Purpose: To examine the relation of visual function to retinal nerve fiber layer (RNFL) thickness as a structural biomarker for axonal loss in multiple sclerosis (MS),and to compare RNFL thickness among MS eyes with a history of acute optic neuritis (MS ON eyes),MS eyes without an optic neuritis history (MS non-ON eyes),and disease-free control eyes. Design: Cross-sectional study. Participants: Patients with MS (n=90; 180 eyes) and disease-free controls (n =36; 72 eyes). Methods: Retinal never fiber layer thickness was measured using optical coherence tomography (OCT; fast RNFL thickness software protocol). Vision testing was performed for each eye and binocularly before OCT scanning using measures previously shown to capture dysfunction in MS patients: (1) low-contrast letter acuity (Sloan charts,2.5% and 1.25% contrast levels at 2 m) and (2) contrast sensitivity (Pelli-Robson chart at 1 m). Visual acuity (retroilluminated Early Treatment Diabetic Retinopathy charts at 3.2 m) was also measured,and protocol refractions were performed. Main Outcome Measures: Retinal nerve fiber layer thickness measured by OCT,and visual function test results. Results: Although median Snellen acuity equivalents were better than 20/20 in both groups,RNFL thickness was reduced significantly among eyes of MS patients (92 μ m) versus controls (105 μ m) (P < 0.001) and particularly was reduced in MS ON eyes (85 μ m; P < 0.001; accounting for age and adjusting for within-patient intereye correlations). Lower visual function scores were associated with reduced average overall RNFL thickness in MS eyes; for every 1-line decrease in low-contrast letter acuity or contrast sensitivity score,the mean RNFL thickness decreased by 4 μ m. Conclusions: Scores for low-contrast letter acuity and contrast sensitivity correlate well with RNFL thickness as a structural biomarker,supporting validity for these visual function tests as secondary clinical outcome measures for MS trials. These results also suggest a role for ocular imaging techniques such as OCT in trials that examine neuroprotective and other disease-modifying therapies. Although eyes with a history of acute optic neuritis demonstrate the greatest reductions in RNFL thickness,MS non-ON eyes have less RNFL thickness than controls,suggesting the occurrence of chronic axonal loss separate from acute attacks in MS patients. Purpose: To examine the relation of visual function to retinal nerve fiber layer (RNFL) thickness as a structural biomarker for axonal loss in multiple sclerosis (MS), and to compare RNFL thickness among MS eyes with a history of acute optic neuritis (MS ON eyes), MS eyes without an optic neuritis history (MS non-ON eyes), and disease-free control eyes. Design: Cross-sectional study. Participants: Patients with MS (n = 90; 180 eyes) and disease- Methods: Retinal never fiber layer thickness was measured using optical coherence tomography (OCT; fast RNFL thickness software protocol). Vision testing was performed for each eye and binocularly before OCT scanning using measures previously shown as capture dysfunction in MS patients: (1) low-contrast letter acuity (Sloan charts, 2.5% and 1.25% contrast levels at 2 m) and (2) contrast sensitivity (Pelli-Robson chart at 1 m) Diabetic Retinopathy charts at 3.2 m) was also measured, and protocol refractions were performed. Main Outcome Measures: Retinal nerve fiber layer thickness measured by OCT, and visual function test results. Results: Although median Snellen acuity equivalents were better than 20/20 in both groups, RNFL thickness was reduced carefully among eyes of MS patients (92 μm) versus controls (105 μm) (P <0.001), especially was reduced in MS ON eyes (85 μm; P <0.001; accounting for age and adjusted for within-patient intereye correlations) For every 1-line decrease in low-contrast letter acuity or contrast sensitivity score, the mean RNFL thickness decreased by 4 μ m. Conclusions: Scores for low- contrast letter acuity and contrast sensitivity correlate well with RNFL thickness as a structural biomarker, supporting validity for these visual function tests as secondary clinical outcome measures for MS trials. These results also suggest a role for ocular imaging techniques such as OCT in trials that examine neuroprotective and other disease-modifying therapies. Although eyes with a history of acute optic neuritis demonstrate the greatest reductions in RNFL thickness, MS non-ON eyes have less RNFL thickness than controls , suggesting the occurrence of chronic axonal loss separate from acute attacks in MS patients.