In Vitro Toxicity of Topical Ocular Prostaglandin Analogs and Preservatives on Corneal Epithelial Cells

Abstract

All 4 PGA formulations tested demonstrated significantly more toxicity in human corneal epithelial cells than the live control, but there were significant differences among the PGAs. Travoprost with sofZia exhibited the least toxicity, followed by travoprost with BAK, and then tafluprost and latanoprost. The stand-alone preservative systems were also tested and showed similar survival percentages to each respective PGA. The true clinical implications of these findings require further investigation.

Safety and Efficacy of Benzalkonium Chloride-optimized Tafluprost in Japanese Glaucoma Patients With Existing Superficial Punctate Keratitis

“…24,25 However, travoprost with sofZia was also found to show cytotoxicity for cultured human corneal epithelial cells when compared with a preservative-free solution. 26 The tendency for the mean AD score to decrease after the switch from travoprost with sofZia (non-BAK group) to BAKoptimized tafluprost might thus reflect the difference in cytotoxicity for corneal epithelial cells between sofZia and an optimized concentration of BAK. Together, our present results and previous findings 12,19,26 suggest that the safety profiles for BAK-optimized tafluprost and preservative-free tafluprost are similar both for corneal epithelial cells in vitro as well as in the clinical setting.…”

“…26 The tendency for the mean AD score to decrease after the switch from travoprost with sofZia (non-BAK group) to BAKoptimized tafluprost might thus reflect the difference in cytotoxicity for corneal epithelial cells between sofZia and an optimized concentration of BAK. Together, our present results and previous findings 12,19,26 suggest that the safety profiles for BAK-optimized tafluprost and preservative-free tafluprost are similar both for corneal epithelial cells in vitro as well as in the clinical setting. The mean TBUT was prolonged significantly at 12 weeks after the switch to BAK-optimized tafluprost for all patients as well as for those in the BAK group (but not for those in the non-BAK group).…”

Toxicity Evaluation of Antiglaucoma Drugs Using Stratified Human Cultivated Corneal Epithelial Sheets

“…19,20 A useful alternative to the reliance on the animal model is in vitro cell culture assays. In previous studies, corneal epithelial and conjunctival cell lines have been widely used for ocular toxicology, 5,10,12,14,15,[21][22][23][24][25] but these cell lines have a single layer and cannot mimic the stratified corneal and conjunctival epithelium. Barrier function is one of the important functions of the corneal epithelium, which is well known to be compromised in eye drop-induced keratopathy.…”

Neurotrophic Keratitis

“…A history of corneal surgery, trauma, abuse of topical anaesthetics, long-term use of topical medications, chemical burns, or contact lens abuse may be contributory. Long-term use of eye drops such as timolol, betaxolol, sulfacetamide sodium, or diclofenac can cause a loss of corneal sensitivity, as can the abuse of topical anaesthetics [3,26,27]. Corneal hypoesthesia can sometimes occur in advanced stromal dystrophies such as latex or granular dystrophies [3].…”