Efficacy and Tolerance of Dorzolamide/Timolol Combination With and Without Preservatives in Patients With Elevated Intraocular Pressure

Methodology and Study Progress

A total of 261 patients with open-angle glaucoma (11.5% of participants) or elevated intraocular pressure (IOP) (94.6% of participants) over the age of 21 were enrolled in a double-blind, randomized study. Initially, patients used eye drops containing 0.5% timolol twice a day (at 9:00 AM and before bed) for 3 weeks. On the last day, their intraocular pressure was measured using a Goldmann applanation tonometer before the morning application and 2 hours after it.

Patients with ocular hypertension (intraocular pressure ≥ 22 mmHg) at this examination were then randomized into 2 groups: 131 subjects (58% men, average age 56.0 years) used a fixed combination of 2% dorzolamide/0.5% timolol without preservatives (PF), and the remaining 130 (33.1% men, average age 54.8 years) used a combination with preservatives (PC; 0.0075% benzalkonium chloride) twice a day for 12 weeks. IOP was measured just before starting the treatment and 2 hours after application. It was then monitored after 2, 6, and 12 weeks of use in the same manner. During each visit, visual acuity was assessed, side effects (SEs) were evaluated, and perimeter exams were conducted before and after the treatment period.

Results

At the beginning of the study, the initial average IOP values measured were: before the first application of the eye drops containing the dorzolamide/timolol combination 23 mmHg in both groups, and 2 hours after the first application 21.2 mmHg in the PF group and 21.4 mmHg in the PC group.

After 12 weeks of use, the IOP values before the morning application were 20.8 mmHg (a reduction of 2.9 mmHg or 12.3% compared to the initial value) in the PF group and 21.1 mmHg (a reduction of 2.6 mmHg or 11.0%) in the PC group. Two hours after the drops were administered, the IOP values were: 18.1 mmHg (a reduction of 3.1 mmHg or 14.0%) in the PF group and 18.2 mmHg (a reduction of 3.2 mmHg or 14.3%) in the PC group.

The difference in IOP between the two groups (PF and PC) after 12 weeks of treatment was not statistically significant. Just before application, it was −0.31 mmHg (95% confidence interval [CI] −0.86 to 0.23) and 2 hours after application 0.14 mmHg (95% CI −0.39 to 0.67). The average difference in IOP between the PF and PC groups at any measurement during weeks 2, 6, and 12 was never more than 0.5 mmHg.

Seven patients did not complete the study (all due to SEs). No significant difference was observed in the number of patients with one or more adverse events in both groups, although it was numerically slightly lower in the PF group. The most frequently reported side effects were eye irritation, such as burning or stinging, which occurred in 16.0% of patients in the PF group and 21.5% of participants in the PC group. Dysgeusia was observed in 3.1% and 5.4% of patients, respectively. The most common adverse ocular finding was punctate epithelial erosion (16.8% vs. 23.8% of subjects using the PF vs. PC combination; p > 0.05).

Conclusion

Both PF and PC combinations of dorzolamide/timolol effectively reduce IOP in patients with open-angle glaucoma. The study supports the hypothesis that the PF combination of dorzolamide/timolol is equivalent to the PC combination. There is no evidence to suggest that adding a preservative increases efficacy; on the contrary, it may cause eye irritation or other adverse reactions in some patients.

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Source: Shedden A., Adamsons I. A., Getson A. J. et al. Comparison of the efficacy and tolerability of preservative-free and preservative-containing formulations of the dorzolamide/timolol fixed combination (COSOPT™) in patients with elevated intraocular pressure in a randomized clinical trial. Graefes Arch Clin Exp Ophthalmol 2010; 248 (12): 1757−1764, doi: 10.1007/s00417-010-1397-7.