Retinal and Cerebral Microvascular Signs and Diabetes

Abstract

OBJECTIVE-Diabetes increases the risk for microvascular disease. The retina and the brain both have intricate microvascular systems that are developmentally similar. We sought to examine whether microvascular lesions in the retina and in the brain are associated and whether this association differs among people with and without diabetes. RESEARCH DESIGN AND METHODS-The analysis included 4,218 participants of the Icelandic population-based Age, Gene/Environment Susceptibility-Reykjavik Study who were born in 1907-1935 and who were previously followed as a part of the Reykjavik Study. Retinal focal arteriolar narrowing, arteriovenous (AV) nicking, and microaneurysms/hemorrhages were evaluated on digital retinal images of both eyes. Cerebral microbleeds (CMBs) were evaluated from magnetic resonance images. Data were analyzed with logistic and multinomial logistic regression models controlling for demographics, major cardiovascular risk factors, cerebral infarcts, and white matter lesions. D evelopmentally, the retina is an outgrowth of the brain and shares with the brain similar microvascular properties in anatomy, physiology, and metabolic activities (1,2). Microvascular systems in both the retina and the brain may be affected by atherosclerotic, hemodynamic, or other metabolic factors that affect large, small, and microblood vessels (3,4). Population-based epidemiological studies have shown that retinal microvascular abnormalities, such as arteriovenous (AV) nicking, microaneurysms, and hemorrhages, are associated with an increased risk of clinical stroke and cerebral white matter lesions (WMLs) (5-8), a marker for small-vessel disease. To date, no population-based studies have examined the relation of retinal microvascular signs to cerebral microbleeds (CMBs), which indicate the presence of hemorrhagic microvascular lesions or microangiopathy in the brain (9). CMBs are histopathologically confirmed signals on magnetic resonance image (MRI) that signify hemosiderin deposits due to frank minor hemorrhages or blood leakage through small blood vessels (10). Clinical studies suggest that CMBs are associated with an increased risk for intracerebral hemorrhages and serve as the basis for a clinical diagnosis of cerebral amyloid angiopathy (9,11,12). RESULTS-EvidenceIndividuals with diabetes are known to be at an increased risk for microvascular lesions of both the retina and the brain. Diabetes also is associated with cognitive disorders (13-15) and with brain structural changes in large and small vessels (16,17). Therefore, it is biologically plausible to hypothesize that the strength of association between retinal and cerebral microvascular lesions may be greater in people with diabetes compared with those without the disease.In this population-based study of older adults, we sought to investigate whether retinal microvascular signs are associated with microbleeds in the brain and whether the association between retinal microvascular lesions and brain microbleeds varies by diabetes status. RESEARCH DESIGN AND METHODS...

Increased Burden of Cerebral Small Vessel Disease in Patients With Type 2 Diabetes and Retinopathy

“…Regarding cross-sectional studies performed in patients with type 2 diabetes who have used the same methods as ours (i.e., visual rating scales), conflicting results have been described to evaluate the presence and severity of WMLs. Some have described (6) a higher frequency and severity of WMLs compared with people without DM (7,25), especially WMLs located in the deep cerebral area, whereas others have found no differences. However, with the use of more sensitive brain magnetic resonance Values are reported as n (%) unless otherwise indicated.…”

Cerebral microbleeds, retinopathy, and dementia

“…Extant studies show that retinal microvascular lesions are strongly correlated with cerebral small vessel disease such as white matter lesions and CMBs, 11,[15][16][17] suggesting that these retinal microvascular signs are markers for cerebral microvascular disease. Thus, studying retinal microvascular signs is another approach to indirectly measuring cerebral microvascular disease.…”

“…Supplemental data at www.neurology.org people with hypertension, [2][3][4] cerebral amyloid angiopathy (CAA), [2][3][4]9 cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, 2,10 stroke, [2][3][4] and diabetes and retinopathy, 11 all conditions reported to be associated with cognitive impairment. 9,10,12,13 Indeed, cognitive consequences of CMBs have been noted in several patient-based studies, [2][3][4]14 but data from population-based studies are lacking.…”

“…11,23 At the Ocular Epidemiology Reading Center, University of Wisconsin, 3 certified graders assessed retinal images for the presence of retinopathy lesions and retinal arteriolar signs (focal arteriolar narrowing and arteriovenous nicking) following a validated protocol. 16 Retinopathy lesions included retinal blot hemorrhages, microaneurysms, soft exudates, and other less common lesions such as hard exudates, macular edema, and optic disc swelling.…”

“…24 The quality control procedure and intergrader and intragrader reliability for assessing retinal microvascular signs have been reported elsewhere. 11,16 MRI acquisition and reading protocol. High-resolution MRI was acquired on a 1.5-T Signa Twinspeed System (General Electric Medical Systems, Waukesha, WI).…”