Structural and Metabolic Correlates of Transsynaptic Neurodegeneration with Eye Morphology and Visual Function in Glaucoma

Abstract

Purpose: Glaucoma is a neurodegenerative disorder of the visual system. To date, the role of transsynaptic degeneration in the pathophysiology of the disease remains incompletely understood. This study evaluated the microstructural and metabolic integrity in the posterior visual pathway in relation to retinal morphology and visual field (VF) function in glaucoma.

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 whole-brain microstructural diffusion tensor imaging (DTI) and single-voxel metabolic proton magnetic resonance spectroscopy (1H-MRS) of the primary visual cortex in a 3 Tesla MRI scanner. DTI parameters [fractional anisotropy (FA), and axial (AD), radial and mean diffusivities] of the optic radiation (OR) and the non-visual corticospinal tract (CST) were extracted and compared with visual brain metabolites [N-acetylaspartate (NAA), choline (Cho), glutamate/glutamine complex (Glx) and myo-inositol (Ins)] as a ratio to creatine (Cr) contents. For each subject, macular ganglion cell complex (GCC) and peripapillary retinal nerve fiber layer (pRNFL) thicknesses were obtained using spectral-domain OCT. VF pattern standard deviation (PSD) and mean deviation (MD) were also obtained for each eye. Associations between DTI, 1H-MRS, OCT and VF were analyzed.

Results: Within the posterior visual pathway, positive correlations were observed from FA vs Cho:Cr (p=0.01) and AD vs Cho:Cr (p=0.04). Comparing between eye and visual brain, positive correlations were obtained from AD vs GCC (p=0.047); Cho:Cr vs GCC, pRNFL and MD (p=0.004, 0.036 and 0.004); and Ins:Cr vs GCC, pRNFL and MD (p=0.04, 0.03, and 0.01), whereas, negative correlations were found from AD vs PSD (p=0.03), Cho:Cr vs PSD (p=0.007) and Glx:Cr vs pRNFL (p=0.04). No significant correlation was obtained in pRNFL vs DTI parameters in OR; DTI in CST vs 1H-MRS, OCT and VF; or age vs DTI, 1H-MRS, OCT and VF (p>0.05).

Conclusions: Current results indicate that FA and AD in microstructural DTI and Cho:Cr, Ins:Cr, and Glx:Cr in metabolic 1H-MRS may be sensitive markers to detect early transsynaptic damages before changes in neuronal integrity marker NAA:Cr occurred in visual cortex. GCC may be more sensitive than pRNFL at detecting abnormal eye-brain microstructural relationships with DTI in glaucoma.

Keywords: 552 imaging methods (CT, FA, ICG, MRI, OCT, RTA, SLO, ultrasound) • 612 neuro-ophthalmology: diagnosis • 755 visual cortex