Standard medication regimens hard to define for treatment of glaucoma

There are well-established guidelines in place for treating glaucoma, but the medical regimen has to be individualized for each patient.

“There are so many different situations and so many different variables that it really is not possible to have a cookbook approach to glaucoma care management,” Louis B. Cantor, MD, OSN Glaucoma Section Board Member, said.

The starting point for the “average” patient is fairly well agreed upon. Use a prostaglandin analogue for primary open-angle glaucoma at an early disease stage with no field loss or optic nerve head damage and IOP in the mid-20 mm Hg range. Use a monocular trial to assess efficacy and side effects. Wait a month to assess complications and then continue with both eyes.

Because the drug class is effective at controlling glaucoma in most patients, Dr. Cantor said that about half the patients in his practice can be controlled this way.

But from there, it can get more complicated. The “average” patient does not really exist, and Dr. Cantor said that by the time a patient presents with glaucoma, half the optic nerve may already be damaged.

Louis B. Cantor, MD, believes that glaucoma patients are not one-size-fits-all, and it is advantageous to have surgical options in addition to medications. Image: Indiana University School of Medicine Visual Media

“Tailoring a glaucoma regimen is about how we meet the patient and where we meet the patient on their continuum of disease,” Jason Bacharach, MD, said. Take, for example, a patient of his who is a television reporter with pigmentary glaucoma and blue-green irides. She was adamantly against the 5% to 10% chance that a prostaglandin might change her eye color, so he had to tailor a regimen for her.

Although there was a standard regimen 20 years ago — medicine, laser, surgery — the new tools that are available have morphed glaucoma management.

“The trend in glaucoma management is getting away from standard decision making and really tailoring the program toward a particular individual based on their needs,” said Dr. Bacharach, who is in practice in Petaluma, Calif.

Second-line therapies and more

Joshua D. Stein, MD, MS, of the Kellogg Eye Center in Michigan, said that prostaglandin analogues surpassed beta-blockers in 2002 as the most commonly prescribed medication for a number of reasons: They have fewer systemic side effects, they are well-tolerated, and they have once-daily administration.

Dr. Cantor said he considers a 30% drop in IOP as acceptable efficacy from a prostaglandin. If patients are 2 mm Hg to 5 mm Hg short of their target IOP with a prostaglandin, they can switch to another medication within the prostaglandin class to maintain monotherapy.

“We can really optimize or maximize the opportunity for controlling a patient on one drug,” he said. “When you go to adjunctive therapy, things get a bit more complicated.”

The second-line choice is not as clear cut as the first-line one. Second-line medications can include carbonic anhydrase inhibitors, alpha-2 agonists and beta-blockers. Some ophthalmologists switch directly to a fixed-combination treatment.

But some patients are contraindicated for certain medications. Prostaglandins can induce hyperemia, brimonidine can trigger an allergic reaction, and beta-blockers can exacerbate asthma or heart disease, Dr. Cantor said.

Ophthalmologists weigh each consideration against the others when deciding upon a second-line therapy.

The likelihood of lowering IOP by an extra 2 mm Hg to 4 mm Hg with just a single agent is feasible, but if more than this is required to reach the IOP target, Dr. Cantor said he turns more often to a fixed combination for that second bottle.

“We need to get to the goal quicker, and we need to give our patients a little more positive reinforcement by getting their pressure under control and not fiddling around so much,” Dr. Cantor said. “It drags out the process, and patients get kind of frustrated.”

Steven D. Vold, MD, in practice in Arkansas, said published studies suggest carbonic anhydrase inhibitors lower IOP more than the other two drug classes when added to a prostaglandin.

Meanwhile, Douglas J. Rhee, MD, OSN Glaucoma Board Member, turns to beta-blockers as his second-line choice.

Douglas J. Rhee

“I find beta-blockers are quite effective,” Dr. Rhee said. “It has the advantage of a single daily dose — once-a-day prostaglandin at night and once-a-day beta-blocker in the morning.”

Dr. Rhee turns to a fixed-combination agent as his third choice and said he will even try a fourth medication. He said that he is more conservative than other ophthalmologists in exhausting medical therapies first.

“Obviously, there are caveats with this,” he said. “If the patient’s pressure is at 40 mm Hg and they are taking three medications, I’ll add the fourth just to temporize. I know it’s not going to work, and then I’ll skip the laser and go right to surgery.”

However, Dr. Bacharach said he does not find much use in adding third and fourth medications.

“I find it’s a law of diminishing returns when I go to the third bottle. Patients find putting five drops in their eye a day onerous. The return on investment is weakened tremendously by the time you get to the third bottle,” he said.

Varying conditions

Ophthalmologists recognize the value in the stepwise approach to glaucoma medications. But because of the complexity of the disease, a variety of factors can force physicians to move faster than usual in trying to lower IOP.

Generating a target IOP is a complex algorithm for which the American Academy of Ophthalmology has preferred practice guidelines. For ocular hypertensive patients, physicians should try to reduce IOP by 20%, early, mild or moderate disease by 30%, and more severe disease by 40%.

“You have to evaluate by percentages and absolute values,” Dr. Rhee said. “If the pressure starts at 40 mm Hg, then 30% gets you to 28 mm Hg. That’s not going to be good enough.”

Jason Bacharach

Diurnal pressures should also be considered, Dr. Bacharach said. IOP fluctuates throughout the day, sometimes from 30 mm Hg in the morning to 18 mm Hg in the afternoon, so an IOP assessment in the office might not reflect what is actually happening in the eye.

“If the glaucoma isn’t so severe that I feel that I need to implement therapy at their first visit, I like to get a diurnal curve of their IOP, at least a reading in the morning and late afternoon, before I initiate therapy so I know what the fluctuation is,” Dr. Bacharach said.

It is important to stay flexible with target pressures.

“Even with all of the excellent data that we have accumulated over the years from NEI- and NIH-sponsored studies, you cannot extrapolate all of that data to a particular patient and assume that your initial target pressure will stay the same for that patient’s life. You have to use your best judgment to set an initial target pressure with the understanding that once you reach that range, you may need to adjust that target pressure again if that disease state continues to progress,” Dr. Bacharach said.

“If I see true visual field loss progression, I immediately alter therapy. I’ve demonstrated to myself that that patient’s disease process is not under good control,” he said.

Cost and compliance

The next steps in the medication process depend on a lot of factors, such as the overall health, age and well-being of the patient, side effects, affordability and the ability to correctly administer drops.

“I like to have a conversation with the patient about their ability to comply or adhere to a medical regimen, what kind of support system they have at home, their financial situation, if they are going to be able to afford the drop that I write,” Dr. Bacharach said.

Some of the medications can be quite costly, Dr. Stein said, especially when patients need them for decades. Laser procedures are a one-time cost, compared with $50 to $100 every month for years.

Prostaglandin analogues can cost more than other regimens, which is important to the Medicare patients in Dr. Vold’s practice. In northern Arkansas, four pharmacy chains dominate the market, so he checks prices quarterly and writes them down for patients.

“That makes a huge difference in compliance, and you cannot imagine how much they appreciate that. That does play a factor in the choice of medical therapy,” he said.

One retail pharmacy’s generic drugs program offers $4 co-pays for a generic beta-blocker, he said. “For $4, patients spend pennies on the dollar when compared to prostaglandin over the course of 1 year,” he said.

Complexity of the regimen is also a deterrent to good compliance.

Steven D. Vold

“Keeping the regimen as simple as possible can be really important to patients as well. Compliance studies show very distinctly that the fewer drops we prescribe, the more likely they are going to follow our recommendations,” Dr. Vold said.

The Glaucoma Adherence and Persistency Study demonstrated that up to 50% of new patients prescribed glaucoma medications become noncompliant between 6 months and 1 year. Patients stopped therapy more than clinicians thought, and physicians were not able to predict which patients stopped therapy.

“We think we know our patients, but in many cases, we’re wrong,” Dr. Vold said.

Dr. Stein said that communication is the key for helping improve adherence.

“Oftentimes, the patients become lost to follow-up because they don’t appreciate that this chronic, relatively asymptomatic disease can actually be causing problems,” he said. “Taking some time to explain about the disease and about how it can impact them down the line can go a long way toward helping with adherence, with whichever regimen one chooses to pursue.”

When medication is not enough

Dr. Cantor said that if his patients are taking a combination of numerous medications, it may be time to have a discussion about the next step in glaucoma management. Efficacy may be diminishing, and so might compliance.

An increasing number of patients choose selective laser trabeculoplasty at this point, he said.

“It really depends on how many issues they’re having with the medications,” he said. “Cost issues enter into the equation. Ability to use the medication enters into the equation, and patients will choose. I try not to direct that choice very much. But I do get a sense in my own mind maybe they’d be better off not adding a third bottle to the mix. So I do lead the conversation a bit.”

For those patients who do not respond to SLT, Dr. Cantor suggests filtering surgery.

“Glaucoma patients aren’t one-size-fits-all. And it’s very advantageous to have surgical options in addition to medications,” he said.

“In general, we as ophthalmologists tend to over-treat patients with mild disease, but we’re not as aggressive as we need to be in patients who have advanced disease,” Dr. Stein said. “If a patient presents to me with extensive visual field loss, I’m going to certainly be monitoring them very closely and trying different regimens. Depending how high the intraocular pressure is and how far it is away from the target, I’ll try within a few weeks different regimens of medications and/or laser to get them to target. And if they’re not at target, they may require incisional surgery.”

Dr. Bacharach said an advantage to laser and surgical procedures is the 50% possibility of reducing the number of medications. Monotherapy patients may be able to stop using medication, and polypharmacy patients may reduce the number of medications in some cases.

“The way I describe it to my patient is, if we can get them off of medicine, that’s not the primary reason that we’re doing surgery,” Dr. Bacharach said. “That’s to get them to their target pressure to slow or stop their disease process.”

Be aggressive with treatment

Dr. Cantor said it is important to be aggressive early in the course of the disease.

“By the time a visual field defect shows up, when a patient walks in with a tiny nasal step and the doc sees that, that is not early glaucoma,” Dr. Cantor said. “Probably half or more of the optic nerve is gone. So we stage disease wrong.”

He considers early glaucoma as optic nerve damage without visual field loss.

“In order to treat early, we have to really be looking at the nerve and detecting early nerve damage before it begins to affect the field. By the time we have a visual field defect, there’s a lot of water over the dam. You’re at least at moderate if not moderately advanced disease at that point. We tend to treat by what stage we think we’re at. So if we mistake an early defect for early glaucoma, we treat like it’s early glaucoma and under-treat, and the patients get worse,” Dr. Cantor said.

Compounding the problem is that visual field tests are insensitive to early damage in glaucoma, and it can take years to assess true progression.

“We’ve got to look at everything, and that’s part of the problem,” Dr. Cantor said. “We’ve got to look at the pressure, look at the visual field, look at the optic nerve head structure and have to correlate it all. We have to ask the patient how they think they are doing because they are often aware of things that our technology may not show.”

“Management is a humbling experience, and it’s a rigorous, long grind,” Dr. Bacharach said. “But in hindsight, it’s very fruitful when you see stability because you came up with a good formula, a good cocktail, for people that you’ve tended to bond with over many years.” – by Ryan DuBosar

How many medications should be tried to lower IOP before moving on to SLT or glaucoma filtering surgery?

References:

• Francis BA, Ianchulev T, Schofield JK, Minckler DS. Selective laser trabeculoplasty as a replacement for medical therapy in open-angle glaucoma. Am J Ophthalmol. 2005;140(3):524-525.
• Friedman DS, Quigley HA, Gelb L, et al. Using pharmacy claims data to study adherence to glaucoma medications: methodology and findings of the Glaucoma Adherence and Persistency Study (GAPS). Invest Ophthalmol Vis Sci. 2007;48(11):5052-5057.
• Lichter PR, Musch DC, Gillespie BW, et al; CIGTS Study Group. Interim clinical outcomes in the Collaborative Initial Glaucoma Treatment Study comparing initial treatment randomized to medications or surgery. Ophthalmology. 2001;108(11):1943-1953.
• Practice guidelines. American Academy of Ophthalmology website. http://one.aao.org/CE/PracticeGuidelines/default.aspx.
• Stein JD, Ayyagari P, Sloan FA, Lee PP. Rates of glaucoma medication utilization among persons with primary open-angle glaucoma, 1992 to 2002. Ophthalmology. 2008;115(8):1315-1319.

• Jason Bacharach, MD, can be reached at North Bay Eye Associates, 104 Lynch Creek Way, Petaluma, CA 94954; 707-762-3573; e-mail: jbacharach@northbayeye.com. Dr. Bacharach is an investigator and receives consultant fees for Allergan, Glaukos and Ista. He is an investigator for Aerie, Alcon and Santen. He is on the speakers bureau for Pfizer, Allergan, Ista and Lumenis.
• Louis B. Cantor, MD, can be reached at Indiana University Department of Ophthalmology, 702 Rotary Circle, Indianapolis, IN 46202-5175; 317-274-8485; fax: 317-278-1007; e-mail: lcantor@iupui.edu. Dr. Cantor is a consultant for and receives research grants and honoraria from Allergan. He has received honoraria from Merck and research support from Alcon and Pfizer.
• Douglas J. Rhee, MD, can be reached at Massachusetts Eye and Ear Infirmary, 243 Charles St., Boston, MA 02144; 617-573-3670; fax: 617-573-3707; e-mail: dougrhee@aol.com. Dr. Rhee is an ad hoc consultant for Alcon, Allergan and Santen.
• Joshua D. Stein, MD, MS, can be reached at University of Michigan Kellogg Eye Center, 1000 Wall St., Ann Arbor, MI 48105; 734-763-7246; e-mail: jdstein@umich.edu. Dr. Stein receives research support from Pfizer.
• Steven D. Vold, MD, can be reached at Boozman-Hof Regional Eye Clinic, 3737 West Walnut, Rogers, AR 72756; 479-246-1700; e-mail: svold@cox.net. Dr. Vold serves as a consultant and receives research support from Alcon, Allergan, NeoMedix, iScience Interventional, Glaukos, Transcend Medical, AqueSys and TrueVision Systems.