Abstract-Abnormalities of the retinal microcirculation are found in hypertension and diabetes and predict cardiovascular mortality. This study examined the relationship between abnormalities of the retinal microvasculature and death from ischemic heart disease (IHD) and stroke. A population-based, nested case-control study was undertaken within the Beaver Dam Eye Study. Subjects (43 to 74 years) who died of IHD (nϭ126) or stroke (nϭ28) over a 10-year period were age and gender matched with controls subjects (nϭ528; case:control matching, Ϸ1:4). Retinal photographs of cases and controls were digitized and analyzed using a computer-based technique. Increased risk of IHD death was associated with a suboptimal relationship of arteriolar diameters at bifurcation (Pϭ0.02 unadjusted) and decreased retinal arteriolar tortuosity (Pϭ0.011 unadjusted). These associations remained significant after adjustment for age, sex, past history of cardiovascular disease, and other known cardiovascular risk factors. Increased arteriolar length:diameter ratio, a measure of generalized arteriolar narrowing, was associated with increased stroke mortality (Pϭ0.02 unadjusted). This association was independent of age and gender but was attenuated by adjustment for systolic blood pressure (Pϭ0.15). Other quantitative measures of the retinal microvascular network (eg, venular tortuosity and arteriolar and venular bifurcation angle) were not associated with death from IHD or stroke. Retinal microvascular abnormalities are predictive of death from IHD and stroke. A detailed assessment of the retinal microvascular network from digitized photographs may be useful in the noninvasive assessment of target organ damage and cardiovascular risk.

BACKGROUND-The impact of early life factors on the microvasculature is relatively unknown.

Background Recent studies have shown that changes in the retinal microvasculature predict cardiovascular disease (CVD); however, little is known regarding influences on the retinal microvasculature in healthy people without overt cardiovascular or metabolic disease. Methods We used a semiautomated computerized technique to analyze digitized retinal photographs from a total of 167 healthy people (age range, 45–75 years; 83 female), without clinical CVD, diabetes, or hypertension, randomly sampled from the population-based Beaver Dam Eye Study. We assessed arteriolar and venular narrowing, arteriolar optimality deviation, and other quantitative aspects of the retinal microvasculature. Results Arterioles were significantly narrower and longer, had wider branching angles, and were more tortuous than venules. Increased arteriolar length to diameter ratio (an index of arteriolar narrowing) was positively and independently associated with older age and elevated systolic blood pressure. Arteriolar optimality deviation (an index of microvascular endothelial dysfunction) increased with greater body mass index. Current smoking and increased white blood cell (WBC) count was associated with wider venules. After controlling for smoking, WBC was no longer a significant predictor of venular diameter. Conclusions CVD risk factors are associated with retinal microvascular changes in healthy individuals without evidence of CVD, diabetes, or hypertension. CVD risk factors have different influences on the arteriolar and venular bed.

Our numerical results are in good agreement with in vivo measurements reported in the literature, demonstrating the potential of our model for prediction of oxygen distribution and intravascular oxygen tension profiles in the retinal arterial network. This paves the way for investigating the effects of parameter variation, simulating cases not available from experimental studies.

Abnormalities of the retinal microvasculature are independently associated with stroke, cerebral infarcts, and white matter lesions.

Changes in the retinal microcirculation are associated with hypertension and predict cardiovascular mortality. There are few data describing the impact of antihypertensive therapy on retinal vascular changes. This substudy of the Anglo-Scandinavian Cardiac Outcomes Trial compared the effects of an amlodipine-based regimen (373 patients) with an atenolol-based regimen (347 patients) on retinal microvascular measurements made from fundus photographs. The retinal photographs were taken at a stage in the trial when treatments were stable and blood pressure was well controlled. Amlodipine-based treatment was associated with a smaller arteriolar length:diameter ratio than atenolol-based treatment (13.32 [10.75 to 16.04] versus 14.12 [11.27 to 17.81], median [interquartile range]; P<0.01). The association remained significant after adjustment for age, sex, cholesterol, systolic and diastolic blood pressures, body mass index, smoking, and statin treatment. This effect appeared to be largely attributable to shorter retinal arteriolar segment lengths in the amlodipine-treated group and is best explained by the vasodilator effects of amlodipine causing the visible emergence of branching side vessels. Photographic assessment of the retinal vascular network may be a useful approach to evaluating microvascular structural responses in clinical trials of antihypertensive therapy.

Arterial diameters at branch points are believed to conform to design principles that optimize circulatory efficiency and maintain constant shear stress across arterial networks. The objective of this study was to examine whether optimality at bifurcations is affected in individuals with atherosclerosis. Retinal images were analysed in normotensive men with abnormal ankle brachial index (n=13) and healthy controls (n=8), matched for age and clinic blood pressure. Compared with controls, men with peripheral vascular disease had adverse metabolic profiles (relative insulin resistance and greater total cholesterol levels). In healthy men, retinal arterial diameters at bifurcations conformed to predicted optimal values but in men with peripheral vascular disease, junction exponents deviated significantly from the optimum. Retinal arteriolar bifurcation angles did not differ significantly between the groups. Atherosclerosis is associated with abnormalities in the arteriolar network of the retina. In view of the importance of the endothelium in maintaining network co-ordination of branch diameters this is suggestive of a generalized abnormality of endothelial function in atherosclerosis.

A B S T R A C TArterial diameters at branch points are believed to conform to design principles that optimize circulatory efficiency and maintain constant shear stress across arterial networks. The objective of this study was to examine whether optimality at bifurcations is affected in individuals with atherosclerosis. Retinal images were analysed in normotensive men with abnormal ankle brachial index (n l 13) and healthy controls (n l 8), matched for age and clinic blood pressure. Compared with controls, men with peripheral vascular disease had adverse metabolic profiles (relative insulin resistance and greater total cholesterol levels). In healthy men, retinal arterial diameters at bifurcations conformed to predicted optimal values but in men with peripheral vascular disease, junction exponents deviated significantly from the optimum. Retinal arteriolar bifurcation angles did not differ significantly between the groups. Atherosclerosis is associated with abnormalities in the arteriolar network of the retina. In view of the importance of the endothelium in maintaining network co-ordination of branch diameters this is suggestive of a generalized abnormality of endothelial function in atherosclerosis.