Retinal prognostic and surrogate markers of cerebrovascular dysfunction in cerebral small vessel disease

Sporadic cerebral small vessel disease (SVD) causes a quarter of strokes and nearly half of dementia cases, likely mediated by cerebrovascular dysfunction. Therefore, measuring small vessel dysfunction in the central nervous system of living humans is important for prognosis, understanding pathogenesis, and ultimately developing better treatments for SVD. The problem is that brain imaging cannot resolve individual cerebral microvessels and is unsuitable for population-level testing. However, retinal imaging can measure retinal vessel structure, as well as vasoreactivity and vascular permeability with micrometre accuracy. Dysfunctional reactivity and permeability are thought to contribute to SVD. I propose that retinal imaging can measure SVD pathogenesis and response to treatment well enough to provide prognostic and surrogate markers of SVD. I will investigate this within two existing longitudinal studies. This will have impact by evaluating retinal biomarkers of cerebrovascular dysfunction in SVD for the first time. Evidence for my hypotheses will support the next phase of clinical development of prognostic markers to forecast disease trajectory and surrogate markers to detect treatment response. Disproving my hypotheses would suggest that mechanisms driving cerebrovascular dysfunction depend on differences between retina and brain and help focus research on these areas.