Association between retinal microvascular pathology and lacunar infarction: a systematic review and meta-analysis

Lacunar infarctions, a subtype of cerebral small vessel disease, arise from occlusion of deep penetrating arterioles and contribute substantially to ischemic stroke burden and long-term disability. Because the retinal microvasculature shares anatomical and physiological features with cerebral arterioles, retinal imaging provides a noninvasive proxy for studying systemic microvascular pathology. Evidence linking retinal vascular abnormalities to lacunar infarction has been inconsistent, warranting systematic evaluation.

We systematically searched PubMed, Embase, Scopus, Web of Science, and the Cochrane Library for studies examining associations between retinal vascular changes and lacunar infarction. The primary outcome was lacunar infarction (confirmed by imaging or clinical diagnosis), while retinal vascular features (focal arteriolar narrowing, arteriovenous nicking, retinopathy, and venular dilation) were analyzed as exposure variables. Odds ratios (ORs) with 95% confidence intervals (CIs) were pooled using a random-effects model. Risk of bias was assessed using the NIH Quality Assessment Tool for Observational Studies.

Eight studies (n = 7277 participants) were included. All studies demonstrated good methodological quality based on the NIH Quality Assessment Tool for Observational Studies. Meta-analyses showed significant associations between lacunar infarction and focal arteriolar narrowing (OR = 1.77, 95% CI 1.14-2.74, p = 0.01, I² = 81%), arteriovenous nicking (OR = 1.70, 95% CI 1.05-2.76, p = 0.03, I² = 69%), retinopathy (OR = 1.99, 95% CI 1.21-3.25, p = 0.006, I² = 46%), and venular dilation (OR = 1.46, 95% CI 1.11-1.93, p = 0.007, I² = 56%). Heterogeneity ranged from moderate to high and was partly reduced in sensitivity analyses. Funnel plot asymmetry suggested potential publication bias for several parameters, supported by Egger's test (focal arteriolar narrowing p = 0.04; arteriovenous nicking p = 0.041; retinopathy p = 0.032), while no significant bias was detected for venular dilation (p = 0.08).

Retinal microvascular abnormalities are significantly associated with lacunar infarction, supporting the retina as a window into cerebral small vessel pathology. These findings emphasize the prospective role of retinal imaging as a noninvasive biomarker for identifying individuals at risk of lacunar stroke. Future large-scale, prospective studies are needed to confirm causality and improve clinical translation.