Only a few years ago, ophthalmologists and glaucoma patients were encouraged by the early promises of neuroprotection, a new concept for many of us. Terms such as apoptosis and free radicals cropped up in dinner meetings for comprehensive ophthalmologists. There was a sense that, after 100 years of glaucoma treatment directed at lowering IOP to prevent visual loss, therapy would soon become more sophisticated and specific to protecting the optic nerve head. The provocative data were initially derived from research using an optic nerve crush model in rats. Brimonidine administered before the injury appeared to partially protect the ganglion cells from the trauma to the optic nerve.1

To its credit, Allergan, Inc. (Irvine, CA), launched what may be the most expensive study yet in treating glaucoma. Many of us clamored to be a part of the clinical study of memantine. Unlike any prior glaucoma trial, this one established a visual field and optic disc reading center to assess progression instead of depending on IOP as an endpoint. Ten years and millions of dollars later, Allergan recently provided us with a glimpse of the data. Surprisingly, the information was not presented at an investigators meeting, at a glaucoma forum, or in a peer-reviewed journal. Instead, it was noted in a brief press release intended for financial analysts.2 The data released were vague but suggest negative results. We can only hope a detailed analysis is presented and published, because we have much to learn about the natural history of advanced glaucoma as assessed from changes in the visual field and optic disc. Whether or not intervention with memantine was successful, future therapeutic studies in glaucoma must go beyond medications that lower IOP if we are to make any progress in helping our patients.

In this issue of Glaucoma Today, Michael Belkin, MA, MD, Professor of Ophthalmology at Tel Aviv University in Israel, offers an analysis of the limited information available on the memantine trial and looks at the hurdles of developing a neuroprotective agent, of which memantine is the latest example. Whether the drug is ultimately found to be clinically useful or not, the challenge remains to develop a therapy for treating glaucoma that moves beyond the lowering of IOP to treat the source of visual loss, the degeneration of the optic disc.

1. Wheeler LA, Gil DW, WoldeMussie E. Role of alpha-2 adrenergic receptors in neuroprotection and glaucoma. Surv Ophthalmol. 2001;45(suppl):S290-S294; discussion: S295-S296.
2. Allergan reports fourth quarter operating results [press release]. Irvine, CA: Allergan, Inc.; January 31, 2007. Available at:
http://www.shareholder.com/agn/ReleaseDetail.cfm?ReleaseID=227679. Accessed February 15, 2007.