glaucoma

How Recent Events are Affecting Glaucoma Care

Four recent developments are shaping the way you treat this ocular condition.

RICHARD MARK KIRKNER, Phoenixville, Pa.

The state of the economy, a greater awareness of a drug's effect on the ocular surface, the availability of combination therapy and new approaches to laser treatment are all recent events that have impacted the management of glaucoma.

Back to beta-blockers

Although prostaglandins have become the first line of defense in glaucoma treatment, experts say the economic downturn has caused optometrists to write an increasing number of prescriptions for an old standby, beta-blockers.

"It's hard to argue with the $4-a-month therapy, especially for patients who are uninsured," says optometrist Joseph A. Sowka, clinical professor at Nova Southeastern University College of Optometry in Fort Lauderdale, Fla. "Beta-blockers work very well, and until a few years ago they were our number one prescribed medication," he says. "They shouldn't be discounted, because they often do hit target pressures and it's very hard to argue with the cost."

Optometrist Mark Dunbar, who practices at the Bascom Palmer Eye Institute in Miami, concurs.

"Over the last five or 10 years, we've seen an evolution away from beta-blockers to carbonic anhydrase inhibitors or alpha agonist agents. But a beta-blocker is still a great drug," says Dr. Dunbar. "It's generic and it's cheap. For $2 or $3, for somebody with an insurance plan that may not cover some of the newer drugs, a beta-blocker is attractive."

Observers caution against using beta-blockers as a single therapy. "Beta-blockers tend not to work at night," Dr. Sowka says. "A few studies have shown that patients who are using beta-blockers, especially beta-blockers alone once a day in the morning, have the same IOP curves as an untreated patient at night."

In addition, recent research suggests "there may be evidence that the autoregulation of blood flow in a glaucomatous eye is dysregulated," says James Fanelli, O.D., of Wilmington, N.C. The theory, presented in recent research by Louis Pasquale, M.D., at Massachusetts Eye and Ear Infirmary, holds that blood flow to the optic nerve increases during sleep, thus causing disc hemorrhages that cause deterioration.¹

Glaucoma drops and the ocular surface

The adverse effects of benzalkonium chloride (BAK), a preservative contained within many glaucoma treatment drops, are well-documented.

"Benzalkonium chloride — over chronic use — can cause a variety of adverse effects to the ocular surface," Dr. Sowka explains. "It can cause ocular surface disease, and can induce subclinical inflammation. This may be detrimental in any ocular surgery the patient may need later on."

As a result of these adverse effects, some glaucoma treatment drop makers have reformulated their solutions and removed this preservative — something you may want to keep in mind prior to prescribing a specific drug.

"I think we're going to see more medications coming out that are going to be using preservatives other than benzalkonium chloride," says Dr. Sowka. That's because studies have shown that ocular surface disease has a prevalence of "nearly 50% in glaucoma patients," says Dr. Sowka.

Ocular redness is one known potential side effect of prostaglandins, but Dr. Dunbar advises that you balance this against this drug class's high efficacy at reaching target IOP.

"When you look at the degree of hyperemia, or redness, it's in that trace range," he says. "By and large, most people do well [with prostaglandins], and the redness really is not that significant."

The effect of BAK on the ocular surface isn't the only issue glaucoma treatment drop manufacturers are starting to consider with regard to their formulations. Some have begun increasing the pH of their medications.

"The idea is that by increasing the pH, it increases the bioavailability of the drug and works just as well in reducing pressures," explains Dr. Dunbar.

As clinicians gain more experience with prostaglandins, mounting data underscores the efficacy of prostaglandins to control IOP.

Dr. Dunbar cites the landmark Xalatan, Lumigan and Travatan (XLT) study led by his Bascom Palmer colleague Richard Parrish, M.D.² "You expect at least a 30% intraocular pressure reduction with a prostaglandin," Dr. Dunbar says. "That's probably the number one big gun in terms of lowering pressure; you expect a third or sometimes more than that."

Sometimes, however, even the first "big gun" fired can miss its mark. This raises the question: Should you switch to another prostaglandin, or add another medication? These experts concur that this is a matter of physician preference. Dr. Dunbar is inclined to try another prostaglandin. "If you can keep it to immunotherapy, with one bottle you're always better off than putting the patient on a second drop, because compliance goes down," he says. "So the issue is, do you switch within the same drug class?"

Likewise, Dr. Fanelli would switch to a different prostaglandin. "That being said, I'm only going to expect a one-, two- or maybe a three-point difference in switching," he says. However, that is significant. Studies have shown that that little bit of change, even if it's just one or two points, can be very important for certain patients, especially those with advanced disease."

Different prostaglandins target different receptors in the eye, Dr. Sowka explains. "That's why all prostaglandins should be tried before the category is abandoned." He has also seen evidence that simply switching a medication can cause a patient to better comply with dosing. "It's simply human nature."

Combination therapy

The recent development of combination glaucoma-treatment drops has afforded doctors the opportunity to lower IOP and prevent a decrease in vision or blindness when one or more of the prostaglandins prescribed aren't meeting IOP-lowering expectations and the concomitant use of another glaucoma medication threatens compliance to prescribed treatment regimen.

"If you're going to follow [glaucoma] patients long enough, the likelihood is they are probably going to need to be on additional therapy," Dr Dunbar says.

Citing the Ocular Hypertension Treatment Study (OHTS), he notes that 40% of patients over a five-year period typically need adjunctive therapy.³

To determine which combination drop to prescribe to a patient, Dr. Sowka suggests you try one in one eye initially.

"If that doesn't achieve the target IOP, titrate it out, and try another drop. That should give you an idea of the IOP-controlling and risk profile properties of each drop," he says.

Of course, cost can be a factor, especially if the patient is already taking a prostaglandin. "That's really the attraction to combination therapy," Dr. Dunbar says. "If you can get two medications in one bottle, you can cut down costs and patients may be more compliant."

New approaches to laser treatment

Three recent events have occurred in the realm of glaucoma laser treatment: a recent shift in preference from argon laser trabeculoplasty (ALT) to selective laser trabeculoplasty (SLT), the pursuit of medications to reduce bleb scarring and a reverse approach to controlling IOP.

To start, many practitioners have chosen to refer patients in whom drug therapy alone hasn't achieved the target IOP for an SLT rather than an ALT because SLT is a repeatable procedure, and ALT is not, says Dr. Dunbar.

"The lifespan of either laser treatment may only be about four or five years," Dr. Dunbar says. "So, at the end of the day, the patient is still going to need more medication and/or an additional laser procedure to facilitate aqueous drainage."

Dr. Fanelli adds that trabeculectomies fail primarily because of scarring at the bleb site, but that researchers are currently pursuing medications that can reduce scarring to increase these procedures' success rates.

Europe reverses its approach to IOP

Finally, in Europe, eyecare practitioners are embracing a reverse approach to controlling IOP: laser treatment first, followed by glaucoma medications, says Dr. Fanelli. The reason:

"A few studies have shown that patients who had been on long-term medical therapy generally fared more poorly following laser surgery than those who had laser surgery right out of the shoot," he explains.

"The implication was that medication use on a long-term basis somehow affected the structure and function of the drainage mechanism. It may take a few more years of journal articles and clinical trial and error for this approach to catch on in the United States," he states.

Sifting through the changes ahead

When sifting through the recent research on glaucoma therapies, Dr. Fanelli asks, "has it fundamentally changed what we do in clinic?" For now the answer is no. "But I do think that with time and with further research, we may end up making some fundamental changes to how we proceed."

When deciding on glaucoma treatment, and for that matter, any treatment, it's essential you be aware of the most recent developments related to the condition, so you can ready your practice for possible change and formulate the best treatment plan. OM

1. Feke GT, Pasquale LR. Retinal blood flow response to posture change in glaucoma patients compared with healthy subjects. Ophthalmology. 2008 Feb;115(2):246-52.
2. Parrish RK, Palmberg B, Sheu W, XLT Study Group. A comparison of latanoprost, bimatoprost, and travoprost in patients with elevated intraocular pressure: A 12-week, randomized, masked-evaluator multicenter study. Am J Ophthalmol. 2003;135;688-703.
3. Ocular Hypertension Treatment Study Group. The Ocular Hypertension Treatment Study: A randomized trial determines that topical ocular hypotensive medication delays or prevents the onset of primary open-angle glaucoma. Arch Ophthalmol. 2002;120:701-713.