Zarbin Marco, Szirth Bernard
Institute of Ophthalmology and Visual Science, New Jersey Medical School, Newark, New Jersey 07103, USA.
Optom Vis Sci. 2007 Jul;84(7):559-72. doi: 10.1097/OPX.0b013e3180de4dd7.
To review proved and experimental treatments for exudative and nonexudative complications of age-related macular degeneration (AMD), to consider the impact of current therapy on the structure of future clinical trials, and to consider the role of improved diagnostic imaging techniques on the effectiveness of current therapy as well as the structure of future clinical trials in AMD patients.
Defining the cell biology of choroidal new vessel (CNV) formation and geographic atrophy will lead to identification of different biochemical pathways that are the target of AMD treatment. Many treatments and treatment combinations are under study for AMD, but all work through a finite number of pathways. Currently, the most effective proved therapy for AMD-associated CNVs is administered by repeated intravitreal injection of agents that inhibit vascular endothelial growth factor, e.g., ranibizumab. Improved drug delivery will enhance patient satisfaction and possibly will enhance the effectiveness and reduce the risk of current pharmacotherapy for AMD-associated CNVs. Combination therapy (e.g., verteporfin-photodynamic therapy + ranibizumab) appears to reduce the risk and enhance the effectiveness of CNV treatment compared with monotherapy with currently available agents. Improved noninvasive diagnostic imaging may lead to better visual outcomes with existing therapeutic modalities. Improved imaging also may alter favorably the design of future clinical trials for AMD-associated CNVs and thus reduce cost and increase the diversity of sight-saving treatments.
Delineation of the biochemical basis for CNV formation has led to development of pathway-based pharmacotherapy for AMD patients. Areas of investigation that will advance the field further include combination therapy, improved drug delivery, and improved noninvasive, high-resolution diagnostic imaging. The logistics of future clinical trials will be complicated by the need for an active treatment control group, more stringent definition of successful treatment, and the increased numbers of patients required for combination therapy studies.
回顾年龄相关性黄斑变性(AMD)渗出性和非渗出性并发症已证实的和实验性治疗方法,考量当前治疗对未来临床试验结构的影响,并探讨改进的诊断成像技术对当前治疗效果以及AMD患者未来临床试验结构的作用。
明确脉络膜新生血管(CNV)形成和地图样萎缩的细胞生物学特性将有助于识别作为AMD治疗靶点的不同生化途径。目前有多种治疗方法和治疗组合正在AMD研究中,但所有治疗都是通过有限的途径起作用。目前,已证实对AMD相关CNV最有效的治疗方法是通过反复玻璃体内注射抑制血管内皮生长因子的药物,如雷珠单抗。改进的给药方式将提高患者满意度,并可能提高当前AMD相关CNV药物治疗的有效性并降低风险。与目前可用药物的单一疗法相比,联合治疗(如维替泊芬光动力疗法+雷珠单抗)似乎能降低CNV治疗的风险并提高有效性。改进的非侵入性诊断成像可能会使现有治疗方式带来更好的视觉效果。改进的成像也可能有利于改变未来AMD相关CNV临床试验的设计,从而降低成本并增加挽救视力治疗方法的多样性。
明确CNV形成的生化基础已促使针对AMD患者开发基于途径的药物治疗。进一步推动该领域发展的研究方向包括联合治疗、改进给药方式以及改进非侵入性高分辨率诊断成像。未来临床试验的后勤工作将因需要设立积极治疗对照组、更严格地定义成功治疗以及联合治疗研究所需患者数量增加而变得复杂。