title: Comparison of the short-term effects on the human corneal surface of topical timolol maleate with and without benzalkonium chloride.
abstract: OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Department of Ophthalmology, Kyoto Prefectural University of medicine, Kyoto, Japan. tishibas@ophth.kpu-m.ac.jp
authors.forename: Takeshi
authors.initials: T
authors.lastname: Ishibashi
authors.forename: Norihiko
authors.initials: N
authors.lastname: Yokoi
authors.forename: Shigeru
authors.initials: S
authors.lastname: Kinoshita
mesh_terms: D000287:Administration, Topical; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D000328:Adult; D001548:Benzalkonium Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D003315:Cornea / Q000187:drug effects* / Q000378:metabolism; D004338:Drug Combinations; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D005260:Female; D019793:Fluorescein / Q000378:metabolism; D015590:Fluorophotometry; D006801:Humans; D008297:Male; D008875:Middle Aged; D009883:Ophthalmic Solutions; D011310:Preservatives, Pharmaceutical / Q000008:administration & dosage / Q000494:pharmacology*; D011446:Prospective Studies; D013666:Tears / Q000378:metabolism; D013999:Timolol / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D000319:Adrenergic beta-Antagonists; D001548:Benzalkonium Compounds; D004338:Drug Combinations; D009883:Ophthalmic Solutions; D011310:Preservatives, Pharmaceutical; D013999:Timolol; D019793:Fluorescein