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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Glaucoma

Intervention / Treatment
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* Drug: Timolol (drug)
* Drug: dorzolamide (drug)
* Drug: brimonidine (drug)
* Device: Laser Doppler flowmetry
* Device: Goldmann applanation tonometer
* Procedure: Suction cup method


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men aged between 19 and 35 years, nonsmokers Body mass index between 15th and 85th percentile Normal findings in the medical history and physical examination unless the investigator considers an abnormality to be clinically irrelevant Normal ophthalmic findings, ametropia < 1 Dpt. Exclusion Criteria: Regular use of medication, abuse of alcoholic beverages, participation in a clinical trial in the 3 weeks preceding the study Treatment in the previous 3 weeks with any drug Symptoms of a clinically relevant illness in the 3 weeks before the first study day Blood donation during the previous 3 weeks Presence of intraocular pathology: ocular hypertension, glaucoma, retinal vasculopathy or other retinal diseases

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 35 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: Timolol (drug)<br>* Timolol (0.5%, non-selective beta-blocker, Timoptic®, Merck Sharp & Dohme, Haarlem, Netherlands), dose 1 drop in one eye twice daily for two weeks<br>Device: Laser Doppler flowmetry<br>* blood flow measurements at the temporal neuroretinal rim of the optic nerve head, in total 4x 9 minutes on 2 study days<br>Device: Goldmann applanation tonometer<br>* intraocular pressure measurements, in total 2x 5 measurements on two study days<br>Procedure: Suction cup method<br>* 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<br>|
| Experimental: 2<br> | Drug: dorzolamide (drug)<br>* Dorzolamide (2%, carbonic anhydrase inhibitor, Trusopt®, Laboratoires Merck Sharp & Dohme - Chibret, France), dose: 1 drop in one eye twice daily for two weeks<br>Device: Laser Doppler flowmetry<br>* blood flow measurements at the temporal neuroretinal rim of the optic nerve head, in total 4x 9 minutes on 2 study days<br>Device: Goldmann applanation tonometer<br>* intraocular pressure measurements, in total 2x 5 measurements on two study days<br>Procedure: Suction cup method<br>* 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<br>|
| Experimental: 3<br> | Drug: brimonidine (drug)<br>* Brimonidine (0.2%. alpha-2 adrenergic agonist, Alphagan®, Allergan Pharmaceuticals, Westport, Ireland), dose: 1 drop in one eye twice daily for two weeks<br>Device: Laser Doppler flowmetry<br>* blood flow measurements at the temporal neuroretinal rim of the optic nerve head, in total 4x 9 minutes on 2 study days<br>Device: Goldmann applanation tonometer<br>* intraocular pressure measurements, in total 2x 5 measurements on two study days<br>Procedure: Suction cup method<br>* 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<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ocular perfusion pressure - ONH blood flow relationship |  | on 2 study days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite measure: Blood pressure, heart rate |  | on 2 study days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ocular Physiology, Brimonidine, Timoptic, Dorzolamide, ocular blood flow, Regional Blood Flow