Performance and Safety of a Sodium Hyaluronate Tear Substitute with Polyethylene Glycol in Dry Eye Disease: A Multicenter, Investigator-Masked, Randomized, Noninferiority Trial

J Ocul Pharmacol Ther. 2022 Nov;38(9):607-616. doi: 10.1089/jop.2022.0048. Epub 2022 Oct 21.


Purpose: To compare the performance and safety of 2 tear substitutes containing sodium hyaluronate (SH); one containing 0.15% SH and polyethylene glycol (PEG) 8000, and the other containing 0.18% SH. Methods: In this multicenter, randomized, investigator-masked, noninferiority trial, 83 patients with moderate or severe dry eye disease underwent a 2-week washout, and were then randomly assigned (1:1) to receive SH plus PEG tear substitute (n = 45) or comparator SH tear substitute (n = 38) 3-6 times daily for 3 months. The primary performance endpoint was the change from baseline in the ocular surface fluorescein staining (OSFS) score on day 28 in the per-protocol (PP) population, according to the 15-point Oxford Scheme, with a noninferiority margin of 2. Results: Both groups improved significantly in terms of signs and symptoms. Among the 78 patients without major protocol deviations (the PP population), the OSFS score decreased by 2.9 ± 2.0 on day 28 from 5.4 ± 1.3 at baseline in the SH plus PEG group and by 2.3 ± 2.2 from 5.2 ± 1.4 in the comparator group (95% confidence interval of the difference: -1.2 to 0.3), demonstrating noninferiority. On day 90, the improvement in OSFS scores was significantly greater in the SH plus PEG group (P = 0.0002). The safety profiles were satisfactory in both groups. Conclusion: SH plus PEG tear substitute was noninferior to SH tear substitute in the studied population and may provide additional benefits in the long term. ID: NCT02975102.

Keywords: clinical study; dry eye; ocular lubricant; polyethylene glycol; sodium hyaluronate; tear substitute.

Publication types

  • Randomized Controlled Trial
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Dry Eye Syndromes* / drug therapy
  • Humans
  • Hyaluronic Acid* / adverse effects
  • Ophthalmic Solutions / adverse effects
  • Polyethylene Glycols / adverse effects
  • Tears


  • Hyaluronic Acid
  • polyethylene glycol 8000
  • Polyethylene Glycols
  • Ophthalmic Solutions

Associated data