Using Prostaglandins for Contemporary Therapy, Part 2
BY LEO SEMES, OD, FAAO
Many use prostaglandins as first-line therapy in treating glaucoma. We should be careful to realize that the FDA approves these medications for the lowering of intraocular pressure (IOP).
The first of the prostaglandins to receive FDA approval for lowering IOP was Xalatan (latanoprost 0.005%, Pharmacia and Upjohn). This product is hydrolyzed to the acid form in the eye and acts on the collagen framework of the ciliary body to lower IOP by creating or enhancing uveoscleral outflow. This mechanism of action complements the traditional trabecular outflow route. In fact, all of what I will call the prostaglandins share this feature.
Another prostaglandin is the eicosanoid, Rescula (unoprostone isopropyl 0.15%, Novartis). This drug has been used in Japan to treat normal-tension, the predominant form of glaucoma there, for a number of years. Its major feature is stabilization of visual field findings. Chemically, it is a docosanoid derivative. Clinically, it has been shown to perform nearly as well as timolol and as well as betaxolol to lower IOP. Also, Rescula seems to keep the all-important diurnal curve from fluctuating widely. This would be an important aspect in any glaucoma patient and especially the normal-tension one once the IOP is lower than baseline.
Recently Approved Drugs
Two medications that were FDA-approved a little over a year ago are Travatan (travaprost 0.004%, Alcon) and Lumigan (bimatoprost 0.03%, Allergan). These are, respectively, prostaglandin analog and prostamide, or ocular hypotensive lipid (OHTL). As an interesting sidelight, the OHTL family counts among its cousins the cannabinoids. In fact, delta-9 tetrahydrocannabinol has been applied topically (in peanut oil) to lower IOP.
One of the unique aspects of Travatan that emerged from the pre-clinical trials was that it not only lowered IOP at least as well as Xalatan, but the effect was greater among black patients. This racial differential may be an important asset among a population whose glaucoma appears to be more prevalent, more severe and begins at an earlier age than among white patients. Another significant advantage of Travatan is the high responder rate. Clinical studies have shown that for various IOP-measurement times, and for various criteria, Travatan is more likely than timolol to produce the desired effect on IOP.
Lumigan has powerful IOP-lowering properties as well. Its unique features include greater scleral than corneal penetration. This may allow it to act more effectively on the ciliary body to increase uveoscleral outflow, one of its proposed mechanisms of action. In addition, primate studies have shown that the trabecular outflow is enhanced as well.
With this arsenal of drugs, we have more and safer weapons to fight glaucoma. Among the prostaglandins, when one fails to produce the desired effect on IOP, another of the same class may be effective. This is true theoretically because they act on different receptors within the eye. They are versatile as initial as well as additive therapy, even though there may be nuances within the group that are beyond the scope of this article to discuss.
The Advanced Glaucoma Intervention Study (AGIS) data suggests that keeping the IOP below 14mm Hg offers the best protection against progression of visual field loss. Although all the patients enrolled in this study had advanced glaucoma, it is my interpretation that lower is better for all of our glaucoma patients. We should be aggressive in attempting to control the IOP in this disease that can eat away inevitably at the visual field.
Dr. Semes is an associate professor at the University of Alabama at Birmingham School of Optometry.