Physical risk factors associated with central serous chorioretinopathy: A protocol for a systematic review and meta-analysis

Background: Central serous chorioretinopathy (CSCR) is a common vision-threatening retinal disease that affects predominantly working-age adults. Although often self-limiting, a substantial proportion of cases are either chronic or recurrent, resulting in significant visual, psychological, social and economic burdens on sufferers. Current treatment options are limited and lack robust long-term evidence, reflecting an incomplete understanding of underlying disease mechanisms. Traditionally, CSCR has been researched as a solely ocular condition, however numerous non-ophthalmic physical risk factors have been implicated in the disease, suggesting a broader systemic aetiology. A comprehensive synthesis of physical risk factors for CSCR is needed to inform future mechanistic research and therapeutic development. Objective: The main objective of this systematic review and meta-analysis is to summarise physical risk factors associated with CSCR, including genetic, hormonal, metabolic and drug- or toxin-related factors. The secondary objective is to describe any associations between individual risk factors and disease severity. Methods and analysis: This protocol has been written in accordance with the Preferred Reporting Items for Systematic review and Meta-Analysis Protocols (PRSIMA-P). The PRISMA-P Checklist for this protocol can be found in Supplemental Information S2: PRISMA-P Checklist. Observational and interventional studies that report on any physical risk factors for CSCR will be included. Eligible participants are adults (≥ 18 years) with CSCR. Searches will be conducted on MEDLINE, Embase, CINAHL, Web of Science, Scopus and CENTRAL, and supplemented by grey literature and clinical trial registry searches. Two reviewers will independently screen studies, extract data and assess the risk of bias, with any disagreements adjudicated by a third reviewer. Where feasible, meta-analyses will be performed using random-effects models to pool odds ratios for associations between risk factors and CSCR. Heterogeneity of the included studies will be assessed using the I2 statistic. A narrative synthesis will be undertaken when meta-analysis is not possible, in accordance with Synthesis Without Meta-Analysis (SWiM) guidelines. Risk of bias will be assessed using the Newcastle-Ottawa Scale. The certainty of evidence will be evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system. Ethics and dissemination: Ethical approval is not required as this study uses previously published aggregate data. Findings will be disseminated through publication in peer-reviewed journal and presentation at relevant scientific conferences. Trial registration: This review protocol is registered with the International Prospective Register of Systematic Reviews (PROSPERO), under registration number CRD420251088489.