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Cytotoxicity of five fluoroquinolone and two nonsteroidal anti-inflammatory benzalkonium chloride-free ophthalmic solutions in four corneoconjunctival cell lines

Authors Masahiko Ayaki, Atsuo Iwasawa, Mitsutaka Soda, et al

Published 17 September 2010 Volume 2010:4 Pages 1019—1024

DOI https://doi.org/10.2147/OPTH.S12452

Review by Single-blind

Peer reviewer comments 3

Masahiko Ayaki1, Atsuo Iwasawa2, Mitsutaka Soda3, Shigeo Yaguchi3, Ryohei Koide4
1Department of Ophthalmology, Saitama National Hospital, Saitama, Japan; 2Department of Clinical Pathology, Showa University Fujigaoka Hospital, Yokohama, Japan; 3Department of Ophthalmology, Showa University Fujigaoka Rehabilitation Hospital, Yokohama, Japan; 4Department of Ophthalmology, Showa University School of Medicine, Tokyo, Japan

Purpose: Epithelial disorders after eye surgery can result in visual deterioration and patient discomfort. Such disorders may be caused by drug toxicity. In the present study, we evaluated the toxicity of ophthalmic solutions, with or without benzalkonium chloride (BAK) as the preservative, used for postoperative care.
Methods: A range of commercially available antibiotic and anti-inflammatory ophthalmic solutions used postoperatively (ie, levofloxacin, moxifloxacin, gatifloxacin, norfloxacin, tosufloxacin, dibekacin, cefmenoxime, diclofenac, bromfenac, pranoprofen, betamethasone, and fluoromethorone) were assessed in three corneal cell lines and one conjunctival cell line. All antibiotic solutions were BAK free. Cell viability was determined with the 3-(4,5-dimethyl-2 thiazoyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay after cells had been exposed to the drugs for 48 h. The effects of preservatives on cell viability were also determined. Toxicity was compared using the cell viability score (CVS).
Results: Based on results of the MTT assay and CVS, the order of cell viability after exposure to the antibiotic solutions was cefmenoxime ≥ tosufloxicin ≥ dibekacin ≥ levofloxacin ≥ norfloxacin = gatifloxacin = moxifloxacin. For the anti-inflammatory solutions, the order of cell viability was betamethasone ≥ betamethasone + fradiomycin > preservative-free diclofenac ≥ preservative-free bromfenac >> 0.02% fluoromethorone ≥ 0.1% fluoromethorone = diclofenac + preservative = bromfenac + preservative = pranoprofen. The anti-inflammatory drugs were more toxic than the antibiotics. The toxicity of antibiotic drugs against ocular surface cells was dependent on the pharmaceutical components of the solution, whereas that of the anti-inflammatory drugs was dependent on both the pharmaceutical components and the preservatives.
Conclusion: Postoperative drug-induced epitheliopathy may be caused primarily by anti-inflammatory drugs. CVS is useful in comparing the cytotoxicity of different drugs.

Keywords: toxicity, preservative, cornea, eye

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