Relationships among Visual Cortex Metabolism, Retinal Morphology and Visual Function in Early and Advanced Glaucoma

Abstract

Purpose: Glaucoma is a neurodegenerative disease of the visual system. Although recent reports indicate the involvement of the visual brain, apart from the eye, in glaucoma, its underlying pathophysiological mechanisms remain largely unknown. This study evaluated the visual cortical metabolism in association with structural and functional ophthalmic clinical measurements in early and advanced glaucoma.

Methods: 5 early (age=68.0±4.6 yrs) and 5 advanced glaucoma patients (age=68.2±3.5 yrs) underwent proton magnetic resonance spectroscopy (1H-MRS) of both left and right primary visual cortex using a 3 Tesla MRI scanner. Peak integrals of visual brain metabolites [N-acetylaspartate (NAA), creatine (Cr), choline (Cho), glutamate/glutamine complex (Glx), myo-inositol (Ins)] were determined from 1H-MRS using the syngo MR software. The global averages of clinical spectral-domain OCT measurements [peripapillary retinal nerve fiber layer (pRNFL) thickness; macular ganglion cell/inner plexiform layer (mGCL+IPL) thickness; cup-to-disc ratio (c/d)] and Humphrey visual field (VF) pattern standard deviation (PSD) were also obtained in each eye of the same patients. The OCT and VF parameters averaged between both eyes or in the worst eye alone were compared with brain metabolite peak integrals relative to Cr. Mann-Whitney tests were also performed between early and advanced glaucoma.

Results: Significant differences were obtained in all OCT and VF measurements between early and advanced glaucoma (p<0.05). In 1H-MRS, Cho:Cr in the visual cortex was lower in advanced glaucoma than in early glaucoma (p<0.05). Positive correlations were found when comparing pRNFL with Cho:Cr and Ins:Cr, mGCL+IPL with Cho:Cr and Ins:Cr, and c/d with Glx:Cr (p<0.05); whereas negative correlations were observed when comparing pRNFL with Glx:Cr, c/d with Cho:Cr and Ins:Cr, and PSD with Cho:Cr (p<0.05). No apparent correlation was found between NAA:Cr and clinical parameters (p>0.05).

Conclusions: The current results indicated the close associations between visual brain metabolisms and structural and functional clinical ophthalmic findings in glaucoma. These changes were detected prior to alterations in neuronal integrity marker NAA:Cr and may be a sensitive means to assess glaucoma. They also suggested the involvement of cholinergic and glutamatergic neurotransmission systems in the mechanisms of glaucoma in visual cortex.

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