Magnetic Resonance Imaging of Cerebral Connectivity and Volume in Neurodegeneration and Glaucoma

Magnetic Resonance Imaging of Cerebral Connectivity and Volume in Neurodegeneration and Glaucoma

The EVOLUTION is a 10-year extension of the ENVOL study. It seeks to compare the evolution of structural and functional connectivity (Hub Disruption Index) and cerebral volume on 3T MRI of the brain in glaucoma patients and matched controls. The study aims to examine the hypothesis that glaucomatous optic neuropathy is not limited solely to the visual pathway, but rather is associated with a broader degeneration of the central nervous system.

Glaucoma is a neurodegenerative disease characterised by a progressive loss of retinal ganglion cells, typical optic neuropathy with a loss of visual field and visual function. High intraocular pressure is it's main risk factor, but the patophysiology hasn't been clearely understood, as there exist forms with normal ocular pressure (NTG - normal tension glaucoma) or mixed forms. Studies have shown that the degeneration is not limited to retinal ganglion cells only, but rather it affects the whole visual pathway including the occipital cortex. The ENVOL study has been able to show microstructural alterations of the optic radiations in glaucoma. Furthermore, glaucomatous patients have been found to be more at risk of developing other neurodegenerative diseases, namely Alzheimer's disease.

The EVOLUTION study is set to repeat 3T brain MRI in patients previously enrolled in ENVOL in order to compare brain microstructure between glaucomatous and matched healthy subjects, assess their ocular status and glaucoma progression over time, as well as compare them with orignal imagery from 10 years prior.

gression over time, as well as compare them with orignal imagery from 10 years prior.

Study subjects will undergo a typical non-invasive ophthalmic screening comprised of best-corrected visual acuity testing, slit-lamp biomicroscopy, gonioscopy, indirect opthalmoscopy, fundus photography, 30° visual field testing and optical coherence tomography of the optic nerve. They will also answer a questionnaire concerning their medical treatment, cardiovascular health and tobacco use. Next, they will undergo a 3T brain MRI comprised of a T1-weighted 3D morphological sequence, 3D FLAIR, resting state fMRI and diffusion tensor imaging.

fMRI and diffusion tensor imaging

Inclusion Criteria:

• having been previously included and completed the ENVOL study
• Ability and willingness to provide informed consent
• Having a valid health insurance in France

In glaucoma group :

• Glaucomatous optic neuropathy, being able to be graded by the vertical C/D ratio

• Open angle on gonioscopy in a dark-room testing according to Shaffer's classification (grade 3 or grade 4)

• Visual field impairement (at least one of the following) :

  • 3 adjacent points with at least 5dB loss
  • one point with a loss of 10dB
  • a difference of at least 10 dB for 2 adjacent points on either side of the horizontal meridian of the nasal visual field

• Mini Mental State Score of at least 28

In control group :

• No personal or family history of glaucoma or ocular hypertension (IOP > 21 mmHg)
• Open angle on gonioscopy in a dark-room testing according to Shaffer's classification (grade 3 or grade 4)
• Intraocular pressure of ≤ 21 mmHg
• Absence of glaucomatous neuropathy
• Normal visual field

Exclusion Criteria:

• Inability/unwillingness to provide informed consent
• Other causes of ocular hypertension (trauma, uveitis)
• Non-glaucomatous optic neuropathy (infectious, inflammatory, compressive, ischemic)
• Unreliable visual field (>15% false positives, >33% false negatives or >20% loss of fixation)
• Severe corneal pathology preventing access to fundus, visual field testing or altering ocular tonometry
• Contraindications to MRI testing (pacemakers or neurosensory stimulators, cochlear implants, ferromagnetic foreign bodies, claustrophobia)
• Patients under guardianship or other form of legal protection