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Stroke. 2014 Apr;45(4):1012-7. doi: 10.1161/STROKEAHA.113.004166. Epub 2014 Feb 18.

Retinal microvascular abnormalities predict progression of brain microvascular disease: an atherosclerosis risk in communities magnetic resonance imaging study.

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From the Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia (T.C.H.); Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD (A.R.S., R.F.G.); Department of Medicine-Geriatrics, University of Mississippi Medical Center, Jackson (T.H.M.); Department of Radiology, University of Washington Medical Center, Seattle (D.S.); Department of Neurology, Mayo Clinic, Rochester, MN (D.S.K.); Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison (R.K., B.E.K.K.); and Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD (R.F.G.).



Brain microvascular disease leads to leukoaraiosis and lacunar infarcts and contributes to risk of stroke and cognitive decline. Given a shared pathophysiology, retinal microvascular signs are expected to predict brain microvascular disease progression. We investigated if either leukoaraiosis volume progression measured continuously or combined with incident lacunar infarcts would better demonstrate expected associations with retinal disease than has previously been shown.


Eight hundred thirty participants in the Atherosclerosis Risk in Communities (ARIC) study aged ≥55 years and without previous stroke received an initial brain magnetic resonance imaging, retinal photography, and, 10 years later, a follow up magnetic resonance imaging. We evaluated retinal vascular sign phenotypes as predictors of (1) leukoaraiosis volume increase, and (2) a new score combining leukoaraiosis volume change and incident lacunar infarcts. Hypertension and diabetes mellitus were evaluated as confounders and effect modifiers.


Individuals with any retinopathy (3.34 cm3; 95% confidence interval [CI], 0.74-5.96) or with arteriovenous nicking (2.61 cm3; 95% CI, 0.80-4.42) each had greater progression of leukoaraiosis compared with those without these conditions. Any retinopathy (odds ratio [OR], 3.18; 95% CI, 1.71-5.89) or its components-microaneurysms (OR, 3.06; 95% CI, 1.33-7.07) and retinal hemorrhage (OR, 3.02; 95% CI, 1.27-7.20)-as well as arteriovenous nicking (OR, 1.93; 95%, CI 1.24-3.02) and focal arteriolar narrowing (OR, 1.76; 95% CI, 1.19-2.59), were associated with a higher quartile of a novel brain microvascular disease score combining leukoaraiosis progression with incident subclinical lacunes.


A novel scoring method revealed associations of retinal signs with leukoaraiosis progression and brain microvascular disease, which have not been shown before.


leukoaraiosis; retina

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