Prostaglandin analogs and blood-aqueous barrier integrity: a flare cell meter study

PURPOSE: To study, with an objective method, inflammation of the anterior segment of the glaucomatous eye after treatment with latanoprost, travoprost and bimatoprost. MATERIALS AND METHODS: Sixty patients with chronic open-angle glaucoma aged between 38 and 76 years (mean 64.0 +/- 12.2) were randomly assigned to latanoprost 0.005, travoprost 0.004 and bimatoprost 0.03%. The study period lasted 6 months. Intraocular pressure (IOP) was measured every 2 weeks. We studied the intraocular inflammation before and after 3 and 6 months of therapy with an instrument composed of a He-Ne laser beam system, a photomultiplier mounted on a slitlamp microscope and a computer. This flare meter allows objective determination of the flare and the number of cells in the aqueous of the anterior chamber. RESULTS: At the baseline, IOP was 26.4 +/- 3.6 mm Hg. After 3 months of treatment, mean IOP in the latanoprost group was 17.9 +/- 0.3 mm Hg (p < 0.001) with a mean cellularity of 12.638 +/- 3.284 photons/ms (p < 0.001). The travoprost group had an IOP of 17.2 +/- 0.3 mm Hg (p < 0.001) with a cellularity of 9.719 +/- 1.927 photons/ms (0.001). Finally, IOP in the bimatoprost group was 17.6 +/- 0.5 mm Hg (p < 0.001) with a cellularity of 6.138 +/- 1.475 photons/ms (p < 0.032). After 6 months of treatment, IOP in the latanoprost group was 18.1 +/- 0.3 (p < 0.001), in the travoprost group 17.3 +/- 0.3 (p < 0.001) and in the bimatoprost group 17.7 +/- 0.5 mm Hg (p < 0.001), whereas cellularity was 11.838 +/- 3.218 (p < 0.001), 8.950 +/- 3.692 (p < 0.001) and 7.617 +/- 2.603 photons/ms (p < 0.001), respectively. After 3 months, the travoprost (p < 0.013) and the bimatoprost groups (p < 0.001) had less flare compared with the latanoprost group and this remained so even at 6 months. When we compared the travoprost group with the bimatoprost group, we found significantly less flare at 3 months in the bimatoprost group (p < 0.001) but not at 6 months (p < 0.246). CONCLUSIONS: The flare meter analysis shows that the eyes treated with bimatoprost and travoprost have a less significantly broken blood-aqueous barrier and their anterior chamber is also significantly less inflamed.     

A comparison of the fixed combination of latanoprost and timolol with the unfixed combination of brimonidine and timolol in patients with elevated intraocular pressure. A six month, evaluator masked, multicentre study in Europe

PURPOSE: To compare the intraocular pressure (IOP) reducing effect and safety of fixed combination (FC) latanoprost/timolol with unfixed combination (UFC) brimonidine/timolol in patients with increased IOP. METHODS: In this 6 month, randomised, evaluator masked, parallel group European study, patients with glaucoma or ocular hypertension and IOP > or =21 mm Hg on monotherapy or >16 mm Hg on dual therapy received either FC latanoprost/timolol at 8:00AM or UFC brimonidine/timolol at 8:00AM and 8:00PM. The primary outcome was the difference from baseline to month 6 in mean diurnal IOP reduction. RESULTS: 325 of 334 randomised patients were included in intent to treat analyses (FC latanoprost/timolol, 163; UFC brimonidine/timolol, 162). Baseline diurnal IOP levels were similar: FC latanoprost/timolol, 26.4 (SD 2.7) mm Hg; UFC brimonidine/timolol, 26.5 (SD 2.8) mm Hg (p = 0.851). At month 6, levels were 16.9 (SD 2.8) mm Hg in FC latanoprost/timolol patients and 18.2 (SD 3.1) mm Hg in UFC brimonidine/timolol patients (p<0.001). No adverse events were reported by 76.4% and 75.5% of patients receiving FC latanoprost/timolol versus UFC brimonidine/timolol, respectively. Larger proportions of brimonidine/timolol treated patients reported study medication related adverse events (18.6% v 7.3%) and discontinued study participation because of this (10.8% v 1.8%). CONCLUSION: Fixed combination latanoprost/timolol administered once daily is both more effective and better tolerated than twice daily dosing with UFC brimonidine/timolol.     

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

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

The effect of latanoprost, bimatoprost, and travoprost on circadian variation of intraocular pressure in patients with open-angle glaucoma

PURPOSE: To evaluate the efficacy of latanoprost, bimatoprost, and travoprost given in the evening over the 24-hour curve in newly diagnosed open-angle glaucoma patients. METHODS: This 8-week, randomized, parallel group, masked evaluator study compared the efficacy of once daily administration of latanoprost 0.005%, bimatoprost 0.03%, and travoprost 0.004% ophthalmic solutions. After enrollment at baseline, 48 patients were randomized to 3 treatment groups: latanoprost (n=17), bimatoprost (n=16), and travoprost (n=15). At baseline and 8 weeks of therapy, masked evaluators measured intraocular pressure (IOP) at 8 AM, 10 AM, 1 PM, 4 PM, 8 PM, 11 PM, and 3 AM. RESULTS: Baseline mean IOP levels were similar across the groups. By week 8, reductions were observed in all 3 groups (P<0.001 for each). Travoprost-treated patients' IOP levels were reduced 8.7 and 8.1 mm Hg at 8 and 10 AM, respectively. Latanoprost-treated patients experienced 4.8 and 5.3 mm Hg reductions, whereas bimatoprost-treated patients experienced 5.5 and 4.9 mm Hg reductions at these time points. The amount of IOP reduction seen at 8 and 10 AM in travoprost group was significantly higher when compared with latanoprost and bimatoprost-treated group (P<0.001). CONCLUSIONS: Latanoprost, bimatoprost, and travoprost were comparable in their ability to reduce IOP in open-angle glaucoma patients. On the basis of our data, the IOP reduction of these drugs is indistinguishable within statistical parameters.     

Additive effect of latanoprost, a prostaglandin F2 alpha analogue, and timolol in patients with elevated intraocular pressure.

A randomised observer masked clinical study was conducted to assess the additive effect of latanoprost (13,14-dihydro-17-phenyl-18,19,20-trinorprostaglandin F2 alpha-isopropylester) to timolol maleate in patients with elevated intraocular pressure (IOP). Patients were randomly assigned to two treatment groups. One group (n = 10) received timolol, the other group (n = 9) received latanoprost twice daily for 1 week. After 1 week all patients received both timolol and latanoprost. Eyes treated with timolol (mean diurnal IOP (SD) day 0, 24.2 (2.8) mm Hg) and latanoprost (mean diurnal IOP day 0, 28.5 (5.6) mm Hg) showed an IOP reduction of 5.9 (2.3) mm Hg (24%) and 8.9 (2.5) mm Hg (31%), respectively after the first week. Adding latanoprost to the eyes treated with timolol as well as timolol to the eyes receiving latanoprost gave a further reduction of 2.6 (1.1) mm Hg (13%) and 2.6 (2.2) mm Hg (14%), respectively. Only mild transient hyperaemia was observed in patients receiving latanoprost. The results indicate that latanoprost and timolol can be combined successfully and that complete or almost complete additivity is reached even at pressure levels below 20 mm Hg.     

Intraocular pressure after replacement of current dual therapy with latanoprost monotherapy in patients with open angle glaucoma

AIMS: To evaluate the efficacy and safety of replacing current dual ocular hypotensive therapy with latanoprost 0.005% monotherapy in patients with open angle glaucoma. METHODS: This randomised, open label, parallel group, multinational study included 466 patients with open angle glaucoma currently on dual ocular hypotensive therapy, including a beta adrenergic receptor antagonist. Patients were assigned (1:3) to ongoing dual therapy or a switch to monotherapy with latanoprost 0.005% once daily for 6 months. Intraocular pressure (IOP) was measured at 10 am and 5 pm at baseline, month 3, and month 6. Groups were compared for differences in diurnal IOP change, IOP success rates (IOP < or =22 mm Hg with < or =15% increase from baseline), and clinical success rates (not requiring change in therapy). RESULTS: Baseline mean diurnal IOP was 17.8 (SD 2.0) mm Hg in the latanoprost group and 17.6 (2.1) mm Hg in the dual therapy group. After 6 months, mean diurnal IOP was reduced by 0.26 (0.18) (SEM 1.4%) mm Hg (p=0.153) in the group switched to latanoprost and by 0.37 (0.25) (2.1%) mm Hg (p=0.138) in those continuing dual therapy (difference: 0.11 mm Hg; p=0.641). Success rates defined by IOP criteria were 83% for latanoprost and 89% for continued dual therapy (difference: 6%; p=0.122). Clinical success rates were 97% for latanoprost and 99% for dual therapy (difference: 2%; p=0.161). Ocular adverse events were reported by 23% of patients in both treatment groups. CONCLUSION: Latanoprost monotherapy is a safe and effective alternative for many patients with open angle glaucoma requiring dual topical ocular hypotensive therapy for IOP control.     

A comparison of latanoprost,bimatoprost, and travoprost in patients with elevated intraocular pressure: a 12-week,randomized, masked-evaluator multicenter study

PURPOSE: To Internet Advance publication at ajo.com Feb 13, 2003. compare the intraocular pressure (IOP)-lowering effect and safety of latanoprost, bimatoprost, and travoprost in patients with open-angle glaucoma (OAG) or ocular hypertension (OH). DESIGN: Interventional study. METHODS: This 12-week, randomized, parallel-group study was conducted at 45 US sites. Previously treated patients with OAG or OH and an IOP > or =23 mm Hg in one or both eyes after washout received either latanoprost 0.005%, bimatoprost 0.03%, or travoprost 0.004% once daily in the evening. At baseline and after 6 and 12 weeks of therapy, masked evaluators measured IOP in triplicate at 8:00 AM, 12 noon, 4:00 PM, and 8:00 PM, and masked investigators graded conjunctival hyperemia before the 8:00 AM IOP measurement. The primary efficacy outcome measure was change between baseline and Week 12 in the 8:00 AM IOP (time of peak drug effect). RESULTS: In all, 410 of 411 randomized patients were included in intent-to-treat analyses (latanoprost, 136; bimatoprost, 136; travoprost, 138). Baseline mean 8:00 AM IOP levels were similar (P =.772); by week 12, reductions were observed in all 3 groups (P <.001 for each). Adjusted (ANCOVA) reductions in mean IOP at 8:00 AM were similar (P =.128) as were those at 12 noon, 4:00 PM, and 8:00 PM. Fewer latanoprost-treated patients reported ocular adverse events (P <.001, latanoprost vs bimatoprost), fewer reported hyperemia (P =.001, latanoprost vs bimatoprost), and average hyperemia scores were lower at week 12 (P =.001, latanoprost vs bimatoprost). CONCLUSIONS: Latanoprost, bimatoprost, and travoprost were comparable in their ability to reduce IOP in OAG and OH patients. Latanoprost exhibited greater ocular tolerability.     

A comparison of latanoprost and dorzolamide in patients with glaucoma and ocular hypertension: a 3 month, randomised study. Ireland Latanoprost Study Group

AIMS: To compare the effects on intraocular pressure (IOP) and side effects of monotherapy with either latanoprost or dorzolamide in patients with glaucoma or ocular hypertension. METHODS: 224 patients with open angle glaucoma or ocular hypertension were recruited to a 3 month open labelled study. Previous glaucoma medications were washed out and the patients were randomised to receive either latanoprost 0.005% once daily or dorzolamide 2% three times daily. RESULTS: Of 224 patients 213 were included in the analysis of efficacy. After 3 months, latanoprost reduced mean baseline diurnal IOP from 27.2 (SD 3.0) mm Hg by 8.5 (3.3) mm Hg. The corresponding figures for dorzolamide were 27.2 (3.4) and 5.6 (2.6) mm Hg. The difference of 2.9 mm Hg (95% CI: 2.3-3.6) was highly significant (p<0.001, ANCOVA). Latanoprost reduced IOP at peak by 8.6 mm Hg (32%) compared with 6.2 mm Hg (23%) for dorzolamide, and the difference of 2.4 mm Hg was significant (p<0.001, ANCOVA). The corresponding figures at trough were 8.1 mm Hg (31%) for latanoprost and 4.7 mm Hg (17%) for dorzolamide, a significant difference of 3.4 mm Hg (p<0.001, ANCOVA). Both drugs were well tolerated systemically and locally. CONCLUSION: Latanoprost was superior to dorzolamide in reducing the IOP, judged both from the effect on IOP at peak and trough and by the effect on diurnal IOP.     

Effects of the combination of bimatoprost and latanoprost on intraocular pressure in primary open angle glaucoma: a randomised clinical trial

AIMS: To evaluate the effect of the combination of bimatoprost and latanoprost on intraocular pressure (IOP) in primary open angle glaucoma (POAG). METHODS: An open label randomised clinical trial was conducted, which included 18 glaucomatous patients (36 eyes). In the first 4 weeks, latanoprost 0.005% was prescribed for both eyes of the patients and any other antiglaucoma medication was discontinued. In the next 4 weeks (phase 1), bimatoprost 0.03% was combined with latanoprost in one randomly assigned eye (case eye) of each patient. In the next 4 weeks (phase 2), bimatoprost was discontinued in the case eyes, while bimatoprost was substituted for latanoprost in the fellow eye (control eye). The IOP was measured at the end of the first 4 weeks (baseline measurement) and weekly during phases 1 and 2. RESULTS: In the case eyes, the mean IOP increased along the first phase (1.8 mm Hg; p = 0.006) when compared to baseline measurements. The IOP returned to previous values after discontinuation of bimatoprost in phase 2. In the control eyes, the mean IOP did not change throughout the study. CONCLUSION: The combination of bimatoprost and latanoprost in POAG increases the IOP and should not be considered as a therapeutic option.     

A comparison of long-term intraocular pressure fluctuation in patients treated with bimatoprost or latanoprost

PURPOSE: To evaluate long-term intraocular pressure (IOP) fluctuation in patients with glaucoma or ocular hypertension treated with bimatoprost or latanoprost. DESIGN: Post hoc analysis of prospectively collected data from a previously reported multicenter, investigator-masked, randomized clinical trial of bimatoprost and latanoprost. METHODS: Patients were treated bilaterally with bimatoprost (n = 133) or latanoprost (n = 136) for six months. IOP measurements were taken at 8 am, 12 pm, and 4 pm at baseline, week 1, and months 1, 3, and 6. Long-term IOP fluctuation during treatment was determined as the standard deviation (SD) of all 12 follow-up measurements. RESULTS: There was no significant between-group difference in short-term daily IOP fluctuation at baseline. Long-term IOP fluctuation over six months of treatment [mean SD (range SD)] was 1.9 (0.5 to 6.3) mm Hg with latanoprost vs 1.7 (0.5 to 3.9) mm Hg with bimatoprost (P = .050). Latanoprost-treated eyes were more likely than bimatoprost-treated eyes to have long-term IOP fluctuation of >/=3 mm Hg (7.8% vs 2.5% of eyes; P = .009). CONCLUSIONS: Bimatoprost-treated eyes demonstrated less long-term fluctuation in IOP compared with latanoprost-treated eyes in this six-month study. Additional studies are needed to confirm these findings and to determine their impact on glaucomatous progression.     

Comparison of the intraocular pressure lowering effect of latanoprost and carteolol-pilocarpine combination in newly diagnosed glaucoma

PURPOSE: To evaluate the comparative efficacy of latanoprost monotherapy versus combined carteolol and pilocarpine therapy in patients with newly diagnosed glaucoma. METHODS: Masked randomized prospective trial. This study included 51 patients (64 eyes) with newly diagnosed glaucoma or ocular hypertension. The cases were randomly divided into two treatment groups for administration of latanoprost 0.005% once daily, or of carteolol 2% twice daily and pilocarpine 2% twice daily. Mean diurnal intraocular pressure (IOP) was measured at baseline, week 2, week 4, and month 3 after the beginning of treatment. Changes in mean IOP from baseline to the 3-month visit were determined by an analysis of variance. RESULTS: Mean diurnal IOP values were 25.1 +/- 3.1 mm Hg and 25.5 +/- 2.5 mm Hg at baseline in the latanoprost monotherapy group and in the carteolol-plus-pilocarpine group, respectively. Diurnal IOP was significantly decreased from baseline to 3 months in both groups (P <.001). At this time point, latanoprost monotherapy had reduced mean diurnal IOP by 7.2 +/- 2.5 mm Hg (28.7%) and carteolol plus pilocarpine had reduced mean diurnal IOP by 7.4 +/- 2.7 mm Hg (29%). There was no difference between the groups in terms of their IOP reduction effect (P =.51). Decreased visual acuity and twilight vision, blurred vision, and headache were more frequent in the carteolol-plus-pilocarpine group than in the latanoprost group (P <.05). CONCLUSIONS: We concluded that latanoprost monotherapy was at least as effective as the carteolol-pilocarpine combination therapy in reducing mean diurnal IOP in newly diagnosed glaucoma or ocular hypertension.     

Inter-visit intraocular pressure range: an alternative parameter for assessing intraocular pressure control in clinical trials

PURPOSE: To evaluate whether inter-visit intraocular pressure (IOP) range, which reflects extreme and potentially damaging IOP fluctuations, provides additional information on IOP control compared to mean IOP. DESIGN: Post hoc analysis of Xalatan/Lumigan/Travatan study data, a masked-evaluator, randomized, parallel-group comparison of 12-week efficacy of latanoprost, bimatoprost, and travoprost in open-angle glaucoma/ocular hypertension patients. METHODS: Pretreatment inter-visit IOP range defined as highest IOP minus lowest IOP at screening, safety check, and baseline (six measurements); posttreatment inter-visit IOP range defined as highest IOP minus lowest IOP at weeks two, six, and 12 or early termination (nine measurements). Ranges dichotomized as "high" (>6 mm Hg) vs "low" (< or =6 mm Hg). RESULTS: Included were 410 patients (latanoprost, 136; bimatoprost, 136; travoprost, 138). Each resulted in significant mean IOP range reductions during 12 weeks. Pretreatment inter-visit IOP range was associated with African-American race, male gender, and presence of visual field defect (P < .05 for all). Percentages with high pretreatment inter-visit IOP ranges were comparable across treatments (63% to 64%). High posttreatment inter-visit IOP range was seen in 21% (28/136), 28% (38/136), and 36% (50/138) of latanoprost, bimatoprost, and travoprost groups, respectively (P = .016, overall; P = .005, latanoprost vs travoprost). High posttreatment inter-visit IOP range was associated with African-American race, high pretreatment inter-visit IOP range, and treatment with travoprost vs latanoprost (P < .05 for all). CONCLUSIONS: Given that high inter-visit IOP range is associated with risk factors for glaucomatous damage and that such differences cannot be evaluated using mean IOPs, inter-visit IOP range may be another useful approach to assessing IOP control in clinical trials.     

三种前列腺素类滴眼液治疗原发性开角型青光眼的降眼压效果比较

目的 比较拉坦前列素、曲伏前列素及贝美前列素3种前列腺素类滴眼液治疗原发性开角型青光眼患者4周后的24h降眼压效果。方法 病例对照研究。选取2009年1月至6月门诊就诊的原发性开角型青光眼患者63例（63只眼）。其中拉坦前列素组21例（21只眼）,曲伏前列素组22例（22只眼）,贝美前列素组20例（20只眼）,分别使用相应的滴眼液,均为每日滴药1次,共观察4周,测量用药前后的24h眼压曲线。3组间用药前或用药后24h不同时间点眼压值比较采用两因素重复测量的方差分析,眼压波动幅度比较采用单因素方差分析。结果 3组患者用药4周后眼压均明显下降,拉坦前列素组眼压从(18.9±2.1)mm Hg（1mm Hg =0.133 kPa）降至(15.3±2.7)mm Hg,下降幅度（用药前后眼压差值/用药前眼压值）为19.0％;曲伏前列素组眼压从(19.1±3.1)mm Hg降至(15.3 ±2.1)mm Hg,下降幅度为19.4％;贝美前列素组眼压从(18.6±1.9) mm Hg降至(14.9±1.9)mm Hg,下降幅度为19.9％。波幅下降幅度（用药前后波幅差值/用药前波幅值）,拉坦前列素组为31.0％,曲伏前列素组为31.1％,贝美前列素组为31.9％。用药前及用药后3组间眼压值随时间点变化差异均无统计学意义(F= 1.501,P=0.110),3组间用药后眼压波幅下降幅度差异无统计学意义(F =0.286,P=0.752)。结论 拉坦前列素、曲伏前列素、贝美前列素3种滴眼液对原发性开角型青光眼的昼夜降眼压效果显著且无明显差别。     

Peak pressures: crossover study of timolol and latanoprost

PURPOSE: To compare the diurnal efficacy and action on peak intraocular pressures (IOP) of 0.005% latanoprost and 0.5% timolol as primary therapy in 60 eyes having dark brown irides with primary open angle glaucoma (POAG). METHODS: A prospective, comparative, observer-masked, crossover, interventional trial including the mean of both eyes of 30 patients with POAG who were randomly started on either latanoprost once daily or timolol twice daily. Three months after treatment with one drug, the second drug was substituted. A masked observer carried out diurnal assessments of IOP before the start of therapy and at 3 and 7 months. The fourth month was the washout period for the first drug. RESULTS: The average baseline IOP was 23.36 +/- 2.14 mm Hg, which was reduced by 8.8 +/- 2.2 mmHg with latanoprost (p < 0.01) and by 6.75 +/- 1.9 mm Hg with timolol (p = 0.01). The reduction was greater for latanoprost (p < 0.005). The average peak IOP at baseline was 27.6 +/- 2.22 mmHg. The effective fall in IOP at the time of new peaks in subsequent diurnal recordings of IOP compared to the baseline diurnal curve was 8.9 mm Hg with latanoprost (p < 0.005) and 5.77 mm Hg with timolol (p < 0.01). This difference in IOP reduction between the two drugs was statistically significant (p < 0.01). Latanoprost had a lower efficacy in peak IOP reduction in eyes with evening peak of IOP than in those with morning peak (p < 0.005). The efficacy of timolol was lower overall compared to latanoprost, but was similar in all circadian rhythms. The shift in timing of IOP peak was greater with latanoprost compared to timolol (4.34 hours vs -0.72 hours, p < .01). A total of 90% of patients on latanoprost and 33.3% on timolol achieved a reduction of > 30% in baseline mean IOP. The average of the trough IOP recorded in each of the individual baseline IOP curves was 19.05 +/- 2.05 mm Hg. CONCLUSIONS: Greater mean and peak IOP reduction was achieved with latanoprost compared to timolol. Dampening of the circadian rhythm was better with latanoprost. Latanoprost appears to be more effective than timolol at all points in time with greater efficacy in eyes with morning peaks compared to evening peaks.     

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

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

A comparison of once-daily morning vs evening dosing of concomitant latanoprost/timolol

PURPOSE: To evaluate morning vs evening once daily concomitant latanoprost 0.005%/timolol maleate 0.5% therapy in ocular hypertensive or primary open-angle glaucoma patients. DESIGN: Prospective single-center double-masked crossover comparison. METHODS: Patients who responded to timolol maleate 0.5% given twice daily were randomized to either evening or morning dosing of concomitant latanoprost 0.005% and timolol maleate 0.5% therapy for 7 weeks. Twenty-four hour diurnal curve intraocular pressure (IOP) testing was performed following each period. RESULTS: Thirty-six patients completed this study. There was a significant reduction at each time point in the 24-hour diurnal curve of both evening (17.1 +/- 2.7 mm Hg) and morning (17.3 +/- 3.1 mm Hg) dosed latanoprost/timolol maleate compared with timolol maleate given twice daily (21.1 +/- 3.3 mm Hg) (P <.0001). When the morning and evening dosing groups were compared directly, the 06:00 time point was statistically lower with evening dosing (16.4 +/- 2.3 mm Hg) vs morning dosing (17.9 +/- 2.8 mm Hg) (P =.01). Overall, a trend existed for greater daytime reduction with night-time dosing of the concomitant therapy, whereas morning dosing tended to give lower night-time pressures. There was a significantly lower mean range of diurnal pressure with evening (3.6 mm Hg) vs morning (4.3 mm Hg) dosing (P =.02). No differences in adverse events existed between the treated arms. CONCLUSIONS: This study suggests that latanoprost and timolol maleate, both given once daily in the morning or evening, effectively reduce the IOP for the 24-hour diurnal curve when compared with timolol maleate twice daily.     

Pooled-data analysis of three randomized, double-masked, six-month studies comparing intraocular pressure-reducing effects of latanoprost and timolol in patients with ocular hypertension

PURPOSE: To assess retrospectively the intraocular pressure (IOP)-reducing effect of latanoprost compared with timolol in the subset of patients with ocular hypertension (OH). METHODS: Three randomized, double-masked, multicenter, parallel group, 6-month studies conducted in the United States, United Kingdom, and Scandinavia compared the efficacy and safety of latanoprost and timolol. The present study represents an analysis of the pooled data for the subset of OH patients. Intent-to-treat analyses were based on all randomized OH patients. RESULTS: Of the 441 patients with OH, 247 were treated with latanoprost and 194 were treated with timolol. Baseline mean diurnal IOP levels were 24.4 +/- 0.2 mm Hg (mean +/- standard error of the mean) in the latanoprost group and 24.2 +/- 0.2 mm Hg in the timolol group. Overall, latanoprost lowered mean diurnal IOP by 1.1 +/- 0.2 mm Hg (95% CI: 1.6 to 0.7 mm Hg, P < 0.001) more than timolol. The difference in IOP-lowering ability between the two drugs was not shown to be related to patient sex, age, race, presence or absence of previous treatment of OH, time elapsed since ocular diagnosis, or family history of glaucoma/OH. Percentage reductions from baseline in diurnal IOP levels of at least 20% were achieved by 83% of patients treated with latanoprost versus 62% of those receiving timolol. CONCLUSION: Latanoprost provides superior IOP reduction compared with timolol in patients with OH.     

The effects of prostaglandin analogues on IOP in prostanoid FP-receptor-deficient mice

PURPOSE: This study was designed to clarify the involvement of the prostanoid FP receptor in the intraocular pressure (IOP)-lowering effects of latanoprost, travoprost, bimatoprost, and unoprostone with the use of FP-receptor-deficient (FPKO) mice. METHODS: FPKO and wild-type (WT) mice were bred and acclimatized under a 12-hour light-dark cycle. IOP was measured under general anesthesia by a microneedle METHOD: To evaluate the effects of each drug, a single drop (3 muL) of each drug solution was topically applied in a masked manner to a randomly selected eye. IOP reduction was evaluated by the difference in IOP between the treated eye and the untreated contralateral eye in the same mouse. First, the diurnal variation and baseline IOP in WT and FPKO mice were measured. Then, to determine the window feasible for demonstrating the most marked ocular hypotensive effect, 0.005% latanoprost was applied to WT mice during the day or at night. The time when the ocular hypotensive effect was larger was selected for further studies to evaluate the effects of latanoprost (0.005%), travoprost (0.004%), bimatoprost (0.03%), and unoprostone (0.12%). In addition, bunazosin (0.1%) was also applied to demonstrate functional uveoscleral outflow in FPKO mice. All experiments were conducted under a masked study design. RESULTS: The baseline IOP (mean +/- SEM) in WT and FPKO mice was 15.0 +/- 0.2 and 15.0 +/- 0.3 mm Hg, respectively, during the day, and 18.9 +/- 0.4 and 19.2 +/- 0.4 mm Hg, respectively, at night. In WT mice, latanoprost significantly lowered IOP both during the day and at night, at 2 to 6 hours and 1 to 6 hours after application, respectively. Maximal IOP reduction was observed at 3 hours after drug instillation both during the day (10.9 +/- 1.8%) and at night (23.2 +/- 1.1%). At 3 hours after instillation, latanoprost (10.9 +/- 1.8% and 23.2 +/- 1.1%, daytime and nighttime, respectively), travoprost (15.9 +/- 1.4% and 26.1 +/- 1.2%) and bimatoprost (8.8 +/- 2.0 and 19.8 +/- 1.5%) significantly lowered IOP in WT mice both during the day and at night; isopropyl unoprostone significantly lowered IOP at night (13.7 +/- 1.9%) but not during the day (5.3 +/- 3.2%). In FPKO mice, latanoprost, travoprost, bimatoprost, and unoprostone showed no significant IOP-lowering effect. Bunazosin significantly lowered IOP in both WT (22.1 +/- 1.6%) and FPKO mice (22.2 +/- 2.1%). CONCLUSIONS: A single application of latanoprost, travoprost, bimatoprost, or unoprostone had no effect on IOP in FPKO mice with presumed functional uveoscleral outflow pathways. The prostanoid FP receptor plays a crucial role in the mechanism of early IOP lowering of all commercially available prostaglandin analogues.     

The efficacy and safety of latanoprost 0.005% once daily versus brimonidine 0.2% twice daily in open-angle glaucoma or ocular hypertension

PURPOSE: To evaluate the efficacy and safety of latanoprost 0.005% given topically every evening versus brimonidine 0.2% given topically twice daily in primary open-angle glaucoma or ocular hypertensive patients. METHODS: This was a multicenter, crossover, double-masked comparison. After a 28-day treatment-free period, patients with primary open-angle glaucoma or ocular hypertension were randomized for 6 weeks to brimonidine or latanoprost and then crossed over to the opposite treatment. At baseline and after each treatment period, patients underwent intraocular pressure measurements every 2 hours from 08:00 to 20:00. RESULTS: In 33 patients the mean baseline trough (08:00) was 23.2 +/- 2.1 mm Hg and the diurnal curve pressure was 19.8 +/- 2.7 mm Hg. The trough and diurnal intraocular pressures for brimonidine were 19.6 +/- 3.4 mm Hg and 17.6 +/- 2.2 mm Hg, respectively. Brimonidine statistically reduced the pressure from baseline at each time point except hours 10 and 12 (P =.14 and P =.21, respectively). For latanoprost, the trough and diurnal pressures were 16.2 +/- 2.9 mm Hg and 15.4 +/- 2.5 mm Hg, respectively, and the pressure was statistically reduced at each time point (P <.001) and for the diurnal curve (P <.001). When compared directly, the intraocular pressure level for latanoprost was lower than brimonidine for the diurnal pressure and at each time point (P <.05). One patient was discontinued early from latanoprost treatment because of eyelid swelling; also, latanoprost caused more hyperemia than brimonidine (P =.04). CONCLUSION: This study suggests latanoprost dosed daily in the evening statistically reduces intraocular pressure more during daytime and evening hours than brimonidine dosed twice daily. Brimonidine may not consistently decrease the pressure 10 and 12 hours past dosing from nontreated levels.     

Diurnal intraocular pressure reduction with latanoprost 0.005% compared to timolol maleate 0.5% as monotherapy in subjects with exfoliation glaucoma

AIMS: To compare the diurnal intraocular pressure (IOP) efficacy and safety of timolol vs latanoprost in subjects with exfoliation glaucoma (XFG). METHODS: A 3-month prospective, single-masked, active-controlled, parallel comparison performed in six centres in Greece that randomized subjects in a 1 : 1 ratio to either latanoprost in the evening (2000 hours) and placebo in the morning (0800 hours), or timolol twice daily (0800 and 2000 hours). RESULTS: In all, 103 subjects completed the study. After 3 months of chronic dosing, the latanoprost group exhibited a trend to a greater diurnal IOP reduction from an untreated baseline (24.9+/-3.2-17.4+/-2.9) compared with timolol (24.7+/-2.8-18.3+/-1.9 mmHg) (P=0.07). Latanoprost showed a significantly greater IOP reduction at 0800 hours (-8.5 vs -6.0 mm Hg for timolol, P<0.0001) whereas no difference was observed between the two medications at 1000, 1400, and 2000 hours after a Bonferroni Correction. In addition, latanoprost demonstrated a narrower range of diurnal IOP (2.4) than timolol (3.2 mmHg)(P=0.0017). Safety was similar between groups, except there was more conjunctival hyperaemia with latanoprost (n=8) than timolol (n=1)(P=0.01). CONCLUSIONS: This study suggests that latanoprost provides a statistically lower 08:00-hour IOP and better range of IOP than timolol in the treatment of XFG glaucoma.