Abstract:AIM: To evaluate 3% diquafosol ophthalmic solution on ocular surface parameters and the alterations of lipid and muco-aqueous layer in tear film of patients with visual display terminal (VDT)-associated dry eye disease (DED). METHODS: This study included patients with VDT-associated DED. It was a prospective single-arm interventional clinical trial. Patients were provided with 3% diquafosol ophthalmic solution for 3mo and were followed up in 1, 2 and 3mo after treatment. Tear breakup time (TBUT), ocular surface staining score, and ocular surface disease index (OSDI) score were ocular surface characteristics. Lipid layer thickness (LLT), tear meniscus height (TMH), and mucin mRNA expression levels (MUC1, MUC4, MUC5AC, MUC16, and MUC20) were used to measure changes in the tear film. The LipiView interferometer was used to measure the partial blink rate (PBR). RESULTS: Sixty-eight eyes of 68 participants (54 females; mean age 25.12±4.10y; mean spherical equivalent -4.35±2.69 D) were enrolled. Compared with the pre-treatment, OSDI scores and TBUT improved significantly at all follow-up time points (all P<0.01), and TMH increased significantly at 1 and 3mo (P<0.01, P<0.001, respectively). Conjunctival lissamine green staining improved only at 2mo (P<0.05), while corneal fluorescein staining showed no significant changes. Overall LLT remained unchanged, but the PBR<1 subgroup exhibited significant LLT elevation at 3mo (P<0.05), unlike the PBR=1 subgroup. Conjunctival mRNA expression of MUC1, MUC5AC, MUC16, and MUC20 was significantly upregulated at 1 and 3mo (all P<0.01), and MUC4 expression increased significantly only at 1mo (P<0.001). CONCLUSION: In patients with VDT-associated DED, 3% diquafosol ophthalmic solution dramatically reduced symptoms and enhanced tear film stability by promoting ocular surface muco-aqueous secretion. Patients with better blinking habits (PBR<1) demonstrate greater LLT improvement than those with poorer habits.