller proportion of baseline iRORA exhibited a DDAF pattern (7.2%; n = 11). At month 18, the proportion of iRORA manifesting QDAF and DDAF patterns increased to 38.1% and 23.0%, respectively, and the none pattern decreased to 16.8%. The majority of lesions that remained as iRORA at month 18 demonstrated either none (52.8%) or QDAF (49.1%). iRORA that progressed to cRORA by month 18 was more likely to have more advanced FAF abnormalities, with 44.4% having IAF, 30.2% QDAF, and 27.3% DDAF. Conclusions: Findings from this large study reporting FAF characteristics of iRORA highlight the heterogeneity of these lesions and the association of the multimodal phenotype on progression over time.