**Background:** Dry eye is a multifactorial disease characterized by unstable tear film, symptoms of discomfort, and potential ocular surface damage. Current treatments include artificial tears that provide temporary relief but do not fully restore tear film stability or repair corneal epithelial damage. Diquafosol sodium, a P2Y2 receptor agonist, promotes secretion of aqueous, mucin, and lipid components of tears, thereby restoring tear film stability. Previous phase III trials in China and Singapore demonstrated efficacy in patients aged 21–70 years, but real-world data in broader populations, especially elderly patients, were lacking. This phase IV study aimed to evaluate the efficacy and safety of 3% diquafosol sodium eye drops in a large, diverse Chinese cohort with mild to moderate dry eye.
**Methods:** This was a phase IV, open-label, single-arm, multicenter study conducted across 30 clinical centers in China. From March 2019 to January 2022, 3,099 patients were screened; 3,000 met inclusion criteria and were enrolled. Inclusion criteria: age ≥18 years, at least one subjective dry eye symptom (dryness, foreign body sensation, burning, fatigue, discomfort, vision fluctuation), tear break-up time (BUT) ≤5 seconds or Schirmer I test (without anesthesia) ≤10 mm/5 min, and positive corneal fluorescein staining (CFS) using NEI scoring. Exclusion criteria included legal blindness, allergy to study components, recent use of other eye drops or contact lenses, and pregnancy. Patients received 3% diquafosol sodium eye drops (Diquas®) one drop six times daily for 4 weeks. Follow-up examinations were performed at baseline, 2 weeks, and 4 weeks, including visual acuity, slit-lamp examination, BUT, CFS, Schirmer I test, and intraocular pressure. The primary efficacy endpoint was change in CFS score. Secondary endpoints included BUT, Schirmer I, visual acuity, and safety (adverse drug reactions, ADRs). Statistical analysis used SAS 9.4; comparisons were made with t-tests or ANOVA as appropriate.
**Key Results:** A total of 2,864 patients (95.47%) completed the trial, and 2,660 adhered to the protocol. Baseline demographics: mean age distribution – Group A (18–29 years, n=593), Group B (30–59 years, n=1,543), Group C (≥60 years, n=524); 680 males, 1,980 females. Baseline CFS score was 3.4 ± 2.25, BUT 4.14 ± 1.85 sec, Schirmer I 9.10 ± 8.14 mm/5 min. After 2 weeks of treatment, CFS decreased to 1.7 ± 1.83 (p<0.05 vs baseline), and after 4 weeks to 1.0 ± 1.54 (p<0.05). At 4 weeks, 90.65% of patients showed improvement in CFS, and 51.90% had negative staining. The elderly group (≥60 years) showed the greatest improvement: CFS change at 4 weeks was −3.02 (95% CI −3.21, −2.84) vs −1.84 in Group A and −2.41 in Group B (p<0.05). BUT improved from 4.14 ± 1.85 sec at baseline to 6.50 ± 3.01 sec at 4 weeks (p<0.05), with the elderly group again showing the largest increase (+2.76 sec, 95% CI 2.52, 3.01). Schirmer I results also improved significantly in all age groups (p<0.05). No significant gender differences were observed. Patients with prior artificial tear use, history of eye surgery, or endocrine disorders also showed significant improvements. Safety: ADRs occurred in 185 patients (6.17%), with 233 ocular ADRs (6.00%) and 11 systemic ADRs (0.30%). The most common ocular ADRs were eye discharge (1.93%), eye pain (1.30%), foreign body sensation (0.87%), and eye pruritus (0.67%). Of all ADRs, 91.80% were mild, 8.20% moderate, and none severe. Recovery occurred in 89.75% of cases, with an average recovery time of 15.6 ± 13.13 days. A total of 41 patients (1.37%) discontinued due to ADRs. Visual acuity and intraocular pressure showed slight but statistically significant improvements (p<0.05).
**Clinical Implications:** This large real-world study confirms that 3% diquafosol sodium eye drops are effective and safe for treating mild to moderate dry eye in Chinese patients, with rapid onset of action (within 2 weeks) and continued improvement at 4 weeks. The drug promotes corneal epithelial repair, increases tear secretion, and prolongs tear film stability. Notably, elderly patients (≥60 years) derived the greatest benefit, which is clinically important given the high prevalence and severity of dry eye in this population. The low incidence of mostly mild, reversible ADRs supports its favorable safety profile. These findings provide robust evidence for the use of diquafosol as a first-line or alternative therapy for dry eye, especially in elderly patients and those who have not responded adequately to conventional artificial tears.