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Jing-Feng Huang, Rolla Yafawi, Yi Zhang, Min H. Zhang, Kay D. Rittenhouse, Michael McDowell, S-H M. Liew, Scott R. Cooper, Eve H. Pickering; Modulation of HLA-DR On Conjunctival Cells And Inflammatory Mediators In Tears In Dry Eye Patients By CP-690,550, A Selective Inhibitor of The JAK Family. Invest. Ophthalmol. Vis. Sci. 2011;52(14):3824.
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© ARVO (1962-2015); The Authors (2016-present)
To evaluate treatment effect of CP-690,550, a selective inhibitor of JAK family, on ocular surface inflammation in dry eye using HLA-DR and inflammatory markers on conjunctival cells and tears.
In a phase I/II prospective, randomized, vehicle- and comparator-controlled, masked, multicenter, clinical trial, patients meeting the inclusion and exclusion criteria received various topical doses of CP-690,550, vehicle control, or comparator for 8 weeks. 82 dry eye patients of the overall study participated in an exploratory biomarker substudy (n=~10 per treatment group) with conjunctival impression cytology (IC) and tear fluids collected at baseline and end of an 8-week treatment period. Conjunctival cells were analyzed by flow cytometry for HLA-DR, and tear fluids by multiplex bead analysis for concentrations of 29 tear protein markers. Main outcome measures of the biomarker substudy include (a) change in expression of cellular inflammatory marker (HLA-DR) on conjunctival cells (b) change in selected tear protein marker(s) from baseline at Week 8.
HLA-DR expression were highly correlated between left eyes and right eyes (r = 0.79 at baseline, and 0.78 at Week 8, P<0.0001) among patients with IC specimens from each eye collected and analyzed independently. Changes from baseline in HLA-DR were also correlated between left and right eyes (r=0.57, P<0.0001). Treatment effects of CP-690,550 were detected: reduction in inflammation was observed as significant decreases, compared to baseline (P<0.20), in HLA-DR levels in the IC specimens and in tear levels of several inflammatory markers (e.g. MMP-3, 9, IL-17, IL-1β and MCP-1), in patients treated with 0.005% QD (HLA-DR and tear markers) and 0.003% BID (in HLA-DR only), while patients in the vehicle group did not show these changes.
Analysis of HLA-DR expression on conjunctival cells and inflammatory mediators in tears has utility for measuring treatment effects on ocular surface inflammation in dry eye clinical study. Topical CP-690,550 modulates ocular surface inflammation in dry eye as evidenced by reduction of HLA-DR in IC, and reduction of MMPs, IL-17, IL-1β and MCP-1 in tears.
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