Schmidt-Erfurth Ursula, Pollreisz Andreas, Mitsch Christoph, Bolz Matthias
Dev Ophthalmol. 2010;46:21-38. doi: 10.1159/000320007. Epub 2010 Aug 10.
Age-related macular degeneration (AMD) is the leading cause of irreversible vision loss in adults aged over 50 years in developed countries. Until recently, argon laser photocoagulation and photo-dynamic therapy (PDT) were the only treatments available for the neovascular form of AMD. The introduction of new intravitreally injectable inhibitors of vascular endothelial growth factor (VEGF) revolutionized the management of the wet form. Pegaptanib was the first anti-VEGF agent to be approved by the US Food and Drug Administration (FDA) for use in neovascular AMD. The VISION study showed that patients receiving pegaptanib lost vision in a smaller rate than those treated with conventional care. Bevacizumab is a full-length recombinant humanized monoclonal antibody which binds to all isoforms of VEGF-A. It is licensed for the intravenous administration for the treatment of malignant solid tumors and is available for off-label use in the treatment of AMD-related CNV. Numerous retrospective studies have shown beneficial effects of bevacizumab in patients with neovascular AMD. Ranibizumab is a recombinant, humanized antibody antigen-binding fragment (Fab) that binds to all known active forms of VEGF-A. The US FDA approved ranibizumab for treatment of all subtypes of choroidal neovascularization secondary to AMD. VEGF trap is a pharmacologically engineered protein that binds VEGF with higher affinity than pegaptanib or ranibizumab and thus prevents VEGF binding to its cellular receptor offering a theoretically longer interval between necessary treatments. A number of studies have shown that OCT imaging allows identification of functionally relevant factors like subretinal fluid or retinal thickness, which are important for the establishment of optimized individual dosing regimen during anti-angiogenesis therapies.
年龄相关性黄斑变性(AMD)是发达国家50岁以上成年人不可逆视力丧失的主要原因。直到最近,氩激光光凝和光动力疗法(PDT)仍是新生血管性AMD仅有的可用治疗方法。新型玻璃体内注射血管内皮生长因子(VEGF)抑制剂的引入彻底改变了湿性AMD的治疗方式。哌加他尼是首个被美国食品药品监督管理局(FDA)批准用于新生血管性AMD的抗VEGF药物。VISION研究表明,接受哌加他尼治疗的患者视力丧失速度低于接受传统治疗的患者。贝伐单抗是一种全长重组人源化单克隆抗体,可与VEGF-A的所有亚型结合。它被批准用于静脉给药治疗恶性实体瘤,也可用于AMD相关脉络膜新生血管(CNV)的非标签治疗。大量回顾性研究表明贝伐单抗对新生血管性AMD患者有有益作用。雷珠单抗是一种重组人源化抗体抗原结合片段(Fab),可与所有已知的活性VEGF-A形式结合。美国FDA批准雷珠单抗用于治疗AMD继发的所有脉络膜新生血管亚型。VEGF陷阱是一种经过药物工程改造的蛋白质,它与VEGF的亲和力高于哌加他尼或雷珠单抗,因此可防止VEGF与其细胞受体结合,理论上可延长必要治疗之间的间隔时间。多项研究表明,光学相干断层扫描(OCT)成像可识别视网膜下液或视网膜厚度等功能相关因素,这些因素对于抗血管生成治疗期间确定优化的个体化给药方案很重要。