A Prospective Cohort Study of Clinical Outcomes, Tear Cytokines and Proteomic Profiles Following Insular Infraorbital Neurovascular Pedicle Labial Salivary Gland Transplantation for Severe Dry Eye Disease

PURPOSE: Insular infraorbital neurovascular pedicle labial salivary gland transplantation (IINPLSGT) is an innovative procedure for the treatment of severe dry eye disease (DED). We aim to evaluate changes in clinical parameters, tear osmolarity, inflammatory cytokine levels, and proteomic profiles following IINPLSGT for severe dry eye patients. METHODS: A single-center, prospective exploratory study was conducted in 10 patients diagnosed with severe DED who underwent IINPLSGT surgery. The Ocular Surface Disease Index (OSDI), tear break-up time (TBUT), Schirmer I test (SIt), corneal fluorescein staining (CFS), ocular manifestations and tear osmolarity were assessed before and after treatment. Tear inflammatory cytokines were analyzed using ELISA; Tear proteomes were characterized using liquid chromatography mass spectrometry. RESULTS: < .05). A total of 111 differentially expressed proteins (DEPs) were identified between preoperative and postoperative samples. Protein dysregulation was associated with inflammatory response. Upregulated proteins were related to mitochondrial energy metabolism and cellular repair. Enrichment analysis revealed that these DEPs were involved in extracellular vesicle, actin-myosin filament sliding and antigen binding. Kyoto Encyclopedia of Genes and Genomes pathway analysis highlighted key roles of the PI3K/AKT, MAPK signaling pathways, cytokine-cytokine receptor interaction and DNA replication. CONCLUSIONS: IINPLSGT was associated with improvements in symptoms and clinical signs of severe DED, accompanied by reductions in tear osmolarity and inflammatory cytokine levels during follow-up. Postoperative tear proteomic analysis further suggests that the protein profiles of secretions from saliva may partially overlap with natural tear protein profiles. These exploratory findings highlight the therapeutic potential of IINPLSGT, but warrant confirmation in larger, controlled studies. TRIAL REGISTRATION NUMBER: ChiCTR2200056015.