Trans-synaptic degeneration could exacerbate neurodegeneration in multiple sclerosis (MS). We aimed to assess whether anterograde trans-synaptic degeneration could be identified in the primary visual pathway in vivo. Diffusion tensor imaging (DTI) was used to assess the optic radiations in 15 patients with previous optic nerve inflammation and 9 healthy volunteers. A probabilistic atlas of the optic radiations was created from healthy diffusion tractography data. Lengthwise profiles for DTI parameters (axial [k , radial [k?] and mean diffusivity [MD], fractional anisotropy [FA] and the angle of deviation of the principal eigenvector [a]) were analyzed for patients and controls. Patients also underwent multifocal visual evoked potential (mfVEP) assessments to characterize the latency and amplitude of cortical potentials. Correlations were performed between mfVEP latency and amplitude in the left and right visual hemi-fields and DTI parameters in the contra-lateral optic radiations. Patients displayed a significant decrease in k within the body of both optic radiations, which significantly correlated with loss of mfVEP amplitude. Abnormal k? and FA were detected bilaterally throughout the optic radiations in patients but the abnormality was not associated with amplitude reduction or latency prolongation of the mfVEP. An abnormal a value was observed in the left optic radiations of patients, and the a value in the body of the optic radiations also correlated with mfVEP amplitude loss. The assocation between bilateral DTI abnormalities within the optic radiations and loss of afferent electrical activity could indicate anterograde trans-synaptic degeneration occurs following optic neuritis.