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.

Retrospective cross-sectional analysis of a community-based cohort.

UK residents 40 to 60 years of age at enrollment of UK Biobank.

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.

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.

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 µm increased the risk of having advanced CKM syndrome by 2.4% (OR 1.024, 95% CI: 1.010-1.039, P = .001) at baseline.

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.