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。     

Daytime diurnal curve comparison between the fixed combinations of latanoprost 0.005%/timolol maleate 0.5% and dorzolamide 2%/timolol maleate 0.5%

PURPOSE: The diurnal efficacy and safety of the fixed combinations of latanoprost/timolol given once daily vs dorzolamide/timolol given twice daily in primary open-angle glaucoma or ocular hypertensive patients. DESIGN: A double-masked, two-centre, crossover comparison. RESULTS: In 33 patients, the mean diurnal IOP (0800-2000, measured every 2 h) for latanoprost/timolol fixed combination was 17.3+/-2.2 mmHg and for dorzolamide/timolol, the fixed combination was 17.0+/-2.0 mmHg (P = 0.36). Additionally, there was no statistical difference for individual time points following a Bonferroni correction. A bitter taste was found more frequently with the dorzolamide/timolol fixed combination (n = 6) than the latanoprost/timolol fixed combination (n = 0) (P = 0.040), while the latanoprost/timolol fixed combination demonstrated more conjunctival hyperaemia (n = 9) than the dorzolamide/timolol fixed combination (n = 2) (P = 0.045). One patient was discontinued early from the dorzolamide/timolol fixed combination due to elevated IOP. CONCLUSION: This study suggests that the daytime diurnal IOP is not statistically different between the dorzolamide/timolol fixed combination and latanoprost/timolol fixed combination in primary open-angle glaucoma and ocular hypertensive patients.     

Comparative studies of initial pressure reduction using 0.3% metipranolol and 0.25% timolol in eyes with wide-angle glaucoma

In a short-term study the pressure-lowering effects of Metipranolol 0.3% and Timolol 0.25% were compared in eyes with open-angle glaucoma by means of one-drop curves, diurnal pressure curves and tonography. It appears that these two drugs may be regarded as equal in respect of extent and duration of action. Aqueous humor outflow was facilitated slightly by both drugs, although increase was only statistically significant with Metipranolol.     

A 3-month comparison of 1% and 2% carteolol and 0.5% timolol in open-angle glaucoma

Carteolol, a nonselective beta-adrenergic antagonist with intrinsic sympathomimetic activity, was compared in 1% and 2% topical solutions with 0.5% timolol in 105 patients with primary open-angle glaucoma. In this double-masked, randomized 3-month trial, all three preparations significantly lowered intraocular pressure throughout the study, with no significant differences being observed. There were also no significant differences among the three preparations with regard to ocular or systemic adverse reactions, including heart rate and blood pressure. Offprint requests to: M.B. Shields     

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.     

Potential systemic and ocular side effects associated with topical administration of timolol maleate

A review of current literary sources disclosed a host of adverse reactions which may potentially be associated with the topical administration of timolol maleate. Systemic complications included a variety of cardiovascular, respiratory, central nervous system, gastrointestinal, and dermatologic reactions. Numerous ocular side effects were also reported including superficial punctate keratitis, ocular pain or discomfort, corneal anesthesia, and vague visual disturbances.     

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

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

Safety and efficacy of bimatoprost 0.03% versus timolol maleate 0.5%/dorzolamide 2% fixed combination

PURPOSE: To determine the efficacy and safety of bimatoprost given every evening versus the dorzolamide/timolol fixed combination (DTFC) given twice daily in open-angle glaucoma and ocular hypertensive patients. METHODS: A double-masked, three-center, prospective, randomized, crossover comparison with two 8-week treatment periods following a 4-week medicine free washout period. Diurnal curve intraocular pressures (IOPs) were taken at 08:00 (trough) and 10:00 and 16:00 hours. RESULTS: A total of 35 patients were enrolled and 32 completed all evaluations. The diurnal untreated baseline intraocular pressures was 24.8 +/- 2.4 mmHg. On the last day of treatment the mean diurnal intraocular pressures was 17.4 +/- 2.9 for bimatoprost and 18.1 +/- 2.8 mmHg for DTFC (p = 0.35). The individual time points for intraocular pressures were not statistically different between groups. Both groups statistically reduced the intraocular pressures from baseline for each time point and for the diurnal curve (p < 0.05). Regarding ocular safety and tolerability, there was more conjunctival hyperemia with bimatoprost (n = 15) than with DTFC (n = 7, p = 0.013) and more burning and stinging with DTFC (n = 12) than with bimatoprost (n = 0, p = 0.0005). Few systemic adverse events were recorded and there was no statistical difference between groups for any individual event (p > 0.05). CONCLUSIONS: This study indicates that the intraocular pressures are lowered to a statistically similar amount with DTFC compared to bimatoprost in open-angle glaucoma and ocular hypertensive patients.     

A comparison of the effects on intraocular pressure of latanoprost 0.005% and the fixed combination of dorzolamide 2% and timolol 0.5% in patients with open-angle glaucoma

PURPOSE: To compare the effects on intraocular pressure (IOP) of latanoprost 0.005% and the fixed combination of dorzolamide 2% and timolol 0.5%. METHODS: Overall, 226 patients whose IOP was insufficiently controlled by timolol alone were randomized to receive either latanoprost once daily or the fixed combination of dorzolamide plus timolol twice daily. Intraocular pressure was measured at 10:00 am and 5:00 pm at baseline and after 3 months of treatment. RESULTS: Mean IOP was reduced from baseline in both groups (p < 0.001), with a mean +/- SEM reduction of - 4.3 +/- 0.3 mmHg (19%) for the latanoprost treatment group and - 4.0 +/- 0.3 mmHg (17%) for the dorzolamide plus timolol treatment group. The two therapies were similarly effective in lowering IOP levels (mean difference in reduction: - 0.4 +/- 0.4; 95% confidence interval: - 1.1, 0.4). CONCLUSIONS: Monotherapy with latanoprost once daily was as effective in reducing mean IOP as the fixed combination of dorzolamide plus timolol twice daily in patients with IOP insufficiently controlled by timolol alone.     

Effect on the 24-hour diurnal curve of intraocular pressure of a fixed ratio combination of timolol 0.5% and pilocarpine 2% in patients with COAG not controlled on timolol 0.5%.

Eight patients with chronic open-angle glaucoma who had an intraocular pressure greater than 24 mm Hg at some time during the day while taking timolol 0.5% twice daily were given the fixed ratio combination of timolol 0.5% with pilocarpine 2% (TP2) twice daily. By comparing full 24-hour diurnal curves on timolol with those on TP2 it was possible to show that all patients except one (at a single timepoint) had an IOP less than 22 mm Hg when changed to TP2. The mean IOPs, the area under the diurnal pressure curve, and the diurnal variation were all significantly lower on TP2 twice daily than on timolol 0.5% twice daily.     

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.     

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

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

Comparison of travoprost 0.0015% and 0.004% with timolol 0.5% in patients with elevated intraocular pressure: a 6-month, masked, multicenter trial

OBJECTIVE: To compare the safety and intraocular pressure (IOP)-lowering efficacy of once-daily travoprost (0.0015% and 0.004%) to twice-daily timolol 0.5%. DESIGN: Prospective, 6-month, randomized, controlled, multicenter, double-masked, phase III study. PARTICIPANTS: Six hundred five patients with open-angle glaucoma or ocular hypertension. METHODS: Patients with an 8 AM IOP between 24 to 36 mmHg in at least one eye (the same eye) at two eligibility visits received either travoprost 0.0015%, travoprost 0.004% (dosed every day), or timolol 0.5% (dosed twice daily). MAIN OUTCOME MEASURES: Mean IOP at 8 AM, 10 AM, and 4 PM in the patient's eye with the higher baseline IOP. RESULTS: The mean IOP was significantly lower for both concentrations of travoprost compared with timolol. Travoprost was statistically superior to timolol at 9 of 13 visits, with differences in IOP reductions ranging from 0.9 to 1.8 mmHg (0.0015%) and 10 of 13 visits with differences in IOP reductions from 0.9 to 2.4 mmHg (0.004%). Mean IOP changes from baseline ranged from -6.0 to -7.5 mmHg (0.0015%), -6.5 to -8.0 mmHg (0.004%), and -5.2 to -7.0 mmHg for timolol. Hyperemia was experienced at rates of 29.2% (59 of 202) for travoprost 0.0015%, 42.8% (86 of 201) for travoprost 0.004%, and 8.9% (18 of 202) for timolol. Iris pigmentation changes were observed in 1.0% (2 of 200) of patients receiving travoprost 0.004% with no changes noted in the travoprost 0.0015% group or the timolol group. A decrease in pulse and systolic blood pressure was observed in the timolol group. There were no other clinically relevant or statistically significant changes from baseline in ocular signs or laboratory values, and no serious, related, unexpected adverse events were reported for any group. CONCLUSIONS: Travoprost (0.0015% and 0.004%), dosed once daily in the evening, is statistically superior or equal to timolol 0.5% dosed twice daily at all treatment visits during this 6-month study. IOP reductions of up to 2.0 mmHg greater than timolol were found in the travoprost 0.004% pooled data group. Travoprost is safe and well tolerated in patients with open-angle glaucoma or ocular hypertension.     

Local anesthetic effect and subjective tolerance of 2% carteolol and 0.6% metipranolol on healthy eyes

In a placebo-controlled, randomized, prospective, parallel, double-blind trial, corneal sensitivity was studied in 35 people with healthy eyes before and 1, 3, 6, 10, 15, and 30 minutes after application of carteolol 2% (20 eyes) and metipranolol 0.6% (20 eyes). Oxybuprocain 0.4% (local anesthetic, 10 eyes) served as a positive control substance, NaCl 0.9% (20 eyes) as a negative one (placebo). The test subjects assessed subjective tolerance of the test drugs on a four-step scale. Carteolol 2% did not decrease corneal sensitivity. There was no statistically significant difference between this group and the placebo group. Metipranolol 0.6% led to a decrease in corneal sensitivity of up to 14 mg (median), lasting up to 15 minutes. The decrease brought about by metipranolol 0.6% is about one-half of that caused by betaxolol 0.5%, but greater than that caused by timolol 0.5%. Oxybuprocain 0.4% causes corneal sensitivity to decrease below the measuring range of Cochet and Bonnet's esthesiometer (200 mg) for about 10 minutes. All but three eyes had returned to their initial corneal sensitivity values after 30 minutes. NaCl 0.9% eye drops do not decrease corneal sensitivity. On the contrary, a gradual increase in sensitivity (exercise effect) was found, which differed significantly from the initial value as of the 10th minute after drug application. These results confirm that it is necessary to check corneal sensitivity during topical beta-blocker therapy. "Responders," "sensitives," contact lens wearers, and patients with decreased corneal sensitivity (e.g., patients suffering from open-angle glaucoma with disk excavations, after cataract extraction or corneal transplantation) need frequent supervision.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

Effect of 1% brinzolamide and 0.5% timolol fixed combination on intraocular pressure after cataract surgery with phacoemulsification

AIM: To evaluate the effect of brinzolamide-timolol fixed combination on intraocular pressure (IOP) after cataract surgery.METHODS:The study included 92 eyes of 87 patients who underwent cataract surgery and intraocular lens implantation. Patients scheduled for phacoemulsification were assigned to 1 of 2 groups. The treatment group received 1 drop of brinzolamide-timolol fixed combination immediately after surgery, and the control group received no treatment. The IOP was measured preoperatively and at 2h and 24h postoperatively.RESULTS: The mean IOP change was lower in the treatment group than in the control group at 2h postoperatively. The difference between the mean IOP values of the two groups at 2h postoperatively was found to be statistically significant. Twenty-four hours after the surgery, the mean IOP change was still higher in the control group when compared to the treatment group.CONCLUSION: The fixed combination brinzolamide-timolol can effectively reduce IOP after cataract surgery.     

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.     

The 12-hour control of intraocular pressure on carteolol 2% twice daily.

In a 15-week double-blind, placebo-controlled, crossover study both carteolol 2% and timolol 0.5% produced a significant reduction in intraocular pressure. Twelve hours after administration the reduction in pressure on carteolol was significantly less than that obtained on timolol.