Intraocular pressure over 24 hours after repeated administration of latanoprost 0.005% or timolol gel-forming solution 0.5% in patients with ocular hypertension

PURPOSE: To compare the effect on intraocular pressure (IOP) over 24 hours after 4 weeks of treatment with latanoprost 0.005% and timolol gel 0.5%. DESIGN: Randomized, open, crossover single-center study. PARTICIPANTS: Twenty-seven patients with ocular hypertension. METHODS: The patients were randomly assigned to 4 weeks of latanoprost 0.005% once daily or timolol gel 0.5% once daily, with a 4-week washout period before switching therapy. MAIN OUTCOME MEASURES: Measurement of IOP during 24 hours of hospitalization. Blood pressure and heart rate were also measured repeatedly over the 24 hours. Daytime mean IOP, nighttime mean IOP, and 24-hour mean IOP were calculated as IOP area under the curve (AUC) divided by time in hours. RESULTS: The mean IOP during daytime (7 AM to 10 PM) was 13.5 +/- 0.4 mmHg (daytime IOP, AUC/15 hours, least square mean +/- standard error of the mean [SEM]) in the latanoprost group, and 14.8 +/- 0.4 mmHg in the timolol gel group. This difference of 1.3 +/- 0.3 mmHg was statistically significant in favor of latanoprost (P < 0.001; 95% confidence interval [CI], 0.7, 2.0). The mean IOP at night (10 PM to 7 AM) was 13.7 +/- 0.4 mmHg for latanoprost (nighttime IOP, AUC/9 hours, least square mean +/- SEM) and 15.9 +/- 0.5 mmHg for timolol gel, with a difference of 2.2 +/- 0.3 mmHg (P < 0.001; 95% CI, 1.5, 2.8). At every measured time point during the 24 hours, latanoprost reduced IOP more than timolol. There was no difference between the two treatment groups regarding blood pressure and heart rate. CONCLUSIONS: Latanoprost reduced mean 24-hour IOP, mean daytime IOP, and mean nighttime IOP statistically significantly more than timolol. Also, latanoprost reduced IOP more effectively at every measured time point over the 24 hours compared with timolol gel.     

Latanoprost administered once daily caused a maintained reduction of intraocular pressure in glaucoma patients treated concomitantly with timolol.

The long term effects of two dose regimens of latanoprost (PhXA41) administered to eyes concomitantly treated with timolol which had not adequately been controlled by timolol alone were compared. A total of 50 patients, 17 with primary open angle glaucoma and 33 with capsular glaucoma, were recruited from five clinics. All had glaucomatous visual field defects and an intraocular pressure (IOP) of at least 22 mm Hg despite treatment with 0.5% timolol twice daily. Patients were randomised to two treatment groups. In one group 0.006% latanoprost was given twice daily, in the other group placebo was given at 8 am and latanoprost at 8 pm for 3 months, with concomitant timolol treatment in both groups. Average daytime IOP (mean (SD)) at baseline (on timolol alone) and after 4 and 12 weeks' treatment was 24.8 (3.6), 16.8 (4.3), and 15.7 (2.4) mm Hg respectively with once daily application of latanoprost and 24.9 (2.9), 18.1 (3.0), and 18.0 (3.6) mm Hg respectively with latanoprost twice daily. No clinically significant side effects were observed during treatment. Latanoprost causes a marked and sustained IOP reduction in eyes which are also being treated with timolol. Latanoprost given once daily is at least as effective and probably superior to a twice daily dose regimen.     

Combined therapy of pilocarpine or latanoprost with timolol versus latanoprost monotherapy

Adjunctive intraocular pressure (IOP)-lowering therapy is widely used today, as one-third of all patients being treated for glaucoma need additional therapy to reach and maintain healthy IOPs. Timolol, latanoprost, and pilocarpine are three potent drugs that have been used in combination to reduce IOP. Timolol reduces the production rate of aqueous humor to achieve the IOP decrease. Latanoprost and pilocarpine both affect aqueous outflow, although by different mechanisms. The IOP efficacy of combined therapy with timolol and pilocarpine compared with timolol and latanoprost or with latanoprost alone has been investigated in three multicenter, randomized, clinical trials in Europe. This is a review of those published trials. In 2 of the 3 studies, the additional IOP lowering effect of latanoprost 0.005% administered once daily was compared with pilocarpine 2% administered 3 times daily in patients with primary open-angle glaucoma (POAG) or ocular hypertension currently on monotherapy with timolol 0.5% twice daily. These 6-month studies found that the timolol and latanoprost combination reduced IOP more and was better tolerated with fewer side-effects than the timolol and pilocarpine combination. At 6 months, there was no evidence of long-term drift in IOP with timolol and latanoprost. This combined therapy provides an effective and safe option for lowering IOP in glaucoma patients. These results suggest that the timolol/latanoprost combination is preferable to the timolol/pilocarpine combination not only with regard to side effects but also to the magnitude of IOP reduction. Two of the 3 studies compared latanoprost monotherapy with timolol and pilocarpine combined therapy in patients with POAG, various other glaucomas, or ocular hypertension. Treatment was for 6 weeks or 6 months. In both studies, latanoprost was more effective and better tolerated than the combination of timolol and pilocarpine. These results suggest that latanoprost alone should be tried before the addition of pilocarpine to timolol therapy is considered. The convenience of daily administration of a single drop of latanoprost versus multiple drops of timolol and pilocarpine should improve patient compliance.     

Efficacy of the dorzolamide/timolol fixed combination versus latanoprost in the treatment of ocular hypertension or glaucoma: combined analysis of pooled data from two large randomized observer and patient-masked studies.

In previous analyses of primary efficacy data from two randomized clinical trials, standard dosing regimens of the dorzolamide/timolol fixed combination (COSOPT) and latanoprost (XALATAN) were shown to have equivalent efficacy with regard to reduction in mean daytime diurnal intraocular pressure (IOP). We performed additional post hoc analyses of pooled data from these studies to compare further the efficacy of the two treatments. The studies used identical 3-month, parallel group, randomized, observer-masked and patient-masked, multicenter designs. Patients with a baseline IOP > or = 24 mm Hg were randomized to either the 2% dorzolamide/0.5% timolol combination eye drops twice daily (n = 273) or 0.005% latanoprost eye drops once daily (n = 271). The IOP measurements were made at 8 AM, 10 AM, 2 PM, and 4 PM at the baseline visit and then on each of the 3 monthly assessment days. The following measures were analyzed on a post hoc basis: 1) percentages of patients meeting target levels of IOP reduction; 2) mean IOP reduction in those patients with high IOP (> or =30 mmHg) at baseline; 3) mean IOP at each of the assessment time points during a day. A total of 259 patients in the dorzolamide/timolol group and 268 patients in the latanoprost group were included in the efficacy analysis. At 3 months, both treatments showed similar efficacy with regard to the percentages of patients who achieved target levels of IOP reduction (e.g., 40% IOP reduction in 15% of dorzolamide/timolol combination patients and 13% of latanoprost patients), mean IOP reduction in those patients with high IOP at baseline (dorzolamide/ timolol combination, 12.5 mmHg, latanoprost, 12.6 mmHg), and mean IOP at each time point during the day. By the measures used in this analysis, the dorzolamide/timolol combination and latanoprost were equally effective at lowering IOP in patients with ocular hypertension or glaucoma.     

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.     

Comparison of the nocturnal effects of once-daily timolol and latanoprost on intraocular pressure

PURPOSE: To compare the nocturnal effects of once-daily timolol and latanoprost on intraocular pressure (IOP) in patients with ocular hypertension or early glaucomatous changes. DESIGN: Prospective, open-label, experimental study with crossover design. METHODS: Eighteen patients with ocular hypertension or early glaucomatous changes (aged 41 to 79 years) each received topical treatments with timolol (0.5% Timoptic-XE), latanoprost (0.005% Xalatan), and no IOP-lowering medication, for at least 4 weeks. Timolol was given once in the morning upon awakening and latanoprost once in the evening at bedtime. At the end of each treatment period, the patient was housed in a sleep laboratory for 24 hours and IOP was measured every 2 hours using a pneumatonometer. Measurements were taken sitting and supine during the 16-hour diurnal/wake period and only supine during the 8-hour nocturnal/sleep period. Mean diurnal and nocturnal IOP levels were compared among the treatments with timolol, latanoprost, and no medication. RESULTS: In the diurnal period, the mean IOP under the timolol or the latanoprost treatment was significantly less than the mean IOP under no medication in both the sitting and the supine positions. There was no statistical difference between the timolol and latanoprost treatments. In the nocturnal period, supine IOP with timolol treatment was not different from the supine IOP with no medication but was significantly higher than supine IOP with the latanoprost treatment. CONCLUSION: Although both once-daily timolol and latanoprost were effective in lowering IOP during the diurnal period, only latanoprost reduced IOP during the nocturnal period.     

Comparison of latanoprost monotherapy to dorzolamide combined with timolol in patients with glaucoma and ocular hypertension — A 3-month randomised study

· Background: The purpose of the study was to compare the effects on intraocular pressure (IOP) of adding dorzolamide to timolol or of switching from timolol to latanoprost monotherapy in glaucoma patients inadequately controlled on timolol. · Methods: The study was designed as a 3-month randomised, open-label, multicentre study comprising 183 patients with primary open-angle glaucoma, capsular glaucoma with IOP above 22 mmHg on treatment with one or two ocular hypotensive drugs, or ocular hypertension with IOP above 27 mmHg. After a 2- to 4-week run-in period on timolol, 0.5% twice daily, the patients were randomised to treatment with either latanoprost, 0.005% once daily, or the combination of timolol, 0.5% twice daily, and dorzolamide, 2% twice daily. The mean diurnal IOP after 3 months of treatment was compared with baseline. · Results: Switching from timolol to latanoprost reduced mean diurnal IOP by 4.5±0.2 mmHg (mean±SEM, ANCOVA; 20%), and adding dorzolamide to timolol reduced mean diurnal by 4.4±0.2 mmHg (mean±SEM, ANCOVA; 20%). No serious side effects were observed with either treatment. · Conclusion: Latanoprost monotherapy can be an alternative to combined treatment with two aqueous flow suppressors in patients whose IOP is insufficiently controlled by timolol alone. Received: 30 March 1999 Revised version received: 27 May 1999 Accepted: 7 June 1999     

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.     

Effect on intraocular pressure during 24 hours after repeated administration of the fixed combination of latanoprost 0.005% and timolol 0.5% in patients with ocular hypertension

PURPOSE: To measure the effect on intraocular pressure (IOP) for 24 hours after repeated administration of the fixed combination of latanoprost 0.005% and timolol 0.5%. METHODS: A randomized, double-masked placebo-controlled crossover study including 20 patients with ocular hypertension was carried out. Patients were randomized to treatment with the fixed combination of latanoprost and timolol or with placebo. The eyedrop was taken at 8 AM. After 2 weeks of treatment, the patients were hospitalized, and the IOP was measured at 8 AM, and thereafter every other hour until midnight, and also at 3 AM, 6 AM, and 8 A.M. After a washout period of 4 weeks, they switched to the other eyedrop, and after 2 weeks of treatment were hospitalized and the IOP measurements were repeated at the same intervals. RESULTS: The mean 24-hour IOP was 14.7 +/- 0.3 mm Hg (mean +/- standard error of the mean) for latanoprost and timolol and 19.4 +/- 0.3 mm Hg for placebo. This corresponds to a significant IOP difference of 4.7 +/- 0.4 mm Hg (95% confidence interval 3.8-5.8; P < 0.001) between the two treatments in favor of the combination. At all measured time points, except at 3 AM, the mean IOP was lower with latanoprost and timolol than with placebo. During daytime measurements the mean IOP was 13.9 +/- 0.7 mm Hg for the fixed combination and 19.5 +/- 0.7 mm Hg for the placebo. Corresponding figures at nighttime were 16.1 +/- 0.7 mm Hg and 19.2 +/- 0.7 mmHg, respectively. CONCLUSIONS: The fixed combination of latanoprost and timolol significantly reduced IOP after administration once daily for 2 weeks in patients with ocular hypertension. A reduction of IOP during a 24-hour period was seen, with a greater IOP reduction during daytime compared with nighttime. The fixed combination applied once daily could be a convenient alternative to concomitant therapy with its individual components.     

Comparison of the intraocular pressure-lowering effect of latanoprost and timolol in patients with chronic angle closure glaucoma: a preliminary study

OBJECTIVE: To compare the intraocular pressure (IOP)-reducing effect and side effects of 0.005% latanoprost once daily to 0.5% timolol twice daily in patients with primary chronic angle closure glaucoma (CACG). DESIGN: Randomized, double-masked two-center clinical trial. PARTICIPANTS: Thirty-two Asian patients with CACG, defined as glaucomatous optic neuropathy with a compatible visual field defect and at least 6 clock hours of synechial angle closure on gonioscopy were recruited. All patients had previous peripheral iridotomy (PI) with IOP >21 mmHg after PI and were thereafter controlled (IOP <22 mmHg) with one or two pressure-reducing drugs. INTERVENTION: After a washout period, the patients were randomized to a 2-week treatment period with either placebo in the morning and 0.005% latanoprost in the evening or 0.5% timolol twice daily. MAIN OUTCOME MEASURES: The short-term IOP reduction of latanoprost and timolol in patients with CACG. IOP was measured at baseline, and after 2, 7, and 14 days of treatment. In addition, the short-term ocular and systemic adverse events of the two drugs were evaluated. RESULTS: Thirty patients completed the study. Two patients in the timolol group were withdrawn because of inadequate IOP control. Compared with baseline, the IOP after 2 weeks of treatment was statistically significantly reduced by 8.8 +/- 1.1 mmHg (mean +/- SEM, P < 0.001) in the latanoprost group, and by 5.7 +/- 0.9 mmHg (P < 0.001) in the timolol group. The difference in IOP reduction between the two treatment groups was 3.1 +/- 1.5 mm Hg in favor of latanoprost (P = 0.04). The main ocular adverse events reported in both treatment groups were conjunctival hyperemia and discomfort. CONCLUSIONS: In this preliminary study, a significantly greater IOP reduction was achieved with 0.005% latanoprost once daily compared with 0.5% timolol twice daily in patients with CACG. The results suggest that latanoprost may be a therapeutic choice for the medical treatment of primary CACG.     

Latanoprost: experience of 2-year treatment in Scandinavia

PURPOSE: The aim of the study was to assess efficacy and side effects of latanoprost during two years of treatment. METHODS: The study was a randomized, parallel group, double-masked, multicenter comparison between latanoprost and timolol in patients with open angle glaucoma or ocular hypertension, followed by an open-label 18-month extension during which all patients were treated with latanoprost. RESULTS: Latanoprost caused a marked and sustained reduction of the intraocular pressure (IOP). IOP was reduced from baseline levels 25.1+/-3.5 mm Hg (mean+/-SD) in 183 patients initially randomized to treatment with latanoprost to 17.4+/-2.9 mm Hg (n=66) after 24 months of treatment. For patients initially randomized to treatment with timolol the corresponding figures were 24.3+/-2.3 mm Hg (n=72) and 17.4+/-2.6 (n=41) mm Hg after 18 months of treatment with latanoprost. Two patients were withdrawn because of uncontrolled IOP and 11 patients required additional timolol treatment to maintain an adequate IOP control. Patients initially treated with timolol and switched to latanoprost had a further reduction of the IOP of 1.0 mm Hg after 6 months of treatment with latanoprost (p<0.005). 46 patients were withdrawn from the study, mostly due to increased iris pigmentation or an iris color with known high risk of developing increased pigmentation. 22 patients developed increased pigmentation of the iris. The follow-up revealed no previously unknown ocular or systemic side effects. CONCLUSION: Once daily applications of latanoprost cause a marked and sustained reduction of the IOP. The only clinically significant side effect noted was the increased pigmentation of the iris, most frequently seen in irides with a mixture of brown and blue/gray or green colors. No systemic side effect was observed.     

拉坦前列素和噻吗心安治疗开角型青光眼、高眼压症的对照研究

目的：观察Ｌａｔａｎｏｐｒｏｓｔ的降眼压效果及安全性。方法：采用随机分组对照组,０．００５％Ｌａｔａｎｏｐｒｏｓｔ每日一次或０．５％Ｔｉｍｏｌｏｌ（噻吗心安）每日２次,治疗原发性开角型青光眼、高眼压症和剥脱性青光眼,共１４例,疗程１２周,观察其眼压及不良反应。结果：Ｌａｔａｎｏｐｒｏｓｔ组和Ｔｉｍｏｌｏｌ组均可有效地降低眼压（Ｐ〈０．０１）,两组间眼压下降值没有差异。两组治疗前后不同时间点眼压下降     

Comparison of the intraocular pressure lowering effect of latanoprost and a fixed combination of timolol-pilocarpine eye drops in patients insufficiently controlled with beta adrenergic antagonists. French Latanoprost Study Group, and the Swedish Latanoprost Study Group

AIMS: To compare the effect on intraocular pressure (IOP) of latanoprost monotherapy and timolol-pilocarpine in patients with glaucoma or ocular hypertension with inadequately controlled IOP on topical beta adrenergic antagonists. METHODS: This was a multicentre, randomised, observer masked, 6 week study performed in France and Sweden. 23 centres enrolled 237 patients with glaucoma or ocular hypertension and an IOP of at least 22 mm Hg on treatment with topical beta adrenergic antagonists, alone or in combination. After a 21 day run in period on timolol 0.5% twice daily, patients were randomised either to latanoprost 0.005% once daily or to a fixed combination of timolol-pilocarpine twice daily. Changes in mean diurnal IOP from the baseline to the 6 week visit were determined with an analysis of covariance. RESULTS: Mean diurnal IOP was statistically significantly decreased from baseline in both groups (p<0.001). Switching to latanoprost treatment reduced mean diurnal IOP by 5.4 (SEM 0.3) mm Hg (ANCOVA -22%) and switching to timolol-pilocarpine treatment reduced mean diurnal IOP by 4.9 (0.4) mm Hg (-20%). Blurred vision, decreased visual acuity, decreased twilight vision, and headache were statistically significantly more frequent in the timolol-pilocarpine group. CONCLUSIONS: Latanoprost monotherapy was at least as effective as fixed combination timolol-pilocarpine twice daily treatment in reducing mean diurnal IOP in patients not adequately controlled on topical beta adrenergic antagonists. Latanoprost was better tolerated than timolol-pilocarpine regarding side effects. These results indicate that a switch to latanoprost monotherapy can be attempted before combination therapy is initiated.     

The effect on diurnal intraocular pressure of the fixed combination of latanoprost 0.005% and timolol 0.5% in patients with ocular hypertension

PURPOSE: To measure the effect on intraocular pressure (IOP) after single-dose administration of the fixed combination of latanoprost 0.005% and timolol 0.5%. METHODS: A randomized, double-masked placebo-controlled parallel-group study was carried out. Twenty patients with ocular hypertension received the fixed combination of latanoprost+timolol, while 10 received placebo eyedrops. On baseline day no eyedrops were given, but IOP was measured repeatedly between 8.00 a.m. and 8.00 p.m. On Day 7 the eyedrops were given at 8.00 a.m., and IOP measured as on baseline day. On Day 8 and Day 9, IOP was again measured at 8.00 a.m. RESULTS: There was no difference in IOP in the placebo group. In the latanoprost+timolol group maximal IOP reduction (12.4+/-2.8 mmHg; mean+/-standard deviation) occurred 6.4 hours after drug administration (5.2--7.7 hours; 95% confidence interval [CI]). The mean IOP reduction after 24 hours was 9.8 mmHg (7.4--12.2 mmHg; 95% CI; p<0.001), and after 48 hours 5.7 mmHg (3.4--8.1 mmHg; 95% CI; p<0.001). CONCLUSIONS: The fixed combination of latanoprost+timolol statistically significantly reduced IOP after single-dose administration. The maximal effect was noted after about 6 hours, and the IOP reduction was still pronounced after 48 hours.     

Rate of response to latanoprost or timolol in patients with ocular hypertension or glaucoma

PURPOSE: This study determined the rate of response to latanoprost compared with timolol in patients with glaucoma or ocular hypertension, whether some patients convert from non-responders to responders after more prolonged therapy, and whether this conversion represents a delayed response or random fluctuation. METHODS: In a previously described, multicenter, randomized, double-masked, parallel group study, patients received either 0.005% latanoprost once daily (n = 128) or 0.5% timolol twice daily (n = 140) for 6 months. Intraocular pressure (IOP) was assessed at baseline and at 0.5, 1.5, 3, 4.5, and 6 months of treatment at 8 am on all visits, and also at noon and 4 pm at baseline and 6 months. Rate of response based on diurnal measurement at 6 months compared with baseline was assessed using several criteria for response. Eyes with an IOP reduction of less than 15% compared with baseline at 8 am arbitrarily were classified as non-responders at each of the 5 visits during treatment. Consistency of non-responder classifications for individual eyes was assessed. RESULTS: Mean IOP reduction was greater (P < 0.001) in latanoprost-versus timolol-treated patients throughout the course of therapy. A greater rate of response occurred in patients treated with latanoprost, and differences in response rates between the 2 drugs increased as the definitions of response became more stringent. A greater percentage of non-responders at any single visit were classified as responders at all other visits with latanoprost in comparison with timolol. CONCLUSIONS: Latanoprost produces a greater rate of response compared with timolol. A higher percentage of non-responders to latanoprost compared with timolol on any individual visit are responders on all other visits. Likewise, a higher proportion of patients who do not initially respond will become responders with continued treatment with latanoprost compared with timolol.     

Additive effect of latanoprost to the combination of timolol and dorzolamide

PURPOSE: To study the additive effect of latanoprost 0.005% in patients who have uncontrolled intraocular pressure (IOP) using timolol 0.5% and dorzolamide 2%. METHODS: Fifty-two consecutive patients with open-angle glaucoma who were using timolol and dorzolamide and were considered to have IOP above their defined target pressure were included in this study. After a baseline diurnal tension curve (DTC) was performed, latanoprost once a day was added to the treatment, and a second DTC was performed 1 week later. RESULTS: Five patients (9.6%) were discontinued from treatment because of side effects. The remaining 47 patients showed a significant IOP reduction of 3.1 mm Hg (16%) from a baseline of 19.3 mm Hg (mean IOP registered during DTC; P < or = 0.0001). Seventeen patients (36.3%) showed a mean IOP reduction greater than 20%. CONCLUSIONS: Latanoprost had an additive effect when used as a third drug for patients on timolol and dorzolamide who were in need of further IOP reduction. These results suggest that latanoprost may be very effective in some patients with poorly controlled glaucoma on multiple therapy.     

A Comparative Study of Latanoprost (Xalatan) and Isopropyl Unoprostone (Rescula) in Normal and Glaucomatous Monkey Eyes

Latanoprost (PhXA41, Xalatan) and isopropyl unoprostone (UF-021, unoprostone, Rescula) two new prostanoid derivatives, have been shown to reduce intraocular pressure (IOP) significantly in patients with glaucoma or ocular hypertension. This study was designed to compare the ocular hypotensive effects of latanoprost and unoprostone in cynomologus monkeys with glaucoma and characterizes the prostanoid’s mechanisms of action in normal cynomolgus monkey eyes. Intraocular pressure was measured daily at 0, 0.5, and 1 hour and hourly for 5 additional hours during 1 baseline day, 1 vehicle-treated day, and 5 days of therapy with either 0.005% latanoprost or 0.12% unoprostone applied twice daily, at 9:30 am and 3:30 pm, to the glaucomatous eye of eight monkeys with unilateral laser-induced glaucoma. Outflow facility was measured in six normal monkeys 3 hours prior to dosing and 1 hour after unilateral dosing with either drug. Aqueous humor flow rates were measured in six normal monkeys hourly for 4 hours on 1 baseline day and on 1 treatment day beginning 1 hour after administration of either drug to one eye. Intraocular pressure was significantly (P < 0.005) reduced after the first application for 4 hours with latanoprost and for 2 hours with unoprostone, up to 5.4±0.8 mm Hg (mean ± SEM) (latanoprost) and 3.8 ± 0.5 mm Hg (unoprostone). Intraocular pressure was significantly (P < 0.005) reduced for at least 18 hours following each pm dose of latanoprost. Intraocular pressure was not reduced (P > .05) 18 hours after each pm dose of unoprostone. An enhancement of the ocular hypotensive effect was observed from day 1 to day 5 with repeated dosing of either drug. Latanoprost produced a greater magnitude of IOP reduction for a longer duration of time than unoprostone after each application. Neither drug altered outflow facility or aqueous humor flow rates. Latanoprost and unoprostone appear to reduce IOP in monkeys by enhancing uveoscleral outflow. Latanoprost appears to be more efficacious and potent than unoprostone in reducing IOP in glaucomatous monkey eyes.     

latanoprost与噻吗心安治疗开角型青光眼及高眼压症的临床？…

验证ｌａｔａｎｏｐｒｏｓｔ对青光眼的治疗价值。方法对１２８例原发性开角型青光眼和高眼压症患者进行为期１２周的多中心、开放式,临床随机对照研究,观察其随眼压疗效和不良反应。分别应用０．００５％ｌａｔａｎｏｐｒｏｓｔ每日滴眼１次及０．５％噻吗心安每日滴眼２次。随访时间为治疗前、治疗后２、６及１２周、测量眼压并观察记录局部、全身不良反应。结果共入选１２８例（ｌａｔａｎｏｐｒｏｓｔ组６３例,噻吗心安组６５     

Effects of topical hypotensive drugs on circadian IOP, blood pressure, and calculated diastolic ocular perfusion pressure in patients with glaucoma

PURPOSE: To compare the short-term effects of timolol 0.5%, brimonidine 0.2%, dorzolamide 2%, and latanoprost 0.005% on intraocular pressure (IOP), blood pressure (BP), and diastolic ocular perfusion pressure (DOPP), calculated as the difference between the diastolic blood pressure (DBP) and IOP. METHODS: According to a 4 x 4 Latin squares design for repeated measures, 27 untreated patients and patients with newly diagnosed primary open-angle glaucoma (POAG) were treated with timolol 0.5% at 8 AM and 8 PM; brimonidine 0.2% at 8 AM and 8 PM; dorzolamide 2% at 8 AM, 2 PM, and 8 PM; and latanoprost 0.005% at 8 PM. The duration of each treatment course was 6-weeks, with a 4-week washout between each treatment. IOP and BP were measured at baseline and at the end of each treatment period. IOP was measured every 2 hours throughout a 24-hour period. Sitting IOP was measured from 8 AM to 10 PM by Goldmann applanation tonometry. Supine IOP was assessed from 12 to 6 AM by means of a handheld electronic tonometer (TonoPen XL; Mentor, Norwell, MA). BP monitoring was performed by means of an automated portable device (TM-2430; A & D Co., Saitama, Japan). RESULTS: All the drugs tested decreased the IOP significantly at all time points in comparison with baseline pressure. The mean 24-hour IOP after latanoprost administration (16.62+/-0.98 mm Hg) was significantly lower than that after timolol, brimonidine, or dorzolamide (P=0.0001). During the 24-hour period, brimonidine induced a significant decrease in systolic BP (SBP) and DBP at all time points when compared with baseline measurements and with those after administration of the other drugs (P<0.0001). Timolol caused a significant decrease in DBP and SBP at all the 24-hour time points when compared with the baseline and with the dorzolamide- and latanoprost-induced changes (P<0.0001). The mean 24-hour DOPPs were 50.7+/-5.9 mm Hg at baseline, 53+/-5.5 mm Hg with timolol, 46.2+/-5.4 mm Hg with brimonidine, 55.9+/-4.6 mm Hg with dorzolamide, and 56.4+/-4.9 mm Hg with latanoprost. Brimonidine induced a significant decrease in the mean 24-hour DOPP compared with that at baseline (P<0.0001), whereas dorzolamide and latanoprost induced a significant increase (P<0.0001). CONCLUSIONS: Latanoprost seemed to induce a uniform reduction in IOP during the 24-hour period, although timolol was as effective as latanoprost during the daytime, and dorzolamide are as effective as latanoprost at night. SBP and DBP were significantly decreased by either timolol or brimonidine. In this study of patients with newly diagnosed POAG, only dorzolamide and latanoprost significantly increased mean 24-hour DOPP.     

Intraocular pressure over 24 hours after single-dose administration of latanoprost 0.005% in healthy volunteers. A randomized, double-masked, placebo controlled, cross-over single center study.

PURPOSE: To measure the effect on intraocular pressure (IOP) over 24 hours after single-dose administration of latanoprost 0.005%. PATIENTS AND METHODS: A randomized, double-masked placebo-controlled cross-over study was carried out. Twenty healthy volunteers were randomly assigned to receive a single drop of latanoprost 0.005% or placebo, with a 2-week wash-out period before switching therapy. After hospitalization, the IOP was measured repeatedly over 24 hours, and again after 36 and 48 hours. RESULTS: The maximum IOP reduction for latanoprost occurred 12 hours after the dose with IOP 11.7+/-0.5 mmHg (least square mean+/-standard standard error of the mean [SEM]) for latanoprost and 13.5+/-0.5 mmHg for placebo. The difference of 1.8+/-0.6 mmHg was statistically significantly in favor of latanoprost (p=0.01; ANCOVA, confidence interval (CI) [-3.1; -0.5] mmHg). The average time to onset of action, defined as 50% of the maximal IOP reduction, was 6.0 hours for latanoprost. Latanoprost consistently reduced IOP over 24 hours after drop application with a difference in IOP reduction of 1.1+/-0.5 mmHg (p=0.03, CI [-2.1, 0.1]) at 24 hours. The corresponding IOP difference at 36 hours was 0.7+/-0.5 mmHg (p=0.20, CI [-1.7, 0.3]), and at 48 hours 0.8+/-0.5 mmHg (p=0.04, CI [-1.5, 0.0]). CONCLUSIONS: Latanoprost applied as a single dose reduced IOP over 24 hours in healthy subjects compared with placebo. The IOP reduction was still present, however, less pronounced, 48 hours after drug application.