Longitudinal association of retinal morphology and white matter progression in retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations

Background Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S) is a rare small vessel disease marked by vision loss and neurocognitive deterioration. We sought to characterize the relatedness of the underlying retinal structure and cerebral disease. Methods Participants with RVCL-S underwent optical coherence tomography (OCT) and brain MRI at baseline and 2 years. Total macular volume (TMV) and central subfield thickness (CST) were generated from OCT images. Neuroimaging metrics of ischemic brain injury included white matter hyperintensity (WMH) volume, white matter microstructure (mean diffusivity), and normalized white matter volume. Associations between retinal and neuroimaging metrics were assessed. Results Eleven RVCL-S participants were included. Reduction in TMV was associated with reduced normalized white matter volume ( β = 0.021, 95% CI [0.006, 0.036], p = 0.0137), increased WMH volume ( β = −11.0, 95% CI [−17.4, −4.0], p = 0.0046), and a near-significant increase in mean diffusivity ( β = −0.017, 95% CI [−0.035, −0.001], p = 0.057). CST was not associated with neuroimaging metrics. Percent change in TMV was associated with percent change in mean diffusivity ( β = −0.61, 95% CI [−1.14, −0.084], p = 0.028). Conclusion A metric of retinal structure, TMV, may provide a marker of cerebral disease severity in RVCL-S. Additional studies are needed to demonstrate whether early measures of TMV predict cerebral disease progression.