Comparative efficacy of gel-forming and ophthalmic solutions of 0.5% timolol in open-angle glaucoma

We compared the efficacy in lowering intraocular pressure (IOP) of 0.5% timolol maleate gel-forming solution (GFS) once daily with 0.5% timolol maleate ophthalmic solution twice daily in patients with open-angle glaucoma. In both treatment groups (30 eyes each), IOP was measured at baseline and weeks 2, 4, 8, 12, and 24. The mean decrease of IOP at trough ranged from 5.5 to 5.9 mm Hg for timolol GFS and from 6.1 to 6.5 mm Hg for timolol solution. The authors have stated that they do not have a significant financial interest or other relationship with any product manufacturer or provider of services discussed in this article.     

Long-term intraocular pressure-lowering efficacy and safety of timolol maleate gel-forming solution 0.5% compared with Timoptic XE 0.5% in a 12-month study

PURPOSE: To evaluate the long-term intraocular pressure-lowering efficacy and safety of timolol maleate gel-forming solution 0.5% (Timolol GFS 0.5%, Alcon Research Ltd, Fort Worth, Texas) compared with Timoptic XE 0.5% (Merck, Inc, West Point, Pennsylvania) in patients with open-angle glaucoma or ocular hypertension. METHODS: Two hundred forty-one patients with open-angle glaucoma or ocular hypertension, who had intraocular pressure between 22 and 36 mm Hg in at least one eye, were randomly assigned in a 2:1 ratio to receive either Timolol GFS 0.5% once daily or Timoptic XE 0.5% once daily, in a 12-month randomized, multicenter, double-masked, prospective study. The primary efficacy variable was mean trough intraocular pressure measured at 8:00 AM, approximately 24 hours after dosing. RESULTS: The Timolol GFS 0.5% group produced significant trough intraocular pressure reductions from a baseline of 4.5 to 5.2 mm Hg (P =.0001), compared with reductions of 4.1 to 5. 3 mm Hg (P =.0001) in the Timoptic XE 0.5% group. The difference in mean intraocular pressure between the two treatments was 0.9 mm Hg or less, and the upper 95% confidence limit between groups was 0.92 mm Hg or less at all time points, demonstrating both clinical and statistical equivalence. A similar percentage of patients in the Timolol GFS 0.5% group (71%) and Timoptic XE group (72%) had clinically relevant reductions in intraocular pressure. There was no significant difference in the safety profiles of the two treatments. CONCLUSION: Both treatments were clinically effective in lowering intraocular pressure and maintaining the reductions over long-term use. Timolol GFS 0.5% is a safe and effective therapy for open-angle glaucoma or ocular hypertension and is both clinically and statistically equivalent to Timoptic XE 0.5% in reducing intraocular pressure.     

A comparison of the efficacy and tolerability of 0.5% timolol maleate ophthalmic gel-forming solution QD and 0.5% levobunolol hydrochloride BID in patients with ocular hypertension or open-angle glaucoma.

The purpose of this study was to compare the ocular hypotensive efficacy and tolerability of 0.5% timolol maleate ophthalmic gel-forming solution (timolol gel) and 0.5% levobunolol hydrochloride (levobunolol). This was a randomized, double-masked, multi-center, active-controlled, 2-period, crossover study. After a 3-week, single-masked placebo run-in phase, patients with ocular hypertension or open-angle glaucoma and an intraocular pressure (IOP) > or = 22 mmHg were randomized to receive timolol gel QD or levobunolol BID for 6 weeks followed by a 3-week, placebo washout period. Patients were then crossed over to the alternate treatment for 6 weeks. IOP and heart rate (HR) were measured at 3 and 6 weeks after the start of therapy with either timolol gel or levobunolol. Of 133 patients randomized, 116 received both treatments. Timolol gel QD was comparable to levobunolol BID in reducing trough and peak IOP. At trough, HR was marginally increased with timolol gel and was decreased with levobunolol (p = < 0.001). At peak, HR was decreased with both treatments, but the decrease was significantly less with timolol gel than with levobunolol (p = 0.049). Significantly more patients experienced at least one adverse event (p = 0.024), adverse events related to special senses (p = 0.002), and burning and stinging (p < 0.001) with levobunolol compared to timolol gel. The study demonstrates that timolol gel QD has IOP-lowering effects comparable to those of levobunolol BID with fewer adverse experiences and less effect on HR.     

Brimonidine 0.2% given two or three times daily versus timolol maleate 0.5% in primary open-angle glaucoma

PURPOSE: To evaluate the efficacy and safety of brimonidine 0.2% two or three times daily versus timolol maleate 0.5% solution twice daily. METHODS: Patients with primary open-angle glaucoma were randomized by Latin square technique to one of the three treatment sequences in this crossover, prospective double-masked trial. Each treatment period consisted of 6 weeks of chronic dosing followed by a diurnal curve for the intraocular pressure measured at 08:00, 10:00, 16:00, 18:00, 20:00, 22:00, and 24:00 hours. Intraocular pressure was measured by applanation tonometry. RESULTS: Thirty patients completed this trial. The average diurnal intraocular pressures in the trial were measured for timolol maleate (17.7 +/- 2.7 mm Hg), brimonidine given three times daily (18.0 +/- 2.2 mm Hg), and brimonidine given twice daily (19.2 +/- 2.4 mm Hg). There was a statistical difference between groups (P <.005). When groups were compared by pairs, three times daily dosing with brimonidine and timolol maleate both reduced the pressure more than twice daily brimonidine at every time point past 10:00 hours and for the diurnal curve (P <.05). In contrast, three times daily brimonidine and timolol maleate were statistically similar for the diurnal pressure, and each time point, except timolol maleate, decreased the pressure more at 16:00 (P =.042). Safety was similar between groups. CONCLUSIONS: This study demonstrated that both timolol maleate twice daily and brimonidine three times daily provide a similar intraocular pressure reduction to each other. Timolol maleate twice daily and brimonidine three times daily provide a greater decrease in pressure in the late afternoon and nighttime hours, compared with brimonidine twice daily.     

Comparison of 24 hour control with Timoptic 0.5% and Timoptic-XE 0.5% in exfoliation and primary open-angle glaucoma.

PURPOSE: To compare the 24 hour intraocular pressure (IOP) curve in exfoliation glaucoma (EXG) and primary open-angle glaucoma (POAG) patients treated first with timolol solution 0.5% (TS) twice daily and then with timolol maleate gel forming solution 0.5% (TXE) once daily. METHODS: We prospectively investigated age-matched, newly diagnosed EXG (n = 25) and POAG (n = 25) patients who were admitted as in-patients for 24 hour phasing first with TS and then TXE. RESULTS: Generally TS and TXE controlled both POAG and EXG patients in a similar fashion. However, a trend to lower pressures was observed in both EXG and POAG patients with TS therapy. At two time points (10:00 and 22:00) in POAG patients, TS (18.4 +/- 3.7 and 17.2 +/- 3.1 mm Hg, respectively) provided lower intraocular pressures than TXE (19.8 +/- 3.5 and 18.9 +/- 3.8 mm Hg, respectively) (p < 0.05). CONCLUSION: Both TS twice daily and TXE once daily control POAG and EXG generally to a similar extent.     

Effect of timolol 0.5% gel and solution on pulmonary function in older glaucoma patients.

PURPOSE: To evaluate the effect of timolol maleate solution or gel forming solution versus placebo on pulmonary function in patients with primary open-angle glaucoma or ocular hypertension without reactive airway disease. METHODS: After a screening visit, each patient was randomized by a Latin square technique to receive placebo twice daily, 0.5% timolol solution twice daily, or 0.5% timolol gel once a day (placebo given as second dose) to each eye for 2 weeks. Subjects then were crossed over to the two other treatments for 2-week treatment intervals. At each visit, patients were received a dose 15 minutes before pulmonary function testing. RESULTS: This study began with 25 patients, and 20 finished the trial. There was no difference between treatment groups for the forced expiratory volume at one second (FEV1), forced vital capacity (FVC), FEV1/FVC ratio (P > 0.1). The mean FEV1 for timolol solution, timolol gel, and placebo was 2.42 L, 2.45 L, and 2.50 L, respectively. The mean FVC for timolol solution, timolol gel, and placebo was 3.33 L, 3.38 L, and 3.44 L, respectively. No difference in intraocular pressure was observed between the timolol solution (17.1 +/- 3.3 mm Hg) and timolol gel (17.1 +/- 3.6 mm Hg) between the treatment periods (P > 0.1). No difference in side effects was observed between treatment groups (P > 0.05). CONCLUSIONS: In older patients with primary open-angle glaucoma or ocular hypertension without reactive airway disease, nonselective beta-blockers should not worsen pulmonary function.     

Timolol maleate in treatment of open angle glaucoma

The effect of Timolol maleate on the intraocular pressure in open angle glaucoma has been examined in 37 patients, of these simple glaucoma in 26 (48 eyes), capsular glaucoma in 9 (14 eyes) and chronic secondary glaucoma in 2 patients (2 eyes). These cases constituded a group which was relatively difficult to manage. The average pressure reduction caused by Timolol maleate alone was about 23%. In 18 patients the intraocular pressure was adequately controlled on Timolol as the only drug and in 10 on additional drug therapy. Five patients failed on drug treatment, and the remaining four failed on one eye while the fellow eye was well regulated. Tonography indicates that the effect is caused by a reduction of the aqueous humour production. Side effects of locally applied Timolol maleate have not been observed. This drug may be the drug of choice in many instances.     

Comparison of the effects of 0.5% timolol maleate, 2% carteolol hydrochloride, and 0.3% metipranolol on intraocular pressure and perimetry findings and evaluation of their ocular and systemic effects

PURPOSE: To compare the effects of 0.5% timolol maleate, 2% carteolol, and 0.3% metipranolol on intraocular pressure (IOP) in 45 patients with primary open-angle glaucoma (POAG) and ocular hypertension. A secondary goal of this study was to evaluate the ocular and systemic side effects of these medications. METHODS: Measurements of IOP were taken at baseline (pretreatment) and 2, 6, and 12 hours after instillation on treatment days 15, 30, 60, and 90. Mean sensitivity (MS) and mean defect (MD) values of perimetry before and after treatment and the effects of the three beta blockers on serum lipid profiles were determined. Ocular and systemic side effects were recorded. RESULTS: The most prominent IOP lowering effect was noted with metipranolol at 2 and 6 hours on day 15, and with timolol maleate at 12 hours on day 15 and at all hours of the subsequent days on which measurements were taken. Timolol maleate produced a significant decrease in IOP at 12 hours on day 15 compared with carteolol. There was not a statistically significant difference between the MS and MD values on perimetry before and after treatment for any treatment. There was a statistically significant decrease in levels of total cholesterol and high-density lipoprotein (HDL) cholesterol and a significant increase in triglyceride levels; these changes were observed for all treatments. CONCLUSION: The effects of the three medications were not statistically different from each other in terms of IOP reduction and visual field changes. Careful monitoring of blood lipid levels is necessary with long-term treatment with beta blockers, because these agents reduced serum levels of HDL and total cholesterol while increasing triglycerides. Such changes in lipid levels could lead to increased incidence of complications, particularly in patients with atherosclerosis or coronary heart disease.     

Timolol 0.5%/dorzolamide 2% fixed combination versus timolol 0.5%/pilocarpine 2% fixed combination in primary open-angle glaucoma or ocular hypertensive patients

PURPOSE: To establish the efficacy and safety of timolol maleate/dorzolamide fixed combination (TDFC) versus timolol maleate/pilocarpine fixed combination (TPFC), each given twice daily, in primary open-angle glaucoma or ocular hypertensive patients. METHODS: In this prospective, multicentred, double-masked trial, 37 patients were treated twice daily with timolol for 4 weeks. They were then randomized to one of the treatment medications for 6 weeks, after which they were treated with timolol again for 2 weeks before being placed on the opposite treatment medication for 6 weeks. RESULTS: A total of 36 patients completed the trial. Their mean baseline intraocular pressure (IOP) was 22.3 +/- 3.7 mmHg. Following 6 weeks of treatment, the mean trough (08.00 hours) IOP was 18.0 +/- 2.2 mmHg for TDFC and 17.4 +/- 2.0 mmHg for TPFC (p = 0.22). The mean diurnal curve IOP was 18.1 +/- 2.2 mmHg for TDFC and 16.7 +/- 1.9 mmHg for TPFC (p = 0.0007). At the remaining time-points (10.00, 18.00 and 20.00 hours), TPFC IOPs were statistically lower than TDFC IOPs (p < 0.03). There were statistically more unsolicited reports of vision change and ocular pain associated with TPFC (p = 0.04). Six patients were discontinued early from TPFC therapy (17%) versus two from TDFC (6%) (p = 0.13). CONCLUSIONS: This study suggests that TPFC can provide at least a similar efficacious reduction in IOP as TDFC in patients with primary open-angle glaucoma or ocular hypertension.     

2%美开朗与0.5%噻吗心安滴眼液治疗开角型青光眼与高眼压症的临床对照研究

目的以噻吗心安滴眼液作对照,在原发性开角型青光眼和高眼压症患者中评价美开朗滴眼液的降眼压、内在拟交感活性作用。方法选择开角型青光眼和高眼压症患者50例50眼,随机分为美开朗组和噻吗心安组2组,各25例25眼。美开朗组滴用2%美开朗眼液,噻吗心安组滴用0.5%噻吗心安眼液,一日2次,共12周,比较两种滴眼液的降眼压作用及局部和全身副作用。结果两组患者用药后眼压均下降,与用药前相比均有显著性差异(P<0.01)。两组间眼压下降值无显著性差异(P>0.05)。用药12周,美开朗组心率平均降低3.6次,噻吗心安组心率平均降低6.5次,两者相比有显著性差异。结论美开朗滴眼液对开角型青光眼和高眼压症患者具有明显的降眼压作用,和噻吗心安滴眼液局部降眼压作用相同,但对心率的抑制作用比噻吗心安小。     

A three-month, multicenter, double-masked study of the safety and efficacy of travoprost 0.004%/timolol 0.5% ophthalmic solution compared to travoprost 0.004% ophthalmic solution and timolol 0.5% dosed concomitantly in subjects with open angle glaucoma or ocular hypertension

PURPOSE: The primary objective of this study was to compare the intraocular pressure (IOP)-lowering efficacy of travoprost 0.004%/timolol 0.5% fixed combination to the concomitant administration of travoprost 0.004% (TRAVATAN) and timolol 0.5% in subjects with open angle glaucoma or ocular hypertension. METHODS: This was a randomized, multicenter, double-masked, active-controlled, parallel group study. Three hundred sixteen patients with open angle glaucoma or ocular hypertension were randomly assigned to travoprost 0.004%/timolol 0.5% ophthalmic solution fixed combination once daily in the morning or concomitant administration of timolol 0.5% once daily in the morning and travoprost 0.004% ophthalmic solution once daily in the evening. The efficacy and safety of the fixed combination were compared with concomitant therapy over three months. The primary efficacy outcome measure was mean intraocular pressure. RESULTS: Both travoprost 0.004%/timolol 0.5% fixed combination and the concomitant administration of travoprost 0.004% and timolol 0.5% produced statistically significant reductions from baseline in IOP, with mean IOP ranging from 15.2 to 16.5 mm Hg in the patients using travoprost 0.004%/timolol 0.5% fixed combination compared with 14.7 to 16.1 mm Hg in the concomitant group. The upper 95.1% confidence limit for the differences in mean IOP (fixed combination minus concomitant) was < or =1.5 mm Hg at 7 of 9 visits, including all three 8 AM time points, 24-hours post-dose. Mean IOP reductions from baseline ranged from 7.4 to 9.4 mm Hg in the fixed combination group compared with 8.4 to 9.4 mm Hg with concomitant therapy. Safety analysis demonstrated equivalent safety between the two treatment groups. CONCLUSIONS: A fixed combination of travoprost 0.004% and timolol 0.5% produced clinically relevant IOP reductions in patients with open angle glaucoma or ocular hypertension that were comparable to concomitant therapy with its components. Safety and tolerability of the fixed combination were also equivalent to concomitant therapy. Travoprost 0.004%/timolol 0.5% fixed combination offers IOP reduction equivalent to concomitant therapy, with potential benefits that include convenience (fewer bottles and drops per day), improved compliance, cost savings (based on fewer co-payments), and elimination of potential washout effects.     

A multicentre, observative, non-invasive study of the tolerance of NYOLOL gel 0,1% in ocular hypertensive patients

PURPOSE: To evaluate the safety and efficacy of Nyolol Gel 0,1%/Novartis vs. regular timolol formulation (Ofterisin 0,5%) in ocular hypertensive patients. MATERIAL AND METHODS: A comparative, multicentred non-invasive, 16-weeks study. 192 glaucoma or ocular hypertensive patients were randomized into 2 groups: patients receiving regular timolol treatment (group I) and patients treated with timolol gel formulation. After 8 weeks of assigned treatment subjects from group I were switched to Nyolol gel and the subjects from group B - to regular timolol respectively. Intraocular pressure (IOP), objective and subjective tolerance of treatment were evaluated. RESULTS: There were no differences between groups as far as level of IOP was concerned. The incidence of ocular adverse events was higher when patients were switched to timolol aqueous eye drops. Subjective local tolerance of timolol gel formulation was better than conventional eye drops. CONCLUSIONS: Timolol 0,1% gel formulation with a once daily application provides an IOP reduction equivalent to timolol 0,5% solution given twice a day. Local tolerability and safety of gel formulation is better than aqueous solution, both in the patient's and physician's opinions.     

Timolol 0.5%/dorzolamide 2% fixed combination vs timolol maleate 0.5% and unoprostone 0.15% given twice daily to patients with primary open-angle glaucoma or ocular hypertension

OBJECTIVE: To compare the efficacy and safety of timolol 0.5%/dorzolamide 2% fixed combination vs timolol maleate 0.5% and unoprostone 0.15% given twice daily. DESIGN: Prospective multicenter, randomized, double-masked, crossover comparison study. METHODS: Primary open-angle glaucoma or ocular hypertension patients were randomly assigned to one of the treatment groups for a 6-week treatment period and then crossed over to the opposite treatment. Diurnal curve testing was performed at 8:00 AM, 10:00 AM, 4:00 PM, 6:00 PM, and 8:00 PM at baseline and the end of each treatment period. The run-in medicine was timolol twice daily for 28 days. RESULTS: Thirty-two patients completed this trial. The baseline trough pressure was 24.3 +/- 3.0 mm Hg, and the diurnal curve was 23.4 +/- 3.2 mm Hg. For the fixed combination the treatment trough pressure was 20.8 +/- 4.1 mm Hg and the diurnal curve was 19.6 +/- 3.6 mm Hg, whereas timolol and unoprostone concomitant therapy showed a treatment trough pressure of 20.1 +/- 4.5 mm Hg and a diurnal pressure of 19.8 +/- 4.1 mm Hg. There was no significant difference between treatment groups at any time point, for the diurnal curve, or in the extended reduction from baseline. There was no difference between treatment groups regarding ocular and systemic unsolicited or solicited adverse events. Burning, stinging, and conjunctival hyperemia were the adverse events most noted. There were no serious adverse events during this trial. CONCLUSIONS: This study suggests that both timolol/dorzolamide 2% fixed combination and concomitant timolol maleate 0.5% and unoprostone 0.15% therapy provide similar efficacy and safety throughout the daytime diurnal curve.     

Plasma timolol concentrations of timolol maleate: timolol gel-forming solution (TIMOPTIC-XE®) once daily versus timolol maleate ophthalmic solution twice daily

Purpose: The objective of this study was to compare plasma concentrations of timolol following multiple dosing of the therapeutic regimens of timolol maleate ophthalmic gel-forming solution (Timolol GS; TIMOPTIC-XE®) and timolol maleate ophthalmic solution. Timolol maleate ophthalmic gel-forming solution is also referred to as Timolol GS, i.e. gel-forming solution. Methods: This was a masked observer, two-period crossover study in six normal male subjects randomized to receive either Timolol GS, 0.5% (TIMOPTIC-XE,) once daily (0530 hours) or timolol maleate ophthalmic solution (0.5% TIMOPTIC®) twice daily (0530 and 1730 hours) for 8 days, in both eyes. On Day 8, a blood sample was obtained prior to treatment, as well as 1, 2, 4, 8, 10, 12, 13, 14, 16, and 24 hours following the morning instillation. After a 7-day inter-period washout interval, subjects received the opposite treatment. Results: Timolol GS (TIMOPTIC-XE): Plasma concentrations of timolol rarely exceeded 0.375 ng/ml (the lower limit of assay quantification). For all subjects, peak plasma concentrations of timolol averaged <0.3 ng/ml within 4 hours after the last dose. The highest single observation was 0.49 ng/ml in one subject (at hour 2). Timolol solution: For all subjects, peak plasma concentrations of timolol averaged about 0.5 ng/ml and 0.3 ng/ml within 4 hours following the first and second dose, respectively, on Day 8. The highest single observation was 0.95 ng/ml in one subject (at hour 2). Conclusions: The data suggest that there is less systemic exposure to timolol following once-daily therapy with Timolol GS 0.5% compared with twice daily therapy with timolol maleate ophthalmic solution 0.5%.     

Timolol increased retrobulbar flow velocities in untreated glaucoma eyes but not in ocular hypertension

PURPOSE: To investigate retrobulbar blood flow velocities and the effects of topical timolol treatment in eyes with newly detected, previously untreated open angle glaucoma or ocular hypertension. METHODS: Fifteen eyes with open angle glaucoma (OAG) and 12 eyes with ocular hypertension (OH), in the same number of patients, all untreated and newly detected, were examined with colour Doppler imaging of retrobulbar vessels before and after 1 month of topical timolol treatment (0.5% Timoptic BID). RESULTS: Baseline central retinal artery end diastolic velocity was lower (48%, p=0.0002) and resistive index higher (7.6%, p=0.018) in the OAG group than in the OH group. In the glaucoma group mean end diastolic velocity increased by 41%, (p=0.006) while resistive index decreased by 5.8%, (p=0.02) on treatment, while no significant changes were seen in the OH group. Blood flow velocities in the ophthalmic artery did not change with treatment. Baseline IOP and IOP reduction did not differ between OAG and OH group. CONCLUSION: Peripheral resistance to blood flow was found to be increased in untreated glaucoma eyes as compared to a similar group of eyes with ocular hypertension. Timolol treatment diminished resistance significantly in the glaucoma group, but not in the ocular hypertension group. Thus the two groups responded differently to timolol treatment. The reaction to IOP lowering treatment could indicate defective autoregulation in the glaucoma group.     

Brimonidine 0.2% vs unoprostone 0.15% both added to timolol maleate 0.5% given twice daily to patients with primary open-angle glaucoma or ocular hypertension

PURPOSE: To compare the efficacy and safety of brimonidine 0.2% vs unoprostone 0.15%, both added to timolol maleate 0.5% each given twice daily. METHODS: In this prospective, multi-centred, double-masked, crossover comparison, patients were randomized to one treatment group for a 6-week treatment period, and then crossed over to the opposite treatment. Measurements were performed at 0800, 1000, 1600, 1800, and 2000 h at baseline and at the end of each treatment period. RESULTS: In all, 33 patients entered this trial and 29 completed. The baseline trough intraocular pressure (IOP) was 23.3+/-2.4 and the diurnal curve IOP was 22.0+/-1.3 mmHg. For the brimonidine and timolol maleate treatment group, the trough IOP was 21.6+/-3.3 and the diurnal curve IOP was 19.8+/-2.1 mmHg, while the timolol and unoprostone treatment showed a trough IOP of 20.9+/-3.8 and a diurnal curve IOP of 19.3+/-2.4 mmHg. There was no significant difference between treatment groups at any time point for the diurnal curve, or in the reduction from baseline (P>0.05). Both treatments failed to statistically reduce the IOP from baseline at 1800 h. There was no difference between treatment groups regarding ocular and systemic unsolicited adverse events, but patients admitted to more dryness (P=0.02) and burning upon instillation (P<0.0001) with unoprostone by survey. CONCLUSION: Brimonidine 0.2% or unoprostone 0.15% added to timolol maleate 0.5% provide similar efficacy and safety throughout the daytime diurnal curve.     

Comparing the Efficacy of Latanoprost (0.005%), Bimatoprost (0.03%), Travoprost (0.004%), and Timolol (0.5%) in the Treatment of Primary Open Angle Glaucoma

Purpose

To compare the efficacy and safety of latanoprost, bimatoprost, travoprost and timolol in reducing intraocular pressure (IOP) in patients with primary open angle glaucoma.

Methods

This was a prospective study conducted at a tertiary-care centre. One hundred and forty patients with newly diagnosed primary open angle glaucoma were randomly assigned to treatment with latanoprost (0.005%), bimatoprost (0.03%), travoprost (0.004%) or timolol gel (0.5%); 35 patients were assigned to each group. All patients were followed for 2, 6, and 12 weeks. The main outcome measure studied was the change in IOP at week 12 from the baseline values. Safety measures included recording of adverse events.

Results

The mean IOP reduction from baseline at week 12 was significantly more with bimatoprost (8.8 mmHg, 35.9%) than with latanoprost (7.3 mmHg, 29.9%), travoprost (7.6 mmHg, 30.8%) or timolol (6.7 mmHg, 26.6%) (ANOVA and Student''s t-tests, p < 0.001). Among the prostaglandins studied, bimatoprost produced a maximum reduction in IOP (-2.71; 95% confidence interval [CI], -2.25 to -3.18) followed by travoprost (-1.27; 95% CI, -0.81 to -1.27) and latanoprost (-1.25; 95% CI, -0.79 to -1.71); these values were significant when compared to timolol at week 12 (Bonferroni test, p < 0.001). Latanoprost and travoprost were comparable in their ability to reduce IOP at each patient visit. Ocular adverse-events were found in almost equal proportion in patients treated with bimatoprost (41.3%) and travoprost (41.9%), with a higher incidence of conjunctival hyperemia (24.1%) seen in the bimatoprost group. Timolol produced a significant drop in heart rate (p < 0.001) at week 12 when compared to the baseline measurements.

Conclusions

Bimatoprost showed greater efficacy when compared to the other prostaglandins, and timolol was the most efficacious at lowering the IOP. Conjunctional hyperemia was mainly seen with bimatoprost. However, the drug was tolerated well and found to be safe.     

A short term study of the additive effect of timolol and brimonidine on intraocular pressure

PURPOSE: To evaluate the additive ocular hypotensive effect of the combination of brimonidine and timolol on intraocular pressure (IOP) reduction in patients with glaucoma. METHODS: This was a prospective, randomized, double-masked, crossover study in 20 patients with primary open angle glaucoma (POAG) on therapy receiving timolol maleate 0.5% twice daily, with IOP greater than or equal to 22 mmHg in one eye. The treatment period was 3 weeks and during this period timolol + brimonidine or timolol + placebo were applied topically twice daily and IOP, blood pressure, heart rate and pupil size were measured. RESULTS: Combined therapy (timolol + brimonidine) had clinically significant IOP-lowering effect during the treatment period P < 0.01). The mean diurnal IOP was significantly reduced by an average of 5.1-5.9 mmHg (21.2-24.5%) compared with baseline value. The timolol + placebo combination had no clinically significant IOP-lowering effect (P > 0.05). No clinically significant side effects were observed during the treatment of both groups. CONCLUSIONS: This study showed that the combination of topically applied brimonidine and timolol cause a marked and sustained IOP reduction.     

Comparison of latanoprost monotherapy and combined therapy of 0.5% timolol and 1% dorzolamide in chronic primary angle-closure glaucoma (CACG) in Japanese patients.

To compare the efficacy, adverse effects, and patient compliance of latanoprost monotherapy with unfixed combination therapy with 0.5% timolol maleate and 1% dorzolamide in the treatment of chronic primary angle-closure glaucoma (CACG), 36 Japanese patients with CACG following laser iridotomy (LPI) were treated for 12 weeks with instillation of latanoprost alone or with unfixed combination therapy of 0.5% timolol maleate and 1% dorzolamide hydrochloride. After 12 weeks of treatment, latanoprost reduced intraocular pressure (IOP) from 22.2 +/- 2.0 mmHg to 14.8 +/- 1.9 mmHg (33% reduction); timolol maleate and dorzolamide hydrochloride also reduced IOP from 22.5 +/- 2.2 mmHg to 17.1 +/- 2.7 mmHg (24% reduction). Latanoprost monotherapy significantly lowered IOP compared with unfixed combination therapy of 0.5% timolol maleate and 1% dorzolamide hydrochloride. Furthermore, a systemic adverse effect of bradycardia was not observed in the latanoprost monotherapy group. Concerning compliance, no significant difference was observed between the two groups. Thus, latanoprost monotherapy is more effective than unfixed combination therapy with 0.5% timolol maleate and 1% dorzolamide in the treatment of CACG following relief of pupillary block in Japanese patients.     

A comparison of morning and evening instillation of a combination travoprost 0.004%/timolol 0.5% ophthalmic solution

PURPOSE: To compare the intraocular pressure lowering efficacy and side effect profile of travoprost 0.004%/timolol 0.5% ophthalmic solution dosed in the morning and evening. METHODS: This was a multicenter, prospective, randomized, double-masked, parallel group clinical study of 92 patients with open-angle glaucoma (with or without pseudoexfoliative or pigmentary glaucoma) or ocular hypertension. After a washout of existing glaucoma medications, patients were randomly assigned to receive one drop of travoprost 0.004%/timolol 0.5% in the morning or evening for 6 weeks. The main outcome measures were mean intraocular pressure (IOP) assessed at 9 am, 11 am, and 4 pm, and safety variables. RESULTS: Travoprost 0.004%/timolol 0.5% ophthalmic solution, dosed in the morning or evening, controlled IOP consistently throughout the day. Mean IOP ranged from 16.5 to 16.7 mmHg in the morning treatment group and from 16.1 to 17.2 mmHg in the evening treatment group. Travoprost 0.004%/timolol 0.5% ophthalmic solution produced statistically significant and clinically relevant reductions in IOP from baseline; mean reductions ranged from approximately 8 to 10 mmHg (32% to 38%). Travoprost 0.004%/timolol 0.5% ophthalmic solution was safe and well tolerated with the most frequently reported adverse event being ocular hyperemia, which occurred in 12.5% of patients in the morning treatment group and 13.6% of patients in the evening treatment group. CONCLUSIONS: Travoprost 0.004%/timolol 0.5% given once daily, either in the morning or evening, is a safe and effective treatment for open-angle glaucoma and ocular hypertension. It may be beneficial for patients judged to be inadequately controlled on a prostaglandin analogue or ophthalmic beta-blocker alone.