Ocular Blood Flow in Early Glaucoma Patients Before and After Treatment With Dorzolamide

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00152932
Recruitment Status : Unknown
Verified September 2005 by University Health Network, Toronto.
Recruitment status was:  Recruiting
First Posted : September 9, 2005
Last Update Posted : July 25, 2007
Merck Frosst Canada Ltd.
Information provided by:
University Health Network, Toronto

Brief Summary:

Impaired ocular blood flow is an important risk factor in the pathogenesis of primary open angle glaucoma (POAG). A few studies suggest that topical dorzolamide 2% may increase optic nerve perfusion. The objectives of this study are to learn the effects of dorzolamide on the retinal and optic nerve blood flow of glaucoma patients.

The present study is a prospective, randomized, double-masked, crossover design study of newly diagnosed or already treated patients with early glaucoma.

The investigators will check ocular blood flow parameters using the Canon Laser Blood Flowmeter (CLBF), used to evaluate retinal arteriole blood flow, and the Heidelberg retinal flowmeter (HRF), which measures blood flow through capillary beds in the retina and optic nerve head.

Any demonstrated improvements to retinal and optic nerve blood flow with dorzolamide, will mean that the drug may protect against ischaemic nerve and retinal damage. Any documented improvement in flow could lead to a major change in the management of glaucoma patients as well as other retinal ischemic diseases such as diabetic retinopathy and central retinal vein occlusion.

Condition or disease Intervention/treatment Phase
Glaucoma Drug: Dorzolamide 2% drops Device: HRF and CLBF Not Applicable

Detailed Description:

High intraocular pressure (IOP) is the major risk factor for glaucoma. Lowering intraocular pressure is still the only accepted form of treatment for glaucoma.

Over the past decade, epidemiological and experimental evidence suggested that impaired ocular blood flow is an important risk factor with an important role in the pathogenesis of primary open angle glaucoma (POAG). Several studies suggest that ischemia-promoting vascular factors may contribute to glaucomatous damage including vasospasm, impaired ocular perfusion pressure and general vascular disorders such as low blood pressure, especially dips in blood pressure at night.

Different techniques are employed to assess vascular dysfunction in the eye. As the methodology of ocular blood flow assessment is complex and differs in various aspects (e.g. target tissue and physiological parameters), comparative studies are required in order to enhance the interpretation of these measurements.

Our laboratory has state of the art equipment to assess ocular blood flow. One study done by us suggested that one drop of Dorzolamide 2% does not improve retinal blood flow in normal eyes. In the present study we plan to extend this study to 2 weeks of treatment in patients with POAG.

Dorzolamide hydrochloride 2% is a topical carbonic anhydrase inhibitor which reduces intraocular pressure (IOP) by decreasing the production of aqueous humour. Pharmacological studies on volunteers and glaucoma patients, using Color Doppler Imaging (measuring the retrobulbar blood flow) and Scanning laser Ophthalmoscopy (measuring arteriovenous passage time), indicate that topically applied Dorzolamide may increase perfusion of the optic nerve and peripapillary retina.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 17 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single
Primary Purpose: Diagnostic
Official Title: Ocular Blood Flow Measured by HRF and CLBF in Newly Diagnosed and Early Glaucoma Patients Before and After Instillation of Dorzolamide 2%
Study Start Date : May 2005
Study Completion Date : June 2006

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Glaucoma

Primary Outcome Measures :
  1. Ocular blood flow measurements

Secondary Outcome Measures :
  1. Intraocular pressure reduction

Information from the National Library of Medicine

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Ages Eligible for Study:   20 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Males or females 20-80 years of age.
  2. Presence of typical early glaucomatous optic disc changes (cup/disc ratio ≤ 0.75) and/or early glaucomatous visual field defects (mean deviation less than 5dB and outside of 10° from fixation) in the study eye at the baseline visit.
  3. Best corrected visual acuity of at least 20/40.
  4. Signed informed consent from the subject
  5. The subject should be able to understand the instructions and perform the HRF and CLBF tests as well as be willing and able to comply with the study schedule and treatment.

Exclusion Criteria:

  1. Pregnant women or nursing mothers.
  2. Any other active ocular disease (ocular infections, Uveitis, etc.)
  3. Known allergy or sensitivity to the study medications.
  4. Functionally significant visual field loss (mean deviation greater than 5dB) or cup/disc ratio greater than 0.75 or evidence of progressive visual field loss within the last 6 months.
  5. Required chronic use of other ocular or systemic hypotensive medications during the study, other than the study medication (e.g. beta-blockers, Ca-channel blockers)
  6. Vascular occlusive disease affecting the ocular circulation such as: diabetic retinopathy, central retinal vein occlusion, central retinal artery occlusion, or non-arteritic ischemic optic neuropathy.
  7. Previous intraocular surgery or ocular traumas.
  8. Any past history of serious systemic condition affecting cerebral circulation including: hypertension, diabetes, cerebral vascular accident (CVA), or coronary artery bypass graft (CABG).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00152932

Contact: Rony Rachmiel, MD 416-603-5317

Canada, Ontario
Department of Ophthalmology and Visual Sciences; Toronto Western Hospital Recruiting
Toronto, Ontario, Canada
Contact: Rony Rachmiel, MD    416-603-5317   
Contact: Graham E Trope, MB PhD, FRCSC    416-603-5317   
Sub-Investigator: Rony Rachmiel, MD         
Sponsors and Collaborators
University Health Network, Toronto
Merck Frosst Canada Ltd.
Principal Investigator: Graham E Trope, MB, FRCSC University of Toronto, Department of Ophthalmology
Study Chair: Chris Hudson, PhD Department of Ophthalmology, Toronto Western Hospital, Toronto
Study Chair: John Flanagan, PhD Department of Ophthalmology, Toronto Western Hospital, Toronto
Study Chair: Yvonne M Buys, MD, FRCSC University of Toronto, Department of Ophthalmology, Toronto Western Hospital, Toronto Identifier: NCT00152932     History of Changes
Other Study ID Numbers: 04-0645-A
First Posted: September 9, 2005    Key Record Dates
Last Update Posted: July 25, 2007
Last Verified: September 2005

Keywords provided by University Health Network, Toronto:
Intraocular pressure
Ocular blood flow
Laser-Doppler Flowmetry

Additional relevant MeSH terms:
Ocular Hypertension
Eye Diseases
Antihypertensive Agents
Carbonic Anhydrase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action