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Eye Drop Preservatives with Malik Kahook, MD
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In general terms, what are the relevant clinical associations between glaucoma and ocular surface disease?
Dr. Kahook: I think the important thing to mention when speaking about both ocular surface disease and glaucoma is that these disease processes increase with age. As patients age, their risk for glaucoma increases with every decade. The same thing happens with ocular surface disease. We know this from extensive research that has been done out of several clinical sites.So it makes sense that ocular surface disease would be more prevalent in patients with glaucoma, but there are many other things that go beyond just the age association. In particular, and most importantly, glaucoma patients tend to use topical drops for treatment—one or several eyedrops on a daily basis, chronically, for multiple years.
The instillation of the drops on the ocular surface usually introduces not just an active ingredient, but also a preservative. In most cases the preservative is benzalkonium chloride (BAK), a detergent that can disrupt the tear film, disrupt the epithelial layers of both the cornea and the conjunctiva, and decrease the goblet cell numbers within the conjunctiva—all of which lead to a disease process that looks similar to the ocular surface disease that happens with the association of dry eye syndrome.
Therefore, it’s not a surprise that glaucoma patients have a higher tendency toward ocular surface disease. When we’re treating our glaucoma patients, we have to select our therapies with that in mind.
People have been using antiglaucoma pharmacotherapy for a century. Why now is there so much attention being paid to the eyedrop preservative?
Dr. Kahook: I get that question a lot: Why the sudden focus on BAK and the deleterious effects that it might have on the ocular surface? The truth is, the issues around BAK have been around for years, multiple decades, in fact. You can go back in the literature and find papers that report on the deleterious effects of BAK in the 1970s.What has changed over the past few years is the introduction of medications that are BAK–free. Research into the formulation of medications has just recently, over the past few years, been advanced enough to introduce alternative preservatives to the market, in particular the oxidizing preservatives including sodium perborate and Sofzia. Along with the new medications, you have a renewed focus on both the clinical and basic science research. Certainly there is also a marketing push by various companies to try to distinguish the novel preservatives from the existing classes that have been on the market for years. Before, in the 1970s and 1980s, we didn’t have many options, and so the discussion took place around not having preservatives in medication. Now that we have alternatives, it seems like the deleterious effects of BAK is a new concept, but the fact is, we’re just hearing more about it because now we have choices.
How does underlying ocular surface disease influence patient adherance with antiglaucoma treatment?
Dr. Kahook: We know that the preservatives and, to some degree, the active ingredients in glaucoma medications can exacerbate ocular surface disease, which leads to side effects like blurry vision, stinging and foreign-body sensation. All of these are undesirable to the patient, and the patient can usually equate the therapy with the side effects that are happening, which could theoretically lead to a decrease in adherence and can ultimately result in a poor response to therapy and potentially to advancing disease or an increase in visual-field defects in these glaucoma patients.Now, all of that is intuitive, but the truth is, we lack data to show that there’s a 1-to-1 relationship between the side effects from the glaucoma drops and the potential for a decrease in adherence. The reason for that is, it’s very tough to measure ocular surface disease in a reproducible way in a clinical trial. Quantifying adherence in patients who have glaucoma and are taking daily drops is also difficult. As a result, conclusively determining if there’s a 1-to-1 effect where if ocular surface disease increases, the patient is less adherent, is challenging.
What I will say, though, is this is a good example of the clinical experience really dictating what we’re doing in clinical practice. On a very basic level, patients come into my clinic and tell me that their drops are bothering them, that they cause symptoms similar to ocular surface disease, and because of that they’re not taking their medications regularly.
So even though we can’t quantify it regularly in clinic because of a limitation of our metrics, I can tell you from a practice standpoint that patients don’t take their drops frequently because they’re seeing side effects.
How do you modify your strategy for lowering intraocular pressure when you also diagnose ocular surface disease?
Dr. Kahook: I’ll start by saying that when glaucoma is diagnosed in my clinic, routinely I start the patients on medication, and my choice for monotherapy is a prostaglandin analog. There are multiple choices, and there are many decision drivers that happen in clinic, including cost, whether the patient has insurance, availability of the medication to a given patient, that all have to be taken into account. But in particular, when we’re talking about a patient with ocular surface disease, I try to avoid the preservative benzalkonium chloride.