Switching drugs to combat dryness may not stop symptomatic complaints

San Antonio, TX-Switching to another prostaglandin analogue that does not contain benzalkonium chloride (BAK) may not be the answer for managing complaints from patients of dryness and irritation while using latanoprost 0.005% (Xalatan, Pfizer), according to the results of a prospective, double-masked, randomized clinical trial conducted by ophthalmologists at Lackland Air Force Base, San Antonio, TX.

The study included 33 patients with glaucoma already being treated with latanoprost for at least 6 months who reported ocular dryness and irritation, according to J. Richard Townley, MD, clinical director of ophthalmology services, Lackland Air Force Base. Patients were randomly assigned to once-daily instillation of latanoprost in one eye and travoprost 0.004% (Travatan Z, Alcon Laboratories) with a proprietary ionic-buffered preservative system (SofZia) in the fellow eye. Latanoprost contains 0.02% BAK and the ionic-buffered preservative system is considered milder and less toxic than BAK.

Study duration was 3 months with monthly follow-up visits. Dryness/irritation were assessed at all visits by the same examiner in masked fashion, using the Oxford Scale to grade corneal staining, and by patient ratings of dryness/irritation, using a simple numeric scale. In addition, patients completed the Ocular Surface Disease Index (OSDI) to compare dryness/irritation between eyes at baseline and study completion.

No differences identified

Both treatments effectively controlled IOP and no differences between groups were identified in Schirmer testing or tear break-up time.

"Ocular irritation and dryness are common complaints among patients using topical IOP-lowering medication, and BAK exposure is considered a cause for this problem," Dr. Townley said. "Animal and human studies have shown less ocular irritation using travoprost with [the ionic-buffered preservative system] compared with the original product containing BAK, and anecdotally, patients outside of this study switched from latanoprost to travoprost without BAK report improvement.

"Therefore our study results were surprising," he said. "Although we can postulate several explanations to account for the findings in this investigation, the main conclusion is that further investigation in a larger patient population seems warranted."

For study recruitment, investigators identified all patients from Wilford Hall Medical Center or Brook Army Medical Center who had a prescription for latanoprost monotherapy. They were able to contact 180 patients, but only 89 (41%) patients were experiencing dryness/irritation, and only 33 patients were interested in participating in the study; 27 patients completed the 3-month treatment period.

"We did not know what magnitude of difference we might see between eyes and arbitrarily used a 10% difference in our power calculation," Dr. Townley said. "Based on that number, it was determined that the study would need to include about 100 patients for adequate statistical power. Therefore, we were surprised to find a statistically significant difference between treatments with our much smaller population."

Fewer corneal changes

Trying to account for the discrepancy between the study findings and previous research, Dr. Townley said that results of a rabbit study found eyes treated with travoprost with the ionic-buffered preservative system exhibited fewer corneal changes and less conjunctival inflammation than eyes treated with latanoprost with BAK. It is possible that human eyes may respond differently to these products.

In addition, the prostaglandin analogue itself, and not just the preservative, may be a cause for ocular surface changes and symptomatic complaints. Repackaging of the two commercial products into similar containers to maintain study blinding may introduce another variable because each formulation may react with the polymer of the container to generate a byproduct that might cause irritation.

"Taking the latter possibility into account, future studies comparing these products should also use containers that have the same composition as the bottles containing the commercially available medications," Dr. Townley concluded.