The limitation of anti-vascular endothelial growth factor treatment for wet age-related macular degeneration_Chinese Journal of Ocular Fundus Diseases

Authors：

Xu Huijuan ,  Yang Zhenglin

Chengdu Institute of Biology, Chinese Academy of Sciences, Department of Ophthalmology, Sicuan Provincial Pepole’s Hospital, Chengdu 610072, China;

Corresponding author：

Yang Zhenglin, Email: zliny@yahoo.com

Keywords：

Wet macular degeneration/drug therapy; Choroidal neovascularization/drug therapy; Angiogenesis inhibitors/therapeutic use; Review

DOI：

10.3760/cma.j.issn.1005-1015.2020.02.017

Video：

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Abstract Full text Figures/Tables Video References Cited by

Wet age-related macular degeneration (wAMD) is caused by choroidal neovascularization (CNV), which occurs when the choroidal new capillaries reach the RPE layer and photoreceptor cell layer through the ruptured Bruch membrane, leading to neovascularization bleeding, leakage, and scarring. In view of the important role of VEGF in the development of CNV, targeted therapy with various intraocular anti-VEGF drugs is the first-line treatment for wAMD. However, the efficacy of anti-VEGF drugs in the treatment of wAMD is affected by a variety of factors, and some patients still have problems such as unresponsiveness, drug resistence, tachyphylaxis, long-term repeated injections, and severe adverse effects. It is the direction of future researches to deeply explore the physiological and pathological process of wAMD, find the cause of CNV formation, and seek better therapies.

Citation： Xu Huijuan, Yang Zhenglin. The limitation of anti-vascular endothelial growth factor treatment for wet age-related macular degeneration. Chinese Journal of Ocular Fundus Diseases, 2020, 36(2): 156-161. doi: 10.3760/cma.j.issn.1005-1015.2020.02.017 Copy

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1. 白玉婧, 黎晓新. 新生血管性老年性黄斑变性药物治疗面临的挑战与未来的发展趋势[J]. 中华眼底病杂志, 2016, 32(1): 3-7. DOI: 10.3760/cma.j.issn.1005-1015.2016.01.002.Bai YJ, Li XX. Progression and challenge of therapeutic strategies in neovascular age-related macular degeneration[J]. Chin J Ocul Fundus Dis, 2016, 32(1): 3-7. DOI: 10.3760/cma.j.issn.1005-1015.2016.01.002.
2. 戴虹, 卢颖毅. 全面评估抗血管内皮生长因子药物治疗新生血管性老年性黄斑变性的影响因素, 努力提高治疗效果的综合收益[J]. 中华眼底病杂志, 2016, 32(1): 8-11. DOI: 10.3760/cma.j.issn.1005-1015.2016.01.003.Dai H, Lu YY. Overall assessment of the factors influencing the effect of anti-vascular endothelial growth factor for neovascular age-related macular degeneration to improve the comprehensive benefit of treatment[J]. Chin J Ocul Fundus Dis, 2016, 32(1): 8-11. DOI: 10.3760/cma.j.issn.1005-1015.2016.01.003.
3. Ambati J, Fowler BJ. Mechanisms of age-related macular degeneration[J]. Neuron, 2012, 75(1): 26-39. DOI: 10.1016/j.neuron.2012.06.018.
4. Ferrara N, CarverMoore K, Chen H, et al. Heterozygous embryonic lethality induced by targeted inactivation of the VEGF gene[J]. Nature, 1996, 380(6573): 439-442. DOI: 10.1038/380439a0.
5. Penn JS, Madan A, Caldwell RB, et al. Vascular endothelial growth factor in eye disease[J]. Prog Retin Eye Res, 2008, 27(4): 331-371. DOI: 10.1016/j.preteyeres.2008.05.001.
6. Jeltsch M, Kaipainen A, Joukov V, et al. Hyperplasia of lymphatic vessels in VEGF-C transgenic mice[J]. Science, 1997, 276(5317): 1423-1425. DOI: 10.1126/science.276.5317.1423.
7. Ogawa S, Oku A, Sawano A, et al. A novel type of vascular endothelial growth factor, VEGF-E (NZ-7 VEGF), preferentially utilizes KDR/FlK-1 receptor and carries a potent mitotic activity without heparin-binding domain[J]. J Biol Chem, 1998, 273(47): 31273-31282. DOI: 10.1074/jbc.273.47.31273.
8. Hiratsuka S, Minowa O, Kuno J, et al. Flt-1 lacking the tyrosine kinase domain is sufficient for normal development and angiogenesis in mice[J]. Proc Natl Acad Sci USA, 1998, 95(16): 9349-9354. DOI: 10.1073/pnas.95.16.9349.
9. 王红. 抗血管内皮生长因子药物治疗肿瘤的耐药性分析[J]. 健康必读, 2012, 11(5): 1.Wang H. Analysis of drug resistance of anti-vascular endothelial growth factor in treating tumor[J]. Gems of Health, 2012, 11(5): 1.
10. Shalaby F, Rossant J, Yamaguchi TP, et al. Failure of blood-island formation and vasculogenesis in Flk-1-deficient mice[J]. Nature, 1995, 376(6535): 62-66. DOI: 10.1038/376062a0.
11. Gragoudas ES, Adamis AP, Cunningham ET, et al. Pegaptanib for neovascular age-related macular degeneration[J]. N Engl J Med, 2004, 351(27): 2805-2816. DOI: 10.1056/NEJMoa042760.
12. Takeda AL, Colquitt J, Clegg AJ, et al. Pegaptanib and ranibizumab for neovascular age-related macular degeneration: a systematic review[J]. Br J Ophthalmol, 2007, 91(9): 1177-1182. DOI: 10.1136/bjo.2007.118562.
13. Chakravarthy U, Harding SP, Rogers CA, et al. Alternative treatments to inhibit VEGF in age-related choroidal neovascularisation: 2-year findings of the IVAN randomised controlled trial[J]. Lancet, 2013, 382(9900): 1258-1267. DOI: 10.1016/s0140-6736(13)61501-9.
14. Martin DF, Maguire MG, Ying GS, et al. Ranibizumab and bevacizumab for neovascular age-related macular degeneration the CATT Research Group[J]. N Engl J Med, 2011, 364(20): 1897-1908. DOI: 10.1056/NEJMoa1102673.
15. Rosenfeld PJ, Brown DM, Heier JS, et al. Ranibizumab for neovascular age-related macular degeneration[J]. N Engl J Med, 2006, 355(14): 1419-1431. DOI: 10.1056/NEJMoa054481.
16. Brown DM, Kaiser PK, Michels M, et al. Ranibizumab versus verteporfin for neovascular age-related macular degeneration[J]. N Engl J Med, 2006, 355(14): 1432-1444. DOI: 10.1056/NEJMoa062655.
17. Rofagha S, Bhisitkul RB, Boyer DS, et al. Seven-year outcomes in ranibizumab-treated patients in ANCHOR, MARINA, and HORIZON[J]. Ophthalmology, 2013, 120(11): 2292-2299. DOI: 10.1016/j.ophtha.2013.03.046.
18. Heier JS, Brown DM, Chong V, et al. Intravitreal aflibercept (VEGF Trap-Eye) in wet age-related macular degeneration[J]. Ophthalmology, 2012, 119(12): 2537-2548. DOI: 10.1016/j.ophtha.2012.09.006.
19. Schmidt-Erfurth U, Kaiser PK, Korobelnik JF, et al. Intravitreal aflibercept injection for neovascular age-related macular degeneration ninety-six-week results of the VIEW studies[J]. Ophthalmology, 2014, 121(1): 193-201. DOI: 10.1016/j.ophtha.2013.08.011.
20. Sarwar S, Clearfield E, Soliman MK et al. Aflibercept for neovascular age-related macular degeneration[J/OL]. Cochrane Database Syst Rev, 2016, 2: cd011346[2016-02-08]. https://doi.org/10.1002/14651858.CD011346.pub2. DOI:10.1002/14651858.CD011346.pub2.
21. Zhang M, Yu D, Yang C, et al. The pharmacology study of a new recombinant human VEGF receptor-Fc fusion protein on experimental choroidal neovascularization[J]. Pharm Res, 2009, 26(1): 204-210. DOI: 10.1007/s11095-008-9718-9.
22. Liu K, Song Y, Xu G, et al. Conbercept for treatment of neovascular age-related macular degeneration: results of the randomized phase 3 PHOENIX study[J]. Am J Ophthalmol, 2019, 197: 156-167. DOI: 10.1016/j.ajo.2018.08.026.
23. Zhang M, Zhang J, Yan M, et al. A phase 1 study of KH902, a vascular endothelial growth factor receptor decoy, for exudative age-related macular degeneration[J]. Ophthalmology, 2011, 118(4): 672-678. DOI: 10.1016/j.ophtha.2010.08.008.
24. Li X, Xu G, Wang Y, et al. Safety and efficacy of conbercept in neovascular age-related macular degeneration results from a 12-month randomized phase 2 study: AURORA study[J]. Ophthalmology, 2014, 121(9): 1740-1747. DOI: 10.1016/j.ophtha.2014.03.026.
25. Bendell JC, Patel MR, Moore KN, et al. Phase Ⅰ, first-in-human, dose-escalation study to evaluate the safety, tolerability, and pharmacokinetics of vorolanib in patients with advanced solid tumors[J]. Oncologist, 2019, 24(4): 455-e121. DOI: 10.1634/theoncologist.2018-0740.
26. 危清泉, 任成达, 时慧, 等. 口服酪氨酸激酶抑制剂CM082对实验大鼠脉络膜新生血管的影响[J]. 眼科新进展, 2016, 36(5): 414-418. DOI: 10.13389/j.cnki.rao.2016.0111.Wei QQ, Ren CD, Shi H, Liu QY, et al. Effects of oral tyrosine kinase inhibitor CM082 on experimental choroidal neovascularization in rat[J]. Rec Adv Ophthalmol, 2016, 36(5): 414-418. DOI: 10.13389/j.cnki.rao.2016.0111.
27. Jackson TL, Boyer D, Brown DM, et al. Oral tyrosine kinase inhibitor for neovascular age-related macular degeneration a phase 1 dose-escalation study[J]. JAMA Ophthalmol, 2017, 135(7): 761-767. DOI: 10.1001/jamaophthalmol.2017.1571.
28. Singerman L. Combination therapy using the small interfering RNA bevasiranib[J]. Retina, 2009, 29(6 Suppl): S49-50. DOI: 10.1097/IAE.0b013e3181ad2341.
29. Fong B, Barkhoudarian G, Pezeshkian P, et al. The molecular biology and novel treatments of vestibular schwannomas[J]. J Neurosurg, 2011, 115(5): 906-914. DOI: 10.3171/2011.6.jns11131.
30. Spooner K, Hong T, Nair R, et al. Long-term outcomes of switching to aflibercept for treatment-resistant neovascular age-related macular degeneration[J]. Acta Ophthalmol, 2019, 97(5): 706-712. DOI: 10.1111/aos.14046.
31. Keane PA, Liakopoulos S, Ongchin SC, et al. Quantitative subanalysis of optical coherence tomography after treatment with ranibizumab for neovascular age-related macular degeneration[J]. Invest Ophthalmol Vis Sci, 2008, 49(7): 3115-3120. DOI: 10.1167/iovs.08-1689.
32. Almony A, Mansouri A, Shah GK, et al. Efficacy of intravitreal bevacizumab after unresponsive treatment with intravitreal ranibizumab[J]. Can J Ophthalmol, 2011, 46(2): 182-185. DOI: 10.3129/i10-095.
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