Abstract:AIM: To assess risk factors for epiretinal membranes (ERM) and examine their interactions in a nationally representative U.S. dataset. METHODS: Data from the 2005–2008 National Health and Nutrition Examination Survey (NHANES) were analyzed, a nationally representative U.S. dataset. ERM was identified via retinal imaging based on the presence of cellophane changes. Key predictors included age group, eye surgery history, and refractive error, with additional demographic and health-related covariates. Weighted univariate and multiple logistic regression models were used to assess associations and interaction effects between eye surgery and refractive error. RESULTS: Totally 3925 participants were analyzed. Older age, eye surgery, and refractive errors were significantly associated with ERM. Compared to those under 65y, the odds ratio (OR) for ERM was 3.08 for ages 65–75y (P=0.0014) and 4.76 for ages 75+ years (P=0.0069). Eye surgery increased ERM risk (OR=3.48, P=0.0018). Moderate to high hyperopia and myopia were also associated with ERM (OR=2.65 and 1.80, respectively). A significant interaction between refractive error and eye surgery was observed (P<0.0001). Moderate to high myopia was associated with ERM only in those without eye surgery (OR=1.92, P=0.0443). Eye surgery was most strongly associated with ERM in the emmetropic group (OR=3.60, P=0.0027), followed by the moderate to high myopia group (OR=3.01, P=0.0031). CONCLUSION: ERM is significantly associated with aging, eye surgery, and refractive errors. The interaction between eye surgery and refractive error modifies ERM risk and highlights the importance of considering combined effects in clinical risk assessments. These findings may help guide individualized ERM risk assessment that may inform personalized approaches to ERM prevention and management.