Nonglaucomatous retinal nerve fibre layer defects as predictors of stroke and coronary heart disease in a large, longitudinal cohort.

OBJECTIVE

To determine whether nonglaucomatous retinal nerve fibre layer (RNFL) defects independently predict incident cerebral infarction or coronary heart disease.

DESIGN

Retrospective, observational cohort study.

PARTICIPANTS

A total of 80,996 adults from a health screening cohort (2011-2022) with gradable serial fundus photographs. Individuals with pre-existing ocular or vascular disease were excluded.

METHODS

RNFL defects were classified as glaucomatous or nonglaucomatous based on predefined imaging criteria. Multivariable logistic regression identified independent predictors. To ensure temporal validity, participants with prior stroke or coronary heart disease were excluded. A 1:3 propensity score-matched analysis compared outcomes between individuals with nonglaucomatous RNFL defects and matched controls. Vascular events were tracked through 2024.

RESULTS

Of 80,996 individuals, 787 had nonglaucomatous RNFL defects, 1,328 had glaucomatous defects, and 78,881 served as controls. Male sex (odds ratio [OR] 1.33), hypertension (OR 2.77), diabetes (OR 1.68), reduced eGFR, and younger age were independently associated with nonglaucomatous RNFL defects (all p < .05). In the matched cohort (747 vs 2,241), incident vascular events occurred in 7.5% of those with nonglaucomatous RNFL defects versus 0.6% in controls (OR 9.11; 95% CI: 5.37-15.48; p < .001).

CONCLUSIONS

Nonglaucomatous RNFL defects are strong independent predictors of future cerebral infarction or coronary heart disease. Routine fundus photography may provide systemic vascular risk insight beyond ophthalmic evaluation.