Comparison of Latanoprost Vs. Timolol

A recent publication by our laboratory has shown that patients with ocular hypertension (OHT)
have reduced uveoscleral outflow and reduced trabecular outflow facility compared with
healthy age-matched controls. These changes are the cause of the elevated intraocular
pressure (IOP). Aqueous flow rate did not change in these patients. It is logical to assume
that it would be more efficacious to treat OHT patients with drugs that reduce IOP by
increasing uveoscleral outflow (which is abnormally low) than with drugs that reduce aqueous
flow (which is normal in OHT).

The primary purpose of this study is to show, through a controlled masked clinical study of
OHT patients, that latanoprost increases the low uveoscleral drainage of aqueous humor (Fu)
back to normal levels, and timolol maleate reduces the formation of aqueous humor (Fa) below
normal. Both of these mechanisms will effectively reduce IOP.

The secondary purpose is to assess the effects of both latanoprost and timolol maleate on the
fluorophotometric outflow facility (Cflu), and episcleral venous pressure (Pev) and on all
parameters over time.

Subjects eligible to participate will be at least 19 years of age and diagnosed with
bilateral ocular hypertension or primary open angle glaucoma and have intraocular pressure
between 20 and 35 mmHg in both eyes on Day 0. Subjects will be treated with either
latanoprost or timolol for 6 weeks and then crossover and be treated similarly with the
alternate drug for an additional 6 weeks. There will be a screening visit and a total of 6
study visits in which aqueous humor flow, uveoscleral outflow, and fluorophotometric outflow
facility will be determined using an instrument called a fluorophotometer. The
fluorophotometer scans the eye for fluorescein dye allowing the investigator to measure and
calculate the above variables. There will be 7 scans taken during each study day and
additionally IOP will be measured after the completion of each scan. An Exit exam will be
performed at the time of exit to ensure the ocular health of the subject.

Subjects will be monitored for adverse events throughout the course of the study and subjects
may discontinue from the study at any time for any reason, or may be discontinued if, in the
opinion of the investigator, there is a risk to the subject.

Inclusion Criteria:

- Minimum of nineteen (19) years of age.

- Diagnosed with bilateral ocular hypertension or primary open angle glaucoma for at
least six months prior to screen visit.

- IOP of 20-35 mmHg in both eyes and not more than 5 mmHg difference between eyes at the
Baseline 0800 ±1 hour IOP measurement.

- Willing and able to provide informed consent.

- Able to adhere to treatment/visit plan.

Exclusion Criteria:

Systemic Conditions:

- History of severe, unstable or uncontrolled cardiovascular, hepatic or renal disease.

- History of bronchial asthma or chronic obstructive pulmonary disease.

- Allergies to sulfa drugs.

Ocular Conditions:

- Chronic or recurrent severe ocular inflammatory disease.

- Ocular infection or inflammation within three (3) months of the study visit.

- Subjects currently treated with more than two ocular hypotensive medications.

- Subjects having previous exposure to: adrenergic antagonists, topical prostaglandin
analogues (including latanoprost, unoprostone, travoprost and bimatoprost) within four
(4) weeks of the baseline visit; adrenergic agonists within two (2) weeks of the
baseline visit; and cholinergic agonists and carbonic anhydrase inhibitors within five
(5) days of the baseline visit.

- History of any severe ocular pathology that would preclude the administration of a
topical prostaglandin or beta-blocker.

- History of severe or serious hypersensitivity to topical or systemic prostaglandins or
beta-blockers.

- Intraocular pressures less than 20 mmHg when off all ocular medications.

- Cornea thickness greater than 600 microns.

Women:

- Women of childbearing potential who are sexually active, or plan to become sexually
active, and don't have a vasectomized partner, must agree to use at least one of the
following acceptable contraceptive methods: condoms (male or female with or without a
spermicidal agent, a diaphragm or cervical cap with spermicide, an intrauterine device
(IUD) or hormonal-based contraception. Women of childbearing potential are defined as
women who are not surgically sterile or not postmenopausal (at least 12 months without
menstrual period).

- Nursing mothers.

- Pregnancy

- General

- Subjects less than nineteen (19) years of age.

- Therapy with another investigational agent within 30 days of Screening Visit.