Assessing Optic Nerve Involvement in Multiple Sclerosis With and Without History of Optic Neuritis Using OCT and MRI
Matilde Inglese1, Alessandro Gualco1, Giacomo Boffa2, Chiara Razzetta1, Sara Garbarino1, Maria Cellerino1
1University of Genoa, 2Department of Neuroscience, University of Genova
Objective:

To validate the 2024 McDonald inter-eye difference (IED) cutoff for optical coherence tomography (OCT) in a large multiple sclerosis (MS) cohort, to assess performance in detecting asymptomatic optic nerve lesions on MRI, and potential discrepancies between OCT and MRI

Background:
Optic nerve involvement was recently recognized as the fifth typical site for DIS in the 2024 McDonald criteria. The relationship between asymptomatic MRI-detected optic nerve lesions and OCT-derived IED in patients with and without prior ON remains scarce
Design/Methods:

A total of 785 consecutive MS patients underwent spectral-domain OCT to assess peripapillary retinal nerve fiber layer (pRNFL) and ganglion cell–inner plexiform layer (GCIPL) thickness. A subset of 260 patients underwent 3T MRI within three months of OCT, including 3D double inversion recovery.

Results:

The final cohort included 740 patients (27% with a history of ON). MRI was analyzed in 240 patients. The 2024 McDonald IED cutoff (GCIPL ≥4 µm or pRNFL ≥6 µm) showed 83% sensitivity, 55% specificity, and 63% overall accuracy for identifying prior ON. In the MRI subgroup, comparable performance was observed for detecting optic nerve involvement on MRI in patients without clinical ON. MRI detected lesions in 30% of asymptomatic eyes from (46%) patients without a history of ON, while OCT-IED was positive in 27% of asymptomatic patients. Concordance between OCT and MRI was 77% overall and 90% in eyes with previous ON. Among asymptomatic patients 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 demonstrated high sensitivity for both clinical and subclinical ON involvement. In patients without a prior history of ON, MRI detected lesions in 46%, while IED cutoff in 27%. OCT and MRI capture complementary yet only partially overlapping features, underscoring the importance of integrating both modalities
10.1212/WNL.0000000000216205
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