Purpose  

The purpose of the study was to compare the systemic safety and risk–benefit ratio of 0.1% timolol hydrogel and 0.5% aqueous timolol eye drops in the treatment of glaucoma.

Methods  

An 8-week randomised, double-blind, cross-over, multicentre study. A total of 25 patients with primary open-angle glaucoma, exfoliation glaucoma, or ocular hypertension was enrolled. After completing a wash-out period, patients were randomly chosen to receive either 0.1% timolol hydrogel once daily or 0.5% aqueous timolol eye drops twice daily. Intraocular pressure and heart rate during rest and exercise, head-up tilt test results, spirometry readings, and plasma concentrations of timolol were recorded. The risk–benefit ratio was determined by calculating the ratio between several heart rate endpoints and the change in intraocular pressure (IOP).

Results  

The mean drug-induced change in the peak heart rate during exercise was −13.5 beats/min (SD 7.6) in the 0.5% aqueous timolol group and −5.1 beats/min (SD 6.7) in the 0.1% timolol hydrogel group (P<0.001; 95% CI 4.06–12.18). There was no significant difference in the IOP-reducing efficacy between these compounds. The risk–benefit ratio was significantly improved when 0.1% timolol hydrogel was used, compared with 0.5% aqueous timolol in the exercise test. In the head-up tilt test the risk–benefit ratio was significantly improved at rest (P<0.05), at 1 min (P<0.05) and at 5 min (P<0.001) after patients had received 0.1% timolol hydrogel. There were, however, no differences in spirometry readings. After patients had been treated with 0.1% timolol hydrogel, plasma concentrations of timolol were 1/6 (at peak) and 1/50 (at trough) of those of 0.5% aqueous timolol.

Conclusions  

Drug-induced changes in the peak heart rate, and head-up tilt test results as well as plasma concentrations of timolol, were significantly more pronounced after treatment with 0.5% aqueous timolol than with 0.1% timolol hydrogel. Because of the statistically similar IOP-reducing efficacy of these formulations the risk–benefit ratio was significantly improved when patients used 0.1% timolol hydrogel instead of 0.5% aqueous timolol.