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Abstract

Purpose: To evaluate retinal and choroidal vascular alterations in multiple sclerosis (MS) using multimodal imaging and determine their association with disability and disease progression.

Design: Prospective, observational, single center, cross-sectional, case–control study.

Participants: Sixteen MS and 25 control participants.

Methods: Multimodal retinal imaging, including color fundus photography, ultra-widefield imaging, OCT, and OCT angiography, were performed. Retinal vascular parameters (RVPs) and choroidal vascular parameters (CVPs) were compared between control eyes and eyes with (eyes with a history of optic neuritis [MSON]) and without optic neuritis (ON) (eyes without a history of ON [MSnON]) using regression models. Associations of RVPs and CVPs with Expanded Disability Status Scale (EDSS) scores and annual EDSS progression rate were assessed. Subanalysis compared RVPs and CVPs between MSnON and MSON eyes using Wilcoxon rank-sum tests.

Main Outcome Measures: Differences in RVPs and CVPs between groups and associations with EDSS and annual rate of EDSS progression.

Results: Compared with controls, MSnON eyes showed narrower central retinal venules (P = 0.014), increased arteriole-to-venule ratio (AVR) (P = 0.031), and reduced venular fractal dimension (FD) (P = 0.013). Disability correlated with increased venular caliber (P < 0.001), vessel density (P = 0.026), superficial vascular complex (SVC) capillary density (P < 0.001), and choroidal thickness (P = 0.006), and decreased AVR (P = 0.006) and choroidal vascularity index (P = 0.030). Annual EDSS progression was associated with increased arteriolar caliber (P = 0.001), AVR (P= 0.025), SVC capillary density (P < 0.001), foveal avascular zone (FAZ) volume (P < 0.001), and deep FAZ area (P < 0.001) and a decreased venular width gradient (P = 0.011) and FD (P < 0.001). Eyes with a history of ON eyes showed narrower venular caliber (P = 0.008), density (P = 0.012), and FD (P = 0.006). When MSON and MSnON are compared, ON affected only central arteriolar caliber (P = 0.010) and global SVC density (P = 0.010).

Conclusions: Structural retinal and choroidal vascular alterations in MS were associated with disability and disease progression. These findings highlight the importance of retinal vascular assessments in the diagnosis, monitoring, and prognostication of MS, warranting confirmation in longitudinal studies. Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Publication Type:	Article
Additional Information:	© 2026 American Academy of Ophthalmology, Inc. Published by Elsevier Inc. This is an open access article distributed under the terms of the Creative Commons CC-BY license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Publisher Keywords:	Multiple sclerosis, Multimodal retinal imaging, Ultra-widefield imaging, Retinal vasculature, Choroidal vasculature
Subjects:	R Medicine > RE Ophthalmology
Departments:	School of Health & Medical Sciences School of Health & Medical Sciences > Department of Optometry & Visual Science
SWORD Depositor:	Symplectic Administrator

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