Background: Previous research has shown that higher levels of moderate to vigorous physical activity (MVPA) associate with lower brain lesion volumes on MRI and disease activity in children with MS. In addition, other research has shown that measures of retinal integrity, as measured using OCT, associate with brain atrophy in MS. Associations between retinal integrity and vigorous physical activity in children with neuroinflammatory conditions have not been investigated to date. Objectives: To determine the relationship between MVPA and OCT metrics (retinal nerve fibre layer (RNFL) thickness, and ganglion cell inner plexiform layer (GCIPL)) in patients with MS, recurrent MOG-IgG Ab related disorders, NMOSD, and monoADS. Methods: Consecutive children with neuroinflammatory conditions (MS, recurrent MOG IgG Ab related disorders, NMOSD and monophasic demyelinating disorders) ?18 y.o who were evaluated at the Pediatric MS and Neuroinflammatory Disorders Center at the Hospital for Sick Children (2012-2020) were included. Outcome metrics included the Godin Leisure Time Activity Questionnaire (physical activity questionnaire (GLTEQ)), and structural visual measures (RNFL and GCIPL) using OCT. We performed Spearmans correlations and linear mixed models using JASP version 0.14.1. Results: 156 patients were included (MS (n=46, 30% F, mean age=17.2±2.9, mean RNFL= 88.6µm (IQR:13.25), mean GCL average=74.8µm(IQR:16.25), mean MVPA =32.8±25.3); NMOSD (n=5, 20%F, mean age=16.0±1.7, mean RNFL= 85.4µm(IQR:8.50), mean GCL average=77.2µm(IQR:9.00), mean MVPA=27.2±24.1); persistent MOG+ (n=26, 27% F, mean age =14.7±4.9, mean RNFL=70.2µm(IQR:24.25), mean GCL average=65.3µm(IQR:21.00), mean MVPA = 34.8±26.6); monoADS (n=79, 51% F, mean age= 12.7±3.9, mean RNFL= 90.8µm(IQR:25.25), mean GCL average=77.5µm(IQR:14.75), mean MVPA=41.6±23.6). In the MS cohort, we found associations between RNFL and strenuous exercise (r=0.315, p=.002), MVPA (r=0.259, p=.013), and total PA (r=0.229, p=.028). We found a significant main effect of strenuous METs on RNFL(F (1,42)=4.550, p=.039). MVPA demonstrated a small main effect on RNFL(F(1,42)=3.342, p=.075). No significant associations between GCL and MVPA metrics were identified in the MS group. OCT metrics and MVPA measures did not associate in the NMOSD, MOG+ or monoADS cohorts. Conclusions: Increased levels of MVPA may be associated with higher RNFL thickness in patients with MS but not patients with recurrent MOG+, NMOSD, or monoADS. Reasons for lack of association in the MOG and NMOSD cohorts is unclear but may be related to small cohort size, lack of within group patient variability, or differences in activity level. Next steps include between group comparisons to better elucidate group level differences. Larger studies are also necessary to further investigate these relationships and the potential disease modifying effect of MVPA in patients with pediatric onset neuroinflammatory conditions.