The effect of 0.1% topical ciclosporin a for 12-weeks on the ocular surface innate and adaptive immune response in dry eye disease: protocol for a randomized controlled clinical trial

Background Ocular surface immune cells and pro-inflammatory cytokines have been reported to be increased in Dry eye disease (DED). Immunosuppressive agents such as topical cyclosporine A (CsA) can inhibit dendritic cell and T cell activation. However, CsA’s impact on ocular surface immune responses and tear cytokines has not been systematically studied. This paper describes a clinical trial protocol to investigate the effects of 0.1% CsA plus mineral oil eye drops, versus mineral oil eye drops alone on the ocular surface immune response in DED.Methods This two-arm examiner-masked randomized controlled trial will enrol 60 eligible participants with moderate-to-severe DED. Participants will be randomized (1:1) either into the CsA plus mineral oil eye drops or mineral oil eye drops alone group and evaluated at baseline, 4-weeks and 12-weeks. Corneal immune cells will be assessed using static in vivo confocal microscopy (IVCM) for total corneal epithelial immune cells and with a novel technique, functional-IVCM (Fun-IVCM), to differentiate corneal epithelial immune cell subsets (i.e. putative T cells from dendritic cells). Conjunctival immune cells will be phenotyped using impression cytology and flow cytometry (CD45, CD3, CD4, CD8, CD11c, HLA-DR). Tear cytokine analyses will be conducted for IL-2, IL-4, IL-6, IL-12, IL-17, IL-23, IFN- γ using a multiplex bead assay.Conclusion The clinical trial combines ocular intravital imaging, immune cell phenotyping and cytokine analysis to advance knowledge on the application of CsA in moderate-to-severe DED. It may also establish new immune cell parameters as biomarkers for monitoring the efficacy of anti-inflammatory DED treatments. Trial registration: ClinicalTrials.gov, NCT06898853.