比马前列素滴眼液的药理和临床应用

比马前列素是合成的前列酰胺F2α衍生物，通过增加小梁网通道和葡萄膜巩膜通道的房水流出而降低眼内压（IOP），被认为是目前降眼压作用最强的局部抗青光眼药物。主要用于开角型青光眼（POAG）或高眼压症（OHT）的患者，全身不良反应较少。现主要综述该药的药理作用、药动学及临床应用。     

Bimatoprost – a review

Bimatoprost is a synthetic prostamide analog that is efficacious in the treatment of open-angle glaucoma, ocular hypertension and other forms of glaucoma. It reduces intraocular pressure (IOP) by increasing uveoscleral and trabecular outflow. When used as a 0.03% topical preparation once daily, it demonstrates sustained lowering of IOP of 7 – 8 mmHg over a 24-h period. The drug has been found to be more effective than timolol. In some studies it has shown greater ability to lower IOP when compared with other prostaglandin analogs; whereas in others all three clinically used prostaglandin analogs were found to be equally effective. It shows good IOP reduction when used in combination with other glaucoma medications. A common side effect includes mild conjunctival hyperemia, which is generally reversible. Other side effects include periorbital pigmentation, discomfort, ocular surface hyperemia and skin changes. Pharmacoeconomic data indicate that bimatoprost is cost effective in the treatment of open-angle glaucoma.     

Bimatoprost: a member of a new class of agents,the prostamides,for glaucoma management

Bimatoprost, a synthetic analogue of endogenous prostamides, is in development as a topical ocular hypotensive agent for the treatment of glaucoma and ocular hypertension. Prostamides are a newly discovered class of compounds that have been shown to have potent ocular hypotensive activity in the laboratory. Bimatoprost mimics the endogenous prostamides by lowering intraocular pressure (IOP). Bimatoprost provides outstanding control of IOP throughout the day, and a high percentage of patients receiving bimatoprost achieve the low target pressures important for clinical success. In controlled clinical trials, bimatoprost 0.03% given once daily has displayed efficacy superior to timolol 0.5% given twice daily, the current standard for therapy. Analysis of pooled six month data from two large Phase III trials demonstrated that mean IOP was consistently 2 - 3 mmHg lower with bimatoprost q.d. than with timolol b.i.d. Bimatoprost 0.03% q.d. has also been shown to provide significantly better diurnal IOP control than latanoprost 0.005% q.d., probably the most efficacious topical medication currently available. Patients receiving bimatoprost q.d. were more likely than timolol or latanoprost patients to achieve low target pressures. In all clinical evaluations, bimatoprost q.d. has been demonstrated to be safe and well-tolerated. Bimatoprost will likely be available for clinical use in 2001 and it has great potential to be superior to all other medications in IOP-lowering efficacy. It is anticipated that bimatoprost will have an important role in therapy for glaucoma and ocular hypertension.     

An update on bimatoprost in glaucoma therapy

Bimatoprost, a prostamide, effectively lowers intraocular pressure (IOP) in patients with open-angle glaucoma and ocular hypertension. In clinical trials, bimatoprost has demonstrated superiority to the beta-adrenergic antagonist timolol and has consistently provided approximately 1-2 mmHg greater mean IOP lowering than the prostaglandin latanoprost. Bimatoprost is more effective than either timolol or latanoprost in allowing patients to reach the low target pressures that best protect the visual field. Patients on bimatoprost therapy achieve low pressures throughout the day and night. Moreover, 1-year trials have shown that the efficacy of bimatoprost is sustained with long-term use. The most common side effects have been conjunctival hyperaemia, graded as trace or mild, and eyelash growth. No safety concerns have arisen in postmarketing surveillance. Bimatoprost appears to be a valuable new agent for glaucoma therapy.     

Fixed-combination and emerging glaucoma therapies

Ocular hypotensive agents are the only approved pharmacotherapy for glaucoma. Despite significant advances during the past two decades, a large proportion of glaucoma patients require more than one drug. The most recent additions to the armamentarium of antiglaucoma drugs are fixed-combination products for the glaucoma patient who is insufficiently responsive to monotherapy. Fixed-combination products have the combined efficacy of two ocular hypotensive drugs, and the convenience of a two-drug treatment regimen in a single container, which may aid patient adherence to treatment. Available fixed-combination products consist of timolol 0.5% as an invariant with brimonidine 0.2%, dorzolamide 2%, travoprost 0.004%, latanoprost 0.005% or bimatoprost 0.03%. Research on more advanced antiglaucoma medications continues. Promising new directions appear to be the Rho-kinase inhibitors, microtubule-disrupting agents, serotonergics and cannabimimetics. Efforts continue to improve existing antiglaucoma drugs in an attempt to design second-generation cholinomimetics, adrenergics, prostaglandins and prostamides.     

A comparative study on the efficacy, safety, and cost-effectiveness of bimatoprost/timolol and dorzolamide/timolol combinations in glaucoma patients

Aim:

This study was designed to compare the bimatoprost/timolol combination and dorzolamide/timolol combination in glaucoma for efficacy, safety, and cost-effectiveness in a local population of Trichy in the state of Tamilnadu.

Materials and Methods:

Eight-week, randomized, parallel group, open-label study was conducted on 48 patients of open angle glaucoma or ocular hypertension. After initial clinical assessment and baseline investigations, bimatoprost/timolol combination (Group A) was prescribed to 22 patients (2 patients lost after initial assessment) and dorzolamide/timolol combination (Group B) to 24 patients. The patients were reviewed after second and eighth weeks for cure rate and adverse drug reaction monitoring.

Results:

At the end of 8 weeks, the mean reduction in intraocular pressure from baseline was 13.04 mmHg (95% confidence interval (CI): 10.67–14.70) with bimatoprost/timolol combination once daily (P < 0.01) and 9.46 mmHg (95% CI: 7.47–10.5) with dorzolamide/timolol combination twice daily. Both the treatments were safe. Cost-effective range of bimatoprost/timolol combination was lower than that of dorzolamide/timolol combination.

Conclusion:

The fixed combination of bimatoprost/timolol was slightly more effective than that of dorzolamide/timolol combination in reducing IOP, and both treatments were generally well tolerated. Bimatoprost/timolol combination was more cost-effective (cost-effective analysis) than dorzolamide/timolol combination.     

Current and emerging medical therapies for glaucoma

Glaucoma is a multifactorial optic neuropathy in which there is a characteristic acquired loss of retinal ganglion cells, at levels beyond normal age-related baseline loss, and corresponding atrophy of the optic nerve. Although asymptomatic in its earlier stages, the disease is nevertheless one of the leading global causes of irreversible blindness. Although elevated intraocular pressure (IOP) is one of the most important risk factors and lowering of IOP is the only proven treatment so far, the definition of glaucoma has evolved from a disease caused by increased IOP to one characterised by an IOP-sensitive, progressive optic neuropathy. In recent years, safer and better tolerated topical medications have been developed to control IOP more effectively, thereby limiting the need for surgery. New research has also noted the importance of diurnal IOP variation as a critical risk factor for progression of glaucomatous optic neuropathy (GON) and subsequent visual field loss. Moreover, new discoveries have further elucidated the basic pathophysiological and genetic mechanisms underlying the elevated levels of IOP, as well as the cellular mechanisms of GON. As our understanding of these complex pathways continues to improve, development opportunities for new therapeutic modalities will be enhanced.     

持续高眼压状态下手术治疗急性闭角型青光眼33例

目的探讨对降眼压治疗效果不佳的闭角型青光眼在高眼压状态下行手术治疗的疗效。方法回顾性分析笔者所在医院2007年5月～2010年10月治疗的33例33眼应用药物不能控制眼压的急性闭角型青光眼患者,所有患者均行复合式小梁切除术治疗。术后随访6～12个月。结果所有患者手术均顺利完成,术中术后均未出现严重并发症,术后视力获得明显的提高;术后1周所有患者眼压均在8～11mmHg,经6～12个月随访,患者眼压基本控制在14.36～21.58mmHg。结论原发性闭角型青光眼持续高眼压状态下的复合式小梁切除术是安全有效的。手术治疗的术前、术中、术后都应积极处理高眼压,提高手术的成功率,预防和减少术中及术后并发症的发生。     

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.     

青光眼治疗药物的研究进展

青光眼造成的失明通常是不可逆的,眼压升高被认为是青光眼的最重要危险因素。降眼压治疗可以延缓青光眼的发生和进展,是目前临床治疗青光眼的主要策略。视神经保护可能是青光眼治疗的新方向。从传统降眼压药物、新型降眼压药物、视神经保护药物3个方面对青光眼治疗药物进行综述和探讨。     

Endothelin antagonism as an active principle for glaucoma therapy

Endothelin, the most potent vasoactive peptide known to date, has been suggested to play a potential role in the pathogenesis of open-angle glaucoma. Open-angle glaucoma is the most common optic nerve head neuropathy and is associated with a loss of retinal ganglion cells and visual field damage. Although an increased intraocular pressure is a major risk factor for glaucomatous optic neuropathy, other factors such as a reduced ocular blood flow play an important role for appearance of the disease. Thus, treatment of glaucoma is focused on lowering of intraocular pressure and preventing the occurrence or progression of glaucomatous optic neuropathy. Endothelin participates in the regulation of intraocular pressure by an effect on trabecular outflow, the main route for aqueous humour outflow from the eye. Trabecular outflow is modulated by trabecular meshwork contractility which is affected by endothelin. In addition to the effects of endothelin in the anterior part of the eye, the vasoconstrictor causes a decrease in ocular blood flow followed by pathological changes in the retina and the optic nerve head which is assumed to contribute to the degeneration of retinal ganglion cells. In sum, inhibition of endothelin signalling leads to lowering of intraocular pressure and exerts neuroprotective effects. Thus, endothelin antagonism in the eye represents a promising approach for pharmacological treatment of glaucoma.     

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.     

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.     

青光眼药物治疗的新进展

青光眼是一种多元性的视神经和视网膜病变。全世界大约有 70 0万病人因青光眼而失明。眼压升高是青光眼发病过程中的主要危险因素。本文简要地回顾目前常用的药物疗法 ,并介绍正在研发中的新降眼压药的药效和药理机制。     

拉坦前列素滴眼液治疗青光眼

目的 :观察用降眼压药物而眼压不能控制的病人 ,加用拉坦前列素滴眼液治疗的临床疗效。方法 :2 4例病人 (共 2 4只病眼 ) ,男性 10例 ,女性 14例 ,年龄 (5 0±s12 )a ,共 2 4只病眼用 2种以上降眼压药物而眼压不能控制 ,加用 0 .0 0 5 %拉坦前列素滴眼液滴病眼 ,每晚 1次 ,疗程至少 3mo。结果 :用2种降眼压药有 9例 (38% ) ,用 3种以上降眼压药15例 (6 2 % ) ,其中有 8例 (33% )需口服乙酰唑胺片降眼压。 2 4例病人加用 0 .0 0 5 %拉坦前列素滴眼液 1wk ,1mo和 3mo后 ,眼压由 (3.6 4± 0 .18)kPa降至 (2 .19± 0 .11)kPa ,(2 .18± 0 .11)kPa ,(2 .14 0± 0 .0 10 )kPa ,均P <0 .0 1。眼压降至正常 15例 (6 2 % ) ,眼压降低但未至正常 7例 (2 9% ) ,无效为 2例 (8% )。结论 :对用降眼压药物而眼压不能控制的病人 ,加用拉坦前列素滴眼液可以有效的控制眼压 ,防止青光眼对视功能的进一步损伤     

The role of endothelin in the pathophysiology of glaucoma

Importance of the field: Glaucoma is the second leading cause of blindness worldwide. To date, treatment of glaucoma has focused on lowering intraocular pressure (IOP) though there are other mechanisms that might damage the optic nerve, leading to characteristic visual field loss. Endothelin, a potent vasoconstrictor, is believed to play a role in the pathogenesis of glaucomatous optic neuropathy.

Areas covered in this review: We review the evidence from the last 20 years exploring the action of endothelin in the eye, its association with the pathophysiology of glaucoma, as well as the potential therapeutic role of targeting the endothelin pathway to affect disease progression in glaucomatous eyes.

What the reader will gain: The goal of this paper is to inform readers about endothelin structure, actions, and role in ocular pathology, pharmacology, and potential areas of future research.

Take home message: Overall, we believe that the body of evidence supports the following conclusions; i) endothelin is a potent vasoconstrictor that plays a role in ocular physiology, ii) endothelin may play a role in the pathophysiology of glaucoma and iii) modulation of the endothelin system with newly discovered potent antagonists holds promise in treating glaucoma through both pressure-dependent and pressure-independent pathways.     

Current status of unoprostone for the management of glaucoma and the future of its use in the treatment of retinal disease

Imatinib mesylate is a selective and potent small-molecule inhibitor of tyrosine kinases, including Kit, platelet-derived growth factor receptor, and the BCR–Abl fusion protein. Kit plays an important role in gastrointestinal stromal tumours (GISTs) and is one of the most exciting therapeutic targets discovered so far. Clinical trials have consistently shown the dramatic efficacy of imatinib mesylate in patients with GIST. This article will review the development and pharmacology of this small-molecule inhibitor and summarise the clinical trials of imatinib mesylate for the treatment of GIST. Although imatinib mesylate has significantly improved the outcomes of most patients with advanced GIST, unanswered questions remain: what is the role of imatinib mesylate in the pre- and postoperative settings? What is the mechanism of the antitumour activity of imatinib? How do you manage patients whose tumours are refractory to imatinib mesylate?     

Comparing bimatoprost and travoprost in black Americans

ABSTRACT

Objective: To compare the intraocular pressurelowering efficacy and safety of topical bimatoprost 0.03% with that of travoprost 0.004% for the reatment of black patients with open-angle glaucoma (OAG) and ocular hypertension (OHT).

Research design and methods: Multicenter, prospective, randomized, investigator-masked trial of 94 black patients previously diagnosed with OAG or OHT. All patients completed washout of ocular hypotensive medications before study participation. Patients were assigned to either once-daily bimatoprost 0.03% or once-daily travoprost 0.004% for 3 months.

Main outcome measures: The primary outcome measures were mean intraocular pressure (IOP), mean change from baseline IOP, and percentage of patients who reached a target IOP reduction. Secondary measures included ophthalmologic examination and adverse events.

Results: Both bimatoprost and travoprost significantly lowered IOP at all study visits (?p < 0.001). Bimatoprost provided mean IOP reductions from baseline that ranged from 6.8?mmHg to 7.8?mmHg (27% to 31%). Travoprost provided mean IOP reductions from baseline that ranged from 6.2?mmHg to 6.9?mmHg (25% to 28%). By month 3, 85% of participants in the bimatoprost group had a mean IOP reduction of at least 20%, compared with 68% of those in the travoprost group. Furthermore, 31.9% of those in the bimatoprost group had a mean IOP reduction of more than 40% at month 3 compared with 20.9% of those in the travoprost group. There were no significant differences in biomicroscopy, ophthalmoscopy, or visual acuity. Ocular redness was the most commonly reported adverse event in both treatment groups. No serious adverse events were reported.

Conclusions: Bimatoprost and travoprost each effectively lowered IOP in this population of black patients. More patients achieved clinically relevant IOP reductions with bimatoprost.     

改良小梁切除术治疗高眼压青光眼临床分析

目的分析改良小梁切除术治疗高眼压青光眼患者的效果。方法对该院收治的80例高眼压青光眼患者进行前房穿刺,将房水缓慢放出,再对患者进行复合性的改良骨小梁的切除手术,手术完成后,对滤过泡、眼压、患者的视力情况、前房进行仔细观察。结果术后1年,患者的眼压控制在21mm Hg以下68例;需进行局部用药控制12例;患者手术后,出院时的视力保持不变或有提高80例。患者在手术后发生瞳孔区渗出8例,前房出血4例,浅前房12例。未发生严重并发症。结论高眼压青光眼患者进行改良小梁切除术,可使高眼压的时间缩短,保护患者的视力及功能。     

Glaucoma: a review of adjunctive therapy and new management strategies

Glaucoma is a major cause of vision loss throughout the world. Treatment for glaucoma consists of reducing intraocular pressure (IOP) to an acceptable target range to prevent further optic nerve damage. Typically, this involves the selection of a topical IOP-lowering agent. Five major classes of glaucoma medications are presently available for clinical use. These include α-adrenergic agonists, β-adrenergic antagonists (β-blockers), carbonic anhydrase inhibitors (CAIs), cholinergics and prostaglandin analogs (PGAs). Although β-blockers enjoyed great success as first-line glaucoma therapy for many years, recently the PGAs have gained favor as the initial treatment of choice for most patients. Although the PGAs offer robust IOP reduction as monotherapy, a significant number of patients will require an adjunctive agent for adequate IOP control. Recent studies have demonstrated that α-agonists, β-blockers and CAIs can be used safely and effectively as adjunctive therapy for patients being treated with a PGA. Comparison studies are beginning to appear in the literature to help determine which adjunctive agent is the most effective when used in combination with a PGA. Additional IOP-lowering efficacy with adjunctive therapy does have limitations, particularly with the addition of a third or fourth agent. For those patients on maximal tolerated medical therapy who still need additional IOP reduction, other available options include laser trabeculoplasty and filtration surgery.