Comparative study of 0.1% hyaluronic acid versus 0.5% carboxymethylcellulose in patients with dry eye associated with moderate keratitis or keratoconjunctivitis

Abstract

Background

Eye drops containing 0.1% hyaluronic acid (HA) and 0.5% carboxymethylcellulose (CMC) applied one drop three times a day per affected eye were compared in patients with moderate keratitis or keratoconjunctivitis related to dry eye disease (DED).

Patients and methods

This was a prospective, randomized, multicenter, Phase IIIB noninferiority study, with a single-masked phase in parallel mode with two groups over 84 days. The primary efficacy outcome was change in ocular surface (OS) staining between day 0 (D0) and day 35 (D35). The conjunctiva and cornea were stained with lissamine green and fluorescein. Secondary efficacy measures at day 84 (D84) were OS-staining score (SS), ocular comfort index, tear-film breakup time and how patients and investigators rated treatment efficacy and safety.

Results

At D35, 0.1% HA achieved a 46.6% reduction in OS-SS (−2.03±1.35 points, n=39 patients) and 0.5% CMC treatment, followed by a 34.9% reduction (−1.61±1.69 points, n=38 patients) compared to D0. At D84, the SS difference to D0 improved by −2.58±1.45 points (−59.2%) for 0.1% HA and −2.59±2.27 points (−54.4%) for 0.5% CMC. Ocular comfort-index scores improved, with significantly lower (better) values for stinging and itching on D84 for 0.1% HA. Patients assessed treatment with 0.1% HA as significantly better than 0.5% CMC (Likert scale, 4.82 vs 3.97; P=0.018). Four adverse events (AEs) occurred in four of 41 patients (9.8%) treated with 0.1% HA, and three AEs in two of 39 patients (5.1%) treated with 0.5% CMC. No serious AEs were noted.

Conclusion

DED signs and symptoms of DED significantly improved with both eye drops. OS staining improved >54% at D84. Treatment was well tolerated, with only minor AEs <10%. 0.1% HA and 0.5% CMC were equally safe and effective. Significant and nonsignificant results were constantly in favor of 0.1% HA.

Keywords:

• hyaluronate
• carboxymethylcellulose
• eye drops
• fluorescein
• lissamine green

Acknowledgments

Ursapharm funded this clinical study. The authors wish to thank Klaus Rudolph of Rudolph Consulting (Freiburg, Germany) for preparing the manuscript and for editorial support, funded by Ursapharm. The authors thank the French study centers involved in this study.

Disclosure

DG is an employee of Ursapharm. MC is the CEO of Laboratoires Delbert. He was appointed as CRO for this clinical study by Ursapharm. JMP reports no conflicts of interest in this work.