Evidence continues to show that diabetic retinopathy (DR) reflects systemic microcirculatory disease affecting not only the eye but also other vital organs, and the presence of DR signifies an heightened risk of life-threatening systemic vascular complications. However, population-based studies have not provided conclusive evidence of the link between DR and stroke, which is what researchers aimed to determine in a recent literature review.

All cohort studies that reported associations between the presence of DR and incident stroke were included. The pooled hazard ratios (HRs) and risk ratios (RRs) were calculated. Though similar, HR describes risk of an event within a fixed time period while RR does not.

The meta-analysis included 19 cohort studies comprising 81,452 diabetic patients. Among any diabetes patient with DR, their stroke HR was 1.25 and RR was 1.96. Subgroup analysis looking at the type of diabetes yielded HR of 1.29 in patients with type 2 diabetes mellitus (T2DM) and RR of 2.29. Two studies addressed the DR-related stroke among type 1 diabetes mellitus (T1DM) patients. One study found a significant association between DR and stroke, while the other did not identify an association between these two conditions.

The authors noted the link between DR and stroke in diabetic patients can be explained by the fact that diabetes-related changes in the retinal microvasculature mirror those in the cerebral microvasculature.

“In the subgroup analysis, we observed a strong association between any DR and stroke in T2DM, but this association was uncertain in T1DM. This could be explained by shared risk factors for DR and stroke, such as poor glycemic control, high blood pressure and dyslipidemia, which are more often present in T2DM than T1DM due to the relatively older age,” the authors explained in their study. “However, the underlying mechanism of the difference between the effects of T2DM and T1DM needs to be further clarified.”

To better understand the pathophysiology of a DR-related stroke, they conducted two subgroup analyses for subtypes of stroke and subtypes of ischemic stroke. The result suggested that DR was significantly associated with ischemic stroke.

“One study showed that DR was a predictor of small-artery ischemic stroke but not large-artery ischemic stroke,” the authors explained. “Moreover, two studies found DR was not associated with hemorrhagic stroke. These findings are consistent with the role of cerebral microvascular dysfunction in diabetes.”

The detailed analysis of the association between DR and stroke documented that the risk of stroke was 2.08 times higher in patients with moderate nonproliferative diabetic retinopathy or more severe DR than in subjects without ocular involvement, which was significantly higher than the risk of stroke in patients with any DR.

Hu K, Jiang M Zhou Q, et al. Association of diabetic retinopathy with stroke: a systemic review and meta-analysis. Front Neurol. 2021;12;626996.