Aimns-The purpose of this study was to assess whether the preservative benzalkonium chloride (BAC 0.01%) present in timolol induced a decrease in basal tear turnover and a deterioration ofprecorneal tear film in patients with glaucoma and ocular hypertension using topical timolol. Methods In a previous study7 we demonstrated a 36% lower mean basal tear turnover in patients with glaucoma using timolol+BAC in comparison with that of healthy controls. The preservative BAC is suggested as a possible cause for this decrease in tear turnover. The present follow up study was initiated to verify this assumption.In this study the tear turnover and break up time (BUT) of the precorneal tear film of patients with open angle glaucoma and ocular hypertension were evaluated when using timolol+BAC and subsequently when using timolol-BAC. In this way we expected to find out if BAC could be held responsible for a decrease in tear production and for a deterioration of tear film stability in patients with glaucoma who use timolol+ BAC. The study was set up in such a way that the same patient was measured when using timolol+BAC as well as when using timolol-BAC in order to avoid the effect of interindividual spread in tear turnover values. Note that the fluorophotometric measurement of tear turnover with a computer fluorophotometer is a quantitative method for the determination of tear production7 and is, because of its objectivity and reproducibility, suitable for unbiased outcomes of the measurements. The precorneal tear film integrity determined by the tear film BUT and the subjective acceptability of timolol+BAC and timolol-BAC were also assessed. Material and methods PATIENTS

Epithelial permeability and autofluorescence of the cornea were determined by fluorophotometry in 21 patients with open-angle glaucoma or ocular hypertension using timolol medication with the preservative benzalkonium chloride (BAC) and 2 weeks after changing to timolol medication without BAC. The investigation was performed to determine whether removal of BAC would reduce toxic effects on the cornea and complaints of sensations of burning or dry eye. Corneal epithelial permeability decreased significantly after changing medication (mean decrease per patient 27%, P = 0.025). Corneal autofluorescence increased significantly after changing medication suggesting an alteration in corneal metabolism (mean increase per patient 6%, P = 0.003). Timolol without BAC was found to be as effective as timolol with BAC in reducing intraocular pressure (P = 0.4). Removal of BAC from timolol resulted in an improvement of corneal epithelial barrier function and in a reduction of complaints. The improvement was found to be proportional to the duration of the preceding BAC-containing therapy.

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This paper reviews previous work done to demonstrate the clinical relevance of the measurement of bluegreen autofluorescence and light transmission of the ocular lens (=450 to 550 nm). These can be determined quantitatively with fluorophotometry in a few seconds. Autofluorescence and transmission values are determined in healthy volunteers, in patients with insulin-dependent diabetes mellitus, and in patients with untreated glaucoma or untreated ocular hypertension. The lens autofluorescence of healthy volunteers increased linearly and transmission decreased exponentially with age. Each year of diabetes induced an increase of autofluorescence equal to one extra year of age. Untreated glaucoma or ocular hypertension had no significant effect on lens autofluorescence and transmission. Increased autofluorescence and decreased transmission values in comparison with values of a healthy population are proved to be indicative for an increased risk of developing cataract and the clinical usefulness of these measures is demonstrated. Diabetes is a risk factor for developing cataract while untreated glaucoma or ocular hypertension is not. © 1996 Society of Photo-Optical Instrumentation Engineers.

(1) open-angle glaucoma or ocular hypertension alone does not affect corneal epithelial permeability; (2) daily instillation of timolol causes impairment of the corneal epithelial barrier; (3) open-angle glaucoma or ocular hypertension are likely to induce an increase of corneal autofluorescence.