Retinal Optical Coherence Tomography-Angiography and Longitudinal Changes in Cognition and Cerebral Small Vessel Disease

BACKGROUND AND OBJECTIVES: Cross-sectional studies suggest that retinal microvascular abnormalities measured by optical coherence tomography angiography (OCTA) are associated with cerebral small vessel disease (cSVD) and cognitive impairment, but longitudinal relationships remain unclear. We investigated whether OCTA measures are associated with brain cSVD markers and cognition over time and whether baseline OCTA was associated with brain and cognitive outcomes after mild ischemic stroke. METHODS: We conducted a prospective longitudinal cohort study recruiting patients with lacunar or mild cortical ischemic stroke (modified Rankin Scale ≤2) from a hospital stroke service. Participants underwent OCTA, brain MRI, and medical and cognitive assessment (MoCA) at baseline and 1 year. OCTA metrics included vessel density (VD), foveal avascular zone area, vessel radius, tortuosity, and flow index from superficial and deep vascular layers. MRI outcomes included white matter hyperintensity (WMH) volume, basal ganglia perivascular space (PVS) volume, and mean diffusivity in normal-appearing white matter. We used linear mixed-effects models to assess (1) whether retinal measures were associated with brain and cognitive markers over time and (2) whether baseline retinal measures were associated with 1-year outcomes, adjusting for age, sex, systolic blood pressure, smoking, diabetes, stroke severity, disability, and stroke subtype. RESULTS: A total of 189 participants (mean age 64.8 years; 37% female) were assessed at baseline and 154 at 1 year. Longitudinal reductions in retinal VD were associated with WMH increase (superficial layer, standardized β [95% CI] -0.045 [-0.067 to -0.023]; deep layer -0.050 [-0.074 to -0.026]). Increases in retinal VD and reductions in retinal flow were associated with increased PVS volume. Lower MoCA over 1 year tracked with decreases in deep retinal VD (0.136 [0.036-0.236]). Baseline retinal measures were associated with future outcomes: In particular, lower baseline VD in both layers was associated with worse MoCA at 1 year (superficial layer 0.125 [0.043-0.207]; deep layer 0.242 [0.162-0.322]). DISCUSSION: OCTA-measured retinal microvascular features are associated with cSVD progression and worsening cognition after mild stroke, while baseline OCTA was associated with future brain and cognitive outcomes. These findings suggest that OCTA holds promise as a noninvasive tool for monitoring retinal microvascular pathology in stroke populations enriched for cSVD, warranting further investigation in larger cohorts.