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
Abstract
Abstract 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%; I 2 = 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%; I 2 = 61.32%). A restricted Tier 1 plus Tier 2 CSC sensitivity analysis yielded 39% (95% CI, 23%–57%; I 2 = 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.
Authors 8
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Bilecik Şeyh Edebali Üniversitesi
Affiliation as printed
Department of Ophthalmology Bilecik Seyh Edebali University, Faculty of Medicine Bilecik Türkiye
Department of Ophthalmology Bilecik Training and Research Hospital Bilecik Türkiye
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Bilecik Şeyh Edebali Üniversitesi
Affiliation as printed
Department of Ophthalmology Bilecik Seyh Edebali University, Faculty of Medicine Bilecik Türkiye
Department of Ophthalmology Bilecik Training and Research Hospital Bilecik Türkiye
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University of Bern · Moorfields Eye Hospital NHS Foundation Trust · University Hospital of Bern
Affiliation as printed
Department of Ophthalmology Inselspital, University Hospital Bern, University of Bern Bern Switzerland
Moorfields Eye Hospital, NHS Foundation Trust London UK
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Elon H. C. van Dijk Aachen Department of Ophthalmology Leiden University Medical Centre Leiden The Netherlands
Leiden University · Leiden University Medical Center · Rotterdam Eye Hospital
Affiliation as printed
Department of Ophthalmology Leiden University Medical Centre Leiden the Netherlands
Department of Vitreoretinal Surgery Rotterdam Eye Hospital Rotterdam the Netherlands
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University of Bern · University Hospital of Bern
Affiliation as printed
Bern Photographic Reading Centre Inselspital, University Hospital Bern Bern Switzerland
Department for bio Medical Research University of Bern Bern Switzerland
Department of Ophthalmology Inselspital, University Hospital Bern, University of Bern Bern Switzerland
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Aalborg University Hospital · Aalborg University
Affiliation as printed
Department of Clinical Medicine Aalborg University Aalborg Denmark
Department of Ophthalmology Aalborg University Hospital Aalborg Denmark
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Aix-Marseille Université · Vitreous Retina Macula Consultants of New York · Hôpital Nord
Affiliation as printed
Department of Ophthalmology Hospital Nord, Aix‐Marseille University Marseille France
Vitreous Retina Macula Consultants of New York New York New York USA
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University of Southern Denmark · Sygehus Sønderjylland
Affiliation as printed
Department of Ophthalmology University Hospital of Southern Denmark Sønderborg Denmark
Department of Regional Health Research University of Southern Denmark Odense Denmark
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