Faculty Bibliography

BACKGROUND:Leucine-rich repeat and immunoglobulin domain-containing Nogo receptor-interacting protein 1(LINGO-1 is a key suppressor of oligodendrocyte differentiation and axonal remyelination and regeneration. This analysis evaluated the potential benefit of opicinumab, a human monoclonal antibody against LINGO-1, vs placebo on exploratory clinical endpoints of patient-reported vision-related functioning and high-contrast visual acuity (HCVA) in RENEW participants with acute optic neuritis (AON). METHODS:Participants were randomized to 100 mg/kg opicinumab intravenous or placebo every 4 weeks (6 infusions). Assessments were conducted in the per-protocol (PP) population and included: 25-item National Eye Institute Visual Functioning Questionnaire (NEI-VFQ-25), 10-item Neuro-Ophthalmic Supplement (NOS-10), and HCVA. RESULTS:The opicinumab group (n = 33) had worse mean (SD) baseline patient-reported vision-related functioning scores vs placebo (n = 36): NEI-VFQ-25 composite, 75.5 (17.6) vs 79.0 (16.6); NOS-10 composite, 63.6 (19.8) vs 69.8 (21.2), respectively. By Week 24, the placebo and opicinumab groups experienced substantial mean improvements from baseline (NEI-VFQ-25 composite, 15.17 vs 13.51 [difference (95% CI): -1.66 (-5.11 to 1.78)]; NOS-10 composite, 17.40 vs 16.04 [difference (95% CI): -1.35 (-7.38 to 4.67)]). Between-treatment differences in mean change from baseline were not significantly different at any time point. Analysis of covariance-adjusted mean recovery from baseline in HCVA at Week 24 for the affected eyes was 11.8 and 8.7 letters for placebo and opicinumab, respectively (P = 0.202). CONCLUSIONS:Most participants in the RENEW PP population demonstrated substantial recovery from baseline in patient-reported vision-related functioning and HCVA, regardless of treatment and structural damage. Average scores after recovery remained lower than those of published disease-free control groups. These results provide important information on visual function recovery in patients with AON, as measured by NEI-VFQ-25 and NOS-10.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

OBJECTIVE:To determine the optimal thresholds for inter-eye differences in retinal nerve fiber and ganglion cell+inner plexiform layer thicknesses for identifying unilateral optic nerve lesions in multiple sclerosis. BACKGROUND:Current international diagnostic criteria for multiple sclerosis do not include the optic nerve as a lesion site despite frequent involvement. Optical coherence tomography detects retinal thinning associated with optic nerve lesions. METHODS:In this multi-center international study at 11 sites, optical coherence tomography was measured for patients and healthy controls as part of the International Multiple Sclerosis Visual System Consortium. High- and low-contrast acuity were also collected in a subset of participants. Presence of an optic nerve lesion for this study was defined as history of acute unilateral optic neuritis. RESULTS:Among patients (n=1,530), receiver operating characteristic curve analysis demonstrated an optimal peripapillary retinal nerve fiber layer inter-eye difference threshold of 5 microns and ganglion cell+inner plexiform layer threshold of 4 microns for identifying unilateral optic neuritis (n=477). Greater inter-eye differences in acuities were associated with greater inter-eye retinal layer thickness differences (p≤0.001). INTERPRETATION/CONCLUSIONS:Inter-eye differences of 5 microns for retinal nerve fiber layer and 4 microns for macular ganglion cell+inner plexiform layer are robust thresholds for identifying unilateral optic nerve lesions. These thresholds may be useful to establish the presence of asymptomatic and symptomatic optic nerve lesions in multiple sclerosis and could be useful in a new version of the diagnostic criteria. Our findings lend further validation for utilizing the visual system in a multiple sclerosis clinical trial setting.

OBJECTIVE:The Mobile Universal Lexicon Evaluation System (MULES) is a test of rapid picture naming under investigation. Measures of rapid automatic naming (RAN) have been used for over 50 years to capture aspects of vision and cognition. MULES was designed as a series of 54 grouped color photographs (fruits, random objects, animals) that integrates saccades, color perception and contextual object identification. We examined MULES performance in youth, collegiate and professional athletes at pre-season baseline and at the sidelines following concussion. METHODS:Our study teams administered the MULES to youth, collegiate and professional athletes during pre-season baseline testing. Sideline post-concussion time scores were compared to pre-season baseline scores among athletes with concussion to determine degrees and directions of change. RESULTS:Among 681 athletes (age 17 ± 4 years, range 6-37, 38% female), average test times at baseline were 41.2 ± 11.2 s. The group included 280 youth, 357 collegiate and 44 professional athletes; the most common sports were ice hockey (23%), soccer (17%) and football (11%). Age was a predictor of MULES test times, with longer times noted for younger participants (P < .001, linear regression). Consistent with other timed performance measures, significant learning effects were noted for the MULES during baseline testing with trial 1 test times (mean 49.2 ± 13.1 s) exceeding those for trial 2 (mean 41.3 ± 11.2 s, P < .0001, paired t-test). Among 17 athletes with concussion during the sports seasons captured to date (age 18 ± 3 years), all showed increases (worsening) of MULES time scores from pre-season baseline (median increase 11.2 s, range 0.6-164.2, P = .0003, Wilcoxon signed-rank test). The Symptom Severity Score from the SCAT5 Symptom Evaluation likewise worsened from pre-season baseline following injury among participants with concussion (P = .002). CONCLUSIONS:Concussed athletes demonstrate worsening performance on the MULES test compared to their baseline time scores. This test samples a wide network of brain pathways and complements other vision-based measures for sideline concussion assessment. The MULES test demonstrates capacity to identify athletes with sports-related concussion.