Three-Times-Daily 5% Diquafosol Versus Six-Times-Daily 3% Diquafosol for Dry Eye Disease: A Randomized, Double-Masked, Multicenter Phase 3 Noninferiority Trial

Purpose: This study aimed to investigate the safety and effectiveness of 5% diquafosol eye drops for treating dry eye disease (DED) in a double-blind, multicenter, phase 3 noninferiority clinical trial. Methods: Of the 271 participants randomized to receive either 5% diquafosol (TJO-083) 3 times per day or an active control [3% sodium diquafosol; Diquas-S (DQS)] 6 times per day for 12 weeks, 268 were included in the full analysis set. The outcome measures included corneal fluorescein staining score (CFS), conjunctival staining score, tear break-up time (TBUT), the Schirmer test, Ocular Surface Disease Index (OSDI), and adverse events (AEs). Results: Baseline demographic and clinical characteristics related to DED did not differ significantly between the 2 groups. At 4 weeks after treatment, mean CFS (95% CI: −0.316, 0.199), TBUT, OSDI scores, and Schirmer test values improved significantly from baseline and were maintained through 12 weeks of treatment in both groups. In between-group analysis, no statistically significant differences were observed in the CFS ( P = 0.6548), TBUT, OSDI scores, and Schirmer values. Regarding tolerability evaluation scores, blurred vision was more frequent in the TJO-083 group ( P = 0.0022). In contrast, photophobia occurred more frequently in the DQS group ( P = 0.0323). Conclusions: This study found that 5% diquafosol demonstrated clinical efficacy and AE rates equivalent to those of 3% diquafosol, despite a halved dosing frequency. Therefore, 5% diquafosol may offer a more convenient treatment option for DED patients by reducing frequency. Clinical Trial Registration: The trial was registered with the U.S. National Library of Medicine at ClinicalTrials.gov (identifier: NCT06427031).