Resting Cerebral Blood Flow in Human Glaucoma

Abstract

Purpose: : Primary open angle glaucoma is a neurodegenerative disorder known to affect the primary visual cortex (V1) of non-human primates. While human post-mortem studies have also found evidence of neurodegeneration in V1, there is no reliable method for quantifying glaucomatous neurodegeneration in vivo. Neuronal degeneration reduces the local cerebral metabolic rate of oxygen (CMRO₂) and the resting cerebral blood flow (CBF) in the brain. Consequently, functional magnetic resonance imaging (fMRI) was used to quantify resting CBF within V1 in human glaucoma.

Methods: : Ten patients with primary open angle glaucoma (POAG) participated in our study. Visual function in both eyes was tested using standard automated perimetry (SITA-SAP) and short-wavelength automated perimetry (SITA-SWAP). Patients presented with superior/inferior visual field asymmetries on both tests of visual function as indicated by the Glaucoma Hemifield Test. Visual field data were combined across both eyes in each subject, and binocular visual field asymmetries were confirmed using a Monte Carlo simulation (all p < 0.05). Mean pattern deviation values were computed for the combined superior and inferior hemifields of each subject (PD_MEAN). Standard blood oxygen level dependent (BOLD) fMRI methods were used to obtain retinotopic maps of dorsal and ventral V1. Arterial Spin Labeling (ASL) fMRI was used to measure the mean resting CBF in dorsal and ventral V1 (CBF_MEAN). During the ASL scans, patients were scanned in the dark with their eyes open, but no visual stimulus was presented. Differences in resting CBF between ventral and dorsal V1 (ΔCBF_MEAN) were compared to differences in visual function between the superior and inferior visual fields (ΔPD_MEAN).

Results: : For both tests of visual function, the hemifield difference in visual function (ΔPD_MEAN) was correlated with the difference between dorsal and ventral cerebral blood flow (ΔCBF_MEAN) across subjects. The correlation statistics (r-values) between ΔPD_MEAN and ΔCBF_MEAN for SITA-SAP and SITA-SWAP were 0.49 and 0.64, respectively (all p < 0.05).

Conclusions: : The severity of vision loss in glaucoma is correlated with chronic alterations of resting blood perfusion in V1. ASL fMRI may be used to measure changes in chronic blood perfusion that are associated with glaucomatous neurodegeneration.

Keywords: blood supply • visual cortex • imaging methods (CT, FA, ICG, MRI, OCT, RTA, SLO, ultrasound)