Retinal Microvascular Correlates of Cerebral Small Vessel Disease in Older Age

BACKGROUND AND OBJECTIVES: Cerebral small vessel disease (cSVD), characterized by pathologic changes in the structure and function of small brain vessels, is detectable on brain MRI in the absence of clinical symptoms. However, imaging cerebral small vessels themselves in vivo remains costly and challenging. There is growing interest in investigating whether retinal microvascular imaging features could be proxies for changes in the brain microvasculature. Using a multipronged approach, we explored the relation of retinal microvascular characteristics with MRI markers of cSVD (MRI-cSVD). METHODS: First, we explored this relationship in older community persons from the population-based 3C-Dijon cohort. MRI-cSVD was assessed on a 1.5-Tesla MRI at baseline, comprising white matter hyperintensity volume (WMHV), lacunes, and a composite extreme cSVD phenotype (WMHV extreme distributions and presence/absence of lacunes). At 10-year follow-up, participants underwent measurements of retinal microvascular features on fundus using the Singapore "I" Vessel Assessment software. To support 3C-Dijon findings, we conducted a comprehensive literature review up to July 2024 from PubMed/EMBASE and used 2-sample Mendelian randomization (MR) leveraging large-scale genome-wide association studies, to assess causality and directionality. RESULTS: = 0.0017 and 0.049), with no evidence for reverse causation. DISCUSSION: We provide multimodal evidence that geometric characteristics of the retinal microvasculature are associated with increased burden of MRI-cSVD and possibly worse executive function.