Application of the fixed combination 2% dorzolamide hydrochloride/0.5% timolol maleate ophthalmic solution (Cosopt, Merck, Sharp & Dohme) resulted in a significant decrease in IOP 6 and 8 weeks after the onset of therapy in patients with ocular hypertension or primary open-angle glaucoma whose IOP had not been controlled by 0.5% timolol alone. The daytime and nighttime IOP values also were significantly reduced at the same time points compared with baseline.
The daytime and nighttime IOP values also were significantly reduced at the same time points compared with baseline, according to Robert M. Feldman, MD, who spoke at the annual meeting of the Association for Research in Vision and Ophthalmology.
"Many patients with open-angle glaucoma have progressive visual field deterioration despite having IOP apparently well-controlled with medication. That may be due to the diurnal IOP fluctuations, resulting in peaks and troughs that are not apparent when the IOP is measured once during normal office hours," said Dr. Feldman, clinical professor, deputy chairman, and director of the glaucoma service, Department of Ophthalmology and Visual Science, University of Texas–Houston.
He and his colleagues performed a randomized, double-masked, parallel group, multicenter clinical trial in which enrolled patients had IOP that exceeded 22 mm Hg after 6 weeks of timolol therapy. Following a washout period of 6 weeks, patients with an increase in IOP of 3 mm Hg or more were randomly assigned to receive either dorzolamide/timolol maleate ophthalmic solution or timolol alone (117 patients and 115 patients, respectively) for 8 weeks. IOP was measured at baseline and at 6 and 8 weeks. IOP was measured at the following eight time points: 6, 8, and 10 p.m.; 2, 6, 8, and 10 a.m.; and 2 p.m., Dr. Feldman explained.
The primary end point was the mean change in IOP from baseline after 8 weeks with the dorzolamide/timolol combination for all eight of the time points at which the IOP was measured over 24 hours.
Following 8 weeks of treatment, Dr. Feldman reported significant (p < 0.001) IOP reductions at each of the eight diurnal time points of measurement for dorzolamide/timolol (p < 0.001 for each time point) compared with baseline. The mean IOP (%) reductions from baseline ranged from –3.23 mm Hg (13.37%) at 2 a.m. to –6.75 mm Hg (26.21%) at 10 a.m. When compared with timolol alone, the combination therapy resulted in significantly greater IOP reductions at 10 a.m. (difference = –1.30 mm Hg; 95% CI: –2.14, –0.46; [p = 0.003]) and 2 p.m. (difference = –1.07 mm Hg; 95% CI: –1.94, –0.20; [p = 0.016]). Significant treatment differences were not seen at other time points.