Anterior Visual Pathway Measures Are Strongly Associated with Cognitive Function in Multiple Sclerosis

Background: Optical coherence tomography (OCT) derived ganglion cell + inner plexiform layer (GCIP) thickness is associated with visual function, gray matter volume, and Expanded Disability Status Scale (EDSS) scores in MS.  Whether or not visual function and GCIP thickness are related to cognitive function in MS, however, remains unclear. 

Objectives: To determine whether visual function and GCIP thickness are associated with cognitive measures including Multiple Sclerosis Functioning Composite (MSFC), California Verbal Learning Test-II (CVLT-II), Single Digit Modalities Test (SDMT), and Brief Visuospatial Memory Test-Revised (BVMT-R) in MS.

Methods: This cross-sectional study included 130 participants (97 relapsing-remitting and 33 progressive MS patients) who underwent Cirrus HD-OCT with automated segmentation and CVLT-II, SDMT, BVMT-R, MSFC, and 100%, 2.5%, and 1.25%-contrast letter-acuity testing. Eyes within 6 months of acute optic neuritis (ON) were excluded. Mixed effects linear regression accounting for within-subject inter-eye correlations, adjusting for age, sex, and disease duration were utilized to assess relationships between anterior visual pathway (AVP) and cognitive measures.   

Results: Relapsing-Remitting MS (RRMS), but not progressive MS (PMS), patients exhibited significant associations between average GCIP thickness and MSFC scores in eyes without ON history (p=0.018), but not in eyes with ON history (p=0.392). Similarly, GCIP thickness corresponded with BVMT-R long-term visuospatial memory in RRMS (p=0.015), but not PMS, with the relationship driven by non-ON eyes.

100%, 2.5%, and 1.25% contrast letter acuity and MSFC scores were associated in RRMS eyes without ON history (p=0.017, p=0.004, p=0.017, respectively), but not in PMS patients. 100%, 2.5%, and 1.25%-contrast letter acuity and BVMT-R total and delayed recall t-scores were associated across the cohort, regardless of ON history (all: p<0.002). 2.5% and 1.25%-contrast letter acuity and SDMT scores were related in RRMS (p=0.036 , p=0.002, respectively), with the relationships driven by non-ON eyes.  

Conclusions: Results of this study suggest AVP measures are associated with cognitive function in MS. Our findings indicate that GCIP thickness and high- and low-contrast letter acuity scores, particularly in RRMS eyes without ON history, provide insight regarding global aspects of the disease process and support their utility as outcomes in trials of neuroprotective therapies in MS.