Pron G
Ont Health Technol Assess Ser. 2014 Aug 1;14(10):1-64. eCollection 2014.
New anti-angiogenesis pharmacotherapies have dramatically altered treatment of age-related macular degeneration (AMD), the leading cause of blindness in older adults. Monthly intraocular injections however, are extremely burdensome to ophthalmologists, patients, and their families. Repeated injections also increase risks of complications or adverse events. Although the pharmacokinetics of anti-vascular endothelial growth factor (A-VEGF) drugs are fairly well known, an individuals' AMD presentation and their pharmacodynamics or response to the drug has been shown to be extremely variable. Therefore treating everyone on the same fixed or standard regimen has potential for undertreating or overtreating patients, and drug costs are not trivial.
To review monitoring strategies and to evaluate the role of optical coherence tomography (OCT) in guiding management of A-VEGF-treated neovascular AMD (n-AMD) patients.
Systematic reviews of biographic databases for studies published between 2008 and February 2013 involving A-VEGF-treated n-AMD patients monitored in longitudinal follow-up.
Studies were grouped according to varying treatments, monitoring schedules, and re-treatment protocols reported for n-AMD patients treated with A-VEGF. Several outcomes were evaluated across strategies including visual acuity (VA), retinal anatomy, re-treatment criteria and frequencies of clinical follow-up, OCT imaging investigations, and intravitreal injections. Results were summarized qualitatively, as heterogeneity in study objectives and methods precluded formal meta-analysis.
A systematic review identified 18 randomized controlled trials (RCTs) and 20 observational studies involving A-VEGF treatment employing various monitoring and as-needed (PRN) re-treatment protocols. Several maintenance strategies were unsuccessful, resulting in lower VA gains and stabilization than monthly injections in A-VEGF-treated n-AMD. These included fixed quarterly treatment; fixed quarterly monitoring and PRN re-treatment; and monthly monitoring with either VA-guided re-treatment or quantitative-only VA/OCT- (central retinal thickness [CRT] > 100 μm) guided re-treatment. PRN re-treatment strategies with A-VEGF on the basis of monthly follow-up and rigorous reviews of OCT qualitative and quantitative measures of disease activity did decrease injection burden while maintaining visual gains. Gains in VA obtained with PRN re-treatment in usual clinical practice, however, were not as high as gains in clinical trials.
To reduce treatment burden and provide a more individualized treatment strategy for n-AMD patients, OCT/VA-guided PRN treatment strategies have become the preferred and the dominant maintenance strategy. Success of these strategies, however, is dependent on close monitoring and adherence to tightly defined re-treatment criteria.
新型抗血管生成药物疗法显著改变了年龄相关性黄斑变性(AMD)的治疗方式,AMD是老年人失明的主要原因。然而,每月进行眼内注射对眼科医生、患者及其家属来说负担极重。反复注射还会增加并发症或不良事件的风险。尽管抗血管内皮生长因子(A-VEGF)药物的药代动力学已为人熟知,但个体的AMD表现及其药效学或对药物的反应却显示出极大的变异性。因此,采用相同的固定或标准治疗方案治疗所有患者可能会导致部分患者治疗不足或过度治疗,而且药物成本也不容小觑。
综述监测策略,并评估光学相干断层扫描(OCT)在指导A-VEGF治疗的新生血管性AMD(n-AMD)患者管理中的作用。
对2008年至2013年2月期间发表的涉及在纵向随访中接受A-VEGF治疗的n-AMD患者的研究的生物数据库进行系统综述。
根据针对接受A-VEGF治疗的n-AMD患者报告的不同治疗方法、监测计划和再治疗方案对研究进行分组。对多种策略评估了多个结果,包括视力(VA)、视网膜解剖结构、再治疗标准以及临床随访频率、OCT成像检查和玻璃体内注射。由于研究目标和方法存在异质性,无法进行正式的荟萃分析,因此对结果进行了定性总结。
一项系统综述确定了18项随机对照试验(RCT)和20项观察性研究,这些研究涉及采用各种监测和按需(PRN)再治疗方案的A-VEGF治疗。几种维持策略未取得成功,导致在接受A-VEGF治疗的n-AMD患者中,与每月注射相比,视力提高和病情稳定程度较低。这些策略包括固定的每季度治疗;固定的每季度监测和PRN再治疗;以及每月监测,采用VA指导的再治疗或仅定量的VA/OCT(中心视网膜厚度[CRT] > 100μm)指导的再治疗。基于每月随访以及对OCT疾病活动定性和定量指标的严格评估的A-VEGF PRN再治疗策略确实减少了注射负担,同时保持了视力提高。然而,在常规临床实践中通过PRN再治疗获得的VA提高不如临床试验中的提高幅度大。
为减轻治疗负担并为n-AMD患者提供更个体化的治疗策略,OCT/VA指导的PRN治疗策略已成为首选且占主导地位的维持策略。然而,这些策略的成功取决于密切监测和严格遵守明确界定的再治疗标准。