Fixel-Based Analysis of Visual Pathway White Matter in Primary Open-Angle Glaucoma

Area of Science:

• Neuroscience
• Ophthalmology
• Medical Imaging

Background:

• White matter degeneration in the visual pathways is a known feature of primary open-angle glaucoma (POAG).
• Previous studies relied on diffusion tensor imaging (DTI), which has limitations in biological interpretation and technical accuracy.
• Fixel-based analysis (FBA) offers a novel approach with biologically meaningful metrics like fiber density (FD) and fiber-bundle cross section (FC).

Purpose of the Study:

• To investigate glaucomatous degeneration in the pregeniculate optic tracts (OTs) and postgeniculate optic radiation (ORs) using FBA.
• To compare the sensitivity of FBA metrics (FD and FC) in assessing white matter changes in POAG.
• To elucidate the pathophysiology of white matter degeneration in the visual pathways of POAG patients.

Main Methods:

• A cross-sectional case-control study involving 12 POAG patients and 16 healthy controls.
• Acquisition of multi-shell diffusion-weighted images.
• Application of FBA to create a population template and probabilistic tractography to track OTs and ORs, followed by comparison of FD and FC between groups.

Main Results:

• POAG patients showed a significant decrease in both FD and FC in the OTs compared to controls.
• A significant decrease in FD, but not FC, was observed in the ORs of POAG patients.
• These findings indicate differential patterns of white matter degeneration between the OTs and ORs in POAG.

Conclusions:

• FBA is a sensitive method for quantifying white matter changes in glaucoma.
• The optic tracts appear to undergo more advanced white matter degeneration than the optic radiations in POAG.
• Anterograde trans-synaptic propagation may be the primary mechanism driving glaucomatous spread along the visual pathways.