Optic nerve volume and diffusivity jointly predict multifocal visual evoked potential amplitude after optic neuritis

Background: Acute inflammatory demyelination of the optic nerve, known as optic neuritis, is a common symptom of multiple sclerosis (MS). In extant optic neuritis, there is often non-recoverable visual dysfunction. Multifocal visual evoked potentials (mfVEP) can sensitively reveal changes in visual function across the visual field. However, it is still unclear how the extent of damage within the optic nerve, measured using magnetic resonance imaging (MRI), relates to changes in mfVEP. Objective: To determine the relationship between macroscopic volumetric and microscopic diffusion changes to the optic nerve, and changes to visual function after optic neuritis. Methods: Sixteen patients with optic neuritis and ten controls underwent optic nerve MRI using diffusion tensor imaging (DTI), high resolution T1 and T2 fluid-attenuated inversion recovery (FLAIR) imaging. For each optic nerve, fractional anisotropy (FA) and volume were measured. The amplitude and latency of mfVEP and logMAR visual acuity was recorded for each eye. The affected side was compared with both the unaffected and control, and asymmetry coefficients ([Unaffected - Affected]/Unaffected) were used to study the relationship between structural and functional measures. Results: Significant abnormalities in MRI and mfVEP measures were detected in the affected side compared with the unaffected or control. There was no relationship between optic nerve FA and volume asymmetries in patients. However, variance in mfVEP amplitude asymmetry was jointly explained by both FA and volume (AMPasymm = (0.60)*VOLasymm + (0.50)*FAasymm; R = 0.80; P = 0.001). Reduced mfVEP amplitude was associated with reduced visual acuity (R = -0.80; P < 0.001). Conclusions: In extant optic neuritis, there are microscopic changes in the optic nerve, which can be detected as reduced diffusion anisotropy, and macroscopic changes detected as optic nerve atrophy. Both diffusivity and volumetric changes are important predictors of visual dysfunction.