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C. B. Toris, S. Fan, T. V. Johnson, III, G. L. Zhan, C. B. Camras; Comparison of Aqueous Humor Dynamics at One versus Six Weeks of Treatment With Timolol or Latanoprost in Patients With Ocular Hypertension. Invest. Ophthalmol. Vis. Sci. 2009;50(13):2031.
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To compare the mechanisms whereby topical timolol and latanoprost reduce intraocular pressure (IOP) in patients with ocular hypertension at 1 versus 6 weeks.
Thirty patients completed the 6-visit study following screening and 6 weeks of washout. On baseline day, intraocular pressure (IOP; 9 AM and 11:30 AM), was determined by pneumatonometry, aqueous flow and outflow facility by fluorophotometry and outflow facility again by tonography. Uveoscleral outflow was calculated mathematically using the Goldmann equation and an episcleral venous pressure of 11 mmHg. Uveoscleral outflow calculations were made twice, once with tonographic outflow facility and once with fluorophotometric outflow facility in the Goldmann equation. In a randomized, double-masked fashion, both eyes of each patient were treated for six weeks either with timolol 0.5% twice-daily or with vehicle in the morning and latanoprost 0.005% in the evening. Measurements were repeated on weeks 1 and 6 of dosing. After another six week washout, the opposite drugs were administered in a crossover manner. One and 6 weeks of treatment were compared with the appropriate baseline and the two drugs were compared at each respective visit using appropriate statistical tests. The left eye was arbitrarily chosen for the analysis as the two eyes were not different at baseline.
Both drugs significantly (p<0.001) reduced IOP at 1 and 6 weeks of treatment with latanoprost producing a greater IOP (11:30 AM) reduction than timolol (by 1.5 mmHg) at week 1 (p=0.04). Timolol reduced aqueous flow by 27% at week 1 (p<0.001) and 16% at week 6 (p<0.007). Latanoprost increased uveoscleral outflow several fold at each visit (p<0.05). Neither drug had consistent effects on outflow facility compared to baseline. Neither timolol nor latanoprost showed a detectable change in aqueous humor dynamics at week 6 compared to week 1. Timolol showed no change in IOP efficacy over time but latanoprost showed a 1 mmHg increase in IOP (11:30 AM, p=0.04) at week 6 compared to week 1.
Timolol and latanoprost significantly reduce IOP by different mechanisms. Timolol reduces aqueous flow whereas latanoprost increases uveoscleral outflow. Significant differences in mechanisms at 1 versus 6 weeks of treatment were not demonstrated. Consistent outflow facility effects were not detected in this study.
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