Contamination of Glaucoma Drugs More a Result of Patient Error Than Absence or Presence of Preservative

April 29, 2008

April 29, 2008 (Fort Lauderdale) — The contamination of glaucoma medications in a clinical setting appears to depend more on patients than on whether the medication contains benzalkonium chloride (BAK) or is BAK-free, according to a new study presented here at the Association for Research in Vision and Ophthalmology 2008 Annual Meeting.

Ophthalmologists have always been concerned about the safety of multiple-use eyedrop bottles. On the one hand, ophthalmic preservatives prevent bacterial contamination and prolong shelf life by limiting biodegradation. On the other hand, the continual use of such preservative-containing topical ophthalmic products for the treatment of glaucoma can often contribute to the worsening of ocular surface disease. In addition, exposure to glaucoma medications containing BAK, the most commonly used preservative in glaucoma medications, can produce alterations in tear film function and conjunctival inflammation.

"Because BAK can cause adverse effects in patients, we decided to look at whether eyedrops without a preservative would cause less contamination. Our findings showed that contamination was more likely to be caused by the patients," lead author Mahendra K. Shah, MS, from the department of Pathology and Laboratory Medicine at the New York Eye and Ear Infirmary in New York City, told Medscape Ophthalmology.

The researchers also wanted to test whether the patients might be contributing to the contamination, as occurred in an outbreak of Fusarium keratitis that occurred with multiple-use contact lens solution.

The authors decided to assess whether patients using the prostaglandin travoprost without BAK (Travatan Z, Alcon, Inc) are at higher risk for microbial contamination than those using a BAK-containing analog, when taken on a normal dosing schedule.

The study involved 82 glaucoma patients: 44 taking travoprost (Travatan) and 38 taking bimatoprost (Lumigan, Allergan, Inc). Each patient's current prostaglandin bottle, as well as a secondary preservative-containing control drop (timolol [Timoptic, Merck], brinzolamide [Azopt, Alcon, Inc], or timolol/dorzolamide [Cosopt, Merck]), was collected. Patients received new, fresh bottles of the prostaglandin and secondary drops on the day of the visit. However, the 44 travoprost patients received a new bottle of BAK-free travoprost in place of the travoprost with BAK. Each patient's new set of drops was collected 2 to 4 weeks later, and the tips and contents of each bottle were swabbed and inoculated in thioglycolate broth by 1 microbiologist.

If turbidity was noted, the swabs were subcultured on appropriate media, and identification was made by a second microbiologist — who did not know the origin of the drops — using either manual methods or the VITEK 3. Bacteria were recovered from the tip or contents of 9% of BAK-containing prostaglandin agents (bimatoprost and travoprost) and from 8% of the BAK-free travoprost (P > .05). Of the BAK-containing control drops (timolol, brinzolamide, and timolol/dorzolamide), bacteria were recovered from the tips or contents of 9% of the bottles. The tips or contents were positive in 1 (13%) of 8 timolol bottles, 5 (12%) of 42 Azopt bottles, and 10 (7%) of 142 Cosopt bottles. These differences were also not statistically significant.

However, when it came to the issue of patience compliance, a statistically significant difference occurred. Bottle tips were more frequently contaminated than the solution, in an approximately 6:1 ratio. Four patients contaminated all 4 bottles, accounting for 16 (44%) of the 36 positive cultures. The researchers determined that having the bottle tips be more frequently contaminated than the solution was indicative of patient noncompliance.

"The study found that there is nodifference in the medication containing BAK or in the solution that did not. The contamination seemed to be due to the patient, and their method of using [the medication],” Mr. Shah said.

According to the researchers, patients need to be educated about the proper techniques for using chronic drops.

"This is interesting research," said Paulo Mello, MD, associate professor of medicine at the School of Medicine at the University of São Paulo, Brazil, who was not involved in the study. He noted that it is a difficult situation in poorer areas of the world, because eyedrops containing BAK can cause irritation, but BAK-free medications are more expensive. Compliance among patients with glaucoma is also a major problem worldwide, with ocular irritation as a contributing factor. Other factors include the cost and number of drops per bottle, because patients try to use eyedrops a little at a time to save money, even when they receive the medicine in single-dose containers.

Alcon Laboratories, the maker of travoprost with and without BAK, provided research support. The authors have disclosed no relevant financial relationships.

Association for Research in Vision and Ophthalmology 2008 Annual Meeting: Abstract 1221. Presented April 28, 2008.