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
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
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
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.
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:
firstname.lastname@example.org. Dr. Fingeret
is a paid consultant for Allergan and a member of the advisory board of Alcon
- 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.
- 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
- Realini T. Selective laser trabeculoplasty: a review. J