Retinal atrophy in multiple sclerosis is similar with extended versus standard interval natalizumab therapy.

Authors

Brenna McCormack, Omar Ezzedin, Ting-Yi Lin, Anna Bacchetti, Giulia S Moretti, Ernest Lievers, Ananya Gulati, Simidele Davis, Gabriel Otero-Duran, Devon J Bonair, Nicole Pellegrini, Georgios Gakis, Angeliki Filippatou, Clare McGarvey Lambert, Martin Maurice O'Donnell, Kathryn Fitzgerald, Elias S Sotirchos, Peter A Calabresi, Scott D Newsome, Ellen M Mowry, Shiv Saidha

Published in

Multiple sclerosis journal - experimental, translational and clinical. Volume 12. Issue 3. Pages 20552173261475496. Epub Aug 06, 2026.

Abstract

Retinal ganglion cell + inner plexiform layer (GCIPL) atrophy reflects global neurodegeneration and disability in multiple sclerosis. Extended interval dosing (EID; every 5-8 weeks) natalizumab reduces progressive multifocal leukoencephalopathy risk in people with relapsing-remitting multiple sclerosis (PwRRMS) versus standard interval dosing (SID; every 4 weeks).
To assess if EID versus SID natalizumab differentially impacts GCIPL atrophy, other retinal layer (peripapillary retinal nerve fiber layer (pRNFL), inner nuclear layer (INL), and outer nuclear layer (ONL)) atrophy, and/or clinical outcomes in PwRRMS.
PwRRMS underwent longitudinal Cirrus high-definition optical coherence tomography (OCT), expanded disability status scale (EDSS), 100% and 2.5% contrast letter-acuity (LA) assessments. Analyses utilized mixed-effects regression models adjusting for age, sex, race, disease duration, optic neuritis history, and interval between treatment initiation and OCT monitoring, accounting for within-subject, inter-eye correlations.
GCIPL and pRNFL atrophy rates were not significantly different between EID (n = 22) and SID (n = 109) natalizumab (p = 0.48, p = 0.24). INL and ONL atrophy were faster with EID versus SID natalizumab (p = 0.02, p < 0.001). Age was higher (44.8 vs. 40.1 years, p = 0.03) and disease duration longer (15.2 vs. 8.4 years, p < 0.001) in the EID natalizumab cohort. Annual EDSS and 100% and 2.5% LA changes were similar between cohorts.
We detected no significant difference in GCIPL or pRNFL atrophy, or clinical outcomes, between EID and SID natalizumab. Faster INL and ONL atrophy may relate to cohort demographic differences.

PMID:
42571199
Bibliographic data and abstract were imported from PubMed on 09 Aug 2026.

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