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

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.