Axonal loss of retinal neurons in multiple sclerosis associated with optic radiation lesions

Abstract

Objective: To investigate the potential links between thinning of retinal ganglion cell axons in eyes of patients with multiple sclerosis (MS) without past optic neuritis (ON) and MS-related inflammatory damage of the posterior visual pathway.

Methods: Temporal retinal nerve fiber layer (tRNFL) thickness was analyzed in eyes with no history of ON (NON) from 53 patients with relapsing-remitting MS. Fifty normal age- and sex-matched controls were examined with optical coherence tomography. Low-contrast visual acuity charts were used for functional assessment of vision. The optic tract (OT) and optic radiation (OR) were identified using probabilistic tractography, and volume of T2 fluid-attenuated inversion recovery lesions and diffusion tensor imaging (DTI) indices were measured within both structures. Cross-sectional diameter of the OT was also calculated.

Results: tRNFL thickness was significantly reduced in NON eyes and was associated with reduced low-contrast visual acuity. Lesions within the OR were detected in the majority of patients. There was a significant correlation between thinning of the tRNFL and OR lesion volume (adjusted for non-OR lesion volume, age, sex, and disease duration). tRNFL thickness also correlated with OR DTI indices. No OT lesions were identified in any of the patients and no relationship between retinal nerve fiber layer loss and potential markers of OT lesions was found.

Conclusion: The results demonstrate a strong tract-specific association between loss of tRNFL fibers and MS-related inflammation within OR.

Figure 1. Consecutive steps of MRI analysis

Quantification of the visual pathway lesions and diffusion tensor imaging indices. (A) 3D posterior visual pathway reconstruction using probabilistic tractography. Green = optic tract, yellow = optic radiation (OR). (B) Brain T2 fluid-attenuated inversion recovery lesions. (C) Coregistration of T2 lesions with visual pathway fibers. (D) Visual pathway lesions (blue). (E) Example of OR radial diffusivity from the same patients. Note significant diffusivity increase at the location of the lesion (arrow). (F) MRI of the optic tract was rotated using 3DSlicer software to provide a parallel view of chiasm and optic tracts. Red arrows indicate the site where diameter of the optic tract was measured. For A and B, T1 is used to display structural brain image.

Figure 2. Partial correlation between temporal retinal nerve fiber layer thickness and optic radiation lesion volume

Partial regression plot between temporal retinal nerve fiber layer (tRNFL) thickness and optic radiation (OR) lesion volume. Dependent variable = tRNFL thickness. Independent variable = OR lesion volume adjusted for lesion volume outside of OR, disease duration, sex, and age. Axes represent residuals. Linear fit and 95% individual confidence intervals are shown.

Figure 3. Partial correlations between temporal retinal nerve fiber layer thickness and optic radiation diffusion tensor imaging indices

Partial correlations between temporal retinal nerve fiber layer (tRNFL) thickness and optic radiation diffusion tensor imaging indices adjusted for disease duration, sex, and age. Axes represent residuals. Linear fit and 95% individual confidence intervals are shown. (A) Fractional anisotropy (FA). (B) Mean diffusivity (MD). (C) Axial diffusivity (AD). (D) Radial diffusivity (RD).