Background: Inner (area adjacent to the fovea) and outer regions of the macula differ with respect to relative thicknesses of the ganglion cell layer (neurons) vs retinal nerve fiber layer (RNFL; axons). Objective: To determine how inner vs outer macular volumes relate to peripapillary RNFL thickness and visual function in multiple sclerosis (MS) and to examine how these patterns differ among eyes with vs without a history of acute optic neuritis (ON). Design: Study using cross-sectional optical coherence tomography. Setting: Three academic tertiary care MS centers. Participants: Patients with MS, diagnosed by standard criteria, and disease-free control participants. Main Outcome Measures: Optical coherence tomography was used to measure macular volumes and RNFL thickness. Visual function was assessed using lowcontrast letter acuity and high-contrast visual acuity (Early Treatment Diabetic Retinopathy Study charts). Results: Among eyes of patients with MS (n=1058 eyes of 530 patients), reduced macular volumes were associated with peripapillary RNFL thinning; 10-µm differences in RNFL thickness (9.6% of thickness in control participants without disease) corresponded to 0.20mm 3 reductions in total macular volume (2.9% of vol

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