Quick Take: Using Acute Optic Neuritis Trials to Assess Neuroprotective and Remyelinating Therapies in Multiple Sclerosis

1. Acute optic neuritis appears may be an appropriate condition to test neuroprotective and re-myelinating therapies after acute inflammation in multiple sclerosis.

Evidence Rating Level: 2 (Good)

Multiple sclerosis (MS) requires the development and implementation of neuroprotective and remyelinating therapies. Acute optic neuritis (AON) may be a potential, reduced-risk proxy condition for the evaluation of these treatments following acute inflammation. The AON-VisualPath prospective cohort study enrolled 60 participants with AON (2011-2018) and followed-up patients for up to 18 months using optical coherence tomography, visual acuity tests, and multifocal visual evoked potentials in a subset of 25 participants. Participants displayed early and significant inner retinal thinning, with a rate of 2.38 μm per week during the first four weeks in the ganglion cell plus inner plexiform layer (GCIPL). Compared to expected changes within the eyes of healthy participants, AON participants demonstrated a six-month change in latency of 20 ms (difference 19.87 ms, 95% CI -0.80 ms to 1.06 ms), though not statistically significant. Six-month visual endpoints were strongly associated with intereye differences in 2.5% low-contrast letter acuity, correlating with changes in mfVEP latency (adjusted R2 0.26), GCIPL thinning (adjusted R2 0.50), and peripapillary retinal nerve fiber layer thinning (RNFL; adjusted R2, 0.57). Five-letter increment in high-contrast visual acuity at presentation was associated with six-month thinning outcomes: 1.41 μm reduction in peripapillary RNFL (p<0.001) and 0.86 μm reduction in GCIPL thinning (p=0.001). No changes were noted in multifocal visual evoked potential latency. Investigators note that a six-month, two-arm, parallel-group trial would require 37-50 participants per group to demonstrate 50% efficacy in GCIPL thinning or change in multifocal visual evoked potential latency. Nonetheless, this study suggests that the evaluation of AON can be used in studying of the effect of neuroprotective and remyelinating therapies in MS.

Click to read the study in JAMA Neurology

Image: PD

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