Glaucoma, Open Angle Clinical Trial
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
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
pressure.
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.
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 α2-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 α2-adrenergic agonists induce
basic fibroblast growth factor mRNA in the retina. Treatment with α2-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 α2-adrenoceptor and provide a neuroprotective effect.
The study hypothesis is to evaluate the ability of topical treatment with 0.2% brimonidine,
a highly selective α2-adrenergic agonist, to impart neuroprotection to the damaged optic
nerve in patients with LPG. Comparison is made to 0.5% timolol, a nonselective β-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.
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Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment
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