A Multi-Arm, Randomized, Blinded, Sham-Controlled Trial of Cognitive Rehabilitation and Aerobic Exercise (The CogEx trial) for cognitive impairment in people with Progressive Multiple Sclerosis

Abstract

Introduction: Trans-synaptic degeneration (TSD) is a putative mechanism of neuronal injury in multiple sclerosis (MS). Retrograde TSD following pathology of the posterior visual pathway has been implicated as a cause of homonymous hemi-macu-lar atrophy (HMA) of the ganglion cell/inner plexiform layer (GCIPL). Optical coherence tomography (OCT) allows qualitative and quantitative identification of HMA. Objectives/Aims: To determine (1) the prevalence of HMA, (2) the clinical significance of HMA, and (3) the associated retinal changes of HMA in people with MS (PwMS). Methods: In this cross-sectional study, 241 healthy controls (HC) and 1130 PwMS underwent Cirrus HD-OCT with automated mac-ular layer segmentation. For quantitative identification of HMA, we used a normalized asymmetry ratio (NAR) for each eye, defined as the temporo-nasal GCIPL difference divided by the thicker side's hemi-macular GCIPL thickness. Normative NAR cutoffs were defined at 1 st and 99 th percentile for NAR in HC. PwMS with HMA were defined as having extreme NAR in both eyes, or in the contralateral eye in the case of known unilateral optic neuritis or segmentation failure in the fellow eye. HMA PwMS were matched to non-HMA PwMS 1:2 according to age, sex, race, and MS sub-type. Linear regression models were used in analyses. Results: In this large cohort, 79 PwMS (143 eyes) exhibited quantitative HMA (prevalence of 7%). The HMA cohort had a mean age of 50.1 years (SD 12.4 years), 72.2% were female, and 31.6% had progressive MS. Compared to matched non-HMA PwMS, HMA PwMS had higher EDSS scores compared to non-HMA PwMS (diff: 0.5 [95%CI 0.1 to 0.9]; p=0.02) and worse 100% visual acuity (VA)