Background: Moderate-to-vigorous physical activity (MVPA) may confer benefits for axonal and/or neuronal integrity in adults with multiple sclerosis (MS). Purpose: Examine the association between device-measured MVPA with optical coherence tomography (OCT) metrics of retinal nerve fiber layer (RNFL) thickness and total macular volume (TMV) in persons with and without MS.

Methods: Adults with MS (N = 41), along with sex-matched healthy control (HC) participants (N = 79), underwent measurements of retinal morphology via OCT and wore an accelerometer for a period of 7 days as a measure of MVPA.

Results: Persons with MS had significantly lower MVPA, RNFL thickness, and TMV compared with HCs. MVPA was correlated with RNFL (r = .38, P < .01) thickness and TMV (r = .49, P < .01). Hierarchical linear regression analyses indicated that addition of MVPA attenuated the Group effect on RNFL and TMV. MVPA accounted for 8% and 3% of the variance in TMV (β = .343, P < .01) and RNFL thickness (β = .217, P = .03), respectively.

Conclusion: MVPA was positively associated with axonal and neuronal integrity assessed by OCT and partially explained group differences in those metrics. These results present possible future targets for MS management by increasing MVPA.