Optical coherence tomography (OCT) measurements and cognitive performance in multiple sclerosis: a systematic review and meta-analysis

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Abstract
Background Several studies report mixed associations between the retinal nerve fiber layer (RNFL) thickness with cognitive and physical disability in persons with multiple sclerosis (PwMS). Systematic synthesis of these findings is crucial in deriving credible conclusions. Methods Five databases were searched from their inception to March 2022. The inclusion criteria for studies were MS-specific and required RNFL and cognitive performance data in order to be analyzed. The selection processes followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Results The systematic review yielded 31 studies that investigated the association between RNFL thickness and cognitive performance. Twenty-two studies reported positive associations, and nine did not. The meta-analysis included 11 studies with a total of 782 PwMS with mean age of 40.5 years, mean Expanded Disability Status Scale (EDSS) of 2.7, and disease duration of 11.3 years. RNFL thickness was significantly associated Symbol Digit Modalities Test (pooled r = 0.306, p < 0.001), Paced Auditory Serial Addition Test (pooled r = 0.374, p < 0.001) and Word List Generation (WLG, pooled r = 0.177, p < 0.001). RNFL was also significantly correlated with visuospatial learning and memory tests (pooled r = 0.148, p = 0.042) and verbal learning and memory tests (pooled r = 0.245, p = 0.005). Within three eligible studies, no significant association between ganglion cell inner-plexiform layer and SDMT 0.083 (95% CI − 0.186, 0.352) was noted. The heterogeneity was high in all correlation studies (I2 > 63% and p < 0.008) except for the WLG and visuospatial memory findings. Conclusion RNFL thickness is associated with cognitive processing speed, verbal learning and memory, visual learning and memory, as well as verbal fluency in PwMS. The number of studies included in the meta-analyses were limited due to non-standardized reporting.

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