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Vatinee Y Bunya, Karen Revere, Simone Iwabe, Maxwell Pistilli, Karla Carlisle, Mina Massaro-Giordano, Gustavo D Aguirre; Safety and Efficacy of Topical Tocilizumab in a Canine Model. Invest. Ophthalmol. Vis. Sci. 2014;55(13):1485.
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Tocilizumab is an interleukin-6 (IL-6) inhibitor that has been used to treat rheumatologic and autoimmune conditions. Inflammatory mediators, especially cytokines, have been implicated in dry eye and other ocular surface disease. Tocilizumab represents a novel therapeutic agent in the form of a topically administered eye drop for local suppression of cytokine activity on the ocular surface. This was a prospective study completed in a canine model aimed at establishing the safety of tocilizumab eye drops.
The right eye of 10 dogs was treated with one drop of 1% tocilizumab three times per day and the left eye with one drop of topical saline three times per day for four weeks. Hand held slit lamp examination of the ocular surface, as well as Schirmer testing, was performed at baseline and then weekly. Schirmer strips were analyzed to quantitate cytokine levels. Conjunctival biopsies from both eyes were collected at week four, and mRNA levels of cytokines were evaluated. Blood was sampled at baseline and at the end of treatment for complete blood count, basic metabolic panel, and liver function tests in order to monitor for systemic toxicity. Median levels of six cytokines in the tear film (IFN-γ, TNF-α, IL-2, IL-6, IL-8, IL-10) and their mRNA were compared among tociliziumab-treated and control eyes. The sign test was used to assess for differences in cytokine and mRNA levels between treated and untreated eyes.
There was no evidence of ocular inflammation or irritation on weekly slit lamp exams in the tocilizumab treated eyes. Blood samples did not show any signs of systemic toxicity after treatment. At four weeks, conjunctival biopsies and Schirmer strips showed no significant differences in either tear cytokine or mRNA levels for IFN-γ, TNF-α, IL-2, IL-6 and IL-10. However, tear and mRNA levels of IL-8 were significantly higher in the treated eye compared to the untreated eye in all but one of the dogs (p-value=0.02 and 0.04, respectively).
In this small pilot study, there was no evidence of ocular or systemic toxicity from tocilizumab eye drops over a four week time period. In the future, studies involving dogs with ocular surface disease would be helpful in further characterizing the effect of topical tocilizumab on the ocular surface.
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