Improvement of the ocular surface using hypotonic 0.4% hyaluronic acid drops in keratoconjunctivitis sicca

Eye (Lond). 2000 Dec;14(Pt 6):892-8. doi: 10.1038/eye.2000.244.


Background: The ocular surface changes of keratoconjunctivitis sicca (KCS) could be the result of the effect of an altered tear film on the epithelial environment.

Purpose: To evaluate the possibility of improving the environmental conditions of the ocular surface by lowering tear osmolarity, increasing tear film volume and stabilising the tear film. Also, to study the effect of such an improvement on the epithelial cells of the ocular surface.

Methods: One hundred and thirty-five patients with a diagnosis of KCS were treated on a randomised basis with either unpreserved hypotonic 0.4% hyaluronic acid (HHA) eye drops or 0.3% hydroxypropylmethylcellulose plus 0.1% Dextran 70 (HPMC) eye drops 6 times a day for 60 or 90 days. In all patients a Schirmer I test, break-up time (BUT), ocular surface staining with 1% Bengal Rose, or 2% fluorescein, as well as subjective symptoms, were recorded before and 15, 30 and 60 days after the beginning of the study. Patients were divided into three subgroups and the effect of the treatment was studied using three different techniques: the tear ferning test, conjunctival impression cytology and tear osmolarity measurement.

Results: Improvements in BUT, vital staining, Schirmer I and symptoms were recorded in both groups of treatment, with significant differences for patients treated with 0.4% HHA. On day 60, 30 min after installation: tear ferning patterns changed from 100% pathological (types III-IV) to 93% physiological (types I-II) in the 0.4% HHA group and from 100% pathological to 78% physiological in the 0.3% HPMC group (p < 0.01 between groups). Tear osmolarity shifted from 353 +/- 23 to 305 +/- 6 mosmol/l in the 0.4% HHA group and from 346 +/- 15 to 336 +/- 8 mosmol/l in the 0.3% HPMC group (p < 0.001 between groups). On day 90, the impression cytology score improved from 1.2 to 1.9 in the 0.4% HHA group while it did not change in the 0.3% HPMC group (p < 0.05 between groups).

Conclusion: In KCS appropriate treatment with a hypotonic 0.4% HHA tear substitute can change the tear environment and results in improvement of the epithelial conditions of the ocular surface.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Adjuvants, Immunologic / pharmacology
  • Adjuvants, Immunologic / therapeutic use*
  • Adult
  • Aged
  • Epithelium, Corneal / drug effects
  • Female
  • Humans
  • Hyaluronic Acid / pharmacology
  • Hyaluronic Acid / therapeutic use*
  • Hypotonic Solutions
  • Keratoconjunctivitis Sicca / drug therapy*
  • Male
  • Middle Aged
  • Multicenter Studies as Topic
  • Ophthalmic Solutions
  • Tears / drug effects
  • Treatment Outcome


  • Adjuvants, Immunologic
  • Hypotonic Solutions
  • Ophthalmic Solutions
  • Hyaluronic Acid