Axonal degeneration is a key pathological driver of disability in multiple sclerosis (MS). Treatments aiming to reduce or reverse axonal degeneration in MS require sensitive and specific markers. Here we explore putative fibre-specific markers of axonal degeneration based on diffusion-weighted MRI metrics – fibre density and fibre bundle cross-section. MS patients with optic neuritis were compared to control subjects. We identified significant reductions to both fibre density and cross-section in the visual pathways of patients. These results indicate the pathological specificity of fibre density and cross-section measures in MS.