Aims The aims of this study was to report anatomical changes of the ganglion cell complex (GCC), retinal nerve fiber layer (RNFL) thickness, and macular volume in patients with multiple sclerosis (MS). We also investigated the correlation between anatomical and functional changes in terms of visual acuity and macular sensitivity investigated and visual fields. Methods Prospective comparative study included 105 eyes of 53 consecutive patients. The patients were divided into two groups: group A included 56 eyes of 28 patients with diagnosis of MS; group B involved 49 eyes of 25 healthy patients. The examination included Goldmann tonometry, biomicroscopic and fundus oculi examination, retinography, GCC examination, circumpapillary RNFL (cpRNFL), and macular volume. The functional test included measurement of best-corrected visual acuity (BCVA), visual field, and MP. Results MS group showed a significant reduced GCC, cpRNFL, macular volume, BCVA, visual field, and macular sensitivity compared with the control group (Po0.001). This reduction was more representative (Po0.001) in patients with MS complicated by optic neuritis (ON). We found in the MS group a strong correlation between GCC thickness and macular volume (r 2 = 0.59, Po0.001) and also between GCC and RNFL thickness (r 2 = 0.48, Po0.001). There was also a correlation between macular sensitivity and macular volume reduction (r 2 = 0.25, Po0.001) and also between RNFL and macular volume (r 2 = 0.43, Po0.001). Conclusions The significant statistical evidence and the strong correlation between anatomical and functional parameters support the use of OCT and MP in the evaluation, treatment, and follow-up of patients diagnosed with MS.