Ocular benzalkonium chloride exposure: problems and solutions

Michael H Goldstein,Trung Tran,Fabiana Q Silva,Nysha Blender,Srilatha Vantipalli

doi:10.1038/s41433-021-01668-x

Abstract

Preservatives in multidose formulations of topical ophthalmic medications are crucial for maintaining sterility but can be toxic to the ocular surface. Benzalkonium chloride (BAK)—used in approximately 70% of ophthalmic formulations—is well known to cause cytotoxic damage to conjunctival and corneal epithelial cells, resulting in signs and symptoms of ocular surface disease (OSD) including ocular surface staining, increased tear break-up time, and higher OSD symptom scores. These adverse effects are more problematic with chronic exposure, as in lifetime therapy for glaucoma, but can also manifest after exposure as brief as seven days. Multiple strategies are available to minimize or eliminate BAK exposure, among them alternative preservatives, preservative-free formulations including sustained release drug delivery platforms, and non-pharmacological therapies for common eye diseases and conditions. In this paper, we review the cytotoxic and clinical effects of BAK on the ocular surface and discuss existing and emerging options for ocular disease management that can minimize or eliminate BAK exposure.

Highlights

PRESERVATIVES USED IN EYE DROPS Preservatives serve a critical role in the formulation of topical ophthalmic medications used to treat a wide variety of ocular conditions
Several newer proprietary preservation systems—such as Polyquad, Purite, and SofZia— have been developed to mitigate undesirable attributes of Benzalkonium chloride (BAK); these are useful in glaucoma medications given the chronic polytherapy nature of glaucoma and the resulting extensive preservative exposure
BAK may act as a corneal penetration enhancer, leading to great ocular penetrance of active ingredients in BAK-preserved formulations [3, 10, 11]

Summary

REVIEW ARTICLE OPEN

Benzalkonium chloride (BAK)—used in approximately 70% of ophthalmic formulations—is well known to cause cytotoxic damage to conjunctival and corneal epithelial cells, resulting in signs and symptoms of ocular surface disease (OSD) including ocular surface staining, increased tear break-up time, and higher OSD symptom scores These adverse effects are more problematic with chronic exposure, as in lifetime therapy for glaucoma, but can manifest after exposure as brief as seven days. Several newer proprietary preservation systems—such as Polyquad, Purite, and SofZia— have been developed to mitigate undesirable attributes of BAK; these are useful in glaucoma medications given the chronic polytherapy nature of glaucoma and the resulting extensive preservative exposure Various others of these preservative classes have both intrinsic antibacterial and antifungal activity and are commonly used in contact lens solutions, artificial tears, and rewetting drops to reduce the risk of contact lensassociated fungal keratitis.

Oxidizing agents

Some artificial tears

Findings

ADDITIONAL INFORMATION