Visual deficits and cognitive assessment of multiple sclerosis: confounder, correlate, or both?

The relationship between visual impairment and cognitive performance in multiple sclerosis (MS) remains poorly understood. To determine associations between visual acuity and optical coherence tomography (OCT) measures with cognitive performance of MS patients and healthy controls (HCs). 141 MS patients (with and without MS optic neuritis; MSON) and 50 HCs underwent neuropsychological, visual, and OCT testing. California Verbal Learning Test (CVLT-II), Brief Visuospatial Memory Test (BVMT-R), and Symbol Digit Modalities Test (SDMT) were used. Patients with test performance below − 1.5 standard deviations of the mean HCs scores were labeled as cognitive impairment. Visual ability was assessed with 100%, 2.5%, and 1.25% low-contrast letter acuity (LCLA) charts. OCT-derived peripapillary retinal nerve fiber layer (pRNFL) thickness, macular volume (MV), macular ganglion cell inner plexiform (mGCIP) thickness (as a sum of GC and IP layers), and macular inner nuclear layer (mINL) were computed. 100% and 2.5% LCLA associated with SDMT in MS and HCs (p < 0.001; and p < 0.012, respectively). In MSON patients, visually demanding tests were explained by pRNFL and macular volume for SDMT (β = 0.172, p = 0.039 and β = 0.27, p = 0.001) and MV for BVMT-R (β = 0.21, p = 0.012). In non-MSON, only mINL was predictor of CVLT-II. pRNFL and MV predicted cognitive impairment with an accuracy of 72.2% (Negelkerke R2 = 0.234). These findings were driven by associations within the progressive MS subgroup. HC’s SDMT performance was explained by mGCIP (β = 0.316, p = 0.001). Both LCLA and OCT-based measures (pRNFL and macular volume) were associated with MS cognitive performance. OCT-based measures were also significant predictors of cognitive status in MS patients. mGCIP associated with cognitive performance in HCs.