PURPOSE: Lifitegrast ophthalmic solution 5% (Xiidra), a leukocyte function-associated antigen-1 (LFA-1) antagonist, is indicated for treatment of signs and symptoms of dry eye disease (DED). This study assessed how lifitegrast reduces CD4+ T cell migration to the cornea and mediates T cell alterations in draining lymph nodes (dLNs) in a murine model of DED.

METHODS: DED was induced in 6–8-week-old mice by exposure to the controlled environmental chamber and subcutaneous injections of scopolamine. Mice were treated with topical lifitegrast (or normal saline [NS]) 3 times daily. DED severity was assessed with corneal fluorescein score (CFS) and T cells were quantified by flow cytometry (FC) of corneal single cell suspensions. Expression of chemokine receptors on T cells from submandibular dLNs was assessed by FC and RT-PCR. T cells from DED mice treated with lifitegrast or NS were sorted and adoptively transferred to RAG knockout mice, and DED severity and T cells (in pooled corneas and dLNs) were assessed after 5 days.

RESULTS: CFS was significantly reduced and tear secretion was significantly improved after 15 days of lifitegrast versus NS treatment in DED mice (P<0.05). compared with ns treatment lifitegrast treatment resulted in reduction of ifn secreting cd4 t cell th1 recruitment to the cornea and significant reductions in cxcr3 and ccr4 chemokine receptor expression by fc and cxcr3 mrna levels in cd4 t cells from dlns p><0.05). adoptively transferred cd4 t cells from lifitegrast-treated versus ns-treated ded mice to rag knockout mice resulted in significant reduction of cfs p><0.05) and 60 reduction in cd4 t cell recruitment into cornea with no change in recruitment in dlns.>

CONCLUSIONS: These results demonstrate that topical application of lifitegrast has an effect beyond the ocular surface, directly on dLNs, and show that topical drug application impacts the efferent arm of immunity as well.