Intraocular pressure reduction with travoprost/timolol fixed combination,with and without adjunctive brinzolamide,in glaucoma

ABSTRACT

Objective: To investigate if combined intraocular pressure (IOP)-lowering medication with travoprost/timolol fixed combination and a carbonic anhydrase inhibitor, brinzolamide, is superior to both travoprost monotherapy and travoprost/timolol fixed-combination therapy in primary open-angle glaucoma and ocular hypertension.

Methods: Following a 4-week wash-out period and using 4-week long treatment periods, 20 primary open-angle glaucoma or ocular hypertension patients were treated with evening travoprost 0.004?%?, then switched to evening travoprost 0.004?%?/timolol 0.5?%?fixed combination, and finally the treatment was combined with adjunctive twice-daily brinzolamide 1?%?ophthalmic suspension. Both eyes were treated, but only one eye per patient (the eye with the higher mean diurnal IOP at baseline), was evaluated. IOP was measured at 8 a.m., 12 noon and 4 p.m. at baseline and at the end of each treatment period.

Results: Mean diurnal IOP (mean (SD)) at baseline was 28.5 (7.3) mmHg which decreased to 22.3 (6.3) mmHg on travoprost, 19.2 (3.4) mmHg on travoprost/timolol fixed combination and 17.3 (3.4) mmHg when the brinzolamide was added to the travoprost/timolol combination (ANOVA, contrast test, p?<?0.003 for all comparisons). The individual time point IOP values showed similar and significant stepwise differences.

Conclusion: Adjunctive brinzolamide medication provided further IOP decrease in patients receiving evening-dosed travoprost/timolol fixed combination. The travoprost/timolol fixed combination was significantly more effective in IOP reduction than travoprost monotherapy, which by itself induced a significant IOP decrease compared to the untreated baseline value. The results of this open label study suggest that combined therapy with travoprost/timolol fixed combination and brinzolamide is clinically useful for IOP-lowering in primary open-angle glaucoma and ocular hypertension.     

Chemotactic response to some arachidonic acid lipoxygenase products in the rabbit eye

The effects of arachidonic acid, its cyclo-oxygenase and lipoxygenase products and the synthetic chemotactic peptide, formyl-methionyl-leucyl-phenylalanine (FMLP) on leukocyte accumulation in the aqueous humour and intraocular pressure in the rabbit were studied in vivo. Substances were injected into the anterior chamber of the eyes of anesthetised rabbits using a closed circuit perfusion system. Injecction of arachidonic acid, prostaglandins E₁ and E₂, and the monohydroperoxy and hydroxy acids of the lipoxygenase pathway did not result in any significant accumulation of leukocytes in the anterior chamber. In contrast, FMLP and 5,12-diHETE (Leukotriene B₄) resulted in significant dose dependent accumulation of leukocytes into the aqueous humour. Leukocytes appeared in the aqueous humour between 2 and 3 h after the injection of either FMLP or LTB₄ and the response was maximal at 4 h. None of the lipoxygenase products tested had any effect on intraocular pressure in contrast to the profound effects observed with arachidonic acid and the E type prostaglandins. FMLP had a small but significant effect on intraocular pressure at the highest dose tested for leukocyte accumulation. These results indicate that the effects of the cyclo-oxygenase products of arachidonate metabolism are mainly vascular in the rabbit eye in contrast to the predominantly cellular effects of lipoxygenase products. Thus in the eye, the interaction of cyclo-oxygenase and lipoxygenase products of arachidonate metabolism may be important in the development of both acute and chronic ocular inflammation.     

Economic evaluation of medication,laser trabeculoplasty and filtering surgeries in treating patients with glaucoma in the US

ABSTRACT

Objective: Despite the significant clinical and economic burden associated with glaucoma, studies evaluating the long-term costs of existing treatments are limited. This study compared the 5-year costs of three treatment strategies: medication, laser trabeculoplasty, and filtering surgeries in managing patients with primary open-angle glaucoma whose intra-ocular pressures were not adequately controlled by two medications.

Research design and methods: A Markov model was developed to simulate the transition of treatment progression over a 5-year period to evaluate the total treatment costs associated with each strategy. In the medication arm, medications were the only available treatment, whereas in the laser trabeculoplasty and surgery arms, patients would receive concomitant medications both at the time of the procedure and in subsequent years. Treatment states were determined by the rate of success in controlling patients’ intra-ocular pressure in each year. The distribution of treatment states and the transition probabilities between these states were derived from published literature, adjusted or supplemented by the authors’ own treatment experiences. Costs assessed in the model included treatment, complications associated with each treatment, and physician office visits obtained from published literature and standardized fees and schedules.

Results: The 5-year cumulative costs were approximately $6571, $4838 and $6363 for patients in the medication, laser trabeculoplasty, and filtering surgery arms, respectively. Costs of third-line medication, first-line medication following laser trabeculoplasty, and post-surgery complications had the greatest impact on the model results in the medication, laser trabeculoplasty, and filtering surgery arms, respectively. Probabilistic sensitivity suggested the results were statistically significant (?p?<?0.001), favoring the use of laser trabeculoplasty.

Conclusions: Over 5?years laser trabeculoplasty was associated with the lowest total costs compared to treatment by medication alone or by filtering surgery for patients who were not adequately controlled by two medications. Future development of glaucoma treatment should focus on reducing the need for post-procedure medical therapy as well as lowering the rate of post-procedure complications. Limited by the availability of the transition probabilities in published literature, the model results need to be validated by prospective or retrospective observational studies.     

眼舒滴眼液在激光泪道成形术中的应用

目的 :评价眼舒滴眼液在激光泪道成形术中应用的疗效。方法 :12 4例病人 ,男性 32例 ,女性92例 ,共 14 0只眼泪道阻塞。行Nd :YAG激光治疗后 ,采用眼舒滴眼液灌注冲洗泪道 ,观察疗效。结果 :病人溢泪症状明显好转 ,冲洗泪道通畅 ,疗效持久 ,治愈率为 95 % ,无不良反应。结论 :眼舒滴眼液有利于提高激光泪道成形术的治愈率。     

Digoxin-induced decrease in intraocular pressure in the cat.

A constant intravenous infusion of digoxin (2 micrograms/kg/min) to alpha-chloralose-anesthetized cats produced a progressive decrease in intraocular pressure with increasing doses of digoxin between 60 micrograms/kg and drug-induced ventricular arrhythmia which occurred at a mean dose of 172 micrograms/kg. Digoxin elicited a 40% decrease in intraocular pressure just prior to ventricular arrhythmia compared to a decrease of only 10% with a control infusion of diluent in the same animal (P less than 0.05). There was no significant difference (P less than 0.1) between changes in blood pressure and heart rate observed in the experimental versus the control infusions. The decrease in intraocular pressure may result from inhibition of the Na-K-ATPase in the ciliary body.     

Intraocular pressure decrease with preservative-free fixed and unfixed combination of tafluprost and timolol in pseudoexfoliative glaucoma

We investigated the intraocular pressure (IOP) lowering efficacy of preservative-free fixed and non-fixed combination of tafluprost 0.0015% and timolol 0.5% in pseudoexfoliative glaucoma (XFG). A per protocol worse eye analysis was made on all XFG patients who participated in a recent 6 month, prospective, randomized, double-masked, parallel group, multicenter phase III study. The mean time-wise IOP decreased by 8.62 to 10.25?mmHg (31.8 to 36.7%) in the fixed dose combination arm (15 patients) and by 5.38 to 11.35?mmHg (21.3 to 41.2%) in the non-fixed combination arm (13 patients), respectively (p?相似文献   

超声乳化白内障吸除后房型人工晶状体植入术对闭角型青光眼合并白内障患者眼压和视力的影响

目的 研究超声乳化白内障吸除之后实施房型人工晶状体植入手术,对于闭角型青光眼并发白内障患者眼压以及视力的影响.方法 选取2014年7月至2016年12月本院共有46例(86眼)门诊闭角型青光眼合并白内障患者入选本研究.以数字法随机分为观察组(42眼)和对照组(44眼).观察组患者使用超声乳化白内障吸除之后实施房型人工晶状体植入手术治疗,对照组根据超声乳化白内障吸除联合人工晶状体植入术式以及小梁切除手术实施治疗,对比两种治疗方式对于患者眼压以及视力的相关影响.结果 观察组疗效为优者占78.57％(33/42)、优良率为90.48％(38/42),均显著高于对照组的52.27％(23/44)、70.45％(31/44),两组比较差异均有统计学意义(均P＜0.05).两组患者经过治疗之后,眼压以及视力得到明显调节,但是观察组改善程度明显大于对照组(P＜0.05).结论 超声乳化白内障吸除之后实施房型人工晶状体植人手术,对于闭角型青光眼合并白内障患者治疗,能够有效缓解患者的眼压,恢复患者的视力,安全性能较高.     

低中心静脉压麻醉联合选择性肝左、右动脉阻断对肝叶切除术出血的影响

目的观察低中心静脉压麻醉联合选择性肝左、右动脉阻断对肝叶切除术出血的影响。方法24例择期肝叶切除患者,随机分为2组：低中心静脉压联合选择性肝左、右动脉阻断组（S组）和低中心静脉压组（LCVP组）,每组12例。2组在肝实质完全离断过程中控制中心静脉压（CVP）在0～5cmH2O。比较2组患者手术总出血量、肝动脉阻断时间、围术期输血例数、术后24h肾功能的变化。结果S组手术总出血量、围术期输血例数明显少于LCVP组（P〈0.05）;2组肝动脉阻断时间、术后24h肾功能无明显影响（P〉0.05）。结论低中心静脉压麻醉联合选择性肝左、右动脉阻断较单纯低中心静脉压可减少肝叶切除术出血和输血,对肾功能无明显影响。     

氩激光周边虹膜成形术治疗急性闭角型青光眼急性发作期临床疗效观察

目的 分析氩激光周边虹膜成形术治疗急性闭角型青光眼急性发作期的临床效果.方法 88例急性闭角型青光眼急性发作期患者,按照奇偶法分为对照组和观察组,每组44例(44只眼).对照组患者接受常规药物治疗,观察组患者接受氩激光周边虹膜成形术治疗.比较两组患者治疗前后患眼和对侧眼角膜内皮细胞数量变化情况及视力、眼压变化情况.结果...     

A long-lasting hypotensive effect of topical diltiazem on the intraocular pressure in conscious rabbits

The effect of calcium channel blockers on intraocular pressure and aqueous humor dynamics remains still controversial, although preliminary evidence suggests that these drugs may be beneficial in the management of ocular hypertension and low-tension glaucoma. Having previously reported the ocular hypotensive effect of topical nifedipine and verapamil in albino rabbits, the original aim of the present work was to evaluate the effect of topical diltiazem on aqueous humor dynamics in this species. Intraocular pressure was measured with a manual applanation tonometer. The experiments examining the ocular actions of diltiazem were carried out in two stages. In the first one, short term effects of topical diltiazem on intraocular pressure were studied in groups of 13 albino rabbits receiving 8 different doses of the drug in order to obtain a dose-response curve. Tonographies were performed in 13 anaesthetized animals before and 90min after drug instillation. In a second phase, the persistence of the effect of diltiazem on intraocular pressure was examined in 6 groups of 10 rabbits each receiving three different doses of the drug. Topical diltiazem was found to lower intraocular pressure in a dose-related fashion. The maximum response to diltiazem was greater and the ED₅₀ lower than those previously reported for nifedipine and verapamil. In the tonographic study, diltiazem was shown to reduce the facility of aqueous humor outflow and inflow. Diltiazem exhibited a long lasting effect on intraocular pressure that was again dose-related. Depending on the dose administered, the calculated time necessary for the peak effect to be halved ranged from 0.6 to 7.0 days. Due to the intensity and the persistence of its intraocular pressure-lowering effect, diltiazem shows great potential for the treatment of glaucoma, since a daily or less frequent administration may be enough to control ocular hypertension. Received: 23 October 1996 / Accepted: 5 February 1997     

不同测量工具下FS-LASIK手术前后眼压测量值一致性及测量变化值影响因素分析

目的 对比分析Goldmann眼压计（GAT）和非接触眼压计（NCT）在FS-LASIK手术前后眼压测量值一致性及其变化。方法 选取2016年12月至2017年9月于安徽医科大学第一附属医院行FS-LASIK手术的近视患者154例（303只眼）,采用横断面研究,对比评估手术前后GAT测量值（IOP-GAT）和NCT测量值（IOP-NCT）的变化及一致性,分析该眼压测量变化值与年龄、术前等效球镜绝对值（|SE_pre|）、术前眼压测量值（IOP-GAT_pre、IOP-NCT_pre）、术前中央角膜厚度（CCT_pre）、切削深度（AD）、切削比（AR）及术前曲率半径（R_pre）的相关性,并给出逐步回归公式。结果 154患者的IOP-GAT_pre平均为（15.60±2.39）mmHg、IOP-NCT_pre的平均为（15.49±2.58）mmHg,两者差异无统计学意义（P=0.192）,而Bland-Altman分析IOP-GAT_pre与IOP-NCT_pre平均值差值为0.11 mmHg,其95%一致性界值为（-2.83,3.06）mmHg。术后IOP-GAT、IOP-NCT均较术前下降,差异有统计学意义（P<0.05）,IOP-NCT下降程度更大。手术前后GAT测量变化值（ΔIOP-GAT）与|SE_pre|、IOP-GAT_pre、CCT_pre、AD、AR呈正相关（P<0.05）,与年龄、R_pre无明显相关（P>0.05）。回归方程为：ΔIOP-GAT=0.635×IOP-GAT_pre+15.633×AR-8.554（R²=0.504,F=204.163,P<0.05）;NCT测量变化值（ΔIOP-NCT）与年龄、|SE_pre|、IOP-NCT_pre、CCT_pre、AD、AR呈正相关（P<0.05）,与R_pre无明显相关,回归方程：ΔIOP-NCT=0.603×IOP-NCT_pre+20.493×AR-5.994（R²=0.653,F=274.921,P<0.05）。结论 FS-LASIK手术前后IOP-GAT、IOP-NCT均不具有较好一致性,术后两者均明显下降,IOP-NCT下降程度更大,两者下降程度与多种因素相关,但均与术前眼压测量值的相关性最高。     

超声乳化联合小梁切除术在慢性闭角型青光眼眼压控制的效果

目的探讨白内障超声乳化摘除联合小梁切除术对慢性闭角型青光眼眼压的控制效果。方法慢性闭角型青光眼伴有白内障患者54例(54只眼),随机分为两组:A组,28例,行超声乳化白内障摘除联合小梁切除术;B组,26例,行单纯超声乳化白内障摘除术。观察两组术前、术后1、3、6、9、12、15、18、21和24个月的眼内压、使用降眼压药物的种数以及术后并发症。结果与B组比较,A组术后的眼压控制效果好,使用降眼压药物的种数少。结论超声乳化联合小梁切除术能够更有效地控制慢性闭角型青光眼眼压。     

普拉洛芬和氟甲松龙滴眼剂治疗激光虹膜切开术经济学分析

目的比较普拉洛芬滴眼剂和氟甲松龙滴眼剂治疗激光虹膜切开术后炎症反应的成本效果。方法将80例（80眼）行激光虹膜切开术后的患者随机分为试验组和对照组,试验组40例（40眼）,选用0.1%普拉洛芬滴眼剂点眼,对照组40例（40眼）,选用0.1%0.1%氟甲松龙滴眼剂点眼,观察疗效并进行药物经济学成本-效果分析。结果效率分别为95%和97.5%。成本分别为51.4元和23.2元,成本效果比分别为0.541和0.238。结论 0.1%氟甲松龙滴眼液滴眼剂治疗激光虹膜切开术后炎症反应比0.1%普拉洛芬滴眼剂更经济。     

羧甲基纤维素钠滴眼液治疗2型糖尿病合并白内障术后干眼症的有效性及安全性

目的 分析羧甲基纤维素钠滴眼液治疗2型糖尿病合并白内障术后干眼症的有效性及安全性.方法 150例2型糖尿病合并白内障患者,根据治疗方法不同分为对照组和观察组,每组75例.对照组予以胰岛素+妥布霉素地塞米松滴眼液治疗,观察组在对照组治疗基础上+羧甲基纤维素钠滴眼液治疗.比较两组患者治疗效果、不良反应发生情况以及治疗前后的...     

人工泪液治疗青光眼白内障联合术后干眼症的临床效果

目的 探讨人工泪液治疗青光眼合并白内障术后干眼症的临床效果.方法 80例青光眼合并白内障手术后干眼症的患者,采用随机数字表法分为观察组与对照组,对照组40例患者给予常规治疗,观察组40例在常规治疗基础上给予人工泪液治疗.对比两组治疗前后泪膜破裂时间(BUT)、基础泪液分泌(SIT)水平及干眼症状评分.结果 观察组治疗后SIT为(13.12-±2.74)mm·(5 min)-1,BUT为(9.83±1.91)s,治疗后2周、4周的干眼症评分分别为(1.43±0.80)分、(0.86±0.51)分;对照组治疗后的SIT为(9.63±1.90)mm·(5 min)-1,BUT为(7.61 ±1.62)s,治疗后2周、4周的干眼症评分分别为(2.92±1.21)分、(1.64±0.82)分;治疗后观察组BUT、SIT水平均优于对照组,差异有统计学意义(P＜0.05);治疗后第2周与第4周,观察组干眼症状评分明显低于对照组,差异有统计学意义(P＜0.05).结论 人工泪液治疗青光眼白内障联合手术后干眼症的临床效果十分显著,可在临床治疗中推广使用.     

The effect of deacetylated gellan gum on aesculin distribution in the posterior segment of the eye after topical administration

The aim of the present work was to evaluate the effect of deacetylated gellan gum on delivering hydrophilic drug to the posterior segment of the eye. An aesculin-containing in situ gel based on deacetylated gellan gum (AG) was prepared and characterized. In vitro corneal permeation across isolated rabbit cornea of aesculin between AG and aesculin solution (AS) was compared. The results showed that deacetylated gellan gum promotes corneal penetration of aesculin. Pharmacokinetics and ocular tissue distribution of aesculin after topical administration in rabbit eye showed that AG greatly improved aesculin accumulation in posterior segmentsrelative to AS, which was probably attributed to conjunctivital/sclera pathway. The area-under-the-curve (AUC) for AG in aqueous humor, choroid-retina, sclera and iris-ciliary body were significantly larger than those of AS. AG can be used as a potential carrier for broading the application of aesculin.     

Cardiovascular effects of selective agonists and antagonists of histamine H3 receptors in the anaesthetized rat

The cardiovascular responses to a series of selective histamine H₃ receptor agonists, (R) -methylhistamine, imetit and immepip and selective antagonists, thioperamide, clobenpropit and clophenpropit, were studied in anaesthetized rats. At 0.003–1 mol/kg i.v. doses, H₃ agonists failed to produce any significant change in the basal blood pressure and heart rate. Larger doses of (R) -methylhistamine increased the blood pressure and heart rate and higher doses of imetit caused vasodepressor responses and reduced heart rate, whereas immepip proved virtually inactive. While (R) -methylhistamine-induced effects were not blocked by histamine H₁-, H₂- and H₃-receptor antagonists, they were however reduced by idazoxan and propranolol, which indicates that the mechanisms involved are adrenergic. The effects induced by imetit are not related to histamine H₃ receptors but are mediated by indirect (via 5HT₃ receptors) cholinergic mechanisms, since these effects were prevented by 1 mg/kg i.v. atropine and by 0.1 mg/kg i.v. ondansetron. Similarly, the H₃ antagonists per se failed to change basal cardiovascular function up to 10 mol/kg i.v. and only at 30 mol/kg i.v. were marked decreases observed in the blood pressure and heart rate with a significant reduction in the effects of noradrenaline. These data indicate that in anaesthetized rats, histamine H₃ receptor activation or blockade has no effect on basal cardiovascular function. The effects recorded after the administration of large doses of (R) -methylhistamine and imetit are clearly unrelated to histamine H₃ receptors and should be taken into account when using these compounds as H₃ ligands for in vivo experiments.     

聚明胶肽预扩减少腰硬联合麻醉后低血压的观察

目的:探讨聚明胶肽(菲可雪浓)预扩减少腰硬联合麻醉后低血压发生的临床效果。方法:120例均采用腰硬联合阻滞麻醉的下肢择期骨科手术,随机平均分3组。Ⅰ组麻醉前30分钟用聚明胶肽500ml预扩,Ⅱ组以复方氯化钠代替聚明胶肽同法预扩,Ⅲ组未预扩。观察记录各组麻醉前Bp和麻醉用药后5、15、30分钟各时点的Bp及麻醉后30分钟内低血压发生例数,并计算出低血压发生率。结果:Ⅰ级麻醉后各时点的Bp与麻醉前差异无显著性,低血压发生率(10%)最低,与另两组(32.5%、55%)比较差异有非常显著性(P<0.01)。结论:聚明胶肽预扩可有效减少腰硬联合麻醉后低血压的发生。     

The effect of prostaglandin synthesis inhibition of the acute blood pressure reduction by captopril in pentobarbital-anaesthetized rats

Treatment of pentobarbital-anaesthetized rats with captopril (SQ 14225) caused a reduction in mean arterial blood pressure (MAP), which lasted for over 1 h when a dose of 5 mg/kg i.p. was used. Pretreatment with the prostaglandin synthesis inhibitors indometacin (IND, 5 mg/kg i.p.) or acetylsalicylic acid (ASA, 100 mg/kg i.p.) did not prevent the initial decrease in MAP after captopril. However, the recovery of the MAP was much faster than after captopril alone. In rats pretreated with IND, the MAP after captopril was significantly higher than after captopril alone from 30 min onwards. With ASA pretreatment the same was observed after 45 min. These data indicate that the subacute blood pressure lowering effect of captopril in pentobarbital-anaesthetized normotensive rats may be at least partly dependent on the presence of an intact prostaglandin biosynthetic pathway. This may be due to activation of prostaglandin synthesis by the accumulation of bradykinin and angiotensin I after captopril.     

The effects of the 5 HT2 antagonist ritanserin on blood pressure and serotonin-induced platelet aggregation in patients with untreated essential hypertension

Summary We have given the selective 5 HT₂ antagonist ritanserin in a dose of 10 mg twice daily for 4 weeks in a double-blind, randomized, placebocontrolled, parallel group study of 18 patients with untreated essential hypertension.The fall in single platelet count due to 5 HT-induced platelet aggregation was significantly reduced by ritanserin compared with placebo (p<0.05).There were no significant changes in supine or erect blood pressure or heart rate after ritanserin compared to placebo. Forearm blood flow, measured by mercury-in-strain gauge venous occlusion plethysmography, was not significantly altered by ritanserin.Ritanserin caused prolongation of the QT_c interval by 41 (SEM 11) ms (p<0.05 compared to placebo) but had no detectable effect on QRS duration, features suggestive of Class III antiarrhythmic activity.These findings do not support an independent role of the 5 HT₂ receptor in maintaining raised arterial pressure in essential hypertension.