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

Masahiko Ayaki¹, Atsuo Iwasawa², Mitsutaka Soda³, Shigeo Yaguchi³, Ryohei Koide^4
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