Comparative assessment of the cytotoxicity of six anti-inflammatory eyedrops in four cultured ocular surface cell lines, as determined by cell viability scores

Abstract

PurposeAnti-inflammatory eyedrops are often used in the treatment of corneal epithelial disorders. In the present study, we evaluated the cytotoxicity of six anti-inflammatory eyedrops in four ocular surface cell lines.MethodsThe cytotoxicity of six commercially available anti-inflammatory ophthalmic solutions (ie, diclofenac, bromfenac, pranoprofen, betamethasone, and fluoromethorone) was assessed in three corneal cell lines and one conjunctival cell line. Cell viability was determined by the 3-(4,5-dimethyl-2 thiazoyl)-2,5-diphenyl-2H-tetrazolium bromide and neutral red assays after exposing the cells to 10, 30, and 60 minutes of onefold, twofold, and tenfold dilutions of the drugs. Cytotoxicity was compared using the cell viability score (CVS), an integrated cytotoxic parameter that takes various factors into account, such as dilution by tear fluid or concentration by evaporation, drug exposure time, and ocular surface cell type.ResultsBased on the CVS scores, the order of the anti-inflammatory eyedrops tested from least to most cytotoxic, with the active ingredient %CVS50, and %CVS40/80 for each solution given in parentheses, was as follows: Rinderon® (betamethasone, 100%, 100%) >0.02% Flumethoron® (fluoromethorone, 68%, 22%) = 0.1% Flumethoron® (fluoromethorone, 76%, 22%) >Bronuck® (0.1% bromfenac, 53%, −8%) = Diclod® (0.1% diclofenac, 44%, −15%) = Niflan® (pranoprofen, 50%, −19%). Rinderon® exhibited the least toxicity of all the anti-inflammatory eyedrops tested. Eyedrops containing non-steroidal anti-inflammatory drugs exhibited greater cytotoxicity than those containing steroids with benzalkonium at comparable concentrations. Concentration was the most significant factor affecting cell viability.ConclusionThe cytotoxicity of the anti-inflammatory eyedrops evaluated in the present study depended on both the pharmaceutical components and preservatives. The CVS is a concise indicator of drug cytotoxicity.

Mild temperature photothermal assisted anti-bacterial and anti-inflammatory nanosystem for synergistic treatment of post-cataract surgery endophthalmitis

“…The situation of release in PBS was also tested and it was similar with in DI water ( Figure S6 ). As reported, the bromfenac sodium had some potential side effects of cornea damage 42 and conjunctiva damage 43 , while the sustained release of the drug could reduce the side effects 44 .…”

Dose dependent cytotoxicity of pranoprofen in cultured human corneal endothelial cells by inducing apoptosis

“…PPF, one of NSAIDs, is considered to be a major causative factor of ocular surface disorders during keratitis treatment (Ayaki et al, 2012). Therefore, it will be of great importance to access its endothelial cytotoxicity.…”

“…At the same time, there have also been reports on side effects of PPF, including irritation, conjunctival congestion, itching, and palpebral edema (Zhu et al, 2009). And it has been found that eyedrops containing NSAIDs exhibited greater cytotoxicity to rabbit and bovine corneal epithelial cells even than those containing steroids with benzalkonium at comparable concentrations (Ayaki et al, 2012).…”

“…Damage by surgical wounds, infection, long-term high eye pressure and drugs can result in excessive loss of HCE cells and lead to decompensation of the endothelium and eventual loss of visual acuity (Joyce, 2003;Schierhölter & Honegger, 1975). Since NSAIDs are considered to be a major causative factor of ocular surface disorders during treatment of inflamed eyes, such as postoperatively or for inflammatory eye diseases (Ayaki et al, 2012), it becomes more and more important to access their endothelial cytotoxicity for us to be aware of their toxicity as well as efficacy. Unfortunately, little is known about the potential endothelial toxicity of PPF till now (Ayaki et al, 2010).…”

Ocular Surface Cytotoxicity and Safety Evaluation of Tafluprost, a Recently Developed Anti-Glaucoma Prostaglandin Analog

“…To reflect the actual situation, we have tried to improve cytotoxicity assays for ocular cells by conducting comprehensive investigations covering a variety of concentrations and treatment times, and based on our studies, we proposed the use of a cell viability score (CVS) as a simple parameter to express the cytotoxic potential of ophthalmic solutions. 21–24…”