One-Year Tear Proteomic Alterations with Topical Cyclosporine-A 0.1% Emulsion in Patients with Allogeneic Stem Cell Transplant

Ocular graft-versus-host disease (GVHD) is a frequent complication after allogeneic hematopoietic stem cell transplant (allo-HSCT). The prophylactic effects and underlying mechanisms of long-term topical cyclosporine-A (CsA) on tear proteomic profiles remain unclear. To profile the longitudinal tear proteomics in allo-HSCT patients received daily topical CsA 0.1% cationic emulsion, and to explore the relationship between tear proteomics and clinical phenotypes. This longitudinal interventional study included 24 participants received 0.1% CsA eye drops from 3 to 5 wk before HSCT to 12 mo after HSCT. Ocular surface clinical examinations were performed, and tear samples were collected at pre-HSCT, at HSCT, 3, 6, and 12 mo post-HSCT. Patients were then categorized into responder (R) group and non-responder (NR) group based on the conjunctival T cell analysis from impression cytology. Tear proteomics was analyzed using liquid chromatography-tandem mass spectrometry, and proteomic analysis was conducted using a data-independent acquisition method, followed by linear mixed model regression analysis. A total of 2570 tear proteins were identified in this study. Significant differences in the expression of AGT, HRG, and SERPIND1 were observed between R and NR groups prior to HSCT (all P < .05). COL6A1, RAB11B, and APOA2 were significantly differentially expressed between R and NR groups post-HSCT (all P < .05). These identified proteins were clustered into 6 modules by WGCNA, which are associated with immune response, neutrophil extracellular trap formation, and glycan biosynthesis and metabolism. These modules demonstrated a significant correlation with ocular clinical manifestations, including Schirmer test values, tear osmolarity, and conjunctival redness (all P < .05). Prophylactic treatment with CsA 0.1% cationic emulsion eye drops may prevent the development of ocular GVHD after allo-HSCT by modulating immunoinflammatory proteins and associated pathways.