Considerations of the Latest Research for Better Glaucoma Management
With new trial results in hand, doctors will
better understand how the different glaucoma agents fit into the therapeutic
Murray Fingeret, O.D.
years, clinicians have considered prostaglandin analogues as the primary therapy
for open-angle glaucoma (OAG). These agents are easy to use, have few side effects
and are safe and effective.
New research continues to support the efficacy
of prostaglandins for lowering IOP associated with OAG and ocular hypertension (OHT)
and provides us with additional information to help us manage the disease. What's
more, we now have additional data on the best adjunctive therapies to use with them.
In this article, I'll discuss the latest
findings and put them into context for clinicians.
In a recent study by Sit, Weinreb and colleagues,1
travoprost 0.004% (TRAVATAN® solution) was shown to have lasting
effects on diurnal and nocturnal IOP even after it was discontinued for several
When patients stopped using travoprost
for approximately 2 days, their IOPs remained low, although not as low as when
they were taking the medication regularly.
Surprisingly, the reduction was greatest
during the nocturnal period, a time of day when IOP is normally higher. Although
we don't want to condone noncompliance, these results are reassuring because we
can prescribe travoprost knowing that if our patients occasionally miss a dose,
their IOPs won't increase dramatically.
Approximately 40% of patients who use prostaglandins
for glaucoma therapy need a second medication to lower IOPs further.2,3
They either don't reach their target IOPs, or they show disease progression in the
optic nerve or visual fields.
Adjunctive therapies can include topical
beta-blockers, alpha2 agonists and topical carbonic anhydrase inhibitors (CAIs).
In the past, conventional wisdom said
topical beta-blockers were the most potent agents when added to a prostaglandin.
Yet, surprisingly, a study by O'Connor and Martone4 found that dorzolamide
was more effective in lowering IOP (additional 19.7%) than timolol (12.3%) or brimonidine
(9.3%) when added to latanoprost (XALATAN*). These results ran counter to popular
opinion, although they were of no surprise to glaucoma specialists.
When the results of the Ocular Hypertension
Treatment Study (OHTS) were reviewed, topical CAIs were the third most commonly
used agent, ahead of alpha2 agonists.5
To examine the issue further, Tsukamoto
and colleagues6 compared the additional IOP-lowering effects of topical
brinzolamide and dorzolamide when given to patients using latanoprost and a beta-blocker.
The study found the two CAIs identical in terms of efficacy, although ocular irritation
was less common with brinzolamide.
A study by Silver and the Brinzolamide
Primary Therapy Study Group7 showed that brinzolamide and dorzolamide
were equally efficacious when used as primary agents, although ocular irritation,
again, was less common with brinzolamide.
In other research, Reis and colleagues8
looked at the hypotensive efficacy of timolol 0.5%, brinzolamide 1% and brimonidine
0.2% ophthalmic solution when given to patients using travoprost. Timolol and brinzolamide
were most effective in lowering IOP when added to travoprost while brimonidine showed
a more recent, prospective, double-masked study that compared the efficacy of brinzolamide
1% and brimonidine 0.15%, Feldman and colleagues found that brinzolamide proved
to be the most effective in lowering IOP when added to travoprost.9
This evidence reinforces the
earlier findings that CAIs, such as brinzolamide, are more effective secondary agents
that should encourage clinicians to combine them with travoprost in patients who
don't meet their target IOPs or show progression.
Efficacy minus BAK
Preservative use in glaucoma drugs is becoming
an important issue because the disease is chronic, requiring patients to take the
medications for long periods of time. And many of them have some form of ocular
Research shows BAK and other types
of preservatives can cause a myriad of ocular problems from irritation and hyperemia
to allergy, inflammation and toxic reactions.11,12
BAK can destabilize the tear film and
may cause filtration surgery failure, cystoid macular edema and even cataract development.12
Some of these side effects may lead to poor compliance. Patients may either reduce
the use of their medications or stop taking them altogether.
Until recently, clinicians have had
little choice but to manage the side effects since all prostaglandins contain BAK
in different concentrations.
The question for doctors whose patients
experience nonspecific side effects has become, "Do we continue to prescribe prosta-
which happen to be the most effective class of drugs for reducing IOP, or do we
switch to a less effective agent that does not contain BAK?"
With all this in mind, Lewis and colleagues10
conducted a double-masked, randomized clinical trial that compared the safety and
efficacy of a newly formulated travoprost 0.004% made without BAK to the currently
marketed travoprost made with the preservative in patients with OAG or OHT.
Study results, presented at the 2006
meeting of The Association for Research in Vision and Ophthalmology, showed that
travoprost BAK-free lowered IOPs as effectively as the original travoprost and was
considered a safe alternative.
The incidence of ocular hyperemia associated
with the BAK-free travoprost was 6.4%.
The significance of the Lewis study
is that it gives clinicians new insight into drugs being developed without BAK that
do not compromise safety and efficacy.
As new formulations made without BAK
become available in the future, doctors will have better therapeutic options to
offer glaucoma patients.
Given all the recent data, clinicians now have
the information they need to prescribe a regimen for each individual patient, including
those who develop side effects, who need adjunctive therapy and may be noncompliant.
*Trademark is the property of its owner.
1. Sit AJ, Weinreb RN, Crowston JG, et al. Sustained
effect of travoprost on diurnal and nocturnal intraocular pressure. Am J Ophthalmol.
2. Kass MA, Heuer DK. The Ocular Hypertension
Treatment Study. Arch Ophthalmol. 2002;120:701-713.
3. Wolters Kluwer Health, Concomitancy
Analysis, May 2006.
4. O'Connor DJ, Martone JF, Mead A.
Additive intraocular pressure-lowering effect of various medications with latanoprost.
Am J Ophthalmol. 2002;133:836-837.
5. Kass MA, Heuer DK, Higginbotham
EJ, et al. 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.
6. Tsukamoto H, Noma H, Matsuyama
S, et al. The efficacy and safety of topical brinzolamide and dorzolamide when added
to the combination therapy of latanoprost and a beta-blocker in patients with glaucoma.
J Ocul Pharmacol Ther. 2005;21:170-173.
7. Silver LH, and the Brinzolamide
Primary Therapy Study Group. Clinical efficacy and safety of brinzolamide (Azopt),
a new topical carbonic anhydrase inhibitor for primary open-angle glaucoma and ocular
hypertension. Am J Ophthalmol. 1998;126:400-408.
8. Reis R, Queiroz CF, Santos LC,
et al. A randomized, investigator-masked, 4-week study comparing timolol maleate
0.5%, brinzolamide 1%, and brimonidine tartrate 0.2% as adjunctive therapies to
travoprost 0.004% in adults with primary open-angle glaucoma or ocular hypertension.
Clin Ther. 2006;28:552-559.
9. Feldman RM, Prager TC, Baker L,
Chuang AZ, Additivity Study Group. Additivity of Brinzolamide vs. Brimonidine 0.15%
to Travoprost 0.004%. Presented at The Association for Research in Vision and Ophthalmology;
April 30-May 4, 2006; Fort Lauderdale, FL.
10. Lewis RA, Weiss MJ, Landry TA,
et al. Travoprost 0.004% With and Without Benzalkonium Chloride: A Comparison of
Safety and Efficacy. Presented at The Association for Research in Vision and Ophthalmology;
April 30-May 4, 2006; Fort Lauderdale, FL.
11. Noecker RJ, Herrygers LA, Anwaruddin
R. Corneal and conjunctival changes caused by commonly used glaucoma medications.
12. Miyake K, Ota I, Ibaraki N, et
al. Enhanced disruption of the blood-aqueous barrier and the incidence of angiographic
cystoid macular edema by topical timolol and its preservative in early postoperative
pseudophakia. Arch Ophthalmol. 2001;119:387-394.
Optometric Management, Issue: August 2006