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Sci Rep. 2016 Aug 11;6:31464. doi: 10.1038/srep31464.

Retinal Structures and Visual Cortex Activity are Impaired Prior to Clinical Vision Loss in Glaucoma.

Murphy MC1,2,3, Conner IP1,2,3,4, Teng CY1,2, Lawrence JD1,2, Safiullah Z1,2, Wang B2,3,4, Bilonick RA2,5, Kim SG1,4,6,7,8, Wollstein G2,3,4, Schuman JS2,3,4,6,9,10, Chan KC1,2,3,4,6,10.

Author information

NeuroImaging Laboratory, University of Pittsburgh, Pittsburgh, PA, USA.
UPMC Eye Center, Ophthalmology and Visual Science Research Center, Department of Ophthalmology, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
Louis J. Fox Center for Vision Restoration, University of Pittsburgh, PA, USA.
Department of Bioengineering, Swanson School of Engineering, University of Pittsburgh, PA, USA.
Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh, PA, USA.
McGowan Institute for Regenerative Medicine, University of Pittsburgh, PA, USA.
Center for Neuroscience Imaging Research, Institute for Basic Science, Suwon, Korea.
Department of Biomedical Engineering, Sungkyunkwan University, Suwon, Korea.
Clinical and Translational Science Institute, University of Pittsburgh, Pittsburgh, PA, USA.
Center for the Neural Basis of Cognition, University of Pittsburgh and Carnegie Mellon University, Pittsburgh, PA, USA.


Glaucoma is the second leading cause of blindness worldwide and its pathogenesis remains unclear. In this study, we measured the structure, metabolism and function of the visual system by optical coherence tomography and multi-modal magnetic resonance imaging in healthy subjects and glaucoma patients with different degrees of vision loss. We found that inner retinal layer thinning, optic nerve cupping and reduced visual cortex activity occurred before patients showed visual field impairment. The primary visual cortex also exhibited more severe functional deficits than higher-order visual brain areas in glaucoma. Within the visual cortex, choline metabolism was perturbed along with increasing disease severity in the eye, optic radiation and visual field. In summary, this study showed evidence that glaucoma deterioration is already present in the eye and the brain before substantial vision loss can be detected clinically using current testing methods. In addition, cortical cholinergic abnormalities are involved during trans-neuronal degeneration and can be detected non-invasively in glaucoma. The current results can be of impact for identifying early glaucoma mechanisms, detecting and monitoring pathophysiological events and eye-brain-behavior relationships, and guiding vision preservation strategies in the visual system, which may help reduce the burden of this irreversible but preventable neurodegenerative disease.

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