Retinal microvascular abnormalities and risk of lacunar stroke: Atherosclerosis risk in communities study

Background and purpose: The retinal microvasculature reflects cumulative small-vessel damage from hypertension and other vascular processes. No study has prospectively examined retinal findings in relation to the incidence of clinical lacunar stroke in comparison with other ischemic stroke subtypes. Methods: In 10 496 adults initially free of stroke, we related retinal findings imaged during 1993 to 1995 with the incidence of hospitalized ischemic strokes through 2005. Results: During a median of 11.2 years of follow-up, 338 incident ischemic strokes occurred (66 lacunar, 192 nonlacunar thrombotic, and 80 cardioembolic). Generalized arteriolar narrowing as measured by the central retinal arteriole equivalent was associated with an increased incidence of lacunar stroke (multivariate-adjusted hazard ratio [HR] per 1-SD decrement of central retinal arteriole equivalent=1.67; 95% CI, 1.23-2.26) but was not associated with other ischemic stroke subtypes. Generalized venular widening as measured by the central retinal venule equivalent was also positively associated with only lacunar stroke (multivariate-adjusted HR per 1-SD increment=1.44; 95% CI, 1.09-1.91). Retinal microvascular abnormalities were positively associated with lacunar stroke incidence (HR for focal arteriolar narrowing=2.22; 95% CI, 1.11=4.48; for arteriovenous nicking, HR=2.38; 95% CI, 1.20-4.71), whereas retinopathy signs (microaneurysms, retinal hemorrhages, and others) were positively associated with nonlacunar thrombotic (HR=2.41; 95% CI, 1.47-3.95) and cardioembolic (HR=2.25; 95% CI, 1.09-4.65) stroke incidence. Conclusions: A narrower central retinal arteriole equivalent, wider central retinal venule equivalent, focal arteriolar narrowing, and arteriovenous nicking were predictive of lacunar stroke. Retinal imaging is useful in understanding the pathophysiology and mechanisms of cerebral small-vessel disease.