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Retinal Vessel Dysfunction in Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and
Yonatan Serlin1, Colyn Munn2,3, Elisa A Ferrante4
1Neurophysiology of Epilepsy Unit, NINDS, National Institutes of Health, Bethesda, MD.
Insights
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) patients show progressive retinal vessel dysfunction. Serial ultra-widefield fluorescein angiography (UW-FA) may serve as a surrogate marker for cerebral small vessel disease (cSVD) progression.
Area of Science:
- Ophthalmology
- Neurology
- Vascular Biology
Background:
- Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common inherited cerebral small vessel disease (cSVD).
- It involves NOTCH3-mediated microvascular pathology, but retinal manifestations remain underexplored.
- Retinal vessel dysfunction may reflect systemic microvascular changes in CADASIL.
Purpose of the Study:
- To characterize dynamic retinal vessel dysfunction in patients with CADASIL using serial ultra-widefield fluorescein angiography (UW-FA).
- To investigate potential surrogate markers for cSVD progression within the retina.
Main Methods:
- Serial UW-FA was performed at baseline and follow-up (13.9 ± 4.5 months) on 19 CADASIL patients and 9 healthy volunteers (HVs).
- Retinal vessel permeability, blood flow, and perfusion were quantified across macular, mid-peripheral, and far-peripheral zones.
- Aberrant pixels were compared to HV thresholds, and longitudinal changes were analyzed.
Main Results:
- Baseline far-peripheral permeability was higher in CADASIL patients compared to 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 patients.
- Longitudinal analysis revealed reduced macular and mid-peripheral blood flow/perfusion and increased mid-peripheral permeability in CADASIL patients.
Conclusions:
- Serial UW-FA detects progressive, region-specific retinal vessel dysfunction in CADASIL.
- These retinal changes may serve as a surrogate marker for the progression of cSVD.
- Further research can explore the clinical utility of UW-FA in monitoring CADASIL and other cSVDs.
Objectives:
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:
UW-FA was performed at baseline and after 13.9 ± 4.5 months. Retinal vessel permeability, blood flow, and perfusion across macular, mid-peripheral, and far-peripheral zones were quantified. Aberrant pixels exceeded healthy volunteer (HV) thresholds. Group differences, longitudinal changes, NOTCH3 variant loci, and stroke-age associations were analyzed.
Results:
Nineteen patients with genetically confirmed CADASIL (mean age 48.4 years; 52.6% female) and 9 matched HVs (mean age 44.3 years, 55.6% female) were included. Baseline far-peripheral permeability was higher in the CADASIL group vs HVs (p = 0.03; r = 0.41). At follow-up, mid-peripheral permeability increased (p = 0.003; r = 0.56) and far-peripheral permeability remained elevated (p = 0.0007; r = 0.64) in patients with CADASIL. Longitudinal analysis showed reduced blood flow and perfusion in the macula and mid-periphery and increased midperipheral permeability (all statistically significant with substantial effect sizes). Neither genotype nor stroke-onset age predicted alterations.
Discussion:
Serial UW-FA scans detect progressive, region-specific retinal vessel dysfunction in a modest-sized cohort with CADASIL, potentially serving as a surrogate marker for cSVD progression.
