Evaluation of Retinal Sensitivity in Complete Retinal-Pigment-Epithelium and Outer Retinal Atrophy (cRORA) Lesions in...

Objective: Lesions characterized as complete retinal pigment epithelium and outer retinal atrophy (cRORA) are linked to the progression of intermediate age-related macular degeneration (iAMD). However, the extent of functional impairment of such precursor lesions remains uncertain. Methods: In this cross-sectional study, 4 participants (mean age ± standard deviation: 71.5 ± 2.1 years) underwent extensive multimodal imaging and psychophysical testing of cRORA lesions secondary to iAMD. Lesion-specific functional testing was performed using patient individualized testing grids with clinical conventional available (Stimulus size: 0.43°, ~125 µm) and experimental adaptive optics scanning light ophthalmoscope (AOSLO, stimulus size 0.07°, ~20 µm) based microperimetry (MP). One cRORA lesion site and one in-eye control region were tested per patient, respectively. Results: AOSLO imaging revealed an overall decrease in photoreceptor reflectivity, areas of hyporeflectivity over drusen, interspersed with hyperreflective foci, and disrupted photoreceptor mosaic in regions of cRORA. Localized retinal sensitivity assessment with clinical conventional MP yielded an average loss of -14.0 ± 3.3 dB at cRORA lesions compared to the in-eye control regions. In contrast, localized visual impairment assessed by high-resolution AOSLO-MP with smaller test stimuli (20 µm) revealed a sensitivity loss of -15.1 ± 5.1 dB at cRORA lesions (p < 0.01). Notably, also the area surrounding cRORA lesions can be impacted. Conclusions: We demonstrated that cRORA lesions are associated with severe localized functional impairment. cRORA precursor lesions may thus be considered as a surrogate outcome measure in future interventional iAMD trials.