SEP 21, 2009
Over the past decade considerable speculation and effort has been invested in examining the neuroprotective properties of brimonidine and related alpha2-receptor agonists in eye disease. This thorough review of the published literature lays out the evidence thus far and provides some insight into why the neuroprotective effects of these agents have not yet been proven in humans.
In 48 articles reviewed, the first three criteria proving the neuroprotective effect of brimonidine appears well satisfied. These include: proven receptors on the target tissues in question, adequate penetration into the vitreous and retina at pharmacologically active levels, and induction of intracellular changes to enhance neuronal resistance to damage or interruption of apoptosis of ganglion cells in animal models.
Despite several well-designed trials involving human subjects with acute ischemic insults to the optic nerve, including nonarteritic anterior ischemic optic neuropathy (NAION) and Leber's optic neuropathy, there is no evidence these agents afford any benefit either after disease onset or in prevention of vision loss in at-risk contralateral eyes.
Why? One major reason is that brimonidine was most effective in animal models when treatment preceded the optic nerve injury. The annual incidence of NAION is too small to make clinical trials practical even in the contralateral eye of patients who suffer vision loss in one eye. Also, animal models have shown that post-injury treatment with alpha agonists is most effective when treatment begins immediately after the injury. Delaying treatment for even a few hours may prevent any beneficial effect. This fact may also account for the difficulty in recruiting subjects into controlled trials. Another explanation is that there may indeed be major differences between species in types of alpha-2 receptors and in the concentration of locations of different receptor types in the target tissues.
As the microcirculation of the optic nerve - as well as its relationship to glaucoma and other diseases - is better understood, perhaps use of similar agents with different characteristics will be indentified and found clinically effective.
Dr.Reynolds has no financial interests to disclose.