Research progress on reactivation of retinopathy of prematurity following anti-vascular endothelial growth factor therapy_Chinese Journal of Ocular Fundus Diseases

Authors：

Wang Hao , Li Manhong ,  Wang Yusheng ,  Zhang Zifeng

S1PLA Ophthalmology Research Institute, Xijing Hospital, Air Force Medical University, Xi'an 710032, China;

Corresponding author：

Wang Yusheng, Email: wangys003@126.com; Zhang Zifeng, Email: zzffmmu@163.com

Keywords：

Retinopathy of prematurity; Anti-vascular endothelial growth factor; Reactivation; Review

DOI：

10.3760/cma.j.cn511434-20250901-00376

Video：

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Retinopathy of prematurity (ROP) is a retinal vascular disease in preterm or low birth weight infants and a leading cause of childhood blindness. Anti-vascular endothelial growth factor (VEGF) therapy offers advantages such as minimal invasiveness and convenient intervention; however, it carries a relatively high risk of disease reactivation, necessitating long-term follow-up due to the potential for severe outcomes. Studies indicate that post-anti-VEGF reactivation rates vary regionally and are related with birth status, ROP severity, and the specific anti-VEGF agent used. Most reactivations occur 6-16 weeks after initial treatment, at a postmenstrual age of 37-60 weeks. Reactivated lesions often develop at the original ridge or the junction of vascularized and avascular retina, and may present with dilation and tortuosity of the posterior retinal vessels, peripheral vascular leakage, neovascularization, or retinal detachment. Fundus fluorescein angiography may reveal Plus disease, posterior arterial tortuosity, abnormal nondichotomous retinal vessel branching at the junction of vascularized and avascular retina, irregular circumferential vessels, vasoobliteration with capillary nonperfusion, neovascularization, and fluorescein leakage. The choice of retreatment (such as retinal laser photocoagulation, intravitreal anti-VEGF injection, or vitrectomy) should be decided by the timing and severity of reactivation, along with prognostic considerations. It is recommended to establish a standardized management protocol for reactivation after anti-VEGF treatment in ROP to enable early detection and intervention, thereby preventing severe visual impairment. Future studies should focus on the mechanisms underlying ROP reactivation, differences in reactivation rates and timing among various anti-VEGF agents, predictive models for reactivation risk, and long-term management of reactivated disease.

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2. Hartnett ME, Lane RH. Effects of oxygen on the development and severity of retinopathy of prematurity[J]. J AAPOS, 2013, 17(3): 229-234. DOI: 10.1016/j.jaapos.2012.12.155.
3. Cavallaro G, Filippi L, Bagnoli P, et al. The pathophysiology of retinopathy of prematurity: an update of previous and recent knowledge[J]. Acta Ophthalmol, 2014, 92(1): 2-20. DOI: 10.1111/aos.12049.
4. 王雨生. 解读2021最新版《早产儿视网膜病变国际分类法(第3版)》[J]. 眼科新进展, 2021, 41(8): 701-705. DOI: 10.13389/j.cnki.rao.2021.0146.Wang YS. Interpretation for the latest edition in 2021 of international classification of retinopathy of prematurity (third edition)[J]. Rec Adv Ophthalmol, 2021, 41(8): 701-705. DOI: 10.13389/j.cnki.rao.2021.0146.
5. Hu J, Blair MP, Shapiro MJ, et al. Reactivation of retinopathy of prematurity after bevacizumab injection[J]. Arch Ophthalmol, 2012, 130(8): 1000-1006. DOI: 10.1001/archophthalmol.2012.592.
6. Mintz-Hittner HA, Geloneck MM, Chuang AZ. Clinical management of recurrent retinopathy of prematurity after intravitreal Bevacizumab monotherapy[J]. Ophthalmology, 2016, 123(9): 1845-1855. DOI: 10.1016/j.ophtha.2016.04.028.
7. Hu Q, Bai Y, Chen X, et al. Recurrence of retinopathy of prematurity in zone II stage 3+ after Ranibizumab treatment: a retrospective study[J]. J Ophthalmol, 2017, 50(78): 565-570. DOI: 10.1155/2017/5078565.
8. Sukgen EA, Kocluk Y. Comparison of clinical outcomes of intravitreal ranibizumab and aflibercept treatment for retinopathy of prematurity[J]. Graefe's Arch Clin Exp Ophthalmol, 2019, 257(1): 49-55. DOI: 10.1007/s00417-018-4168-5.
9. Bassiouny RM, Gaafar WM, El Nokrashy A, et al. Clinical outcome following reinjection of Ranibizumab for reactivation of retinopathy of prematurity[J]. Eye (Lond), 2022, 36(11): 2137-2143. DOI: 10.1038/s41433-021-01814-5.
10. 姜海涛, 李国仁. 我国早产儿视网膜病变的筛查现状[J]. 国际眼科杂志, 2021, 21(8): 1386-1389. DOI: 10.3980/j.issn.1672-5123.2021.8.15.Jiang HT, Li GR. Screening status of prematurity in China[J]. Int Eye Sci, 2021, 21(8): 1386-1389. DOI: 10.3980/j.issn.1672-5123.2021.8.15.
11. Sabri K, Ells AL, Lee EY, et al. Retinopathy of prematurity: a global perspective and recent developments[J/OL]. Pediatrics, 2022, 150(3): e2021053924[2022-09-01]. https://pubmed.ncbi.nlm.nih.gov/35948728/. DOI: 10.1542/peds.2021-053924.
12. Huang Q, Zhang Q, Fei P, et al. Ranibizumab injection as primary treatment in patients with retinopathy of prematurity: anatomic outcomes and influencing factors[J]. Ophthalmology, 2017, 124(8): 1156-1164. DOI: 10.1016/j.ophtha.2017.03.018.
13. Kang HG, Choi EY, Byeon SH, et al. Anti-vascular endothelial growth factor treatment of retinopathy of prematurity: efficacy, safety, and anatomical outcomes[J]. Korean J Ophthalmol, 2018, 32(6): 451-458. DOI: 10.3341/kjo.2018.0011.
14. Fleck BW, Reynolds JD, Zhu Q, et al. Time course of retinopathy of prematurity regression and reactivation after treatment with Ranibizumab or laser in the RAINBOW trial[J]. Ophthalmol Retina, 2022, 6(7): 628-637. DOI: 10.1016/j.oret.2022.02.006.
15. 李曼红, 王亮, 张自峰, 等. 两种抗VEGF药物治疗1型早产儿视网膜病变的疗效比较[J]. 国际眼科杂志, 2021, 21(5): 866-871. DOI: 10.3980/j.issn.1672-5123.2021.5.24.Li MH, Wang L, Zhang ZF, et al. Comparison of the effectiveness of Conbercept versus Ranibizumab in the treatment of type 1 retinopathy of prematurity[J]. Int Eye Sci, 2021, 21(5): 866-871. DOI: 10.3980/j.issn.1672-5123.2021.5.24.
16. Cheng Y, Zhu X, Ling DH, et al. Comparison of the effectiveness of conbercept and ranibizumab treatment for retinopathy of prematurity[J/OL]. Acta Ophthalmol, 2020, 98(8): e1004-e1008[2020-05-08]. https://pubmed.ncbi.nlm.nih.gov/32385940/. DOI: 10.1111/aos.14460.
17. 尹雪, 杨晖, 傅征, 等. 早产儿视网膜病变抗VEGF治疗后复发的危险因素分析[J]. 国际眼科杂志, 2020, 20(6): 1105-1108. DOI: 10.3980/j.issn.1672-5123.2020.6.40.Yin X, Yang H, Fu Z, et al. Risk factors for recrudescence of ROP after anti-VEGF treatment[J]. Int Eye Sci, 2020, 20(6): 1105-1108. DOI: 10.3980/j.issn.1672-5123.2020.6.40.
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