Extensive macular atrophy with pseudodrusen-like appearance: clinical findings, multimodal imaging and natural history

Abstract Background Extensive macular atrophy with pseudodrusen-like appearance (EMAP) is a rare macular degenerative disease characterised by bilateral, rapidly progressive atrophy, widespread reticular pseudodrusen, and progressive choroidal vascular depletion, frequently misdiagnosed as age-related macular degeneration or inherited retinal dystrophies. Despite growing recognition, population-specific cohorts remain scarce and its natural history is incompletely characterised. We describe the clinical features, multimodal imaging findings, and longitudinal natural history of the first Portuguese EMAP cohort. Methods Retrospective, observational study of EMAP diagnosed patients at a tertiary referral centre. Clinical, genetic and multimodal imaging data (ultra-widefield fundus autofluorescence, colour fundus photography and optical coherence tomography) were analysed. Primary outcomes included annual macular atrophy progression rate and best-corrected visual acuity decline. Secondary outcomes included longitudinal choroidal structural parameters. Results Nine patients (17 eyes; 7 women, 77.8%) were included, with a mean age at baseline of 65.4 ± 8.6 years and mean follow-up of 41.9 ± 10.3 months. Mean atrophy area increased from 17.8 ± 14.9 to 28.1 ± 23.2 mm² ( p < 0.001), with a mean annual progression rate of 2.97 ± 2.83 mm²/year (0.315 ± 0.184 mm/year after square-root transformation). Eyes with hyperautofluorescent junctional borders showed significantly faster progression, both untransformed (4.99 vs. 1.21 mm²/year; p < 0.001) and after square-root transformation (0.429 vs. 0.215 mm/year; p = 0.014). Mean BCVA declined from 49.9 ± 22.0 to 38.5 ± 20.8 ETDRS letters ( p = 0.034; -2.8 ± 5.7 letters/year). Longitudinal choroidal analysis demonstrated significant reductions in total choroidal area (-27.5%), vascular area (-39.5%), and CVI (-18%). Conclusions This cohort confirms the aggressive natural history described previously, with faster atrophy expansion than typical geographic atrophy, marked visual loss, and progressive choroidal structural and vascular depletion. Hyperautofluorescent junctional borders predicted faster anatomical progression. Choroidal area and vascular area declined in every eye in this exploratory subgroup, suggesting a possible role in EMAP progression that larger prospective studies should confirm.