Purpose: To examine the associations among objectively-measured physical activity with the optical coherence tomography (OCT) metrics of retinal nerve fiber layer (RNFL) thickness and total macular volume (TMV) in persons with multiple sclerosis (MS). Methods: Eighty four participants with MS, without ocular disease or high myopia underwent a neurological examination for Expanded Disability Status Scale (EDSS) scoring, followed by OCT. Participants then wore an accelerometer during the waking hours of a 7-day period to objectively measure physical activity as steps/day. Results: Mean RNFL thickness for the sample was 91.46 mu m (SD= 15.0), and mean TMV was 6.61 mm(3) (SD=0.5). The mean score from the accelerometer was 4287 steps/day (SD= 2563). Steps/day was significantly associated with both RNFL thickness (Wald chi(2)=46.48, p<0.001) and TMV (Wald chi(2)=1798.27, p<0.001). After controlling for sex, MS subtype, disease duration, disability, and visual function, steps/day was significantly associated with TMV (Wald chi(2)=58.93, p<0.001), but not RNFL (Wald chi(2)=0.001, p=0.973). Conclusions: Physical activity was associated with integrity of the anterior visual pathway, assessed by OCT, in persons with MS, and this association was independent of sex, MS subtype, disease duration, disability, and visual function. Researchers should consider examining the causal nature of the association between physical activity and markers of the visual system in MS. (C) 2013 Elsevier B.V. All rights reserved.