Abstract
Vascular changes and alterations of oxygen metabolism are suggested to be implicated in multiple sclerosis (MS) pathogenesis and progression. Recently developed in vivo retinal fundus imaging technologies provide now an opportunity to non-invasively assess metabolic changes in the neural retina. This study was performed to assess retinal oxygen metabolism, peripapillary capillary density (CD), large vessel density (LVD), retinal nerve fiber layer thickness (RNFLT) and ganglion cell inner plexiform layer thickness (GCIPLT) in patients with diagnosed relapsing multiple sclerosis (RMS) and history of unilateral optic neuritis (ON). 16 RMS patients and 18 healthy controls (HC) were included in this study. Retinal oxygen extraction was modeled using O2 saturations and Doppler optical coherence tomography (DOCT) derived retinal blood flow (RBF) data. CD and LVD were assessed using optical coherence tomography (OCT) angiography. RNFLT and GCIPLT were measured using structural OCT. Measurements were performed in eyes with (MS+ON) and without (MS-ON) history for ON in RMS patients and in one eye in HC. Total oxygen extraction was lowest in MS+ON (1.8 ± 0.2 μl O2/min), higher in MS-ON (2.1 ± 0.5 μl O2/min, p = 0.019 vs. MS+ON) and highest in HC eyes (2.3 ± 0.6 μl O2/min, p = 0.002 vs. MS, ANOVA p = 0.031). RBF was lower in MS+ON (33.2 ± 6.0 μl/min) compared to MS-ON (38.3 ± 4.6 μl/min, p = 0.005 vs. MS+ON) and HC eyes (37.2 ± 4.7 μl/min, p = 0.014 vs. MS+ON, ANOVA p = 0.010). CD, LVD, RNFLT and GCIPL were significantly lower in MS+ON eyes. The present data suggest that structural alterations in the retina of RMS patients are accompanied by changes in oxygen metabolism, which are more pronounced in MS+ON than in MS-ON eyes. Whether these alterations promote MS onset and progression or occur as consequence of disease warrants further investigation.Clinical Trial Registration: ClinicalTrials.gov registry, NCT03401879.
Highlights
Multiple sclerosis (MS) is a demyelinating disease of the central nervous system with a global median prevalence of approximately 33 people per 100,000 and one of the major reasons for permanent disability in young adults (Reich et al, 2018)
As both eyes were measured in MS patients with history of unilateral optic neuritis (ON) a total of 16 MS+ON, 16 MS-ON and 18 healthy eyes were enrolled in this study
To the best of our knowledge, the data from our study shows for the first time that retinal oxygen extraction is reduced in patients with MS and history of unilateral ON when compared to healthy subjects, suggesting an impaired oxygen metabolism in patients with MS and ON
Summary
Multiple sclerosis (MS) is a demyelinating disease of the central nervous system with a global median prevalence of approximately 33 people per 100,000 and one of the major reasons for permanent disability in young adults (Reich et al, 2018). It has been shown that local oxygen supply insufficiency leads to hypoxic damage, resulting in neuroinflammation and demyelination of nerve fibers with the known clinical consequences, while in turn neuroinflammation per se can trigger hypoxia (Yang and Dunn, 2019; Halder and Milner, 2021). Studying microvascular and metabolic changes in MS is hampered by a paucity of available non-invasive methods to measure oxygen metabolism in the human brain. In this context, the anterior visual system – mainly the neural retina and the optic nerve – offers unique possibilities to non-invasively gain insight into the metabolic and microvascular processes in unprecedented resolution. As much as 70% of patients with MS are affected by ON at some time during the disease (Toosy et al, 2014)
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