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

We’ll check ocular blood flow parameters using the Canon Laser Blood Flowmeter (CLBF), used to evaluate retinal arterioles blood flow, and the Heildelberg Retinal Flowmetry ( HRF ), which measure 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	Intervention
Laser-Doppler Flowmetry	Drug: Patients will be treated with Dorzolamide 2% drops  Device: HRF and CLBF

Further Study Details: 

Primary Outcomes: Ocular blood flow measurements
Secondary Outcomes: Intraocular pressure reduction
Expected Total Enrollment:  17

High intraocular pressure ( IOP) is the major risk factor for glaucoma1 . 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 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 peripapilary retina.

Ages Eligible for Study:  20 Years   -   80 Years,  Genders Eligible for Study:  Both

Criteria

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 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, Non arteritic ischemic optic neuropathy.
7. Previous intraocular surgery or ocular trauma.
8. Any past history of serious systemic condition affecting cerebral circulation including: Hypertension, Diabetes, CVA, CABG.

Please refer to this study by ClinicalTrials.gov identifier  NCT00152932

Rony Rachmiel, MD      416-603-5317    rachmiel_r@hotmail.com

Canada, Ontario
      Department of Ophthalmology and visual sciences; Toronto Western Hospital, Toronto,  Ontario,  Canada; Recruiting

Study chairs or principal investigators

Graham E Trope, MB, FRCSC,  Principal Investigator,  University of Toronto, Department of Ophthalmology   
Chris Hudson, PhD,  Study Chair,  Department of Ophthalmology, Toronto Western Hospital, Toronto   
John Flanagan, PhD,  Study Chair,  Department of Ophthalmology, Toronto Western Hospital, Toronto   
Yvonne M Buys, M.D., FRCSC,  Study Chair,  University of Toronto, Department of Ophthalmology, Toronto Western Hospital, Toronto   

Study ID Numbers:  04-0645-A
Last Updated:  September 8, 2005
Record first received:  September 8, 2005
ClinicalTrials.gov Identifier:  NCT00152932
Health Authority: Canada: Health Canada
ClinicalTrials.gov processed this record on 2005-09-13