MAY 03, 2011
While laboratory studies have demonstrated that alpha2-adrenergic agonists are neuroprotective in experimental models of glaucoma, clinical trials in nonglaucomatous diseases have failed to show treatment benefit. However, this study suggests alpha2-adrenergic agonists may indeed have a neuroprotective benefit in normal-tension glaucoma. It showed that low-pressure glaucoma patients randomized to monotherapy with the alpha2-adrenergic agonist brimonidine tartrate 0.2% were statistically less likely to have progressive visual field loss than those patients randomized to monotherapy with the beta-adrenergic antagonist timolol maleate 0.5%.
The authors performed a double-masked study randomized of 178 patients with normal-tension glaucoma to brimonidine or timolol monotherapy twice daily in both eyes. After a mean follow-up of 30 months, brimonidine-treated patients were statistically less likely to have progressive visual field loss than timolol-treated patients, (P = .001). Mean treated IOP was similar for both groups at all time points. However, more brimonidine-treated patients suffered adverse events, mainly ocular allergy, and left the study (28.3 percent vs. 11.4 percent).
Given that the IOP reduction was similar between groups, the lower rate of visual field progression in brimonidine-treated patients could result from either an unknown IOP effect or an IOP-independent process. It is possible that brimonidine was more effective than timolol in lowering diurnal, peak, mean, or nocturnal IOP. These IOP parameters were not measured in the current study. A related explanation could be different mechanisms of action. The reduction of aqueous humor production by timolol is minimal at night, while brimonidine has been reported to both reduce aqueous humor production and increase uveoscleral outflow.
The authors conclude that validation of a neuroprotective mechanism of action requires additional basic science and clinical research to confirm the present results prior to altering current clinical patient care paradigms. Additionally, the effectiveness of brimonidine in delaying or preventing visual field progression has to be judged in context of brimonidine's adverse event profile, primarily localized external ocular allergy.