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prostaglandin platform or intended to serve as adjunctive therapy to prostaglandins. New possibilities Bausch + Lomb (Bridgewater, N.J.) is developing a compound called latanoprostene bunod, which—as the name implies—is a modified version of latanoprost that also fea- tures a nitric oxide-donating moiety. It is currently in 2 separate clinical trials, named APOLLO and LUNAR. Rho kinase inhibitors In the trabecular meshwork, activation of the rho kinase pathway leads to contraction of the actin and myosin structural skeleton of the extracellular matrix, decreasing aqueous outflow, said Paul Kaufman, MD, University of Wisconsin, Madison. Conversely, inhibition of the rho kinase pathway leads to relaxation of the actin-my- osin system and increases aqueous outflow through the meshwork. "This is the first class of drugs that has its primary mechanism of action in the trabecular meshwork," he said, "and there are currently five rho kinase inhibitors in clinical trials." Average IOP reductions in phase 2 studies of rho kinase inhibitors demonstrate that they lower IOP on average between 4 and 6 mmHg when used as monotherapy, Dr. Kaufman said. This modest performance is not likely to significantly alter the first line IOP-lowering landscape. Recognizing this, at least one drug company has begun exploring fixed combination products containing a rho kinase inhibitor. One of these combines a rho kinase inhibitor with latanoprost and, if approved, would be the first latanoprost-con- taining fixed combination product in the U.S. marketplace. Marijuana "There are cannabinoid receptors in the eye," said Henry Jampel, MD, Johns Hopkins University, Baltimore, "and marijuana has been of interest for IOP reduction in glaucoma for decades." The problem is one of drug delivery. "Topical formulations have been unable to penetrate into the eye," he said. Likewise, trans- alveolar delivery (via smoking) produces only modest IOP reduc- tions of impractically short duration. The issue of medical marijuana for glaucoma therapy has been made relevant recently by the legalization of recreational marijuana use in Washington and Colorado, as well as the approval of medical marijuana use in 22 states and the District of Columbia. A recent study evaluated attitudes toward marijuana use by glaucoma patients conducted by David Belyea, MD, and colleagues at George Washington University in D.C. In this study, 204 glauco- ma patients completed a survey that included items related to their perceptions toward marijuana and their intentions to use marijuana for glaucoma. The results showed that prior use of marijuana, false be- liefs about marijuana, perceptions that marijuana should be legal, and lower satisfaction with glaucoma management are significant predic- tors to use marijuana. Surprisingly, neither glaucoma diagnosis nor the severity of glaucoma disease were found to be correlated with inten- tions to use marijuana (presented as a poster at the American Glaucoma Society annual meeting in March 2014). Clinical implications The current landscape of innova- tion in glaucoma therapy is en- couraging and may well produce approved products that will enable us all to better care for our patients and preserve their visual function. Prostaglandins have set the bar very high for a paradigm shift in first-line therapy, but the adjunctive market remains wide open. Perhaps one of these new agents will meet the unmet need for an effective adjunct to the prostaglandin class. Another area of unmet need is in the arena of drug delivery. Developing a drug or drug delivery system that obviates the need for daily topical therapy would be paradigm-changing. It can be done—as evidenced by steroid implants, intravitreal injections of vascular endothelial growth factor inhibitors, and even the ancient pilocarpine Ocusert. A number of promising technologies are in various stages of investigation. With luck and persistence, one or more of these may come to fruition. EW Editors' note: Dr. Kaufman has financial interests with Bausch + Lomb and other ophthalmic companies. Drs. Belyea and Jampel have no financial interests related to this article. Contact information Belyea: dbelyea@mfa.gwu.edu Jampel: hjampel@jhmi.edu Kaufman: kaufmanp@mhub.ophth.wisc.edu August 2014 Glaucoma drug continued from page 53