Hussain Rehan M, Ciulla Thomas A
a Department of Ophthalmology , Indiana University School of Medicine , Indianapolis , IN , USA.
b Retina Service , Midwest Eye Institute , Indianapolis , IN , USA.
Expert Opin Emerg Drugs. 2017 Sep;22(3):235-246. doi: 10.1080/14728214.2017.1362390. Epub 2017 Aug 4.
Evolving anti-vascular endothelial growth factor (VEGF) treatments for neovascular age-related macular degeneration (nAMD) include long acting agents, combination strategies involving new pathways, topical agents, sustained-release, and genetic therapy strategies. Areas covered: Brolucizumab and abicipar pegol have smaller molecular size, facilitating higher concentrations and potentially longer duration than current anti-VEGF agents. Agents being combined with anti-VEGFs include OPT-302 (to inhibit VEGF-C and VEGF-D); pegpleranib and rinucumab (to inhibit platelet derived growth factor, PDGF - but both failed to show consistently improved visual outcomes compared to anti-VEGF monotherapy); and RG7716, ARP-1536 and nesvacumab (to activate the Tie-2 tyrosine kinase receptor, which reduces permeability). X-82 is an oral anti-VEGF and anti-PDGF being tested in phase 2 studies. Topical anti-VEGF ± anti-PDGF drugs under study include pazopanib, PAN-90806, squalamine lactate, regorafinib, and LHA510. Sustained-release anti-VEGF delivery treatments, such as the ranibizumab Port Delivery System, GB-102, NT-503, hydrogel depot, Durasert, and ENV1305 aim to reduce the burden of frequent injections. Gene therapies with new viral vectors hold the potential to induce sustained expression of anti-angiogenic proteins via the retina's cellular apparatus, and include AVA-101/201, ADVM-202/302, AAV2-sFLT01, RGX314, and Retinostat. Expert opinion: There are many emerging anti-VEGF treatments that aim to improve visual outcomes and reduce the treatment burden of nAMD.
用于治疗新生血管性年龄相关性黄斑变性（nAMD）的抗血管内皮生长因子（VEGF）疗法不断发展，包括长效制剂、涉及新途径的联合策略、局部用药、缓释制剂以及基因治疗策略。涵盖领域：布罗珠单抗和阿柏西普分子尺寸更小，与目前的抗VEGF药物相比，可实现更高浓度且作用时间可能更长。与抗VEGF联合使用的药物包括OPT-302（抑制VEGF-C和VEGF-D）；培格乐尼布和利努单抗（抑制血小板衍生生长因子，PDGF，但与抗VEGF单药治疗相比，二者均未始终显示出视觉效果的持续改善）；以及RG7716、ARP-1536和奈斯伐单抗（激活Tie-2酪氨酸激酶受体，从而降低通透性）。X-82是一种正在进行2期研究的口服抗VEGF和抗PDGF药物。正在研究的局部抗VEGF±抗PDGF药物包括帕唑帕尼、PAN-90806、乳酸鲨胺、瑞戈非尼和LHA510。缓释抗VEGF给药治疗，如雷珠单抗眼内植入系统、GB-102、NT-503、水凝胶贮库、Durasert和ENV1305，旨在减轻频繁注射的负担。采用新型病毒载体的基因疗法有可能通过视网膜细胞机制诱导抗血管生成蛋白的持续表达，包括AVA-101/201、ADVM-202/302、AAV2-sFLT01、RGX314和Retinostat。专家观点：有许多新兴的抗VEGF疗法旨在改善nAMD的视觉效果并减轻治疗负担。
