Sex differences and subclinical retinal injury in pediatric-onset MS

Abstract

Objective: To assess retinal ganglion cell (RGC) injury and sex differences in axon loss in pediatric multiple sclerosis (MS). Methods: This is a cross-sectional evaluation of consecutive pediatric MS subjects and controls. Eyes with acute optic neuritis (ON) within 6 months of visit were excluded. Spectral domain optical coherence tomography (OCT) included peripapillary ring and macular scans with post-acquisition segmentation of retinal layers using automated software (Heidelberg v1.8.6.0). Generalized estimating equations (GEEs) measured associations of sex, history of ON, disease duration, and age with OCT outcomes. Results: In all, 53 MS subjects (100 eyes, median disease duration = 1.0 years, interquartile range (IQR) = 0.3, 2.5) were compared to 19 control subjects (38 eyes). Eyes with history of ON showed reduced retinal nerve fiber layer (RNFL: −26.8 µm, 95% confidence interval (CI) = −38.9, −14.8, p < 0.001) and 26% lower ganglion cell layer (GCL) volumes (−0.12 mm3, 95% CI = −0.16, −0.072, p < 0.001) compared to control eyes. Non-ON MS eyes had lower temporal RNFL (−11.9 µm, 95% CI = −18.6, −5.3, p < 0.001) and GCL volumes (−0.036 mm3, 95% CI = −0.06, −0.011, p = 0.004) than control eyes. In MS eyes, males versus females had lower global RNFL (−9.4 µm, 95% CI = −17.4, −1.33, p = 0.022) and in ON eyes had lower temporal quadrant RNFL (−9.6 µm, 95% CI = −15.1, −4.15, p = 0.001). Conclusion: Subclinical retinal injury occurs in pediatric-onset MS patients without a history of ON. As in adult-onset MS, substantial GCL thinning is present in eyes with prior ON. Finally, greater retinal axonal injury occurs in boys compared to girls.