Abstract
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.
Highlights
Glaucoma is commonly considered an eye-only disease, increasing evidence suggests the involvement of the brain’s visual system in glaucoma[5,6,7,8,9,10,11,12]
These basic gaps in knowledge must be filled before early intervention and targeted treatment of both the eye and the brain can be exploited for vision preservation or restoration
We looked beyond the retinal nerve fiber layer (RNFL) into other ocular structural measures, and a tipping point was detected between visual field function and macular ganglion cell-inner plexiform layer (GCIPL) thickness and optic nerve head cupping (Fig. 3a), indicating substantial structural loss throughout the inner retina and optic nerve head before functional visual field defects become detectable
Summary
Glaucoma is commonly considered an eye-only disease, increasing evidence suggests the involvement of the brain’s visual system in glaucoma[5,6,7,8,9,10,11,12]. The cause and pathogenesis of glaucoma in both the eye and the brain are still largely undetermined. These basic gaps in knowledge must be filled before early intervention and targeted treatment of both the eye and the brain can be exploited for vision preservation or restoration. We aim to understand the mechanisms of glaucoma in the visual system by investigating its structural, metabolic and functional changes in patients with different degrees of vision loss using non-invasive and multi-modal magnetic resonance imaging (MRI) techniques in a 3-Tesla human scanner. We characterized the eye-brain-behavior relationships by comparing MRI measures with glaucoma disease severity assessed clinically via spectral-domain OCT and Humphrey visual field tests. Our central hypothesis is that visual impairments in glaucoma involve early deterioration in both the eye and the brain that can be detected and monitored by non-invasive multi-modal imaging techniques
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
