BRIEF RESEARCH REPORT article
Front. Neurol.
Sec. Neurological Biomarkers
This article is part of the Research TopicIdentification of Neurological Biomarkers for Neurodegenerative DisordersView all 6 articles
Longitudinal Association of Retinal Morphology and White Matter Progression in Retinal Vasculopathy with Cerebral Leukoencephalopathy and Systemic Manifestations
Provisionally accepted
Henok Getahun1
Rajendra S. Apte1
Wilson X. Wang1Vivian Chen1Mae Gordon1Julia Huecker1
John Patterson Atkinson1
M. Kathryn Liszewski1
Slim Fellah1
Serguei Astafiev1
Jonathan Miner2
Andria Ford1*- 1Washington University in St Louis School of Medicine, St. Louis, United States
- 2University of Pennsylvania Department of Medicine, Philadelphia, United States
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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 two 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.
Keywords: imaging, Retina, biomarkers, vasculopathy, leukoencephalopathy
Received: 13 Oct 2025; Accepted: 24 Nov 2025.
Copyright: © 2025 Getahun, Apte, Wang, Chen, Gordon, Huecker, Atkinson, Liszewski, Fellah, Astafiev, Miner and Ford. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Andria Ford
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