Optometry

There has recently been renewed interest in using topical beta-blockers as the primary agent for the therapy of open-angle glaucoma. The driving force behind this change in the paradigm is economic, with some patients having problems affording their medications. Does this make sense? After 13 years of using prostaglandins and watching them evolve into the most commonly prescribed glaucoma agent, does going backwards provide any benefit besides cost? More importantly, may this be harmful for some patients?

Topical beta-blockers were first introduced in 1976 and soon became the first-line agent. Their strengths include the ability to reduce intraocular pressure efficiently with a reasonable dosing schedule and few topical side effects. Bear in mind that the first beta-blocker (timolol maleate) was replacing pilocarpine, so the dosing and side effect profile were a marked improvement.

Systemic side effects

The concern regarded systemic side effects, which may be significant and include reduced pulmonary capacity and bradycardia. Beta-blockers reduce the IOP approximately 22% to 25%, with the morning dosage the most important. Numerous studies show that beta-blockers have little effect when dosed at night. Tachyphylaxis often develops, which is a problem as the drug loses its ability to lower the IOP in some individuals.

For most formulations, beta-blockers come in two concentrations. While many clinicians gravitate toward the higher concentration, many studies have shown that the lower concentration is often similar in efficacy to the higher concentration, questioning whether some individuals are taking a higher concentration than required.

Beta-blockers are found in several fixed-combination agents such as Cosopt (dorzolamide HCI, timolol maleate ophthalmic solution, Merck) and Combigan (0.2% brimonidine tartrate, 0.5% timolol maleate). Several years ago the patent expired on Timoptic (timolol maleate, Aton Pharma), leading to generic versions of timolol becoming available. Other beta-blockers such as levobunolol are also available generically, affording significant cost savings.

While there was a concern with topical beta-blockers regarding their potential for pulmonary and cardiac complications, the Ocular Hypertension Treatment Study showed that when patients are carefully screened for contraindications to a medication(s), few systemic side effects occur.

Topical beta-blockers vs. oral

Another issue with topical beta-blockers is the common use of oral beta-blockers for different cardiovascular conditions. It was recognized years ago that systemic beta-blockers often reduce IOP, though probably not as much as if used topically. The recognition of reduced IOP with propranolol usage led to the introduction of timolol.

In some individuals, IOP reduction with systemic beta-blockers is significant and may complement other glaucoma agents. When systemic beta-blockers are in use, it is not clear if adding a topical beta-blocker will offer any additional IOP reduction, and additional systemic side effects are a possibility.

Prostaglandins as first choice

Latanoprost was the first of the prostaglandins (PGs) introduced and was quickly embraced as a first-line agent for the therapy of open angle glaucoma. There were several reasons why PGs displaced beta-blockers relatively quickly.

First, PGs reduce the IOP more (30% to 35%) and do a better job of flattening the diurnal curve. They are a true once-per-day medication, with little evidence that tachyphylaxis develops. PGs are complementary to all other classes of glaucoma agents with few reports of systemic side effects.

They do have ocular side effects that include hyperemia, increased eyelash length and iris color change. The side effects with PGs tend to be cosmetic, though they can be bothersome for some individuals. They tend to be well tolerated, though side effects such as iritis or cystoid macular edema associated with intraocular surgery have been reported.

While recent studies have shown the difficulty with many individuals complying with their glaucoma therapy, PGs tend to be the class of glaucoma agents showing the best overall pattern of adherence.

Why would we want to move the clock backwards and use a drug more now than we did 10 years ago? Yes, there are circumstances in which some individuals are unable to afford their glaucoma agents. If a person does not take their medication for whatever reason, it negates all the diagnostic and therapeutic work done.

Some clinicians are supporting the concept of dosing prostaglandins on an every-other-day basis, given the duration of their IOP reduction. I do not recommend this practice. The drug’s endurance will vary among patients, and a more complex dosing regimen may challenge compliance.

Evaluate patients’ ability to pay

We need to carefully question our patients about their ability to pay for their medications. Does the patient have health insurance? If so, what are the drug benefits? We need to understand what medications are included in the plan. Is the problem that the medication is too expensive based upon its formulary’s tier status?

When individuals have difficulty obtaining their medications due to cost, we need to consider alternatives such as a lower cost medication. In these situations, topical beta-blockers make sense to prescribe because they are available generically.

Other agents that are also available as generics include alpha agonists (brimonidine), miotics (pilocarpine), topical carbonic anhydrase inhibitors (dorzolamide) and fixed combination agents (timolol-dorzolamide). Still, in situations when patients can afford their drugs, PGs make the most sense.

Consider laser trabeculoplasty

Another alternative may be the use of laser trabeculoplasty (argon or selective) as primary therapy when cost is an issue. In certain circumstances when individuals are not compliant, this may offer consistent IOP reduction.

The advantages of laser trabeculoplasty are the reduction of IOP without the involvement of the patient. There are few side effects, and the cost of laser trabeculoplasty is probably equal to less than a year’s worth of a PG.

The disadvantages are that the efficacy is usually less than that of a PG, and it often loses its ability to reduce the IOP over time. At 5 years, 50% of patients who underwent laser trabeculoplasty are back to their original IOP.

It is not clear if repeating the procedure will further reduce the IOP. Argon laser trabeculoplasty is not repeatable; selective laser trabeculoplasty professes to be.

There are situations in which economic concerns are real and the clinician needs to do everything he or she can to ensure that the patient receives the needed therapy. Alternatives to the use of PGs include using generic agents such as timolol and enrolling the patient in a pharmaceutical company’s program to receive free medications.

Beta-blocker proponents

Proponents to moving back to topical beta-blockers as the first-line agent for everyone cite the lack of evidence in glaucoma patients being better controlled with the use of a PG. This is an interesting point, but because there is a lack of evidence does not mean that we should use inferior products until a study is done to prove or disprove this point.

The study has not been done because of its difficulty. Hundreds of patients need to be enrolled and followed over years, and it would best be done longitudinally (not cross-sectionally). This would be an expensive study and there is no obvious stake holder interested in pursuing it. Another reason why the study has not been done is that most clinicians recognize the superiority of the PGs in all aspects, when compared to topical beta-blockers.

Glaucoma is a long-term condition requiring effective IOP reduction over a patient’s lifetime, especially because changes in visual function often take years to manifest themselves. PGs offer our patients the best chance to reduce visual morbidity, and the idea that we should roll back the clock does not make sense for most of our patients. For the few who are in an economic predicament, we need to individualize care and ensure they also achieve effective IOP control.

For more information:

• Murray Fingeret, OD, is chief of the optometry section at the Department of Veterans’ Affairs Medical Center in Brooklyn and Saint Albans, N.Y., a professor at SUNY College of Optometry and a member of the PCON Editorial Board. He may be contacted at St. Albans VA Hospital, Linden Blvd. & 179th St., St. Albans, NY 11425; (718) 298-8498; e-mail: murrayf@optonline.net. Dr. Fingeret is a paid consultant for Allergan and a member of the advisory board of Alcon and Pfizer.

References:

• Friedman DS, Hahn SR, Gelb L et al. Doctor-patient communication, health-related beliefs and adherence in glaucoma results from the Glaucoma Adherence and Persistency Study. Ophthalmology. 2008;115(8):1320-1327.
• Girkin CA. Selective vs. argon laser trabeculoplasty: controversy in evolution. Am J Ophthalmol. 2007;144(1):120-121.
• Liu JH, Kripke DF, Weinreb RN. Comparison of the nocturnal effects of once-daily timolol and latanoprost on intraocular pressure. Am J Ophthalmol. 2004;138:389-395.
• Realini T. Selective laser trabeculoplasty: a review. J Glaucoma. 2008;17(6):497-502.