Clinical trial NCT02776449: Pressure Difference Between Brain and Eye: a Possible Cause to Normal Tension Glaucoma.
Official title: Pathological Cerebral Venous Drainage System Giving Large Pressure Difference Between Brain and Eye at Upright Posture: a Possible Cause to Normal Tension Glaucoma.
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Normal Tension Glaucoma
Lead sponsor: Umeå University
Sponsor class: OTHER
Collaborators: name: Västerbotten County Council, Sweden
First posted: 2016-05-18
Enrollment: 17
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Normal tension glaucoma patients

Brief summary: The main aim of this study is to determine the trans-laminal cribrosa pressure difference (TLCPD) for normal tension glaucoma (NTG) patients from the brain and the eye in supine, upright and minor head down tilt positions. It is also to investigate the venous drainage system in the same body positions.

Detailed description: The trans-lamina cribrosa pressure difference (TLCPD), i.e. the difference between the intraocular pressure (IOP) and the intracranial pressure (ICP) has been suggested as a pathophysiological component in glaucoma. The theory is that high TLCPD, either due to elevated IOP or reduced ICP, can cause glaucomatous damage.

Normal tension glaucoma (NTG) patients has been found to have a slightly reduced ICP when measured in horizontal position. However, in a previous study in healthy adult volunteers the investigators have measured TLCPD at supine, sitting and 9 degree head down tilt positions and found that the TLCPD was posture dependent, with the largest difference in the upright position. Since humans are upright approximately two thirds of the day, one can expect that TLCPD in a diurnal perspective is primarily influenced by the ICP in the upright position.

In this study the TLCPD in different positions in patients with NTG will therefore be measured.

The study will be carried out in three parts.

1. TLCPD will be investigated by simultaneous measurements of IOP and ICP. For IOP the Applanation resonance tonometer (ART), developed by our research group, will be used. ART is independent of gravitation and possible to use in all body postures. In this study measurements will be performed in supine, sitting and head down tilt positions. ICP is measured continuously during the period of body position changes with a CELDA lumbar pressure measurement apparatus.
2. Brain and eye MRI investigation will be performed at a 3 Tesla GE scanner with a new generation 32-channels head coil. The images will be used to measure the cross-section area, the blood flow velocity and the flow direction in the jugular veins, as well as the structural properties of the optic nerve and optic nerve head.
3. Ultrasound imaging, using a high-resolution apparatus, will be performed to study the effects of postural changes on the blood flow velocity and the cross-section area of the right and left internal jugular veins and external jugular veins.

Eligibility criteria: Inclusion Criteria:

* Subject has normal tension glaucoma in one or both eyes (glaucomatous optic nerve head and corresponding visual field defects)
* Intraocular pressures before treatment did not exceed 21 mmHg. Occasional measurement up to 24 is accepted.

Exclusion Criteria:

* History of brain disease or brain surgery
* History of other neurologic or ocular disease causing visual field loss
* Use of anticoagulants other than acetylsalicylic acid
* Use of carbonic anhydrase inhibitors
* Previous lumbar puncture
* Claustrophobia

Primary outcomes:
measure: Trans-lamina cribrosa pressure difference (TLCPD)
timeFrame: 1 day Single time point measurement
Secondary outcomes:
measure: Postural changes on blood flow velocity and cross-section area of right and left internal jugular veins (IJV) and external jugular veins (EJV)
timeFrame: 1 day Single time point measurement
Other outcomes:
measure: Retinal perfusion using 3D Phase contrast magnetic resonance imaging (3DPCMRI)
timeFrame: 1 day Single time point measurement
Locations:
city: Umeå
country: Sweden
facility: Umeå University
Study officials:
affiliation: Umeå University
name: Jan Malm, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Linden C, Qvarlander S, Johannesson G, Johansson E, Ostlund F, Malm J, Eklund A. Normal-Tension Glaucoma Has Normal Intracranial Pressure: A Prospective Study of Intracranial Pressure and Intraocular Pressure in Different Body Positions. Ophthalmology. 2018 Mar;125(3):361-368. doi: 10.1016/j.ophtha.2017.09.022. Epub 2017 Oct 31.