Tear Cytokine Changes up to One Year After Allogeneic Hematopoietic Stem Cell Transplant: Effect of Daily Topical Cyclosporine-A 0.1% Emulsion

Purpose: To profile tear cytokine changes in Allogeneic Hematopoietic Stem Cell Transplant (HSCT) patients after instillation of daily topical cyclosporine-A 0.1% cationic emulsion. Methods: Participants in a longitudinal study were given cyclosporine eyedrops daily from 3 to 5 weeks before and 3 months, 6 months, and 12 months post-HSCT. The outcomes included tear cytokine concentration assayed by the Proximity Extension Assay O-linked target 96 platform. The patients were divided into two groups: Group 1 (n = 8 conjunctival CD4 cells responding to cyclosporine) and Group 2 (n = 5 conjunctival CD4 cells not suppressed after cyclosporine, where patients were non-compliant with cyclosporine). All participants had a standardized clinical examination, including meibomian gland evaluation and tear breakup times. Results: The levels of 38 cytokines/chemokines showed significant changes (p < 0.05) over time, and in many, the elevation was marked at one year. These include gamma-interferon, CXCL9, CCL3, and CCL4 (all p < 0.0001). For gamma-interferon, there was significant interaction between group and time at 1 year (p = 0.022), where the cytokine was significantly suppressed in Group 1. Four other cytokines showed significant group and time interaction at 1 year: FGF23, FGF5, LIFR, and Enrage (all p < 0.05). All patients had either withdrawal or a reduction in systemic immunomodulation between 6 months and 1 year. We found several cytokines to be associated with changes in tear osmolarity or symptom scores. Conclusions: HSCT induces significant elevation of 38 tear cytokines/chemokines even without the occurrence of ocular graft-versus-host disease when systemic immunosuppression is reduced within the first year. Topical daily cyclosporine eyedrops can reduce some pro-inflammatory tear cytokines.