Department of Ophthalmology, University of Colorado, Denver, Aurora, USA.
Adv Ther. 2011 Jun;28(6):501-10. doi: 10.1007/s12325-011-0029-x. Epub 2011 May 16.
The aim of this study is to investigate potential adverse effects of fixed combination glaucoma medications preserved with either benzalkonium chloride (BAK) or Polyquad® (PQ; Alcon Research Ltd., Fort Worth, TX, USA) on cultured ocular epithelial cells.
Confluent cultures of human cornea and conjunctival cell lines were exposed for 25 minutes to different glaucoma medications as well as a range of concentrations of BAK (0.001%-0.050%). Balanced salt solution was used as the "live" control and a solution containing 70% methanol and 0.2% saponin was used as a "dead" control. The number of dead and live cells were determined via ethidium homodimer (Eth-1) and calcein acetoxymethyl ester (AM) fluorescence, respectively.
The toxicity of the prostaglandin analog with beta-blocker timolol fixed-combination formulations preserved with BAK was different from that observed in the respective BAK concentrations. Travoprost plus timolol fixed combination with BAK performed better than its respective BAK concentration alone, while the latanoprost plus timolol fixed combination performed worse than its respective BAK concentration. Travoprost plus timolol fixed combination preserved with PQ had greater corneal and conjunctival cell survival than either the travoprost plus timolol fixed combination preserved with BAK or the latanoprost plus timolol fixed combination.
Ocular surface side effects have previously been demonstrated with chronic, long-term exposure to intraocular-pressure-lowering medications containing the common preservative BAK. BAK alone has significant in-vitro cytotoxicity to cultured ocular epithelial cells. Substitution of BAK with PQ resulted in significantly higher percentages of live conjunctival and corneal cells. Further studies are needed to understand the clinical implications of these findings.
本研究旨在探讨含有苯扎氯铵（BAK）或 Polyquad®（PQ；Alcon Research Ltd.，Fort Worth，TX，USA）的固定组合青光眼药物对培养的眼上皮细胞的潜在不良影响。
将人角膜和结膜细胞系的汇合培养物暴露于不同的青光眼药物以及不同浓度的 BAK（0.001%-0.050%）25 分钟。平衡盐溶液用作“活”对照，含有 70%甲醇和 0.2%皂角苷的溶液用作“死”对照。通过 ethidium homodimer（Eth-1）和 calcein acetoxymethyl ester（AM）荧光分别确定死细胞和活细胞的数量。
含有 BAK 的前列腺素类似物与β-阻滞剂噻吗洛尔固定组合制剂的毒性与观察到的 BAK 浓度不同。含有 BAK 的 travoprost 加噻吗洛尔固定组合的效果优于其各自的 BAK 浓度，而 latanoprost 加噻吗洛尔固定组合的效果则不如其各自的 BAK 浓度。含有 PQ 的 travoprost 加噻吗洛尔固定组合的角膜和结膜细胞存活率高于含有 BAK 的 travoprost 加噻吗洛尔固定组合或 latanoprost 加噻吗洛尔固定组合。
先前已经证明，含有常见防腐剂 BAK 的降眼压药物长期慢性暴露会引起眼表面副作用。BAK 单独对培养的眼上皮细胞具有显著的体外细胞毒性。用 PQ 替代 BAK 可显著提高结膜和角膜细胞的存活率。需要进一步研究以了解这些发现的临床意义。
