Glaucoma, Healthy
Conditions
Keywords
glaucoma, aqueous humor dynamics, intraocular pressure
Brief summary
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.
Interventions
DRUGVariation in eye pressure response to timolol and latanoprost treatment
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.
Sponsors
University of Nebraska
Mayo Clinic
National Eye Institute (NEI)
University of Michigan
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Variation in Eye Pressure Between Individuals. | Measurement after 1 week of drug treatment | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Variation in Aqueous Flow Between Individuals. | 1 week after treatment | Aqueous flow production (microliters/minute) will be determined under baseline condition and under glaucoma drug treatment. |
| Variation in Episcleral Venous Pressure. | 1 week treatment | Episcleral venous pressure (mm Hg) of the eye will be determined under baseline condition and under glaucoma drug treatment. |
Countries
United States
Participant flow
Pre-assignment details
135 consented. Prior to baseline measures: 4 were excluded for ineligibility; 6 withdrew consent fully prior to baseline measurements. After baseline measures: an additional 2 were excluded based on physician decision, and 2 withdrew for participant decision. Thus, 121 participants are included for period 1.
Participants by arm
| Arm | Count |
|---|---|
| Baseline of Entire Population Both arms are included because the study design was a cross over intent to treat with glaucoma medications. All participants were treated with both medications. | 125 |
| Total | 125 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Initial Assignment | Adverse Event | 0 | 1 |
| Initial Assignment | Protocol Violation | 0 | 1 |
| Second Assigment | Adverse Event | 1 | 3 |
| Second Assigment | Withdrawal by Subject | 2 | 2 |
Baseline characteristics
| Characteristic | Baseline of Entire Population |
|---|---|
| Age, Continuous | 55.1 years STANDARD_DEVIATION 8.8 |
| Aqueous humor flow Left eye | 2.9 microliters/min STANDARD_DEVIATION 0.9 |
| Aqueous humor flow Right eye | 3.1 microliters/min STANDARD_DEVIATION 1.2 |
| Episcleral venous pressure Left eye | 7.9 mmHg STANDARD_DEVIATION 1.5 |
| Episcleral venous pressure Right eye | 8.3 mmHg STANDARD_DEVIATION 1.7 |
| Intraocular pressure Left eye | 13.9 mmHg STANDARD_DEVIATION 3.5 |
| Intraocular pressure Right eye | 14.4 mmHg STANDARD_DEVIATION 3.5 |
| Race/Ethnicity, Customized American Indian | 1 Participants |
| Race/Ethnicity, Customized Asian | 2 Participants |
| Race/Ethnicity, Customized Black or African American | 12 Participants |
| Race/Ethnicity, Customized Hispanic | 3 Participants |
| Race/Ethnicity, Customized White | 107 Participants |
| Region of Enrollment United States | 125 participants |
| Sex: Female, Male Female | 94 Participants |
| Sex: Female, Male Male | 31 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 119 | 0 / 121 |
| other Total, other adverse events | 0 / 119 | 0 / 121 |
| serious Total, serious adverse events | 0 / 119 | 0 / 121 |
Outcome results
Primary
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.
Time frame: Measurement after 1 week of drug treatment
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Timolol | Variation in Eye Pressure Between Individuals. | RIght Eyes | 11.5 mmHg | Standard Deviation 3.2 |
| Timolol | Variation in Eye Pressure Between Individuals. | Left Eyes | 11.0 mmHg | Standard Deviation 3 |
| Latanoprost | Variation in Eye Pressure Between Individuals. | RIght Eyes | 11.3 mmHg | Standard Deviation 3.2 |
| Latanoprost | Variation in Eye Pressure Between Individuals. | Left Eyes | 11.0 mmHg | Standard Deviation 2.9 |
Comparison: Right Eye treated vs. untreatedp-value: 0.000195% CI: [2.4, 3.3]t-test, 2 sided
Comparison: Left Eye treated vs. untreatedp-value: 0.000195% CI: [2.5, 3.2]t-test, 2 sided
Comparison: Right Eye treated vs. untreatedp-value: 0.000195% CI: [2.5, 3.4]t-test, 2 sided
Comparison: Left Eye, treated vs. untreatedp-value: 0.000195% CI: [2.5, 3.3]t-test, 2 sided
Secondary
Variation in Aqueous Flow Between Individuals.
Aqueous flow production (microliters/minute) will be determined under baseline condition and under glaucoma drug treatment.
Time frame: 1 week after treatment
Population: These measurements can be difficult for participants to tolerate, so sometimes values are missing.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Timolol | Variation in Aqueous Flow Between Individuals. | Right eye | 1.9 microliters/min | Standard Deviation 0.6 |
| Timolol | Variation in Aqueous Flow Between Individuals. | Left eye | 2.0 microliters/min | Standard Deviation 0.6 |
| Latanoprost | Variation in Aqueous Flow Between Individuals. | Right eye | 2.8 microliters/min | Standard Deviation 0.9 |
| Latanoprost | Variation in Aqueous Flow Between Individuals. | Left eye | 3.0 microliters/min | Standard Deviation 1 |
Comparison: Right Eye treated to untreatedp-value: 0.000195% CI: [0.9, 1.3]t-test, 2 sided
Comparison: Left Eye, treated vs. untreatedp-value: 0.000195% CI: [0.7, 1.1]t-test, 2 sided
Comparison: Right Eye, treated vs. untreatedp-value: 0.9495% CI: [-0.2, 0.2]t-test, 2 sided
Comparison: Left Eye, treated vs. untreatedp-value: 0.5495% CI: [-0.1, 0.2]t-test, 2 sided
Secondary
Variation in Episcleral Venous Pressure.
Episcleral venous pressure (mm Hg) of the eye will be determined under baseline condition and under glaucoma drug treatment.
Time frame: 1 week treatment
Population: These measures can be difficult to obtain, so sometimes participants do not tolerate it and some values are missing.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Timolol | Variation in Episcleral Venous Pressure. | Right eye | 7.6 mmHg | Standard Deviation 1.5 |
| Timolol | Variation in Episcleral Venous Pressure. | Left eye | 7.3 mmHg | Standard Deviation 1.5 |
| Latanoprost | Variation in Episcleral Venous Pressure. | Right eye | 7.7 mmHg | Standard Deviation 1.9 |
| Latanoprost | Variation in Episcleral Venous Pressure. | Left eye | 7.4 mmHg | Standard Deviation 1.7 |
Comparison: Right Eye, treated vs. untreatedp-value: 0.0495% CI: [0.01, 0.7]t-test, 2 sided
Comparison: Left eye, treated vs. untreatedp-value: 0.1595% CI: [-0.1, 0.6]t-test, 2 sided
Comparison: Right Eye, treated vs. untreatedp-value: 0.5295% CI: [-0.3, 0.6]t-test, 2 sided
Comparison: Left Eye, treated vs. untreatedp-value: 0.8895% CI: [-0.4, 0.4]t-test, 2 sided