Visual dysfunction in multiple sclerosis correlates better with optical coherence tomography derived estimates of macular ganglion cell layer thickness than peripapillary retinal nerve fiber layer thickness

Background: Post-mortem analyses of multiple sclerosis (MS) eyes demonstrate prominent retinal neuronal ganglion cell layer (GCL) loss, in addition to related axonal retinal nerve fiber layer (RNFL) loss. Despite this, clinical correlations of retinal neuronal layers remain largely unexplored in MS. Objectives: To determine if MS patients exhibit in vivo retinal neuronal GCL loss, deeper retinal neuronal loss, and investigate correlations between retinal layer thicknesses, MS clinical subtype and validated clinical measures. Methods: Cirrus HD-optical coherence tomography (OCT), utilizing automated intra-retinal layer segmentation, was performed in 132 MS patients and 78 healthy controls. MS classification, Expanded Disability Status Scale (EDSS) and visual function were recorded in study subjects. Results: GCL+inner plexiform layer (GCIP) was thinner in relapsing-remitting MS (RRMS; n=96, 71.6 mu m), secondary progressive MS (SPMS; n=20, 66.4 mu m) and primary progressive MS (PPMS; n=16, 74.1 mu m) than in healthy controls (81.8 mu m; p<0.001 for all). GCIP thickness was most decreased in SPMS, and although GCIP thickness correlated significantly with disease duration, after adjusting for this, GCIP thickness remained significantly lower in SPMS than RRMS. GCIP thickness correlated significantly, and better than RNFL thickness, with EDSS, high-contrast, 2.5% low-contrast and 1.25% low-contrast letter acuity in MS. 13.6% of patients also demonstrated inner or outer nuclear layer thinning. Conclusions: OCT segmentation demonstrates in vivo GCIP thinning in all MS subtypes. GCIP thickness demonstrates better structure-function correlations (with vision and disability) in MS than RNFL thickness. In addition to commonly observed RNFL/GCIP thinning, retinal inner and outer nuclear layer thinning occur in MS.