Brief Summary

Glaucoma is characterized by a progressive loss of retinal ganglion cells (RGCs) leading to optic nerve head (ONH) damage and associated visual field defects. The main risk factor for glaucoma is elevated intraocular pressure (IOP). Reducing IOP slows down the progression of the disease as several large multicenter trials have shown. Some patients, however, still progress despite adequately controlled IOP. As such, there is considerable interest in approaches that rescue RGCs independent of IOP, a strategy called neuroprotection. Although this field was actively discovered in the last 20 years in the brain and the eye, no non-IOP related treatment is clinically available to date. Various approaches are currently studied in some detail. One interesting strategy focuses on the neurovascular unit. The blood flow of the human retina is controlled by complex mechanisms that include myogenic, metabolic and hormonal factors. The high consumption of oxygen in the human retina is crucial for normal functioning of the organ. As in the brain, blood flow in the retina is also controlled by neurovascular coupling. This means that the retina increases its blood flow to regions in which neurons are activated. This is done in an effort to provide more oxygen and glucose to the active neurons. In the recent years evidence has accumulated that astrocytes play a key role in mediating this vasodilator signal. In the brain, abnormalities in neurovascular coupling have been observed in diseases like stroke, hypertension, spinal-cord injury and Alzheimer's disease. This break-down of neurovascular coupling is considered to play a key role in neuronal death in these diseases. In the retina, abnormalities in neurovascular coupling have been observed in diseases as diabetes and glaucoma. Most of the data obtained in the human retina stem from a system that measures retinal vasodilatation during stimulation with flickering light. The investigators have previously shown that flicker stimulation of the retina is, however, also associated with a pronounced increase in retinal blood velocities. In this study the investigators employed laser Doppler velocimetry (LDV) for the measurement of retinal blood velocities, but this technique is not clinically applicable because it requires excellent fixation of the subject under study. In the present study, the investigators propose to use an alternative system for neurovascular coupling that they have developed recently. In this approach, the investigators use bi-directional Fourier-domain optical coherence tomography for the assessment of retinal blood flow. Optical coherence tomography (OCT) is a non-invasive optical imaging modality enabling cross-sectional tomographic in vivo visualization of internal microstructure in biological systems. In ophthalmology, OCT has become a standard tool in visualizing the retina and nowadays is considered also as a standard tool in the diagnosis of retinal disease. In the recent years, conventional time domain OCT was replaced by Fourier domain OCT providing significantly improved signal quality. This bidirectional system overcomes the limitations of previously realized techniques, which include doubtful validity and limited reproducibility. In addition, pattern ERG, multifocal ERG and oscillatory potentials will be measured to allow for concomitant assessment of neural function. The investigators seek to measure neurovascular coupling in the human retina in patients with early primary open angle glaucoma (POAG), normal tension glaucoma, ocular hypertension and a healthy control group. In order to obtain information on neurovascular coupling, both neuronal function as well as retinal blood flow need to be measured. In the present study, the investigators will employ pattern ERG, multifocal ERG as well as oscillatory potentials to assess the function of the inner retina. Retinal blood flow through major retinal arterial and venous branch vessels will be measured before, during and after flicker stimulation with the dual-beam bidirectional Fourier Domain Doppler OCT coupled to the commercially available Dynamic Vessel Analyzer (DVA) produced by IMEDOS, Jena, Germany, which provides adequate resolution to study the retinal circulation.

Trial Health

Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date

Enrollment

120

participants targeted

Target at P50-P75 for not_applicable

Timeline

Completed

Started Dec 2017

Longer than P75 for not_applicable

Geographic Reach

1 country

1 active site

Status

recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

8.3 years study duration

Study Start

First participant enrolled

December 1, 2017

Completed

1.3 years until next milestone

First Submitted

Initial submission to the registry

March 8, 2019

Completed

4 days until next milestone

First Posted

Study publicly available on registry

March 12, 2019

Completed

7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 1, 2026

Completed

Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

March 1, 2026

Completed

Last Updated

May 23, 2025

Status Verified

April 1, 2025

Enrollment Period

8.3 years

First QC Date

March 8, 2019

Last Update Submit

May 20, 2025

Conditions

Glaucoma, Open-Angle Normal Tension Glaucoma Ocular Hypertension

Outcome Measures

Primary Outcomes (1)

Flicker induced blood flow alterations
Response of retinal blood flow to flicker light
1 day

Study Arms (6)

POAG MD<10dB

EXPERIMENTAL

patients with primary open angle glaucoma with MD in visual field less than or equal 10dB

Device: Fourier Domain Doppler Optical Coherence Tomography (FDOCT)Device: Dynamic Vessel Analyzer (DVA)Device: Pattern Electroretinography (pERG)Device: Optical coherence tomography (OCT)Device: Laser Speckle Flowgraphy (LSFG)

POAG MD>10dB

EXPERIMENTAL

patients with primary open angle glaucoma with MD in visual field more than 10dB

NTG MD<10dB

EXPERIMENTAL

patients with normal tension glaucoma with MD in visual field less than or equal 10dB

NTG MD>10dB

EXPERIMENTAL

patients with normal tension glaucoma with MD in visual field more than 10dB

OHT

EXPERIMENTAL

patients with ocular hypertension

controls

EXPERIMENTAL

healthy, age and sex matched, control subjects