Abstract DP245: Retinal Vessel Dysfunction in CADASIL: an Ultra-Widefield Fluorescein Angiography Study

Introduction: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), the most common inherited cerebral small vessel disease (cSVD), involves NOTCH3 -mediated microvascular pathology. As retinal health remains underexplored, serial ultra-widefield fluorescein angiography (UW-FA) was used to characterize dynamic vessel dysfunction. Methods: Nineteen genetically-confirmed CADASIL patients (mean age 48.4 ± 12.1 years; 52.6% female) underwent UW-FA at baseline and after 13.9 ± 4.5 months. Nine matched healthy volunteers (HVs) were imaged once. Retinal vessel permeability, blood flow, and perfusion across macular (6mm), mid-peripheral (6-20mm), and far-peripheral (>20mm) zones were quantified. Aberrant pixels exceeded HVs thresholds (0.5 th -99.5 th percentile). Group differences, longitudinal changes, NOTCH3 variant loci and stroke-age associations were analyzed. Results: Baseline far-peripheral permeability was higher in CADASIL versus HVs (p = 0.03). At follow-up, mid-peripheral permeability increased (p = 0.003), and far-peripheral permeability remained elevated (p = 0.0007) in CADASIL. Longitudinal analysis showed reduced macular (p = 0.01) and mid-peripheral (p = 0.05) blood flow, reduced macular (p = 0.01) and mid-peripheral (p = 0.03) perfusion, and increased mid-peripheral permeability (p = 0.01). Neither genotype nor stroke-onset age predicted alterations. Conclusions: Serial UW-FAs detect progressive, region-specific retinal vessel dysfunction in CADASIL, potentially serving as a surrogate marker for cSVD progression.