BAK linked to ocular surface damage in animal studies

January 15, 2008
Nancy Groves

Prostaglandin analogues preserved with benzalkonium chloride (BAK) can cause more extensive loss of goblet cells and a breakdown of cell-cell adhesions, which could increase the risk of ocular surface disease, according to findings from a pair of studies conducted in rabbits.

Key Points

Dr. Kahook, assistant professor, University of Colorado Denver, discussed the findings of two studies that he and Robert J. Noecker, MD, MBA, performed to investigate the effect on the ocular surface of rabbits of travoprost preserved with the ionic-buffered preservative system compared with latanoprost preserved with 0.02% BAK. They analyzed changes in conjunctival goblet cells and corneal epithelial desmosomes after exposure to the drops.

"Part of the problem with using BAK as a preservative in glaucoma medications is the toxic effect that builds up over time," Dr. Kahook said. "It is not just the initial use of the preserved drop; it is the cumulative effect.

First study

In the first study, 15 New Zealand white rabbits randomly were assigned into groups of five and were treated with once-daily topical application of travoprost, latanoprost, or preservative-free artificial tears. This dosing was chosen to mimic the clinical dosing of prostaglandin analogues in humans, Dr. Kahook said.

The rabbits were treated for 30 days, at which time the investigators harvested conjunctiva and performed histologic analysis using mucin stains to count the number of goblet cells on the conjunctival surface.

Investigators found a statistically significant difference between latanoprost with BAK and travoprost with the ionic-buffered preservative system. The mean number of goblet cells per high-power field was 2.21 (± 0.40) in the latanoprost with BAK group, 6.02 (± 1.20) in the travoprost with ionic-buffered preservative group, and 7.03 (± 1.33) in the preservative-free artificial tear group.

"The number of goblet cells in the latanoprost with BAK group was significantly lower than the other two groups [p = 0.0001]," Dr. Kahook said.

The difference in goblet cell numbers between the travoprost with ionic-buffered preservative group and the control group was not statistically significant (p = 0.24).

Second study

In a second study, the investigators also compared the formulations of travoprost and latanoprost, using preservative-free artificial tears in the control group. They followed the same protocol, treating 15 New Zealand white rabbits divided into three groups, with once-daily application of one of the three drops for 30 days.

At the end of treatment, the central cornea of each rabbit was harvested, and transmission electron microscopy was performed on it. The number of desmosomal attachments per photomicrograph (×3,400) was quantified and analyzed using Student's t-test to compare means between groups.