The treatment of glaucoma using topical preservative-free agents: an evaluation of safety and tolerability

ABSTRACT

Introduction: Preservative-free (PF) medications represent a valuable treatment strategy in the lifelong management of glaucoma. By removing preservative toxicity, PF formulations provide tangible clinical benefits to glaucoma patients worldwide. They improve tolerability and adherence, leading to a positive impact in long-term intraocular pressure (IOP) control.

Areas covered: A critical review of the subject is provided, including selected evidence on the safety and tolerability of currently available topical PF formulations. Cumulative evidence confirms that topical PF medications are at least equally efficacious to their preserved equivalents. There is convincing short-term evidence for superior tolerability and safety of PF formulations compared to preserved medications. The long-term benefits and success of PF therapy requires further elucidation.

Expert opinion: Successful stepwise administration of medical therapy for glaucoma remains elusive. There is a greater risk for ocular toxicity and therapy failure with preserved topical glaucoma therapy. Currently available and emerging PF therapy options potentially optimize lifelong stepwise glaucoma therapy and may enhance outcome. To avert complications from preservatives leading to poor adherence, ideally, future antiglaucoma therapy should become 100% PF. There are still key aspects of PF therapy that warrant further investigation.

KEYWORDS:

• BAK
• benzalconium chloride
• dry eye
• glaucoma
• intraocular pressure
• IOP
• ocular surface
• ocular surface disease
• OSD
• preservative-free

Authorship

All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published.

Article highlights

• Topical glaucoma medications are associated with a significant incidence of progressive glaucoma therapy-related ocular surface disease (OSD). This not only affects millions of glaucoma patients worldwide, but also reduces the success of long-term medical therapy.

• This OSD is becoming a major concern, because 45-60% of patients employing preserved eyedrops are clinically affected. Moreover, it is plausible that in up to 80% of medically treated glaucoma patients, the ocular surface is impaired at various levels from subtle subclinical inflammation to devastating pathology like that seen in cases of toxic pseudopemphigoid.

• OSD can decrease long-term tolerance and adherence to topical therapy owing to a diverse range of adverse events emerging within a few months of therapy initiation.

• Prevention, or improvement of OSD in glaucoma can be achieved by eliminating exposure to benzalkonium chloride (BAK). Mounting evidence demonstrates that OSD significantly improves upon discontinuation of topical BAK-preserved glaucoma eyedrops.

• Short-term evidence demonstrates that changing to PF formulations improves tolerability and consequently may also enhance the success of stepwise medical therapy. In the future, PF formulations are expected to gain a greater market share.

• As yet there is limited evidence on the long-term benefits and value of PF medications.

This box summarizes key points contained in the article.

Declaration of interest

AG Konstas has received research funding from Allergan, Bayer and Santen; travel support from Vianex; and honoraria from Allergan, Mundipharma, Santen and Vianex. A Katsanos has received research funding from Laboratoires Théa, and congress expenses/speaker fees from Santen, Vianex and Cooper. F Meier-Gibbons has received speaker fees from Alcon, Allergan, Glaukos, Heidelberg Engineering, Novartis, Santen and Laboratoires Théa. G Holló has served as a consultant for Aerie and Santen, and has received speaker fees from Aerie, Santen and Mundipharma. 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

No funding or sponsorship was received for this study, or publication of this article.