Peripapillary vessel wall changes correlate with disease severity in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL).

INTRODUCTION: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a cerebral small vessel disease caused by NOTCH3 mutations. This study explores retinal vascular changes and their associations with neuroimaging biomarkers in preclinical carriers and symptomatic CADASIL patients METHOD: This prospective case-control study enrolled six preclinical NOTCH3 mutations carriers, 21 symptomatic CADASIL patients and 17 controls. Participants underwent Optical coherence tomography (OCT) and OCT-angiography. Brain magnetic resonance imaging, mini-mental state examination, and trail making test A were conducted in CADASIL patients and carriers. White matter hyperintensity (WMH) severity was scored by modified Scheltens scale.

RESULTS: There was a significant difference in the retinal arteriolar wall thickness among CADASIL patients (mean, 15.14 μm), carriers (mean, 14.30 μm), and controls (mean, 13.43 μm) (p = 0.009). OCT revealed significantly thinner peripapillary retinal nerve fiber layer thickness in CADASIL patients compared to the controls (p = 0.003), but there were no differences in the thickness of ganglion cell-inner plexiform layer or macular vessel densities among three groups. Multivariate regression analysis found that increased venular inner and outer diameters correlated with a greater WMH severity (p = 0.026 and 0.018), and an increased risk of lacunae and stroke in CADASIL patients.

CONCLUSION: Symptomatic CADASIL patients have the greatest retinal arteriolar wall thickness, followed by preclinical carriers, and healthy controls. Larger venular inner and outer diameters were correlated with the WMH severity and presence of lacunae in CADASIL patients, which may be utilized to assess the disease severity of CADASIL.