Prostaglandins changed glaucoma treatment algorithms

The first-line treatments for open-angle glaucoma and ocular hypertension have assisted in both patient care and research.

Issue: November 15, 2006

ByErin L. Boyle

Prostaglandins, prostaglandin analogues and prostamides, now considered the first-line treatments for patients with open-angle glaucoma, have changed treatment algorithms permanently and for the better, according to one glaucoma specialist.

The ophthalmic drugs derived from prostaglandins are the most recently introduced class of glaucoma therapy agents. Since the appearance of the first prostaglandin analogue for ophthalmic use 10 years ago, the drugs have replaced beta-blockers as first-line therapy for glaucoma, a position the beta-blockers held since their introduction in 1978.

Pfizer’s Xalatan (latanoprost) is the No. 1 prescribed IOP-lowering medication for patients with open-angle glaucoma or ocular hypertension on the market, according to data from IMS Health and the National Pharmacy Association. It was also the first on the market, celebrating its 10th anniversary this year. The other glaucoma drugs in the prostaglandin family are Travatan (travoprost ophthalmologic solution 0.004%, Alcon), Travatan Z (benzalkonium chloride-free travaprost 0.004%) and Lumigan (bimatoprost ophthalmic solution 0.03%, Allergan).

Douglas J. Rhee, MD [photo]
Douglas J. Rhee

Glaucoma specialist Douglas J. Rhee, MD, said in a telephone interview with Ocular Surgery News that immediately after Xalatan went on the market, the use of laser treatment and surgery for glaucoma began to decline. That decline was only a “lull,” he said, as laser and surgery are still being used, but often after a prostaglandin has ceased to be effective in lowering a patient’s IOP.

“These medications were so effective that they actually decreased the rate of any sort of interventional procedure,” Dr. Rhee said.

He said that the benefits of having the prostaglandin medicine class for use in glaucoma treatment are twofold. The first benefit is that the drugs proved that medications can be effective in lowering IOP with minimal side effects and a dosing schedule that is “reasonable” for patient compliance.

The second benefit is that the drugs have enhanced the concept of glaucoma management with their effectiveness in increasing aqueous outflow. The mechanism of action of the prostaglandins highlighted the importance of aqueous outflow, rather than aqueous production, as a therapeutic target, Dr. Rhee said.

“It has helped highlight the benefit and effectiveness of targeting aqueous drainage compared with the traditional approach of decreasing production,” he said.

Before prostaglandins

Before the U.S. Food and Drug Administration’s approval of Xalatan, which was introduced by Pharmacia in 1996, the available glaucoma agents focused on decreasing aqueous production, Dr. Rhee said. Without other options for pharmaceutical IOP-lowering available, physicians often recommended argon laser trabeculoplasty or filtering surgery fairly early in the course of a patient’s disease, he said.

Prostaglandins have become the “go-to” class of drugs, the first-line medical treatment for glaucoma, for about the past 5 years, Dr. Rhee said. In the first 5 years of their availability, not all physicians had adopted the new class of drugs, he said, but time has shown their effectiveness.

“It’s now regarded as our first-line agent by the majority of glaucoma specialists, indicating its clinical effectiveness,” he said. “This has often allowed many patients to perhaps avoid surgery or any interventional procedures or delay them by a large degree.”

He said the prostaglandin class will most likely remain the first-line approach to glaucoma therapy for years to come, even with the advent of minimally invasive laser treatments such as selective laser trabeculoplasty (SLT).

The effect of the introduction of the prostaglandin class has been an “evolution, not a revolution,” Dr. Rhee said. While it changed the algorithm for glaucoma treatment, it did not “completely alter” the accepted knowledge about glaucoma itself, he said.

“Prostaglandins have been what I would consider one of the most significant advances in glaucoma care in a long time,” Dr. Rhee said. “But we have lived, in the last decade, through an era where we have seen a number of exciting advances, not only with prostaglandins, but also with [topical carbonic anhydrase inhibitors] and selective alpha-2 agonists.”

In addition to an “explosion of effective new medications” and the introduction of SLT, Dr. Rhee said, glaucoma specialists have also achieved a better understanding of how to use glaucoma drainage devices.

“In the last 10 years, I think we’ve made more progress in glaucoma care than we had in the preceding 40 years,” he said.

Benefit to research

Not only have prostaglandins had an impact on patient care, they have also been important to scientific research into glaucoma, Dr. Rhee said. He said the prostaglandin class has advanced the understanding of the disease and of normal ocular physiology, as evidenced by an ever-expanding body of research.

“By increased understanding of how prostaglandins work in terms of mechanism of action, it’s really given us a better insight into the fundamental regulation of IOP and what might be wrong in glaucoma,” Dr. Rhee said.

He said the drugs work by a mechanism that degrades the extracellular matrix. One of the reasons why it is still unknown what causes glaucoma is because no one knows exactly how IOP is regulated, he said. (See “Did you ever wonder about … why we don’t know what causes glaucoma.”)

“We do have some idea,” Dr. Rhee said. “But prostaglandins and their effectiveness have really shown us the importance of matrix turnover in the regulation of IOP.”

For more information:

Douglas J. Rhee, MD, is an assistant professor of ophthalmology at Harvard Medical School and on the faculty of the Massachusetts Eye and Ear Infirmary. He can be reached at 243 Charles St., Boston, MA 02144; 617-573-3670; fax: 617-573-3707; e-mail: dougrhee@aol.com.

Alcon, maker of Travatan, can be reached at 6201 South Freeway, Fort Worth, TX 76134; 817-293-0450; fax: 817-568-6142; Web site: www.alconlabs.com.
Allergan Inc., maker of Lumigan, can be reached at P.O. Box 19534, Irvine, CA 92623; 714-246-4500; fax: 714-246-4971; Web site: www.allergan.com.
Pfizer, maker of Xalatan, can be reached at 235 East 42nd Street, New York, NY 10017; 212-573-343; fax: 212-672-7926; Web site: www.pfizer.com.

Erin L. Boyle is an OSN Staff Writer who covers all aspects of ophthalmology.