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Hong Liang, Karima KESSAL, Christophe Baudouin, Philippe Daull, Jean-Sebastien Garrigue, Françoise Baudouin; EVALUATION OF BAK-FREE PROSTAGLANDIN ANALOGUES IN A RABBIT MODEL OF REPEATED INSTILLATIONS. Invest. Ophthalmol. Vis. Sci. 2014;55(13):4892.
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Repeated instillations of benzalkonium chloride (BAK)-preserved eye drops for the treatment of chronic diseases were reported to induce ocular surface toxic side effects, the severity of which being correlated to the BAK-concentration and to the number of instilled drops. Here, we used a rabbit model of repeated instillations to assess the ocular surface tolerance of several BAK-free prostaglandin analogues available on the market.
New Zealand rabbit eyes (n=6/gp) were treated with 15 instillations (one instillation every 5 min) of preservative-free (PF) 0.0015% tafluprost, 0.03% bimatoprost, or 0.005% latanoprost, as well as BAK-free preserved 0.004% travoprost. Phosphate buffered saline (PBS) and 0.02% BAK solution served as positive and toxic controls, respectively. Observations were scored using ocular irritation criteria and in vivo confocal microscopy (IVCM) was used for detailed examination of the eye, corneal epithelium, stroma, limbus, and conjunctiva-associated lymphoid tissue (CALT) structures, as well as goblet cell density. Inflammatory cell infiltration was assessed by immunohistochemistry (CD45, RLA-DR).
The ocular irritation scores demonstrated that all BAK-free formulations were generally well tolerated. Among these, some slight differences without statistical significance were noticed suggesting that the excipient composition and/or the prostaglandin analogues themselves may affect the tolerance of the formulations, as evidenced by the level of conjunctival hyperemia. IVCM analysis confirmed the good tolerance of the different formulations in the cornea as well as in CALT structures with lower density of infiltrating inflammatory cells in the PF-formulations versus BAK. These results were confirmed by immunohistochemistry. .
This repeated instillation toxicity model confirmed that BAK-free formulations are very well tolerated by the rabbit eye. In PF formulations, the excipient composition is not neutral and may modulate the performance of the formulation in the long term.
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