Comparison of 0.1%, 0.18%, and 0.3% Hyaluronic Acid Eye Drops in the Treatment of Experimental Dry Eye

J Ocul Pharmacol Ther. 2018 Oct;34(8):557-564. doi: 10.1089/jop.2018.0032. Epub 2018 Jul 23.


Purpose: To compare the efficacy of 0.1%, 0.18%, and 0.3% hyaluronic acid (HA) artificial tear in the treatment of experimental dry eye (EDE).

Methods: EDE was established in female C57BL/6 mice through an air draft and subcutaneous scopolamine injection. The mice were divided into 5 groups according to topical treatment regimens (n = 5 each): EDE control, balanced salt solution (BSS), preservative-free 0.1% HA, 0.18% HA, and 0.3% HA. The tear film break-up time (TBUT) and corneal fluorescein staining scores were measured 5, 10, 14, 21, and 28 days after treatment. The corneal smoothness scores were measured. In addition, periodic acid-Schiff (PAS) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining were performed.

Results: The values for TBUT and corneal fluorescein staining showed greater improvements in all the HA groups (P < 0.05) than in the EDE and BSS groups after 10 days of treatment. Mice treated with 0.3% HA showed a more significant improvement in all clinical parameters than did those in the EDE control, BSS, 0.1% HA, and 0.18% HA groups (all P < 0.05) after 28 days of treatment. The goblet cell counts were higher in the 0.3% and 0.18% HA groups than in the 0.1% HA group. The number of TUNEL-positive cells was the lowest in the 0.3% HA group.

Conclusions: In EDE, 0.3% HA artificial tears are more effective than the 0.1% and 0.18% HA in improving tear film instability and ocular surface staining and irregularity, in increasing the number of conjunctival goblet cells, and in decreasing corneal epithelial apoptosis.

Keywords: 0.1% hyaluronic acid; 0.18% hyaluronic acid; 0.3% hyaluronic acid; dry eye disease.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Dry Eye Syndromes / drug therapy*
  • Dry Eye Syndromes / pathology
  • Female
  • Hyaluronic Acid / administration & dosage
  • Hyaluronic Acid / therapeutic use*
  • Mice
  • Mice, Inbred C57BL
  • Ophthalmic Solutions / administration & dosage
  • Ophthalmic Solutions / therapeutic use*
  • Tears / drug effects


  • Ophthalmic Solutions
  • Hyaluronic Acid