Glaucoma Biomarkers

Study Overview
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Brief Summary
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Glaucoma is a major cause of blindness. The inability to predict a patient's IOP response to medications is a critical barrier for the clinician to consistently provide highly effective IOP-based treatments. Current trial-and error approaches to glaucoma management are inefficient and have not addressed this barrier as there are no predictive factors for drug response. Our long-term goal is to improve outcomes by identifying biomarkers and environmental factors that profile a patient at risk for glaucoma by age-of-onset, rate of disease progression, poor response to treatment, and large IOP fluctuation. Our purpose of this research project is to address this critical barrier by focusing on physiological factors that predict IOP response to drugs.

Official Title
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Aqueous Humor Dynamic Components That Determine Intraocular Pressure Variance

Conditions
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Glaucoma, Healthy

Intervention / Treatment
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* Drug: Variation in eye pressure response to timolol and latanoprost treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Either gender. Any self-declared ethnoracial category. Greater than or equal to 40 years. Healthy eyes with the crystalline lens, without glaucoma (cup:disc ratio < 0.8 both eyes; asymmetry of cup:disc ratio between eyes < 0.2). Open angles. Ability to cooperate for aqueous humor dynamic studies. Nonprescription and prescription topical ophthalmic products and systemic medications other than those mentioned in the exclusion criteria will be allowed during the study. Contact lenses removed prior to topical fluorescein instillation, and not used until the end of each fluorophotometry session. Able to participate on site over the multi-visit study period. Exclusion Criteria: Women who are pregnant due to IOP changes. Any form of glaucoma, including extremely narrow angle with complete or partial closure. Current use of any glaucoma medication, either topically or orally. Chronic or recurrent inflammatory eye disease. Ocular trauma within the past 6 months. Ocular infection or ocular inflammation in the past 3 months. Clinically significant retinal disease. Any abnormality preventing reliable fluorophotometry of either eye, such as corneal scarring or severe dry eye that results in punctate fluorescein staining of the cornea. Intraocular surgery within 6 months. Serious hypersensitivity to any components of the study medications or risk from treatment with glaucoma medications, such as severe asthma or emphysema. Subjects must be on a stable regimen for at least 30 days prior to the Visit 1 regarding a chronic systemic medication that may affect IOP (i.e., sympathomimetic agents, beta-blockers, alpha-adrenergic agonists, alpha-adrenergic blockers, calcium channel blockers, angiotensin converting enzyme inhibitors, etc.). Any change of such medication during the study period will result in exclusion. Use of any glucocorticoid by any route. Subject must be washed out of the glucocorticoid for at least 2 weeks before study entry.

Ages Eligible for Study
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Minimum Age: 40 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: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: timolol<br>To compare the variation in response to timolol between individuals | Drug: Variation in eye pressure response to timolol and latanoprost treatment<br>* Arm 1 is to test for variation in eye pressure response to timolol. Arm 2 is to test for variation in eye pressure response to latanoprost.<br>|
| Active Comparator: latanoprost<br>To compare the variation in response to latanoprost between individuals | Drug: Variation in eye pressure response to timolol and latanoprost treatment<br>* Arm 1 is to test for variation in eye pressure response to timolol. Arm 2 is to test for variation in eye pressure response to latanoprost.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Variation in Eye Pressure Between Individuals. | Eye pressure is a steady state quantitative trait that is measured in mm Hg. Eye pressure is determined by the following physiological factors (units of measure): eye fluid or aqueous humor production (microliters/minute), aqueous humor outflow (microliters/minute), outflow resistance (microliters/minute/mm Hg) and venous pressure (mm Hg) of the eye. All of these physiological factors will be determined under baseline condition and under glaucoma drug treatment. | Measurement after 1 week of drug treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Variation in Aqueous Flow Between Individuals. | Aqueous flow production (microliters/minute) will be determined under baseline condition and under glaucoma drug treatment. | 1 week after treatment | 
| Variation in Episcleral Venous Pressure. | Episcleral venous pressure (mm Hg) of the eye will be determined under baseline condition and under glaucoma drug treatment. | 1 week treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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glaucoma, aqueous humor dynamics, intraocular pressure