Consider BAK's effects in glaucoma patients

Patients with glaucoma may have an increase in morbidity and reduced quality of life. They often require multiple medications, which increases exposure to preservatives such as benzalkonium chloride (BAK) and can contribute to the development of ocular surface disease (OSD).

The use of medications without BAK may improve patient satisfaction and, in turn, compliance.

BAK, which is present in 72% of current ophthalmic preparations, is the most commonly used preservative, according to Abelson. This preservative can damage healthy ocular surfaces.

BAK further compromises ocular surface health by decreasing epithelial cell integrity, increasing conjunctival inflammatory cells and goblet cell loss and adversely affecting tear film break up time (TBUT). This shortening of TBUT may result in ocular symptoms and affect visual acuity and many activities of daily living. Most significantly, the toxic effects of BAK are dose-dependent, with both high concentrations and cumulative exposure producing increased risk for damage, according to Cha and colleagues.

Studies: BAK's adverse effects

According to Pisella and colleagues, patients on glaucoma medications reported significantly more adverse effects, with dry eye symptoms more frequent in those receiving higher doses.

Jaenen and colleagues found that of 9,658 patients studied, the 74% who had received preserved medications experienced significantly more complaints of burning or stinging, dry eye, discomfort or pain during instillation, and eyelid twitching.

In a recent study using the Ocular Surface Disease Index (OSDI), Fechtner and colleagues found that 50% of glaucoma patients had OSD. Furthermore, OSDI severity correlated with the number of topical ophthalmic preparations used, suggesting cumulative preservative effects.

Interestingly, Baudouin and colleagues found that patients receiving multiple antiglaucoma medications for more than 1 year had the greatest cellular changes to ocular tissue taken during trabeculectomy surgery. Leung and colleagues recently reported that 59% of open angle glaucoma or ocular hypertension patients had OSD symptoms in at least one eye when the OSDI was applied, and for each additional BAK-containing eye drop a patient received, the odds for an abnormal lissamine green stain was two times higher.

Studies of BAK-free agents

BAK-free treatment options for glaucoma may improve patient compliance, thus improving outcomes and, potentially, satisfaction.

In 12-month study of 1,147 patients evaluating Alphagan P (brimonidine-Purite 0.15%, Allergan) or 0.2% compared to Alphagan (brimonidine 0.2%, Allergan) with BAK, those receiving Alphagan P had significant reductions in adverse events (P < .05), according to Katz and colleagues. Similarly, in 3-month trial by Mundorf and colleagues of 407 patients, those receiving brimonidine with Purite 0.15% reported fewer adverse events compared to those receiving the BAK formulation.

In a case series of 20 patients on Travatan Z (travoprost-sofZia, Alcon) who were previously treated with latanoprost, Horsley and colleagues found significant improvements compared to baseline in TBUT (6.34 ± 1.31 seconds vs. 2.02 ± 0.71 seconds; P < .001) and in OSDI scores (16.56 ± 6.19 vs. 26.31 ± 8.25; P < .001), indicating regression from moderate to mild disease.

In a recent study involving 690 patients previously treated with latanoprost or bimatoprost, Henry and colleagues reported significant improvements in OSDI scores and hyperemia at 3 months with BAK-free travoprost. In the 72% of patients who preferred the travoprost, they reported significant improvements in visual acuity, light sensitivity, grittiness, blurred or poor vision, driving at night, computer work, windy conditions, difficulty reading and low humidity (P≤.0001). This preference implies that patients value therapies that can minimize adverse effects.

Practical considerations

Achieving optimal IOP can frequently require multiple medications. The Ocular Hypertension Treatment Study observed that at least 40% of patients required treatment with two or more medications to reach target IOP (Kass and colleagues). Many of these medications contain BAK. Using medications with lower concentrations of BAK and, optimally, those without BAK may improve patient outcomes. By focusing upon not only IOP management, but also on medication regimens, practitioners can reduce the risk of OSD, minimize exposure so patients will suffer from fewer adverse effects and help improve compliance as a result.

Practical approaches to minimizing BAK toxicity include awareness of preservative free options and BAK concentration in available products and over-the-counter ophthalmic medications as well as thorough patient histories. Preservative free ophthalmics, including tears, should be recommended.

BAK-free glaucoma medications should be considered when possible to minimize overall exposure. It is important to counsel patients that improvements do take a period of time and are not immediate, as we are dealing with an inflammatory condition.

For more information:

• Michael Chaglasian, OD, FAAO, is chief of staff at the Illinois Eye Institute and associate professor at Illinois College of Optometry. He can be reached at 3241 South Michigan Ave., Chicago, IL 60616; (312) 949-7303; e-mail: MChaglas@ico.edu.
• Ronald Carr, OD, FAAO, practices at Midwest Eye Professionals in Palos Heights, Ill., and is a member of the adjunct clinical faculty at Illinois College of Optometry, Chicago. He can be reached at (708) 361-6141; e-mail: roncarr@mweye.com. Dr. Carr has no direct financial interest in the products mentioned in this article, nor is he a paid consultant for any companies mentioned.

References:

• Abelson MB, Fink K. How to handle BAK talk. Rev Ophthalmol. 2002;9(12). http://www.revophth.com/index.asp?page=1_247.htm. Accessed November 18, 2008.
• Baudouin C, Riancho L, Warnet JM, Brignole F. In vitro studies of antiglaucomatous prostaglandin analogues: travoprost with and without benzalkonium chloride and preserved latanoprost. Invest Ophthalmol Vis Sci. 2007;48:4123-4128.
• Cha SH, Lee JS, Oum BS, Kim CD. Corneal epithelial cellular dysfunction from benzalkonium chloride (BAC) in vitro: Clin Exp Ophthalmol. 2004;32:180-184.
• Fechtner, R, Budenz, D, Godfrey D. Prevalence of ocular surface disease symptoms in glaucoma patients on IOP-lowering medications. Poster presented at: annual meeting of the American Glaucoma Society; March 2008; Washington DC.
• Henry JC, Peace JH, Stewart JA, Stewart WC. Efficacy, safety and improved tolerability of travoprost BAK-free ophthalmic solution compared with prior prostaglandin therapy. Clin Ophthalmol. 2008;2(3):613-621.
• Horsley M, Kahook MY. Changes in tear break-up time and ocular surface disease index after initiation of travoprost with sofZia in patients previously using latanoprost with benzalkonium chloride. Poster presented at: annual meeting of the American Glaucoma Society; March 2008; Washington, DC.
• Jaenen N, Baudouin C, Poulique P, et al. Ocular symptoms and signs with preserved and preservative-free glaucoma medications. Eur J Ophthalmol. 2007;17(3):341-349.
• Kass MA, Heuer DK, Higginbotham EJ, et al. The Ocular Hypertension Treatment Study: a randomized trial determines that topical ocular hypotensive medication delays or prevents the onset of primary open-angle glaucoma. Arch Ophthalmol. 2002;120(6):701-713.
• Katz LJ. Twelve-month evaluation of brimonidine-purite versus brimonidine in patients with glaucoma or ocular hypertension. J Glaucoma. 2002;11(2):19-26.
• Leung EW, Medieros FA, Weinreb RN. Prevalence of ocular surface disease in glaucoma. J Glaucoma. 2008;17:350-355.
• Mundorf T, Williams R, Whitcup S, et al. A 3-month comparison of efficacy and safety of brimonidine-Purite 0.15% and brimonidine 0.2% in patients with glaucoma or ocular hypertension. J Ocular Pharmacol Ther. 2003;19:37-44.
• Pisella PJ, Pouliquen P, Baudouin C. Prevalence of ocular symptoms and signs with preserved and preservative free glaucoma medication. Br J Ophthalmol. 2002;86(4):418-423.