Ocular surface toxicity from glaucoma topical medications and associated preservatives such as benzalkonium chloride (BAK)

ABSTRACT

Introduction: This review discusses the evidence concerning the effect of topical medications and their preservatives on the ocular surface in glaucoma patients. The role of topical anti-glaucoma medication remains critical in the management of chronic glaucoma worldwide but the beneficial effects of treatment are counterbalanced by the adverse effects of corneal and conjunctival toxicity.

Areas covered: This article covers the effect of topical ocular drops and preservatives, particularly benzalkonium chloride, on the cornea and conjunctiva. Both basic science and clinical evidence will be presented. The first part reviews the relationship between ocular surface disease and benzalkonium chloride and the evidence from non-benzalkonium chloride preserved drops. The second part discusses the effects of benzalkonium chloride on the histopathology of the conjunctiva and its impact on clinical care as well as quality of life.

Expert opinion: Topical anti-glaucoma medication will continue to be used in the management of this blinding disease for the foreseeable future. Treatment outcomes will benefit from minimized exposure to benzalkonium chloride. The development of alternative preservatives, preservative-free topical options, and non-drop therapeutics such as drug-eluting systems for the delivery of ocular medications, will be very helpful in the care of glaucoma patients.

KEYWORDS:

• Benzalkonium chloride
• conjunctiva
• cornea
• glaucoma
• preservatives
• toxicity

Article highlights

• Preservatives are essential in multi-dose bottles of anti-glaucoma medications to minimize bacterial contamination; however, the same preservatives, especially benzalkonium chloride (BAK), has toxic effects that can lead to or worsen ocular surface disease (OSD)

• BAK disrupts corneal epithelium cellular architecture by damaging DNA, disrupting tight junctions and induces cell apoptosis or necrosis. These result in decreased cellular viability, greater inflammatory response, and impaired cell proliferation.

• BAK causes subconjunctival fibrosis and loss of goblet cells which worsens tear film quality and lead to symptoms of ocular surface diseases.

• BAK can also negatively affect the long-term success rate of glaucoma filtering surgery

• Clinical evidence suggests BAK has negative effect on glaucoma patients and their quality of life. When this offending agent is removed or replaced, OSD symptoms are reduced with minimal effect on anti-glaucoma efficacy

• Novel non-topical and sustained release methods of anti-glaucoma medication delivery provide avenues of eliminating BAK and its adverse effects on the ocular surface

This box summarizes key points contained in the article.

Declaration of interest

CC Chan has received honoraria from Allergan, Alcon Labs Inc, and Bausch & Lomb. CM Birt has received honoraria from Merck and Alcon Labs Inc. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

This paper was not funded.