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Glaucoma Medications
What's new for 2002? For the first time in a long time, the answer is:
"Not much"...and thankfully so.
There are some slight refinements, but there have been no substantial
changes or additions to glaucoma medications in the past year. However, two
concerns endure: one-half of all patients with glaucoma remain undiagnosed;
and those that are diagnosed generally receive poor care, mostly through over-
medication along with its attendant expense (both of which hinder compliance).
Patients with glaucoma represent some of the most poorly cared for people in
Review of Ophthalmology the U.S., and probably worldwide. If there is one area where optometry can
make a major contribution to public health, it's in the care of patients with
glaucoma.
We have "inherited" hundreds of patients with glaucoma over the years, and it
has been the rare patient who was not being over-medicated. This leads to
Vision Web
increased side effects, poor compliance and excessive costs. This chapter will
address these three areas and others that, when understood and embraced in
practice, can dramatically elevate the level of care for patients with glaucoma.
Nearly all states have improved practice acts to allow for the care of glaucoma
patients. Now the challenge before us is to collectively set new standards of
excellence in glaucoma care for our patients. We hope the knowledge shared
in this chapter will be a significant step in the pursuit of this goal.
And, as if mastering the drugs themselves were not challenge enough, there is
the hype of neuroprotection and ocular blood flow, and all the new whiz-bang,
high-tech glaucoma image analyzers. We think we can help simplify your life a
bit. Put neuroprotection and blood flow out of your mind. It may well be several
years before anything clinically meaningful will be available in this area. Just
focus on reducing IOP sufficiently and efficiently while trying to minimize
expense.
The non-selective beta-blockers are all similar in efficacy, causing about a 25%
reduction in IOP. We now know that the most commonly prescribed beta-
blockers--timolol and levobunolol, because of their half-lives--are just as
effective taken as one drop of 0.25% solution once daily in the morning as
0.5% solutions taken bid. (An exception is a patient of African descent, who
Simple math shows the bid 0.5% regimen, which most glaucoma patients take,
amounts to considerable overdosage, not to mention twice the expense and
dosage complexity compared to qd therapy.
Also bear in mind that these drugs are not without potential side
effects. Because beta receptor blockage of the pulmonary
tissues can result in bronchospasm, use of beta-blockers is
contraindicated in asthmatic patients. It is also wise to avoid
these with patients having significant heart disease. At least
consult with such a patient's physician prior to prescribing a beta-
blocker. Also, keep in mind that if the patient is taking a beta-
blocker systemically, the efficiency of topical beta-blocker
therapy can be significantly muted.
The Timolols
Levobunolol
Carteolol
It also does not aggravate cholesterol or lipid profiles as much as the bid use
of first-generation, non-selective beta-blockers. Therefore, it may be more
appropriate for patients at risk for coronary or atherosclerotic disease and
those with dyslipidemia.
However, it is our belief that when traditional beta-blockers are used only qd,
this advantage would be muted or eliminated. One way to mark these patients
is a historical review of antihyperlipidemic drugs such as Questran, niacin,
Zocor, Pravachol, Lopid, Mevacor, Lescol, Lipitor or other such therapeutic
agents.
Ocupress also tends to sting less than most of the other beta-blockers, which
may help with compliance. This is especially true for patients with dry eyes.
Carteolol is used q12h.
Betaxolol
Levobetaxolol
Metipranolol
Prostaglandin Analogs
Latanoprost
Studies have shown that latanoprost 0.005%, at one drop per day, reduces
IOP more than timolol 0.5% bid, with a much better safety profile. About 90%
of patients respond to latanoprost therapy, a rate similar to that of all other
topical glaucoma medications.
The average price to the patient is about $50 to $60 per bottle. That translates
to about $450-$500 per year for bilateral therapy. Latanoprost is additive to all
other glaucoma drugs with the exception of pilocarpine. The cholinergic
agonist pilocarpine enhances trabecular outflow by contracting the longitudinal
muscle of the ciliary body. This contraction also tightens the intercellular
junctions on the face of the ciliary body, thus potentially reducing uveoscleral
outflow and dampening the effectiveness of latanoprost.
All medicines seem to have an Achilles' heel, and the prostaglandin class is no
exception. Years of clinical experience have shown that while prostaglandins
can cause iris darkening, especially in mixed-colored irides, it is considerably
less than originally predicted. These changes are largely cosmetic and carry
no known pathological implications. The pigmentary changes represent
enhanced production of melanin pigment within the stromal melanocytes and
not an increase in the number of melanocytes. There is no "leakage" of
pigment from the iris into other ocular tissues.
Now that latanoprost has been used extensively, its side effect profile, while
minimal, is beginning to show itself. Approximately 5% of patients in one study
developed uveitis, and approximately 2% of patients developed CME. The
latanoprost-associated iritis was generally low grade and did not develop until
after two months of therapy. Iritis or CME, on the rare occasions when it
occurs, almost always does so in patients with a history of these conditions,
and hardly ever in patients without prior disease.
A recent article has reported a few cases of herpes simplex keratitis thought to
be causally related to topical latanoprost. It therefore seems prudent to try
other therapies for this small subset of patients until this association is more
It generally takes about two weeks for the prostaglandins to achieve maximum,
or near-maximum, therapeutic effect. For this reason, start the patient on a
monocular therapeutic trial and reevaluate the patient in two to three weeks.
Once a therapeutic benefit has been established, continue with bilateral
therapy, if indicated.
Travoprost
One interesting outcome from the phase III studies was a disproportionate
decrease of IOP in the patients of African descent. On average, this subset of
patients had an IOP 1.8 mm lower than the white subset. Whether this finding
is spurious or real will only be known after a year or so of widespread clinical
use. At this time, we think the drug will prove to be equally effective across
race and ethnic groups. It is interesting that in the May 15, 2001
Ophthalmology Times, Wiley Chambers, M.D., Chief of
Ophthalmology for the FDA, says, "If you cross-compare
Xalatan, Travatan, and Lumigan, they all have a similar profile.
They're comparable." Dr. Chambers said travoprost's claim
regarding its effectiveness in black patients probably could be
applied to bimatoprost and latanoprost. He said all three
effectively reduce pressure and have similar side effects,
including sometimes turning blue or green eyes brown.
Bimatoprost
Lumigan is the third member of this elite drug class. Because of its somewhat
unique chemical structure, it has to be more concentrated, i.e., 0.03% (versus
0.005% latanoprost and 0.004% travoprost).
A careful read of the package inserts of Lumigan, Travatan and Xalatan shows
virtually identical language regarding their side effect profiles. Widespread
clinical use of these three drugs will allow subtle differences among these
drugs to be appreciated.
Since the three prostaglandin drugs are roughly clinically equivalent, the main
deciding factor may be as simple as price.
Lumigan is the only prostaglandin to come in an opaque bottle. This has the
advantage of preventing patients from complaining about the bottle being only
half-full, as some do who use the clear-bottled prostaglandins.
The disadvantage is that patients cannot judge when the bottle is nearly
empty, and may cause some patients who fail to plan ahead to occasionally
miss dosing.
Docosanoid Compounds
Unoprostone
Brimonidine
There is some debate on whether tid or bid dosing is better. While tid
administration will give maximum IOP reduction, most studies have found that
bid administration will adequately reduce IOP in most patients. Since
compliance decreases as the complexity of the dosing increases, we generally
prescribe brimonidine bid.
We tell the patient to instill the first drop within the first hour upon awakening,
and the second drop by mid- to late afternoon. This hopefully achieves
maximum IOP lowering when it's at its highest, during waking hours. We
occasionally recommend three minutes of gentle eyelid closure to maximize
ocular absorption and effectiveness, and minimize systemic absorption. (We
employ this technique in patients on multiple po medications and/or those who
have poorer health when prescribing adrenergic acting medications, i.e., the
beta-blockers and the alpha adrenergic receptor agonists.)
CAIs work by reducing the carbonic anhydrase activity in the ciliary processes.
In the ciliary epithelium, the production of aqueous humor is a function of the
production of bicarbonate. By reducing bicarbonate production, aqueous
formation is reduced, thus decreasing IOP. These drugs can be valuable in
certain patients. However, with the advent of the more clinically efficacious
drugs latanoprost and brimonidine, this class of drugs has a relatively limited
role in reducing IOP.
Since these drugs inhibit bicarbonate function, there is some concern that
corneal endothelial function may be partially compromised. Likewise, mucin
production by corneal epithelial cells is somewhat dependent on bicarbonate
function. These concerns are gaining more ground in the literature, and until
research further elucidates the impact of CAIs on endothelial and epithelial
function, it would be wise to use these drugs with caution in patients with
clinically significant guttata, endothelial compromise, those with significant
ocular surface disease, and especially in eyes that have sustained surgery.5
Dorzolamide
Dorzolamide is FDA-approved for tid use, but clinical studies have shown that
bid administration is nearly as effective as tid dosing, particularly when used in
additive therapy. For the rare occasions when a CAI would be used as
monotherapy, tid administration may be needed to achieve maximum IOP
reduction.
In most cases, topical therapy with this CAI can replace systemic
CAI therapy with good preservation of IOP control. If you
undertake a systemic-to-topical switch (which is a wise
therapeutic trial), be sure to monitor IOP to ensure no
unacceptable loss of IOP control has occurred. An excellent
study in the January 1997 Archives of Ophthalmology
demonstrated that systemic acetazolamide reduced aqueous flow by 30%
whereas topical dorzolamide reduced flow only 17%. They conclude:
"Clinicians who prescribe dorzolamide should expect less of an ocular
hypotensive effect than that experienced from systemically administered
acetazolamide."6
The judicious use of systemic therapy may well enable the achievement of
target IOP with minimal side effects, and remains a viable therapeutic
approach in select patients. About 75% of patients taking an oral CAI can
switch to dorzolamide with no loss of IOP control.
Brinzolamide
Clinical data does show that it tends to produce less stinging and burning than
dorzolamide does. Although it is a suspension, minimal shaking is required
because of Alcon's unique proprietary carbopol suspension system, which is
also the suspension vehicle in Betoptic-S and Vexol. While both brinzolamide
and dorzolamide are very much interchangeable, we generally use
brinzolamide for the above stated reasons. Because topical CAIs can cause
corneal decompensation in diseased post-operative corneas, avoid topical
CAIs in this tiny subset of patients.
Dorzolamide/Timolol Maleate
This is the first combination drug for glaucoma (dorzolamide 2% with timolol
maleate 0.5% ophthalmic solution) since pilocarpine/epinephrine, and far more
advanced. Cosopt (Merck) is intended to be used when beta-blocker therapy
alone does not achieve the target IOP. It may reduce IOP about 30% in most
patients responsive to each of its component drugs. Cosopt is to be used bid.
We are disappointed that Cosopt is only available with 0.5% timolol maleate.
This will force the prescriber to needlessly overexpose the patient to the
potential adverse effects of beta-blockade. Combining dorzolamide with 0.25%
timolol maleate would have honored the knowledge extensively published in
the ophthalmic literature. For this reason, our use of Cosopt will be reserved
for unique cases where the risk/benefit to our patient is met.
response to a beta-blocker, and where the 0.25% nearly achieved target IOP.
The addition of newer drugs in the anti-glaucoma cauldron does indeed make
therapeutic decision-making more complex. Where will Cosopt fit into the
algorithm of glaucoma therapy? Our opinion is that it could be used after a
therapeutic trial of a beta-blocker where...
Once these two criteria have been met, only then is it prudent to do a trial with
Cosopt to determine if it can indeed achieve target IOP.
Alternatively, what if the beta blocker qd combined with one of the "big
three"(total daily instillation frequency of bid) does not achieve target IOP?
Rather than add brimonidine to the beta-blocker (which would now result in tid
therapy), consider a trial of Cosopt bid, based on the principle that the simpler
the therapy, the better the patient compliance.
There are now several ways to mix and mingle the glaucoma drugs, so try to
use the least amount of drug to met the IOP target goal while minimizing the
impact on the patients overall quality of life.
— References —
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