BAK RISKS

More research is needed to determine the possible effect of chronic BAK use on trabecular meshwork pathology Douglas J Rhee MD

The common preservative benzalkonium chloride (BAK) has long been known to exacerbate inflammatory ocular surface disease. But does BAK also accelerate the glaucoma disease process? While research has not demonstrated that it does, recent studies suggest mechanisms by which it might, Douglas J Rhee MD of Harvard Medical School told the 2013 American Society of Cataract and Refractive Surgery Symposium. An anti-microbial detergent, BAK is toxic to both pathogens, corneal epithelial cells and trabecular meshwork endothelial cells. Epithelium disruption also increases corneal permeability, boosting the effectiveness of some topical glaucoma medications, particularly timolol. BAK does enter the eye – a potential problem because it can be highly toxic to endothelial cells, Dr Rhee noted. “If you infuse a rabbit with 0.05 per cent BAK in the anterior chamber for 10 seconds, you get total and permanent endothelial cell destruction.” (Maurice D, Perlman M. Invest Ophthalmol 1977; 16:646.)

Recent mass spectrometry ion imaging studies confirm that topical BAK does indeed penetrate. It has been detected in the corneal endothelium, iris and trabecular meshwork, causing inflammation, Dr Rhee said (Brignole-Baudouin F et al. PLoS One 2012;7:e50180. Desbenoit et al. Anal Bioanal Chem 2013). BAK also has been shown to kill trabecular meshwork cells in vitro (Ammar DA, Kahook MY. Mol Vis. 2011;17:1806-1813). However, this may not be relevant to glaucoma progression, Dr Rhee added. “For most patients, inflammation in the trabecular meshwork is not the primary disease point; it is basically cell death and changes in the extracellular matrix.” More research is needed to determine the possible effect of chronic BAK use on trabecular meshwork pathology, he said.

Ocular surface disease

Evidence for BAK exacerbating ocular surface disease is much stronger, Dr Rhee said. Several studies of ocular surface disease in glaucoma patients since 2008 report rates from 30 per cent to 70 per cent, averaging around 50 per cent, compared with about 30 per cent for controls. In addition, the number of daily eye drops and duration of topical treatment are risk factors for ocular surface disease in glaucoma patients. (Rossi GC et al. Eur J Ophthalmol. 2012. Dec 17 e. pub. Labbe A et al. Cornea 2012;31:994-999. Ghosh S et al. Clin Experiment Ophthalmol. 2012;40:675- 681. Valente C et al. J Ocul Pharmacol Ther. 2011;27:281-285. Leung EW et al. J Glaucoma 2008;17:350-355.) Eyes with filtering blebs also have a higher incidence of surface disease (Neves Mendes CR et al. Curr Eye Res. 2012;37:309-311), and surface disease is associated with poorer quality of life in glaucoma patients (Skalicky ES et al. Am J Ophthalmol. 2012;153:1-9).

Long-term BAK use also promotes conjunctival inflammation, decreasing trabeculectomy success, Dr Rhee noted. However, this may be reversed with preoperative steroids (Broadway DC et al. Arch Ophthalmol. 1996; 114: 262-7). Avoiding BAK may help reduce both surface and conjunctival inflammation risks, Dr Rhee said. Preservative-free glaucoma treatment options include timolol maleate (Timoptic), dorzolamide/ timolol combination (Cosopt) and tafluprost (Zioptan). In addition, alternatively preserved options include brimonidine 0.1 and 0.15 per cent (Alphagan P), preserved with Purite, a stabilsed oxycholoro complex; and travoprost 0.015 per cent (Travata), preserved with Sofzia, an ionic buffer containing borate, sorbitol, polylene, glycol and zinc, Dr Rhee said. “These are a little gentler than BAK, but their exact chemical structure is proprietary.”