Assessment of Optic Nerve Radiation in Patients With Glaucoma and Ocular Hypertension by 7 Tesla Diffusion Tensor Imaging

Glaucoma is among the leading causes for blindness in the western world. Elevated intraocular pressure (IOP) has been identified as the most important risk factor. However, some patients progress despite adequate IOP lowering while some subjects with elevated IOP never develop glaucoma. Other patients develop glaucoma although IOP measurements were always in the normal range. Therefore, other factors must be involved. In the last years, studies using MRI have been performed and evidence has accumulated that also changes in retrobulbar structures are present, in particular in the lateral geniculate nucleus and the visual cortex. However, these studies were limited by the low spatial resolution of the MRI instruments used.

The investigators propose to overcome this problem by using an ultrahigh-field Magnetom 7T whole-body MR scanner (Siemens Medical, Germany) installed at the MR Centre of Excellence at the Medical University of Vienna. This scanner is equipped with a 32-channel head coil and the SC72 high-performance gradient system and is thus perfectly suited for structural and functional imaging. The aim of the present study is to investigate whether structural and functional parameters are altered in patients with primary open angle glaucoma (POAG), normal tension glaucoma (NTG), ocular hypertension (OHT) compared to healthy control subjects. The exact topographical survey of intracranial structures such as the LGN and the assessment of neuronal structures by DTI may allow for the better assessment of therapeutic responses to new neuroprotective agents.

Study Overview

• Status: Terminated
• Conditions: Primary Open Angle Glaucoma; Ocular Hypertension; Normal Tension Glaucoma
• Intervention / Treatment: Device: 7-Tesla MRI; Other: Optical Coherence Tomography; Other: Heidelberg Retina Tomography; Other: Scanning Laser Polarimetry; Other: Humphrey Perimetry; Other: Applanation Tonometry

• Study Type: Interventional
• Enrollment (Anticipated): 120
• Phase: Phase 2

Contacts and Locations

Study Locations

• Austria
  • Vienna, Austria, 1090
    • Department of Clinical Pharmacology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Healthy controls

• Men and women aged over 18 years
• Normal findings in the medical history unless the investigator considers an abnormality to be clinically irrelevant
• Normal ophthalmic findings

Patients with ocular hypertension

• Men and women aged over 18 years
• Normal findings in the medical history unless the investigator considers an abnormality to be clinically irrelevant
• Normal ophthalmic findings except presence of ocular hypertension (defined as untreated IOP ≥ 21 mmHg on at least three measurements in the medical history, no signs of glaucomatous damage in the optic disc or the glaucoma hemifield test)

Patients with primary open angle glaucoma

• Men and women aged over 18 years
• Normal findings in the medical history unless the investigator considers an abnormality to be clinically irrelevant
• Diagnosis of manifest primary open angle glaucoma (defined as pathological optic disc appearance, glaucoma hemifield test outside normal limits and untreated IOP > 20 mmHg on at least three measurements in the medical history)
• Mean Deviation in the visual field test ≥ 10dB

Patients with normal-tension glaucoma

• Men and women aged over 18 years
• Normal findings in the medical history unless the investigator considers an abnormality to be clinically irrelevant
• Diagnosis of normal-tension glaucoma (defined as pathological optic disc appearance, glaucoma hemifield test outside normal limits and untreated IOP ≤ 20 mmHg on at least three measurements in the medical history)
• Mean Deviation in the visual field test ≥ 10dB

Exclusion Criteria:

• Symptoms of a clinically relevant illness in the 3 weeks before the first study day
• Presence or history of a severe medical condition as judged by the clinical investigator
• Abuse of alcoholic beverages, participation in a clinical trial in the 3 weeks preceding the study
• Exfoliation glaucoma, pigmentary glaucoma, history of acute angle closure
• Intraocular surgery within the last 6 months
• Ocular inflammation or infection within the last 3 months
• Pregnancy, planned pregnancy or lactating
• Any metallic, electric, electronic or magnetic device or object not removable except dental fillings
• Claustrophobia

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Primary Open Angle Glaucoma; 30 patients with primary open angle glaucoma	Device: 7-Tesla MRI; High resolution functional and structural imaging of the visual pathway; Other: Optical Coherence Tomography; Measurement of retinal nerve fiber thickness; Other: Heidelberg Retina Tomography; Measurement of retinal nerve fiber thickness; Other: Scanning Laser Polarimetry; Measurement of retinal nerve fiber thickness; Other: Humphrey Perimetry; Visual Field Testing; Other: Applanation Tonometry; Measurement of Intraocular Pressure
Experimental: Normal Tension Glaucoma; 30 patients with normal tension glaucoma	Device: 7-Tesla MRI; High resolution functional and structural imaging of the visual pathway; Other: Optical Coherence Tomography; Measurement of retinal nerve fiber thickness; Other: Heidelberg Retina Tomography; Measurement of retinal nerve fiber thickness; Other: Scanning Laser Polarimetry; Measurement of retinal nerve fiber thickness; Other: Humphrey Perimetry; Visual Field Testing; Other: Applanation Tonometry; Measurement of Intraocular Pressure
Experimental: Ocular Hypertension; 30 patients with ocular hypertension	Device: 7-Tesla MRI; High resolution functional and structural imaging of the visual pathway; Other: Optical Coherence Tomography; Measurement of retinal nerve fiber thickness; Other: Heidelberg Retina Tomography; Measurement of retinal nerve fiber thickness; Other: Scanning Laser Polarimetry; Measurement of retinal nerve fiber thickness; Other: Humphrey Perimetry; Visual Field Testing; Other: Applanation Tonometry; Measurement of Intraocular Pressure
Other: Healthy subjects; 30 healthy control subjects	Device: 7-Tesla MRI; High resolution functional and structural imaging of the visual pathway; Other: Optical Coherence Tomography; Measurement of retinal nerve fiber thickness; Other: Heidelberg Retina Tomography; Measurement of retinal nerve fiber thickness; Other: Scanning Laser Polarimetry; Measurement of retinal nerve fiber thickness; Other: Humphrey Perimetry; Visual Field Testing; Other: Applanation Tonometry; Measurement of Intraocular Pressure

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
High resolution functional and structural imaging of the visual pathway	The visual pathway will be imaged with 7-Tesla MRI. The images will be compared between the study groups.	once on the study day (approximately 1 hour)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Retinal nerve fiber thickness	Parameters obtained from GDX and OCT measurements will be compared between groups.	once on the study day (approximately 10 minutes)
Visual field test	Parameters from the Humphrey visual field test will be used for classification of severity of glaucoma or to prove that subjects are healthy.	once on the study day (approximately 20 minutes)
Intraocular Pressure	Goldmann applanation tonometry will be used for measurement of intraocular pressure.	once on the study day (1 minute)

Collaborators and Investigators

• Sponsor: Medical University of Vienna

Study record dates

Study Major Dates

• Study Start: November 1, 2015
• Primary Completion (Actual): December 1, 2015
• Study Completion (Actual): December 1, 2015

Study Registration Dates

• First Submitted: May 3, 2013
• First Submitted That Met QC Criteria: May 24, 2013
• First Posted (Estimate): May 29, 2013

Study Record Updates

• Last Update Posted (Actual): August 22, 2019
• Last Update Submitted That Met QC Criteria: August 21, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Keywords: Intraocular Pressure; 7-Tesla Magnetic Resonance Imaging; Retinal Nerve Fiber Thickness; Visual Field Test
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Eye Diseases; Optic Nerve Diseases; Glaucoma; Glaucoma, Open-Angle; Ocular Hypertension; Hypertension; Low Tension Glaucoma
• Other Study ID Numbers: OPHT-220213