Clinical analysis and curative effect of reactivation of retinopathy of prematurity after intravitreous injection of ranibizumab_Chinese Journal of Ocular Fundus Diseases

Authors：

Lan Fengxia ¹ ,  Zhang Guoming ² , He Honghui ² , Tian Ruyin ² , Chen Yi ² , Zeng Xianlu ² , Chen Miaohong ²

1. Department of Ophthalmology, Guangxi Maternal and Child Health Hospital, Nanning 530001, China;
2. Shenzhen Eye Hospital Affiliated to Jinan University, Shenzhen 518000, China;

Corresponding?author：

Zhang Guoming, Email: zhang-guoming@163.com

Keywords：

Retinopathy of prematurity; Reactivation; Angiogenesis inhibitor; Ranibizumab

DOI：

10.3760/cma.j.cn511434-20220304-00116

Video：

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Objective To observe the clinical characteristics and therapeutic effect of reactivation of retinopathy of prematurity (ROP) patients after intravitreal injection of ranibizumab (IVR). Methods A retrospective case series study. Eleven children with ROP (21 eyes) who were reactivated after IVR in Shenzhen Eye Hospital from January 2019 to October 2021 were included in the study. Among them, there were 6 males (11 eyes) and 5 females (10 eyes), with the gestational age of (27.6±2.2) weeks and birth weight of (1 034.6±306.5) g. At the first IVR treatment, 14 eyes (63.7%, 14/22) had acute ROP (AROP), 8 eyes (36.3%, 8/22) had threshold lesions. Post-reactivation treatments include IVR, retinal laser photocoagulation (LP), or minimally invasive vitrectomy (MIVS). The follow-up time after treatment was 12 to 18 months. Birth gestational age, birth weight, treatment method, corrected gestational age at treatment, lesion stage before and after treatment, lesion reactivation and regression time were recorded. The clinical characteristics and efficacy were observed and analyzed. Results The time from initial IVR treatment to reactivation was (8.2±3.5) weeks. The corrected gestational age of the child was (43.62±4.08) weeks. In 21 eyes, AROP, threshold lesion, pre-threshold lesion, and stage 4 lesion were in 2, 4, 12, and 3 eyes, respectively. The patients were treated with IVR, LP, IVR+LP, IVR+MIVS in 2, 13, 4 and 2 eyes, respectively. After the first reactivation treatment, the time of regression and stability was (8.4±4.9) weeks after treatment. There were 5 eyes with secondary reactivation of the lesion, and the lesion stages were stage 3, stage 4a and stage 5 in 2, 1 and 2 eyes, respectively. The mean reactivation time was (19.3±6.0) weeks after the last treatment. The patients in stage 3, stage 4a and stage 5 were treated with LP, LP+MIVS and IVR, respecitively, and the lesions subsided steadily during follow-up. At the last follow-up, 19 out of 21 eyes showed complete regression of the lesions, stable photocoagulation, regression of crista-like lesions, no additional lesions, and retinal leveling. All retinal detachment was "funnel-shaped" in 2 eyes. Conclusions The lesion reactivation of AROP after IVR treatment is more common. The early reactivation rate is higher after treatment. There is a possibility of reactivation twice after re-treatment.

Citation： Lan Fengxia, Zhang Guoming, He Honghui, Tian Ruyin, Chen Yi, Zeng Xianlu, Chen Miaohong. Clinical analysis and curative effect of reactivation of retinopathy of prematurity after intravitreous injection of ranibizumab. Chinese Journal of Ocular Fundus Diseases, 2023, 39(6): 471-475. doi: 10.3760/cma.j.cn511434-20220304-00116 Copy

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4.	王雨生. 解讀2021最新版《早產兒視網膜病變國際分類法(第3版)》[J]. 眼科新進展, 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.
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7.	楊小元, 蔡瑜婷, 李蕓. 日本眼科學會《早產兒視網膜病變的抗VEGF療法臨床指南》解讀[J]. 中華實驗眼科雜志, 2021, 39(11): 1003-1009. DOI: 10.3760/cma.j.cn115989-20210520-00313.Yang XY, Cai YT, Li Y. Interpretation of Clinical Guideline for Anti-vascular Endothelial Growth Factor Therapy of Retinopathy of Prematurity by Japanese Ophthalmological Society[J]. Chin J Exp Ophthalmol, 2021, 39(11): 1003-1009. DOI: 10.3760/cma.j.cn115989-20210520-00313.
8.	王翠, 張國明, 陳懿, 等. 微創玻璃體切割手術聯合雷珠單抗治療早期干預失敗的早產兒視網膜病變臨床觀察[J]. 中華眼底病雜志, 2020, 36(8): 590-594. DOI: 10.3760/cma.j.cn511434-20200305-00095.Wang C, Zhang GM, Chen Y, et al. Clinical observations of micro-incision vitrectomy surgery for retinopathy of prematurity with early intervention failure[J]. Chin J Ocul Fundus Dis, 2020, 36(8): 590-594. DOI: 10.3760/cma.j.cn511434-20200305-00095.
9.	尹虹, 黎曉新. 早產兒視網膜病變全視網膜脫離的玻璃體視網膜手術治療預后[J]. 中華眼底病雜志, 2008, 24(1): 5-8.Yi H, Li XX. Prognosis after vitreoretinal surgery for retinal detachment in patients with retinopathy of prematurity[J]. Chin J Ocul Fundus Dis, 2008, 24(1): 5-8.
10.	Chan-Ling T, Gole GA, Quinn GE, et al. Pathophysiology, screening and treatment of ROP: a multi-disciplinary perspective[J]. Prog Retin Eye Res, 2018, 62: 77-119. DOI: 10.1016/j.preteyeres.2017.09.002.
11.	Zhang Q, Qi Y, Chen L, et al. The relationship between anti-vascular endothelial growth factor and fibrosis in proliferative retinopathy: clinical and laboratory evidence[J]. Br J Ophthalmol, 2016, 100(10): 1443-1450. DOI: 10.1136/bjophthalmol-2015-308199.
12.	Semeraro F, Morescalchi F, Parmeggiani F, et al. Systemic adverse drug reactions secondary to anti-VEGF intravitreal injection in patients with neovascular age-related macular degeneration[J]. Curr Vasc Pharmacol, 2011, 9(5): 629-646. DOI: 10.2174/157016111796642670.
13.	Stahl A, Hellstrom A, Smith LE. Insulin-like growth factor-1 and anti-vascular endothelial growth factor in retinopathy of prematurity: has the time come?[J]. Neonatology, 2014, 106(3): 254-260. DOI: 10.1159/000365132.
14.	Xiang N, Zhao MJ, Li XY, et al. Redundant mechanisms for vascular growth factors in retinopathy of prematurity in vitro[J]. Ophthalmic Res, 2011, 45(2): 92-101. DOI: 10.1159/000316134.
15.	尹雪, 楊暉, 傅征, 等. 早產兒視網膜病變抗VEGF治療后復發的危險因素分析[J]. 國際眼科雜志, 2020, 20(6): 1105-1108. DOI: 10.3980/j.issn.1672-5123.2020.6.40.Yin X, Yang H, Bo 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.
16.	阮鵬. 抗VEGF治療早產兒視網膜病變復發的影響因素分析[D]. 鄭州大學, 2021. DOI:10.27466/d.cnki.gzzdu.2021.002464.Ruan P. Analysis of factors influencing the recurrence of retinopathy of prematurity after anti-VEGF treatment[D]. Zhengzhou University, 2021. DOI:10.27466/d.cnki.gzzdu.2021.002464.
17.	陳宜, 馮婧, 孟憲芬, 等. 玻璃體腔注射雷珠單抗治療早產兒視網膜病變療效觀察[J]. 中華眼底病雜志, 2015, 31(1): 6-9. DOI: 10.3760/cma.j.issn.1005-1015.2015.01.003.Chen Y, Feng J, Meng XF, et al. Effects of ranibizumab in zone Ⅰ and zone Ⅱ retinopathy of prematurity patients[J]. Chin J Ocul Fundus Dis, 2015, 31(1): 6-9. DOI: 10.3760/cma.j.issn.1005-1015.2015.01.003.
18.	Ittiara S, Blair MP, Shapiro MJ, et al. Exudative retinopathy and detachment: a late reactivation of retinopathy of prematurity after intravitreal bevacizumab[J]. J AAPOS, 2013, 17(3): 323-325. DOI: 10.1016/j.jaapos.2013.01.004.
19.	Ells AL, Wesolosky JD, Ingram AD, et al. Low-dose ranibizumab as primary treatment of posterior type I retinopathy of prematurity[J]. Can J Ophthalmol, 2017, 52(5): 468-474. DOI: 10.1016/j.jcjo.2017.02.012.
20.	Gunay M, Sukgen EA, Celik G, et al. Comparison of bevacizumab, ranibizumab, and laser photocoagulation in the treatment of retinopathy of prematurity in Turkey[J]. Curr Eye Res, 2017, 42(3): 462-469. DOI: 10.1080/02713683.2016.1196709.

1. 黎曉新. 中國早產兒視網膜病變篩查指南(2014年)[J]. 中華眼科雜志, 2014, 50(12): 933-935. DOI: 10.3760/cma.j.issn.0412-4081.2014.12.017.Li XX. Guidelines for screening retinopathy of premature infants in China(2014)[J]. Chin J Ophthalmol, 2014, 50(12): 933-935. DOI: 10.3760/cma.j.issn.0412-4081.2014.12.017.
2. 趙歡歡, 李靜, 穆歌, 等. 玻璃體腔注射雷珠單抗治療早產兒視網膜病變的臨床療效[J]. 中國斜視與小兒眼科雜志, 2018, 26(3): 20-23. DOI: 10.3969/j.issn.1005-328X.2018.03.007.Zhao HH, Li J, Mu G, et al. Clinical efficacy of intravitreal injection of ranibizumab in the treatment of retinopathy of prematurity[J]. Chinese Journal of Strabismus & Pediatric Ophthalmology, 2018, 26(3): 20-23. DOI: 10.3969/j.issn.1005-328X.2018.03.007.
3. 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.
4. 王雨生. 解讀2021最新版《早產兒視網膜病變國際分類法(第3版)》[J]. 眼科新進展, 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. 張國明, 李娜, 吳本清. 早產兒視網膜病變抗VEGF治療[M]//張國明, 李娜, 吳本清. 新生兒視網膜疾病篩查與防治. 北京: 人民衛生出版社, 2021: 145-149.Zhang GM, Li N, Wu BQ. Anti-vascular Endothelial Growth Factor Therapy of Retinopathy of Prematurity [M]//Zhang GM, Li N, Wu BQ. Screening, prevention and treatment of neonatal retinal diseases. Beijing: People's Medical Publishing House, 2021: 145-149.
6. GoodWV, Early Treatment for Retinopathy of Prematurity Cooperative Group. Final results of the Early Treatment for Retinopathy of Prematurity (ETROP) randomized trial[J]. Trans Am Ophthalmol Soc, 2004, 102: 233-248; discussion 248-250.
7. 楊小元, 蔡瑜婷, 李蕓. 日本眼科學會《早產兒視網膜病變的抗VEGF療法臨床指南》解讀[J]. 中華實驗眼科雜志, 2021, 39(11): 1003-1009. DOI: 10.3760/cma.j.cn115989-20210520-00313.Yang XY, Cai YT, Li Y. Interpretation of Clinical Guideline for Anti-vascular Endothelial Growth Factor Therapy of Retinopathy of Prematurity by Japanese Ophthalmological Society[J]. Chin J Exp Ophthalmol, 2021, 39(11): 1003-1009. DOI: 10.3760/cma.j.cn115989-20210520-00313.
8. 王翠, 張國明, 陳懿, 等. 微創玻璃體切割手術聯合雷珠單抗治療早期干預失敗的早產兒視網膜病變臨床觀察[J]. 中華眼底病雜志, 2020, 36(8): 590-594. DOI: 10.3760/cma.j.cn511434-20200305-00095.Wang C, Zhang GM, Chen Y, et al. Clinical observations of micro-incision vitrectomy surgery for retinopathy of prematurity with early intervention failure[J]. Chin J Ocul Fundus Dis, 2020, 36(8): 590-594. DOI: 10.3760/cma.j.cn511434-20200305-00095.
9. 尹虹, 黎曉新. 早產兒視網膜病變全視網膜脫離的玻璃體視網膜手術治療預后[J]. 中華眼底病雜志, 2008, 24(1): 5-8.Yi H, Li XX. Prognosis after vitreoretinal surgery for retinal detachment in patients with retinopathy of prematurity[J]. Chin J Ocul Fundus Dis, 2008, 24(1): 5-8.
10. Chan-Ling T, Gole GA, Quinn GE, et al. Pathophysiology, screening and treatment of ROP: a multi-disciplinary perspective[J]. Prog Retin Eye Res, 2018, 62: 77-119. DOI: 10.1016/j.preteyeres.2017.09.002.
11. Zhang Q, Qi Y, Chen L, et al. The relationship between anti-vascular endothelial growth factor and fibrosis in proliferative retinopathy: clinical and laboratory evidence[J]. Br J Ophthalmol, 2016, 100(10): 1443-1450. DOI: 10.1136/bjophthalmol-2015-308199.
12. Semeraro F, Morescalchi F, Parmeggiani F, et al. Systemic adverse drug reactions secondary to anti-VEGF intravitreal injection in patients with neovascular age-related macular degeneration[J]. Curr Vasc Pharmacol, 2011, 9(5): 629-646. DOI: 10.2174/157016111796642670.
13. Stahl A, Hellstrom A, Smith LE. Insulin-like growth factor-1 and anti-vascular endothelial growth factor in retinopathy of prematurity: has the time come?[J]. Neonatology, 2014, 106(3): 254-260. DOI: 10.1159/000365132.
14. Xiang N, Zhao MJ, Li XY, et al. Redundant mechanisms for vascular growth factors in retinopathy of prematurity in vitro[J]. Ophthalmic Res, 2011, 45(2): 92-101. DOI: 10.1159/000316134.
15. 尹雪, 楊暉, 傅征, 等. 早產兒視網膜病變抗VEGF治療后復發的危險因素分析[J]. 國際眼科雜志, 2020, 20(6): 1105-1108. DOI: 10.3980/j.issn.1672-5123.2020.6.40.Yin X, Yang H, Bo 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.
16. 阮鵬. 抗VEGF治療早產兒視網膜病變復發的影響因素分析[D]. 鄭州大學, 2021. DOI:10.27466/d.cnki.gzzdu.2021.002464.Ruan P. Analysis of factors influencing the recurrence of retinopathy of prematurity after anti-VEGF treatment[D]. Zhengzhou University, 2021. DOI:10.27466/d.cnki.gzzdu.2021.002464.
17. 陳宜, 馮婧, 孟憲芬, 等. 玻璃體腔注射雷珠單抗治療早產兒視網膜病變療效觀察[J]. 中華眼底病雜志, 2015, 31(1): 6-9. DOI: 10.3760/cma.j.issn.1005-1015.2015.01.003.Chen Y, Feng J, Meng XF, et al. Effects of ranibizumab in zone Ⅰ and zone Ⅱ retinopathy of prematurity patients[J]. Chin J Ocul Fundus Dis, 2015, 31(1): 6-9. DOI: 10.3760/cma.j.issn.1005-1015.2015.01.003.
18. Ittiara S, Blair MP, Shapiro MJ, et al. Exudative retinopathy and detachment: a late reactivation of retinopathy of prematurity after intravitreal bevacizumab[J]. J AAPOS, 2013, 17(3): 323-325. DOI: 10.1016/j.jaapos.2013.01.004.
19. Ells AL, Wesolosky JD, Ingram AD, et al. Low-dose ranibizumab as primary treatment of posterior type I retinopathy of prematurity[J]. Can J Ophthalmol, 2017, 52(5): 468-474. DOI: 10.1016/j.jcjo.2017.02.012.
20. Gunay M, Sukgen EA, Celik G, et al. Comparison of bevacizumab, ranibizumab, and laser photocoagulation in the treatment of retinopathy of prematurity in Turkey[J]. Curr Eye Res, 2017, 42(3): 462-469. DOI: 10.1080/02713683.2016.1196709.

Chinese Journal of Ocular Fundus Diseases

Clinical analysis and curative effect of reactivation of retinopathy of prematurity after intravitreous injection of ranibizumab

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