April 2012




Pharmaceutical focus

Preservative use in allergy medications

by Michelle Dalton EyeWorld Contributing Editor


Although not an ideal situation for allergy sufferers, in most short-term courses of treatment, preservatives will not harm the ocular surface

Summary table of allergy medications

When one-quarter of the U.S. population is affected by a disease state and 90% of those patients exhibit ocular manifestations, it's safe to say ophthalmologists will see a good number of patients on a fairly routine basis for treatment. When that disease state is allergic conjunctivitis and the most common topical treatments include preservatives known to adversely affect the ocular surface, it's not as clear-cut.

Ocular allergies are usually seasonal or occasionally perennial, but more chronic forms include atopic keratoconjunctivitis (AKC) and vernal keratoconjunctivitis (VKC), the latter two being more difficult to treat as well. VKC is more typically present in children, with AKC mostly affecting men under age 50.

Current medical treatments range from antihistamines, mast cell stabilizers, combination antihistamine/mast cell stabilizers, decongestants, nonsteroidal anti-inflammatory drugs (NSAIDs), steroids, and vasoconstrictors. Most of the prescription medications use benzalkonium chloride in various strengths (see Table 1), a preservative reported to harm the ocular surface when used in chronic diseases such as glaucoma. "Fundamentally, the issue is that we don't have a good test to determine which patient is going to have a problem with the preservative and which won't," said Ira J. Udell, M.D., chairman, ophthalmology department, North Shore Long Island Jewish Health System, Great Neck, N.Y.

That does not imply ophthalmologists should ignore the status of the corneal surface when they're evaluating allergy patients, he said.

"The preservative is going to irritate the surface as soon as it hits it and will do so chronically over time," said Leonard Bielory, M.D., medical staff, Robert Wood Johnson University Hospital; professor, Rutgers University Center for Environmental Prediction; and director, STARx Allergy & Asthma Center, New Brunswick, N.J. "For instance, people think they've developed an allergy to a topical glaucoma med that is not actually an allergy to the med but a secondary irritation that has developed to the preservative." (For more on allergic reactions to topical medications, see sidebar.) In seasonal or perennial conjunctivitis, "the mast cells remain below the conjunctival surface so you have the integrity of that surface protecting the allergic trigger cells; the conjunctival surface of allergic patients appears to be more porous," Dr. Bielory said. In the more chronic forms, mast cells move to the surface of the conjunctiva and further accentuate allergic inflammation.

"When there is a defect in the epithelial junction between cells of the conjunctiva, there will be cracks for allergens and pollutants to get through the deeper layers of the substantia propria; when one has allergic inflammation it increases the gaps between the cells and causes further leakage that exacerbates the allergic response, creating a vicious cycle," he said.

Dr. Bielory's general rule of thumb is to prescribe medications with preservatives for most seasonal sufferers, "unless the surface is really raw. Someone with the potential for a leaky surface, such as a chronic seasonal [patient], may already have a defect that's occurring," he said, although he noted there have not been any clinical studies to confirm his observations. There is no doubt preservatives adversely affect the ocular surface, Dr. Udell said, noting that the preservative "may counteract the positive anti-inflammatory effects" of the topical medication. "When I'm referred patients with major irritation in the eye, the first thing I want to know is what they've been treated with," he said. His group studied a cohort of 31 patients with chronic ocular surface disease who had been treated with preserved steroids, topical cyclosporine 0.05%, or both.1 In this study of recalcitrant ocular irritation, patients were switched to a "very weak unpreserved steroid0.01% dexamethasone." Only four patients (13%) reported no improvement in symptoms, with most (n=20; 65%) showing 50-100% improvement. "Just by switching to an unpreserved steroidand an extremely weak one at thatpatients had huge improvements in their symptoms," Dr. Udell said.

Stepwise treatments

Lubricating eye drops will likely be a starting point for many clinicians, Dr. Udell said. Next, he suggests using a combination antihistamine/ mast cell stabilizer. If the first combination drug is unsuccessful, Dr. Udell recommended switching to another combination drug. "But a short pulse of steroids in a very severe case for a short time is fine," he said. "If combination drugs aren't working, I'll move them to a steroid and taper quickly to get them on a safer drug." He tries to avoid vasoconstrictor drugs"the chronic use of them is almost as bad as drops with BAK because of the rebound effect," he said. On a routine basis, Dr. Bielory prefers drops with once- or twice-daily dosing. "Once-daily dropseven those that are preservedare better than those that are twice- or four-times daily," he said. But preservatives will continue to be a "double-edged sword," he said. "They prevent the active ingredient from being contaminated with microbial organisms, which would cause a secondary inflammation or infection, but the preservative used may in and of itself cause the chronic irritation," he said. And because using preservatives keeps the costs down, Dr. Bielory believes preservatives will continue to be present in most allergy medications. For those patients with more severe chronic forms or for those who can't tolerate the preservative, single-unit dosing (and therefore, non-preserved dosing) may be preferable.


1. Jonisch J, Steiner M, Udell IJ. Preservative-free low-dose dexamethasone for the treatment of chronic ocular surface disease refractory to standard therapy. Cornea. 2010;29(7):723-6.

Editors' note: Dr. Bielory consults for ophthalmology. Dr. Udell has financial interests with Merck (Whitehouse Station, N.J.).

Contact information

Bielory: Bielory@envsci.Rutgers.edu
Udell: nrubinst@nshs.edu

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