Association of retinal vascular signs with intracranial atherosclerotic stenosis

BACKGROUND AND PURPOSE: Given that early screening for intracranial atherosclerotic stenosis (ICAS) is crucial for preventing ischemic cerebrovascular events and that the retinal and cerebral vasculature exhibit parallel anatomical and physiological characteristics, this study investigate the association between retinal vascular signs and ICAS, exploring their potential as noninvasive biomarkers and providing novel pathophysiological insights. METHODS: Participants aged 30 years or older who had undergone computed tomography angiography (CTA), magnetic resonance angiography (MRA), and fundus photography were recruited from three general hospitals for this multi-center, cross-sectional study. Intracranial atherosclerotic stenosis was evaluated based on CTA or MRA images. Qualitative assessment of retinal vascular signs was performed using fundus photographs, and retinal vascular parameters were automatically quantified by a semi-automated, deep learning-based algorithm. RESULTS: A total of 531 participants from three hospitals were included in this study, comprising 272 individuals with ICAS and 259 without ICAS. Compared to those without ICAS, participants with ICAS showed a significantly higher prevalence of focal arteriolar narrowing (FAN) (14.3% vs. 7.7%, P = 0.015), enhanced arterial light reflex (EALR) (34.2% vs. 22.8%, P = 0.004), and any retinal vessel wall signs (46.0% vs. 30.9%, P = 0.001), as well as wider retinal venules (213.0 µm vs. 206.7 µm, P = 0.015). In multivariate-adjusted analyses, FAN (odds ratio [OR], 2.4; 95% confidence interval [CI] (1.3–4.4)), EALR (OR, 2.3; 95% CI [1.5–3.6]), and any retinal vessel wall signs (OR, 2.5; 95% CI [1.7–3.8]) remained significantly associated with ICAS. These associations persisted even after excluding participants with extracranial artery stenosis. Furthermore, any retinal vessel wall signs were independently associated with ICAS both in participants with (OR, 2.4; 95% CI [1.3–4.5]) or without (OR, 6.1, 95% CI [1.7–22.3]) hypertension and diabetes. CONCLUSIONS: Retinal vessel wall signs are independently associated with intracranial atherosclerotic stenosis, indicating their potential as a noninvasive biomarker for ICAS. These signs likely reflect intracranial atherosclerotic injury to the vascular wall and may thus provide insights for the development of early screening protocols and clinical management strategies for ICAS.