Fixed versus pro-re-nata dosing of polyethylene glycol/propylene glycol-based artificial tears: A randomized clinical trial

Abstract

Purpose : Artificial tears are usually dosed on an as needed basis (PRN). This study evaluated the clinical benefits of a fixed (4 times daily/QID) versus PRN dosing of polyethylene glycol/propylene glycol (PEG/PG)-based artificial tears (Systane^®Ultra) in patients with dry eye disease (DED).

Methods : This was a phase IV, prospective, randomized (1:2), multicenter, observer-masked, active-control, parallel-group study (NCT02446015). Patients with DED, ≥18 years old, with a total ocular staining score (TOSS) of ≥4 to ≤9 on the 15-point Oxford scale were eligible. Patients instilled 1 drop of PEG/PG either QID or PRN for 28 days. The primary endpoint was the change from baseline in the TOSS score at Day 28 (superiority of QID to PRN was established if the upper limit of one-sided 95% confidence interval [CI] for least square mean difference [QID−PRN] was <0). Change from baseline in Impact of Dry Eye on Everyday Life (IDEEL) scores for symptom-bother (SB), treatment effectiveness (TE) and inconvenience (TI) were also assessed.

Results : Of the 101 patients randomized, 97 (QID=34; PRN=63) received treatment; mean age±SD was 50.4±17.7 years and 79.4% of patients were female. At Day 28, TOSS score decreased for both groups; the TOSS score change (mean±SE) from baseline was -1.19±0.26 in QID and -0.94±0.24 PRN groups (treatment difference:-0.26±0.28; 95% CI=-∞ to 0.21; p=0.184). At Day 28, the change from baseline in IDEEL SB score (mean±SE) was -7.0±2.01 in QID and -2.94±1.85 in PRN groups with a treatment difference of -4.06±2.25 (p=0.037). The treatment difference between QID and PRN groups for IDEEL TE score was 2.28±3.84 (p=0.277) and IDEEL TI score was -8.8±3.21 (p=0.996). A negative correlation was observed for change from baseline in TOSS score and (1) TE score (r=-0.405; p=0.019), and (2) TI score (r=-0.239; p=0.18), only in the QID group. Adverse events (AEs) were reported by 2.9% and 3.2% of patients in the QID and the PRN groups, respectively. No serious AEs were reported.

Conclusions : PEG/PG eye drops, instilled QID or PRN, were well tolerated and reduced ocular staining (TOSS). While patient-rated inconvenience was higher, the SB score improved notably with QID dosing suggesting that the regular use of artificial tears may provide better symptomatic relief. Further evaluation of fixed dosing may be helpful to determine best dosing for symptom relief in DED.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.