Assessing Optic Nerve Involvement in Multiple SclerosisUsing Optical Coherence Tomography and Magnetic Resonance Imaging

Background: Optic nerve involvement in Multiple Sclerosis (MS) can be detected with Optical Coherence Tomography (OCT) based on intereye difference (IED). We aimed to assess optic nerve involvement in a large real-world MS cohort applying the 2024 McDonald IED cut off criteria, and to investigate OCT-MRI concordance. Methods: OCT measurements of peripapillary-retinal-nerve-fiber-layer (pRNFL) and ganglion-cell-inner-plexiform-layer (GCIPL) thickness were analyzed in 740 MS patients. Clinical histories of optic neuritis (ON) were reviewed. Three-dimensional double inversion recovery MRI sequences for optic nerve assessment were available for 240 patients. Results: The IED cutoff (GCIPL ≥ 4 μm or pRNFL ≥ 6 μm) demonstrated 83% sensitivity and 55% specificity for identifying prior ON. In the MRI subgroup, it yielded 67% sensitivity and 83% specificity for detecting asymptomatic optic nerve lesions. MRI identified lesions in 46% of patients without a prior history of ON, whereas OCT-IED was positive in 40%, resulting in an overall OCT-MRI concordance of 77%. Among asymptomatic patients (n = 164), 25 were OCT-negative/MRI-positive (11 with bilateral optic nerve involvement) and 15 were OCT-positive/MRI-negative, mostly with isolated GCIPL or pRNFL asymmetry. Conclusions: The 2024 McDonald IED cutoff demonstrates high sensitivity for prior ON but reduced sensitivity for subclinical optic nerve involvement. MRI appears slightly more sensitive, with both modalities providing complementary information on optic nerve pathology.