Tan Colin S, Ngo Wei Kiong, Chay Isaac W, Ting Dominic S, Sadda SriniVas R
National Healthcare Group Eye Institute, Tan Tock Seng Hospital, Singapore.
Fundus Image Reading Centre, National Healthcare Group Eye Institute, Singapore.
Clin Ophthalmol. 2022 Mar 25;16:917-933. doi: 10.2147/OPTH.S231913. eCollection 2022.
Neovascular age-related macular degeneration (nAMD) is a common world-wide cause of visual loss. Intravitreal anti-vascular endothelial growth factor (anti-VEGF) agents are an effective means to treat nAMD and reduce its impact on vision compared to either sham treatment or photodynamic therapy. Currently, the approved anti-VEGF drugs include ranibizumab, aflibercept and brolucizumab. In addition, bevacizumab, used as an off-label drug, and has been shown to be effective in treating nAMD. While anti-VEGF agents are effective, its limitations include the requirement for frequent, often monthly injections, and the need for long-term treatment of nAMD. These present significant burdens on the healthcare system and on the patients. In addition, reviews of patients with nAMD treated with anti-VEGF have reported deterioration of vision over time with progression of geographic atrophy. These limitations are partly addressed by exploring different treatment regimens that reduce the frequency of treatments. Newer anti-VEGF drugs have been shown in Phase III clinical trials to have injection intervals as long as 12 or even 16 weeks for a proportion of patients. There is research on newer drugs that affect other pathways, such as the angiopoietin pathway, which may impact nAMD by extending the treatment interval and reducing the burden of treatment. Other measures include the use of sustained-release implants that release the drug regularly over a period of time, and can be refilled periodically, as well as hydrogel platforms that serve to release the drug. The use of biosimilars will also serve to reduce the cost of treatment for nAMD. A new frontier of gene therapy, primarily targeting genes involved in the transduction of retinal cells to produce anti-VEGF proteins intraocularly, also opens a new avenue of therapeutic approaches that can be used for treatment. This review paper will discuss both current treatment options and the newer treatments under development.
新生血管性年龄相关性黄斑变性（nAMD）是全球范围内导致视力丧失的常见原因。与假治疗或光动力疗法相比，玻璃体内注射抗血管内皮生长因子（抗VEGF）药物是治疗nAMD并减轻其对视力影响的有效手段。目前，已获批的抗VEGF药物包括雷珠单抗、阿柏西普和布罗利尤单抗。此外，贝伐单抗作为一种未获批准的药物使用，已被证明对治疗nAMD有效。虽然抗VEGF药物有效，但其局限性包括需要频繁（通常每月一次）注射，以及nAMD需要长期治疗。这些给医疗系统和患者带来了巨大负担。此外，对接受抗VEGF治疗的nAMD患者的回顾报告显示，随着地图样萎缩的进展，视力会随着时间推移而恶化。通过探索减少治疗频率的不同治疗方案，这些局限性在一定程度上得到了解决。在III期临床试验中，已证明新型抗VEGF药物对一部分患者的注射间隔长达12周甚至16周。正在研究影响其他途径（如血管生成素途径）的新型药物，这可能通过延长治疗间隔和减轻治疗负担来影响nAMD。其他措施包括使用能在一段时间内定期释放药物且可定期补充药物的缓释植入物，以及用于释放药物的水凝胶平台。生物类似药的使用也将有助于降低nAMD的治疗成本。基因治疗这一全新领域主要针对参与视网膜细胞转导以在眼内产生抗VEGF蛋白的基因，也开辟了一条可用于治疗的新治疗途径。本文将讨论当前的治疗选择以及正在研发的新治疗方法。
