Observational study of patients switched to the fixed travoprost 0.004%/timolol 0.5% combination in Croatia

The purpose of this study was to assess both the benefits of a 3-month travoprost 0.004%/timolol 0.5%fixed combination (trav/tim) regimen in comparison with previous medications for the control of intraocular pressure (IOP) and the tolerability of these drug regimens in glaucoma patients. An observational, non-interventional, open-label study of 406 eyes with primary open angle glaucoma and ocular hypertension was thus undertaken. One drop of trav/tim fixed combination was administered in the evening for 3 months. Patients were divided into five groups according to previous drug regimens: timolol 0.5% monotherapy; betaxolol 0.5% monotherapy; latanoprost 0.005% monotherapy; travoprost 0.004% monotherapy; and dorzolamide 2%/timolol 0.5% fixed combination. Upon medication substitution, the trav/tim fixed combination provided better IOP control and tolerability in all five patient groups. At the 3-month follow up, the mean IOP changes from previous therapy were as follows: 5.2 ± 2.7 mmHg (20.8% change) in timolol 0.5% group; 5.7 ± 2.2 mmHg (22.5% change) in betaxolol 0.5% group; 3.8 ± 2.6 mmHg (24.5% change) in latanoprost 0.005% group; 4.4 ± 2.8 mmHg (20% change) in travoprost 0.004% group; and 3.4 ± 4.1 mmHg (14.5% change) in dorzolamide 2%/timolol 0.5% fixed combination group. The difference between baseline and trav/tim combination patient satisfaction at the 3-month follow-up was significant. Thus, the trav/tim fixed combination provided better IOP control and tolerability than previous mono- or polytherapies.     

Travoprost/timolol

Travoprost 0.004%/timolol 0.5% fixed combination (travoprost/timolol) is a once-daily eyedrops solution comprising the prostaglandin F(2alpha) analogue travoprost and the beta-adrenoceptor antagonist timolol. It is indicated for the treatment of patients with open-angle glaucoma or ocular hypertension who are insufficiently responsive to topical beta-adrenoceptor antagonists or prostaglandin analogues. Once-daily travoprost/timolol had generally similar efficacy to travoprost plus timolol and was more effective than travoprost or timolol monotherapy in reducing intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension in randomised, well designed studies. Both travoprost/timolol and latanoprost plus timolol maintained IOP control, and travoprost/timolol was shown to be noninferior to latanoprost/timolol in randomised, well designed studies. Travoprost/timolol was generally well tolerated, with a tolerability profile similar to those of travoprost plus timolol, travoprost or timolol monotherapy and latanoprost plus timolol. The majority of adverse events, such as ocular hyperaemia, were mild and resolved with or without treatment.     

A cost-effectiveness analysis of fixed-combination therapies in patients with open-angle glaucoma: a European perspective

ABSTRACT

Objective: To compare the efficacy and cost implications of the use of the intraocular pressure-lowering prosta­glandin analogues bimatoprost, travoprost, and latano­prost as fixed-combination therapies with timolol, a β-adrenergic receptor antagonist.

Methods: A decision analytic cost-effectiveness model was constructed. Since no head-to-head studies comparing the three treatment options exist, the analysis was based on an indirect comparison. Hence, the model was based on efficacy data from five randomized, controlled, clinical studies. The studies were comparable with respect to study design, time horizon, patient population and type of end point presented. The measure of effectiveness was the percentage reduction of the intraocular pressure level from baseline. The cost evaluated was the cost of medication and clinical visits to the ophthalmologist. All drug costs were market prices inclusive of value-added tax, and visit costs were priced using official physician fees. Cost-effectiveness analyses were carried out in five European countries: Spain, Italy, United Kingdom, Norway and Sweden. The time horizon for the analyses was 3 months.

Results: The analysis showed that fixed-combination bimatoprost/timolol was more effective and less costly than fixed-combination travoprost/timolol and fixed-combination latanoprost/timolol in three out of the five countries analyzed. In two countries, bimatoprost/timolol was less costly than latanoprost/timolol, and cost the same as travoprost/timolol.

Conclusions: This cost-effectiveness analysis showed that the fixed combination of bimatoprost 0.03%/timolol 0.5% administered once daily was a cost-effective treatment option for patients with primary open-angle glaucoma. This study was limited by available clinical data: without a head-to-head trial, indirect comparisons were necessary. In the United Kingdom, Sweden, Norway, Italy, and Spain, from a health service viewpoint, bimatoprost/timolol was a slightly more effective as well as less costly treatment strategy when compared to both travoprost/timolol and latanoprost/timolol.     

Intraocular pressure reduction with travoprost/timolol fixed combination,with and without adjunctive brinzolamide,in glaucoma

ABSTRACT

Objective: To investigate if combined intraocular pressure (IOP)-lowering medication with travoprost/timolol fixed combination and a carbonic anhydrase inhibitor, brinzolamide, is superior to both travoprost monotherapy and travoprost/timolol fixed-combination therapy in primary open-angle glaucoma and ocular hypertension.

Methods: Following a 4-week wash-out period and using 4-week long treatment periods, 20 primary open-angle glaucoma or ocular hypertension patients were treated with evening travoprost 0.004?%?, then switched to evening travoprost 0.004?%?/timolol 0.5?%?fixed combination, and finally the treatment was combined with adjunctive twice-daily brinzolamide 1?%?ophthalmic suspension. Both eyes were treated, but only one eye per patient (the eye with the higher mean diurnal IOP at baseline), was evaluated. IOP was measured at 8 a.m., 12 noon and 4 p.m. at baseline and at the end of each treatment period.

Results: Mean diurnal IOP (mean (SD)) at baseline was 28.5 (7.3) mmHg which decreased to 22.3 (6.3) mmHg on travoprost, 19.2 (3.4) mmHg on travoprost/timolol fixed combination and 17.3 (3.4) mmHg when the brinzolamide was added to the travoprost/timolol combination (ANOVA, contrast test, p?<?0.003 for all comparisons). The individual time point IOP values showed similar and significant stepwise differences.

Conclusion: Adjunctive brinzolamide medication provided further IOP decrease in patients receiving evening-dosed travoprost/timolol fixed combination. The travoprost/timolol fixed combination was significantly more effective in IOP reduction than travoprost monotherapy, which by itself induced a significant IOP decrease compared to the untreated baseline value. The results of this open label study suggest that combined therapy with travoprost/timolol fixed combination and brinzolamide is clinically useful for IOP-lowering in primary open-angle glaucoma and ocular hypertension.     

Latanoprost : an update of its use in glaucoma and ocular hypertension

Latanoprost (Xalatan) is an ester analogue of prostaglandin F2alpha that reduces intraocular pressure (IOP) by increasing uveoscleral outflow. The IOP-lowering efficacy of latanoprost 0.005% lasts for up to 24 hours after a single topical dose, which allows for a once-daily dosage regimen. In patients with ocular hypertension or open-angle glaucoma, a single drop of latanoprost 0.005% solution (about 1.5 microg) administered topically once daily reduced diurnal IOP by 22 to 39% over 1 to 12 months' treatment in well-controlled trials; efficacy was maintained during treatment periods of up to 2 years. At this dosage, latanoprost was significantly more effective than timolol 0.5% twice daily in 3 of 4 large, double-blind, randomised studies, was generally as effective as bimatoprost or travoprost, and was significantly more effective than dorzolamide, brimonidine or unoprostone. Furthermore, in patients whose IOP was poorly controlled with timolol, switching to latanoprost monotherapy was at least as effective at lowering IOP as adding dorzolamide or pilocarpine to the regimen. Latanoprost has also shown significant additive effects when used in combination with one or more other glaucoma medications. The fixed combination of latanoprost plus timolol was significantly more effective than either of its individual components in two double-blind randomised studies and more effective than the fixed combination of dorzolamide and timolol in a 3-month, evaluator-masked study. Data in patients with angle-closure glaucoma are limited, but in patients with elevated IOP after undergoing iridotomy, latanoprost 0.005% once daily was significantly more effective than timolol 0.5% twice daily at reducing IOP over 12 weeks of treatment in a large double-blind, randomised study. Latanoprost is generally well tolerated and, unlike timolol, induces minimal systemic adverse events. In well-controlled, 6-month trials, the most commonly occurring drug-related ocular events in latanoprost recipients were mild to moderate conjunctival hyperaemia (3 to 15%) and iris colour change (2 to 9%); these seldom required patient withdrawal although the latter may be permanent. Latanoprost 0.005% as a single daily drop has shown good IOP-lowering efficacy in patients with open-angle glaucoma or ocular hypertension and does not produce the cardiopulmonary adverse effects associated with beta-blockers. Thus, latanoprost is a valuable addition to the first-line treatment options for patients with open-angle glaucoma or ocular hypertension. In addition, adjunctive treatment with latanoprost in patients who are refractory to beta-blocker therapy is a viable, second-line treatment option. Although preliminary findings are promising, wider clinical experience is required to define the place of latanoprost in the treatment of angle-closure glaucoma.     

Fixed-combination and emerging glaucoma therapies

Ocular hypotensive agents are the only approved pharmacotherapy for glaucoma. Despite significant advances during the past two decades, a large proportion of glaucoma patients require more than one drug. The most recent additions to the armamentarium of antiglaucoma drugs are fixed-combination products for the glaucoma patient who is insufficiently responsive to monotherapy. Fixed-combination products have the combined efficacy of two ocular hypotensive drugs, and the convenience of a two-drug treatment regimen in a single container, which may aid patient adherence to treatment. Available fixed-combination products consist of timolol 0.5% as an invariant with brimonidine 0.2%, dorzolamide 2%, travoprost 0.004%, latanoprost 0.005% or bimatoprost 0.03%. Research on more advanced antiglaucoma medications continues. Promising new directions appear to be the Rho-kinase inhibitors, microtubule-disrupting agents, serotonergics and cannabimimetics. Efforts continue to improve existing antiglaucoma drugs in an attempt to design second-generation cholinomimetics, adrenergics, prostaglandins and prostamides.     

Fixed-combination and emerging glaucoma therapies

Ocular hypotensive agents are the only approved pharmacotherapy for glaucoma. Despite significant advances during the past two decades, a large proportion of glaucoma patients require more than one drug. The most recent additions to the armamentarium of antiglaucoma drugs are fixed-combination products for the glaucoma patient who is insufficiently responsive to monotherapy. Fixed-combination products have the combined efficacy of two ocular hypotensive drugs, and the convenience of a two-drug treatment regimen in a single container, which may aid patient adherence to treatment. Available fixed-combination products consist of timolol 0.5% as an invariant with brimonidine 0.2%, dorzolamide 2%, travoprost 0.004%, latanoprost 0.005% or bimatoprost 0.03%. Research on more advanced antiglaucoma medications continues. Promising new directions appear to be the Rho-kinase inhibitors, microtubule-disrupting agents, serotonergics and cannabimimetics. Efforts continue to improve existing antiglaucoma drugs in an attempt to design second-generation cholinomimetics, adrenergics, prostaglandins and prostamides.     

Travoprost versus latanoprost combinations in glaucoma: economic evaluation based on visual field deficit progression

OBJECTIVE: Changes in intraocular pressure (IOP) are known to be related to visual field deficit progression, although multiple models of this relationship exist. In addition, visual functioning is known to affect medical costs. The objective of this study was to project visual field deficit progression and subsequent costs based on clinical trial data. RESEARCH DESIGN AND METHODS: Using data from a randomized, 12-month, double-masked study, we compared the use of a fixed combination of travoprost 0.004%/timolol 0.5% (T/T) versus a fixed combination of latanoprost 0.005%/timolol 0.5% (L/T) on visual field deficit progression and associated costs. We applied published algorithms linking IOP to visual field changes to calculate the likelihood of visual field deterioration by treatment group. Differences in medical care costs were estimated using guideline-recommended practice patterns, Medicare hospital costs, and published estimates of differences in hospitalization by visual functioning. MAIN OUTCOME MEASURES: Increase in visual field deficit progression rates, increase in annual hospital days per subject, and increase in annual hospital, outpatient, and total costs per subject. RESULTS: Predicted visual field deficit progression for T/T patients was less than that for L/T patients (not statistically significant). Projected annual medical care costs were 43 dollars lower for T/T vs. L/T patients. CONCLUSIONS: By applying published algorithms linking IOP to visual field changes, this study projected long-term visual field deficit and associated costs. Use of a fixed travoprost/timolol solution may lead to less long-term visual field deficit progression and lower annual medical care costs than a fixed latanoprost/timolol solution. DISCUSSION: The use of clinical trial data may limit the applicability of these findings. However, this analysis of direct medical costs only is likely a conservative estimate of the costs associated with visual field deficits.     

Concomitant administration of travoprost and brinzolamide versus fixed latanoprost/timolol combined therapy: three-month comparison of efficacy and safety

PURPOSE: To compare the efficacy and safety of the concomitant administration of travoprost 0.004% once daily and brinzolamide 0.1% twice daily with those of a fixed combination of latanoprost 0.005%/timolol 0.5% once daily. RESEARCH, DESIGN AND METHODS: Forty-four patients with primary open-angle glaucoma or ocular hypertension with elevated IOP insufficiently responsive to monotherapy were randomly assigned to one of the two treatment groups: concomitant administration of travoprost 0.004% once daily and brinzolamide 0.1% twice daily (TB group: 22 patients) or latanoprost 0.005% plus timolol 0.5% once daily (LT group: 22 patients). Visits were undertaken at screening (current ocular hypotensive therapy was discontinued), baseline (randomization), and after 2 weeks, 1 month, 2 months and 3 months of therapy. MAIN OUTCOME MEASURES: IOP was determined at 9 a.m., 12 p.m. and 4 p.m. at each study visit, and diurnal IOP was calculated as the mean of these recordings. Adverse events were recorded at each visit. RESULTS: IOP at the baseline visit was similar in both groups. Overall mean IOP was significantly lower in the TB as compared to the LT group after 1 month, 2 month and 3 month follow-up; only 9 a.m. measurements were significantly different, reaching a maximum difference (16.9 +/- 0.9 mmHg vs 18.4 +/- 1.8 mmHg, p < 0.001) at the 3 month check. The percentage of responders (IOP decrease > or = 30%) was higher in the TB group. Both treatments were well tolerated and there were no cases of withdrawal from treatment. CONCLUSIONS: Travoprost 0.004% and brinzolamide 0.1% concomitant therapy showed a greater efficacy than the fixed latanoprost 0.005%/timolol 0.5% combination in terms of absolute IOP decreases. Travoprost/brinzolamide therapy also offered the advantages of a greater percentage of responders.     

Topical brimonidine 0.2%/timolol 0.5% ophthalmic solution: in glaucoma and ocular hypertension

A fixed combination of brimonidine (a highly selective alpha(2)-adrenergic agonist) and timolol (a non-selective beta-blocker) [brimonidine 0.2%/timolol 0.5% ophthalmic solution; brimonidine/timolol] is available for the topical treatment of glaucoma and ocular hypertension (OH). Brimonidine and timolol decrease elevated intraocular pressure (IOP) by complementary mechanisms of action and have an additive effect when coadministered to healthy volunteers and patients with glaucoma or OH. When assessed over a 3- or 12-month period in large, well designed clinical studies, brimonidine/timolol instilled twice daily (one drop in each eye) was superior to monotherapy with the individual components instilled two (brimonidine) or three (timolol) times daily, and noninferior to concomitant therapy with the individual components instilled twice daily, in lowering raised IOP in patients with glaucoma or OH. In small, randomised, comparative studies of 1 or 3 months' duration, the IOP-lowering effect of brimonidine/timolol twice daily was similar or superior to that of fixed combination dorzolamide 2%/timolol 0.5% ophthalmic solution (dorzolamide/timolol) twice daily (preliminary data). Brimonidine/timolol is generally well tolerated with a predictable local and systemic adverse event profile based on that of the individual components used alone and concomitantly. No unexpected or serious adverse events associated with the fixed combination were reported in key clinical trials. Brimonidine/timolol may be advantageous over dorzolamide/timolol with respect to ocular tolerability and comfort (preliminary data).     

Travoprost versus latanoprost combinations in glaucoma:economic evaluation based on visual field deficit progression

ABSTRACT

Objective: Changes in intraocular pressure (IOP) are known to be related to visual field deficit progression, although multiple models of this relationship exist. In addition, visual functioning is known to affect medical costs. The objective of this study was to project visual field deficitprogression and subsequent costs based on clinical trial data.

Research design and methods: Using data from a randomized, 12‐month, double-masked study, we compared the use of a fixed combination of travoprost 0.004%/timolol 0.5% (T/T) versus a fixed combination of latanoprost 0.005%/timolol 0.5% (L/T) on visual field deficit progression and associated costs. We applied published algorithms linking IOP to visual field changes to calculate the likelihood of visual field deterioration by treatment group. Differences in medical care costs were estimated using guideline-recommended practice patterns, Medicare hospital costs, and published estimates of differences in hospitalization by visual functioning.

Main outcome measures: Increase in visual field deficit progression rates, increase in annual hospital days per subject, and increase in annual hospital, outpatient, and total costs per subject.

Results: Predicted visual field deficit progression for T/T patients was less than that for L/T patients (not statistically significant). Projected annual medical care costs were $43 lower for T/T vs. L/T patients.

Conclusions: By applying published algorithms linking IOP to visual field changes, this study projected long-term visual field deficit and associated costs. Use of a fixed travoprost/timolol solution may lead to less long-term visual field deficit progression and lower annual medical care costs than a fixed latanoprost/timolol solution.

Discussion: The use of clinical trial data may limit the applicability of these findings. However, this analysis of direct medical costs only is likely a conservative estimate of the costs associated with visual field deficits.     

In vitro evaluation for corneal damages by anti-glaucoma combination eye drops using human corneal epithelial cell (HCE-T)

The combination of anti-glaucoma eye drops is frequently used in clinical treatment, and it is known that the combination can cause corneal damage. Recently, an anti-glaucoma combination eye drops is developed, and the treatment by the combination eye drops is expected to enhance quality of life. However, effects of the combination eye drops on corneal epithelial cell damage have not been clarified. In this study, we investigated the corneal epithelial cell damage of commercially available anti-glaucoma combination eye drops, such as Xalacom? (latanoprost/timolol maleate combination eye drops), Duotrav? (travoprost/timolol maleate combination eye drops) and Cosopt? (dorzolamide hydrochloride/timolol maleate combination eye drops) using the human corneal epithelial cell (HCE-T). The cytotoxicity in Xalacom? was higher than that in Xalatan? (eye drops containing latanoprost) and Timoptol? (eye drops containing timolol maleate), and the benzalkonium chloride (BAC) and timolol maleate were related to cytotoxicity in Xalacom?. The cytotoxicity in Duotrav? and Cosopt? was lower than that in Timoptol?. The Duotrav? is preserved with a non-BAC system (POLYQUAD, polidronium chloride). Therefore, it was suggested that the POLYQUAD related to the low cytotoxicity in Duotrav?. On the other hand, the D-mannitol reduced the cytotoxicity by BAC in this study. This result suggested that the cytotoxicity in Cosopt? was reduced by D-mannitol. The Duotrav? and Cosopt? may be less damaging to the ocular surface of glaucoma patients receiving long-term eye drop therapy in compared with the combination of anti-glaucoma eye drops.     

Travoprost/timolol fixed combination in the management of open-angle glaucoma: a clinical review

INTRODUCTION: many patients with glaucoma require multiple medications for adequate disease control. This review summarizes the efficacy and safety of the travoprost/timolol fixed combination in lowering intraocular pressure in eyes with glaucoma. AREAS COVERED: phase III and IV evaluations of travoprost/timolol are reviewed, including trials comparing the fixed combination with constituents, with unfixed concomitant therapy and with other unfixed and fixed combinations of glaucoma medications. The safety of travoprost/timolol is also reviewed. EXPERT OPINION: the role of fixed-combination drugs, including travoprost/timolol, in the management of glaucoma is discussed. Unmet needs in glaucoma therapy, including long-acting drug delivery systems and therapies that treat glaucoma via mechanisms other than reduction of intraocular pressure, are also presented.     

Analytic review of bimatoprost, latanoprost and travoprost in primary open angle glaucoma

OBJECTIVE: The objective of this review was to evaluate different measures of efficacy of the intraocular pressure (IOP) lowering lipid class agents bimatoprost, latanoprost and travoprost in the treatment of primary open angle glaucoma. Study arms of timolol in trials including the above mentioned lipid class drugs were also included. METHODS: MEDLINE and EMBASE were searched for randomized clinical trials including one or more of the lipid class drugs bimatoprost, latanoprost and travoprost. The study results were pooled, and the simple, weighted IOP-lowering efficacy was compared among the lipid class drugs and timolol, where data were available. Efficacy parameters were reviewed, including mean reduction of IOP and percentage of patients achieving different levels of IOP. RESULTS: 161 articles were identified of which 42 were included in the analysis. A total of 9295 patients participated in the included trials. Based on all studies, timolol on average had a weighted mean IOP reduction of 22.2%, while latanoprost, travoprost and bimatoprost had a weighted mean IOP reduction of 26.7%, 28.7% and 30.3%, respectively. Analysis of target achievement to various IOP levels shows that bimatoprost seems more efficacious than latanoprost. The direct comparisons (head-to-head studies) also show that bimatoprost is the most efficacious treatment, however it is not conclusive whether latanoprost or travoprost is better in reducing IOP. CONCLUSIONS: This review shows that bimatoprost seems to be the most efficacious treatment in lowering IOP. Head-to-head studies confirm this.     

Concomitant administration of travoprost and brinzolamide versus fixed latanoprost/timolol combined therapy: three-month comparison of efficacy and safety

SUMMARY

Purpose: To compare the efficacy and safety of the concomitant administration of travoprost 0.004% once daily and brinzolamide 0.1% twice daily with those of a fixed combination of latanoprost 0.005%/timolol 0.5% once daily.

Research, design and methods: Forty-four patients with primary open-angle glaucoma or ocular hypertension with elevated IOP insufficiently responsive to monotherapy were randomly assigned to one of the two treatment groups: concomitant administration of travoprost 0.004% once daily and brinzolamide 0.1% twice daily (TB group: 22 patients) or latanoprost 0.005% plus timolol 0.5% once daily (LT group: 22 patients). Visits were undertaken at screening (current ocular hypotensive therapy was discontinued), baseline (randomization), and after 2 weeks, 1 month, 2 months and 3 months of therapy.

Main outcome measures: IOP was determined at 9 a.m., 12 p.m. and 4 p.m. at each study visit, and diurnal IOP was calculated as the mean of these recordings. Adverse events were recorded at each visit.

Results: IOP at the baseline visit was similar in both groups. Overall mean IOP was significantly lower in the TB as compared to the LT group after 1?month, 2?month and 3?month follow-up; only 9 a.m. measurements were significantly different, reaching a maximum difference (16.9 ± 0.9?mmHg vs 18.4 ± 1.8?mmHg, p < 0.001) at the 3?month check. The percentage of responders (IOP decrease ≥ 30%) was higher in the TB group. Both treatments were well tolerated and there were no cases of withdrawal from treatment.

Conclusions: Travoprost 0.004% and brinzolamide 0.1% concomitant therapy showed a greater efficacy than the fixed latanoprost 0.005%/timolol 0.5% combination in terms of absolute IOP decreases. Travoprost/brinzolamide therapy also offered the advantages of a greater percentage of responders.     

Travoprost

Travoprost is a synthetic ester prodrug of a prostaglandin F(2alpha) analogue used in the treatment of open-angle glaucoma and ocular hypertension. Intraocular travoprost 0.004% once daily was significantly more effective at reducing intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension than placebo or timolol 0.5% twice daily and was at least as effective as latanoprost 0.005% once daily in randomised, double-blind studies. When used as adjunctive therapy with timolol 0.5% twice daily in patients with elevated IOP not adequately controlled by timolol alone, travoprost 0.004% showed significant additional IOP reduction in a randomised double-blind trial. Travoprost 0.004% was well tolerated in clinical trials. The majority of adverse events such as ocular hyperaemia and eyelash changes were mild and resolved without treatment.     

拉坦前列素滴眼液与其复合剂的降眼压作用的比较

目的：评价0.005%拉坦前列素滴眼液＋0.5%噻吗洛尔滴眼液治疗原发性开角形青光眼患者的替代降眼压作用及其安全性。方法应用0.005%拉坦前列素滴眼液单一治疗的原发性开角型青光眼患者31例,给予0.005%拉坦前列素滴眼液＋0.5%噻吗洛尔滴眼液替代治疗。每晚点药1次,每次1滴。将连续点药后4、8、12周的眼压与基线眼压进行比较研究,同时观察血压、心率等全身及局部不良反应。结果0.005%拉坦前列素滴眼液＋0.5%噻吗洛尔滴眼液可以更有效降低眼压。连续点药4、8、12周后,与基线相比,眼压分别额外下降（2.2±1.1）mmHg、（2.0±0.9）mmHg、（2.2±1.0）mmHg,差异均具有统计学意义（P〈0.05）。连续点药4、8、12周后,获得至少2mmHg眼压下降值的患者百分率分别为64.5%、61.3%、64.5%。心动过缓（3.2%）是最严重的不良反应。结论0.005%拉坦前列素＋0.5%噻吗洛尔复方滴眼液能够更加有效的降低目标眼压,可以作为0.005%拉坦前列素滴眼液的替代治疗手段。     

Analytic review of bimatoprost,latanoprost and travoprost in primary open angle glaucoma

ABSTRACT

Objective: The objective of this review was to evaluate different measures of efficacy of the intraocular pressure (IOP) lowering lipid class agents bimatoprost, latanoprost and travoprost in the treatment of primary open angle glaucoma. Study arms of timolol in trials including the above mentioned lipid class drugs were also included.

Methods: MEDLINE and EMBASE were searched for randomized clinical trials including one or more of the lipid class drugs bimatoprost, latanoprost and travoprost. The study results were pooled, and the simple, weighted IOP-lowering efficacy was compared among the lipid class drugs and timolol, where data were available. Efficacy parameters were reviewed, including mean reduction of IOP and percentage of patients achieving different levels of IOP.

Results: 161 articles were identified of which 42 were included in the analysis. A total of 9295 patients participated in the included trials. Based on all studies, timolol on average had a weighted mean IOP reduction of 22.2%, while latanoprost, travoprost and bimatoprost had a weighted mean IOP reduction of 26.7%, 28.7% and 30.3%, respectively. Analysis of target achievement to various IOP levels shows that bimatoprost seems more efficacious than latanoprost. The direct comparisons (head-to-head studies) also show that bimatoprost is the most efficacious treatment, however it is not conclusive whether latanoprost or travoprost is better in reducing IOP.

Conclusions: This review shows that bimatoprost seems to be the most efficacious treatment in lowering IOP. Head-to-head studies confirm this.     

Circadian IOP-lowering efficacy of travoprost 0.004% ophthalmic solution compared to latanoprost 0.005%

PURPOSE: The primary objective of this study was to determine the intraocular pressure- (IOP) lowering efficacy over two consecutive 24-h periods of travoprost 0.004% ophthalmic solution (Travatan) compared to latanoprost 0.005% (Xalatan) dosed once daily in patients with primary open-angle glaucoma or ocular hypertension. METHODS: This was a double-masked trial conducted at the Hospital Clínico San Carlos, Madrid, Spain. The primary objective of this study was to determine the IOP lowering efficacy of travoprost and latanoprost. During the eligibility visit, patients' IOP was measured throughout two consecutive 24-h periods every 4 h. Patients were then randomized to travoprost or latanoprost (one drop at 8 p.m. daily for 2 weeks). Sixty-two patients were randomized (travoprost n = 32; latanoprost n = 30). IOP was measured at week 2 every 4 h throughout two 24-h periods. All measurements were taken in both supine and sitting positions with the aid of Perkins applanation tonometry. Limitations of the study include a small sample size (due to the difficulty in recruiting patients in a study of this type) which enrolled only Caucasian patients and a short study duration. However, with 25 subjects per group, there was at least 90% power to detect a mean IOP change from baseline of 2.9 mmHg and 80% power to detect a difference of 2.5 mmHg between treatments. RESULTS: Patients on travoprost therapy showed lower mean IOP levels than those on latanoprost. This difference was statistically significant (p < 0.05) at 12, 16, 20, 24, 36, 40, and 48 h after the last dose for the supine position. The mean IOPs in the supine position throughout the first and the second 24-h period of the week 2 visit as well as for the 48-h visit were statistically lower (p < 0.05) for the travoprost group. Adverse events were mild and included hyperemia and corneal staining. Travoprost and latanoprost were both well tolerated. CONCLUSION: Mean IOP values were significantly lower for patients on travoprost for the majority of time points in the supine position.     

Switching from concomitant latanoprost 0.005% and timolol 0.5% to a fixed combination of travoprost 0.004%/timolol 0.5% in patients with primary open-angle glaucoma and ocular hypertension: a 6-month,multicenter, cohort study

Purpose: To assess the usefulness and tolerability of systematically switching glaucoma patients from latanoprost 0.005% and timolol 0.5% (Lat + Tim) to a fixed combination of travoprost 0.004%/timolol 0.5% (TTFC), and to record the effects of this switch on tear-film break-up time (TBUT). Main outcome measures: Intraocular pressure (IOP) reduction, patients reaching IOP < 18 mmHg; the rate of discontinuation; TBUT; and the onset of adverse events (AEs). Methods: Multicenter, observational cohort, 6-month study: 309 patients on concomitant Lat + Tim were switched to TTFC (evening dosage). IOP, TBUT, and AEs were recorded at baseline and after 1 and 6 months. Results: IOP was significantly decreased (from 18.3 ± 2.9 to 16.6 ± 2.7 mmHg) after substitution (p < 0.0001). Many patients (82%) reached an IOP < 18 mmHg (p < 0.0001). TBUT improved significantly (from 8.4 ± 3.6 to 9.2 ± 3.8 s, p < 0.0001). A few patients reported AEs (8.7%), which caused discontinuation in a low percentage (4.5%). Conclusion: TTFC appeared useful in this selected population. In this study, patients who underwent a regimen modification to TTFC obtained further reduction in IOP with a lower exposition to preservative toxicity. The low discontinuation rate at 6 months indicates a good tolerability profile.