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Observational Study
. 2023 Nov 28:14:1284986.
doi: 10.3389/fimmu.2023.1284986. eCollection 2023.

Association of retinal vessel pathology and brain atrophy in relapsing-remitting multiple sclerosis

Eva Feodora Romahn  1 , Tun Wiltgen  1 , Matthias Bussas  1 , Lilian Aly  1 , Rebecca Wicklein  1 , Christina Noll  1 , Achim Berthele  1 , Vera Dehmelt  1 , Christian Mardin  2 , Claus Zimmer  3 , Thomas Korn  1   4   5 , Bernhard Hemmer  1   5 , Jan S Kirschke  3 , Mark Mühlau #  1 , Benjamin Knier #  1
Affiliations
Observational Study

Association of retinal vessel pathology and brain atrophy in relapsing-remitting multiple sclerosis

Eva Feodora Romahn et al. Front Immunol. .

Abstract

Background: Optical coherence tomography angiography (OCTA) allows non-invasive assessment of retinal vessel structures. Thinning and loss of retinal vessels is evident in eyes of patients with multiple sclerosis (MS) and might be associated with a proinflammatory disease phenotype and worse prognosis. We investigated whether changes of the retinal vasculature are linked to brain atrophy and disability in MS.

Material and methods: This study includes one longitudinal observational cohort (n=79) of patients with relapsing-remitting MS. Patients underwent annual assessment of the expanded disability status scale (EDSS), timed 25-foot walk, symbol digit modalities test (SDMT), retinal optical coherence tomography (OCT), OCTA, and brain MRI during a follow-up duration of at least 20 months. We investigated intra-individual associations between changes in the retinal architecture, vasculature, brain atrophy and disability. Eyes with a history of optic neuritis (ON) were excluded.

Results: We included 79 patients with a median disease duration of 12 (interquartile range 2 - 49) months and a median EDSS of 1.0 (0 - 2.0). Longitudinal retinal axonal and ganglion cell loss were linked to grey matter atrophy, cortical atrophy, and volume loss of the putamen. We observed an association between vessel loss of the superficial vascular complex (SVC) and both grey and white matter atrophy. Both observations were independent of retinal ganglion cell loss. Moreover, patients with worsening of the EDSS and SDMT revealed a pronounced longitudinal rarefication of the SVC and the deep vascular complex.

Discussion: ON-independent narrowing of the retinal vasculature might be linked to brain atrophy and disability in MS. Our findings suggest that retinal OCTA might be a new tool for monitoring neurodegeneration during MS.

Keywords: brain atrophy; disability; magnetic resonance imaging; multiple sclerosis; optical coherence tomography; optical coherence tomography angiography.

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Conflict of interest statement

LA received travel and research support by Novartis Deutschland GmbH. RW received a poster grant from Novartis Deutschland GmbH. AB has received consulting and/or speaker fees from Alexion, Bayer Healthcare, Biogen, Celgene, Novartis Deutschland GmbH, Roche and Sandoz/Hexal. CM is a medical advisor to Heidelberg Engineering, Heidelberg, Germany, receives lecture honorarium by Heidelberg Engineering and Bayer AG, Leverkusen, Germany. CZ has served on scientific advisory boards for Philips and Bayer Schering; serves as co-editor on the Advisory Board of Clinical Neuroradiology; has received speaker honoraria from Bayer-Schering and Philips and has received research support and investigator fees for clinical studies from Biogen Idec, Quintiles, MSD Sharp & Dome, Boehringer Ingelheim, Inventive Health Clinical UK Ltd., Advance Cor, Brainsgate, Pfizer, Bayer-Schering, Novartis, Roche, Servier, Penumbra, WCT GmbH, Syngis, SSS Internartional Clinical Research, PPD Germany GmbH, Worldwide Clinical Trials Ltd., Phenox, Covidien, Actelion, Medivation, Medtronic, Harrison Clinical Research, Concentric, Penumbra, Pharmtrace, Reverse Medical Corp., Premier Research Germany Ltd., Surpass Medical Ltd. and GlaxoSmithKline. TK received travel support and speaking honoraria from Novartis Deutschland GmbH and Merck. BH has served on scientific advisory boards for Novartis Deutschland GmbH; he has served as DMSC member for AllergyCare, Sandoz, Polpharma and TG therapeutics; he or his institution have received speaker honoraria from Desitin; his institution received research grants from Regeneron for multiple sclerosis research. He holds part of two patents; one for the detection of antibodies against KIR4.1 in a subpopulation of patients with multiple sclerosis and one for genetic determinants of neutralizing antibodies to interferon. All conflicts are not relevant to the topic of the study. JK received speaking honoraria from Novartis Deutschland GmbH. BK received travel support and speaking honoraria from Novartis Deutschland GmbH, Teva, Heidelberg Engineering and served at the advisory board of Merck. He received a research grant from Novartis Deutschland GmbH. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.

Figures

Figure 1
Figure 1
Association of the retinal architecture and brain atrophy. (A) Correlation of annualized changes of the peripapillary retinal nerve fiber layer (pRNFL) thickness and annualized changes of total grey matter volume, cortical thickness, and grey matter volume of the putamen. (B) Correlation of annualized changes of the combined ganglion cell and inner plexiform layer (GCIP) thickness and changes of total grey matter volume, cortical thickness and volume of the putamen. (A, B) Multiple linear regression models corrected for age, sex, disease duration, total intracranial volume; β estimates (line) and 95% confidence interval (CI; dotted lines).
Figure 2
Figure 2
Association of the retinal vasculature, brain atrophy and disability. (A) Association of annualized changes of vessel densities of the superficial vascular complex (SVC) and annualized changes of the grey and white matter volumes. (B) Association of annualized changes of vessel densities of the deep vascular complex (DVC) and annualized changes of the grey matter volume. (C) Correlation of annualized changes of vessel densities of the DVC and annualized changes of the EDSS. (A, B) Multiple linear regression models corrected for age, sex, disease duration; (C) Multiple linear regression models corrected for age, sex, disease duration, total intracranial volume; β estimates (line) and 95% confidence interval (CI; dotted lines).
Figure 3
Figure 3
Alteration of the retinal vasculature in patients with and without disability worsening. (A) Annualized changes of vessel densities of the superficial (SVC) and deep vascular complex (DVC) in patients with and without confirmed worsening of the expanded disability status scale (EDSS). (B) Annualized changes of vessel densities of the SVC and DVC in patients with and without confirmed worsening of the symbol digit modalities test (SDMT). (C) Annualized changes of vessel densities of the SVC and DVC in patients with and without confirmed worsening of the timed 25-foot walk test (T25W). (A-C) Unpaired t test or non-parametric Mann–Whitney U test (depending on normal distribution); bars reveal median values and the 75% measure of the 25%-75% interquartile range.
See this image and copyright information in PMC

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