拉坦前列素治疗残余性闭角型青光眼的临床研究

目的观察拉坦前列素用于外滤过或虹膜周切术后的残余性闭角型青光眼的降眼压效果。方法采用随机、单盲、平行对照试验,选取外滤过或虹膜周切术后的残余性闭角型青光眼患者(眼压≥21mmHg且≤35mmHg,前房角检查至少累计90度范围内看到部分睫状体带),拉坦前列素组每晚一次,噻吗心安对照组早、晚各用一次,共观察8周。分别记录用药前、用药后1周、2周、4周、8周9am以及用药前、用药后8周4pm的眼压值。结果拉坦前列素组入选25例(25只眼),噻吗心安组入选24例(24只眼),两组用药后眼压都明显下降,拉坦前列素组从用药前的(24.73±3.90)mmHg(1mmHg=0.133kPa)降至8周时的(16.08±3.86)mmHg,下降幅度为35.0%;噻吗心安组从(26.00±4.44)mmHg降至(17.53±3.97)mmHg,下降幅度为32.6%。不同时间点上午两组眼压没有显著差异,而用药后8周4pm拉坦前列素组的眼压(15.33±3.16)mmHg明显低于噻吗心安组(18.76±4.13)mmHg(t=-3.016,P<0.05)。结论拉坦前列素可有效降低外滤过或虹膜周切术后的残余性闭角型青光眼的眼压,其作用较噻吗心安更持久。     

Melanin in the trabecular meshwork is associated with age, POAG but not Latanoprost treatment. A masked morphometric study

We wished to conduct a light and electron microscopic investigation of pigmentation within the trabecular meshwork of normals and primary open angle glaucoma (POAG) patients. In particular we wished to get a precise determination of whether there was a relationship between pigmentation and age. In addition we wanted to know if there was a difference between normals and POAGs and whether trabecular meshwork hyperpigmentation was associated with topical latanoprost medication. A total of 25 sham trabeculectomies conducted on post mortem donor eyes provided the age-matched normals and there were 62 trabeculectomy specimens from POAG patients. These were masked and the meshwork subjected to qualitative and quantitative morphological investigation. Light and electron microscopy confirmed that most of the trabecular meshwork melanin was phagocytosed and within meshwork cells. The granules were measured and found to be of the large iris epithelial type. Light microscopic morphometric analysis showed that the number of meshwork cell profiles that contained melanin increased both in normals and POAGs with age. However there was nearly three times more pigmented meshwork cells in the POAGs than the normals. The POAGs were divided into three groups of (1) minimal or no medication prior to surgery, (2) maximal medical therapy and (3) maximum medical therapy including latanoprost (12 specimens). All groups were significantly greater that the normals but of the three it was the maximal medical therapy group (without latanoprost) that had the highest pigmentation. We concluded that pigmentation of the meshwork is age-related and it is elevated in POAG by mechanisms unknown. The melanin accumulation seems to be partly due to the disease process, partly as a consequence of chronic antiglaucoma medication but interestingly not due to latanoprost even in patients where there is iris darkening (four specimens).     

曲伏前列腺素和卡巴胆碱对白内障术后眼压的影响

目的 评估白内障术中使用曲伏前列腺素和卡巴胆碱对术后眼压的影响.方法 将120例顺利行超声乳化加人工晶状体植入术的白内障患者平均分为4组.A组患者术毕结膜囊内滴入曲伏前列腺素滴眼液1滴,B组患者术毕前房注射卡巴胆碱0.2 mL加结膜囊内滴入曲伏前列腺素滴眼液1滴,C组患者术毕前房注射卡巴胆碱0.2 mL,D组患者术毕不使用药物,作为对照.分别于术前1 d及术后12、24、48 h对4组患者进行眼压测量,并对各组间的测量结果 进行比较.结果 A组、D组间各时间点眼压相比差异无统计学意义(P>0.05);B组、C组术后12、24 h眼压与D组相比差异均有统计学意义(P<0.01),但术后48 h眼压与D组相比差异无统计学意义(P>0.05);B组、C组各时间点间眼压相比差异无统计学意义(P>0.05). 结论 与对照组相比,白内障超声乳化加人工晶状体植入术中使用曲伏前列腺素不能降低患者术后眼压;使用卡巴胆碱可在术后早期(24 h内)明显降低眼压;曲伏前列腺素和卡巴胆碱联合应用不会产生协同或拮抗作用.(中国眼耳鼻喉科杂志,2009,9:155-156)     

Ocular hypotensive efficacy of travoprost in patients unsuccessfully treated with latanoprost

SUMMARY

Objective: To evaluate the efficacy of travoprost 0.004% monotherapy in patients unsuccessfully treated with latanoprost monotherapy.

Research design and methods: Open-label, non-comparative study conducted at US academic and private practice clinics in adult patients with ocular hypertension or primary open-angle glaucoma who required a change in therapy (due to either inadequate efficacy or safety issues) as judged by the investigator. Intraocular pressure (IOP) was measured at entry and 30?days later.

Main outcome measures: Mean change in intra-ocular pressure (mm Hg).

Results: Reported here are 488 per-protocol patients from 330 centers who were using latanoprost monotherapy prior to study entry, and who received travoprost monotherapy during the study. Patients had a mean age of 69?years, were approximately two-thirds Caucasian, 60% female, predominantly brown or blue eyes, and 91% were diagnosed as having primary open-angle glaucoma. The mean days in treatment were 31.9 ± 6.4. Mean IOP at study entry was 21.2?mm Hg. Following travoprost monotherapy, this was reduced by a mean of 3.2?mm Hg to 18?mm Hg (?p < 0.0001, paired t-test). There were 21 adverse events reported in the intent-to-treat (ITT) population for an incidence of 3.5%. There were some limitations to the current study including: no washout period, no control therapy, single IOP determinations at the beginning and the end of the study; patient compliance with the initial therapy was not measured, and the study was not masked. This study reflects a real-life situation of what a clinician can expect when he changes a patient from latanoprost monotherapy to travoprost monotherapy.

Conclusion: This study showed that travoprost provided a statistically and clinically significant reduction (?p < 0.0001) in IOP of 3.2?mm Hg for patients who had not been successfully treated with latanoprost monotherapy. The results of this trial demonstrate the potential benefit of using travoprost as a replacement therapy in order to ensure adequate IOP control.     

Concomitant administration of travoprost and brinzolamide versus fixed latanoprost/timolol combined therapy: three-month comparison of efficacy and safety

SUMMARY

Purpose: To compare the efficacy and safety of the concomitant administration of travoprost 0.004% once daily and brinzolamide 0.1% twice daily with those of a fixed combination of latanoprost 0.005%/timolol 0.5% once daily.

Research, design and methods: Forty-four patients with primary open-angle glaucoma or ocular hypertension with elevated IOP insufficiently responsive to monotherapy were randomly assigned to one of the two treatment groups: concomitant administration of travoprost 0.004% once daily and brinzolamide 0.1% twice daily (TB group: 22 patients) or latanoprost 0.005% plus timolol 0.5% once daily (LT group: 22 patients). Visits were undertaken at screening (current ocular hypotensive therapy was discontinued), baseline (randomization), and after 2 weeks, 1 month, 2 months and 3 months of therapy.

Main outcome measures: IOP was determined at 9 a.m., 12 p.m. and 4 p.m. at each study visit, and diurnal IOP was calculated as the mean of these recordings. Adverse events were recorded at each visit.

Results: IOP at the baseline visit was similar in both groups. Overall mean IOP was significantly lower in the TB as compared to the LT group after 1?month, 2?month and 3?month follow-up; only 9 a.m. measurements were significantly different, reaching a maximum difference (16.9 ± 0.9?mmHg vs 18.4 ± 1.8?mmHg, p < 0.001) at the 3?month check. The percentage of responders (IOP decrease ≥ 30%) was higher in the TB group. Both treatments were well tolerated and there were no cases of withdrawal from treatment.

Conclusions: Travoprost 0.004% and brinzolamide 0.1% concomitant therapy showed a greater efficacy than the fixed latanoprost 0.005%/timolol 0.5% combination in terms of absolute IOP decreases. Travoprost/brinzolamide therapy also offered the advantages of a greater percentage of responders.     

Circadian IOP-lowering efficacy of travoprost 0.004% ophthalmic solution compared to latanoprost 0.005%*

ABSTRACT

Purpose: The primary objective of this study was to determine the intraocular pressure- (IOP) lowering efficacy over two consecutive 24-h periods of travoprost 0.004% ophthalmic solution (Travatan^?) compared to latanoprost 0.005% (Xalatan^?) dosed once daily in patients with primary open-angle glaucoma or ocular hypertension.

Methods: This was a double-masked trial conducted at the Hospital Clínico San Carlos, Madrid, Spain. The primary objective of this study was to determine the IOP lowering efficacy of travoprost and latanoprost. During the eligibility visit, patients’ IOP was measured throughout two consecutive 24‐h periods every 4?h. Patients were then randomized to travoprost or latanoprost (one drop at 8 p.m. daily for 2 weeks). Sixty-two patients were randomized (travoprost n = 32; latanoprost n = 30). IOP was measured at week 2 every 4?h throughout two 24‐h periods. All measurements were taken in both supine and sitting positions with the aid of Perkins applanation tonometry. Limitations of the study include a small sample size (due to the difficulty in recruiting patients in a study of this type) which enrolled only Caucasian patients and a short study duration. However, with 25 subjects per group, there was at least 90% power to detect a mean IOP change from baseline of 2.9?mmHg and 80% power to detect a difference of 2.5?mmHg between treatments.

Results: Patients on travoprost therapy showed lower mean IOP levels than those on latanoprost. This difference was statistically significant (?p < 0.05) at 12, 16, 20, 24, 36, 40, and 48?h after the last dose for the supine position. The mean IOPs in the supine position throughout the first and the second 24‐h period of the week 2 visit as well as for the 48‐h visit were statistically lower (?p < 0.05) for the travoprost group. Adverse events were mild and included hyperemia and corneal staining. Travoprost and latanoprost were both well tolerated.

Conclusion: Mean IOP values were significantly lower for patients on travoprost for the majority of time points in the supine position.     

A cost-effectiveness analysis of fixed-combination therapies in patients with open-angle glaucoma: a European perspective

ABSTRACT

Objective: To compare the efficacy and cost implications of the use of the intraocular pressure-lowering prosta­glandin analogues bimatoprost, travoprost, and latano­prost as fixed-combination therapies with timolol, a β-adrenergic receptor antagonist.

Methods: A decision analytic cost-effectiveness model was constructed. Since no head-to-head studies comparing the three treatment options exist, the analysis was based on an indirect comparison. Hence, the model was based on efficacy data from five randomized, controlled, clinical studies. The studies were comparable with respect to study design, time horizon, patient population and type of end point presented. The measure of effectiveness was the percentage reduction of the intraocular pressure level from baseline. The cost evaluated was the cost of medication and clinical visits to the ophthalmologist. All drug costs were market prices inclusive of value-added tax, and visit costs were priced using official physician fees. Cost-effectiveness analyses were carried out in five European countries: Spain, Italy, United Kingdom, Norway and Sweden. The time horizon for the analyses was 3 months.

Results: The analysis showed that fixed-combination bimatoprost/timolol was more effective and less costly than fixed-combination travoprost/timolol and fixed-combination latanoprost/timolol in three out of the five countries analyzed. In two countries, bimatoprost/timolol was less costly than latanoprost/timolol, and cost the same as travoprost/timolol.

Conclusions: This cost-effectiveness analysis showed that the fixed combination of bimatoprost 0.03%/timolol 0.5% administered once daily was a cost-effective treatment option for patients with primary open-angle glaucoma. This study was limited by available clinical data: without a head-to-head trial, indirect comparisons were necessary. In the United Kingdom, Sweden, Norway, Italy, and Spain, from a health service viewpoint, bimatoprost/timolol was a slightly more effective as well as less costly treatment strategy when compared to both travoprost/timolol and latanoprost/timolol.     

Neuroprotective effect of latanoprost on rat retinal ganglion cells

Background To investigate the neuroprotective effect of intravitreal administration of latanoprost on retinal ganglion cell (RGC) damage induced by N-methyl-D-aspartic acid (NMDA) or optic nerve axotomy.Methods Using Sprague-Dawley rats, retinal ganglion cell damage was induced by either intravitreal administration of NMDA or optic nerve axotomy. Latanoprost at doses of 0.03, 0.3, 3, 30 and 300 pmol was administered intravitreally before NMDA injection or optic nerve axotomy. Retinal damage was evaluated by counting the number of surviving RGCs retrogradely labeled with fluorogold under the microscope.Results Seven days after the NMDA injury, the number of surviving RGCs was significantly increased at doses of more than 30 pmol atanoprost (846±178 cells/mm² P=0.0166) compared with vehicle control (556±122 cells/mm²). Ten days after the optic nerve axotomy, the number of surviving RGC was significantly increased even at a dose of 0.3 pmol (815±239 cells/mm², P=0.0359) compared with control (462±75 cells/mm²).Conclusions Intravitreal administration of latanoprost has a neuroprotective effect on rat RGC damage induced by either NMDA or optic nerve axotomy, while its pharmacological features are different.     

拉坦前列素、曲伏前列素和噻吗洛尔治疗原发性开角型青光眼的疗效比较分析

目的：比较拉坦前列素、曲伏前列素及噻吗洛尔滴眼液治疗原发性开角型青光眼（ POAG）的效果。方法将收治的120例患者随机分为A、B、C组,每组均为40例,其中A 组患者给予拉坦前列素滴眼液;B组患者给予曲伏前列素滴眼液;C组患者给予马来酸噻吗洛尔滴眼液,A、B组均为每天晚上约20：00给药1次,每次1滴,疗程为4周,C组为每天早上约08：00给药1次,每次1滴,疗程为4周。结果三组患者治疗前比较,眼压无统计学差异（ P ＞0．05）,三组患者用药治疗4周眼压值均有显著下降,用药前后差异具有统计学意义（ P ＜0．05）;拉坦前列素和曲伏前列素两种滴眼液组间治疗无显著性差异（ P ＞0．05）,但与噻吗洛尔治疗分别进行组间效果比对具有显著性差异（ P ＜0．05）。结论拉坦前列素、曲伏前列素及噻吗洛尔滴眼液治疗POAG在一个疗程内（4周）均能有效降低眼压,疗效持久,且两种前列素降眼压作用明显优于噻吗洛尔滴眼液治疗效果。