Treating Glaucoma and Concomitant OSD

BAK-free medications provide multiple benefits to patients

By Clark Springs, MD

There are a number of factors that contribute to Ocular Surface Disease (OSD) including a patient's age, medications, health disorders and environmental factors. OSD is multifactorial, so therapy needs to be tailored to the individual. However, reviewing a patient's topical medication regimen and removing BAK-containing products when possible is easy to do and can significantly improve OSD symptoms, regardless of the severity or cause of OSD.

OSD: General Population vs Glaucoma Patients

The Women's Health Study showed that the prevalence of OSD in the general population was less than 10% in women over 75 years old. The study also showed that Hispanics and Asians were more likely to develop dry eye. A similar study for men, the Physicians Health Study, which was a 25,000-patient study showing prevalence of dry eye in men, showed that OSD appeared in 7% of men over the age of 80. A population-based study of 2500 patients in Salisbury, Md., found that the prevalence of dry eye was 14.6% in patients 65 and older and increased with age. So, even if we consider the most robust estimates of OSD in the general population, the prevalence is around 15%.

In comparison, if we review glaucoma studies, the prevalence of dry eye is four times greater. Lueng and colleagues¹ found that 59% of glaucoma patients using topical therapy had an abnormal Ocular Surface Disease Index (OSDI) in a single-center study. In addition, Robert Fechtner, MD, reported² similar findings in a multicenter study of 10 sites with a 48.4% prevalence of OSD in glaucoma patients. If you stratify those data according to drop use, Lueng found that with each added drop, there was an increase in prevalence of OSD. Fechtner found similar results, as did Rossi and colleagues.³

While OSD appearance in the general population is 15%, in the glaucoma population it's closer to 50% and half of those patients will have moderate to severe OSD. From a quality-of-life standpoint, moderate to severe ocular surface disease is as debilitating as moderate angina pectoris.⁴ In patients with moderate to severe OSD, patients typically stop a vision-related task, such as benefireading or computer work, because of ocular surface symptoms at least once per week.⁵ Further, these symptoms can adversely affect work and leisure time, and negatively impact their sense of well-being and confidence.⁶

Figure 1. Lissamine green staining of cornea and bleb in patient with OSD and bleb dysthesia.

Steps in Treatment

While some patients have a robust tear film and may be able to use a glaucoma treatment that contains BAK for a number of years, certain patients are at a higher risk for developing earlier problems with these medications. If you had to pick the ideal patient to develop an OSD problem, it would be someone with glaucoma. They're often elderly and using at least one oral medication that has anticholinergic properties (these drugs have drying effects) such as an antihypertensive or antidepressant. Added to that are their glaucoma drugs, most of which contain BAK as their preservative, which provide the perfect storm of dry eye waiting to happen in these patients.

Glaucoma medications seem to be the culprits that are tipping the scales from the 15% prevalence rate of OSD seen in the general population to the 50% prevalence rate seen in glaucoma patients. Glaucoma is usually an asymptomatic disease until it reaches its late stages and central vision is affected. So, in many cases, you're asking a previously asymptomatic patient to use a topical medication that may cause ocular irritation. This irritation causes a decrease in patient compliance.

The first step in treatment is to review a patient's medications and see if you can easily make a switch from a BAK-containing drop to a BAK-free drop. There is one prostaglandin analog that is BAK-free, travoprost (Travatan Z, Alcon). If you need an alpha agonist, consider brimonidine tartrate (Alphagan P, Allergan). Timolol is also available as a preservativefree unit dose, but it is expensive and often difficult to find in local pharmacies.

I've had some patients receive the generic version of brimonidine (which is preserved with BAK) from their pharmacist. Then they return to my office for a follow-up visit and they're complaining of ocular irritation because the pharmacist has replaced the branded BAK-free medication with a product that contains BAK. Be sure to specify when a prescription should not be replaced with a generic.

It's also important to make patients aware that non-branded or "house brand" artificial tears may be preserved with BAK.

The adverse affects of BAK on the ocular surface are well characterized. Histopathologically, they include an increase in inflammatory mediators, reduction in goblet cell density and increased cellular apoptosis. Clinically, this negatively impacts tear film function and leads to symptomatic OSD.⁷

Michael Horsley, MD, and Malik Kahook, MD, conducted a study in which they switched patients from latanoprost (Xalatan, Pfizer) to Travatan Z (Alcon).⁸ Patients in this study were on monotherapy Xalatan and had an abnormal tear breakup time and OSDI. After 2 months on Travatan Z, their tear film breakup time increased from 2 to 6 seconds and the OSDI scores improved from moderate dry eye to mild dry eye. This is a quality-of-life improvement equating to a 10-point improvement on the OSDI, which is significant.

For those glaucoma patients on multiple topical medications, reducing the BAK load by utilizing combination products can be helpful. For instance, utilizing combination products such as a betablocker and a carbonic anhydrase inhibitor or a beta-blocker and an alpha-agonist. Utilizing combination agents in selected patients, allows them to step down from 4 drops a day to 2, which is beneficial in terms of reducing BAK load and increasing the likelihood of compliance.

Figure 2. Patient with prior trabeculectomy with OSD and superior limbal stem cell deficiency.

It's also necessary to review systemic medications and inquire about any recent additions or changes. For instance, if the patient has recently started an oral antihistamine or sleep medication, this can tip the scale toward symptomatic dry eye. In such situations, I also check with the patient's primary doctor or allergist to see if there are less drying alternatives available.

If a patient presents with severe dry eye on multiple topical glaucoma and OSD medications, I may discontinue all topical medications with the exception of preservative- free tears and even consider a brief course of oral carbonic anhydrase inhibitors under the direction of one of my glaucoma colleagues. The patient will typically note an immediate benefit. I then discontinue the oral glaucoma medications and add topical glaucoma and OSD medications in a stepwise fashion over several weeks or months with the goal of limiting BAK-exposure.

In treating glaucoma patients who are already taking several medications, it's essential to find the best treatment for their OSD and to ensure that you find a regimen that will encourage patient compliance.

BAK-related ocular surface complications are somewhat like second-hand smoke. They may not affect everyone immediately or in the same way, but over time, complications can, and do, develop. Regardless of the class of medication, be it topical glaucoma medication or artificial tears, utilizing BAK-free topical medications is the best practice whenever possible.

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Clark Springs, MD, is an assistant professor of ophthalmology at Indiana University Medical Center in Indianapolis and director of Cornea and Refractive Surgery.

References

1. Leung EW, Medeiros FA, Weinreb RN. Prevalence of ocular surface disease in glaucoma patients. J Glaucoma. 2008;17:350-355.
2. Fechtner RD, Godfrey DG, Budenz D, Stewart J, Stewart WC, Jasek MC. Prevalence of ocular surface complaints in patients with glaucoma using topical intraocular pressure-lowering medications. Cornea. 2010;29:618-621.
3. Rossi G, Pasinetti GM, Tinelli C, Milano G, Bianchi PE. Dry eye related quality of life in glaucoma patients. Program and abstracts of the World Glaucoma Congress 2009; July 8-11, 2009; Boston, Massachusetts. Abstract P023.
4. Schiffman RM, Walt JG, Jacobsen G, Doyle JJ, Lebovics G, Sumner W. Utility assessment among patients with dry eye disease. Ophthalmology. 2003;110:1412-1419.
5. Miljanovic B, Dana R, Sullivan DA, Schaumberg DA. Impact of dry eye syndrome on visionrelated quality of life. Am J Ophthalmol. 2007;143:409-415.
6. Nelson DJ, Helms H, Fiscella R, Southwell Y, Hirsch JD. A new look at dry eye disease and its treatment. Adv Ther. 2000;17:84-93.
7. International Dry Eye Workshop. 2007 report of the International Dry Eye Workshop (DEWS). Ocular Surf. 2007;5:75-200, 2007.
8. Horsley MB, Kahook MY. Effects of prostaglandin analog therapy on the ocular surface of glaucoma patients. Clin Ophthalmol. 2009;3:291-295.