Associations between Visual Cortex Metabolism and Visual Field Loss Patterns in Glaucoma

Abstract

Purpose : Recent magnetic resonance spectroscopy (MRS) studies in glaucoma patients and experimental glaucoma suggest that brain metabolite levels are associated with glaucomatous neurodegeneration. However, it remains unclear how these brain metabolites influence visual field (VF) function. This study examined the associations between metabolic profiles in the visual cortex and VF loss patterns in glaucoma.

Methods : Twenty early glaucoma, 28 advanced glaucoma, and 19 healthy subjects underwent 3-Tesla proton MRS of the visual cortex using a 2.2×2.2×2.2 cm³ voxel centered at the calcarine sulcus. Gamma-aminobutyric acid (GABA), glutamate (Glu), and choline (Cho) levels were quantified from the spectra using LCModel and compared between groups using ANOVA and post-hoc Tukey’s tests. Partial correlation analyses were performed to associate metabolite levels with total deviations of 24-2 VF tests. The resulting VF models were aligned with 16 predefined archetypal (AT) patterns of VF loss (PMID: 25505132) using multivariate linear regression to characterize VF loss regions.

Results : Clinical ophthalmic measurements were significantly different between subject groups, whereas age and sex were not (Fig. 1). Lower GABA, Glu, and Cho levels were found in both early and advanced glaucoma patients compared to healthy subjects (Fig. 2). In archetypal analyses, GABA, Glu and Cho were positively associated with the normal VF archetype (AT1) in both eyes. Decreasing GABA was associated with worse VF loss in the superonasal step area (AT3), whereas decreasing Glu was associated with worse VF loss in the inferonasal step (AT5) and inferior altitudinal (AT13) areas in the left eye. Decreasing Cho was also associated with worse VF loss in the inferonasal (AT10) and inferior altitudinal (AT13) areas in the left eye, as well as worse VF loss in the inferonasal (AT10) and nasal (AT15) areas in the right eye.

Conclusions : GABA, Glu, and Cho levels were lower in both early and advanced glaucoma patients. These neurometabolites also appeared to associate with complementary regional patterns of VF loss in glaucoma, with GABA affecting the superonasal areas more, and Glu and Cho affecting the inferior areas more. These spectral biomarkers may help determine the glaucoma pathogenesis and plasticity in the brain with relevance to regional VF loss in both eyes.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.