Glaucoma is the second leading cause of blindness in the United States. Specifically, open-angle glaucoma is progressive and asymptomatic, with elevated intraocular pressure causing a gradual increase in cupping of the optic nerve disc. The effect of this cupping on the retina is the diminishment of the patient's visual field.
There are several predisposing factors, including family history, concurrent diabetes, or severe myopia. Black patients over the age of 40 and white patients over the age of 65 also have an increased risk of developing open-angle glaucoma.
Although elevated intraocular pressure is considered a major risk factor, it is not completely effective as a diagnostic tool. Patients may have normal pressures within the eye and still have glaucoma. Visual field testing is the mainstay of glaucoma diagnosis and its progressive management.
Without treatment, open-angle glaucoma will result in irreversible loss of vision. Before aggressive treatments involving lasers or surgery are employed, therapy involves sterile ophthalmic solutions that affect sympathetic receptors in the eye. Brimonidine, at a 0.2% concentration, creates changes at the alpha-receptor level in order to reduce intraocular pressure.
Reduction in intraocular pressure generally is accomplished either by decreasing the production of aqueous humor entering the eye or by increasing its outflow through the trabecular meshwork or uveoscleral pathways. Brimonidine is a relatively selective alpha-2 receptor agonist and reduces intraocular pressure by both decreasing the production of aqueous humor and increasing its outflow through the uveoscleral pathway. This alpha-2 receptor agonist property reduces both elevated and normal pressure in the eye, regardless of the presence of glaucoma. The maximum reduction in pressure is seen within 2 to 3 hours following the administration of brimonidine. Overall, ophthalmic pressure is reduced by ~25%.
Administration and Dosing
The recommended dosing of brimonidine for open-angle glaucoma is 1 drop in the affected eye 3 times daily, spaced at 8-hour intervals. Response to the initial therapy should be checked after 4 weeks and then monitored periodically to observe effectiveness and to look for potential side effects.
As with any sterile ophthalmic preparation, care should be taken when handling brimonidine solution to prevent contamination. Patients should be advised to wash their hands before and after using this solution. In addition, when using multiple ophthalmic therapies, the patient needs to wait at least 5 minutes before the administration of other eyedrops.
Side Effects and Drug Interactions
Adverse effects occur frequently with brimonidine (at a rate of 10-30%) and include localized burning, headache, the sensation of a foreign body in the eye, ocular pruritus, blepharitis, xerophthalmia, tearing, corneal staining, and blurred vision.
Although systemic effects of alpha-2 agonists may result in vasoconstriction, the topical use of brimonidine among adults appears to generate minimal concern among clinicians regarding this effect. The manufacturers do recommend caution, however, when using brimonidine in patients with severe cardiovascular conditions, orthostatic hypotension, cerebral or coronary insufficiency, or Raynaud's phenomenon.
Although concern over systemic effects is slight among adults, it should be noted that ophthalmic use of brimonidine among children under the age of 2 has resulted in apnea and lethargy, and that, in early studies, treatment was discontinued in 16% of children aged 2 to 7 due to sleepiness. Somnolence in these reports appears to be age-and weight-related. Therefore, the use of brimonidine requires cautious monitoring in children under the age of 7 and is actively discouraged in children under the age of 2.
In general, patients have allergic reactions to brimonidine at a rate of 10% to 20%. The high frequency of allergic reactions to brimonidine appears to sensitize the patient to subsequent drugs used to treat open-angle glaucoma. A special formulation using a Purite product as a preservative has been introduced to the market in an effort to reduce the rate of allergy. This form, however, is still under patent protection.
The consequences of untreated glaucoma can be devastating. Before today's commonly available treatments, blindness generally was inevitable. This progressive condition can now be treated with several agents. Although patients with glaucoma can experience an increased quality of life with their use, the treatments themselves possess side effects that require repeated assessment. Brimonidine is available as a 0.2% sterile ophthalmic solution from Bausch and Lomb, Allergan, and Falcon Pharmaceuticals.
Mr. Middleton is an instructor of pharmacology at Kellogg Community College in Battle Creek, Mich.
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