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

Abstract

Objective: Retinal 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.

Methods: In 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.

Results: A 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.

Conclusion: In 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.

Figure 1. Flowchart

Study flowchart depicting exclusions, dropouts, and the final sample. Of 64 study participants, 59 underwent OCT. After quality control and excluding missing data and data of eyes having a history of ON or lacking information on ON, data of 79 eyes were included in analyses regarding pRNFL and data of 77 eyes in analyses with mRNFL, GCIPL, and INL, respectively. “n” refers to the number of study participants. Numbers in brackets display the number of eyes. GCIPL = macular ganglion cell-inner plexiform layer; INL = inner nuclear layer; mRNFL = macular retinal nerve fiber layer; OCT = optical coherence tomography; ON = optic neuritis; pRNFL = peripapillary retinal nerve fiber layer.

Figure 2. Scatterplots

Scatterplots depicting associations between thickness in pRNFL, mRNFL, GCIPL, and cognitive performance in TMT-B. Excluded outliers in each analysis n = 1. GCIPL = ganglion cell-inner plexiform layer; mRNFL = macular retinal nerve fiber layer; pRNFL = peripapillary retinal nerve fiber layer; TMT-B = Trail Making Test–B.

Figure 3. Boxplots-Revised

Boxplots and point clouds depicting raw scores on cognitive performance per RLT extreme group. (A) Cognitive performance in Trail Making Test–B (TMT-B), Verbaler Lern-und Merkfaehigkeitstest (VLMT), and Brief Visuospatial Memory Test–Revised (BVMT-R), each divided into the low tertile and high tertile of retinal layer thickness (RLT) of macular ganglion cell-inner plexiform layer (mGCIPL). (B) Cognitive performance in Trail Making Test–B (TMT-B) divided into low tertile and high tertile of retinal layer thickness (RLT) of macular ganglion cell-inner plexiform layer (mGCIPL) (all analyses including TMT-B: excluded outliers n = 2). *Raw scores in designated cognitive test differ significantly between low and high tertile of RLT referring to uncorrected p values.