Retinal and Cerebral Microvasculopathy: Relationships and Their Genetic Contributions

Invest Ophthalmol Vis Sci. 2018 Oct 1;59(12):5025-5031. doi: 10.1167/iovs.18-25341.


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 = 0.004) and fractal dimension in arteries (P = 0.001) and veins (P = 0.032), periventricular white matter hyperintensities volume was positively associated with retinal venous width (P = 0.028). Intratwin pair correlations were moderate to high for all small vessel disease/retinal vascular parameter variables (r = 0.49-0.87, P < 0.001). Cross-twin cross-trait analyses showed that retinal venous tortuosity of twin 1 could predict deep white matter hyperintensities volume of the co-twin (r = 0.23, P = 0.030). Within twin-pair differences for retinal venous tortuosity were associated with within twin-pair differences in deep white matter hyperintensities volume (r = 0.39, P = 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Twin Study

MeSH terms

  • Aged
  • Cardiovascular Diseases / epidemiology
  • Cerebrovascular Disorders / diagnostic imaging
  • Cerebrovascular Disorders / genetics*
  • Cohort Studies
  • Female
  • Gene-Environment Interaction*
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Registries
  • Retinal Diseases / diagnostic imaging
  • Retinal Diseases / genetics*
  • Retinal Vessels / pathology*
  • Risk Factors
  • Twins, Monozygotic / genetics*
  • White Matter / diagnostic imaging
  • White Matter / pathology*