Progressive retinal changes in pediatric multiple sclerosis

Objectives To determine to what extent acute demyelinating episodes versus chronic degenerative phenomena drive retinal neuroaxonal damage in pediatric acquired demyelinating syndromes (ADS). Methods We acquired optical coherence tomography (OCT) data (follow-up range: 2 weeks - 5 years, at variable intervals from presentation) in pediatric participants who had multiple sclerosis (MS), monophasic ADS, or were healthy. Multivariable mixed effects models were used to assess the association of the number of demyelinating episodes (either optic neuritis [ON], or non-ON relapses) with changes in retinal nerve fiber layer (RNFL) or ganglion cell layer-inner plexiform layer (GCIPL) thickness. Results 64 OCT sans from 23 MS, and 33 scans from 12 monophasic ADS participants were compared with 68 scans from 62 healthy participants. The first ON episode had the biggest impact on RNFL or GCIPL thickness in monophasic ADS (RNFL: -7.9 µm, CI=5.5, p = 0.0056; GCIPL: -8.4 µm, CI=4.4, p = 0.0002) and MS (RNFL: -16 µm, CI = 3.7, p < 10^-6; GCIPL: -15 µm, CI = 2.6, p < 10^-6). Non-ON relapses were also associated with small but significant retinal thickness reductions in MS (RNFL: -2.6 µm/relapse, CI = 1.4, p = 0.0003; GCIPL: -2.8 µm/relapse, CI = 0.89, p < 10^-6). MS participants showed progressive GCIPL thinning independent of acute demyelinating episodes (-2.7 µm/year, CI = 1.9, p = 0.0058). Conclusions We showed a prominent impact of early ON episodes on OCT measures of neuroaxonal structure in patients with ADS. We also demonstrated negative effects of non-ON relapses, and the presence of chronic retinal neurodegenerative changes, in youth with MS.