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Combining inter-eye differences enhances detection of optic nerve involvement in multiple sclerosis.
Ting-Yi Lin1,2,3, Brenna McCormack1, Anna Bacchetti1
1Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Brain : a Journal of Neurology
|November 26, 2025
Summary
Combining optical coherence tomography measures of retinal nerve fiber layer and ganglion cell-inner plexiform layer inter-eye differences improves detection of optic nerve involvement in multiple sclerosis. These findings offer a more precise diagnostic approach for this common neurological condition.
Area of Science:
- Ophthalmology and Neuroscience
- Neuroimmunology
- Medical Imaging
Background:
- The 2024 revised McDonald criteria for multiple sclerosis (MS) include the optic nerve as a site for dissemination in space.
- Optical coherence tomography (OCT) measures of inter-eye differences in retinal nerve fiber layer (RNFL) and ganglion cell-inner plexiform layer (GCIPL) thicknesses are proposed for identifying unilateral optic nerve involvement in MS.
- The diagnostic utility of combining these OCT measures and assessing temporal-quadrant RNFL inter-eye differences requires further investigation.
Purpose of the Study:
- To investigate the diagnostic performance of combined OCT inter-eye difference measures for unilateral optic nerve involvement in MS.
- To evaluate the added value of temporal-quadrant RNFL inter-eye differences.
- To examine the influence of time, prior optic neuritis frequency, sex, and race on these inter-eye differences.
Main Methods:
- Retrospective analysis of OCT images from 1854 individuals with MS, with external validation on 254 individuals.
- Receiver operating characteristic (ROC) analyses to determine optimal inter-eye difference thresholds (RNFL ≥6μm, GCIPL ≥4μm, temporal-quadrant RNFL ≥8μm).
- Mixed-effects models to assess the impact of clinical factors (time, prior optic neuritis, sex, race) on inter-eye differences.
Main Results:
- Combined RNFL (≥5μm) and GCIPL (≥3μm) inter-eye differences demonstrated improved sensitivity (72.5%) and specificity (86.6%) for unilateral optic nerve involvement compared to individual measures.
- Temporal-quadrant RNFL inter-eye differences did not enhance diagnostic performance.
- Inter-eye differences remained stable longitudinally (median 5.1 years) and were unaffected by prior optic neuritis frequency or sex; thresholds were comparable across races.
Conclusions:
- Concurrent use of lower thresholds for RNFL (≥5μm) and GCIPL (≥3μm) inter-eye differences enhances the detection of unilateral optic nerve involvement in MS.
- OCT-derived inter-eye differences are stable over time and reliable across different demographic groups.
- These findings support the integration of combined OCT inter-eye difference measurements into MS diagnostic protocols.
