Association between optical coherence tomography–quantified retinal features and cardiovascular risk in cardiovascular–kidney–metabolic syndrome stages 0–3: An analysis of a prospective UK biobank cohort

BACKGROUND: Cardiovascular-kidney-metabolic (CKM) syndrome is strongly associated with cardiovascular disease (CVD) and mortality. Stages 0-3 represent a key preclinical window for early intervention. Retinal optical coherence tomography (OCT) enables non-invasive evaluation of systemic microcirculation, but its prognostic value for CVD in CKM 0-3 remains undetermined. METHODS: We conducted a prospective study of 40,516 UK Biobank participants with CKM syndrome stages 0-3 who had retinal OCT. Cox regression, trend tests, and predictive metrics (NRI, IDI, AUC) were used to evaluate associations and incremental prognostic value of retinal structural markers. RESULTS: Baseline thinner retinal nerve fiber layer (RNFL) and macular thickness were independently associated with higher risks of incident CVD, coronary heart disease, all-cause mortality, and cardiovascular mortality over a subsequent median 14.6-year follow-up (all P < 0.001). Significant linear dose-response relationships were observed. Adding these markers to traditional risk models improved risk classification and discrimination (all P < 0.001). CONCLUSION: Thinner RNFL and macular thickness are independent predictors of adverse cardiovascular outcomes in CKM 0-3. Integrating these OCT-derived biomarkers improves risk stratification, supporting a non-invasive approach for early cardiovascular risk assessment in this high-risk population.