Effects of Common Topical Glaucoma Therapy on Optic Nerve Head Blood Flow Autoregulation During Increased Arterial Blood Pressure and Artificially Elevated Intraocular Pressure in Healthy Humans

Summary

Background

Autoregulation is the ability of a vascular bed to maintain blood flow despite changes in perfusion pressure. The existence of an effective autoregulation in the optic nerve circulation has been shown in animals and humans. The exact mechanism behind this autoregulation is still unknown. The motive for the investigation of optic nerve head (ONH) blood flow autoregulation is to enhance the understanding of pathologic eye conditions associated with ocular vascular disorders. To clarify the regulatory mechanisms of ONH microcirculation is of critical importance to understand the pathophysiology of glaucoma, because there is evidence that glaucoma is associated with optic nerve head ischemia. Several studies indicate that a disturbed autoregulation might contribute to glaucomatous optic neuropathy. Currently, five classes of intraocular pressure (IOP) reducing drugs are available for topical therapy in patients with glaucoma or elevated intraocular pressure. These drugs have also vasoactive properties, which may influence both the resting ocular circulation and the autoregulatory mechanisms of blood flow during changes in ocular perfusion pressure.

Study objective

To investigate the influence of common topical glaucoma therapy on ONH blood flow regulation during changes in IOP and systemic arterial blood pressure.

Conditions

• Glaucoma

Interventions

DRUG

Timolol (drug)

Timolol (0.5%, non-selective beta-blocker, Timoptic®, Merck Sharp \& Dohme, Haarlem, Netherlands), dose 1 drop in one eye twice daily for two weeks

DRUG

dorzolamide (drug)

Dorzolamide (2%, carbonic anhydrase inhibitor, Trusopt®, Laboratoires Merck Sharp \& Dohme - Chibret, France), dose: 1 drop in one eye twice daily for two weeks

DRUG

brimonidine (drug)

Brimonidine (0.2%. alpha-2 adrenergic agonist, Alphagan®, Allergan Pharmaceuticals, Westport, Ireland), dose: 1 drop in one eye twice daily for two weeks

DEVICE

Laser Doppler flowmetry

blood flow measurements at the temporal neuroretinal rim of the optic nerve head, in total 4x 9 minutes on 2 study days

DEVICE

Goldmann applanation tonometer

intraocular pressure measurements, in total 2x 5 measurements on two study days

PROCEDURE

Suction cup method

The IOP will be raised by an 11 mm diameter, standardized suction cup placed on the temporal sclera with the anterior edge at least 1 mm from the limbus; 4x 8 minutes on 2 study days

Sponsors & Collaborators

• Medical University of Vienna

  lead OTHER

Principal Investigators

• Gabriele Fuchsjaeger-Mayrl, MD · Department of Clinical Pharmacology

Study Design

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

DOUBLE

Model

PARALLEL

Eligibility

Min Age

19 Years

Max Age

35 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2008-09-30

Primary Completion

2014-11-30

Completion

2014-11-30

Countries

• Austria

Study Locations