Effects of intravitreal injection of anti-vascular endothelial growth factor drugs on retinal blood circulation_Chinese Journal of Ocular Fundus Diseases

Authors：

Qiu Xu ¹ ,  Dou Hongliang ² , Chen Fenghua ¹ , Song Zongyan ¹

1. Department of Ophtalmology, The First People’s Hospital of Guiyang, Guiyang 550001, China;
2. Eye Center of Peking University Third Hospital, Key Laboratory of Visual Impairment and Restoration of Ministry of Education, Beijing 100191, China;

Corresponding author：

Dou Hongliang, Email: douhl@aliyun.com

Keywords：

Angiogenesis inhibitors/adverse effects; Retina; Microcirculation; Review

DOI：

10.3760/cma.j.cn511434-20180926-00324

Video：

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Anti-VEGF therapies have been widely used in the treatment of age-related macular degeneration, diabetic macular edema, retinal vein occlusion with macular edema and other retinal diseases. It have achieved remarkable treatment effect with relatively high safety, but there are still reports of adverse reactions in cardio-cerebral vessels and eyes. There are many methods to measure retinal blood flow. Although the principles of these methods are different, the results are different, and there is no uniform standard, it has been observed that anti-VEGF drugs may cause some changes in retinal vessel diameter, arterial blood flow velocity and blood flow parameters. Especially after multiple injections, the effect may be more obvious.

Citation： Qiu Xu, Dou Hongliang, Chen Fenghua, Song Zongyan. Effects of intravitreal injection of anti-vascular endothelial growth factor drugs on retinal blood circulation. Chinese Journal of Ocular Fundus Diseases, 2020, 36(7): 565-570. doi: 10.3760/cma.j.cn511434-20180926-00324 Copy

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1. Gao Y, Yu T, Zhang Y, et al. Anti-VEGF monotherapy versus photodynamic therapy and anti-VEGF combination treatment for neovascular age-related macular degeneration: a meta-analysis[J]. Invest Ophthalmol Vis Sci, 2018, 59(10): 4307-4317. DOI: 10.1167/iovs.17-23747.
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3. Schutz FA, Je Y, Azzi GR, et al. Bevacizumab increases the risk of arterial ischemia: a large study in cancer patients with a focus on different subgroup outcomes[J]. Ann Oncol, 2011, 22(6): 1404-1412. DOI: 10.1093/annonc/mdq587.
4. Tatlipinar S, Dinç UA, Yenerel NM, er al. Short-term effects of a single intravitreal bevacizumab injection on retinal vessel calibre[J]. Clin Exp Optom, 2012, 95(1): 94-98. DOI: 10.1111/j.1444-0938.2011.00662.x.
5. Kurt MM, Çekiç O, Akpolat Ç, et al. Comparative retinal vessel size study of intravitreal ranibizumab and bevacizumab in eyes with neovascular age-related macular degeneration[J]. Ophthalmologica, 2017, 238(3): 147-153. DOI: 10.1159/000477180.
6. Mohamed R, Saunders DC, Mathews JP. Consulting the patients: Avastin in the treatment of wet AMD (Part Ⅱ)[J]. Eye (Lond), 2019, 33(6): 871-873. DOI: 10.1038/s41433-019-0366-6.
7. De Jong FJ, Vernooij MW, Ikram MK, et al. Arteriolar oxgen saturation, cerebral blood flow, and retinal vessel diameter. The Rotterdam Study[J]. Ophthalmology, 2008, 115(5): 887-892. DOI: 10.1016/j.ophtha.2007.06.036.
8. Soliman W, Vinten M, Sander B, et al. Optical coherence tomography and vessel diameter changes after intravitreal bevacizumab in diabetic macular oedema[J]. Acta Ophthalmol, 2008, 86(4): 365-371. DOI: 10.1111/j.1600-0420.2007.01057.x.
9. Park J, Lee S, Son Y. Effects of two different doses of intravitreal bevacizumab on subfoveal choroidal thickness and retinal vessel diameter in branch retinal vein occlusion[J]. Int J Ophthalmol, 2016, 9(7): 999-1005. DOI: 10.18240/ijo.2016.07.11.
10. Papadopoulou DN, Mendrinos E, Mangioris G, et al. Intravitreal ranibizumab may induce retinal arteriolar vasoconstriction in patients with neovascular age-related macular degeneration[J]. Ophthalmology, 2009, 116(9): 1755-1761. DOI: 10.1016/j.ophtha.2009.03.017.
11. Mendrinos E, Mangioris G, Papadopoulou DN, et al. Long-term results of the effect of intravitreal ranibizumab on the retinal arteriolar diameter in patients with neovascular age-related macular degeneration[J]. Acta Ophthalmol, 2013, 91(3): 184-190. DOI: 10.1111/aos.12008.
12. Sacu S, Pemp B, Weigert G, et al. Response of retinal vessels and retrobulbar hemodynamics to intravitreal anti-VEGF treatment in eyes with branch retinal vein occlusion[J]. Invest Ophthalmol Vis Sci, 2011, 52(6): 3046-3050. DOI: 10.1167/iovs.10-5842.
13. Fontaine O, Olivier S, Descovich D, et al. The effect of intravitreal injection of bevacizumab on retinal circulation in patients with neovascular macular degeneration[J]. Invest Ophthalmol Vis Sci, 2011, 52(10): 7400-7405. DOI: 10.1167/iovs.10-6646.
14. Bonnin P, Pournaras JA, Lazrak Z, et al. Ultrasound assessment of short-term ocular vascular effects of intravitreal injection of bevacizumab (Avastin^®) in neovascular age-related macular degeneration[J]. Acta Ophthalmol, 2010, 88(6): 641-645. DOI: 10.1111/j.1755-3768.2009.01526.x.
15. Mete A, Saygili O, Mete A, et al. Effects of intravitreal bevacizumab (Avastin) therapy on retrobulbar blood flow parameters in patients with neovascular age-related macular degeneration[J]. J Clin Ultrasound, 2010, 38(2): 66-70. DOI: 10.1002/jcu.20650.
16. Mete A, Saygili O, Mete A, et al. Does ranibizumab (Lucentis) change retrobulbar bloos flow in patients with neovascular age-related macular degeneration[J]. Ophthalmic Res, 2012, 47(3): 141-145. DOI: 10.1159/000330509.
17. Hosseini H, Lotfi M, Esfahani MH, et al. Effect of intravitreal bevacizumab on retrobulbar blood flow in injected and uninjected fellow eyes of patients with neovascular age-related macular degeneration[J]. Retina, 2012, 32(5): 967-971. DOI: 10.1097/IAE.0b013e31822c28d6.
18. Örnek N, Inal M, Erbahceci IE, et al. Effect of intravitreal bevacizumab on retrobulbar blood flow of patients with diabetic macular edema[J]. Eur J Ophthalmol, 2015, 25(6): 539-545. DOI: 10.5301/ejo.5000617.
19. Toklu Y, Cakmak HB, Raza S, et al. Short-term effects of intravitreal bevacizumab (Avastin^®) on retrobulbar hemodynamics in patients with neovascular age-related macular degeneration[J]. Acta Ophthalmol, 2011, 89(1): 41-45. DOI: 10.1111/j.1755-3768.2010.02075.x.
20. 赵露, 谢国丽, 王艳玲. 玻璃体腔注射雷珠单抗对湿性年龄相关性黄斑变性患者眼血流动力学的影响[J]. 山东大学耳鼻喉眼学报, 2016, 30(4): 101-104. DOI: 10.6040/j.issn.1673-3770.0.2015.481.Zhao L, Xie GL, Wang YL. Changes of ocular hemodynamics after intravitreal ranibizumab injection in patients with wet age-related macular degeneration[J]. J Otolaryngol Ophthal Shandong Univ, 2016, 30(4): 101-104. DOI: 10.6040/j.issn.1673-3770.0.2015.481.
21. Gunay M, Tuten A, Sancak S, et al. Effect of single intravitreal bevacizumab on ophthalmic and middle cerebral arterial blood flow in retinopathy of prematurity[J]. Ophthalmic Res, 2016, 55(4): 165-171. DOI: 10.1159/000443208.
22. Nagahara M, Tamaki Y, Tomidokoro A, et al. In vivo measurement of blood velocity in human major retinal vessels using the laser speckle method[J]. Invest Ophthalmol Vis Sci, 2011, 52(1): 87-92. DOI: 10.1167/iovs.09-4422.
23. 张锦德, 檀邹, 林黎升, 等. 激光散斑成像在血流监测中的研究进展[J]. 中国激光医学杂志, 2016, 25(5): 233-241, 244-245. DOI: 10.13480/j.issn1003-9430.2016.0233.Zhang JD, Tan Z, Lin LS, et al. Recent advances in monitoring blood flow with laser speckle imaging[J]. Chinese Journal of Laser Medicine & Surgery, 2016, 25(5): 233-241, 244-245. DOI: 10.13480/j.issn1003-9430.2016.0233.
24. Sugiyama T, Araie M, Riva CE, et al. Use of laser speckle flowgraphy in ocular blood flow research[J]. Acta Ophthalmol, 2010, 88(7): 723-729. DOI: 10.1111/j.1755-3768.2009.01586.x.
25. Tamaki Y, Araie M, Tomita K, et al. Real-time measurement of human optic nerve head and choroid circulation, using the laser speckle phenomenon[J]. Ophthalmol, 1997, 41(1): 49-54. DOI: 10.1016/S0021-5155(96)00008-1.
26. Matsumoto M, Suzuma K, Fukazawa Y, et al. Retinal blood flow levels measured by laser speckle flowgraphy in patients who received intravitreal bevacizumab injection for macular edema secondary to central retinal vein occlusion[J]. Retina Cases Brief Rep, 2014, 8(1): 60-66. DOI: 10.1097/ICB.0000000000000005.
27. Yamada Y, Suzuma K, Matsumoto M, et al. Retinal blood flow correlates to aqueous vasular endothelial growth factor in central retinal vein occlusion[J]. Retina, 2015, 35(10): 2037-2042. DOI: 10.1097/IAE.0000000000000595.
28. Matsumoto M, Suzuma K, Yamada Y, et al. Retinal blood flow after intraviteal bevacizumab is a predictive factor for outcomes of macular edema associated with central retinal vein occlusion[J]. Retina, 2018, 38(2): 283-291. DOI: 10.1097/IAE.0000000000001531.
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