Association Between Retinal Nerve Fiber Layer Cardiovascular-Kidney-Metabolic Syndrome: A UK Biobank Cohort Study

Abstract

center dot OBJECTIVE: To examine the association between retinal nerve fiber layer (RNFL) thickness and the severity of cardiovascular-kidney-metabolic (CKM) syndrome in a large community cohort. center dot DESIGN: Retrospective cross-sectional analysis of a community-based cohort. center dot PARTICIPANTS: UK residents 40 to 60 years of age at enrollment of UK Biobank. center dot METHODS: The cohort underwent baseline examination from April 2007 to October 2010. We analyzed high-quality optical coherence tomography images and identified the presence of CKM syndrome. We explored associations between RNFL and CKM syndrome severity using multivariable logistic regression. center dot MAIN OUTCOME MEASURES: Odds ratios (OR) for having advanced CKM syndrome (stage 3 or higher) at baseline were calculated after adjustment for age, sex, ethnicity, intraocular pressure, education and socioeconomic status. center dot RESULTS: A total of 17,082 participants were included (mean age 57.63 +/- 7.66 years old, 56.8% females) in the study, and 15,892 participants (93.0%) had CKM syndrome stage 1 or higher at baseline. Advanced CKM syndrome was observed more frequently in the thinnest quintile of RNFL thickness (14.8%) in comparison to the thickest quintile (9.1%). A multivariate regression controlling for potential confounders showed that decrease in RNFL thickness by 1 & micro;m increased the risk of having advanced CKM syndrome by 2.4% (OR 1.024, 95% CI: 1.010-1.039, P = .001) at baseline. center dot CONCLUSIONS: Thinner RNFL is associated with advanced CKM syndrome in individuals without a previous neurodegenerative or ocular disease. Our findings suggest that RNFL may serve as a valuable marker for monitoring disease severity of CKM syndrome. Further research, however, is warranted to investigate the pathways linking RNFL and CKM syndrome and to validate RNFL as a prognostic marker for CKM syndrome in larger populations. (Am J Ophthalmol 2026;288: 173-181. (c) 2026 Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)