BAK-free travoprost may be a useful addition to the IOP-lowering armamentarium.
By Francisco E. Fantes, M.D., Richard A. Lewis, M.D., and Jess Thomas Whitson, M.D., F.A.C.S.
Patients with glaucoma often have ocular surface disorders resulting
from blepharitis, lid problems such as deformities or blinking issues
and aqueous deficiency. Chronic use of topical medications preserved
with benzalkonium chloride (BAK) can exacerbate these problems.
More than two-thirds of glaucoma medications contain BAK, a preservative
that, although effective, can damage healthy cells on the ocular surface
with chronic use. BAK produces changes in surface epithelial cells that
impair the eye�s ability to preserve the mucin layer and sustain
tear-film stability. BAK can also alter the tight junctions between the
epithelial cells morphologically.
More importantly, as the BAK load increases, toxicity to the corneal
epithelium and conjunctiva may be increased, as has been demonstrated in
human and animal models and cell cultures. Increased toxicity could
result in exacerbation of ocular surface irritation for many patients
who already have signs or symptoms of ocular surface disease.
Travoprost ophthalmic solution 0.004% (Travatan Z, Alcon) is a BAK-free
prostaglandin analogue that has demonstrated IOP-lowering efficacy equal
to the original Travatan formulation, as well as better ocular surface
safety and potentially improved corneal health.
Tell-tale Dry Eye
�Do your eyes feel dry?� When we ask that question, we get many positive
responses in our patient populations. But we get more telling responses
when we ask questions such as, �Do you use artificial tears?�, �How do
your eyes feel when you read?� and �Do your eyes ever water or get
teary?�
Patients with dry eye symptoms might feel ocular discomfort (foreign
body sensation, pain, itching, photophobia or tearing), ocular fatigue
after just a short period of reading or visual symptoms such as
blurriness. We sometimes overlook these concerns, focusing instead on
the patient�s sight-threatening glaucoma.
To complicate matters further, we commonly experience a disconnect
between dry eye signs and symptoms. Patients might have considerable
complaints and very few signs of dry eye, or they might have extensive
corneal staining with few, if any, complaints.
When we go beyond �Do your eyes feel dry?� to ask the questions that
reveal patients� symptoms, some of us conservatively estimate that about
two-thirds of our patients have ocular surface disease. Some of these
patients arrived in our practices or were referred to us with this
problem, but others may have developed ocular surface disease as a
result of using topical medications preserved with BAK.
Ocular surface disease is considered a disease with a significant
inflammatory component, which can cause corneal epithelial and
conjunctival damage and affect the outcomes of filtering surgery. If a
patient with glaucoma has severe ocular surface disease, the cornea must
be restored to health. In our opinion, this means switching patients to
BAK-free medications or even prescribing oral medications.
BAK-free Prostaglandin Analogue
Switching to a BAK-free prostaglandin analogue is an excellent first
step in helping alleviate ocular surface disease among glaucoma
patients. With BAK-free travoprost, we have the option of avoiding a
toxic, injurious substance. It offers several benefits:
Dry eye resolution. For patients with moderate to severe dry eye,
clinicians usually order unpreserved artificial tears and an
anti-inflammatory agent, such as unpreserved cyclosporine, or a mild
steroid to address the chronic inflammation associated with dry eye. The
third component to therapy may be blepharitis treatment, including warm
compresses, eyelid scrubs and perhaps an antibiotic, such as doxycycline,
to reduce eyelid inflammation.
Simplicity and accessibility.
Preservative-free
timolol is often difficult to find, is dispensed in multiple unit-dose
vials and may not be covered by insurance. Oral carbonic anhydrase
inhibitors can produce significant systemic side effects and are,
therefore, usually a temporary option for lowering IOP. Brimonidine (Alphagan
P, Allergan) uses an alternative preservative to BAK, but requires b.i.d.
or t.i.d. dosing.
Comfort and adherence. Adherence is a major issue with glaucoma
therapy; discomfort from topical glaucoma medications may potentially
lead to non-adherence in some patients.
Equal Efficacy
Several studies have shown the role BAK plays in ocular surface disease
� in particular, to what degree it causes toxicity to corneal and
conjunctival epithelial cells. When researchers compared BAK-free
travoprost to latanoprost (Xalatan, Pfizer) with BAK in immortalized
human corneal epithelial cells (HCEs), a live/dead assay showed BAK-free
travoprost was significantly less toxic to HCEs than latanoprost.1
Researchers pointed out this difference might have an impact on the drug
tolerance of patients using glaucoma medications in the long term.
Another recently completed 3-month study compared BAK-free travoprost to
travoprost preserved with BAK.2 The double-masked, multicenter study
enrolled 690 patients who had open-angle glaucoma with ocular
hypertension. Patients with secondary glaucoma were excluded.
Half the patients were randomized to receive the BAK-preserved
prostaglandin, and half received the BAK-free formulation. Results
showed that travoprost was equally efficacious with or without BAK. The
decrease in IOP for BAK-free travoprost averaged about 8.5 mm Hg, which
is statistically equivalent to the reduction in IOP from travoprost with
BAK.
Not only was IOP lowered equally in both groups, but there was also no
difference in adverse effects. However, we still need to see how BAK-free
travoprost performs in the long term.
Given the equivalent efficacy and similar complication rates, BAK-free
travoprost can be prescribed for any patient who is initiating therapy
with a prostaglandin analogue. In addition, when a patient using a BAK-preserved
prostaglandin has ocular surface disease or eye irritation, it may be
beneficial to switch to a BAK-free agent to help improve the condition
and try to prevent further surface damage.
Ocular Health Important for Long-term Therapy
Every clinician should be aware of the impact of chronic exposure to BAK
on a patient�s ocular surface health. Fortunately, glaucoma therapy no
longer needs to contribute to that damage through chronic exposure to
BAK. With BAK-free therapy, we now have the potential to prevent or
alleviate ocular surface disease for many of our patients.
This change will not only help to improve overall ocular health, but it
may also enhance compliance among our patients with ocular surface
disease. Without the exacerbation of dry eye through continual exposure
to BAK, patients may be less likely to skip their drops. Comfortable
eyes can now become part of our achievable goals with glaucoma therapy.
For many glaucoma specialists, this combination of IOP-lowering efficacy
and low toxicity will be a useful addition to their armamentarium. OM
Francisco E. Fantes, M.D., is a glaucoma specialist at Bascom Palmer Eye
Institute in Miami. Dr. Fantes is also trained in corneal disease.
Richard A. Lewis, M.D., is a cataract surgeon and glaucoma specialist in
Sacramento, Calif.
Jess Thomas Whitson, M.D., F.A.C.S., is a glaucoma specialist and
associate professor of ophthalmology at the University of Texas
Southwestern Medical School in Dallas.
References
1. Yee RW, Norcom EG, Zhao XC.
Comparison of the relative toxicity of travoprost 0.004% without
benzalkonium chloride and latanoprost 0.005% in an immortalized human
cornea epithelial cell culture system. Adv Ther. 2006;23:511-519.
2. Lewis RA, Katz G, Weiss MJ, et al. Travoprost 0.004% with and without
benzalkonium chloride: a comparison of safety and efficacy. J Glaucoma.
In press.
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