Neurophysiology of Occipital Cortex Deterioration and its Relationships to Clinical Ophthalmic Measures in Glaucoma

Abstract

Purpose: Glaucoma is a neurodegenerative disease of the visual pathway. The effects of this disease on the visual processing of the cerebral cortex are still largely unknown. This study evaluated the functional activity of the visual brain in association with visual cortical metabolisms and clinical ophthalmic measures in glaucoma and healthy controls.

Methods: 8 early glaucoma (age=63.3±7.6 yrs), 9 advanced glaucoma (age=65.7±8.5 yrs), and 7 healthy control subjects (age=64.1±8.4 yrs) underwent blood-oxygen-level-dependent functional MRI (fMRI) upon 8Hz flickering visual presentation to each eye, followed by single-voxel metabolic proton magnetic resonance spectroscopy (1H-MRS) of the primary visual cortex (PVC) in a 3 Tesla MRI scanner. The strength of the hemodynamic response to the visual presentation (Z-score) and activated brain volumes (voxels) in the occipital cortex were calculated from fMRI using FSL and ImageJ software. Peak integrals of visual brain metabolites [N-acetylaspartate (NAA), creatine (Cr), choline (Cho), glutamate/glutamine complex (Glx) and myo-inositol (Ins)] were determined from 1H-MRS using the syngo MR software. Clinical spectral-domain OCT measurements of peripapillary retinal nerve fiber layer (pRNFL) thickness and macular ganglion cell complex (mGCC) thickness, and Humphrey visual field (VF) pattern standard deviation (PSD) and mean deviation (MD) were also obtained in each eye of the same patients.

Results: When comparing between fMRI and clinical ophthalmic measures, positive correlations were found in Z-score relative to pRNFL (p<0.05) and mGCC (p=0.07) thicknesses. When comparing fMRI to 1H-MRS, positive correlations were found in Z-score (p=0.08) and activated voxels (p<0.05) relative to Cho:Cr ratio. No significant correlation was found in Z-score or activated voxels compared to NAA:Cr, Glx:Cr, Ins:Cr, PSD and MD (p>0.1), or in age relative to fMRI, 1H-MRS, OCT and VF parameters (p>0.05).

Conclusions: The current results indicate strong structural, metabolic and functional associations between eye morphology and occipital cerebral cortex metabolism and hemodynamic activity in glaucoma. The positive fMRI-Cho:Cr correlations also suggest the early involvement of cholinergic pathways in the alterations in brain function before changes in neuronal integrity marker NAA:Cr take place in the PVC.

Keywords: 552 imaging methods (CT, FA, ICG, MRI, OCT, RTA, SLO, ultrasound) • 592 metabolism • 755 visual cortex