Prostaglandin analogs: the “gold standard” for glaucoma

Issue: July 2005

ByJennifer Byrne

In a Primary Care Optometry News article published in July 1996, Editorial Board member Alan L. Robin, MD, discussed the most promising drugs for the treatment of glaucoma.

At that time, Dr. Robin, an associate professor of ophthalmology at Johns Hopkins University, considered Xalatan (latanoprost, Pfizer) to be the most noteworthy emerging drug for glaucoma.

"The most exciting new drug is latanoprost, brand name Xalatan. I was one of the phase 2 investigators in the U.S. studies," he said in the 1996 interview. "Xalatan is a much more powerful drug than timolol. Timolol given twice a day has a mean eye pressure lowering effect of about 25%. Latanoprost given once a day has a mean IOP lowering of about 35%, so it's a third more powerful. It also adds well to most of the other medications we have."

Nearly a decade later, Dr. Robin revisited the topic in an interview with Primary Care Optometry News, discussing his current favorite tools for managing glaucoma.

PCON July 1996 [cover]
July 1996:This issue, which spotlighted glaucoma, also discussed a new technology, blue-yellow perimetry, as well as the recent FDA approval of Xalatan.

The gold standard

Xalatan remains high on Dr. Robin's list, as are the other two prostaglandin analogs that were subsequently developed — Lumigan (bimatoprost, Allergan) and Travatan (travoprost, Alcon). "These drugs really have become the new gold standard for glaucoma therapy," he said. "They have been the most successful in lowering intraocular pressure a mean of 30% to 35%, and they offer the convenience of once-daily therapy."

Dr. Robin said these drugs also have the highest percentage of successful IOP-lowering effect. "If you give these drugs to 100 people, a higher percentage of those 100 people will experience high pressure lowering with this class of drugs than with any other class of drugs," he said.

In addition, he said, the prostaglandin analog class has the fewest systemic side effects of any class and is, therefore, very well tolerated.

"Proof of this is the Medicare data on surgical treatment for glaucoma, which is usually reserved for those individuals in whom medical therapy doesn't work. The numbers have continually gone down since the introduction of latanoprost," he said.

Dr. Robin said the only drawbacks of these drugs are lash lengthening and hyperemia. "The lash lengthening happens in all prostaglandin analogs, while the hyperemia occurs less frequently in Xalatan than in Lumigan."

Other options

Dr. Robin said prior to the prostaglandin analogs, the gold standard drugs for glaucoma treatment were nonselective beta-blockers such as timolol.

"Timolol's major problems were depression, impotence for men, asthma and heart failure," Dr. Robin said. "Most patients with glaucoma are older, so the risk of having these side effects is greater. It becomes a major issue."

Dr. Robin said while these side effects do not rule out timolol as an effective tool for glaucoma, they do diminish it to some extent. "It is still a very good drug, but it is not as good as the prostaglandin analogs," he said.

Dr. Robin said another class of drugs that appears to have declined in popularity is the alpha agonists, which are now available in generic form. "These appear to me to be losing favor," he said. "They really should be three-times-daily drugs. They have a peak-and-trough effect, which means that at peak, they work really well, but 4 to 6 hours later, the pressure lowering is not as good."

Dr. Robin added that there is also a significant percentage — between 15% and 20% — of patients who develop an allergy to alpha agonists.

Promise of combination drugs

pcon, july 96
Side effect of prostaglandins: One drawback of this class of drugs is the potential for lash lengthening.

According to Dr. Robin, combination drugs also hold a great deal of promise for glaucoma treatment. Cosopt (dorzolamide HCl, timolol maleate ophthalmic solution, Merck) is the only combination drug currently approved by the Food and Drug Administration. "These are tremendous drugs, because they allow us to give patients three medicines with two eye drops," he said. "The FDA has not allowed the other drugs to be approved."

He said the approval of these drugs would offer a convenient option for patients, and would most likely increase compliance as well. "I think it would be a good thing if the FDA allowed these medicines to be approved," he said. "I think it would truly help facilitate patient compliance."

The next decade

Dr. Robin looked to the Ocular Hypertension Treatment Study (OHTS) to determine what is needed for future glaucoma drugs. "In the OHTS study, for at least 40% of individuals to obtain a consistent 20% decrease in eye pressure, more than one medicine was required," he said. "It would be nice to have a medication that worked for a larger percent of people and provided more eye pressure lowering."

He looked back at the drugs that were promising 10 years ago and evaluated the way these drugs turned out. "The question from a pharmaceutical perspective is during the past 10 years, did they make it?" he said. "Prostaglandins did. Alpha agonists sort of did. But the ones that have really changed the way we treat patients are the prostaglandin analogs."

For Your Information:

Alan L. Robin, MD, is an associate professor of ophthalmology at Johns Hopkins University and a Primary Care Optometry News Editorial Board member. He can be reached at 6115 Falls Rd., Ste. 333, Baltimore, MD 21209-2226; (410) 377-2422; fax: (410) 377-7960; e-mail: Glaucomaexpert@cs.com. Dr. Robin has no direct financial interest in the products mentioned in this article, nor is he a paid consultant for any companies mentioned.