眼科新一代抗血管内皮生长因子药物的基础研究及临床试验进展

视网膜新生血管形成是眼部多种疾病共有的病理改变，其造成的眼部功能损害是致盲的重要原因之一。血管内皮生长因子（VEGF）是治疗新生血管性眼病的重要靶点。进入抗VEGF治疗眼病的纪元以来，单靶点抗VEGF—A药物在新生血管性眼病的治疗中取得了良好的效果。近两年来，以阿柏西普（aflibercept，VEGF Trap—Eye，Eylea）和康柏西普（conbercept，KH902）为代表的多靶点[包括VEGF—A、VEGF—B和胎盘生长因子（P1GF）]抗VEGF药物逐步进入临床。新一代多靶点抗VEGF药物可改善一些对单靶点抗VEGF药物治疗无反应患者的临床症状。同时，因为延长了两次用药之间的间隔又可达到同样的疗效，可减少多次眼内注射带来的相关风险。但是此类药物的新增靶点在维持血管和神经元正常功能方面可能起着作用。因此，虽然目前还没有关于这类新药引起严重不良反应的报道，但仍需进一步评价这类新药潜在的不良反应。就眼科新一代抗VEGF药物，aflibercept和conbercept的基础研究、药代动力学、疗效、安全性及目前存在的问题进行综述。

Curative effect and safety of the new generation of anti-vascular endothelial growth factor drugs in neovascular eye diseases

Retinal neovascularization, a common pathological process of a variety of eye diseases,is a major cause of blindness. Vascular endothelial growth factor （VEGF） has been believed to be the most important therapeutic target of neovaseular eye diseases. In the era of anti-VEGF for retinal diseases, several drugs aiming at the single molecular target VEGF-A have achieved considerable success in decreasing neovascularization and relieving the symptoms. In the past two years, novel anti-VEGF drugs aiming at multiple molecular targets including VEGF-A, VEGF-B and P1GF have surged into clinic service. Represented by aflibercept （VEGF Trap-Eye, Eylea） and conbercept （KH902）, multiple targets anti-VEGF drugs relieve the clinical symptoms in patients resistant to single target anti-VEGF drugs. In addition,because similar curative effects are achieved with longer injection interval,risk of complications related to the intraocular injection procedure is reduced. However, it is reported that the additional inhibited targets are associated with maintaining the normal functions of blood vessels and neurons. Therefore, although there are still no severe adverse effects for these new developed drugs, further long-term observation is mandatory to evaluate their safety. In this review,we summarized the characteristics of aflibercept and conbercept,a new generation of anti-VEGF drugs, from the aspects of basic research, pharmacokinetics, efficacy, safety and the existing problems.