A double-masked, randomized clinical trial comparing latanoprost with unoprostone in patients with open-angle glaucoma or ocular hypertension

PURPOSE: To compare the intraocular pressure (IOP) reducing effect and safety of latanoprost 0.005% once daily with unoprostone 0.12% twice daily in patients with primary open-angle glaucoma (POAG) or ocular hypertension (OH). DESIGN: An 8-week, double-masked, randomized, parallel-group, single-center clinical trial. PARTICIPANTS: A total of 108 patients with POAG or OH were enrolled. INTERVENTIONS: After completing a wash-out of ocular hypotensive medications, patients were randomized to receive either latanoprost once daily in the evening plus placebo once daily in the morning, or unoprostone twice daily (morning and evening). MAIN OUTCOME MEASURES: IOP was measured at 10:00 AM and at 5:00 PM at baseline and at week 8, and before 12:00 noon at week 2. Ocular and systemic safety assessments were performed. RESULTS: From an overall baseline of 24.1 mmHg, latanoprost reduced IOP by 6.7 mmHg (28%) and unoprostone reduced IOP by 3.3 mmHg (14%). The difference between the groups of 3.4 mmHg was significant (P: < 0.001, analysis of covariance; 95% confidence interval [CI]: -4.7 to -2.1) in favor of latanoprost. A >/=30% reduction in mean IOP from baseline was achieved by 44% of latanoprost-treated patients compared with 8% of unoprostone-treated patients. The incidence of adverse events was low and comparable between the groups. CONCLUSIONS: Latanoprost administered once daily was significantly more effective in reducing IOP compared with unoprostone administered twice daily in patients with POAG and OH.     

A six-month randomized clinical trial comparing the intraocular pressure-lowering efficacy of bimatoprost and latanoprost in patients with ocular hypertension or glaucoma

PURPOSE: To compare the intraocular pressure (IOP)-lowering efficacy and safety of topical bimatoprost 0.03% with latanoprost 0.005%. DESIGN: Multicenter, randomized, investigator-masked clinical trial. METHODS: After washout of glaucoma medications, ocular hypertension or glaucoma patients were randomly assigned to once-daily bimatoprost 0.03% (n = 133) or latanoprost 0.005% (n = 136) for 6 months. The primary outcome measure was mean change from baseline IOP (8 AM, 12 PM, 4 PM). Secondary measures included mean IOP, ophthalmologic examination, adverse events, and the percentage of patients reaching specific target IOPs. RESULTS: Mean change from baseline IOP was significantly greater for bimatoprost patients than for latanoprost patients at all measurements on each study visit; 1.5 mm Hg greater at 8 AM (P <.001), 2.2 mm Hg greater at 12 PM (P <.001), and 1.2 mm Hg greater at 4 PM (P =.004) at month 6. At the end of the study, the percentage of patients achieving a > or = 20% IOP decrease was 69% to 82% with bimatoprost and 50% to 62% with latanoprost (P < or = .003). In addition, the distribution of patients achieving target pressures in each range (< or = 13 to < or = 15 mm Hg, >15 to < or = 18 mm Hg, and > 18 mm Hg) showed that bimatoprost produced lower target pressures compared with latanoprost at all times measured (P < or = .026). Few patients were discontinued for adverse events (6 on bimatoprost; 5 on latanoprost). On ophthalmologic examination, conjunctival hyperemia (P <.001) and eyelash growth (P =.064) were more common in bimatoprost patients. CONCLUSIONS: Bimatoprost is more effective than latanoprost in lowering IOP. Both drugs were well tolerated, with few discontinuations for adverse events.     

A 12-month, randomized, double-masked study comparing latanoprost with timolol in pigmentary glaucoma

OBJECTIVE: To compare the efficacy and side effects and the effect on aqueous humor dynamics of 0.005% latanoprost applied topically once daily with 0.5% timolol given twice daily for 12 months to patients with pigmentary glaucoma. DESIGN: Prospective, randomized, double-masked, clinical study. PARTICIPANTS: Thirty-six patients affected with bilateral pigmentary glaucoma controlled with no more than a single hypotensive medication were enrolled in the study. INTERVENTION: The sample population was randomly divided into 2 age- and gender-matched groups each of 18 patients. Group 1 received 0.005% latanoprost eyedrops once daily and the vehicle (placebo) once daily; group 2 was assigned to timolol 0.5% eyedrops twice daily. MAIN OUTCOME MEASURES: Diurnal curves of intraocular pressure (IOP) were performed on the baseline day and after 0.5, 3, 6, and 12 months of treatment. The IOP measurements were performed at 8:00 AM, 12:00 noon, 4:00 PM, and 8:00 PM. Outflow facility ("C") was measured on the baseline day and on the last day of the study with a Schiotz electronic tonometer. A two-tailed Student's t test for paired or unpaired data was used for statistical evaluation of differences between treatment and baseline values or between the latanoprost and timolol group. Diurnal IOP measurements were compared hour by hour. Mean values of the two eyes IOP and "C" were used for analysis. RESULTS: Compared with baseline measurements, both latanoprost and timolol caused a significant (P < 0.001) reduction of IOP at each hour of diurnal curve throughout the duration of therapy. Reduction of IOP was 6.0 +/- 4.5 and 5.9 +/- 4.6 with latanoprost and 4.8 +/- 3.0 and 4.6 +/- 3.1 with timolol after 6 and 12 months, respectively. Comparison of mean diurnal measurements with latanoprost and timolol showed a statistical significant (P < 0.001) difference at 3, 6, and 12 months. Mean "C" was found to be significantly enhanced (+30%) only in the latanoprost-treated group compared with the baseline (P = 0.017). Mean conjunctival hyperemia was graded at 0.3 in latanoprost-treated eyes and 0.2 in timolol-treated eyes. A remarkable change in iris color was observed in both eyes of 1 of the 18 patients treated with latanoprost and none of the 18 patients who received timolol. Darkening of the peripheral iris stroma was suspected in two patients treated with latanoprost. In the timolol group, heart rate was significantly reduced from 72 +/- 9 at baseline to 67 +/- 10 beats per minute at 12 months. CONCLUSIONS: Although further studies may need to confirm these data on a larger sample and to evaluate the side effect of increased iris pigmentation on long-term follow-up, in patients with pigmentary glaucoma, 0.005% latanoprost taken once daily was well tolerated and more effective in reducing IOP than 0.5% timolol taken twice daily.     

A randomized double-masked crossover study comparing latanoprost 0.005% with unoprostone 0.12% in patients with primary open-angle glaucoma and ocular hypertension

PURPOSE: To compare the intraocular pressure)-lowering effect and side effects of latanoprost 0.005% once daily with unoprostone 0.12% twice daily. METHODS: Sixty patients with primary open-angle glaucoma or ocular hypertension were randomized to receive either latanoprost once daily in the evening and placebo once daily in the morning, or unoprostone twice daily in the morning and evening. The study was double masked and followed a crossover design with two treatment periods of 1 month separated by a 3-week washout period. The intraocular pressure was measured at 9 AM and 5 PM on the baseline and day 28 visits, and at 9 AM on day 2 and day 14 visits of each treatment period. The 9 AM measurement was taken 2 hours and 13 hours after the last drop of unoprostone and latanoprost, and the 5 PM measurement was at 10 and 21 hours, respectively. The mean of the measurements was calculated. Safety parameters were also recorded. RESULTS: Fifty-six patients completed both treatment periods and had intraocular pressure data available for evaluation. After 1 month of treatment, latanoprost significantly reduced intraocular pressure (mean +/- SEM) by 6.1 +/- 0.5 mm Hg (P <.001) and unoprostone by 4.2 +/- 0.4 mm Hg (P <.001) adjusted from an overall baseline of 22.3 +/- 0.5 mm Hg and 23.2 +/- 0.4 mm Hg, respectively. The difference of 1.9 mm Hg between treatments was statistically significant in favor of latanoprost [P =.003, analysis of covariance (ANCOVA)]. Unadjusted analysis of responders using the percentage decrease in intraocular pressure showed that the proportion of responders in the latanoprost-treated group was greater than in the unoprostone-treated group. Adverse ocular symptoms and findings were mild in both treatment groups. Eye redness and ocular irritation were the most frequently reported events. CONCLUSIONS: Latanoprost once daily was significantly more effective in reducing intraocular pressure compared with unoprostone twice daily after 1 month of treatment in patients with primary open-angle glaucoma and ocular hypertension. Both drugs were well tolerated with few ocular adverse events.     

Intraocular pressure-reducing effects and safety of latanoprost versus timolol in patients with chronic angle-closure glaucoma

OBJECTIVE: To demonstrate that the intraocular pressure (IOP)-reducing effect of latanoprost once daily is at least as good as that of timolol twice daily in patients with chronic angle-closure glaucoma (CACG). DESIGN: Randomized, double-masked, multicenter 12-week study. PARTICIPANTS: In all, 137 patients with unilateral or bilateral CACG were treated with latanoprost, and 138 were treated with timolol. METHODS: Patients received either latanoprost (9 pm) and a placebo (9 am) or timolol (both 9 am and 9 pm). Intraocular pressure was measured at 9 am and 5 pm at baseline and weeks 2, 6, and 12. MAIN OUTCOME MEASURES: The difference between groups in daily IOP (average of 9 am and 5 pm measures) reduction was the primary outcome. Secondary outcomes included differences between groups in IOP reductions at 9 am and 5 pm, and in proportions of patients reaching specified daily IOP levels. RESULTS: Using repeated measures (analysis of covariance: intent to treat), mean changes from baseline in daily IOP levels during 12 weeks were -8.2 mmHg and -5.2 mmHg for latanoprost- and timolol-treated patients, respectively (difference: -3.0 mmHg [95% confidence interval: -4.0, -2.1], P<0.001). Greater reductions in IOP levels at both 9 am and 5 pm were found in latanoprost-treated patients (P<0.001 for both), and greater proportions of patients receiving latanoprost reached prespecified target daily IOP levels (P<0.001 for all 3 target levels tested). Both drugs were well tolerated. CONCLUSION: Latanoprost administered once daily provides significantly greater IOP reduction in CACG patients than does timolol instilled twice daily.     

Two-year double-masked comparison of bimatoprost with timolol in patients with glaucoma or ocular hypertension

The object of this study was to compare the long term efficacy and safety of bimatoprost with timolol in patients with glaucoma or ocular hypertension. In a 12-month extension of two identically designed 1-year, multicenter, randomized, double-masked clinical trials, patients were treated topically with bimatoprost 0.03% QD (n=167), bimatoprost 0.03% BID (n=131), or timolol 0.5% BID (n=81). Main outcome measures were IOP at 8 am and 10 am and safety parameters. Bimatoprost QD provided significantly greater mean reduction from baseline IOP than did timolol at both measurements at each study visit (P< or =.001). At 10 am (peak timolol effect) at month 24, the mean reduction from baseline IOP was 7.8 mm Hg with bimatoprost QD and 4.6 mm Hg with timolol (P<.001). Patients treated with bimatoprost QD also sustained significantly lower mean IOP than timolol-treated patients at every follow-up visit throughout the 2-year study period (P< or =.006). At 10 am at month 24, a significantly greater proportion of bimatoprost QD than timolol patients achieved target pressures of < or =13-18 mm Hg (P< or =.010). Bimatoprost sustained an excellent safety profile during the second year of treatment. Most adverse events were mild, and there were no reports of increased iris pigmentation, uveitis, or CME. The incidence of hyperemia was significantly higher with bimatoprost QD (13.8%) than with timolol (2.5%) (P=.006). Mean reduction from baseline IOP with bimatoprost BID was not significantly different from that with timolol at month 24 at 10 am (P=.474). We conclude that bimatoprost QD provides superior IOP lowering to timolol, and is safe and well tolerated over 24 months of treatment.     

Long-term effects of timolol therapy in ocular hypertension: a double-masked, randomised trial

Background: Increased intraocular pressure (IOP) has been shown to be one of the most important risk factors for developing glaucoma. Yet it has not been clearly demonstrated that IOP-lowering treatment can reduce the incidence of glaucoma damage in patients with ocular hypertension. The aim of the current paper was to report the results of a long-term study addressing this very problem. Methods: We conducted a randomised, double-masked study comparing timolol and placebo treatment in 90 patients with ocular hypertension plus some additional risk factor. Patients were followed at 3-month intervals prospectively for 10 years or until glaucomatous field loss could be demonstrated with computerised perimetry. A post-study analysis was performed including all available data, thus extending maximum follow-up to 17 years. Results: After 5 years of follow-up eight patients in the placebo group and five patients in the timolol group had developed glaucomatous field loss (NS); the corresponding figures after 10 years were 15 patients in the placebo group and seven patients in the timolol group. Survival analysis showed a tendency but no statistically significant difference between treatment groups (P=0.07). Study attrition was large. Eighteen patients in each group had developed glaucomatous field loss when also post-study data were included. IOP reduction was greater in eyes passing the 10-year visit without field loss (5.7 mmHg), than in those that reached an endpoint (2.3 mmHg; P=0.0002). Conclusion: In this long-term study we found a tendency but failed to prove a beneficial effect of topical timolol treatment in patients with elevated IOP, normal visual fields and some additional risk factor. The intent-to-treat analysis showed no difference between treatment groups. The high attrition shows the difficulties associated with very long follow-up. Received: 19 April 2000 Revised: 7 June 2000 Accepted: 19 June 2000     

Travoprost compared with latanoprost and timolol in patients with open-angle glaucoma or ocular hypertension

PURPOSE: This study evaluated the safety and intraocular pressure-lowering efficacy of two concentrations of travoprost (0.0015% and 0.004%) compared with latanoprost 0.005% and timolol 0.5% in patients with open-angle glaucoma or ocular hypertension. METHODS: Eight hundred one patients with open-angle glaucoma or ocular hypertension were randomly assigned to travoprost 0.0015%, travoprost 0.004%, latanoprost 0.005%, or timolol 0.5%. The efficacy and safety of travoprost (0.0015% and 0.004%) daily was compared with latanoprost daily and timolol twice daily for a period of 12 months. RESULTS: Travoprost was equal or superior to latanoprost and superior to timolol with mean intraocular pressure over visits and time of day ranging from 17.9 to 19.1 mm Hg (travoprost 0.0015%), 17.7 to 19.1 mm Hg (travoprost 0.004%), 18.5 to 19.2 mm Hg (latanoprost), and 19.4 to 20.3 mm Hg (timolol). For all visits pooled, the mean intraocular pressure at 4 PM for travoprost was 0.7 mm Hg (0.0015%, P =.0502) and 0.8 mm Hg (0.004%, P =.0191) lower than for latanoprost. Travoprost 0.004% was more effective than latanoprost and timolol in reducing intraocular pressure in black patients by up to 2.4 mm Hg (versus latanoprost) and 4.6 mm Hg (versus timolol). Based on a criterion of 30% or greater intraocular pressure reduction from diurnal baseline or intraocular pressure 17 mm Hg or less, travoprost 0.0015% and 0.004% had an overall response to treatment of 49.3% and 54.7%, respectively, compared with 49.6% for latanoprost and 39.0% for timolol. Iris pigmentation change was observed in 10 of 201 of patients (5.0%) receiving travoprost 0.0015%, six of 196 of patients (3.1%) receiving travoprost 0.004%, 10 of 194 of patients (5.2%) receiving latanoprost, and none of the patients receiving timolol (0 of 196). The average ocular hyperemia score was less than 1 on a scale of 0 to 3, indicating that on average patients experienced between none/trace and mild for all treatment groups. There were no serious, unexpected, related adverse events reported for any therapy. CONCLUSIONS: Travoprost (0.0015% and 0.004%), a highly selective, potent prostaglandin F (FP) receptor agonist, is equal or superior to latanoprost and superior to timolol in lowering intraocular pressure in patients with open-angle glaucoma or ocular hypertension. In addition, travoprost 0.004% is significantly better than either latanoprost or timolol in lowering intraocular pressure in black patients. Travoprost is safe and generally well tolerated in the studied patient population.     

A double-masked comparison of carteolol and timolol in ocular hypertension

We performed a double-masked study in which 98 patients with ocular hypertension who had been previously treated with timolol received either timolol 0.25% or carteolol 1%, a beta-blocker with intrinsic sympathomimetic activity. The drugs were administered topically twice daily for one month after a one-week washout period. Intraocular pressure was measured at baseline and after one and four weeks of treatment. The appearance of the fundus, external eye, visual fields, tear secretion, blood pressure, and pulse were recorded. Adverse symptoms were elicited using a menu-type questionnaire and an overall judgment of therapy was recorded. Carteolol was as effective as timolol in reducing intraocular pressure. There were significantly fewer patients reporting adverse events overall (P = .019), and eye irritation specifically (P = .02), in the group treated with carteolol.     

拉坦前列腺素与噻吗心安治疗原发性开角型青光眼和高眼压症对照研究

目的　以噻吗心安为对照,评估新型异丙酯前列腺素Ｆ２α的苯基替代衍生物拉坦前列腺素（ＰｈＸＡ４１）对于眼压升高病人的降眼压疗效和副作用。方法　３４ 例（６６ 只眼） 原发性开角型青光眼或高眼压症患者入选,随机分组,１７ 例（３２ 只眼）滴用０．０５ｇ·Ｌ－１ 拉坦前列腺素每天１ 次,１７ 例（３４ 只眼）滴用５ｇ·Ｌ－１ 噻吗心安每天２ 次,共治疗１２ｗｋ。结果　１２ｗｋ治疗期间,两种药物均能有效降低眼压（Ｐ＜ ０－０１） ,且效应持续。各次随访均显示,拉坦前腺素的降眼压效果显著优于噻吗心安（Ｐ＜ ０－０５）。１２ｍｏ 时,拉坦前列腺素组的眼压降低了９－５±３－１ｍ ｍＨｇ（３６－８ ％）（１ｍ ｍＨｇ＝ ０．１３３ｋＰａ） ,噻吗心安组降低了７－４±２－６ｍ ｍＨｇ（２９－６％ ）（ Ｐ＜ ０－０１）。拉坦前列腺素治疗后,少数病例发现角膜上皮点状脱落。噻吗心安组的平均心率减少４ 次·ｍｉｎ－１（Ｐ＜ ０－０５） 。结论　０ ．０５ｇ·Ｌ－１ 拉坦前列腺素每天１ 次与５ｇ·Ｌ－１ 噻吗心安每天２ 次相比,具有更强的降眼压作用,而且耐受性良好。因此,拉坦前列腺素将成为青光眼药物治疗的有效选择。     

Rate of response to latanoprost or timolol in patients with ocular hypertension or glaucoma

PURPOSE: This study determined the rate of response to latanoprost compared with timolol in patients with glaucoma or ocular hypertension, whether some patients convert from non-responders to responders after more prolonged therapy, and whether this conversion represents a delayed response or random fluctuation. METHODS: In a previously described, multicenter, randomized, double-masked, parallel group study, patients received either 0.005% latanoprost once daily (n = 128) or 0.5% timolol twice daily (n = 140) for 6 months. Intraocular pressure (IOP) was assessed at baseline and at 0.5, 1.5, 3, 4.5, and 6 months of treatment at 8 am on all visits, and also at noon and 4 pm at baseline and 6 months. Rate of response based on diurnal measurement at 6 months compared with baseline was assessed using several criteria for response. Eyes with an IOP reduction of less than 15% compared with baseline at 8 am arbitrarily were classified as non-responders at each of the 5 visits during treatment. Consistency of non-responder classifications for individual eyes was assessed. RESULTS: Mean IOP reduction was greater (P < 0.001) in latanoprost-versus timolol-treated patients throughout the course of therapy. A greater rate of response occurred in patients treated with latanoprost, and differences in response rates between the 2 drugs increased as the definitions of response became more stringent. A greater percentage of non-responders at any single visit were classified as responders at all other visits with latanoprost in comparison with timolol. CONCLUSIONS: Latanoprost produces a greater rate of response compared with timolol. A higher percentage of non-responders to latanoprost compared with timolol on any individual visit are responders on all other visits. Likewise, a higher proportion of patients who do not initially respond will become responders with continued treatment with latanoprost compared with timolol.     

Meta-analysis of randomised controlled trials comparing latanoprost with timolol in the treatment of patients with open angle glaucoma or ocular hypertension

AIM: To evaluate the comparative efficacy and tolerance of latanoprost versus timolol through a meta-analysis of randomised controlled trials (RCTs). METHODS: Systematic retrieval of RCTs of latanoprost versus timolol to allow pooling of results from head to head comparison studies. Quality of trials was assessed based on randomisation, masking, and withdrawal. Sensitivity analyses were used to estimate the effects of quality of study on outcomes. The data sources were Medline, Embase, Scientific Citation Index, Merck Glaucoma, and Pharmacia and Upjohn ophthalmology databases. There were 1256 patients with open angle glaucoma or ocular hypertension reported in 11 trials of latanoprost versus timolol. The main outcome measures were (i) percentage intraocular pressure (IOP) reduction for efficacy; (ii) relative risk, risk difference, and number needed to harm for side effects such as hyperaemia, conjunctivitis, increased pigmentation, hypotension, and bradycardia expressed as dichotomous outcomes; and (iii) reduction in systemic blood pressure and heart rate as side effects. RESULTS: Both 0.005% latanoprost once daily and 0.5% timolol twice daily reduced IOP. The percentage reductions in IOP from baseline (mean (SE)) produced by latanoprost and timolol were 30.2 (2.3) and 26.9 (3.4) at 3 months. The difference in IOP reduction between the two treatments were 5.0 (95% confidence intervals 2.8, 7.3). However, latanoprost caused iris pigmentation in more patients than timolol (relative risk = 8.01, 95% confidence intervals 1.87, 34.30). The 2 year risk with latanoprost reached 18% (51/277). Hyperaemia was also more often observed with latanoprost (relative risk =2.20, 95% confidence intervals 1.33, 3.64). Timolol caused a significant reduction in heart rate of 4 beats/minute (95% confidence interval 2, 6). CONCLUSION: This meta-analysis suggests that latanoprost is more effective than timolol in lowering IOP. However, it often causes iris pigmentation. While current evidence suggests that this pigmentation is benign, careful lifetime evaluation of patients is still justified.     

拉坦前列素和噻吗心安治疗开角型青光眼、高眼压症的对照研究

目的：观察Ｌａｔａｎｏｐｒｏｓｔ的降眼压效果及安全性。方法：采用随机分组对照组,０．００５％Ｌａｔａｎｏｐｒｏｓｔ每日一次或０．５％Ｔｉｍｏｌｏｌ（噻吗心安）每日２次,治疗原发性开角型青光眼、高眼压症和剥脱性青光眼,共１４例,疗程１２周,观察其眼压及不良反应。结果：Ｌａｔａｎｏｐｒｏｓｔ组和Ｔｉｍｏｌｏｌ组均可有效地降低眼压（Ｐ〈０．０１）,两组间眼压下降值没有差异。两组治疗前后不同时间点眼压下降