Clinical and Multimodal Imaging Findings in Extensive Macular Atrophy With Pseudodrusen (EMAP): A Systematic Review and Meta-Analysis.

Abstract

This systematic review and meta-analysis aimed to integrate the clinical and multimodal imaging features of extensive macular atrophy associated with pseudodrusen (EMAP), and to evaluate its progression and associated risk factors. EMAP is a retinal disorder with a distinct phenotype and poor visual prognosis that typically affects patients in their middle age. There is no standardized classification for EMAP nor a clear understanding of its etiology. Identifying clinical and imaging biomarkers is critical to improve EMAP diagnosis and guiding future research. We conducted a systematic review and meta-analysis following PRISMA guidelines (PROSPERO, CRD42024474924). A comprehensive literature search of MEDLINE, EMBASE, Web of Science, and ClinicalTrials.gov was performed up to June 19, 2025. Randomized and nonrandomized studies of EMAP were eligible. Meta-analyses were performed using random-effects models. Heterogeneity was assessed with the I² statistic, and risk of bias by the NOS. The examined outcomes were disease symptoms, best-corrected visual acuity (BCVA), progression of macular atrophy, imaging biomarkers, and systemic associations. EMAP was diagnosed using multimodal imaging analysis. Sixteen studies met the inclusion criteria for qualitative analysis, and 12 datasets were included (N = 1096 eyes). The mean BCVA at diagnosis was 0.62 logMAR (95% CI: 0.47-0.76; I² = 95.6%), with a mean worsening of 0.41 logMAR (3 lines of vision) over 2.1 years. Disease progression involved an increase in the macular atrophy area by an average of 8.3 mm² over 3.9 years (95% CI: 3-3.57; I² = 69.8%). Optical coherence tomography showed a mean central choroidal thickness of 135.8 (95% CI: 113.3-158.3; I² = 94.4%). Electroretinography data indicated a rod dysfunction with abnormal photopic response. Rheumatic fever was reported in 89% of patients across Brazilian cohorts (95% CI: 83.2-93; I² = 0%). This meta-analysis has limitations, mostly due to heterogeneity and biases inherent to non-randomized studies of this disease, hence the inconsistencies in the results and hypothesized associations underlying EMAP. Despite the different imaging modalities used to diagnose EMAP, the results demonstrate the common features that characterize and support its diagnosis.