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 >= 1 visit including mesopic and red scotopic microperimetry using a validated 20-stimulus grid and multimodal imaging (blue autofluorescence and spectral-domain OCT) were included. Associations between square root-transformed RPE atrophy size and functional metrics (best-corrected visual acuity [BCVA], mesopic RS [mRS], and scotopic RS [sRS]) were analyzed using mixed-effects models adjusted for age and intereye 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, mRS, and sRS (all P < 0.001), with the strongest association observed for paramacular mRS (R(2)m = 0.42). Forty-five eyes contributed to longitudinal analysis (median follow-up, 20.5 months). Retinal pigment epithelium atrophy enlarged linearly at 3.7 mm(2)/year, while mRS declined linearly at -1.3 dB/year. Best-corrected visual acuity and sRS demonstrated logarithmic decline patterns. Among eyes without baseline foveal involvement, faster macular mRS decline was the only significant predictor of subsequent foveal involvement (hazard ratio, 0.43 [95% confidence interval, 0.20-0.96]; P = 0.04), corresponding to a 133% increased risk per 1-dB decrease. Conclusions In EMAP, mRS demonstrated stronger structure-function associations with RPE atrophy and a more consistent longitudinal decline than BCVA and sRS. Decline in macular mRS independently predicted subsequent foveal involvement, supporting microperimetry as a sensitive functional endpoint for patient stratification and interventional trials.