In this installment of Interventional Mindset, Gregory Katz, MD, an ophthalmologist specializing in glaucoma, reviews the importance of considering preservative-free medications when prescribing treatment for glaucoma patients. Glaucoma is the second leading cause of blindness in the US and is the number one leading cause of preventable blindness worldwide.
One key reason for this is that glaucoma often goes undiagnosed in many patients until they present with advanced disease. The prevalence of glaucoma is likely also caused by the core compliance shown with treatment.
Hundreds of studies have shown that adherence to glaucoma regimens is very poor in patients and is even poorer when the glaucoma drop causes ocular side effects, such as dry eye.
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History of preservatives in artificial tear glaucoma medications
While preservatives are very useful for prolonging the shelf life of medications and preventing contamination, they can cause unwanted ocular side effects. For example, thimerosal was one of the first preservatives used in eye drops, and it worked well as a preservative, but it was associated with a very high rate of allergy.
This was then replaced by benzalkonium chloride (BAK), which worked well for many years to follow but also showed side effects in users. As early as the 1970s, BAK has been associated with ocular surface disease. BAK's effects on the ocular system are so well documented and understood that BAK has even been used in an animal model to study ocular surface diseases.
Numerous studies have shown that glaucoma patients have a very high incidence of ocular surface disease, and BAK-containing glaucoma drops have almost been universally found to exacerbate this. So having a preservative-free glaucoma drop option can be very useful when treating glaucoma patients.
Preservative-free glaucoma drops on the market
Since BAK has been shown to exacerbate ocular surface disease, it should be no surprise that prescription drops used to treat dry eye are all preservative-free, including medications like Restasis, Xiidra, and Cequa.
There are also preservative-free artificial tears for patients who need to frequently dose them, and while not necessarily preservative-free, almost all branded artificial tear drops are BAK-free. Other medications formulated without BAK have been brought to the market to help decrease ocular surface disease, including Durezol and Vigamox.
There is a clear advantage to using a preservative-free glaucoma medication. The first preservative-free glaucoma drop was introduced in 2003 with the Timoptic in ocudose. The only other preservative-free glaucoma drop on the market in the US was Zioptan, until recently, with the approval of preservative-free latanoprost (Iyuzeh).
Disadvantages of preservative-free drops
While preservative-free drops decrease ocular surface inflammation, they offer some unique disadvantages to patients. Some disadvantages that glaucoma patients might encounter with preservative-free drops are the cost, as these preservative-free medications can be quite expensive, and ease of use, as these drops are often inconvenient for many patients because they are supplied in single-dose vials.
Available BAK-free glaucoma medication drops:
- Travatan Z, which is preserved with non-BAK-containing SofZia
- In clinical trials, the SofZia formulation elicited significantly less ocular surface disease than the BAK-containing Travoprost
- Xelpros is a BAK-free formulation of latanoprost which is preserved with potassium sorbate
- Alphagan P is preserved with purite
- Iyuzeh, preservative-free latanoprost 0.005%
Advantages of using the preservative BAK in glaucoma medications
Benzalkonium chloride helps increase absorption through the cornea of the eye drop; however, the currently available BAK-free medications have shown adequate absorption without the BAK, but this is not the case with all medications. While most pharmaceutical companies would likely prefer to avoid using BAK, unfortunately, with many compounds, the absorption isn’t good enough to be effective.
An example of this is Bimatoprost, which was introduced as a 0.03% concentration, and while it worked well, there was a relatively high incidence of ocular surface disease. So Allergan decreased the concentration to 0.01%, but they had to quadruple the BAK concentration to allow for adequate absorption.
Conclusion
When choosing a medication to treat glaucoma, there are many things to consider, such as the patient’s medical history, allergies, cost, dosing schedule, and an often-overlooked consideration, the risk of BAK exacerbating ocular surface disease and decreasing compliance.
Choosing a preservative- or BAK-free glaucoma drop is almost always in the best interest of the patient and should be considered when choosing which medication to prescribe.
