The Inner Nuclear Layer in Pediatric Multiple Sclerosis

Pediatric onset multiple sclerosis (POMS) leads to optic nerve and retinal damage from optic neuritis (ON) and potential subclinical disease activity. Neuroaxonal retinal damage manifests in peripapillary retinal nerve fiber layer (pRNFL) and macular ganglion cell and inner plexiform layer (GCIP) thinning. Inner nuclear layer (INL) thickness has been suggested to increase with inflammatory activity or after acute ON, and decrease from chronic neurodegeneration. Macular microcysts in the INL have been described in patients with adult MS. The objective of this study was to investigate the INL in a large cohort of POMS as a potential biomarker for evaluation of disease course and therapeutic success.

For this cross-sectional case-control study, we prospectively recruited 153 patients with POMS and 92 controls, including asymptomatic healthy volunteers and children admitted to the hospital with nonretinal disorders. Optical coherence tomography was performed including intraretinal segmentation. Visual function was determined as best corrected visual acuity (BCVA).

Eyes of children with POMS with prior ON had increased INL thickness (44.31 µm) compared with control eyes (42.96 µm, p = 0.014), whereas pRNFL (83 µm, p < 0.001) and GCIP thickness (68.42 µm, p < 0.001) were reduced compared with control eyes (pRNFL 97 µm, GCIP 78.53 µm). In eyes without history of ON, INL and other layer thicknesses were not different from controls. pRNFL (B = -2, p < 0.001) and GCIP loss (B = -1.6, p < 0.001), but not INL, were associated with worse BCVA. We found macular microcysts in 1 eye of 1 patient with a history of severe ON (0.3%). INL thickness was not associated with age, sex, disease duration, immunotherapy, disability or the MRI parameters T2 lesion count, T2 lesion volume, contrast-enhancing lesions, or contrast-enhancing lesion volume.

The INL in POMS shows changes similar to what has been reported in adults, with macular microcysts being much rarer. A lack of cross-sectional association between INL thickness and disease severity may represent the early disease stage with neuroinflammation instead of neurodegeneration being in focus.