Impaired Retinal Vasoreactivity: An Early Marker of Stroke Risk in Diabetes

Abstract

Diabetes is a common cause of small vessel disease leading to stroke and vascular dementia. While the function and structure of large cerebral vessels can be easily studied, the brain's microvasculature remains difficult to assess. Previous studies have demonstrated that structural changes in the retinal vessel architecture predict stroke risk, but these changes occur at late disease stages. Our goal was to examine whether retinal vascular status can predict cerebral small vessel dysfunction during early stages of diabetes. Retinal vasoreactivity and cerebral vascular function were measured in 78 subjects (19 healthy controls, 22 subjects with prediabetes, and 37 with type-2 diabetes) using a new noninvasive retinal imaging device (Dynamic Vessel Analyzer) and transcranial Doppler studies, respectively. Cerebral blood vessel responsiveness worsened with disease progression of diabetes. Similarly, retinal vascular reactivity was significantly attenuated in subjects with prediabetes and diabetes compared to healthy controls. Subjects with prediabetes and diabetes with impaired cerebral vasoreactivity showed mainly attenuation of the retinal venous flicker response. This is the first study to explore the relationship between retinal and cerebral vascular function in diabetes. Impairment of venous retinal responsiveness may be one of the earliest markers of vascular dysfunction in diabetes possibly indicating subsequent risk of stroke and vascular dementia.

Non-invasive Assessment of Neurovascular Coupling After Aneurysmal Subarachnoid Hemorrhage: A Prospective Observational Trial Using Retinal Vessel Analysis

“…Because cerebral and retinal microvasculature bear a close anatomical correlation and are governed by common regulatory mechanisms, retinal vascular changes are increasingly recognized as potential screening option for altered NVC in the brain ( 14 , 15 ). For example, a potential role of RVA for predicting cerebrovascular changes has previously been shown in elderly adults ( 16 , 17 ), after coarctation repair ( 18 ) and in patients with diabetes ( 19 ) or Alzheimer's disease ( 20 ). During aSAH, the sudden rise of intracranial pressure often forces subarachnoid blood into the pre-retinal space ( 21 ), which may expose retinal micro-vessels to the same blood degradation products and inflammatory cytokines thought to be responsible for microvascular dysfunction in the brain.…”

Retinal microvascular function is associated with the cerebral microcirculation as determined by intravoxel incoherent motion MRI

“…Furthermore, transcranial Doppler measures blood flow in the larger cerebral vessels, while IVIM measures properties of the microvasculature. These previous studies did also show an inversed association between retinal arteriolar and venular dilation response and the pulsatility index as well as the resistency index in the middle cerebral artery [11,25], which both are considered to be indirect measures of microvascular compliance. The latter is more consistent with the findings in our study.…”

“…However, the exact pathophysiological mechanisms differing between arterioles and venules remain elusive. Two previous studies have examined the relation between retinal vasoreactivity and cerebral blood vessel function [11,25]. In one of these studies, patients were included based on the presence of WMH on brain MRI, and in the other one, patients were included based on the presence of diabetes mellitus.…”

Association between prediabetes/hyperglycemia and retinal diseases: A meta-analysis

“…26,30 Some studies have shown that retinal reactivity was impaired in prediabetes and type 2 diabetes and these results suggest that attenuation of the retinal venous flicker response occur during prediabetes and early stages of diabetes. 31,32 These studies included double-blind research method and also compared the measurement data directly, and the conclusions supported that prediabetes contribute to retinal structural or functional changes by new technology. In addition, the other studies found a positive correlation between macular choroidal thickness with fasting plasma glucose and HbA1c levels in prediabetic and diabetic patients.…”