We do not have currently satisfactory clinical and anatomical correlates to gauge disability in multiple sclerosis. Structural biomarkers (such as MRI) are hindered because they cannot precisely segregate demyelination from axonal elements of tissue injury within the CNS. Axonal degeneration in multiple sclerosis is related to irreversible disability, which suggests that the confirmation of neuroprotective strategies needs highly quantifiable measures of axon loss that can be correlated with reliable measures of physiological function. The coupling of quantifiable measures of visual function with ocular imaging techniques, such as optical coherence tomography, enables us to begin to understand how structural changes in the visual system influence function in patients with multiple sclerosis. In this review, we consider the usefulness of optical imaging of the retina as a biomarker for neurodegeneration in multiple-sclerosis.