Mesopic Microperimetry Captures Extensive Macular Atrophy with Pseudodrusen-Like Appearance Progression Beyond Visual Acuity: A Longitudinal Analysis

Purpose To quantify longitudinal changes in mesopic and scotopic retinal sensitivity (RS) and evaluate their relationship with retinal pigment epithelium (RPE) atrophy progression and foveal involvement in extensive macular atrophy with pseudodrusen-like appearance (EMAP). Design Retrospective longitudinal observational study. Participants One hundred twenty-eight eyes from 66 patients with clinically confirmed EMAP followed at a tertiary inherited retinal diseases clinic. Methods Eyes with at least one visit including mesopic and red scotopic microperimetry using a validated 20-stimulus grid and multimodal imaging (blue autofluorescence and spectral-domain optical coherence tomography) were included. Associations between square root-transformed RPE atrophy size and functional metrics (best-corrected visual acuity [BCVA], mesopic RS, and scotopic RS) were analyzed using mixed-effects models adjusted for age and inter-eye correlation. Longitudinal rates of functional and structural change were estimated in eyes with ≥2 visits. Cox proportional hazards regression evaluated predictors of foveal involvement. Main Outcome Measures Structure-function relationships, yearly rates of functional decline, and predictors of foveal involvement. Results Among 128 eyes (median age, 59.5 years; 69.7% female), larger RPE atrophy size was significantly associated with worse BCVA, mesopic RS, and scotopic RS (all p<0.001), with the strongest association observed for paramacular mesopic RS (R 2 m=0.42). Forty-five eyes contributed to longitudinal analysis (median follow-up, 20.5 months). RPE atrophy enlarged linearly at 3.7 mm 2 /year, while mesopic RS declined linearly at -1.3 dB/year. BCVA and scotopic RS demonstrated logarithmic decline patterns. Among eyes without baseline foveal involvement, faster macular mesopic RS decline was the only significant predictor of subsequent foveal involvement (hazard ratio, 0.43 [95% CI, 0.20-0.96]; p=0.04), corresponding to a 133% increased risk per 1-dB decrease. Conclusions In EMAP, mesopic RS demonstrated stronger structure-function associations with RPE atrophy and a more consistent longitudinal decline than BCVA and scotopic RS. Decline in macular mesopic RS independently predicted subsequent foveal involvement, supporting microperimetry as a sensitive functional endpoint for patient stratification and interventional trials.