Abstract
Abstract: :
Purpose:To evaluate and compare the short-term effect of 0.5% timolol maleate with and without preservative (0.005% benzalkonium chloride) on precorneal tear film stability and corneal epithelial barrier function. Methods:Enrolled in this study were 11 healthy volunteers [age: 31 - 56 yrs (44.0 9.9 yrs: Mean SD)]. Individuals with external eye disease, eye drop medication, contact lenses, and/or circulatory or respiratory disease were excluded from this study. Seven days before study commencement, precorneal tear film non-invasive breakup time (NIBUT) was measured using a tear specular microscope (DR-1®, Kowa, Japan); corneal fluorescein uptake was measured by a fluorophotometer (FL-500®, Kowa, Japan). Preservative-free or preserved 0.5% timolol was instilled in masked fashion to the right eye of each subject; the other topical drug was instilled to the left eye. At 30 minutes after instillation, the same examinations were reperformed. Results:Preservative-free timolol did not significantly change the NIBUT (baseline: 11.5 7.6 sec.; after instillation: 10.9 5.4 sec.). In contrast, NIBUT was significantly reduced from the baseline by preserved timolol (baseline: 10.3 7.1 sec.; after instillation: 5.0 2.9 sec., p = 0.03). Corneal fluorescein uptake, on the other hand, was significantly increased after instillation of both topical drugs [preservative-free timolol (baseline: 35.3 23.1 ng/ml; after instillation: 59.0 29.3 ng/ml, p = 0.01), preserved timolol (baseline: 43.6 22.2 ng/ml; after instillation: 87.4 40.0 ng/ml, p = 0.003)]. Conclusion:Preserved timolol caused significant instability in precorneal tear film after instillation, though preservative-free timolol did not affect precorneal tear film stability. However, both preserved and preservative-free timolol significantly disrupted corneal epithelial barrier function. These results suggest that the precorneal tear film was destabilized by benzalkonium chloride and the corneal epithelial barrier function was disrupted mainly by timolol. Preservative-free drugs could be of potential benefit in protecting ocular surface integrity.
Keywords: 390 drug toxicity/drug effects • 372 cornea: epithelium • 514 pharmacology