Retinal Vascular Morphology Reflects and Predicts Cerebral Small Vessel Disease: Evidences from Eye-Brain Imaging Analysis.

Abstract

Cerebral small vessel disease (SVD) involves ischemic white matter damage and choroid plexus (CP) dysfunction for cerebrospinal fluid (CSF) production. Given the vascular and CSF links between the eye and brain, this study explored whether retinal vascular morphology can indicate cerebrovascular injury and CP dysfunction in SVD. We assessed SVD burden using imaging phenotypes like white matter hyperintensities (WMH), perivascular spaces, lacunes, and microbleeds. Cerebrovascular injury was quantified by WMH volume and peak width of skeletonized mean diffusivity (PSMD), while CP volume measured its dysfunction. Retinal vascular markers were derived from fundus images, with associations analyzed using generalized linear models and Pearson correlations. Path analysis quantified contributions of cerebrovascular injury and CP volume to retinal changes. Support vector machine models were developed to predict SVD severity using retinal and demographic data. Among 815 participants, 578 underwent ocular imaging. Increased SVD burden markedly correlated with both cerebral and retinal biomarkers, with retinal alterations equally influenced by cerebrovascular damage and CP enlargement. Machine learning models showed robust predictive power for severe SVD burden (AUC was 0.82), PSMD (0.81), WMH volume (0.77), and CP volume (0.80). These findings suggest that retinal imaging could serve as a cost-effective, noninvasive tool for SVD screening based on vascular and CSF connections.