Objective:

To find the optimal retinal nerve fiber layer (RNFL) thickness difference threshold as a biomarker of prior unilateral optic neuritis (ON) in pediatric-onset multiple sclerosis (POMS) and examine its relationship with global and regional brain volumes.

Background:

Optical coherence tomography (OCT) offers a rapid, noninvasive means to detect axonal injury. Adult multiple sclerosis criteria use an RNFL inter-eye difference (IOD) ≥ 5 µm to indicate prior ON, but pediatric eyes are more symmetric and may require lower thresholds. Establishing pediatric-specific cutoffs and linking them to central nervous system structural integrity could enhance early diagnosis and prognostication.

Design/Methods:

In a cross-sectional case-control study, 20 POMS patients with prior unilateral ON (mean onset 15.1 y, exam 20.6 y) and 20 age-matched controls underwent bilateral spectral-domain OCT. Global RNFL thickness, inter-eye difference, and best-corrected visual acuity were measured. Whole-brain, gray-matter, and cerebellar volumes were derived from MRI. Group comparisons used Mann–Whitney U tests; correlations used Pearson r. ROC analysis with Youden’s J identified the optimal IOD threshold.

Results:

ON-affected eyes showed thinner RNFL versus controls (82.9 ± 21.7 µm vs 99.8 ± 9.8 µm, p = 0.0024). Median RNFL IOD was 8.5 µm in POMS vs 2.5 µm in controls (p = 0.0024). ROC analysis (AUC = 0.78) identified 4 µm as the optimal discrimination threshold. RNFL IOD correlated with inter-eye visual acuity difference (r = 0.41, p = 0.008) and inversely with whole-brain (p = 0.02), gray-matter (p = 0.03), and cerebellar volumes (p = 0.04).

Conclusions:

A 4 µm RNFL IOD reliably identifies prior ON in pediatric MS and associates with reduced brain, gray-matter, and cerebellar volumes, supporting its value as a marker of both localized and global neuroaxonal loss. Integrating OCT-based asymmetry metrics with volumetric MRI may improve early diagnosis and risk stratification in pediatric MS.