Comparison of the short-term effects on the human corneal surface of topical timolol maleate with and without benzalkonium chloride

J Glaucoma. 2003 Dec;12(6):486-90. doi: 10.1097/00061198-200312000-00008.


Purpose: To compare the short-term effects of timolol maleate with and without preservative (0.005% benzalkonium chloride) on pre-corneal tear film stability and corneal epithelial barrier function.

Subjects and methods: The study population consisted of 20 healthy volunteers. To obtain baseline values, 7 days before the experiment the non-invasive breakup time of the pre-corneal tear film was measured using a tear specular microscope; corneal fluorescein uptake was measured with a fluorophotometer. Unpreserved or preserved 0.5% timolol was applied to one eye; the contralateral eye was exposed to the other drug. At 30 minutes after instillation, the pre-study tests were repeated.

Results: Preserved timolol did, while unpreserved timolol did not, significantly reduce the non-invasive breakup time from the baseline values (baseline and post-exposure values 11.4 and 6.8 seconds, respectively, P = 0.008 for preserved timolol, and 11.7 vs. 11.0 seconds, P = 0.55 for unpreserved timolol). Corneal fluorescein uptake, on the other hand, was significantly increased upon exposure to either preserved or unpreserved timolol (baseline and post-exposure values 37.5 and 82.0 ng/ml, P < 0.001 for preserved timolol, and 35.4 vs. 57.6 ng/ml, P < 0.001 for unpreserved timolol). Preserved timolol exerted the greater effect (P = 0.028).

Conclusions: Exposure to preserved timolol resulted in significant instability in the pre-corneal tear film. Moreover, it disrupted the corneal epithelial barrier function to a greater degree than unpreserved timolol. The elimination of preservatives may be desirable in efforts to protect the integrity of the corneal surface and its interaction with the tear film.

Publication types

  • Comparative Study

MeSH terms

  • Administration, Topical
  • Adrenergic beta-Antagonists / administration & dosage
  • Adrenergic beta-Antagonists / pharmacology*
  • Adult
  • Benzalkonium Compounds / administration & dosage
  • Benzalkonium Compounds / pharmacology*
  • Cornea / drug effects*
  • Cornea / metabolism
  • Drug Combinations
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism
  • Female
  • Fluorescein / metabolism
  • Fluorophotometry
  • Humans
  • Male
  • Middle Aged
  • Ophthalmic Solutions
  • Preservatives, Pharmaceutical / administration & dosage
  • Preservatives, Pharmaceutical / pharmacology*
  • Prospective Studies
  • Tears / metabolism
  • Timolol / administration & dosage
  • Timolol / pharmacology*


  • Adrenergic beta-Antagonists
  • Benzalkonium Compounds
  • Drug Combinations
  • Ophthalmic Solutions
  • Preservatives, Pharmaceutical
  • Timolol
  • Fluorescein