Travoprost compared with other prostaglandin analogues or timolol in patients with open-angle glaucoma or ocular hypertension: meta-analysis of randomized controlled trials

BACKGROUND: It is still uncertain whether travoprost has comparable or better efficacy compared with other prostaglandin analogues or timolol in patients with open-angle glaucoma or ocular hypertension. The authors performed a meta-analysis of randomized controlled trials to evaluate the incidence of reported side-effects and intraocular pressure (IOP)-lowering effect of travoprost versus other prostaglandin analogues (latanaprost, bimatoprost, unoprostone) or timolol. METHODS: Systematic literature retrieval was conducted in Pubmed, EMBASE, Chinese Bio-medicine Database and Cochrane Controlled Trials Register to identify the potentially relevant randomized controlled trials. The statistical analysis was performed by RevMan 4.1 software that was provided by the Cochrane Collaboration. The outcome measures were the incidence of reported side-effects (hyperaemia, iris pigmentation, eyelash changes) and mean IOP pooled over treatment visits. RESULTS: In total, 12 articles involving 3048 patients with open-angle glaucoma or ocular hypertension were included in this meta-analysis. The combined results showed that travoprost 0.004% was more effective than timolol or travoprost 0.0015% in lowering IOP, but not more effective than bimatoprost or latanoprost. Travoprost 0.004% caused a higher percentage of hyperaemia than timolol, latanoprost, or travoprost 0.0015%. There was an increased incidence of pigmentation with travoprost than timolol. Travoprost 0.004% caused a higher percentage of eyelash changes than timolol, latanoprost, or travoprost 0.0015%. CONCLUSION: According to data available, travoprost is more effective than timolol in lowering IOP in patients with open-angle glaucoma or ocular hypertension. Compared with other prostaglandin analogues, travoprost appears to be equivalent to bimatoprost and latanoprost. Although a limited number of local side-effects were reported, no serious treatment-related side-effects were reported.     

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。     

Dorzolamide/timolol fixed combination versus latanoprost/timolol fixed combination in patients with primary open-angle glaucoma or ocular hypertension

PURPOSE: The efficacy of dorzolamide/timolol fixed combination (DTFC) versus latanoprost/timolol fixed combination (LTFC) in open-angle glaucoma or ocular hypertensive patients. METHODS: Patients were randomized to DTFC or LTFC for 6 weeks and switched to opposite treatment for Period 2. RESULTS: Thirty-two completed patients had a mean diurnal IOP of 19.5+/-3.2 mmHg for DTFC and 18.9+/-3.4 mmHg for LTFC (p=0.12), with no significant difference found between DTFC and LTFC at any timepoint following a Bonferroni correction (p>or=0.01). CONCLUSIONS: Patients treated with DTFC and LTFC have a statistically similar ocular hypotensive effect.     

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.     

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     

Pneumatic trabeculoplasty vs latanoprost as adjunctive therapy to timolol in primary open-angle glaucoma or ocular hypertension

Purpose  To evaluate the efficacy and safety of pneumatic trabeculoplasty (PNT) compared with latanoprost 0.005%, in primary open-angle glaucoma (POAG) and ocular hypertension (OH) not controlled by timolol 0.5%. Procedures  In a randomized clinical study, 18 patients affected with primary open-angle glaucoma (POAG) or ocular hypertension (OH) with intraocular pressure (IOP) >20 mmHg after timolol 0.5% in one eye were treated with PNT; 18 control eyes received adjunctive therapy with latanoprost 0.005%. Visual acuity, IOP, visual field, biomicroscopy findings and fundus appearance were evaluated at each month. Patients with IOP >20 mmHg were excluded from the study. The study was continued until in one group no patients were left. Results  At 1 month, IOP had decreased significantly in both groups. In PNT-treated eyes the mean IOP decrease was 4.5 ± 1.8 mmHg (19.1 ± 7.8%) and in latanoprost-treated eyes was 6.6 ± 1.3 mmHg (28.2 ± 5.7%) (between two groups, P < 0.001). Eleven PNT-treated eyes (61%) and 17 latanoprost-treated eyes (94%) had an IOP reduction of more than 20% of baseline value (P = 0.049); two PNT-treated patients received additional therapy. At the following months, in the latanoprost group, IOP was stable: an IOP reduction of 20% or more was seen in 89% of the eyes. In some PNT-treated eyes IOP increased: at 2 months, an IOP reduction≥20% was seen in 50%, at 3 months in 33%, and at 4 months in 17% of the eyes. (between the two groups, respectively, P = 0.03, P = 0.002, P < 0.001). The number of eyes that required therapy increased progressively in the PNT group, and at 8 months all eyes had required therapy, whereas one latanoprost-treated eye had had additional therapy. After PNT, no patients had visual acuity reduction or intraocular inflammation; three eyes had subconjunctival hemorrhage and five eyes a hyperemia that regressed within 1 week. No posterior segment changes or visual field progression were detected in either groups. Conclusions  In eyes with glaucomatous damage that is not advanced, PNT can reduce the IOP in 60% of the eyes at 1 month, and in 33% of the eyes at 3 months, without significant side-effects. The indications, efficacy and safety of PNT retreatments remain to be investigated. IOP reduction is less and of shorter duration than that obtained by latanoprost adjunctive therapy. No financial relationship     

Comparison of latanoprost monotherapy with timolol-dorzolamide combination in patients with open-angle glaucoma or ocular hypertension

PURPOSE: To compare the efficacy and safety of latanoprost monotherapy to dorzolamide combined with timolol from pooled data of five multicenter, randomized, 3-month, observer-masked trials with identical study design. METHODS: Patients who were on a beta-blocker or dual therapy where one agent was a beta-blocker were eligible after a 2- to 4-week run-in period on timolol 0.5%, twice daily. Patients then either discontinued timolol treatment and received latanoprost monotherapy n=345) or continued on timolol and received dorzolamide add-on therapy (n=352). Data from these 697 patients were included in the meta-analysis. RESULTS: From an overall baseline of 22.8mmHg, the mean IOP reduction was 4.8mmHg (21%) in latanoprost-treated patients and 4.1mmHg (18%) in timolol + dorzolamide-treated patients p<0.001). A reduction in diurnal IOP of >=20% was achieved in 54% of the latanoprost-treated patients compared with 44% of the timolol + dorzolamide-treated patients. There was no marked difference between the two groups in the incidence of ocular and systemic events. CONCLUSION: This meta-analysis provides further support that a switch to latanoprost monotherapy can be an alternative to combined treatment with timolol + dorzolamide.     

Therapeutic success of latanoprost 0.005% compared to brimonidine 0.2% in patients with open-angle glaucoma or ocular hypertension.

The purpose of this study was to evaluate the success rate ofmonotherapy with latanoprost 0.005% once daily versus brimonidine 0.2% twice daily in patients with open-angle glaucoma or ocular hypertension. Patients who were prescribed latanoprost or brimonidine as monotherapy were included in this study, and their consecutive charts were retrospectively reviewed. The primary efficacy variable was success of therapy, defined as a reduction in intraocular pressure > or =3 mm Hg without an adverse event leading to discontinuation over a potential of six months of therapy. We included 157 patients in this study. In the latanoprost group, 64 of 92 (70%) were considered successes; 26 of 65 (40%) were successful with brimonidine (P < 0.001). Nine failed brimonidine therapy, and one latanoprost, because of an adverse event, and the rest failed because of inadequate intraocular pressure response. The change from baseline in intraocular pressure was significantly greater with latanoprost (mean +/- S.D., 21.6 +/- 5.1 to 17.1 +/- 3.3 mm Hg) than brimonidine (23.7 +/- 5.6 to 21.9 +/- 5.7 mm Hg) (P = 0.001). Overall, 52 (80%) brimonidine- and 41 (45%) latanoprost-treated patients required additional visit(s) to adjust therapy to further lower intraocular pressure or to assess an adverse event (P < 0.001). In conclusion, latanoprost more likely provides a successful response to therapy than brimonidine when used as monotherapy in primary open-angle glaucoma or ocular hypertensive patients.     

Levobunolol vs timolol for open-angle glaucoma and ocular hypertension

A group of 162 patients with chronic open-angle glaucoma or ocular hypertension were treated twice daily for up to 15 months with one of the following topical ophthalmic solutions: 0.5% levobunolol, 1% levobunolol, or 0.5% timolol. Overall mean reductions in intraocular pressure were 8 mm Hg for patients receiving 0.5% levobunolol or timolol and 8.2 mm Hg for patients receiving 1% levobunolol. There were no significant differences between levobunolol and timolol in mean reductions in intraocular pressure, percent of patients with adequately controlled intraocular pressure, or life-table estimates of the probability of successful treatment.     

Short-term effect of latanoprost and timolol eye drops on tear fluid and the ocular surface in patients with primary open-angle glaucoma and ocular hypertension

PURPOSE: To investigate and compare the short term effects of topical latanoprost and timolol on the tear fluid and ocular surface condition in patients with bilateral primary open angle glaucoma or ocular hypertension. METHODS: Thirty-seven patients were included in this randomized, double-masked, parallel group study. Patients received either latanoprost 0.005% (n= 18) or timolol 0.5% (n= 19) instilled once daily in the morning for a treatment period of 27 days. Routine ophthalmic examinations, including intraocular pressure measurement, as well as tests to evaluate tear fluid and the ocular surface were performed. RESULTS: After one drop of medication, tear secretion was significantly reduced by timolol, but not by latanoprost. At the end of the study the break-up time (BUT) was significantly decreased in the timolol group but not in the latanoprost group. The BUT still remained in the normal range in both groups, although it is important to note that timolol was administered at half the clinical dose. Both latanoprost and timolol tended to increase Rose-Bengal staining of the cornea and conjunctiva after one month of treatment but no statistically significant difference was found between the groups. Corneal sensitivity was within the normal range for all patients during the study. CONCLUSION: Regarding ocular surface effects, no clinically important differences between latanoprost and timolol were observed as all the effects remained in the normal range.     

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.     

Effect of bimatoprost on patients with primary open-angle glaucoma or ocular hypertension who are nonresponders to latanoprost

PURPOSE: To test the efficacy of bimatoprost 0.03% 2D for lowering intraocular pressure (IOP) in patients affected by primary open-angle glaucoma or ocular hypertension who did not respond to treatment with latanoprost 0.005% 2D. DESIGN: Prospective, randomized clinical trial with a cross over design (two 30-day treatment phases with a 30-day washout phase in between). PARTICIPANTS: Fifteen patients were enrolled. Random allocation to treatment to a single eye only of every subject. Eligibility criteria: (1) IOP > 22 mmHg in both eyes on current treatment (on three separate readings > 24 hours apart), (2) angle wide open in both eyes, (3) no pseudoexfoliation and/or pigment dispersion in either eye, (4) documented medical history consistent with < 10% IOP decrease in both eyes on 2-month treatment with latanoprost 0.005% every day. METHOD: The following variables were measured at each study visit: (1) IOP (Goldmann applanation tonometry, 5 readings, 8 AM, 12 noon, 4 PM, 8 PM, and 12 midnight); (2) visual acuity (Early Treatment of Diabetic Retinopathy Study chart, logarithm of the minimum angle of resolution); (3) estimate of conjunctival hyperemia based on 5 standard photographs (graded as "none," "trace," "mild," "moderate," and "severe"). MAIN OUTCOME MEASURE: IOP. RESULTS: IOP data (mean and standard deviation) were the following: baseline = 24.7 +/- 0.9 mmHg, after washout = 24.8 +/- 1.1 mmHg, after latanoprost phase = 24.1 +/- 0.9 mmHg, after bimatoprost phase = 18.1 +/- 1.7 mmHg. IOP on bimatoprost proved lower than both baseline (P < 0.0001) and latanoprost (P = 0.0001). Thirteen of 15 patients showed a > or =20% IOP decrease with bimatoprost treatment. None of the 15 patients showed a > or =20% decrease of IOP after 30 days of latanoprost treatment. No significant IOP changes were observed in the fellow untreated eye in each patient throughout the study. Trace-to-mild conjunctival hyperemia was recorded more often with bimatoprost phase (P = 0.035). CONCLUSIONS: Thirteen of 15 patients, who were nonresponders to latanoprost, 0.005%, 2D, were successfully treated with bimatoprost, 0.03%, 2D. Bimatoprost treatment was associated with a higher incidence of trace-to-mild conjunctival hyperemia than latanoprost.     

Latanoprost versus timolol gel-forming solution once daily in primary open-angle glaucoma or ocular hypertension

BACKGROUND: To compare the efficacy and safety of latanoprost and timolol gel-forming solution (GFS). METHODS: This was a randomized, crossover, investigator-masked, active-control study of patients with primary open-angle glaucoma and ocular hypertension. Patients received either once-daily 0.5% timolol GFS (n=40) or once-daily 0.005% latanoprost (n=35) for 8 weeks (period 1). Patients were then crossed over to the other medication and treated for another 8 weeks (period 2). Intraocular pressure (IOP) was determined every 2 hours from 8:00 to 20:00 at baseline and weeks 8 and 16. Safety was assessed by visual acuity, slit-lamp biomicroscopy, and adverse event reports. RESULTS: During period 1, reduction in mean (SD) diurnal IOP was significantly greater in latanoprost-treated patients (-6.9 [3.0] mm Hg) than in timolol GFS-treated patients (-5.5 [2.4] mm Hg), p=0.034. There was also a significant reduction in IOP from baseline after switching from timolol GFS to latanoprost (p<0.001), not observed when patients were switched from latanoprost to timolol GFS. After results from each drug's treatment periods were combined between treatment arms, latanoprost reduced IOP more (-6.9 [2.9] mm Hg) than did timolol GFS (-6.2 [2.7] mm Hg), p=0.018. Hyperemia was the most common adverse event in both treatment groups, with 5 incidences in timolol GFS-treated patients, and 10 in latanoprost. INTERPRETATION: Latanoprost is more effective than timolol GFS in reducing IOP, and patients switched from timolol GFS to latanoprost have a further significant reduction in IOP.     

A persistency and economic analysis of latanoprost, bimatoprost, or beta-blockers in patients with open-angle glaucoma or ocular hypertension.

PURPOSE: The aim of this study was to evaluate differences in the persistency and treatment costs for latanoprost, bimatoprost, or beta-blockers in open-angle glaucoma or ocular hypertensive patients. METHODS: This study was a retrospective, multicenter, parallel, active-controlled comparison of patients who were prescribed with ocular hypotensive monotherapy between September 1996 and August 2002. RESULTS: 1,182 patients were included. The Kaplan Meier life table analysis showed that latanoprost was continued longest among the groups for the first year of therapy (p=0.02). A significant difference existed between groups in the final intraocular pressure for latanoprost (17.3+/-3.9, N=357), for bimatoprost (18.0+/-3.6, N=146), and for the beta-blockers (17.9+/-3.7, N=335) (p=<0.0001). The average number of visits was statistically higher for beta-blockers (3.3), compared to latanoprost (2.9) and bimatoprost (3.1) (p=0.01). Further, the mean number of medicine changes was greater for bimatoprost (0.45) and beta-blockers (0.47) than for latanoprost (0.27) (p=0.0008). The cost of visits and medications was lowest for beta-blockers ($119.3+/-$78.9) and highest for bimatoprost ($163.8+/-$51.2) (p<0.0001). CONCLUSIONS: Patients were more persistent with latanoprost and demonstrated lower intraocular pressure, fewer visits, and fewer medicine changes when compared to bimatoprost or beta-blocker therapy. In contrast, the beta-blocker group provided lower overall cost.     

Effect of timolol, latanoprost, and dorzolamide on circadian IOP in glaucoma or ocular hypertension

PURPOSE: To compare the around-the-clock intraocular pressure (IOP) reduction induced by timolol 0.5%, latanoprost 0.005%, and dorzolamide in patients with primary open-angle glaucoma (POAG) or ocular hypertension (OHT). METHODS: In this crossover trial, 20 patients with POAG (n = 10) or OHT (n = 10) were treated with timolol, latanoprost, and dorzolamide for 1 month. The treatment sequence was randomized. All patients underwent measurements for four 24-hour tonometric curves: at baseline and after each 1-month period of treatment. The patients were admitted to the hospital, and IOP was measured by two well-trained evaluators masked to treatment assignment. Measurements were taken at 3, 6, and 9 AM and noon and at 3, 6, and 9 PM and midnight by handheld electronic tonometer (TonoPen XL; Bio-Rad, Glendale, CA) with the patient supine and sitting, and a Goldmann applanation tonometer (Haag-Streit, Bern, Switzerland) with the patient sitting at the slit lamp. Systemic blood pressure was recorded at the same times. The between-group differences were tested for significance by means of parametric analysis of variance. The circadian IOP curve of a small group of untreated healthy young subjects was also recorded using the same procedures. To compare the circadian IOP rhythms in the POAG-OHT and control groups, the acrophases for each subject were calculated. RESULTS: When Goldmann sitting values were considered, all the drugs significantly reduced IOP in comparison with baseline at all times, except for timolol at 3 AM. Latanoprost was more effective in lowering IOP than timolol at 3, 6, and 9 AM (P = 0.03), noon (P = 0.01), 9 PM, and midnight (P = 0.05) and was more effective than dorzolamide at 9 AM, noon (P = 0.03), and 3 and 6 PM (P = 0.04). Timolol was more effective than dorzolamide at 3 PM (P = 0.05), whereas dorzolamide performed better than timolol at midnight and 3 AM (P = 0.05). An ancillary finding of this study was that in the group of healthy subjects, the pattern of IOP curve was different that in patients with eye disease. CONCLUSIONS: Latanoprost seemed to lead to a fairly uniform circadian reduction in IOP, whereas timolol seemed to be less effective during the nighttime hours. Dorzolamide was less effective than latanoprost but led to a significant reduction in nocturnal IOP. The reason for the difference in the pattern of the IOP curve of healthy subjects is currently unknown and deserves further investigation.