Assessing Visual Pathway White Matter Degeneration in Primary Open-Angle Glaucoma Using Multiple MRI Morphology and Diffusion Metrics

Abstract

Background

Primary open-angle glaucoma (POAG), a leading cause of irreversible blindness, is associated with neurodegeneration in the visual pathway, but the underlying pathophysiology remains incompletely resolved.

Purpose

To characterize macro- and microstructural white matter abnormalities in optic tract (OT) and optic radiation (OR) of POAG.

Study type

Prospective.

Populations

A total of 34 POAG patients (21 males, 13 females) and 25 healthy controls (HCs) (16 males, nine females).

Field Strength/Sequence

3 T; multiband spin-echo echo planar diffusion spectrum imaging (DSI).

Assessment

We compared multiple morphology metrics, including volume, area, length, and shape metrics, as well as diffusion metrics such as diffusion tensor imaging (fractional anisotropy [FA], mean diffusivity, radial diffusivity, and axial diffusivity), mean apparent propagator (mean squared displacement, q-space inverse variance, return-to-origin probability, return-to-axis probabilities [RTAP] and return-to-plane probabilities, non-Gaussianity, perpendicular non-Gaussianity, parallel non-Gaussianity), and neurite orientation dispersion and density imaging (intracellular volume fraction, orientation dispersion index [ODI], and isotropic volume fraction of the OT and OR).

Statistical Tests

Statistical comparisons and classifications employed linear mixed model and logistic regression. Diagnostic performance was assessed using area under the receiver operating characteristic curve (AUC). P-value <0.05 was statistically significant.

Results

Morphology analysis in POAG revealed a lower span in the OR (29.43 ± 2.30 vs. 30.59 ± 2.01, 3.8%) and OT (19.73 ± 2.21 vs. 20.68 ± 1.37, 4.6%), and a higher curl (3.03 ± 0.22 vs. 2.90 ± 0.16, 4.5%) in OT. Diffusion metrics revealed lower mean FA (OR: 0.328 ± 0.03 vs. 0.340 ± 0.018, 3.5%; OT: 0.255 ± 0.022 vs. 0.268 ± 0.018, 4.9%) and lower mean RTAP (OR: 5.919 ± 0.529 vs. 6.216 ± 0.489, 4.8%; OT: 4.089 ± 0.402 vs. 4.280 ± 0.353, 4.5%), with higher mean ODI in the OT (0.448 ± 0.029 vs. 0.433 ± 0.025, 3.5%). Combined models, incorporating these MRI metrics, effectively discriminated POAG from HCs, achieving AUCs of 0.84 for OR and 0.83 for OT.

Data Conclusions

DSI-derived morphology and diffusion metrics demonstrated macro- and micro abnormalities in the visual pathway, providing insights into POAG-related neurodegeneration.

Level of Evidence

2

Technical Efficacy

Stage 3