Long-term efficacy and safety of bimatoprost for intraocular pressure lowering in glaucoma and ocular hypertension: year 4.

BACKGROUND: Bimatoprost 0.03% has been shown to consistently reduce mean intraocular pressure (IOP) more than timolol 0.5% over 2 years. To further evaluate long-term safety and efficacy, once-daily bimatoprost 0.03% was compared with timolol 0.5% twice daily through year 4. METHODS: In this multicentre, double-masked, randomised, controlled trial, glaucoma and ocular hypertension patients (n = 152) who completed phase III bimatoprost trials through month 36 were enrolled in a study extension through month 48. Patients randomised to bimatoprost once daily (n = 78) or timolol twice daily (n = 35) continued on the same regimen for a fourth year. Patients randomised to bimatoprost twice daily had been switched to bimatoprost once daily dosing at month 24 (bimatoprost twice daily/once daily treatment group), and continued with once daily dosing through month 48 (n = 39). IOP was measured at 08:00 and 10:00 at months 39, 42, 45 and 48. Safety measures included adverse events, biomicroscopy, ophthalmoscopy, visual acuity and visual field. RESULTS: Baseline IOP was comparable among groups. During year 4, mean IOP reductions from baseline were 7.0 to 8.1 mm Hg with bimatoprost once daily and 6.5 to 7.9 mm Hg with bimatoprost twice daily/once daily, significantly greater than with timolol twice daily (3.8 to 5.8 mm Hg, p< or =0.035) at all measurements. Over 4 years, the mean IOP reduction from baseline at 08:00 and 10:00 was 1.9 to 3.9 mm Hg (35% to 100%) greater with bimatoprost once daily than with timolol (p< or =0.013). Low IOPs were achieved by more bimatoprost than timolol patients (p< or =0.042). No safety concerns developed during long-term bimatoprost treatment; two patients in the timolol treatment group discontinued after month 36 because of adverse events. The most common treatment-related adverse event in the bimatoprost treatment groups was conjunctival hyperaemia. CONCLUSION: Bimatoprost once daily provided sustained IOP lowering greater than timolol twice daily and was well tolerated over long-term use.

[Comparison of the effectiveness and safety of levobunolol and timolol in ocular hypertension and chronic open-angle glaucoma]. / Vergleich der Wirksamkeit und Anwendungssicherheit von Levobunolol und Timolol bei okulärer Hypertension und chronischem Offenwinkelglaukom.

Twenty-six patients with open-angle glaucoma or ocular hypertension were studied in a concomitant double-masked clinical trial lasting three months, in which the ocular hypotensive efficacy and safety of levobunolol (0.5%) and timolol (0.5%), topically administered twice daily, were compared. At all follow-up examinations there was a significant decrease in mean intraocular pressure from baseline in both treatment groups, with no significant difference between them in this regard. Few changes were seen in either treatment group in cup/disk ratio, visual fields, visual acuity, biomicroscopy, or ophthalmoscopy. In both groups slight decreases in mean blood pressure were observed. Levobunolol and timolol were similarly effective and safe in reducing intraocular pressure in patients with chronic open-angle glaucoma and those with ocular hypertension.

Long-term evaluation of 0.25% levobunolol and timolol for therapy for elevated intraocular pressure.

In a one-year, double-masked, randomized study, the ocular hypotensive efficacy of twice-daily treatment with 0.25% levobunolol hydrochloride or timolol maleate was evaluated in 78 patients with glaucoma or ocular hypertension (phase 1). If intraocular pressure (IOP) was not well controlled during the study, the concentration of medication was increased to 0.5%, and the patient was followed up for an additional three months (phase 2). During phase 1, the mean IOP was reduced by 4.6 mm Hg in the timolol treatment group and by 5.1 mm Hg in the levobunolol treatment group. Seventy-one percent (29/41) of the patients in the timolol treatment group and 70% (26/37) of the patients in the levobunolol treatment group successfully completed phase 1. Of those patients who required the higher concentration of medication, 89% (8/11) in the timolol treatment group and 75% (3/4) in the levobunolol treatment group successfully completed phase 2. Higher concentration, however, did not produce greater IOP reduction. No statistically or clinically significant differences between the groups were noted in any of the efficacy or safety variables evaluated.

Effect of changing medication regimens in glaucoma patients.

When glaucoma medication fails to adequately control intraocular pressure (IOP), a second medication is frequently added. Before adding a second drug to patients whose IOP was no longer controlled by 0.5% timolol, we tested the effect of switching to another beta blocker, levobunolol (0.5 or 1%). We also evaluated the effect of study participation on compliance in the control group continuing to receive 0.5% timolol. In each treatment group, the IOP of approximately 30-40% of the patients was successfully controlled for the 3-month study period. The remaining patients did not exhibit significant pressure reductions and were dropped from the study within 2 weeks. We concluded that (1) the results of 'switch' studies without a control group must be interpreted carefully, and (2) the initiation of a 'new regimen' with an equieffective beta blocker may be sufficient to increase compliance and thereby control IOP.

Treatment of elevated intraocular pressure with concurrent levobunolol and pilocarpine.

Between July 1983 and January 1986, 54 patients with open-angle glaucoma or ocular hypertension were treated for 3 months with 2% pilocarpine hydrochloride (given four times daily) and one of two beta-adrenoceptor blocking drugs, levobunolol hydrochloride (0.5% [17 patients] or 1% [19 patients]) or 0.5% timolol maleate (18 patients), given twice daily. Before entry into the study all patients had had stable intraocular pressure (IOP) with treatment with 0.5% timolol and 2% pilocarpine. Stable IOP was successfully maintained in up to 88% of the patients in the two levobunolol-pilocarpine groups and in 83% of those in the timolol-pilocarpine group. Two patients experienced adverse reactions: one, who received timolol and pilocarpine, suffered blepharoconjunctivitis, and the other, who received 1% levobunolol and pilocarpine, experienced bradycardia. The results indicate that the levobunolol-pilocarpine regimens were as safe and effective as the timolol-pilocarpine regimen in stabilizing IOP.