Early changes in basal cerebral blood flow and GABAergic activity in the visual cortex of glaucoma patients

Abstract

Purpose : Recent studies have indicated reduced blood flow in not only the eye but also the brain in patients with late glaucoma (LG). In contrast, patients with early glaucoma (EG) appear to show increased ocular blood flow, but little is known about their corresponding brain changes and their specific pathology. This study utilized non-invasive functional and molecular imaging biomarkers to determine cerebral blood flow (CBF) and neurochemical changes in the visual cortex of EG and LG patients.

Methods : Four EG (age=67.00±5.26 years; 2F), 6 LG (age=65.33±2.75 years; 1F), and 5 healthy controls (age=63.00±3.11 years; 1F) underwent pseudo-continuous arterial spin labeling (pCASL) functional MRI and MEGA-PRESS magnetic resonance spectroscopy (MRS) at rest using a 3-Tesla MRI scanner. Basal CBF was measured from pCASL in the visual and motor cortices (Figure 1a). For MRS, the level of gamma-aminobutyric acid (GABA) in the visual cortex was quantified through the LCModel software (Figure 2a), and normalized over the N-acetyl aspartate and N-acetyl aspartyl glutamic acid complex (NAA+NAAG) to account for systematic fluctuations following LCModel guidelines.

Results : Basal CBF in the white matter (WM) of the visual cortex was significantly higher for EG compared to LG (p=0.021) and controls (p=0.045), whereas basal CBF in the gray matter (GM) of the visual cortex was significantly higher for EG compared to LG (p=0.042) (Figure 1b). No apparent CBF difference was found within the motor cortex across groups (p>0.05). For MRS, normalized GABA levels appeared lower in EG than in controls (p=0.021), while LG had a trending decease compared to controls (p=0.092) (Figure 2b). Within the glaucoma groups, we also found a negative association between basal CBF and normalized GABA levels in both WM (p=0.038) and GM (p=0.039) (Figures 2c-d).

Conclusions : The elevated basal CBF and lower baseline GABA levels in the visual cortex of EG suggest that vascular autoregulation dysfunction and/or neurochemical adaptation may be occurring in the brain’s visual system apart from the eye during the initial phases of glaucoma pathogenesis. Within glaucoma groups, the inverse correlations demonstrated between basal CBF and baseline GABA levels may also offer a quantitative framework for interrogating inhibitory GABAergic activity and hemodynamic reactivity relationships in the glaucomatous brain during disease progression.

This is a 2020 ARVO Annual Meeting abstract.