Conjunctival and corneal reactions in rabbits following short- and repeated exposure to preservative-free tafluprost, commercially available latanoprost and 0.02% benzalkonium chloride.
OBJECTIVE
To compare the conjunctival and corneal reactions of commercially available solution of latanoprost (Xalatan) and preservative-free (PF) tafluprost in rabbits.


METHODS
The rabbits received 50 microl of phosphate-buffered saline (PBS), PF-tafluprost 0.0015%, latanoprost 0.005% or benzalkonium chloride (BAK) 0.02%; all solutions were applied at 5 min intervals for a total of 15 times. The ocular surface toxicity was investigated using slit-lamp biomicroscopy examination, flow cytometry (FCM) and on imprints for CD45 and tumour necrosis factor-receptor 1 (TNFR1) conjunctival impression cytology (CIC) and corneal in vivo confocal microscopy (IVCM). Standard immunohistology also assessed inflammatory/apoptotic cells.


RESULTS
Clinical observation and IVCM images showed the highest ocular surface toxicity with latanoprost and BAK, while PF-tafluprost and PBS eyes presented almost normal corneoconjunctival aspects. FCM showed a higher expression of CD45+ and TNFR1+ in latanoprost- or BAK-instilled groups, compared with PF-tafluprost and PBS groups. Latanoprost induced fewer positive cells for inflammatory marker expressions in CIC specimens compared with BAK-alone, both of which were higher than with PF-tafluprost or PBS. Immunohistology showed the same tendency of toxic ranking.


CONCLUSIONS
The authors confirm that rabbit corneoconjunctival surfaces presented a better tolerance when treated with PF-tafluprost compared with commercially available latanoprost or BAK solution.
Liang
H
H
Department of Toxicology, Faculty of Biological and Pharmacological Sciences, University Paris Descartes, Paris, France.
Baudouin
C
C
Pauly
A
A
Brignole-Baudouin
F
F
D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000633:toxicity*; D001548:Benzalkonium Compounds / Q000008:administration & dosage / Q000633:toxicity*; D048588:Benzoxazines; D004396:Coloring Agents; D003228:Conjunctiva / Q000187:drug effects*; D003315:Cornea / Q000187:drug effects*; D004847:Epithelial Cells / Q000473:pathology; D007150:Immunohistochemistry; D007637:Keratoconjunctivitis / Q000139:chemically induced / Q000473:pathology; D000077338:Latanoprost; D008297:Male; D009883:Ophthalmic Solutions; D010078:Oxazines; D011310:Preservatives, Pharmaceutical / Q000633:toxicity*; D011460:Prostaglandins F / Q000008:administration & dosage / Q000633:toxicity*; D011461:Prostaglandins F, Synthetic / Q000008:administration & dosage / Q000633:toxicity*; D011817:Rabbits
D000959:Antihypertensive Agents; D001548:Benzalkonium Compounds; D048588:Benzoxazines; D004396:Coloring Agents; D009883:Ophthalmic Solutions; D010078:Oxazines; D011310:Preservatives, Pharmaceutical; D011460:Prostaglandins F; D011461:Prostaglandins F, Synthetic; C485333:tafluprost; C028911:cresyl violet; D000077338:Latanoprost