Retinal Vasculopathy – A Potential Early Predictor of Stroke Risk

Impaired retinal vasodilator responses may be an early marker of microvascular disease or endothelial dysfunction and a potential predictor of cerebrovascular risk based on findings from studies in diabetic and prediabetic patients.1,2 Kerstin Bettermann, MD, PhD, associate professor, department of neurology, Penn State Health Milton S. Hershey Medical Center, explains, “Retinal blood flow is controlled by autoregulatory metabolic and pressure mechanisms, which are impaired in diabetes. We also know that impairment of the retinal microvasculature is associated with cerebral ischemia.3 Given these two facts, looking at retinal vasodilator responses may be a low-cost, non-invasive strategy to assess risk for stroke and possibly other cerebrovascular risks in a wide range of individuals in the community.” Dr. Bettermann believes that with further validation, screening for retinal vasculopathy may become part of routine eye exams.

Retinal arterial vasoreactivity over time following flicker light stimulation

Retinal arterial vasoreactivity over time following flicker light stimulation

The retina is a unique site to study the human microcirculation. Through their research program, Dr. Bettermann and colleagues have been focused on characterizing the nature and underlying mechanisms of attenuated retinal vasodilator responses in patients with prediabetes and diabetes. Using a retinal dynamic vessel analyzer (Imedos Inc., Germany), vasoreactivity to dilatory stimuli, such as a flickering light, is similarly and significantly attenuated in both prediabetic and diabetic patients, compared with healthy controls. In healthy controls, mean percent increase (± standard deviation) in retinal vessel diameter was 5.6 percent ± 2.6, versus only 3.3 percent ± 1.8 in diabetics and 3.3 percent ± 2.2 in prediabetics. Dr. Bettermann notes, “We were somewhat surprised to find that very significant changes in the vasculoreactivity are already present in prediabetics. These findings suggest that retinal vasoreactivity is very sensitive to changes in endothelial function and can detect vasculopathy very early in the disease process when interventions are most likely to have an impact.”

This and other more recent research has more closely examined the inflammatory markers that may play a role in retinal vasculopathy. While C-reactive protein is not correlated with observed vasculopathy,2 Dr. Bettermann has uncovered evidence demonstrating a link between other inflammatory markers and vasculopathy, which point the way toward molecular targets for intervention, and are expected to be published later in 2016.

As retinal and cerebral microcirculatory systems share key anatomical and physiological similarities, retinal vasoreactivity may serve as an accessible surrogate for the cerebral microvasculature, which is not currently feasible to routinely visualize. Dr. Bettermann says, “Our pilot studies provide strong support and a rationale for conducting large, long-term prospective studies to determine whether impaired retinal vasoreactivity predicts events like stroke or myocardial infarction. Measuring retinal vasoreactivity is easy to perform, non-invasive and low in cost, making it a potential screening tool in routine eye exams. Early detection of vasculopathy may serve as a means for intervention and possible prevention of major cerebrovascular events.”

Photo of Kerstin Bettermann, MD, PhDKerstin Bettermann, MD, PhD
Associate Professor, Department of Neurology
PHONE: 717-531-3828
FELLOWSHIP: Stroke, Wake Forest University Baptist Medical Center, Winston Salem, N.C.
RESIDENCIES: Neurology, Wake Forest University Baptist Medical Center, Winston Salem, N.C.; Psychiatry, University of Duesseldorf, Duesseldorf, Germany; Neurology, Technical University of Munich, Munich, Germany
MEDICAL SCHOOL: University of Heidelberg, Heidelberg, Germany
Connect with Dr. Bettermann on Doximity


  1. Lott ME, Slocomb JE, Gao Z, Gabbay RA, Quillen D, Gardner TW, Bettermann K. 2015. Impaired coronary and retinal vasomotor function to hyperoxia in individuals with Type 2 diabetes. Microvasc Res. 101:1-7.
  2. Lott ME, Slocomb JE, Shivkumar V, Smith B, Quillen D, Gabbay RA, Gardner TW, Bettermann K. 2013. Impaired retinal vasodilator responses in prediabetes and type 2 diabetes. Acta Ophthalmol. 91(6):e462-9.
  3. Bettermann K, Slocomb JE, Shivkumar V, Lott ME. 2012. Retinal vasoreactivity as a marker for chronic ischemic white matter disease? J Neurol Sci. 322:206-10.

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