New glaucoma drugs maximized through sound treatment strategy

The development and improvement of glaucoma drugs is a crucial and ongoing process, resulting in an ever-growing therapeutic armamentarium. However, the art of glaucoma management is not limited to pharmaceutical innovations — practitioners must also assess treatment strategies and their overall effect on quality of life.

“You really have to look at the overall clinical situation,” said Jimmy D. Bartlett, OD, FAAO, a professor of optometry at the University of Alabama at Birmingham School of Optometry. “New treatment strategies are evolving. The real goal in glaucoma management is to preserve visual function while maintaining some degree of control for the patient.”

Practitioners can maximize the emergence of new medications by evaluating the visual and lifestyle needs of each glaucoma patient.

Neuroprotectors: an exciting possibility

A promising new approach to glaucoma management is neuroprotection. Medications with neuroprotective capabilities prevent the death of the optic nerve. In animal studies, some drugs have appeared to prevent nerve damage in ways not related to lowering intraocular pressure (IOP).

“I think what separates neuroprotection in the treatment of glaucoma is the fact that it takes the component of intraocular pressure out of the treatment mix,” said David P. Sendrowski, OD, FAAO, a clinical faculty member based in California. “Intraocular pressure is certainly one trigger factor for the apoptotic death of the cells in the nerve fiber layer. These neuroprotective drugs are working on the chemical transmitters, the apoptotic messengers that encourage cell death to occur.”

Although neuroprotectors do not decrease IOP or may decrease it only slightly, they shore up the nerve fiber layer of the optic nerve head, making it less susceptible to pressure-related damage, Dr. Sendrowski said.

“Both oral and presently available topical medications fall under this category,” he said. One oral medication considered to be a neuroprotector is memantine (Merz + Co., Frankfurt, Germany), a glutamate blocker that is thought to inhibit the destruction of neurons.

Dr. Sendrowski said memantine is currently being tested in Europe and in the United States for use in treating glaucoma. “As the trials are going on, it is being used in conjunction with present topical glaucoma medications,” he said, “to see if the addition of this oral medication actually makes the topical medication work better and stop the destruction of nerve fiber layer.”

The topical formulation of verapamil (manufactured by both Searle and Knoll Labs) has also been tested as a neuroprotector, according to Dr. Sendrowski. Verapamil is a calcium channel-blocker that is used in cardiology; however, the topical formulation of the drug initially did not receive Food and Drug Administration approval as a topical medication for glaucoma. “It didn’t really lower IOP enough, so the FDA did not approve it as a topical medication,” Dr. Sendrowski said. “But because it is a calcium channel-blocker, it may prevent some of the apoptotic events that occur during glaucoma.”

Dr. Sendrowski said verapamil allows blood flow to continue even during the higher elevations of IOP. “There is the potential that perhaps verapamil can be combined with another medication,” he said. “The goal would be to make it a better IOP-lowering medication or make it more specific for the eye in terms of optic nerve head neuroprotection.”

Another potential neuroprotector currently under FDA consideration is eliprodil (Alcon Laboratories, Fort Worth, Texas), Dr. Sendrowski said. This drug acts to inhibit glutamate toxicity and would fall into the category of neuroprotector, he said.

Betoptic S (betaxolol HCl, Alcon), which is classified as a beta-blocker, is also considered to have neuroprotective effects. “Betoptic S does not inhibit ocular blood flow like other beta-blockers do and additionally acts like a mild calcium-channel blocker,” Dr. Sendrowski said. “To that extent, it provides neuroprotection.”

Another medication thought to provide some degree of neuroprotection is Alphagan (brimonidine tartrate, Allergan).

Dr. Bartlett cautioned, however, that it would be premature for practitioners to invest too much hope in neuroprotection at this time.

“There are actually no clinical studies whatsoever that show any glaucoma medication to be neuroprotective — all of the studies have been done on animals,” he said. “You can’t translate that to the real-world clinical practice. I think a lot of clinicians are premature in that. There is a lot of excitement about it, and it is potentially a benefit, but we have to do the clinical studies first.”

Alphagan P

Last year, the FDA approved Alphagan P, a new formulation of Alphagan, for treating glaucoma. Alphagan P includes Purite, a preservative used by Allergan in its Refresh Tears product. This preservative, once it enters the tear film, dissipates into sodium chloride and water, Dr. Bartlett said.

“One of the problems with Alphagan has been allergic hypersensitivity; probably 15% to 20% of patients become allergic to it,” Dr. Bartlett said. “So even though it is an excellent drug to reduce pressure, it has a problem in some patients in terms of red eye and itching.”

Because Alphagan P uses a Purite preservative, it has a 40% less incidence of allergy, Dr. Bartlett said. “The product is also 0.15% brimonidine, instead of 0.2%, but without any decrease in efficacy,” Dr. Bartlett said. “So, they have essentially lowered the concentration of the active compound, and they have changed to the Purite preservative. And that combination has resulted in far less incidence of allergic reaction.”

Other drugs

Lumigan (0.03% bimatoprost ophthalmic solution, Allergan) is part of a separate class of drugs called prostamides. “It is probably still in the broad prostaglandin family of agents, but because of the chemistry and how the drug appears to work, it has some uniqueness. So, it is being classified as a separate class of glaucoma drugs, called prostamides,” Dr. Bartlett said.

Dr. Bartlett said Lumigan, which is used once in the evening, appears to be as effective as Xalatan (latanoprost, Pharmacia), the first prostaglandin. “In some cases, it may be even better than Xalatan in terms of reducing pressure,” he said. “I think that makes it particularly well-suited for patients who have normal-tension glaucoma.”

Some degree of redness is a fairly common side effect of Lumigan, Dr. Bartlett said. “It often will dissipate after a few weeks of treatment,” he added. “But sometimes it doesn’t. So that is the downside of Lumigan.”

Dr. Bartlett said there have also been some changes to Xalatan. “The package insert previously said it needed to be stored in the refrigerator until it was dispensed to the patient,” he said. “Now, the new package insert indicates that Xalatan does not need to be refrigerated.”

A drug called Xalcom (0.0005% latanoprost, 0.5% timolol, Pharmacia), which is a combination of latanoprost and timolol, is currently awaiting FDA approval. “The obvious advantage of that will be convenience,” Dr. Bartlett said. “It is hoped that the single-bottle combination will achieve the same or better pressure control than the individual drops.”

Travatan, a recently approved prostaglandin analog, has been shown to be more effective than timolol and equal to or more effective than Xalatan. Travatan has also been shown to achieve greater effectiveness in African-American patients, according to data pooled from several travaprost studies. Southwestern Medical School in Dallas. Patients of African-American descent are four times more likely to suffer from glaucoma than are individuals of other races.

“We’ve been pleased with that, actually,” Dr. Bartlett said. “We have switched a number of our African-American patients from their existing therapies to Travatan, and we have had some pretty good results.”

Selective laser trabeculoplasty

In addition to the variety of new glaucoma medications, there have also been innovations in the area of glaucoma laser surgery. Dr. Sendrowski discussed a procedure called selective laser trabeculoplasty (SLT).

“The nice thing about SLT is that it’s repeatable,” Dr. Sendrowski said. “Normally, when patients have argon laser trabeculoplasty, it involves heat. SLT can be repeated again and again, because it is a non-heat-inducing laser.”

Dr. Sendrowski said the SLT procedure has an effect on the trabecular meshwork, where it seems to stimulate production of a certain group of white blood cells. “These cells then clean out the trabecular meshwork or some of the buildup,” he said. “It seems to stimulate a group of white blood cells that cause some of these resistant proteins.”

Dr. Sendrowski said he thinks SLT holds a great deal of hope for the future of glaucoma management. “I think it will make an impact,” he said. “It certainly may help patients who are noncompliant or who have difficulty taking their medications.”

New treatment strategies

Dr. Bartlett discussed a new treatment strategy for glaucoma, which involves switching medications rather than adding them.

“Years ago, we had only a handful of medications, and we progressed in treatment by adding the second one to the first, and the third to the second, until we reached what is called maximum medical therapy,” he said. “Now, the new strategy is to switch, rather than adding one drug to the previous drug. It really can be quite helpful and effective.”

Dr. Bartlett said patients enjoy the convenience and economy of this approach, adding that, in many cases, it achieves the same benefits with fewer side effects. “Often, it works just as well,” he said. “You do have to choose carefully which drugs you can do that with.”

Dr. Bartlett emphasized the importance of carefully assessing each patient and his or her individual needs. “You have to look at the age of your patient — patients in their 80s, for example, don’t need to be as aggressively treated as patients in their 50s,” he said. “When patients are older and have limited responsibilities for their vision, we don’t want to expose them to additional costs and side effects. It is very important to consider each patient’s quality of life.”

For Your Information:

• Jimmy D. Bartlett, OD, FAAO, is an professor of optometry in the School of Optometry and professor of pharmacology in the School of Medicine at the University of Alabama-Birmingham. He can be reached at School of Optometry, University of Alabama at Birmingham, Birmingham, AL 35294-0110; (205) 934-3036; fax: (205) 934-6758.
• David P. Sendrowski, OD, FAAO, is an associate professor at the Southern California College of Optometry. He can be reached at 2575 Yorba Linda Blvd., Fullerton, CA 92832; (714) 449-7414; fax: (714) 992-7848.
• Neither Dr. Bartlett nor Dr. Sendrowski have a direct financial interest in the products mentioned in this article, nor are they paid consultants for any companies mentioned.