- Purpose: To evaluate symptom relief in patients with dry eye disease (DED) following a single drop of propylene glycol-hydroxypropyl guar (PG-HPG) nanoemulsion (Systane® Complete) lubricant eye drops. Methods: This was a Phase IV, multicenter, open-label, interventional study in adult patients with DED of aqueous-deficient, evaporative, and mixed subtypes. Patients instilled one drop of PG-HPG in each eye at Day 1. Endpoints included change from baseline in dry eye symptom and soothing sensation scores on Day 1 at 0, 4, and 8 hours post-dose. Symptom scores were assessed on a 0-10 scale (0=no symptoms; 10=worst imaginable symptom). Tolerability of the drop was assessed based on assessment score on Day 1 following instillation for overall cohort and by DED subtype. Results: A total of 134 patients received treatment (mean age: 56.6 years; female: 75.4%). Median changes from baseline at Day 1 in dry eye symptom scores were -1.0 (95% confidence interval [CI]:-3.0,-1.0), -2.0 (95% CI:-3.0,-2.0), and -2.0 (95% CI:-2.0,-1.0) at 0, 4, and 8 hours respectively. Subgroup analysis showed a median change from baseline in dry eye symptom score of -2 (95% CI:-3.0,-1.0) for aqueous-deficient and evaporative subtypes and -1 (95% CI:-3.0,-1.0) for mixed subtype at 8 hours. Median soothing sensation scores were 3 at 0 and 4 hours and 3.5 at 8 hours, with a range of 0-10. Median (range) tolerability assessment scores were 0 (0-8) for burning sensation, stinging sensation, blurring, and 0 (0-10) for foreign body sensation. Tolerability assessment scores by DED subtype confirmed that the majority of patients reported scores in the range of 0-5 for all components and in all subgroups analyzed. Conclusion: Our study demonstrated that PG-HPG nanoemulsion provided instant/immediate and sustained symptom relief for 8 hours post-single application and was well tolerated in patients with DED, demonstrated by their responses on each of the assessment scales.