Background: The retinal and cerebral microvasculature share many morphological and physiological properties. Perivascular Spaces (PVS), also known as Virchow-Robin spaces, are visible with increasing resolution with the ongoing improvement of brain MRI technology. We investigated the associations between quantitative retinal measurements and novel computational PVS parameters in a cohort of older people in their eighth decade. Methods: We analysed data from community-dwelling individuals (n=381 of 866) from the Lothian Birth Cohort 1936, who underwent multimodal brain MRI and retinal fundus camera imaging at mean age 72.55 years (SD=0.71). We assessed PVS computationally in the centrum semiovale. We calculated the total volume and count of PVS, and the mean per-subject individual PVS length, width and size. Digital retinal images were analysed using the VAMPIRE software suite, obtaining the Central Retinal Artery and Vein Equivalents (CRVE and CRAE), Arteriole-to-Venule ratio (AVR), and fractal dimension (FD) of both eyes. We investigated the associations between computational PVS measurements and retinal vascular measurements using general linear models. We adjusted for age, gender and important covariates (hypertension, diabetes, cholesterol, cardiovascular disease history and smoking). Results: In 381 subjects with all measures, increasing total volume and count of PVS were associated with decreased CRAE in the left eye (volume β=-0.170 p<0.001; count β=-0.184, p<0.001). No associations of PVS with CRVE were found. The PVS total volume, individual width and size were associated with the FD of the arterioles (a) and venules (v) of the left eye (total volume: FDa β=-0.137, FDv β=-0.139, both p<0.01; width: FDa β=-0.144, FDv β=-0.158, both p<0.01; size: FDa β=-0.157, p=0.002; FDv β=-0.162, p=0.001). Conclusions: We show that worse brain PVS computational metrics associate with narrower retinal arterioles and lower retinal microvessel branching complexity, providing more direct evidence in vivo in humans of the microvessel changes underlying brain small vessel disease.

Quantitative Measurements of Enlarged Perivascular Spaces in the Brain are Associated with Retinal Microvascular Parameters in Older Community-Dwelling Subjects