Purpose: The present study was conducted to investigate alterations in the innermost layers of the retina using optical coherence tomography (OCT) and to assess potential associations of structural measures with functional markers in patients with Multiple Sclerosis (MS).Materials and Methods: Ninety-four eyes of 47 MS patients and 60 eyes of 30 healthy individuals were included in the study. All patients underwent complete ophthalmological examination and OCT imaging to analyze peripapillary retinal nerve fiber layer (RNFL) and ganglion cell-inner plexiform layer (GCIPL) thickness. Visual evoked potentials (VEPs) and expanded disability status scale (EDSS) score were assessed for MS patients.Results: The average RNFL and GCIPL thicknesses were thinner in MS patients (86.2 11.9 mu m and 73.6 +/- 9.7 mu m, respectively) when compared with those of healthy controls (96.7 +/- 8.2 mu m and 85.9 +/- 4.6 mu m, respectively, p < 0.001 for both). Within MS patients, the average RNFL and GCIPL thicknesses were lower in eyes with a prior history of optic neuritis (MS ON) than in eyes with no optic neuritis history (MS non-ON) (p = 0.012 and p < 0.001, respectively). RNFL and GCIPL thicknesses were inversely correlated with VEP latency (r = -0.40, p < 0.001 and r = -0.36, p < 0.001, respectively) in MS patient eyes. There was a correlation between GCIPL thickness and VEP amplitude in eyes with previous ON history (r = 0.34, p = 0.035). No significant correlations were found between OCT measurements and EDSS score.Conclusions: Innermost layers of the retina are highly affected by the pathophysiologic process in MS disease, manifesting as a reduction in RNFL and GCIPL thickness. The structural retinal changes show correlation with alterations in potentials showing the optic pathway function.