Complete Retinal Pigment Epithelial and Outer Retinal Atrophy in Age-Related Macular Degeneration: A Longitudinal Evaluation.

PURPOSE: There is a need for robust earlier biomarkers of atrophic age-related macular degeneration (AMD) that could act as surrogate endpoints for the geographic atrophy (GA) in early interventional trials. This study sought to examine the risk of progression of complete retinal pigment epithelium and outer retinal atrophy (cRORA) to the traditional atrophic endpoint of GA on color fundus photography (CFP). This study also compared the risk of progression for cRORA to that associated with the specific OCT features that define nascent GA (nGA), a strong predictor for GA development.

METHODS: One-hundred and forty participants with bilateral large drusen at baseline underwent OCT imaging and CFP at 6-monthly intervals for up to 36 months. OCT volume scans were graded for the presence of cRORA and nGA, and CFPs were graded for the presence of GA. The association and rate of progression to GA for cRORA and nGA were examined.

RESULTS: Both cRORA and nGA were significantly associated with GA development (adjusted hazard ratio [HR], 65.7 and 76.8 respectively; both P<0.001). The probability of progression of cRORA to GA over 24-months (26%) was significantly lower than the probability for progression of nGA (38%; P=0.039).

CONCLUSIONS: This study confirmed that cRORA was a significant risk factor for developing GA, although its rate of progression was slightly lower compared to nGA. Whilst requiring replication in future studies, these findings suggest that the specific features of photoreceptor degeneration used to define nGA appear important when assessing risk of progression.