Functional Evaluation of Retinal Pigment Epithelium and Outer Retinal Atrophy by High-Density Targeted Microperimetry Testing

Purpose Complete retinal pigment epithelium (RPE) and outer retinal atrophy (cRORA) on optical coherence tomography (OCT) imaging has recently been proposed to describe end-stage atrophy in age-related macular degeneration (AMD) by international consensus and expected to be associated with a " dense scotoma ", but such functional evidence is lacking. This study sought to examine the visual sensitivity defects associated with cRORA, and to determine OCT features associated with deep defects. Design Observational study. Participants Sixty eyes from 53 participants, including 342 microperimetry tests over 171 study visits. Methods Participants underwent targeted high-density threshold-based microperimetry testing of atrophic lesions (with at least incomplete RPE and outer retinal atrophy [iRORA]) with a 3.5º diameter grid. The maximum extent of signs of atrophy for all lesions were graded on OCT imaging. Main Outcome Measures Number of deep visual sensitivity defects (threshold ≤10dB). Results Presence of choroidal signal hypertransmission ≥500μm, complete RPE loss ≥250μm, and inner nuclear layer (INL) and outer plexiform layer (OPL) subsidence, and/or hyporeflective wedge-shaped band (defined as nascent geographic atrophy [nGA]) ≥500μm ( P ≤0.020), but not RPE attenuation or disruption ( P ≥0.192), were all independently associated with a significant increase in the number of deep visual sensitivity defects ≤10dB. Only cRORA lesions with hypertransmission ≥500μm or complete RPE loss ≥250 μm, or with both of these features ( P <0.001), but not lesions with only hypertransmission 250-499μm ( P ≥0.303), had significantly more deep visual sensitivity defects ≤10dB compared to iRORA lesions. Lesions with nGA ≥500 μm, irrespective of the presence of hypertransmission ≥500μm and/or complete RPE loss ≥250μm, also showed a higher number of deep visual sensitivity defects ≤10dB compared to lesions without nGA ≥500μm ( P ≤ 0.011). Conclusions Not all cRORA lesions show a difference in the number of deep visual sensitivity defects compared to iRORA. Instead, hypertransmission ≥500 μm, complete RPE loss ≥250 μm and nGA ≥500 μm are all OCT features independently associated with deep visual sensitivity detects that could help inform the definition of end-stage atrophy on OCT imaging.