Retinal capillary microvessel morphology changes are associated with vascular damage and dysfunction in cerebral small vessel disease

Abstract

Cerebral small vessel disease (SVD) is a cause of stroke and dementia. Retinal capillary microvessels revealed by optical coherence tomography angiography (OCTA) are developmentally related to brain microvessels. We quantified retinal vessel density (VD) and branching complexity, investigating relationships with SVD lesions, white matter integrity on diffusion tensor imaging (DTI) and cerebrovascular reactivity (CVR) to CO₂ in patients with minor stroke. We enrolled 123 patients (mean age 68.1 ± SD 9.9 years), 115 contributed retinal data. Right (R) and left (L) eyes are reported. After adjusting for age, eye disease, diabetes, blood pressure and image quality, lower VD remained associated with higher mean diffusivity (MD) (standardized β; R -0.16 [95%CI -0.32 to -0.01]) and lower CVR (L 0.17 [0.03 to 0.31] and R 0.19 [0.02 to 0.36]) in normal appearing white matter (NAWM). Sparser branching remained associated with sub-visible white matter damage shown by higher MD (R -0.24 [-0.08 to -0.40]), lower fractional anisotropy (FA) (L 0.17 [0.01 to 0.33]), and lower CVR (R 0.20 [0.02 to 0.38]) in NAWM. OCTA-derived metrics provide evidence of microvessel abnormalities that may underpin SVD lesions in the brain.

Keywords: OCTA; capillary branching; cerebrovascular reactivity; perivascular spaces; vessel density.

Figure 1.

(a) Enface optical coherence tomography angiography (OCTA) transverse image of the superficial vascular complex with (b) corresponding structural and OCTA flow image where yellow colouration represents blood flow in vessels and segmentation (red dotted lines) bounds the internal limiting membrane to inner plexiform layer. Processed images: (c) adaptive threshold with Hessian filter and (d) skeletonized image.

Figure 2.

Fully adjusted models. OCTA vessel density (panels a and b) and vessel branching complexity (panels c and d) in relation to brain imaging variables characterizing SVD, after adjustment for age, eye disease, diabetes, systolic blood pressure and OCTA image quality. CSO PVS: centrum semiovale perivascular spaces; CVR: cerebrovascular reactivity; FA: fractional anisotropy; MD: mean diffusivity; OCTA: optical coherence tomography angiography; SVD: small vessel disease; WMH: white matter hyperintensities.