Comparison of the ocular tolerability of a latanoprost cationic emulsion versus conventional formulations of prostaglandins: an in vivo toxicity assay

[摘要] Purpose: Using an established rabbittoxicological model, this in vivo study compared the ocularcytotoxicity of four topical intraocular pressure (IOP)-loweringagents: the commercial benzalkonium chloride (BAC)-containing solutionsof 0.005% latanoprost, 0.004% travoprost, 0.03% bimatoprost (containing0.02%, 0.015%, and 0.005% BAC, respectively), and 0.005% latanoprost ina new cationic emulsion (LCEm) formulation. Methods: Thirty adult male New Zealandalbino rabbits were used in this study. They were randomly divided intofive groups: 50 µl of sterile phosphate-buffered saline (PBS) alongwith each formulation was applied onto rabbit eyes 15 times at 5 minintervals. The ocular surface changes were investigated using slit-lampexamination, corneal in vivo confocal microscopy (IVCM) for cornea,limbus, conjunctiva/conjunctiva-associated lymphoid tissue (CALT)investigations, and conjunctival imprints for cytology and flowcytometry (FCM) analyses. Results: Antiglaucoma eye drops inducedan ocular surface cytotoxicity primarily related to the concentrationof their common BAC preservative (0.02%BAC+latanoprost> 0.015%BAC+travoprost>0.005%BAC+bimatoprost). LCEm did not induce any obvioussigns of toxicity on the rabbit ocular surface with results similar tothose of PBS; moreover, the conjunctiva/CALT and cornea had almostnormal aspects. Conclusions: These in vivo and ex vivotoxicological procedures performed in an acute stress model confirmedthe ocular surface cytotoxicity of BAC-containing antiglaucomatous eyedrop solutions. The new formulation, LCEm, was well tolerated withoutinducing ocular surface damage or CALT activation. The cationicemulsion of latanoprost will most likely have fewer long-term adverseeffects on the ocular surface than formulations containing toxicpreservative BAC and may improve long-term tolerance overBAC-containing antiglaucomatous topical treatments.

[学科分类] 生物化学/生物物理