PURPOSE: Retinal microvasculopathy may reflect small vessel disease in the brain. Here we test
the relationships between retinal vascular parameters and small vessel disease, the influence
of cardiovascular risk factors on these relationships, and their common genetic background in
a monozygotic twin cohort.
METHODS: We selected 134 cognitively healthy individuals (67 monozygotic twin pairs) aged
‡60 years from the Netherlands Twin Register for the EMIF-AD PreclinAD study. We measured
seven retinal vascular parameters averaged over both eyes using fundus images analyzed with
Singapore I Vessel Assessment. Small vessel disease was assessed on MRI by a volumetric
measurement of periventricular and deep white matter hyperintensities. We calculated
associations between RVPs and WMH, estimated intratwin pair correlations, and performed
twin-specific analyses on relationships of interest.
RESULTS: Deep white matter hyperintensities volume was positively associated with retinal
tortuosity in veins (P ¼ 0.004) and fractal dimension in arteries (P ¼ 0.001) and veins (P ¼
0.032), periventricular white matter hyperintensities volume was positively associated with
retinal venous width (P ¼ 0.028). Intratwin pair correlations were moderate to high for all
small vessel disease/retinal vascular parameter variables (r ¼ 0.49–0.87, P < 0.001). Crosstwin
cross-trait analyses showed that retinal venous tortuosity of twin 1 could predict deep
white matter hyperintensities volume of the co-twin (r ¼ 0.23, P ¼ 0.030). Within twin-pair
differences for retinal venous tortuosity were associated with within twin-pair differences in
deep white matter hyperintensities volume (r ¼ 0.39, P ¼ 0.001).
CONCLUSIONS: Retinal arterial fractal dimension and venous tortuosity have associations with
deep white matter hyperintensities volume. Twin-specific analyses suggest that retinal venous
tortuosity and deep white matter hyperintensities volume have a common etiology driven by
both shared genetic factors and unique environmental factors, supporting the robustness of
this relationship