Concurrent macular neovascularization in shallow irregular retinal pigment epithelium elevation phenotypes in age-related macular degeneration and chronic central serous chorioretinopathy: A systematic review and meta-analysis.

This systematic review and meta-analysis synthesized the reported frequency of concurrent macular neovascularization (MNV) among selected eyes with author-defined shallow irregular retinal pigment epithelium (RPE) elevations in age-related macular degeneration (AMD) and chronic central serous chorioretinopathy (CSC). Nine databases were searched on 3 May 2026 for observational studies assessing contemporaneous MNV in phenotype-positive eyes. Studies were classified according to phenotype definition, disease context, unit of analysis and MNV ascertainment directness. Principal quantitative syntheses were restricted to clinically comparable Tier 1 eye-level cohorts, while Tier 2 evidence was examined in a restricted sensitivity analysis. Random-effects meta-analysis of logit-transformed proportions was performed separately by disease, with binomial-normal generalized linear mixed models (GLMM) used as sensitivity analyses. Certainty was assessed using a GRADE-style framework, and the review was registered in PROSPERO (CRD420261384416). Twenty-two reports were included, comprising five AMD and 17 CSC reports. Three selected fellow-eye AMD cohorts contributed 160 double-layer sign (DLS)-positive eyes to the principal AMD analysis; the pooled frequency of contemporaneous MNV was 52% (95% confidence interval [CI], 19%-84%; I2 = 72.52%). Five selected chronic CSC cohorts contributed 232 flat irregular pigment epithelial detachment (FIPED)-positive eyes to the principal CSC analysis; the pooled frequency was 43% (95% CI, 25%-63%; I2 = 61.32%). A restricted Tier 1 plus Tier 2 CSC sensitivity analysis yielded 39% (95% CI, 23%-57%; I2 = 77.89%). GLMM sensitivity analyses produced similar point estimates, although confidence and prediction intervals remained wide. Certainty of evidence was very low. In selected phenotype-positive cohorts, contemporaneous MNV was identified in approximately one-half of DLS-positive AMD eyes and two-fifths of FIPED-positive chronic CSC eyes, but the estimates were imprecise. These findings should not be interpreted as diagnostic, prognostic, population-prevalence or treatment thresholds. Structural OCT phenotypes should prompt disease-contextualized multimodal characterization rather than stand-alone inference of MNV activity or treatment need.