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Editors Selection IGR 15-2
Eyedrop Formulation: Side effects of preservatives
Comment by Malik Kahook on:
51897 A new safety concern for glaucoma treatment demonstrated by mass spectrometry imaging of benzalkonium chloride distribution in the eye, an experimental study in rabbits, Brignole-Baudouin F; Desbenoit N; Hamm G et al., PLoS ONE, 2012; 7: e50180
Benzalkonium chloride (BAK) is a detergent preservative commonly found in multi-dose drop bottles used for treating glaucoma. It has been implicated as a causative factor of ocular surface disease by inducing damage to surface epithelial cells as well as disrupting the tear film. The effect of BAK on intraocular cells has not been well characterized. Brignole-Baudoui and colleagues have recently published their study which investigates the ocular penetration and distribution of BAK in New Zealand White rabbits. They reported that BAK was localized to ocular surface structures as well as in deeper structures such as trabecular meshwork and the optic nerve. Inflammatory cell infiltration and Muller glial cell activation was also reported and attributed to a direct effect from BAK. The authors concluded that their findings 'highlight the importance of the safetyfirst principle for the treatment of glaucoma patients'.
The physiologic effect on the eye is not substantial enough to induce measurable damage and/or that the eye can overcome such effects by inherent compensatory mechanisms such as anti-oxidant reserves. Alternatively, the very treatment being prescribed to patients may lead to damage that could potentially worsen disease
There is now ample evidence that BAK causes damage to ocular surface cells as well as trabecular meshwork cells in vitro and indication that it might lead to ocular surface disease in vivo in specific patient populations.1-3 What remains unclear is how BAK influences intraocular cells in patients who are chronically using BAK preserved topical ophthalmic drops and whether any clinically significant effect exists. We are limited in our current in vivo diagnostic devices and lack the ability to measure real-time effects of BAK on both ocular surface and intraocular cell lines. Glaucoma topical therapeutics preserved with BAK have been used chronically by patients for decades and appear to be safe and well-tolerated in the overwhelming majority of those treated. The current report and others before it implicate BAK in ongoing damage to various ocular cell lines that could lead to deleterious effects. It is possible that the physiologic effect on the eye is not substantial enough to induce measurable damage and/or that the eye can overcome such effects by inherent compensatory mechanisms such as anti-oxidant reserves. Alternatively, the very treatment being prescribed to patients may lead to damage that could potentially worsen disease. Further research is needed to elucidate this matter and help direct our treatment of glaucoma patients.
References
- Pellinen P, Huhtala A, Tolonen A, Lokkila J, Mäenpää J, Uusitalo H. The cytotoxic effects of preserved and preservative-free prostaglandin analogs on human corneal and conjunctival epithelium in vitro and the distribution of benzalkonium chloride homologs in ocular surface tissues in vivo. Curr Eye Res 2012; 37(2): 145-514.
- Hamard P, Blondin C, Debbasch C, Warnet JM, Baudouin C, Brignole F. In vitro effects of preserved and unpreserved antiglaucoma drugs on apoptotic marker expression by human trabecular cells. Graefes Arch Clin Exp Ophthalmol 2003; 241(12): 1037-1043.
- Fechtner RD, Godfrey DG, Budenz D, Stewart JA, Stewart WC, Jasek MC. Prevalence of ocular surface complaints in patients with glaucoma using topical intraocular pressure-lowering medications. Cornea 2010; 29(6): 618-621.
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