Efficacy and safety of the fixed combinations latanoprost/timolol versus dorzolamide/timolol in patients with elevated intraocular pressure

PURPOSE: To compare the efficacy and safety of the fixed combination of latanoprost and timolol with those of the fixed combination of dorzolamide and timolol in patients with elevated intraocular pressure (IOP). DESIGN: Three-month, randomized, parallel group, evaluator-masked, multicenter study. PARTICIPANTS: Patients with primary open-angle glaucoma or ocular hypertension with elevated IOP insufficiently responsive to monotherapy; 253 randomized: 125 to receive a fixed combination of latanoprost 0.005% and timolol 0.5% once daily, and 128 to receive a fixed combination of dorzolamide 2% and timolol 0.5% twice daily. METHODS: Visits were at screening (current ocular hypotensive therapy was discontinued), 2 weeks (if needed for an IOP-safety check), baseline (randomization), and after 1 and 3 months of therapy. Intraocular pressure was measured in triplicate at 8 am, 12 pm, and 4 pm at each study visit, and diurnal IOP was calculated as the mean value of these recordings. Adverse events were recorded at each visit. MAIN OUTCOME MEASURE: The difference between treatment groups in the change in mean diurnal IOP from baseline to month 3. RESULTS: Mean diurnal IOP levels were similar at baseline. Mean (+/- standard error of the mean) reductions in diurnal IOP from baseline to month 3 were 9.4+/-0.27 mmHg in the latanoprost/timolol fixed-combination group, versus 8.4+/-0.26 mmHg in patients receiving the dorzolamide/timolol fixed combination. The mean difference in diurnal IOP reduction between treatments was 1.00 mmHg (95% confidence interval, 0.31-1.69; P = 0.005) in favor of the latanoprost/timolol fixed combination. Both treatments generally were well tolerated. CONCLUSIONS: The fixed combination of latanoprost and timolol was slightly more effective than that of dorzolamide and timolol in reducing mean diurnal IOP, and both treatments were generally well tolerated.     

A comparison of the fixed combination of latanoprost and timolol with its individual components

PURPOSE: To evaluate the intraocular pressure (IOP)-reducing effect of the fixed combination of 0.005% latanoprost and 0.5% timolol compared with the individual monotherapies. METHODS: A 6-month, randomised, double-masked, controlled multicentre study followed by 6 months of open-label treatment was carried out in patients with glaucoma or ocular hypertension with pre-enrolment IOP >/=25 mmHg on glaucoma medication or >/=30 mmHg if untreated. Following a 2- to 4-week run-in period on timolol twice daily, 436 patients were randomised: 140 to fixed combination therapy once daily in the morning, 147 to latanoprost once daily in the morning and 149 to timolol twice daily. During the open-label extension, patients received fixed combination drug once daily in the morning. RESULTS: The difference in mean change from baseline in diurnal IOP from week 2 to week 26 was -1.2 mmHg between fixed combination and latanoprost (95% confidence interval. CI: -1.8 to -0.5; P<0.001; repeated-measures analysis of covariance). The corresponding difference between fixed combination and timolol was -1.9 mmHg (95% CI -2.5 to -1.2; P<0.001). No long-term drift in IOP was detected in patients treated for 12 months with fixed combination. All treatments were well tolerated with no major differences among groups in the incidence of clinically relevant adverse events. CONCLUSION: The fixed combination of 0.005% latanoprost and 0.5% timolol administered once daily in the morning for 6 months was more effective in reducing IOP than the individual components alone and was effective over 12 months.     

Efficacy and tolerability of the dorzolamide 2%/timolol 0.5% combination (COSOPT) versus 0.005% (XALATAN) in the treatment of ocular hypertension or glaucoma: results from two randomized clinical trials

PURPOSE: To compare the efficacy of the fixed dorzolamide 2%/timolol 0.5% combination (COSOPT) versus latanoprost 0.005% (XALATAN). METHODS: Two 3-month, parallel group, randomized, observer-masked and patient-masked, multicentre, clinical trials were performed in patients with ocular hypertension or open-angle glaucoma. Study 1 (n=256) was conducted in the United States and Study 2 (n=288) was conducted in Europe/Israel. Patients could be included whether or not they were currently taking ocular hypotensive therapy, and regardless of the effectiveness of any previous therapy. Patients were washed out from their usual ocular hypotensive medications and then those with a baseline intraocular pressure (IOP) >/= 24 mmHg were randomized to either the dorzolamide/timolol combination eye drops twice daily or latanoprost eye drops once daily in both eyes. Efficacy was assessed by daytime diurnal IOP (the mean of measurements made at 0800, 1000, 1400 and 1600 h). RESULTS: At baseline, the mean daytime diurnal IOP was 26.1 mmHg in the dorzolamide/timolol combination group versus 25.6 mmHg in the latanoprost group in Study 1, and 25.3 mmHg in the dorzolamide/timolol combination group versus 24.7 mmHg in the latanoprost group in Study 2. After 3 months, the mean daytime diurnal IOP was 18.9 mmHg for the dorzolamide/timolol combination versus 18.4 mmHg for latanoprost in Study 1, and 17.4 mmHg for the dorzolamide/timolol combination versus 17.5 for latanoprost in Study 2. The difference between treatments in mean IOP change at 3 months was -0.04 mmHg [95% confidence interval (CI) -0.85, 0.77] in Study 1, and -0.57 mmHg (95% CI -1.31, 0.16) in Study 2. The probability that the true difference lay between -1.5 and 1.5 mmHg, the predefined bounds for equivalence, was >0.950 in both studies. Both treatments were well tolerated over 3 months, although ocular stinging occurred more frequently with the dorzolamide/timolol combination. CONCLUSIONS: The dorzolamide/timolol combination and latanoprost were equally effective at lowering IOP.     

A comparison of the effects on intraocular pressure of latanoprost 0.005% and the fixed combination of dorzolamide 2% and timolol 0.5% in patients with open-angle glaucoma

PURPOSE: To compare the effects on intraocular pressure (IOP) of latanoprost 0.005% and the fixed combination of dorzolamide 2% and timolol 0.5%. METHODS: Overall, 226 patients whose IOP was insufficiently controlled by timolol alone were randomized to receive either latanoprost once daily or the fixed combination of dorzolamide plus timolol twice daily. Intraocular pressure was measured at 10:00 am and 5:00 pm at baseline and after 3 months of treatment. RESULTS: Mean IOP was reduced from baseline in both groups (p < 0.001), with a mean +/- SEM reduction of - 4.3 +/- 0.3 mmHg (19%) for the latanoprost treatment group and - 4.0 +/- 0.3 mmHg (17%) for the dorzolamide plus timolol treatment group. The two therapies were similarly effective in lowering IOP levels (mean difference in reduction: - 0.4 +/- 0.4; 95% confidence interval: - 1.1, 0.4). CONCLUSIONS: Monotherapy with latanoprost once daily was as effective in reducing mean IOP as the fixed combination of dorzolamide plus timolol twice daily in patients with IOP insufficiently controlled by timolol alone.     

Daytime diurnal curve comparison between the fixed combinations of latanoprost 0.005%/timolol maleate 0.5% and dorzolamide 2%/timolol maleate 0.5%

PURPOSE: The diurnal efficacy and safety of the fixed combinations of latanoprost/timolol given once daily vs dorzolamide/timolol given twice daily in primary open-angle glaucoma or ocular hypertensive patients. DESIGN: A double-masked, two-centre, crossover comparison. RESULTS: In 33 patients, the mean diurnal IOP (0800-2000, measured every 2 h) for latanoprost/timolol fixed combination was 17.3+/-2.2 mmHg and for dorzolamide/timolol, the fixed combination was 17.0+/-2.0 mmHg (P = 0.36). Additionally, there was no statistical difference for individual time points following a Bonferroni correction. A bitter taste was found more frequently with the dorzolamide/timolol fixed combination (n = 6) than the latanoprost/timolol fixed combination (n = 0) (P = 0.040), while the latanoprost/timolol fixed combination demonstrated more conjunctival hyperaemia (n = 9) than the dorzolamide/timolol fixed combination (n = 2) (P = 0.045). One patient was discontinued early from the dorzolamide/timolol fixed combination due to elevated IOP. CONCLUSION: This study suggests that the daytime diurnal IOP is not statistically different between the dorzolamide/timolol fixed combination and latanoprost/timolol fixed combination in primary open-angle glaucoma and ocular hypertensive patients.     

Comparison of latanoprost monotherapy to dorzolamide combined with timolol in patients with glaucoma and ocular hypertension — A 3-month randomised study

· Background: The purpose of the study was to compare the effects on intraocular pressure (IOP) of adding dorzolamide to timolol or of switching from timolol to latanoprost monotherapy in glaucoma patients inadequately controlled on timolol. · Methods: The study was designed as a 3-month randomised, open-label, multicentre study comprising 183 patients with primary open-angle glaucoma, capsular glaucoma with IOP above 22 mmHg on treatment with one or two ocular hypotensive drugs, or ocular hypertension with IOP above 27 mmHg. After a 2- to 4-week run-in period on timolol, 0.5% twice daily, the patients were randomised to treatment with either latanoprost, 0.005% once daily, or the combination of timolol, 0.5% twice daily, and dorzolamide, 2% twice daily. The mean diurnal IOP after 3 months of treatment was compared with baseline. · Results: Switching from timolol to latanoprost reduced mean diurnal IOP by 4.5±0.2 mmHg (mean±SEM, ANCOVA; 20%), and adding dorzolamide to timolol reduced mean diurnal by 4.4±0.2 mmHg (mean±SEM, ANCOVA; 20%). No serious side effects were observed with either treatment. · Conclusion: Latanoprost monotherapy can be an alternative to combined treatment with two aqueous flow suppressors in patients whose IOP is insufficiently controlled by timolol alone. Received: 30 March 1999 Revised version received: 27 May 1999 Accepted: 7 June 1999     

Efficacy and side effects of latanoprost monotherapy compared to adding dorzolamide to timolol in patients with glaucoma and ocular hypertension--a three-month randomised study. Spanish Latanoprost Study Group

PURPOSE: To compare the efficacy and safety of latanoprost monotherapy or dorzolamide and timolol in glaucoma patients inadequately controlled on adrenergic beta-receptor antagonist therapy. METHODS: A total of 164 patients with primary open-angle glaucoma, capsular glaucoma or ocular hypertension were included in a three-month, open-label, randomised multicentre study. Patients with open-angle glaucoma were required to have IOP at least 22 mmHg and patients with ocular hypertension were required to have IOP at least 27 mmHg, on treatment with one or two ocular hypotensive drugs of which at least one had to be a beta-blocker. All patients were treated with timolol, 5 mg/ml twice daily, for a 2-4 week run-in period. They were then randomised to latanoprost, 50 microg/ml once daily, or timolol 5 mg/ml plus dorzolamide, 20 mg/ml twice daily. The difference in mean diurnal IOP change from baseline to month 3 was compared in the two groups. RESULTS: When patients were switched to latanoprost, mean diurnal IOP was reduced by 5.2 mmHg (23%) compared to 4.0 mmHg (17%) in the group in which dorzolamide was added to timolol. The difference of 1.2 mmHg was statistically significant (p = 0.005). The majority of adverse events during both treatments were judged as mild. CONCLUSIONS: The results suggest that a switch to latanoprost monotherapy is an alternative to combined treatment with timolol and dorzolamide in patients inadequately controlled on a topical adrenergic beta-receptor antagonist alone.     

Effect on intraocular pressure during 24 hours after repeated administration of the fixed combination of latanoprost 0.005% and timolol 0.5% in patients with ocular hypertension

PURPOSE: To measure the effect on intraocular pressure (IOP) for 24 hours after repeated administration of the fixed combination of latanoprost 0.005% and timolol 0.5%. METHODS: A randomized, double-masked placebo-controlled crossover study including 20 patients with ocular hypertension was carried out. Patients were randomized to treatment with the fixed combination of latanoprost and timolol or with placebo. The eyedrop was taken at 8 AM. After 2 weeks of treatment, the patients were hospitalized, and the IOP was measured at 8 AM, and thereafter every other hour until midnight, and also at 3 AM, 6 AM, and 8 A.M. After a washout period of 4 weeks, they switched to the other eyedrop, and after 2 weeks of treatment were hospitalized and the IOP measurements were repeated at the same intervals. RESULTS: The mean 24-hour IOP was 14.7 +/- 0.3 mm Hg (mean +/- standard error of the mean) for latanoprost and timolol and 19.4 +/- 0.3 mm Hg for placebo. This corresponds to a significant IOP difference of 4.7 +/- 0.4 mm Hg (95% confidence interval 3.8-5.8; P < 0.001) between the two treatments in favor of the combination. At all measured time points, except at 3 AM, the mean IOP was lower with latanoprost and timolol than with placebo. During daytime measurements the mean IOP was 13.9 +/- 0.7 mm Hg for the fixed combination and 19.5 +/- 0.7 mm Hg for the placebo. Corresponding figures at nighttime were 16.1 +/- 0.7 mm Hg and 19.2 +/- 0.7 mmHg, respectively. CONCLUSIONS: The fixed combination of latanoprost and timolol significantly reduced IOP after administration once daily for 2 weeks in patients with ocular hypertension. A reduction of IOP during a 24-hour period was seen, with a greater IOP reduction during daytime compared with nighttime. The fixed combination applied once daily could be a convenient alternative to concomitant therapy with its individual components.     

Intraocular pressure-lowering effects of latanoprost monotherapy versus latanoprost or pilocarpine in combination with timolol: a randomized, observer-masked multicenter study in patients with open-angle glaucoma. Italian Latanoprost Study Group

PURPOSE: To compare intraocular pressure (IOP) after adding either latanoprost or pilocarpine to timolol treatment or switching to latanoprost monotherapy in glaucomatous eyes in which IOP was inadequately controlled with timolol. METHODS: This 6-month randomized study comprised 148 patients with primary open-angle or pseudoexfoliation glaucoma, which was inadequately controlled with topical beta-adrenergic antagonists. After a 2- to 4-week run-in period with timolol 0.5% twice daily, patients were assigned in randomized fashion to three study groups: one group received add-on therapy of latanoprost 0.005% once daily, the second group received add-on therapy of pilocarpine 2% three times daily, and the third group switched to latanoprost 0.005% once daily. Mean diurnal IOP was measured at baseline and after 3 and 6 months of treatment. RESULTS: At 6 months, 128 patients had completed the study. Diurnal IOP was significantly reduced from baseline in all groups. Adding latanoprost to timolol treatment reduced diurnal IOP by 6.1+/-0.3 mmHg (-28%), adding pilocarpine to timolol treatment reduced diurnal IOP by 4.2+/-0.3 mmHg (-19%), and switching from timolol to latanoprost monotherapy reduced diurnal IOP by 5.5+/-0.3 mmHg (-25%). CONCLUSION: A significantly greater reduction in diurnal IOP was achieved after addition of latanoprost than after addition of pilocarpine in patients in whom IOP was not adequately controlled with timolol alone. Further, the results of this study indicate that a switch to latanoprost monotherapy can be attempted before combination treatment is initiated.     

A comparison of the fixed combination of latanoprost and timolol with the unfixed combination of brimonidine and timolol in patients with elevated intraocular pressure. A six month, evaluator masked, multicentre study in Europe

PURPOSE: To compare the intraocular pressure (IOP) reducing effect and safety of fixed combination (FC) latanoprost/timolol with unfixed combination (UFC) brimonidine/timolol in patients with increased IOP. METHODS: In this 6 month, randomised, evaluator masked, parallel group European study, patients with glaucoma or ocular hypertension and IOP > or =21 mm Hg on monotherapy or >16 mm Hg on dual therapy received either FC latanoprost/timolol at 8:00AM or UFC brimonidine/timolol at 8:00AM and 8:00PM. The primary outcome was the difference from baseline to month 6 in mean diurnal IOP reduction. RESULTS: 325 of 334 randomised patients were included in intent to treat analyses (FC latanoprost/timolol, 163; UFC brimonidine/timolol, 162). Baseline diurnal IOP levels were similar: FC latanoprost/timolol, 26.4 (SD 2.7) mm Hg; UFC brimonidine/timolol, 26.5 (SD 2.8) mm Hg (p = 0.851). At month 6, levels were 16.9 (SD 2.8) mm Hg in FC latanoprost/timolol patients and 18.2 (SD 3.1) mm Hg in UFC brimonidine/timolol patients (p<0.001). No adverse events were reported by 76.4% and 75.5% of patients receiving FC latanoprost/timolol versus UFC brimonidine/timolol, respectively. Larger proportions of brimonidine/timolol treated patients reported study medication related adverse events (18.6% v 7.3%) and discontinued study participation because of this (10.8% v 1.8%). CONCLUSION: Fixed combination latanoprost/timolol administered once daily is both more effective and better tolerated than twice daily dosing with UFC brimonidine/timolol.     

Comparison of the intraocular pressure lowering effect of latanoprost and a fixed combination of timolol-pilocarpine eye drops in patients insufficiently controlled with beta adrenergic antagonists. French Latanoprost Study Group, and the Swedish Latanoprost Study Group

AIMS: To compare the effect on intraocular pressure (IOP) of latanoprost monotherapy and timolol-pilocarpine in patients with glaucoma or ocular hypertension with inadequately controlled IOP on topical beta adrenergic antagonists. METHODS: This was a multicentre, randomised, observer masked, 6 week study performed in France and Sweden. 23 centres enrolled 237 patients with glaucoma or ocular hypertension and an IOP of at least 22 mm Hg on treatment with topical beta adrenergic antagonists, alone or in combination. After a 21 day run in period on timolol 0.5% twice daily, patients were randomised either to latanoprost 0.005% once daily or to a fixed combination of timolol-pilocarpine twice daily. Changes in mean diurnal IOP from the baseline to the 6 week visit were determined with an analysis of covariance. RESULTS: Mean diurnal IOP was statistically significantly decreased from baseline in both groups (p<0.001). Switching to latanoprost treatment reduced mean diurnal IOP by 5.4 (SEM 0.3) mm Hg (ANCOVA -22%) and switching to timolol-pilocarpine treatment reduced mean diurnal IOP by 4.9 (0.4) mm Hg (-20%). Blurred vision, decreased visual acuity, decreased twilight vision, and headache were statistically significantly more frequent in the timolol-pilocarpine group. CONCLUSIONS: Latanoprost monotherapy was at least as effective as fixed combination timolol-pilocarpine twice daily treatment in reducing mean diurnal IOP in patients not adequately controlled on topical beta adrenergic antagonists. Latanoprost was better tolerated than timolol-pilocarpine regarding side effects. These results indicate that a switch to latanoprost monotherapy can be attempted before combination therapy is initiated.     

Efficacy of the dorzolamide/timolol fixed combination versus latanoprost in the treatment of ocular hypertension or glaucoma: combined analysis of pooled data from two large randomized observer and patient-masked studies.

In previous analyses of primary efficacy data from two randomized clinical trials, standard dosing regimens of the dorzolamide/timolol fixed combination (COSOPT) and latanoprost (XALATAN) were shown to have equivalent efficacy with regard to reduction in mean daytime diurnal intraocular pressure (IOP). We performed additional post hoc analyses of pooled data from these studies to compare further the efficacy of the two treatments. The studies used identical 3-month, parallel group, randomized, observer-masked and patient-masked, multicenter designs. Patients with a baseline IOP > or = 24 mm Hg were randomized to either the 2% dorzolamide/0.5% timolol combination eye drops twice daily (n = 273) or 0.005% latanoprost eye drops once daily (n = 271). The IOP measurements were made at 8 AM, 10 AM, 2 PM, and 4 PM at the baseline visit and then on each of the 3 monthly assessment days. The following measures were analyzed on a post hoc basis: 1) percentages of patients meeting target levels of IOP reduction; 2) mean IOP reduction in those patients with high IOP (> or =30 mmHg) at baseline; 3) mean IOP at each of the assessment time points during a day. A total of 259 patients in the dorzolamide/timolol group and 268 patients in the latanoprost group were included in the efficacy analysis. At 3 months, both treatments showed similar efficacy with regard to the percentages of patients who achieved target levels of IOP reduction (e.g., 40% IOP reduction in 15% of dorzolamide/timolol combination patients and 13% of latanoprost patients), mean IOP reduction in those patients with high IOP at baseline (dorzolamide/ timolol combination, 12.5 mmHg, latanoprost, 12.6 mmHg), and mean IOP at each time point during the day. By the measures used in this analysis, the dorzolamide/timolol combination and latanoprost were equally effective at lowering IOP in patients with ocular hypertension or glaucoma.     

Comparison of the intraocular pressure-lowering effect of latanoprost and timolol in patients with chronic angle closure glaucoma: a preliminary study

OBJECTIVE: To compare the intraocular pressure (IOP)-reducing effect and side effects of 0.005% latanoprost once daily to 0.5% timolol twice daily in patients with primary chronic angle closure glaucoma (CACG). DESIGN: Randomized, double-masked two-center clinical trial. PARTICIPANTS: Thirty-two Asian patients with CACG, defined as glaucomatous optic neuropathy with a compatible visual field defect and at least 6 clock hours of synechial angle closure on gonioscopy were recruited. All patients had previous peripheral iridotomy (PI) with IOP >21 mmHg after PI and were thereafter controlled (IOP <22 mmHg) with one or two pressure-reducing drugs. INTERVENTION: After a washout period, the patients were randomized to a 2-week treatment period with either placebo in the morning and 0.005% latanoprost in the evening or 0.5% timolol twice daily. MAIN OUTCOME MEASURES: The short-term IOP reduction of latanoprost and timolol in patients with CACG. IOP was measured at baseline, and after 2, 7, and 14 days of treatment. In addition, the short-term ocular and systemic adverse events of the two drugs were evaluated. RESULTS: Thirty patients completed the study. Two patients in the timolol group were withdrawn because of inadequate IOP control. Compared with baseline, the IOP after 2 weeks of treatment was statistically significantly reduced by 8.8 +/- 1.1 mmHg (mean +/- SEM, P < 0.001) in the latanoprost group, and by 5.7 +/- 0.9 mmHg (P < 0.001) in the timolol group. The difference in IOP reduction between the two treatment groups was 3.1 +/- 1.5 mm Hg in favor of latanoprost (P = 0.04). The main ocular adverse events reported in both treatment groups were conjunctival hyperemia and discomfort. CONCLUSIONS: In this preliminary study, a significantly greater IOP reduction was achieved with 0.005% latanoprost once daily compared with 0.5% timolol twice daily in patients with CACG. The results suggest that latanoprost may be a therapeutic choice for the medical treatment of primary CACG.     

Intraocular pressure over 24 hours after repeated administration of latanoprost 0.005% or timolol gel-forming solution 0.5% in patients with ocular hypertension

PURPOSE: To compare the effect on intraocular pressure (IOP) over 24 hours after 4 weeks of treatment with latanoprost 0.005% and timolol gel 0.5%. DESIGN: Randomized, open, crossover single-center study. PARTICIPANTS: Twenty-seven patients with ocular hypertension. METHODS: The patients were randomly assigned to 4 weeks of latanoprost 0.005% once daily or timolol gel 0.5% once daily, with a 4-week washout period before switching therapy. MAIN OUTCOME MEASURES: Measurement of IOP during 24 hours of hospitalization. Blood pressure and heart rate were also measured repeatedly over the 24 hours. Daytime mean IOP, nighttime mean IOP, and 24-hour mean IOP were calculated as IOP area under the curve (AUC) divided by time in hours. RESULTS: The mean IOP during daytime (7 AM to 10 PM) was 13.5 +/- 0.4 mmHg (daytime IOP, AUC/15 hours, least square mean +/- standard error of the mean [SEM]) in the latanoprost group, and 14.8 +/- 0.4 mmHg in the timolol gel group. This difference of 1.3 +/- 0.3 mmHg was statistically significant in favor of latanoprost (P < 0.001; 95% confidence interval [CI], 0.7, 2.0). The mean IOP at night (10 PM to 7 AM) was 13.7 +/- 0.4 mmHg for latanoprost (nighttime IOP, AUC/9 hours, least square mean +/- SEM) and 15.9 +/- 0.5 mmHg for timolol gel, with a difference of 2.2 +/- 0.3 mmHg (P < 0.001; 95% CI, 1.5, 2.8). At every measured time point during the 24 hours, latanoprost reduced IOP more than timolol. There was no difference between the two treatment groups regarding blood pressure and heart rate. CONCLUSIONS: Latanoprost reduced mean 24-hour IOP, mean daytime IOP, and mean nighttime IOP statistically significantly more than timolol. Also, latanoprost reduced IOP more effectively at every measured time point over the 24 hours compared with timolol gel.     

Comparison of two fixed combinations of latanoprost and timolol in open-angle glaucoma

· Objective: To compare the intraocular pressure (IOP)-reducing effect of the fixed combinations of timolol 0.5% and latanoprost 0.001% or 0.005% after 4 weeks’ treatment. · Design: Following a 1-week run-in period on timolol 0.5% once daily, 139 patiens were randomized to once-daily treatment with a fixed combination of timolol 0.5% and latanoprost 0.001% (comb. 10) or latanoprost 0.005% (comp. 50) or to the individual monotherapies. The IOP was measured at inclusion and at 8 a.m., noon and 4 p.m. on days 1, 7 and 28. · Results: Comb. 10, comb. 50, latanoprost and timolol reduced IOP by 3.7, 6.1, 4.9 and 2.1 mmHg, respectively, from a baseline mean diurnal IOP (±SEM) of 24.8±0.5, 24.1±0.4, 25.2±1.2 and 24.8±0.9 mmHg, respectively. The difference in IOP reduction was significant between comb. 50 and comb. 10 (P<0.001), latanoprost (P=0.046) and timolol (P<0.001) in favor of comb. 50. There was also a significant difference between latanoprost and timolol (P=0.007), in favor of latanoprost. All treatments were generally well tolerated. · Conclusion: This study indicates that a fixed combination of latanoprost 0.005% and timolol 0.5% could be useful in the treatment of glaucoma. Received: 6 October 1997 Revised version received: 16 December 1997 Accepted: 7 January 1998     

Comparison of the nocturnal effects of once-daily timolol and latanoprost on intraocular pressure

PURPOSE: To compare the nocturnal effects of once-daily timolol and latanoprost on intraocular pressure (IOP) in patients with ocular hypertension or early glaucomatous changes. DESIGN: Prospective, open-label, experimental study with crossover design. METHODS: Eighteen patients with ocular hypertension or early glaucomatous changes (aged 41 to 79 years) each received topical treatments with timolol (0.5% Timoptic-XE), latanoprost (0.005% Xalatan), and no IOP-lowering medication, for at least 4 weeks. Timolol was given once in the morning upon awakening and latanoprost once in the evening at bedtime. At the end of each treatment period, the patient was housed in a sleep laboratory for 24 hours and IOP was measured every 2 hours using a pneumatonometer. Measurements were taken sitting and supine during the 16-hour diurnal/wake period and only supine during the 8-hour nocturnal/sleep period. Mean diurnal and nocturnal IOP levels were compared among the treatments with timolol, latanoprost, and no medication. RESULTS: In the diurnal period, the mean IOP under the timolol or the latanoprost treatment was significantly less than the mean IOP under no medication in both the sitting and the supine positions. There was no statistical difference between the timolol and latanoprost treatments. In the nocturnal period, supine IOP with timolol treatment was not different from the supine IOP with no medication but was significantly higher than supine IOP with the latanoprost treatment. CONCLUSION: Although both once-daily timolol and latanoprost were effective in lowering IOP during the diurnal period, only latanoprost reduced IOP during the nocturnal period.     

The effect on diurnal intraocular pressure of the fixed combination of latanoprost 0.005% and timolol 0.5% in patients with ocular hypertension

PURPOSE: To measure the effect on intraocular pressure (IOP) after single-dose administration of the fixed combination of latanoprost 0.005% and timolol 0.5%. METHODS: A randomized, double-masked placebo-controlled parallel-group study was carried out. Twenty patients with ocular hypertension received the fixed combination of latanoprost+timolol, while 10 received placebo eyedrops. On baseline day no eyedrops were given, but IOP was measured repeatedly between 8.00 a.m. and 8.00 p.m. On Day 7 the eyedrops were given at 8.00 a.m., and IOP measured as on baseline day. On Day 8 and Day 9, IOP was again measured at 8.00 a.m. RESULTS: There was no difference in IOP in the placebo group. In the latanoprost+timolol group maximal IOP reduction (12.4+/-2.8 mmHg; mean+/-standard deviation) occurred 6.4 hours after drug administration (5.2--7.7 hours; 95% confidence interval [CI]). The mean IOP reduction after 24 hours was 9.8 mmHg (7.4--12.2 mmHg; 95% CI; p<0.001), and after 48 hours 5.7 mmHg (3.4--8.1 mmHg; 95% CI; p<0.001). CONCLUSIONS: The fixed combination of latanoprost+timolol statistically significantly reduced IOP after single-dose administration. The maximal effect was noted after about 6 hours, and the IOP reduction was still pronounced after 48 hours.     

Peak pressures: crossover study of timolol and latanoprost

PURPOSE: To compare the diurnal efficacy and action on peak intraocular pressures (IOP) of 0.005% latanoprost and 0.5% timolol as primary therapy in 60 eyes having dark brown irides with primary open angle glaucoma (POAG). METHODS: A prospective, comparative, observer-masked, crossover, interventional trial including the mean of both eyes of 30 patients with POAG who were randomly started on either latanoprost once daily or timolol twice daily. Three months after treatment with one drug, the second drug was substituted. A masked observer carried out diurnal assessments of IOP before the start of therapy and at 3 and 7 months. The fourth month was the washout period for the first drug. RESULTS: The average baseline IOP was 23.36 +/- 2.14 mm Hg, which was reduced by 8.8 +/- 2.2 mmHg with latanoprost (p < 0.01) and by 6.75 +/- 1.9 mm Hg with timolol (p = 0.01). The reduction was greater for latanoprost (p < 0.005). The average peak IOP at baseline was 27.6 +/- 2.22 mmHg. The effective fall in IOP at the time of new peaks in subsequent diurnal recordings of IOP compared to the baseline diurnal curve was 8.9 mm Hg with latanoprost (p < 0.005) and 5.77 mm Hg with timolol (p < 0.01). This difference in IOP reduction between the two drugs was statistically significant (p < 0.01). Latanoprost had a lower efficacy in peak IOP reduction in eyes with evening peak of IOP than in those with morning peak (p < 0.005). The efficacy of timolol was lower overall compared to latanoprost, but was similar in all circadian rhythms. The shift in timing of IOP peak was greater with latanoprost compared to timolol (4.34 hours vs -0.72 hours, p < .01). A total of 90% of patients on latanoprost and 33.3% on timolol achieved a reduction of > 30% in baseline mean IOP. The average of the trough IOP recorded in each of the individual baseline IOP curves was 19.05 +/- 2.05 mm Hg. CONCLUSIONS: Greater mean and peak IOP reduction was achieved with latanoprost compared to timolol. Dampening of the circadian rhythm was better with latanoprost. Latanoprost appears to be more effective than timolol at all points in time with greater efficacy in eyes with morning peaks compared to evening peaks.     

A comparison of the effects of dorzolamide/timolol fixed combination versus latanoprost on intraocular pressure and pulsatile ocular blood flow in primary open-angle glaucoma patients

PURPOSE: To evaluate the effects of dorzolamide/timolol fixed combination (D/T) compared to latanoprost on intraocular pressure (IOP) and pulsatile ocular blood flow (POBF) in primary open-angle glaucoma (POAG) patients. METHODS: Thirty patients with POAG were randomized in an open-label, cross-over study. Intraocular pressure reduction was achieved by 4 weeks medical therapy with D/T twice daily or latanoprost 0.005% dosed once in the evening. During a 4-week run-in and a 4-week wash-out period between study arms, patients ceased use of all other glaucoma medications and used timolol maleate 0.5% twice daily. Primary efficacy variables were IOP and POBF. RESULTS: There was no difference in baseline IOP and POBF parameters between the two study arms. Both D/T and latanoprost statistically significantly reduced IOP by 4.6 mmHg (p < 0.0001) and 3.75 mmHg (p < 0.0001) and increased POBF by 2.048 microl/second (p = 0.0030) and 2.147 microl/second (p = 0.0009), respectively. Repeated measures anova detected significant changes in POBF with treatment (p = 0.0361). Dorzolamide/timolol fixed combination statistically significantly increased pulse volume by 0.767 microl (p = 0.0087), while latanoprost therapy had no significant effect (p = 0.2407). CONCLUSIONS: Both drugs had similar effects in terms of IOP reduction. Dorzolamide/timolol significantly increased pulse volume while latanoprost had no effect. Further studies are necessary to establish whether the enhancement of choroidal blood flow can prevent glaucoma progression.     

latanoprost与噻吗心安治疗开角型青光眼及高眼压症的临床？…

验证ｌａｔａｎｏｐｒｏｓｔ对青光眼的治疗价值。方法对１２８例原发性开角型青光眼和高眼压症患者进行为期１２周的多中心、开放式,临床随机对照研究,观察其随眼压疗效和不良反应。分别应用０．００５％ｌａｔａｎｏｐｒｏｓｔ每日滴眼１次及０．５％噻吗心安每日滴眼２次。随访时间为治疗前、治疗后２、６及１２周、测量眼压并观察记录局部、全身不良反应。结果共入选１２８例（ｌａｔａｎｏｐｒｏｓｔ组６３例,噻吗心安组６５