Study of Medical Treatment of Low-Pressure (Normal Tension) Glaucoma
Information source: Chicago Center for Vision Research
Information obtained from ClinicalTrials.gov on June 20, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Glaucoma, Open Angle
Intervention: brimonidine, timolol (Drug)
Phase: Phase 2
Sponsored by: Chicago Center for Vision Research
Official(s) and/or principal investigator(s):
Theodore Krupin, M.D., Study Chair, Affiliation: Feinberg School of Medicine, Northwestern University
Low-pressure (normal tension) glaucoma is a type of open-angle glaucoma resulting in damage
to the optic nerve and abnormalities of the visual field. Eye (intraocular) pressure in this
type of glaucoma is not higher than that usually considered to be normal (less than 21 mmHg)
for the eye. The present treatment of low-pressure glaucoma is also directed to lowering the
“normal” eye pressure. Both medications in this study, brimonidine and timolol, lower eye
Laboratory research over the past decade indicates the potential to treat glaucoma not only
by lowering eye pressure, but with treatments aimed at the damage occurring at the optic
nerve. One group of drugs, selective alpha2-adrenergic agonists, have been shown in
laboratory animals to protect against the effects of nerve damage following local stroke.
Brimonidine, one of the medications in the current study, is a selective alpha2-adrenergic
agonist which protects against damage to optic nerve in animal models of glaucoma..
The hypothesis of the present study is that brimonidine eye drops provide protection to the
damaged optic nerve independent of lowering eye pressure in patients with low-pressure
glaucoma. This will be determined by (1) measuring eye pressure, (2) performing visual field
examinations, and (3) examination of the optic nerve.
Official title: A Multicenter, Double-Masked, 2-Arm Parallel Group Study Comparing the Effect of Brimonidine 0.2% Versus Timolol 0.5% on Visual Field Stability in Patients With Low-Pressure Glaucoma
Study design: Treatment, Randomized, Double-Blind, Active Control, Parallel Assignment, Efficacy Study
Primary outcome: To compare changes in automated static visual field decibel values at 4 month intervals over 4 years of monotherapy with either brimonidine or timolol eye drops.
To characterize the intraocular pressure throughout the study period.
To characterize optic disc changes (e.g., cupping and disc hemorrhages) over the 4 years of treatment with brimonidine or timolol.
To follow the safety parameters throughout the study period.
To determine risk factors for visual field progression in low-pressure glaucoma
The term glaucoma describes a specific pattern of optic nerve head and visual field damage
caused by a number of different diseases of the eye, most (but not all) of which are
associated with an elevated eye pressure. Glaucoma is currently considered to be a
progressive neurodegenerative disorder. Low-pressure glaucoma (LPG) is a type of open-angle
glaucoma (OAG) with progressive visual field and optic nerve damage despite an untreated eye
pressure in the statistically normal (mean 15. 9, SD 2. 9 mmHg) range, usually less than 21
mmHg. Therefore, in this condition, pressure-independent mechanisms (e. g., vascular or
structural defects of the optic nerve) may be the main, if not the sole, cause of the optic
neuropathy. LPG represents 6. 7% to 68. 3% of all OAGs.
Current glaucoma treatment is directed to lowering eye pressure using medical therapy (eye
drops), laser treatment, and/or surgery, to a level that stops progressive optic nerve
damage. The efficacy of lowering eye pressure in LPG has been reported. Both protocol medical
treatments, brimonidine and timolol, show similar efficacy to lower eye pressure.
Laboratory research over the past decade indicates the potential to manage glaucoma not only
by lowering eye pressure, but with treatment modalities aimed at the damage occurring at the
optic nerve. Possible therapies may include agents effective as neuronal protectants to
increase or prolong the survival rate of injured retinal ganglion cells. Treatments could
also be directed to the rescue of nerve fibers from secondary degeneration, as stimulants to
expand dendritic fields, and to promote nerve regeneration or neural transplantation.
Selective Î±2-adrenergic agonists have been shown to have a neuroprotective effect in animal
models of focal cerebral ischemia. Brimonidine is reported to protect the optic nerve and
retinal ganglion cells from secondary degeneration following a partial crush lesion to the
adult rat optic nerve. One molecular mechanism for this neuroprotection may relate to
up-regulation of neuronal survival factors. In rats, systemic Î±2-adrenergic agonists induce
basic fibroblast growth factor mRNA in the retina. Treatment with Î±2-agonists before and
during constant light exposure reduces retinal photoreceptor degeneration in albino rats.
Animal studies demonstrate that topical administration of brimonidine results in
pharmacologic concentrations of drug in the vitreous (100-170 nM). Therefore, ocular dosing
with brimonidine provides a route for drug delivery to the retina in amounts sufficient to
bind and activate the Î±2-adrenoceptor and provide a neuroprotective effect.
The study hypothesis is to evaluate the ability of topical treatment with 0. 2% brimonidine, a
highly selective Î±2-adrenergic agonist, to impart neuroprotection to the damaged optic nerve
in patients with LPG. Comparison is made to 0. 5% timolol, a nonselective Î²-adrenergic
antagonist, without reported neuroprotective properties. Patients will be randomly assigned
to twice daily double-masked treatment with one of these drugs. Neuroprotection will be
assessed by evaluation of automated static visual fields performed at 4 month intervals for 4
years of treatment.
Minimum age: 30 Years.
Maximum age: N/A.
- Age: 30 years or older.
- Low-pressure glaucoma in at least one eye: untreated IOP < 21 mmHg, glaucomatous field
loss on Humphrey 24-2 perimetry, and optic disc cupping.
- Best corrected visual acuity at least 20/40 in at least one eye.
- At least two visual fields within the 6 months prior to enrollment.
- Phakic or pseudophakic (cataract surgery > one year to enrollment) eye.
Either eye patient exclusion:
- Past history of confirmed treated or untreated applanation IOP > 21 mmHg.
- Untreated IOP of > 21 mmHg on diurnal curve on Study Day 0.
- Untreated IOP > 4 mmHg difference between the two eyes.
- Extensive field damage: MD > 15 dB or threat fixation in both hemi fields.
- Evidence of exfoliation or pigment dispersion.
- History of angle-closure or occludable gonioscopic anterior chamber angle.
- Prior filtration surgery.
- Prior laser iridotomy.
- Laser trabeculoplasty < 6 months prior enrollment or for an IOP > 21 mmHg.
- History of chronic inflammatory eye diseases (e. g., scleritis, uveitis).
- History or signs of intraocular trauma.
- Severe or potentially progressive retinal disease.
- Any abnormality preventing reliable applanation tonometry.
- History of hypersensitivity to study medications or their components.
- Current use of any ophthalmic, dermatologic or systemic steroid preparation.
- Therapy with another investigational agent within the past 30 days.
Single eye exclusion:
- Cataract surgery within the past year.
- Only sighted eye.
- Resting pulse < 50 beats per minute.
- Unstable or uncontrolled cardiovascular, renal, or pulmonary disease.
- Recent heart attack or stroke.
- Women contemplating pregnancy, who are pregnant or are a nursing mother.
Locations and Contacts
Little Rock Eye Clinic, Little Rock, Arkansas 72205, United States
Bascom Palmer Eye Institute, Palm Beach Gardens, Florida 33418, United States
University of Florida, Gainesville, Florida 32610, United States
University Eye Specialists, Chicago, Illinois 60611, United States
Wheaton Eye Clinic, Wheaton, Illinois 60187, United States
University of Chicago, Chicago, Illinois 60637, United States
Indiana University, Indianapolis, Indiana 46202, United States
New York Eye & Ear Infirmary, New York, New York 10003, United States
Wills Eye Hospital, Philadelphia, Pennsylvania 19107, United States
Scheie Eye Institute University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States
Black Hills Regional Eye Institute, Rapid City, South Dakota 57701, United States
Cullen Eye Institute Baylor University, Houston, Texas 77030, United States
Krupin T, Liebmann JM, Greenfield DS, Rosenberg LF, Ritch R, Yang JW; Low-Pressure Glaucoma Study Group. The Low-pressure Glaucoma Treatment Study (LoGTS) study design and baseline characteristics of enrolled patients. Ophthalmology. 2005 Mar;112(3):376-85.
Starting date: December 1998
Ending date: May 2004
Last updated: April 23, 2006