Comparison of the ocular tolerability of a latanoprost cationic emulsion versus conventional formulations of prostaglandins: an in vivo toxicity assay.
OBJECTIVE
Using an established rabbit toxicological model, this in vivo study compared the ocular cytotoxicity of four topical intraocular pressure (IOP)-lowering agents: the commercial benzalkonium chloride (BAC)-containing solutions of 0.005% latanoprost, 0.004% travoprost, 0.03% bimatoprost (containing 0.02%, 0.015%, and 0.005% BAC, respectively), and 0.005% latanoprost in a new cationic emulsion (LCEm) formulation.


METHODS
Thirty adult male New Zealand albino rabbits were used in this study. They were randomly divided into five groups: 50 microl of sterile phosphate-buffered saline (PBS) along with each formulation was applied onto rabbit eyes 15 times at 5 min intervals. The ocular surface changes were investigated using slit-lamp examination, corneal in vivo confocal microscopy (IVCM) for cornea, limbus, conjunctiva/conjunctiva-associated lymphoid tissue (CALT) investigations, and conjunctival imprints for cytology and flow cytometry (FCM) analyses.


RESULTS
Antiglaucoma eye drops induced an ocular surface cytotoxicity primarily related to the concentration of their common BAC preservative ((0.02%BAC+)latanoprost> (0.015%BAC+)travoprost> (0.005%BAC+)bimatoprost). LCEm did not induce any obvious signs of toxicity on the rabbit ocular surface with results similar to those of PBS; moreover, the conjunctiva/CALT and cornea had almost normal aspects.


CONCLUSIONS
These in vivo and ex vivo toxicological procedures performed in an acute stress model confirmed the ocular surface cytotoxicity of BAC-containing antiglaucomatous eye drop solutions. The new formulation, LCEm, was well tolerated without inducing ocular surface damage or CALT activation. The cationic emulsion of latanoprost will most likely have fewer long-term adverse effects on the ocular surface than formulations containing toxic preservative BAC and may improve long-term tolerance over BAC-containing antiglaucomatous topical treatments.
Liang
Hong
H
Paris Descartes University, Faculty of Biological and Pharmacological Sciences, Department of Toxicology, Paris, France.
Baudouin
Christophe
C
Faure
Marie-Odile
MO
Lambert
Grégory
G
Brignole-Baudouin
Françoise
F
D000818:Animals; D002412:Cations; D003228:Conjunctiva / Q000166:cytology / Q000187:drug effects; D004655:Emulsions; D005123:Eye / Q000166:cytology / Q000187:drug effects*; D005434:Flow Cytometry; D007150:Immunohistochemistry; D000077338:Latanoprost; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008221:Lymphoid Tissue / Q000187:drug effects; D008297:Male; D018613:Microscopy, Confocal; D009883:Ophthalmic Solutions / Q000494:pharmacology*; D011453:Prostaglandins / Q000494:pharmacology*; D011461:Prostaglandins F, Synthetic / Q000009:adverse effects* / Q000633:toxicity*; D011817:Rabbits; D018675:Toxicity Tests
D002412:Cations; D004655:Emulsions; D009883:Ophthalmic Solutions; D011453:Prostaglandins; D011461:Prostaglandins F, Synthetic; D000077338:Latanoprost; D017493:Leukocyte Common Antigens