In vitro toxicity of topical ocular prostaglandin analogs and preservatives on corneal epithelial cells.
OBJECTIVE
To determine the effect of 4 formulations of commercially available prostaglandin analogs (PGAs) on human corneal epithelial cells in vitro.


METHODS
The test solutions (PGAs) examined were tafluprost 0.005% with 0.010% benzalkonium chloride (BAK), travoprost 0.004% with 0.015% BAK, travoprost 0.004% with sofZia, and latanoprost 0.005% with 0.020% BAK. Also tested independently were the 4 respective BAK or sofZia concentrations related to each PGA. Balanced salt solution (BSS) was used as the live control, and a fixative solution containing 70% methanol and 0.2% saponin was used as the dead control. Immortalized human corneal epithelial cells were exposed to test or control solution for 25 min at 37 degrees C and 5% CO(2). A live/dead assay was used to measure the toxicity of the PGAs.


RESULTS
The percentage of live cells in the PGA groups ranged from 2% to 72% of the BSS group (live control). The PGA with the highest relative live cell percentage, at 72% of the live control, was travoprost with sofZia. The next highest PGA, exhibiting 14% live cells, was the formulation of travoprost containing BAK. The other 2 PGAs, tafluprost and latanoprost, had few surviving cells, with 3% and 2% live cells, respectively. The BAK concentrations exhibited 4%, 3%, and 3% for the 0.01%, 0.015%, and 0.02% concentrations, respectively. The stand-alone sofZia cell survival was 68% of the live control.


CONCLUSIONS
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.
Kahook
Malik Y
MY
Department of Ophthalmology, Rocky Mountain Lions Eye Institute, University of Colorado Denver School of Medicine, Aurora, Colorado 80045, USA. malik.kahook@gmail.com
Ammar
David A
DA
D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000633:toxicity; D001548:Benzalkonium Compounds / Q000008:administration & dosage / Q000633:toxicity*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003008:Cloprostenol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D019573:Epithelium, Corneal / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D000077338:Latanoprost; D011310:Preservatives, Pharmaceutical / Q000008:administration & dosage / Q000633:toxicity; D011460:Prostaglandins F / Q000008:administration & dosage / Q000633:toxicity; D011461:Prostaglandins F, Synthetic / Q000008:administration & dosage / Q000633:toxicity*; D000069557:Travoprost
D000959:Antihypertensive Agents; D001548:Benzalkonium Compounds; D011310:Preservatives, Pharmaceutical; D011460:Prostaglandins F; D011461:Prostaglandins F, Synthetic; C485333:tafluprost; D003008:Cloprostenol; D000077338:Latanoprost; D000069557:Travoprost