The Toxicity of Nonsteroidal Anti-inflammatory Eye Drops against Human Corneal Epithelial Cells in Vitro

Abstract

This study investigated the toxicity of commercial non-steroid anti-inflammatory drug (NSAID) eye solutions against corneal epithelial cells in vitro. The biologic effects of 1/100-, 1/50-, and 1/10-diluted bromfenac sodium, pranoprofen, diclofenac sodium, and the fluorometholone on corneal epithelial cells were evaluated after 1-, 4-, 12-, and 24-hr of exposure compared to corneal epithelial cell treated with balanced salt solution as control. Cellular metabolic activity, cellular damage, and morphology were assessed. Corneal epithelial cell migration was quantified by the scratch-wound assay. Compared to bromfenac and pranoprofen, the cellular metabolic activity of diclofenac and fluorometholone significantly decreased after 12-hr exposure, which was maintained for 24-hr compared to control. Especially, at 1/10-diluted eye solution for 24-hr exposure, the LDH titers of fluorometholone and diclofenac sodium markedly increased more than those of bromfenac and pranoprofen. In diclofenac sodium, the Na+ concentration was lower and amount of preservatives was higher than other NSAIDs eye solutions tested. However, the K+ and Cl- concentration, pH, and osmolarity were similar for all NSAIDs eye solutions. Bromfenac and pranoprofen significantly promoted cell migration, and restored wound gap after 48-hr exposure, compared with that of diclofenac or fluorometholone. At 1/50-diluted eye solution for 48-hr exposure, the corneal epithelial cellular morphology of diclofenac and fluorometholone induced more damage than that of bromfenac or pranoprofen. Overall, the corneal epithelial cells in bromfenac and pranoprofen NSAID eye solutions are less damaged compared to those in diclofenac, included fluorometholone as steroid eye solution.

Amnwiotic Membrane Transplantation as a Treatment for Sterile Infiltration and Corneal Melting after Corneal Crosslinking for Keratoconus

“…NSAIDs are widely used after various ocular surgeries, expecting anti-inflammatory and analgesic effects via inhibition of the enzymes cyclooxygenase 1/2. On the other hand, the toxicity of NSAIDs against corneal re-epithelialization has been investigated both in vitro [ 4 ] and in vivo [ 8 ]. Çerman et al [ 9 ] suggested that proinflammatory cytokines directly secreted from damaged epithelial cells may be released into the stroma and consequently trigger the migration of inflammatory cells to the affected stroma.…”

“…NSAIDs inhibit cyclooxygenases and decrease prostaglandin production; their use for corneal wound healing is a matter of debate. Postoperative use of topical NSAIDs promotes faster wound healing [ 3 ]; however, Lee et al [ 4 ] investigated the toxicity of NSAID eye solutions against corneal epithelial cells in vitro. Asai et al [ 5 ] reported 3 cases of corneal melting caused by bromfenac sodium used to treat surface and postoperative inflammation.…”

Bromfenac Inhibits TGF-β1–Induced Fibrotic Effects in Human Pterygium and Conjunctival Fibroblasts

“…27 Bromfenac is usually used to prevent macular edema and inflammation after cataract and complex ocular surgeries, [27][28][29] which is less toxic toward corneal epithelial cells. 30 Our study intended to explore whether bromfenac has the potential to prevent the excessive wound healing that takes place after the pterygium surgeries.…”

“…33 To assess the antifibrotic effects of bromfenac on TGF-b1-induced cells, the cultured HPFs and HConFs were divided into the following groups and treated for 48 hours: the control group; the TGF-b1 group, in which the cells were exposed to 20 ng/mL TGF-b1 (200-1; PeproTech, Rocky Hill, NJ, USA); the bromfenac group, in which the cells were treated with 90 lg/mL bromfenac (bromfenac active components were from Senju Pharmaceutical, Osaka, Japan); the TGF-b1 þ bromfenac group, in which the cells were treated with 20 ng/mL TGF-b1 plus 90 lg/mL bromfenac. For the dose-effect relationship study, HPFs and HConFs were treated with three concentrations of bromfenac (30,60, and 90 lg/mL) for 48 hours. For the inhibitors studies, 200 nM wortmannin (#S2758; Selleck, Houston, TX, USA) (PI3K inhibitor) and 20 lM U0126 (#9903S; CST, Waltham, MA, USA) (MEK inhibitor) were added 2 hours before the TGF-b1 treatment, and the HPFs and HConFs were collected 48 hours after TGF-b1 treatment to evaluate the changes.…”

Contact lens-related keratitis and purulent corneal ulcers

“…Нестероидные противовоспалительные средства назначали, как правило, коротким курсом на 3-5 дней для купирования/уменьшения болевого синдрома и потенцирования мидриаза. Более длительное их применение представляется нецелесообразным из-за возможного подавления процессов заживления роговицы (вплоть до развития местных трофических нарушений) [18][19][20].…”