Glaucoma Drug Preservatives: 'Disease' or 'Minimal' Problem?

Laird Harrison

March 12, 2012

March 12, 2012 — A group of ophthalmology professors hired by the maker of a preservative-free glaucoma medication is calling adverse reactions to preservatives in glaucoma medication a "disease in itself."

In a news release, Valeant Ophthalmics, a division of Valeant Pharmaceutical North America, said the 8 experts from 7 US universities and 1 from the University of Paris in France found that preservatives can kill cells and blur patients' vision, as well as causing inflammation.

In contrast, Richard Bensinger, MD, an American Academy of Ophthalmology clinical correspondent, told Medscape Medical News that adverse reactions to preservatives in glaucoma drugs are not a big problem.

"In my opinion, it's pretty minimal," said Dr. Bensinger, who has a private ophthalmology practice in Seattle, Washington.

Concerns about toxicity in glaucoma medication preservatives began with real toxicity from thimerosal, a preservative used in some medications, but this compound is no longer being used to preserve glaucoma medications, Dr. Bensinger said.

Although some patients still develop irritation in response to the preservatives now in use, the problem can usually be handled by switching medications, he noted.

Dr. Bensinger acknowledged that preservative-free glaucoma medicines are probably safe. These preservatives are added mainly to avoid bacterial growth in the container, and this growth is unlikely because a bottle typically contains only a 1-month supply of the drug, he said.

However, pharmaceutical companies are focusing on the preservative issue as a way to differentiate their products in the marketplace, Dr. Bensinger said. "My personal feeling is that these things are largely a matter of marketing, and very little a matter of actual clinical risk." Preservative-free medication is typically more expensive, he added.

On February 10, the US Food and Drug Administration approved Merck's tafluprost 0.0015%, the first preservative-free prostaglandin analog ophthalmic solution for open-angle glaucoma or ocular hypertension.

Valeant makes Timoptic, a preservative-free solution of the beta-blocker timolol, which is also used in treating glaucoma.

Valeant's Working Group on Preservatives Toxicity identified multiple problems with preservatives: First, they can cause inflammation, which is not a normal symptom of glaucoma. The inflammation can cause glaucoma surgery to fail, said Paul Kaufman, MD, from the University of Wisconsin–Madison, in the news release.

Second, the preservatives can cause blurred vision, said Stephen C. Pflugfelder, MD, from Baylor College of Medicine in Houston, Texas, in the release. "It has been recognized for decades that preservatives are detergents," he noted.

"They break the tight junctions in the apical epithelial cells in the cornea and probably the conjunctiva also. They may have some cytotoxic activity themselves and in certain concentrations will cause apoptosis or programmed cell death or necrosis."

However, few patients are likely to suffer from these effects, Dr. Bensinger said. "The surface of the eye is pretty tough," he said. "And the cornea replaces itself every 2 to 3 days."

The press release cited a July 2010 article on preservatives from Progress in Retinal and Eye Research.

Stephen Obstbaum, MD, from New York University in New York City, who was listed as the chair of the working group, declined to comment for this article. Two other members named in the press release, Robert J. Noecker, MD, from Ophthalmic Consultants of Connecticut, and Robert Fechtner, MD, director, Glaucoma Division, Institute of Ophthalmology and Visual Sciences, New Jersey Medical School–UMDNJ did not return calls from Medscape Medical News.

The members of the working groups were paid by Valeant Pharmaceuticals, a maker of preservative-free glaucoma medications. Dr. Bensinger has disclosed no relevant financial relationships.

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