This article was originally published in a sponsored newsletter.
Benzalkonium chloride (BAK) and other preservatives in eyedrops have been a topic of considerable discussion within the ophthalmic community due to their potential adverse effects on the cornea. BAK, a quaternary ammonium compound, is the most commonly used preservative in ophthalmic solutions and is valued for its effective bactericidal properties. However, its impact on the ocular surface has raised concerns about its safety in long-term use.
A significant amount of what is known about BAK toxicity comes from glaucoma patients who have been on chronic therapy with one or more medications that contain BAK. The toxic effects of BAK on the cornea and ocular surface have been extensively studied and include disruption of the corneal epithelial barrier, induction of epithelial cell apoptosis, conjunctival goblet cell loss, delayed corneal wound healing and elevated inflammatory cell markers in ocular tissues. These changes can lead to clinical manifestations such as pain, discomfort, corneal and conjunctival staining, decreased tear break-up time, lower Schirmer scores and subconjunctival fibrosis.
Many studies have demonstrated an inverse relationship between BAK use and glaucoma surgical efficacy. In fact, limited evidence has even suggested the possibility of BAK-associated toxicity to the conventional outflow system, potentially having an adverse effect on trabecular meshwork cells.
Given these adverse effects, there has been growing interest in BAK-sparing treatments. For patients using multiple BAK-containing products, which is frequently seen in glaucoma patients, using fixed-combination products can reduce the total number of drops needed. Numerous BAK-free and preservative-free formulations have entered the glaucoma therapeutic landscape. Preservative-free options include tafluprost (Zioptan, Théa) as well as two novel formulations of latanoprost (Iyuzeh, Théa and Xelpros, Sun Ophthalmics). Preservative-free dorzolamide/timolol (Cosopt, Merck) is also an option. Alternative preservative options include travoprost (Travatan Z, Novartis) and brimonidine tartrate ophthalmic solution (Alphagan P, Abbvie). Compounding pharmacies have also begun to introduce preservative-free formulations of common ocular hypotensive agents including brimonidine, dorzolamide, timolol, latanoprost and bimatoprost.
Preservative-free eyedrops are naturally less toxic to the ocular surface and serve as an effective alternative to BAK-containing products. However, the number of available preservative-free formulations is limited. Accessibility remains a challenge, and coverage by insurance carriers is frequently poor. It is also important to remember that topical drug administration itself presents numerous challenges. A need for sufficient manual dexterity and vision to self-administer, as well as the management of potential systemic and periocular effects of the pharmaceutical agents, are among top concerns.
The emergence of microinvasive glaucoma surgery (MIGS) and intracameral sustained drug delivery has given patients multiple alternatives to topical drug therapy. Intracameral bimatoprost (Durysta, Abbvie) and travoprost (iDose TR, Glaukos) are powerful options for delivering pharmacotherapy without the ocular surface and periocular side effect profiles. Standalone MIGS continues to grow as a therapeutic modality, with increasingly more surgical options becoming available every day. And, of course, MIGS at the time of cataract surgery for patients with glaucoma or on topical hypotensive therapy is increasingly becoming more available, with residency training programs including MIGS in their graduation requirements.
While BAK and other perservatives play a crucial role in preventing microbial contamination of eyedrops, their adverse effects on the ocular surface cannot be overlooked. The disruption of ocular surface homeostasis is a significant concern associated with the use of preservative-containing eyedrops. As such, there is a clear need for the development of safer preservative systems or preservative-free formulations to minimize the risk of ocular surface damage, particularly for patients requiring chronic use of topical ophthalmic medications.
