Preservative-free versus preserved latanoprost eye drops in patients with open-angle glaucoma or ocular hypertension

Objective: This study compared the efficacy, safety, and pharmacokinetics of a preservative-free latanoprost formulation to an established, benzalkonium chloride (BAK) containing formulation for the treatment of open-angle glaucoma or ocular hypertension.

Methods: This was a phase II, randomized, cross-over, investigator-masked, multi-center, pilot study (NCT01494753). A total of 30 untreated adult patients (aged ≥18 years) with primary open angle glaucoma, pseudo-exfoliative glaucoma, pigmentary glaucoma, or ocular hypertension received either preservative-free or preserved latanoprost once daily in both eyes for 6 weeks, before crossing over to receive the other treatment. Efficacy (intraocular pressure [IOP] at 8 am, midday, 4?pm and 8?pm, and global efficacy assessment by investigator), safety (adverse events, ocular symptoms and global tolerance, slit lamp examination, funduscopy, visual field examination, visual acuity, and heart rate), and pharmacokinetics were assessed at Days 0, 42, and 84.

Results: Both treatments resulted in a reduction in IOP that was similar for the preservative-free and the preserved formulation at all time points. Similarly, the overall diurnal reduction was similar in both groups (6.3?mmHg [27.9% reduction] and 6.4?mmHg [28.1% reduction] for preserved and preservative-free latanoprost, respectively). There were no differences in global efficacy assessment or in the safety and tolerance of each treatment. Systemic concentrations of latanoprost were very low; AUC_0–30 and C_max were lower and t_max was longer for preservative-free latanoprost.

Conclusions: Preservative-free latanoprost showed similar efficacy at all time points compared to BAK preservative containing formulation, with no difference in tolerance, allowing progression to phase III clinical development.     

他氟前列素治疗开角型青光眼和高眼压症的有效性及安全性评价

目的:综述他氟前列素滴眼液降低开角型青光眼和高眼压症患者眼内压的有效性及安全性评价。方法:使用"他氟前列素"、"开角型青光眼"、"高眼压症"、"有效性"、"安全性"作为检索词在PubMed数据库和中文数据库维普全文、电子期刊等对已发表的文献进行检索,检索2004年至2015年英文文献共52篇及中文文献多篇,包括多中心临床研究及药品信息资料,并对检索结果进行归纳性分析。结果:现有的研究已显示,他氟前列素是一种有效降低眼内压的药物。循证医学也发现他氟前列素安全有效,患者依从性良好。不含防腐剂他氟前列素的降眼压效果与含防腐剂的相同。结论:研究提示,他氟前列素每日1次滴眼可安全有效地降低开角型青光眼及高眼压症患者的眼内压。     

科比根治疗开角型青光眼和高眼压症的疗效及安全性

目的：研究科比根治疗开角型青光眼和高眼压症的疗效及安全性。方法采用对照研究手段,将符合条件的患者随机分组进行科比根?（溴莫尼定和噻吗洛尔固定复合滴眼液）和非固定联合制剂治疗（0．2％酒石酸溴莫尼定滴眼液及0．5％噻吗洛尔滴眼液）比较。结果在5周的对比治疗后,分析疗效、治疗安全性,科比根?治疗效果与非固定联合制剂治疗效果接近,未出现新的与治疗有关不良事件,未观察到其他治疗安全性的明显差异。结论科比根治疗开角型青光眼和高眼压症的方法与非固定联合制剂的疗效和安全性相似。     

Brinzolamide/timolol fixed combination: a new ocular suspension for the treatment of open-angle glaucoma and ocular hypertension

For the treatment of open-angle glaucoma, the most frequent cause of irreversible visual loss, fixed combinations of different topical intraocular pressure (IOP) lowering molecules have gained an important role in recent years. The use of fixed combinations reduces the number of daily instillations, which promotes adherence to the prescribed medication and diminishes the exposition of the ocular surface to preservatives. The fixed combination of brinzolamide and timolol was recently approved by the European Medicines Agency (EMEA) and is now available in several countries in Europe. It contains two molecules widely used to treat glaucoma: timolol 0.5% (5 mg/ml) and brinzolamide 1% (10 mg/ml) in ophthalmic suspension formulation. This fixed combination is approved for twice-daily instillation to reduce elevated IOP in open-angle glaucoma and ocular hypertension. The brinzolamide/timolol fixed combination provides an approximately 30 – 33% IOP reduction from the untreated baseline IOP of 25 – 27 mmHg; thus, it is more potent than either of its ingredients alone. It is similarly effective but better tolerated than the dorzolamide/timolol fixed combination, which consists of molecules from the same pharmacological classes. The brinzolamide/timolol fixed combination can be used by itself as a separate therapy, but owing to the additivity of its ingredients to IOP-lowering drugs belonging to other classes, it may also be administered adjunctive to other IOP-reducing molecules, most importantly topical prostaglandin analogues. The ocular and systemic tolerance of the brinzolamide/ timolol fixed combination was reported favorable in Phase III studies, but no long-term clinical experience with this preparation is available at present.     

0.15%阿法根P治疗开角型青光眼或高眼压症患者临床应用观察

目的 分析比较0.15%阿法根P(0.15%酒石酸溴莫尼定滴眼液)和阿法根(0.2%酒石酸溴莫尼定滴眼液)治疗开角型青光眼或高眼压症患者的应用临床效果.方法 随机分组,观察组32例患者(0.15%阿法根P,Bid)和对照组35例(阿法根,bid),随访1年.结果 0.15%阿法根P的降眼压疗效与阿法根相同,而0.15%阿法根P的安全性和耐受性优于阿法根.结论 0.15%阿法根P在临床中应用安全有效,优于阿法根.     

Efficacy and safety of tafluprost 0.0015% and timolol maleate 0.5% fixed combination in patients with ocular hypertension or open-angle glaucoma

Introduction: Lowering intraocular pressure (IOP) is at present the only therapeutic approach to the treatment of glaucoma proven to be successful. The choice of therapy must take into account efficacy, tolerability, safety, quality of life, adherence and cost. Monotherapy fails to achieve a satisfactory IOP reduction in 40 – 75% of glaucoma patients after > 2 years of therapy. So far, three prostaglandin/timolol maleate 0.5% fixed combinations (FCs) are available.

Areas covered: This review provides a background on the tafluprost–timolol FC (TTFC, Santen Oy) and its individual compounds. It summarizes the data on efficacy and safety, including comparative data with prostaglandin/timolol FCs already available.

Expert opinion: Tafluprost is a preservative-free prostaglandin analog with a similar IOP efficacy when compared with other prostaglandin analogs. However, its improved adverse effect profile seems to be beneficial in patients sensitive to preservatives. The preservative-free TTFC has no market authorization yet. Only one Phase III trial was published so far, but results are promising in terms of efficacy, tolerability and safety. It is likely that the TTFC will play a role in the treatment of open-angle glaucoma and ocular hypertension.     

An evaluation of the fixed-combination of latanoprost and timolol for use in open-angle glaucoma and ocular hypertension

Glaucoma is one of the leading causes of irreversible blindness worldwide. Although there is no cure for this chronic disease, medical treatment is aimed at reducing levels of intraocular pressure (IOP) using ocular hypotensive agents. Very often, patients require more than one IOP-reducing drug, resulting in complex medication regimens that may be difficult to maintain and that can lead to non-compliance. A fixed-combination (FC) ophthalmic solution consisting of the prostaglandin, latanoprost (0.005%), and the β-blocker, timolol (0.5%), is now available. The primary mechanism of action of latanoprost is to increase uveoscleral outflow whereas timolol lowers IOP levels by decreasing the formation of aqueous humor in the ciliary epithelium. Due to the unique mechanism of action of latanoprost, once-daily dosing of one drop of FC latanoprost/timolol results in additional IOP reduction compared with either drug administered separately. FC latanoprost/timolol is well-tolerated and has a safety profile similar to that of its individual components. This combination drug provides a safe, effective and convenient alternative for the treatment of patients with elevated IOP levels uncontrolled with monotherapy.     

Brinzolamide plus brimonidine for the treatment of glaucoma: an update

Introduction: Glaucoma is a common sight-threatening condition that is primarily treated by lowering intraocular pressure (IOP). Today the mainstay of treatment is topical ocular hypotensive medications; many patients require more than one agent to achieve target IOP. For such patients, fixed combination formulations have several advantages including simplicity of treatment regimen, adherence to the treatment regimen, efficacy, improved ocular surface comfort and reduced cost. All currently available fixed combinations contain a β-blocker, which is contraindicated in some patients. Hence there is a clinical need for fixed-combination preparations without a β-blocker. This paper reviews the current literature on a new fixed-combination drug containing brinzolamide 1% and brimonidine 0.2% (BBFC).

Areas covered: A PubMed, Embase and ClinicalTrials.gov registry search was performed to identify all relevant studies. Four published clinical papers pertaining to three randomized controlled trials were identified for review. All studies demonstrated a significant reduction (p < 0.01) in mean IOP in patients administered with BBFC compared with its individual components, brinzolamide 1% or brimonidine 0.2%. Adverse effects from BBFC were no different from each of the individual components, the most common being blurred vision, eye irritation and dysgeusia (abnormal taste sensation). Although BBFC use was associated with more adverse effects compared with the individual components used as monotherapy (p < 0.001), the cumulative adverse effect profile from BBFC did not appear greater than one would expect from the simultaneous use of the two components.

Expert opinion: BBFC is a potential alternative to other fixed-combination medications and is especially useful when topical β-blockers are contraindicated. Longer-term experience will determine if additional adverse effects occur or if efficacy is maintained over longer periods.     

Brimonidine-purite 0.1% versus brimonidine-purite 0.15% twice daily in glaucoma or ocular hypertension: a 12-month randomized trial*

ABSTRACT

Objective: To compare the safety and intraocular pressure (IOP)-lowering effects of brimonidine-purite^? 0.1% with the marketed formulation of brimonidine-purite 0.15% (Alphagan P^§ 0.15%) when used twice daily (BID) by patients with glaucoma or ocular hypertension previously treated with brimonidine-purite 0.15% for at least 6 weeks.

Methods: In a 12-month, randomized, double-masked, multicenter, parallel group, non-inferiority study, patients with glaucoma or ocular hypertension who were treated with brimonidine-purite 0.15% BID were randomly assigned to continue brimonidine-purite 0.15% (n = 102) or to administer brimonidine-purite 0.1% (n = 105) BID for 12 months. IOP was measured at approximately 8 a.m. (hour 0) and 10 a.m. (hour 2).

Main outcome measures: Mean change from baseline IOP and adverse events.

Results: Demographics and baseline characteristics were similar between treatment groups. Treated-baseline mean IOPs at both timepoints were similar between groups (p ≥ 0.606). Brimonidine-purite 0.1% provided IOP-lowering that was non-inferior to brimonidine-purite 0.15% at each of the 12 follow-up timepoints, and there were no statistically significant between-group differences at any timepoint. The most commonly reported adverse event was conjunctival hyperemia (13.5% for brimonidine-purite 0.1%; 10.8% for brimonidine-purite 0.15%). No significant differences in the incidence of adverse events were noted between the two formulations.

Conclusions: Brimonidine-purite 0.1% BID is as effective as brimonidine-purite 0.15% BID in lowering IOP in patients with glaucoma or ocular hypertension who were previously treated with brimonidine-purite 0.15%, and both formulations are well tolerated. Limitations of the study include enrollment of only patients who were already on treatment with brimonidine-purite 0.15%. The 0.1% formulation of brimonidine-purite allows for decreased exposure to brimonidine while providing an IOP-lowering effect comparable to that of the 0.15% formulation. Clinical trial registered at clinicaltrials.gov; identifier: NCT00168363.     

Preservative-free tafluprost/timolol fixed combination: a new opportunity in the treatment of glaucoma

Introduction: Medical therapy of glaucoma aims to maintain the patient’s visual function and quality of life. This generally commences with monotherapy, but it is often difficult to reach the predetermined target pressure with this approach. Fixed combinations (FCs) are therefore selected as the next step of the medical therapy algorithm. By employing a prostaglandin/timolol fixed combination (PTFC) the desired target 24-hour intraocular pressure can be reached in many glaucoma patients with the convenience of once-a-day administration and the associated high rate of adherence.

Areas covered: The current role and value of FCs in the medical therapy of glaucoma is critically appraised. Special attention is paid to the PTFCs and the emerging role of preservative-free PTFCs. This review summarizes existing information on the efficacy and tolerability of the new preservative-free tafluprost/timolol FC (Taptiqom®).

Expert opinion: The preservative-free tafluprost/timolol FC represents a promising stepwise treatment option for those patients whose intraocular pressure is insufficiently controlled with available monotherapy options. This novel FC has the potential to substantially improve glaucoma management and through evolution of the current glaucoma treatment paradigm, to become a core therapeutic option in the future. Nonetheless, future research is needed to better delineate the therapeutic role of current and future preservative-free FCs in glaucoma therapy.     

Efficacy and safety of brimonidine and dorzolamide for intraocular pressure lowering in glaucoma and ocular hypertension

ABSTRACT

Background: Brimonidine and dorzolamide are intraocular pressure (IOP)-lowering medications most commonly used in second-line treatment of glaucoma and ocular hypertension.

Scope: An evidence-based review of comparative clinical trials of brimonidine and dorzolamide was undertaken to determine the relative efficacy and safety of these drugs in reducing IOP. Using the keywords ‘brimonidine’ and ‘dorzolamide’, all articles describing such trials from September 1966 to July 2007 were found in MEDLINE and EMBASE.

Findings: In all identified studies, brimonidine and dorzolamide were both found to provide significant IOP reduction from treated or untreated baseline levels. Results of eight trials reported to date indicate that brimonidine produced either a lower treated IOP or greater pressure reduction from baseline than dorzolamide at one or more measured timepoints, and provided comparable IOP lowering over all other measurements. Differences between the IOP reductions provided by brimonidine and dorzolamide were more pronounced when the medications were used adjunctively with other classes of drugs. Six other trials showed similar efficacy, and one additional monotherapy study showed lower IOP with dorzolamide treatment. Ocular burning was noted with dorzolamide more than any other adverse event with either drug. Trials ranged widely in duration of therapy and the time of day IOP measurements were taken, and many were too small for sufficient statistical power.

Conclusion: Brimonidine and dorzolamide are both efficacious and reasonably well tolerated. Possible overall distinctions in efficacy were obscured by differences in study designs and treatment regimens, but adjunctive therapy with brimonidine may reduce IOP as effectively or more effectively than adjunctive or fixed combination dorzolamide therapy. In certain patients with glaucoma and ocular hypertension brimonidine may be a better choice than dorzolamide for second-line treatment.     

Signs and symptoms of ocular surface status in glaucoma patients switched from timolol 0.5% to brinzolamide 1%/timolol 0.5% fixed combination: a 6-month efficacy and tolerability,multicenter, open-label prospective study

Purpose: To examine the impact of switching glaucoma patients from timolol 0.5% to brinzolamide 1%/timolol 0.5% fixed combination (Brinz/Tim FC) on quality of life and on ocular surface status; to assess efficacy after the switch.

Methods: 6-month, multicenter, open-label, prospective, switch study in 119 early to moderate glaucoma patients. Intraocular pressure (IOP), tear film break-up time (TF-BUT), fluorescein staining and Glaucoma Symptom Scale (GSS) questionnaire were recorded at baseline and after 6 months.

Results: Median (interquartile range) IOP significantly decreased from 20 to 16 mmHg, independent of sex and age. Most patients (95.8%) reached an IOP < 18 mmHg. TF-BUT improved, with a negative weak correlation to age at baseline and at 6 months. The percentage of patients with no fluorescein staining improved. The quality of life recorded by GSS also improved, being related both to age and corneal staining.

Conclusion: Brinz/Tim FC is effective and well tolerated. In this study, patients switched to Brinz/Tim FC obtained further reduction in IOP with no effects on ocular surface status and improved quality of life perception: a better quality of life could determine a better adherence to prescribed therapy.     

低浓度丝裂霉素联合羊膜移植治疗原发性青光眼的近期疗效分析

目的探讨羊膜移植联合低浓度丝裂霉素、小梁切除治疗原发性青光眼的效果。方法选择本院2011年6月～2012年12月收治的42例（60眼）原发性青光眼患者,将其随机分为研究组22例（30眼）和对照组20例（30眼）,研究组患者给予小梁切除、羊膜移植联合低浓度丝裂霉素治疗,对照组患者给予小梁切除治疗,观察两组患者治疗后眼压、视力的改变情况,并统计两组患者的并发症情况。结果研究组患者术后视力改善优良率明显高于对照组,组间差异有统计学意义（P〈0．05）;两组术后1、6个月眼压均较治疗前明显降低,差异有统计学意义（P〈0．05）;研究组术后1、6个月时的眼压明显低于对照组（P〈0．05）;研究组复发率及并发症发生率明显低于对照组,差异有统计学意义（P〈0．05）。结论低浓度丝裂霉素、羊膜移植、小梁切除治疗原发性青光眼可有效改善患者视力,眼压控制满意,复发率及并发生症发生率较低,值得推广。     

Evaluating the novel application of cyclosporine 0.1% in ocular surface disease

Introduction: Ocular surface disease (OSD) is a highly prevalent symptomatic condition caused by dry eye disease (DED), intrinsic, environmental, or iatrogenic causes. It affects patient’s visual function and quality of life. Its pathophysiology is centered on tear hyperosmolarity, inflammation, and epithelial damage. Current management is suboptimal and includes artificial tear supplementation and short-term use of topical steroids in severe cases. The recent approval of cyclosporine 0.1% has transformed management strategies of severe DED and moderate-to-severe OSD.

Areas covered: This review summarizes existing information on the efficacy, safety, and tolerability of the new cyclosporine 0.1% formulation.

Expert opinion: Topical cyclosporine A 0.1% represents a promising, novel medication for the management of DED, Meibomian gland dysfunction, and inflammatory OSD. It is primarily beneficial for those patients requiring topical immunomodulatory therapy. This topical formulation also has the potential to meaningfully improve the management of moderate-to-severe glaucoma therapy-related OSD. Currently there is limited published clinical data concerning the efficacy of topical cyclosporine. There are, however, theoretical advantages when comparing this cyclosporine formulation with other established commercial preparations. Future research is needed to delineate the precise role and value of this medication.     

Influence of timolol,benzalkonium-preserved timolol,and benzalkonium-preserved brimonidine on oxidative stress biomarkers in the tear film

Abstract

Purpose

The objective of this study was to investigate the influence of topical preservative-free timolol, benzalkonium chloride(BAC)-preserved timolol, BAC-preserved timolol, and BAC-preserved brimonidine on total protein concentration, advanced oxidation protein products (AOPP) content, total sulfhydryl groups content, the activity of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), as well as Total Oxidant Status (TOS), Total Antioxidant Response, and Oxidative Stress Index (OSI) in the tear film.     

Efficacy,safety, and current applications of brimonidine

Background: The use of brimonidine to lower intraocular pressure has been the subject of considerable investigation. Variations of the initially approved drug including agents of a lower concentration (Alphagan^® P 0.15 and 0.1%, Allergan, Inc., Irvine, CA, USA) and a fixed-combination mating brimonidine with timolol (Combigan^®, Allergan) evolved the marketing and application of this therapy. Objective: We review available evidence regarding the efficacy and side effect profile of brimonidine as well as its role in glaucoma management. Results/conclusion: Brimonidine is an important component of topical glaucoma treatment that is most limited by local ocular intolerance.     

原发性闭角型青光眼虹膜周切孔切除宽度与术后近、远期疗效相关性研究

目的探讨原发性闭角型青光眼虹膜周切孔切除宽度与术后近期、远期疗效关系,筛选出术后近、远期疗效的预测方法,提高虹膜周边切除术的成功率。方法90例（116眼）原发性闭角型青光眼随机分为三组：A组（虹膜周切孔切除宽度1．5mm）,30例42眼;B组（虹膜周切孔切除宽度2mm）30例40眼;C组（虹膜周切孔切除宽度3mm）30例34眼,术后随诊1月以上,观察眼压、房角宽度深度、视功能、虹膜周切孔以及近、远期并发症。结果A组：近期手术成功率为85．79％,远期手术成功率为76．19％;B组近期手术成功率87．5％,远期手术成功率82．5％;C组近期手术成功率94．11％,远期手术成功率88．23％,x2检验其差异有显著性（P〈0．05）;三组术后眼压均有不同程度下降与术前比较差异均有显著性（P〈0．01）;周边房角深度术后随机均值：A组≥1／3CT,术前术后比较其差异有显著性（P〈0．01）;B组和C组〉1／2CT,两组术前术后比较其差异有极显著性（P〈0．05）。结论虹膜周边切除术是治疗原发性闭角型青光眼安全有效方法,虹膜周切孔宽度以2—3mm为宜,有利于防治虹膜周切孔前粘连和房角变浅变窄。     

Ocular hypotensive efficacy and safety of brinzolamide ophthalmic suspension 1% added to travoprost ophthalmic solution 0.004% therapy in patients with open-angle glaucoma or ocular hypertension

OBJECTIVE: The primary objective of this study was to determine if combined travoprost ophthalmic solution 0.004% and brinzolamide ophthalmic suspension 1% therapy is superior in lowering intraocular pressure (IOP) compared to travoprost monotherapy for patients with open angle glaucoma or ocular hypertension. The secondary objective was to measure the percentage of patients achieving IOP levels of 18 mmHg or less. STUDY DESIGN AND METHODS: Single arm, open-label. PARTICIPANTS: eighty-two patients with inadequate IOP control with travoprost monotherapy. INTERVENTION: the addition of brinzolamide ophthalmic suspension 1% twice daily. MAIN OUTCOME MEASURES: The primary endpoint was mean IOP reduction from baseline at 4 and 12 weeks. The percentage of patients who achieved IOP values 相似文献   

改良小梁切除术联合丝裂霉素在新生血管性青光眼中的临床疗效评价

目的评价改良小梁切除术联合丝裂霉素在新生血管性青光眼的临床疗效。方法选择我院收治的35例（35眼）新生血管性青光眼患者,予以控制眼压、血糖等措施后采取改良小梁切除术联合丝裂霉素进行治疗,术中应用可调节缝线,并针对患者的眼压及滤过泡来决定可调节缝线的拆除时间。并对35例患者术前及术后6个月的眼压、滤过泡、视力、前房深度及新生血管情况进行随访。结果35例患者（35眼）术后当日高眼压的症状及体征均消除。术后6个月,35例患者平均眼压为（15．8±7．2）mmHg,与术前的平均眼压（53.3±9．7）mmHg比较,眼压显著降低（P〈0．01）;功能性滤过泡约占88．6％;29例患者（29眼）视力较术前均存在程度不一的提高。35例患者（35眼）均保持良好的前房深度;虹膜新生血管全部消退约占31．4％,消退在50％以上约占48．6％,消退在50％以下约占20．0％。结论改良小梁切除术联合丝裂霉素治疗新生血管性青光眼,能有效重建房水循环路径,使患者的症状大大减轻,提高了手术的成功率及安全性。     

Efficacy and safety of bimatoprost/timolol fixed combination in the treatment of glaucoma or ocular hypertension

When a single medication does not adequately control intraocular pressure, additional intraocular hypotensive agents are often added to the therapeutic regime. However, regimen complexity has been associated with reduced patient compliance. Treatment with a fixed combination may, therefore, increase compliance as a result of simplifying the dosage regimen. Bimatoprost/timolol fixed combination (BTFC) combines two clinically effective agents that decrease elevated intraocular pressure by independent mechanisms. In two clinical studies, BTFC was more effective than its individual components. Furthermore, in a non-inferiority study BTFC has been shown to be as effective as the association of its individual components. BTFC was clinically effective and generally well tolerated, with no unexpected adverse reactions reported for the BTFC compared with those reported for bimatoprost or timolol monotherapies.