Retinal Microvascular Abnormalities Predict Progression of Brain Microvascular Disease An Atherosclerosis Risk in Communities Magnetic Resonance Imaging Study
ABSTRACT 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 cm(3); 95% confidence interval [CI], 0.74-5.96) or with arteriovenous nicking (2.61 cm(3); 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.
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ABSTRACT: BACKGROUND AND PURPOSE: The retinal and cerebral vasculature share similar anatomic, physiological, and embryological characteristics. We reviewed the literature, focusing particularly on recent population-based studies, to examine the relationship between retinal signs and stroke. Summary of Review- Hypertensive retinopathy signs (eg, focal retinal arteriolar narrowing, arterio-venous nicking) were associated with prevalent stroke, incident stroke, and stroke mortality, independent of blood pressure and other cerebrovascular risk factors. Diabetic retinopathy signs (eg, microaneurysms, hard exudates) were similarly associated with incident stroke and stroke mortality. Retinal arteriolar emboli were associated with stroke mortality but not incident stroke. There were fewer studies on the association of other retinal signs such as retinal vein occlusion and age-related macular degeneration with stroke, and the results were less consistent. CONCLUSIONS: Many retinal conditions are associated with stroke, reflecting possible concomitant pathophysiological processes affecting both the eye and the brain. However, the incremental value of a retinal examination for prediction of future stroke risk remains to be determined.Stroke 05/2008; 39(4):1371-9. DOI:10.1161/STROKEAHA.107.496091 · 6.02 Impact Factor
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ABSTRACT: Retinal microvascular abnormalities reflect cumulative small vessel damage from elevated blood pressure and may reflect subclinical cerebral microvascular changes. We examined their associations with MRI-defined cerebral infarcts. Population-based, cross-sectional study of 1684 persons 55 to 74 years of age without a history of clinical stroke, sampled from 2 US southeastern communities. Retinal photographs were obtained and graded for presence of retinal microvascular abnormalities, including arteriovenous nicking, focal arteriolar narrowing, retinal hemorrhages, soft exudates and microaneurysms. Photographs were also digitized, and retinal vessel diameters were measured and summarized as the arteriole-to-venule ratio (AVR). Cerebral MRI scans were graded for presence of cerebral infarct, defined as a lesion > or =3 mm diameter in a vascular distribution with typical imaging characteristics. There were a total of 183 MRI cerebral infarcts. After adjustment for age, gender, race, 6-year mean arterial blood pressure, diabetes, and other stroke risk factors, cerebral infarcts were associated with retinal microvascular abnormalities, with odds ratios 1.90 (95% CI, 1.25 to 2.88) for arteriovenous nicking, 1.89 (95% CI, 1.22 to 2.92) for focal arteriolar narrowing, 2.95 (95% CI, 1.30 to 6.71) for blot hemorrhages, 2.08 (95% CI, 0.69, 6.31) for soft exudates, 3.17 (95% CI, 1.05 to 9.64) for microaneurysms, and 1.74 (95% CI, 0.95 to 3.21) for smallest compared with largest AVR. In stratified analyses, these associations were only present in persons with hypertension. Retinal microvascular abnormalities are associated with MRI-defined subclinical cerebral infarcts independent of stroke risk factors. These data suggest that retinal photography may be useful for studying subclinical cerebrovascular disease in population-based studies.Stroke 01/2006; 37(1):82-6. DOI:10.1161/01.STR.0000195134.04355.e5 · 6.02 Impact Factor
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ABSTRACT: OBJECTIVE: Brain atrophy is common in subcortical ischemic vascular disease, but the underlying mechanisms are poorly understood. We set out to examine the effects of incident subcortical infarcts on cortical morphology. METHODS: A total of 276 subjects with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, an inherited small vessel disease, were enrolled in a prospective study. Incident subcortical infarcts were identified on follow-up magnetic resonance scans after 18, 36, and 54 months using difference images. Probabilistic fiber tracking and cortical thickness measurements were applied to study the longitudinal relationship between incident infarcts and connected cortical areas. Cortical thickness was assessed before and after infarction using FreeSurfer software. Focal cortical thinning was defined as change of cortical thickness in the connected region of interest exceeding the global change of cortical thickness. RESULTS: Nine subjects had a single incident infarct during the follow-up and were suitable for analysis. There was a strong correlation between the probability of connectivity and mean focal cortical thinning (p = 0.0039). In all subjects, there was focal cortical thinning in cortical regions with high probability of connectivity with the incident infarct. This pattern was not observed when using control tractography seeds. CONCLUSIONS: Our findings provide in vivo evidence for secondary cortical neurodegeneration after subcortical ischemia as a mechanism for brain atrophy in cerebrovascular disease.Neurology 10/2012; 79(20). DOI:10.1212/WNL.0b013e3182749f39 · 8.30 Impact Factor