Benzalkonium chloride and glaucoma

Abstract

Glaucoma patients routinely take multiple medications, with multiple daily doses, for years or even decades. Benzalkonium chloride (BAK) is the most common preservative in glaucoma medications. BAK has been detected in the trabecular meshwork (TM), corneal endothelium, lens, and retina after topical drop installation and may accumulate in those tissues. There is evidence that BAK causes corneal and conjunctival toxicity, including cell loss, disruption of tight junctions, apoptosis and preapoptosis, cytoskeleton changes, and immunoinflammatory reactions. These same effects have been reported in cultured human TM cells exposed to concentrations of BAK found in common glaucoma drugs and in the TM of primary open-angle glaucoma donor eyes. It is possible that a relationship exists between chronic exposure to BAK and glaucoma. The hypothesis that BAK causes/worsens glaucoma is being tested experimentally in an animal model that closely reflects human physiology.

FIG. 1.

(A) BAK is reported to affect/accumulate in the cornea, lens, conjunctiva, iris, ciliary muscle epithelium, and trabecular meshwork. Adapted from the National Eye Institute, National Institutes of Health Ref#: NEA04. (B) The trabecular meshwork and Schlemm's canal are less than 1 mm away from the corneal and conjunctival surfaces, where drops are applied. Image courtesy of Dr. Morton Smith. BAK, benzalkonium chloride.

FIG. 2.

Proposed experimental protocols for studies on the effects of BAK on aqueous humor dynamics in cynomolgus monkeys. IOP, as measured by Goldmann applanation tonometry; AHF, as measured by scanning ocular fluorophotometry; outflow facility, as measured by the 2-level constant pressure perfusion of the anterior chamber technique. All monkeys determined to be ocularly normal by slit-lamp biomicroscopy before each experiment.