Comparison of topical travoprost eye drops given once daily and timolol 0.5% given twice daily in patients with open-angle glaucoma or ocular hypertension.

PURPOSE: This 9-month study compared the intraocular pressure (IOP)-lowering efficacy and safety of once-daily travoprost ophthalmic solutions (0.0015% and 0.004%) with twice-daily timolol 0.5%. PATIENTS AND METHODS: This study was conducted using a double-masked, randomized, parallel-group design; adult patients with open-angle glaucoma or ocular hypertension (IOP between 24 and 36 mm Hg, inclusive at 9 am and between 21 and 36 mm Hg, inclusive, at 11 am and 4 pm on two eligibility visits after an appropriate washout of previous treatments). In both eyes, the travoprost vehicle (placebo) was instilled at 9 am and travoprost (0.0015% or 0.004%) was instilled at 9 pm, or timolol 0.5% was instilled at both times. The primary efficacy variable was mean IOP measured at 9 am, 11 am, and 4 pm at baseline and follow-up visits. RESULTS: Five hundred seventy-three patients were randomized to the study treatments. Mean IOP, which was combined across study visits, was lower with travoprost 0.004% than with timolol 0.5% at 9 am (P = 0.0246), 11 am (P = 0.0039), and 4 pm (P = 0.0004). Intraocular pressure was lower with travoprost 0.004% than with travoprost 0.0015% at 11 am (P = 0.0314), the time of peak drug activity. Mean IOP was consistently lower with travoprost 0.0015% than with timolol 0.5%. Mean IOP reductions from baseline were significantly (P less than equal 0.0001) greater with travoprost 0.004% (8.0-8.9 mm Hg) than with timolol 0.5% (6.3-7.9 mm Hg). The most frequent related adverse events were hyperemia, pruritus, discomfort, pain, and iris pigmentation changes. The local tolerance was better in the timolol group compared with patients receiving travoprost. There were no serious unexpected treatment-related adverse events in any group. CONCLUSIONS: Travoprost 0.004% reduced diurnal mean intraocular pressure significantly more than timolol 0.5%. Both concentrations of travoprost were well tolerated and safe for use in patients with open-angle glaucoma or ocular hypertension.     

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.     

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.     

The efficacy and safety of timolol maleate versus brinzolamide each given twice daily added to travoprost in patients with ocular hypertension or primary open-angle glaucoma

PURPOSE: To compare the efficacy and safety of timolol maleate 0.5% versus brinzolamide 1% when added to travoprost 0.004% in patients with ocular hypertension or primary open-angle glaucoma. DESIGN: A prospective, double-masked, randomized, active-controlled, parallel comparison. METHODS: Qualified patients at Visit 1 were placed on travoprost dosed every evening for 4 weeks and then were randomized at baseline (Visit 2) to the addition of timolol maleate or brinzolamide each given twice daily. Patients returned to clinic at Week 4 (Visit 3) for a safety visit and Week 12 (Visit 4) for an efficacy visit. At Visits 2 and 4 the intraocular pressure (IOP) was measured at 08:00, 12:00, and 16:00 hours. RESULTS: Ninety-seven patients on brinzolamide had a baseline diurnal IOP of 21.5+/-2.2 mmHg and 95 on timolol maleate had 21.3+/-2.5 mmHg, each added to travoprost. The diurnal mean IOP at Week 12 was 18.1+/-2.7 mmHg for brinzolamide and 18.1+/-3.0 mmHg for timolol maleate (p=0.96). There was no statistical difference found between treatment groups in the absolute level of pressure, or in the reduction in IOP from baseline, at each time point or for the diurnal curve (p>0.05). There was no significant difference for any adverse event between groups (p>0.05), with the most common side effect being conjunctival hyperemia in 15/97 (16%) brinzolamide and 6/95 (6%) timolol treated patients (p=0.06). CONCLUSIONS: This study showed that brinzolamide provides similar safety and efficacy compared to timolol maleate when added to travoprost.     

Effect of dorzolamide timolol combination versus timolol 0.5% on ocular bloodflow in patients with primary open-angle glaucoma

PURPOSE: Addition of dorzolamide to timolol in primary open-angle glaucoma shows augmented reduction of intraocular pressure. It is unknown as yet if addition of dorzolamide will alter hemodynamics. METHODS: Fifteen patients with primary open-angle glaucoma were placed on a medication-dependent 1-week to 4-week washout that included maintenance on timolol. After washout, baseline measurements were taken (timolol). They were studied after a month on timolol or dorzolamide-timolol (Cosopt; Merck, Inc, Whitehouse Station, New Jersey), with the second drug preceded by another month of timolol maintenance and second baseline measurements. At each visit, visual function, intraocular pressure, and ocular hemodynamics were monitored, including indocyanine green and fluorescein angiography and color Doppler imaging. RESULTS: Cosopt significantly reduced intraocular pressure (14.7 to 13.4 mm Hg, P <.05) and increased arteriovenous passage time (superior temporal artery) of fluorescein dye (2.13 to 1.76 seconds, P =.01) but had no effect on visual function. CONCLUSIONS: When compared with timolol in primary open-angle glaucoma, Cosopt augments ocular tension reduction and reduces the amount of time required for blood to pass through the superior retinal vasculature.     

Short-term ocular tolerability of dorzolamide 2% and brinzolamide 1% vs placebo in primary open-angle glaucoma and ocular hypertension subjects

PURPOSE: To compare ocular tolerability of dorzolamide 2%, brinzolamide 1%, and placebo given three times daily. METHODS: A prospective, double-masked, three-centre, crossover comparison in which 25 ocular hypertensive or primary-open angle glaucoma subjects were randomized to receive dorzolamide, brinzolamide, or placebo three times daily for 3 days. Intraocular pressure, visual acuity, a visual analogue scale, and ocular and systemic symptom queries were completed at the end of each period. RESULTS: After chronic dosing, there was a significant difference in ocular pain on the visual analogue scale among the groups at the 10-s postinstillation time point with dorzolamide having the highest level (22.5+/-28.9) compared to brinzolamide (5.0+/-8.7) or placebo (3.2+/-10.4) (P=0.0006). No differences between groups were observed preinstillation nor following dosing at 3 or 10-min postinstillation. On the initial instillation, the 10-s postinstillation pain was rated as 43.3+/-77.1, which was significantly higher than after chronic dosing (P=0.017). On the ocular symptom query, dorzolamide had the highest incidence of burning/stinging and redness compared to the other groups, but was generally characterized as mild. There were no significant differences in the visual acuity at any time point. CONCLUSIONS: This study suggests that subjects treated with dorzolamide suffer more ocular pain upon instillation compared to brinzolamide or placebo. However, pain symptoms are fewer following chronic dosing and are generally characterized as mild.     

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.     

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.     

Brimonidine purite 0.15% versus dorzolamide 2% each given twice daily to reduce intraocular pressure in subjects with open angle glaucoma or ocular hypertension

BACKGROUND/AIMS: To evaluate the efficacy of brimonidine purite versus dorzolamide given twice daily in primary open angle glaucoma or ocular hypertensive subjects. METHODS: In this double masked, multicentre, prospective, crossover comparison 33 subjects were randomised to brimonidine purite or dorzolamide for the first 4 week treatment period after a 4 week washout. Subjects began the opposite treatment for the second 4 week period after another 4 week washout. Intraocular pressure (IOP) was measured at 08:00 (trough) and 10:00, 18:00, and 20:00 hours after dosing at each baseline and at the end of each treatment period. RESULTS: The baseline diurnal IOP was 22.9 (SD 2.8) for brimonidine purite and 22.2 (SD 2.4) mm Hg for dorzolamide. The trough IOP following 4 weeks of therapy was 21.0 (SD 3.7) for brimonidine purite and 21.0 (SD 3.1) mm Hg for dorzolamide (p = 0.90). The mean diurnal IOP was 19.3 (SD 3.1) for brimonidine purite and 19.8 (SD 2.4) mm Hg for dorzolamide (p = 0.46). Dorzolamide caused more ocular stinging upon instillation (n = 8) than brimonidine purite (n = 1) (p = 0.02). No statistical differences existed between groups for systemic adverse events. CONCLUSIONS: This study suggests that brimonidine purite and dorzolamide each given twice daily have similar efficacy in primary open angle glaucoma or ocular hypertensive subjects. However, a trend was observed at 10:00 of greater brimonidine purite efficacy compared with dorzolamide.     

Comparison of the efficacy and safety of dorzolamide 2% when added to brimonidine 0.2% or timolol maleate 0.5% in patients with primary open-angle glaucoma.

OBJECTIVE: To determine the ocular hypotensive efficacy and safety of dorzolamide when added to brimonidine or timolol in patients with uncontrolled primary open-angle glaucoma (POAG). PATIENTS AND METHODS: This is a 1-year prospective open-label clinical trial of 48 consecutive POAG patients with inadequate intraocular pressure (IOP) control while using brimonidine 0.2% (23 patients) and timolol 0.5% (25 patients), 2 times daily. Patients were assigned to receive dorzolamide 2% as adjunctive therapy, added 3 times daily to brimonidine or timolol. IOP was measured on week 2, and months 3, 6, 9, and 12. RESULTS: A significant reduction in IOP from the baseline was observed after dorzolamide use in both groups at visits during that year (P < 0.001). Overall, mean IOP reduction was 5.6 +/- 1.9 mmHg with the brimonidine-dorzolamide combination, and 6.8 +/- 1.7 mmHg with timolol-dorzolamide after 1 year of treatment; the difference was significant (P = 0.029). No statistical differences existed between the groups for adverse events (P < 0.05). CONCLUSION: The addition of dorzolamide to brimonidine or timolol has significant IOP-lowering efficacy during 1 year in patients with POAG whose IOPs were inadequately controlled with brimonidine or timolol alone. The IOP-lowering effect of the timolol-dorzolamide combination at 1 year was more pronounced than brimonidine-dorzolamide. Both combinations were well-tolerated by the patients.     

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。     

Adjunctive therapy with brinzolamide 1% ophthalmic suspension (Azopt) in patients with open-angle glaucoma or ocular hypertension maintained on timolol therapy

This prospective, multicenter, double-masked, placebo-controlled study evaluated the safety and efficacy of brinzolamide 1% ophthalmic suspension (Azopt) when used adjunctively with open-label timolol maleate 0.5% (Timoptic). One-hundred-thirty-two patients requiring an adjunctive therapy to timolol 0.5% for the treatment of open-angle glaucoma or ocular hypertension were randomized to receive brinzolamide or placebo three times daily (t.i.d.) in addition to timolol 0.5% twice daily (b.i.d.) for 3 months. Qualifying intraocular pressure (IOP) on timolol 0.5% b.i.d. was 24-36 mm Hg in at least one eye at 8:00 A.M. and 21-36 mm Hg at 10:00 A.M., with no greater than a 5-mm Hg difference between eyes, during two eligibility visits separated by at least 7 days. Treatments were compared using a repeated-measures analysis of variance. Adjunctive therapy with brinzolamide resulted in clinically and statistically significant reductions in IOP from the timolol baseline at all visits. IOP changes from a diurnal baseline ranged from -3.3 mm Hg to -4.1 mm Hg for brinzolamide (N = 53) compared with -0.9 mm Hg to -2.5 mm Hg for placebo (N = 55). Abnormal taste (7.7%) and transient blurred vision (6.2%) were the most frequently reported adverse events. No clinically significant differences in the incidence or severity of ocular signs, visual acuity, cup/disk ratio, or parameters studied on dilated fundus examination were observed between treatment groups. Brinzolamide 1% t.i.d., used adjunctively with timolol 0.5% b.i.d., is safe and well tolerated, and produces clinically and statistically significant additional IOP reductions.     

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.     

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。     

Comparison of the efficacy and safety of latanoprost 0.005% compared to brimonidine 0.2% or dorzolamide 2% when added to a topical beta-adrenergic blocker in patients with primary open-angle glaucoma or ocular hypertension.

The purpose of this study was to evaluate the ocular hypotensive efficacy and safety of latanoprost 0.005% (Xalatan, Pharmacia & Upjohn), brimonidine (Alphagan, Allergan), and dorzolamide (Trusopt, Merck Inc.) when added to a beta-blocker in patients with ocular hypertension or primary open-angle glaucoma. This was a multicenter, retrospective analysis which included all reviewed patient records in which latanoprost, brimonidine or dorzolamide were added to a beta-blocker for at least three months. Patients who were treated for less than three months, who failed therapy due to ineffectiveness of the medicine or an adverse event also were included. The study included 141 patients. Latanoprost (n = 50) showed an intraocular pressure of 16.7 +/- 3.3 mm Hg (-6.3 +/- 4.1 mm Hg, P < 0.001), brimonidine (n = 24) 17.4 +/- 4.9 mm Hg (-4.2 +/- 4.5 mm Hg, P < 0.001), and dorzolamide (n = 67) 20.1 +/- 6.1 mm Hg (-3.1 +/- 5.1 mm Hg, P < 0.001) at three months. A significant difference was observed in the absolute level of intraocular pressure (P < 0.005) and the change from baseline between groups (P < 0.005) at three months. A significant difference was observed between groups in the success rate of therapy between latanoprost (70%), brimonidine (58%) and dorzolamide (40%) (P = 0.008). No significant differences were observed between groups for rate or type of adverse events leading to discontinued therapy. This study showed that latanoprost, when added to beta-blockers, compares favorably in ocular hypotensive efficacy and is similar in safety to brimonidine and dorzolamide.     

Predictors for visual field progression and the effects of treatment with dorzolamide 2% or brinzolamide 1% each added to timolol 0.5% in primary open‐angle glaucoma

Purpose: This study aims to identify progression factors in patients with primary open‐angle glaucoma (POAG), including the effects of treatment with dorzolamide 2% or brinzolamide 1%, each added to timolol 0.5%. Methods: A sample of 161 POAG patients were prospectively randomized to receive either dorzolamide 2% (DT) or brinzolamide 1% (BT) b.i.d., each added to timolol 0.5%, during a 60‐month, evaluator‐masked study. Progression was determined by perimetric criteria. Factors associated with visual field progression were estimated using a conditional Cox hazard model with patient intraclass correlation and were expressed as hazard ratios (HRs) with 95% confidence intervals (95% CIs). Results: Predictive baseline factors were lower diastolic blood pressure (DBP), lower mean arterial pressure (MAP), antihypertensive treatment, lower end‐diastolic velocity (EDV) in the ophthalmic artery (OA) and short posterior ciliary artery (SPCA), and a higher resistivity index (RI) in the OA and SPCA. Progression risk decreased by approximately 30% and 20% with each centimetre per second increase of EDV in the OA and SPCA, respectively, from baseline to the last follow‐up visit. Each RI decrease (or increase) of 0.01 unit in the OA or SPCA was associated with an approximate 20% decrease (or increase) in risk for progression. In a multivariate analysis, progression risk was significantly lower in eyes treated with DT (HR = 0.65, 95% CI 0.41–0.90) compared with those treated with BT. Conclusions: Progression increased with lower DBP, lower MAP, antihypertensive medication, lower EDV in the OA and SPCA, and higher RI in the OA and SPCA. The risk for progression in patients treated with DT was half that in patients treated with BT.     

A 1-year study to compare the efficacy and safety of once-daily travoprost 0.004%/timolol 0.5% to once-daily latanoprost 0.005%/timolol 0.5% in patients with open-angle glaucoma or ocular hypertension

PURPOSE: The objective of the study was to compare the intraocular pressure (IOP)-lowering efficacy and safety of travoprost 0.004%/timolol 0.5% ophthalmic solution (Trav/Tim) to latanoprost 0.005%/timolol 0.5% ophthalmic solution (Lat/Tim), dosed once daily in the morning, in patients with open-angle glaucoma (OAG) or ocular hypertension (OH). METHODS: This was a randomized, double-masked, multicenter, parallel group, active-controlled study conducted at 41 sites. At the eligibility visit the patients were randomized (1:1) to the assigned masked medication if they met inclusion/exclusion criteria, and the mean IOP values in the eligible eyes were > or =24 mmHg at 9 AM and > or =21 mmHg at 11 AM and 4 PM. Patients were excluded if the mean IOP in either eye was >36 mmHg. Patients were instructed to administer the assigned medication each morning at 9 AM. During the treatment phase of the study, IOP was measured at 9 AM at week 2, week 6, month 3, and month 9. At the month 6 and month 12 visits, IOP was measured at 9 AM, 11 AM, and 4 PM. Statistical methods included a repeated measures analysis of variance (ANOVA); to test for noninferiority, a 95% confidence interval for the treatment group difference was constructed based on the ANOVA results for each time point at month 12. RESULTS: Patients (n=408) with OAG or OH were enrolled at 41 sites. One patient withdrew prior to receiving medication so 207 in the Trav/Tim group and 200 in the Lat/Tim group were evaluable for safety. Baseline demographic characteristics as well as IOP values showed no statistical differences between the two groups. Trav/Tim provided lower mean IOP values than Lat/Tim that were statistically significant at the week 2 9 AM (p=0.0081), month 6 9 AM (p=0.0056), and month 6 11 AM (p=0.0128) time points and at 9 AM time point pooled across all visits (p=0.0235) when mean IOP was 0.6 mmHg lower in the Trav/Tim group. Treatment-related adverse events were mild in both groups. Although hyperemia was reported from a higher percentage of patients in Trav/Tim group, differences in average hyperemia scores between the two groups were not considered clinically relevant. CONCLUSIONS: Travoprost 0.004%/timolol 0.5% ophthalmic solution produced mean IOP levels that are statistically noninferior to latanoprost 0.005%/timolol 0.5% ophthalmic solution. Furthermore, at 9:00 AM, 24 hours after dosing, IOP was statistically lower for travoprost 0.004%/timolol 0.5% pooled across all visits. Travoprost 0.004%/timolol 0.5% fixed combination ophthalmic solution is an effective treatment for reducing IOP and it is safe and well-tolerated in patients with OAG or OH.