Association of Retinal Layer Thickness With Cognition in Patients With Multiple Sclerosis

Abstract

ObjectiveRetinal layer thickness (RLT) measured by optical coherence tomography (OCT) is considered a noninvasive, cost-efficient marker of neurodegeneration in multiple sclerosis (MS). We aimed to investigate associations of RLT with cognitive performance and its potential as indicator of cognitive status in patients with MS by performing generalized estimating equation (GEE) analyses.MethodsIn this cross-sectional study, patients with at least mild signs of cognitive impairment were examined by OCT as well as by the Brief International Cognitive Assessment for MS and tests assessing attention and executive functions (Trail Making Test [TMT] A and B). Associations of these factors were investigated using GEE models controlling for demographic and disease-related factors and correcting for multiple testing.ResultsA total of 64 patients entered the study. In the final sample (n = 50 [n = 14 excluded due to missing data or drop-outs]; n = 44 relapsing-remitting MS and n = 6 secondary progressive MS, mean Expanded Disability Status Scale score = 2.59 [SD = 1.17], disease duration [median] = 7.34 [interquartile range = 12.1]), 36.0% were cognitively impaired. RLT of the macular retinal nerve fiber layer was associated with performance in TMT-B (β = −0.259). Analyses focusing on the upper and lower tertile of RLT additionally revealed associations between macular ganglion cell-inner plexiform layer and TMT-B and verbal short-term memory and learning, respectively.ConclusionIn patients with MS, at less advanced disease stages, RLT was especially associated with cognitive flexibility promoting OCT as a potential marker advocating further extensive neuropsychological examination.

Retinal layer thinning as a biomarker of long-term disability progression in multiple sclerosis

“…While within the OCTiMS trial, no robust association between retinal layer thinning and performance in SDMT could be demonstrated, and a recently published study observed an association between attention and executive function tests and retinal layer thickness. 17,31 Despite some advantages of GCIPL over pRNFL and more pronounced effects in EDSS than in SDMT prognostication, the findings of the present study demonstrate that the prognostic value to predict disability progression still prevails after a long-term follow-up of approximately 6 years. This prognostic potential is based on (1) smaller values of baseline thickness of retinal layers and (2) higher annual thinning rates of retinal layers.…”

“…While within the OCTiMS trial, no robust association between retinal layer thinning and performance in SDMT could be demonstrated, and a recently published study observed an association between attention and executive function tests and retinal layer thickness. 17,31…”

Detecting ongoing disease activity in mildly affected multiple sclerosis patients under first-line therapies

“…Such a future study could also integrate potential other measurements of disease progression, that were not assessed in this work. These might include cognitive tests such as the Symbol Digits Modality Test (SDMT), spinal lesions in MRI or other new imaging modalities like optical coherence tomography [Baetge et al, 2021]. As clinical measures of disease progression have limitations, finding a suitable fluid biomarker that could help identify patients at risk of long-term worsening appears even more pressing.…”

Retinal ganglion cell loss is associated with future disability worsening in early relapsing–remitting multiple sclerosis

“…It is assumed that subclinical ganglion cell loss during MS might result—in addition to subclinical optic neuropathy—from retrograde transsynaptic degeneration and might be a measure for chronic CNS neurodegeneration [20‐22]. In line with this concept, GCIP thinning has been shown to correlate with both brain and spinal cord atrophy and disability in patients with MS [23‐29]. Similar associations have been reported in individuals with CIS and radiologically isolated syndrome [13,28,30,31].…”