N. Orzalesi

Purpose. To compare around-the-clock intraoculare pressure (IOP) reduction induced by timolol, latanoprost, dorzolamide, brimonidine, and a fixed combination of timolol and dorzolamide in patients with primary open angle glaucoma (POAG) and ocular hypertension (OHT).

Methods. In two cross-over trials, 20 patients with POAG and 20 with OHT were treated with timolol, latanoprost, dorzolamide, brimonidine and a fixed combination of timolol and dorzolamide, for one month. Treatment sequence was randomized. All patients underwent around-the-clock tonometric curves: a baseline and after one month of treatment with each trial drug. IOP was measured at 3, 6, 9, 12 a.m., and at 3, 6, 9, 12 p.m. with a handheld electronic tonometer with the patient in supine and sitting positions, and with a Goldmann applanation tonometer by two well-trained evaluators masked to treatment assignment. Sample size was estimated assuming a difference in mean IOP of 2.5 mmHg as clinically relevant, a=0.05, 1-b=0.90, and a sd=2 mmHg.

Results. All drugs significantly reduced IOP as compared with baseline at all times except for timolol at 3 a.m. and for brimonidine at midnight, 3, and 6 a.m.; Latanoprost was more effective in lowering IOP as compared with timolol at 3, 6, 9 a.m. (p<0.03) and at 6, 12 p.m. (p<0.05), with dorzolamide at 9, 12 a.m. (p<0.03) and at 3, 6 p.m. (p<0.04), with brimonidine at 3, 6 a.m. and at 3, 6 p.m.. Timolol was more effective than dorzolamide at noon (p<0.05), while dorzolamide performed better than timolol at 3 a.m. (p<0.05). The combination of timolol with dorzolamide was more effecting as compared with brimonidine at 3, 9 a.m. (p<0.04) and at 3, 6 p.m. (p<0.05), with latanoprost at 9 a.m. (p<0.05). Conclusions. Latanoprost and the combination of timolol with dorzolamide seemed to provide uniform circadian IOP reduction whereas timolol and brimonidine were less effective in lowering IOP particularly during nighttime hours. Dorzolamide was less effective than latanoprost, though provided significant nocturnal IOP reduction.