Progress of intravitreal anti-vascular endothelial growth factor during pregnancy_Chinese Journal of Ocular Fundus Diseases

Authors：

Lao Jimeng , Mao Jianbo ,  Shen Lijun

The Eye Hospital of Wenzhou Medical University, Hangzhou 310020, China;

Corresponding author：

Shen Lijun, Email: slj@mail.eye.ac.cn

Keywords：

Pregnant women; Angiogenesis inhibitors/adverse effects; Review

DOI：

10.3760/cma.j.cn511434-20180731-00261

Video：

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Intravitreal anti-VEGF injection have been widely used in retinal vascular diseases and achieved good efficacy. Early pregnancy is an important period for fetal organ formation and vascular development. Studies have proved that VEGF plays an important role in maintaining the fetal and placental vascular system, and its loss or decline will affect embryonic development and lead to abortion. The use of intravitreal anti-VEGF during pregnancy is controversial, which may cause systemic side effects to the mother and fetus. This paper summarizes the literature of 23 cases on the use of anti-VEGF during pregnancy. Three cases reported loss of pregnancy with concomitant exposure to intravitreal bevacizumab, which suggested that we should be careful about the use of anti-VEGF during pregnancy and explain the possibility of ocular and systemic side effects to patients in detail. When deciding whether to use anti-VEGF, we should consider the relationship between exposure time and the critical period of vascular development and the systemic exposure of different drugs. Currently, there is a lack of large sample size studies on the use of anti-VEGF in pregnancy, and its safety needs to be further observed.

Citation： Lao Jimeng, Mao Jianbo, Shen Lijun. Progress of intravitreal anti-vascular endothelial growth factor during pregnancy. Chinese Journal of Ocular Fundus Diseases, 2020, 36(4): 323-326. doi: 10.3760/cma.j.cn511434-20180731-00261 Copy

1.	闵晓雪, 牟佳, 刘依琳, 等. 抗血管内皮生长因子时代糖尿病视网膜病变的治疗演变[J]. 华西医学, 2017, 32(10): 1615-1619. DOI: 10.7507/1002-0179.201708076.Min XX, Mu J, Liu YL, et al. Evolution of the treatment of diabetic retinopathy in the age of vascular endothelial growth factor[J]. West Chin Med J, 2017, 32(10): 1615-1619. DOI: 10.7507/1002-0179.201708076.
2.	Kim HS, Cho HJ, Yoo SG, et al. Intravitreal anti-vascular endothelial growth factor monotherapy for large submacular hemorrhage secondary to neovascular age-related macular degeneration[J]. Eye (Lond), 2015, 29(9): 1141-1151. DOI: 10.1038/eye.2015.131.
3.	Farinha C, Martins A, Neves A, et al. Ranibizumab for the treatment of diabetic macular oedema in the real-world clinical setting in portugal: a multicentre study[J]. Ophthalmologica, 2019, 241(1): 1-8. DOI: 10.1159/000489046.
4.	Jang JH, Kim KH, Lee SJ, et al. Photodynamic therapy combined with intravitreal bevacizumab in a patient with choroidal neovascularization secondary to choroidal osteoma[J]. Korean J Ophthalmol, 2012, 26(6): 478-480. DOI: 10.3341/kjo.2012.26.6.478.
5.	Bennett N, John L, Likhar N, et al. Clinical efficacy and safety of current interventions for choroidal neovascularization associated with rare diseases: a systematic literature review[J]. Adv Ther, 2018, 35(5): 591-603. DOI: 10.1007/s12325-018-0698-9.
6.	Al-Dhibi H, Hamade IH, Al-Halafi A, et al. The effects of intravitreal bevacizumab in infectious and noninfectious uveitic macular edema[J/OL]. J Ophthalmol, 2014, 2014: 729465[2014-07-21]. https://doi.org/10.1155/2014/729465. DOI: 10.1155/2014/729465.
7.	Torry DS, Leavenworth J, Chang M, et al. Angiogenesis in implantation[J]. J Assist Reprod Genet, 2007, 24(7): 303-315. DOI: 10.1007/s10815-007-9152-7.
8.	Kim M, Park HJ, Seol JW, et al. VEGF-A regulated by progesterone governs uterine angiogenesis and vascular remodelling during pregnancy[J]. EMBO Mol Med, 2013, 5(9): 1415-1430. DOI: 10.1002/emmm.201302618.
9.	Vuorela P, Carpén O, Tulppala M, et al. VEGF, its receptors and the tie receptors in recurrent miscarriage[J]. Mol Hum Reprod, 2000, 6(3): 276-282. DOI: 10.1093/molehr/6.3.276.
10.	Al-Khateeb GM, Mustafa FE, Sater MS, et al. Effect of the functional VEGFA-583C/T variant on vascular endothelial growth factor levels and the risk of recurrent spontaneous miscarriage[J]. Fertil Steril, 2011, 95(8): 2471-2473. DOI: 10.1016/j.fertnstert.2011.03.010.
11.	Carmeliet P, Ferreira V, Breier G, et al. Abnormal blood vessel development and lethality in embryos lacking a single VEGF allele[J]. Nature, 1996, 380(6573): 435-439. DOI: 10.1038/380435a0.
12.	Evans PW, Wheeler T, Anthony FW, et al. A longitudinal study of maternal serum vascular endothelial growth factor in early pregnancy[J]. Hum Reprod, 1998, 13(4): 1057-1062. DOI: 10.1093/humrep/13.4.1057.
13.	Shiraishi S, Nakagawa K, Kinukawa N, et al. Immunohistochemical localization of vascular endothelial growth factor in the human placenta[J]. Placenta, 1996, 17(2-3): 111-121. DOI: 10.1016/s0143-4004(96)80004-x.
14.	Goldman CK, Kendall RL, Cabrera G, et al. Paracrine expression of a native soluble vascular endothelial growth factor receptor inhibits tumor growth, metastasis, and mortality rate[J]. Proc Natl Acad Sci USA, 1998, 95(15): 8795-8800. DOI: 10.1073/pnas.95.15.8795.
15.	Keskin U, Ulubay M, Dede M, et al. The relationship between the VEGF/sVEGFR-1 ratio and threatened abortion[J]. Arch Gynecol Obstet, 2015, 291(3): 557-561. DOI: 10.1007/s00404-014-3452-9.
16.	Cross SN, Ratner E, Rutherford TJ, et al. Bevacizumab-mediated interference with VEGF signaling is sufficient to induce a preeclampsia-like syndrome in nonpregnant women[J]. Rev Obstet Gynecol, 2012, 5(1): 2-8.
17.	Wang Y, Fei D, Vanderlaan M, et al. Biological activity of bevacizumab, a humanized anti-VEGF antibody in vitro[J]. Angiogenesis, 2004, 7(4): 335-345. DOI: 10.1007/s10456-004-8272-2.
18.	Kubota T, Kiuchi Y, Sheridan C. Anti-vascular endothelial growth factor agents for ocular angiogenesis and vascular permeability[J/OL]. J Ophthalmol, 2012, 2012: 898207[2012-03-18]. https://doi.org/10.1155/2012/898207. DOI: 10.1155/2012/898207.
19.	Wang F, Bai Y, Yu W, et al. Anti-angiogenic effect of KH902 on retinal neovascularization[J]. Graefe's Arch Clin Exp Ophthalmol, 2013, 251(9): 2131-2139. DOI: 10.1007/s00417-013-2392-6.
20.	Csaky K, Do DV. Safety implications of vascular endothelial growth factor blockade for subjects receiving intravitreal anti-vascular endothelial growth factor therapies[J]. Am J Ophthalmol, 2009, 148(5): 647-656. DOI: 10.1016/j.ajo.2009.06.014.
21.	Sawada O, Kawamura H, Kakinoki M, et al. Vascular endothelial growth factor in fellow eyes of eyes injected with intravitreal bevacizumab[J]. Graefe’s Arch Clin Exp Ophthalmol, 2008, 246(10): 1379-1381. DOI: 10.1007/s00417-008-0874-8.
22.	Bakri SJ, Snyder MR, Reid JM, et al. Pharmacokinetics of intravitreal bevacizumab (Avastin)[J]. Ophthalmology, 2007, 114(5): 855-859. DOI: 10.1016/j.ophtha.2007.01.017.
23.	Avery RL, Castellarin AA, Steinle NC, et al. Systemic pharmacokinetics following intravitreal injections of ranibizumab, bevacizumab or aflibercept in patients with neovascular AMD[J]. Br J Ophthalmol, 2014, 98(12): 1636-1641. DOI: 10.1136/bjophthalmol-2014-305252.
24.	Gu X, Yu X, Dai H. Intravitreal injection of ranibizumab for treatment of age-related macular degeneration: effects on serum VEGF concentration[J]. Curr Eye Res, 2014, 39(5): 518-521. DOI: 10.3109/02713683.2013.848899.
25.	Jin E, Bai Y, Luo L, et al. Serum levels of vascular endothelial growth factor before and after intravitreal injection of ranibizumab or conbercept for neovascular age-related macular age-related macular degeneration[J]. Retina, 2017, 37(5): 971-977. DOI: 10.1097/IAE.0000000000001274.
26.	Zehetner C, Kirchmair R, Huber S, et al. Plasma levels of vascular endothelial growth factor before and after intravitreal injection of bevacizumab, ranibizumab and pegaptanib in patients with age-related macular degeneration, and in patients with diabetic macular oedema[J]. Br J Ophthalmol, 2013, 97(4): 454-459. DOI: 10.1136/bjophthalmol-2012-302451.
27.	Pentsuk N, van der Laan JW. An interspecies comparison of placental antibody transfer: new insights into developmental toxicity testing of monoclonal antibodies[J]. Birth Defects Res B Dev Reprod Toxicol, 2009, 86(4): 328-344. DOI: 10.1002/bdrb.20201.
28.	Briggs GG, Freeman RK, Yaffe SJ. Drugs in pregnancy and lactation: a reference guide to fetal and neonatal risk[M]. Philadelphia: Wolters Kluwer/Lippincott Williams & Wilkins Health, 2015.
29.	Thorn M, Piche-Nicholas N, Stedman D, et al. Embryo-fetal transfer of bevacizumab (Avastin) in the rat over the course of gestation and the impact of neonatal Fc receptor (FcRn) binding[J]. Birth Defects Res B Dev Reprod Toxicol, 2012, 95(5): 363-375. DOI: 10.1002/bdrb.21026.
30.	Sullivan L, Kelly SP, Glenn A, et al. Intravitreal bevacizumab injection in unrecognised early pregnancy[J]. Eye (Lond), 2014, 28(4): 492-494. DOI: 10.1038/eye.2013.311.
31.	Introini U, Casalino G, Cardani A, et al. Intravitreal bevacizumab for a subfoveal myopic choroidal neovascularization in the first trimester of pregnancy[J]. J Ocul Pharmacol Ther, 2012, 28(5): 553-555. DOI: 10.1089/jop.2012.0067.
32.	Jouve L, Akesbi J, Nordmann JP. Safety and efficacy of ranibizumab for pregnant women in idiopathic choroidal neovascularization[J]. Acta Ophthalmol, 2015, 93(7): 597-598. DOI: 10.1111/aos.12611.
33.	Fossum P, Couret C, Briend B, et al. Safety of intravitreal injection of ranibizumab in early pregnancy: a series of three cases[J]. Eye (Lond), 2018, 32(4): 830-832. DOI: 10.1038/eye.2017.305.
34.	Petrou P, Georgalas I, Giavaras G, et al. Early loss of pregnancy after intravitreal bevacizumab injection[J]. Acta Ophthalmol, 2010, 88(4): 136. DOI: 10.1111/j.1755-3768.2009.01572.x.
35.	Kianersi F, Ghanbari H, Naderi Beni Z, et al. Intravitreal vascular endothelial growth factor (VEGF) inhibitor injection in unrecognised early pregnancy[J]. Invest New Drugs, 2016, 34(5): 650-653. DOI: 10.1007/s10637-016-0361-8.
36.	Tarantola RM, Folk JC, Boldt HC, et al. Intravitreal bevacizumab during pregnancy[J]. Retina, 2010, 30(9): 1405-1411. DOI: 10.1097/IAE.0b013e3181f57d58.
37.	Rosen E, Rubowitz A, Ferencz JR. Exposure to verteporfin and bevacizumab therapy for choroidal neovascularization secondary to punctate inner choroidopathy during pregnancy[J]. Eye, 2009, 23(6): 1479. DOI: 10.1038/eye.2008.218.
38.	Wu Z, Huang J, Sadda S. Inadvertent use of bevacizumab to treat choroidal neovascularisation during pregnancy: a case report[J]. Ann Acad Med Singap, 2010, 39(2): 143-145.
39.	Sarhianaki A, Katsimpris A, Petropoulos IK, et al. Intravitreal administration of ranibizumab for idiopathic choroidal neovascularization in a pregnant woman[J]. Klin Monatsbl Augenheilkd, 2012, 229(4): 451-453. DOI: 10.1055/s-0031-1299207.
40.	Polizzi S, Ferrara, G, Restaino S, et al. Inadvertent use of bevacizumab in pregnant women with diabetes mellitus type 1[J]. J Basic Clin Physiol, 2015, 26(2): 161-163. DOI: 10.1515/jbcpp-2014-0058.
41.	Polizzi S, Mahajan VB. Intravitreal anti-VEGF injections in pregnancy: case series and review of literature[J]. J Ocul Pharmacol Ther, 2015, 31(10): 605-610. DOI: 10.1089/jop.2015.0056.
42.	Granger JP. Vascular endothelial growth factor inhibitors and hypertension: a central role for the kidney and endothelial factors[J]. Hypertension, 2009, 54(3): 465-467. DOI: 10.1161/HYPERTENSIONAHA.109.132274.
43.	Sane DC, Anton L, Brosnihan KB. Angiogenic growth factors and hypertension[J]. Angiogenesis, 2004, 7(3): 193-201. DOI: 10.1007/s10456-004-2699-3.
44.	He B, Yang X, Li Y, et al. TLR9(toll-like receptor 9) agonist suppresses angiogenesis by differentially regulating VEGFA (vascular endothelial growth factor A) and sFLT1(soluble vascular endothelial growth factor receptor 1) in preeclampsia[J]. Hypertension, 2018, 71(4): 671-680. DOI: 10.1161/HYPERTENSIONAHA.117.10510.
45.	Raiser R, Artunay O, Yuzbasioglu E, et al. The effect of intravitreal bevacizumab (Avastin) administration on systemic hypertension[J]. Eye, 2009, 23(8): 1714-1718. DOI: 10.1038/eye.2008.360.

1. 闵晓雪, 牟佳, 刘依琳, 等. 抗血管内皮生长因子时代糖尿病视网膜病变的治疗演变[J]. 华西医学, 2017, 32(10): 1615-1619. DOI: 10.7507/1002-0179.201708076.Min XX, Mu J, Liu YL, et al. Evolution of the treatment of diabetic retinopathy in the age of vascular endothelial growth factor[J]. West Chin Med J, 2017, 32(10): 1615-1619. DOI: 10.7507/1002-0179.201708076.
2. Kim HS, Cho HJ, Yoo SG, et al. Intravitreal anti-vascular endothelial growth factor monotherapy for large submacular hemorrhage secondary to neovascular age-related macular degeneration[J]. Eye (Lond), 2015, 29(9): 1141-1151. DOI: 10.1038/eye.2015.131.
3. Farinha C, Martins A, Neves A, et al. Ranibizumab for the treatment of diabetic macular oedema in the real-world clinical setting in portugal: a multicentre study[J]. Ophthalmologica, 2019, 241(1): 1-8. DOI: 10.1159/000489046.
4. Jang JH, Kim KH, Lee SJ, et al. Photodynamic therapy combined with intravitreal bevacizumab in a patient with choroidal neovascularization secondary to choroidal osteoma[J]. Korean J Ophthalmol, 2012, 26(6): 478-480. DOI: 10.3341/kjo.2012.26.6.478.
5. Bennett N, John L, Likhar N, et al. Clinical efficacy and safety of current interventions for choroidal neovascularization associated with rare diseases: a systematic literature review[J]. Adv Ther, 2018, 35(5): 591-603. DOI: 10.1007/s12325-018-0698-9.
6. Al-Dhibi H, Hamade IH, Al-Halafi A, et al. The effects of intravitreal bevacizumab in infectious and noninfectious uveitic macular edema[J/OL]. J Ophthalmol, 2014, 2014: 729465[2014-07-21]. https://doi.org/10.1155/2014/729465. DOI: 10.1155/2014/729465.
7. Torry DS, Leavenworth J, Chang M, et al. Angiogenesis in implantation[J]. J Assist Reprod Genet, 2007, 24(7): 303-315. DOI: 10.1007/s10815-007-9152-7.
8. Kim M, Park HJ, Seol JW, et al. VEGF-A regulated by progesterone governs uterine angiogenesis and vascular remodelling during pregnancy[J]. EMBO Mol Med, 2013, 5(9): 1415-1430. DOI: 10.1002/emmm.201302618.
9. Vuorela P, Carpén O, Tulppala M, et al. VEGF, its receptors and the tie receptors in recurrent miscarriage[J]. Mol Hum Reprod, 2000, 6(3): 276-282. DOI: 10.1093/molehr/6.3.276.
10. Al-Khateeb GM, Mustafa FE, Sater MS, et al. Effect of the functional VEGFA-583C/T variant on vascular endothelial growth factor levels and the risk of recurrent spontaneous miscarriage[J]. Fertil Steril, 2011, 95(8): 2471-2473. DOI: 10.1016/j.fertnstert.2011.03.010.
11. Carmeliet P, Ferreira V, Breier G, et al. Abnormal blood vessel development and lethality in embryos lacking a single VEGF allele[J]. Nature, 1996, 380(6573): 435-439. DOI: 10.1038/380435a0.
12. Evans PW, Wheeler T, Anthony FW, et al. A longitudinal study of maternal serum vascular endothelial growth factor in early pregnancy[J]. Hum Reprod, 1998, 13(4): 1057-1062. DOI: 10.1093/humrep/13.4.1057.
13. Shiraishi S, Nakagawa K, Kinukawa N, et al. Immunohistochemical localization of vascular endothelial growth factor in the human placenta[J]. Placenta, 1996, 17(2-3): 111-121. DOI: 10.1016/s0143-4004(96)80004-x.
14. Goldman CK, Kendall RL, Cabrera G, et al. Paracrine expression of a native soluble vascular endothelial growth factor receptor inhibits tumor growth, metastasis, and mortality rate[J]. Proc Natl Acad Sci USA, 1998, 95(15): 8795-8800. DOI: 10.1073/pnas.95.15.8795.
15. Keskin U, Ulubay M, Dede M, et al. The relationship between the VEGF/sVEGFR-1 ratio and threatened abortion[J]. Arch Gynecol Obstet, 2015, 291(3): 557-561. DOI: 10.1007/s00404-014-3452-9.
16. Cross SN, Ratner E, Rutherford TJ, et al. Bevacizumab-mediated interference with VEGF signaling is sufficient to induce a preeclampsia-like syndrome in nonpregnant women[J]. Rev Obstet Gynecol, 2012, 5(1): 2-8.
17. Wang Y, Fei D, Vanderlaan M, et al. Biological activity of bevacizumab, a humanized anti-VEGF antibody in vitro[J]. Angiogenesis, 2004, 7(4): 335-345. DOI: 10.1007/s10456-004-8272-2.
18. Kubota T, Kiuchi Y, Sheridan C. Anti-vascular endothelial growth factor agents for ocular angiogenesis and vascular permeability[J/OL]. J Ophthalmol, 2012, 2012: 898207[2012-03-18]. https://doi.org/10.1155/2012/898207. DOI: 10.1155/2012/898207.
19. Wang F, Bai Y, Yu W, et al. Anti-angiogenic effect of KH902 on retinal neovascularization[J]. Graefe's Arch Clin Exp Ophthalmol, 2013, 251(9): 2131-2139. DOI: 10.1007/s00417-013-2392-6.
20. Csaky K, Do DV. Safety implications of vascular endothelial growth factor blockade for subjects receiving intravitreal anti-vascular endothelial growth factor therapies[J]. Am J Ophthalmol, 2009, 148(5): 647-656. DOI: 10.1016/j.ajo.2009.06.014.
21. Sawada O, Kawamura H, Kakinoki M, et al. Vascular endothelial growth factor in fellow eyes of eyes injected with intravitreal bevacizumab[J]. Graefe’s Arch Clin Exp Ophthalmol, 2008, 246(10): 1379-1381. DOI: 10.1007/s00417-008-0874-8.
22. Bakri SJ, Snyder MR, Reid JM, et al. Pharmacokinetics of intravitreal bevacizumab (Avastin)[J]. Ophthalmology, 2007, 114(5): 855-859. DOI: 10.1016/j.ophtha.2007.01.017.
23. Avery RL, Castellarin AA, Steinle NC, et al. Systemic pharmacokinetics following intravitreal injections of ranibizumab, bevacizumab or aflibercept in patients with neovascular AMD[J]. Br J Ophthalmol, 2014, 98(12): 1636-1641. DOI: 10.1136/bjophthalmol-2014-305252.
24. Gu X, Yu X, Dai H. Intravitreal injection of ranibizumab for treatment of age-related macular degeneration: effects on serum VEGF concentration[J]. Curr Eye Res, 2014, 39(5): 518-521. DOI: 10.3109/02713683.2013.848899.
25. Jin E, Bai Y, Luo L, et al. Serum levels of vascular endothelial growth factor before and after intravitreal injection of ranibizumab or conbercept for neovascular age-related macular age-related macular degeneration[J]. Retina, 2017, 37(5): 971-977. DOI: 10.1097/IAE.0000000000001274.
26. Zehetner C, Kirchmair R, Huber S, et al. Plasma levels of vascular endothelial growth factor before and after intravitreal injection of bevacizumab, ranibizumab and pegaptanib in patients with age-related macular degeneration, and in patients with diabetic macular oedema[J]. Br J Ophthalmol, 2013, 97(4): 454-459. DOI: 10.1136/bjophthalmol-2012-302451.
27. Pentsuk N, van der Laan JW. An interspecies comparison of placental antibody transfer: new insights into developmental toxicity testing of monoclonal antibodies[J]. Birth Defects Res B Dev Reprod Toxicol, 2009, 86(4): 328-344. DOI: 10.1002/bdrb.20201.
28. Briggs GG, Freeman RK, Yaffe SJ. Drugs in pregnancy and lactation: a reference guide to fetal and neonatal risk[M]. Philadelphia: Wolters Kluwer/Lippincott Williams & Wilkins Health, 2015.
29. Thorn M, Piche-Nicholas N, Stedman D, et al. Embryo-fetal transfer of bevacizumab (Avastin) in the rat over the course of gestation and the impact of neonatal Fc receptor (FcRn) binding[J]. Birth Defects Res B Dev Reprod Toxicol, 2012, 95(5): 363-375. DOI: 10.1002/bdrb.21026.
30. Sullivan L, Kelly SP, Glenn A, et al. Intravitreal bevacizumab injection in unrecognised early pregnancy[J]. Eye (Lond), 2014, 28(4): 492-494. DOI: 10.1038/eye.2013.311.
31. Introini U, Casalino G, Cardani A, et al. Intravitreal bevacizumab for a subfoveal myopic choroidal neovascularization in the first trimester of pregnancy[J]. J Ocul Pharmacol Ther, 2012, 28(5): 553-555. DOI: 10.1089/jop.2012.0067.
32. Jouve L, Akesbi J, Nordmann JP. Safety and efficacy of ranibizumab for pregnant women in idiopathic choroidal neovascularization[J]. Acta Ophthalmol, 2015, 93(7): 597-598. DOI: 10.1111/aos.12611.
33. Fossum P, Couret C, Briend B, et al. Safety of intravitreal injection of ranibizumab in early pregnancy: a series of three cases[J]. Eye (Lond), 2018, 32(4): 830-832. DOI: 10.1038/eye.2017.305.
34. Petrou P, Georgalas I, Giavaras G, et al. Early loss of pregnancy after intravitreal bevacizumab injection[J]. Acta Ophthalmol, 2010, 88(4): 136. DOI: 10.1111/j.1755-3768.2009.01572.x.
35. Kianersi F, Ghanbari H, Naderi Beni Z, et al. Intravitreal vascular endothelial growth factor (VEGF) inhibitor injection in unrecognised early pregnancy[J]. Invest New Drugs, 2016, 34(5): 650-653. DOI: 10.1007/s10637-016-0361-8.
36. Tarantola RM, Folk JC, Boldt HC, et al. Intravitreal bevacizumab during pregnancy[J]. Retina, 2010, 30(9): 1405-1411. DOI: 10.1097/IAE.0b013e3181f57d58.
37. Rosen E, Rubowitz A, Ferencz JR. Exposure to verteporfin and bevacizumab therapy for choroidal neovascularization secondary to punctate inner choroidopathy during pregnancy[J]. Eye, 2009, 23(6): 1479. DOI: 10.1038/eye.2008.218.
38. Wu Z, Huang J, Sadda S. Inadvertent use of bevacizumab to treat choroidal neovascularisation during pregnancy: a case report[J]. Ann Acad Med Singap, 2010, 39(2): 143-145.
39. Sarhianaki A, Katsimpris A, Petropoulos IK, et al. Intravitreal administration of ranibizumab for idiopathic choroidal neovascularization in a pregnant woman[J]. Klin Monatsbl Augenheilkd, 2012, 229(4): 451-453. DOI: 10.1055/s-0031-1299207.
40. Polizzi S, Ferrara, G, Restaino S, et al. Inadvertent use of bevacizumab in pregnant women with diabetes mellitus type 1[J]. J Basic Clin Physiol, 2015, 26(2): 161-163. DOI: 10.1515/jbcpp-2014-0058.
41. Polizzi S, Mahajan VB. Intravitreal anti-VEGF injections in pregnancy: case series and review of literature[J]. J Ocul Pharmacol Ther, 2015, 31(10): 605-610. DOI: 10.1089/jop.2015.0056.
42. Granger JP. Vascular endothelial growth factor inhibitors and hypertension: a central role for the kidney and endothelial factors[J]. Hypertension, 2009, 54(3): 465-467. DOI: 10.1161/HYPERTENSIONAHA.109.132274.
43. Sane DC, Anton L, Brosnihan KB. Angiogenic growth factors and hypertension[J]. Angiogenesis, 2004, 7(3): 193-201. DOI: 10.1007/s10456-004-2699-3.
44. He B, Yang X, Li Y, et al. TLR9(toll-like receptor 9) agonist suppresses angiogenesis by differentially regulating VEGFA (vascular endothelial growth factor A) and sFLT1(soluble vascular endothelial growth factor receptor 1) in preeclampsia[J]. Hypertension, 2018, 71(4): 671-680. DOI: 10.1161/HYPERTENSIONAHA.117.10510.
45. Raiser R, Artunay O, Yuzbasioglu E, et al. The effect of intravitreal bevacizumab (Avastin) administration on systemic hypertension[J]. Eye, 2009, 23(8): 1714-1718. DOI: 10.1038/eye.2008.360.

Chinese Journal of Ocular Fundus Diseases

Progress of intravitreal anti-vascular endothelial growth factor during pregnancy

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