Review

Clinical research progress on ranibizumab in the treatment of retinopathy of prematurity

  • Chen Zhijun ,
  • Peng Jie ,
  • Zhang Xuerui ,
  • Zhao Peiquan
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  • Department of Ophthalmology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
Zhao Peiquan, E-mail: zhaopeiquan@xinhuamed.com.cn.

Received date: 2025-03-12

  Accepted date: 2025-05-21

  Online published: 2026-01-29

Supported by

National Natural Science Foundation of China(82201201);Special Project of Shanghai Municipal Health Commission for Clinical Research(20224Y0108);Clinical Research Fund of Xinhua Hospital, Shanghai Jiao Tong University School of Medicine(24XHCR04A);Project of Data Sharing and Emulation of Clinical Trials (CCS-DASET) for Ocular Fundus Diseases, Shanghai Second Round of "Three-Year Plan for Promoting Clinical Skills and Innovation in Municipal Hospitals (2023?2025)"(SHDC2024CRI011)

Abstract

Retinopathy of prematurity (ROP) is a retinal vascular proliferative fundus disease that occurs in premature infants with low birth weight. Currently, a widely used treatment is intravitreal injection of anti-vascular endothelial growth factor (VEGF) drugs. Ranibizumab is the only anti-VEGF drug approved by the National Medical Products Administration for the treatment of ROP in China. Ranibizumab is a humanized recombinant monoclonal antibody Fab fragment that can inhibit pathological neovascularization. A single intravitreal injection of ranibizumab is effective for active ROP lesions; but there is a high risk of recurrence, which usually requires multiple repeated injections. The long-term efficacy of ranibizumab can promote the development of retinal vascularization, but it may have certain effects on the retinal structure. Low-dose ranibizumab has been shown to achieve favorable therapeutic outcomes, which may be beneficial in improving the safety of the drug. For the safety of ranibizumab, compared with laser photocoagulation treatment, ranibizumab has a lower incidence of high myopia and structural abnormalities. However, further research is needed to evaluate its long-term systemic effects. Combination therapy with ranibizumab and supplementary laser photocoagulation, individualized treatment strategies, standardized follow-up systems, and the exploration of novel drug delivery routes are the future research directions. This article reviews the latest research on the treatment of ROP with ranibizumab, providing reference for clinical practice.

Cite this article

Chen Zhijun , Peng Jie , Zhang Xuerui , Zhao Peiquan . Clinical research progress on ranibizumab in the treatment of retinopathy of prematurity[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2026 , 46(2) : 227 -234 . DOI: 10.3969/j.issn.1674-8115.2026.02.012

References

[1] Chiang M F, Quinn G E, Fielder A R, et al. International classification of retinopathy of prematurity, third edition[J]. Ophthalmology, 2021, 128(10): e51-e68.
[2] Kim S J, Port A D, Swan R, et al. Retinopathy of prematurity: a review of risk factors and their clinical significance[J]. Surv Ophthalmol, 2018, 63(5): 618-637.
[3] The BOOST Ⅱ United Kingdom, Australia, and New Zealand Collaborative Groups. Oxygen saturation and outcomes in preterm infants[J]. N Engl J Med, 2013, 368(22): 2094-2104.
[4] Bental Y, Reichman B, Shiff Y, et al. Impact of maternal diabetes mellitus on mortality and morbidity of preterm infants (24?33 weeks' gestation)[J]. Pediatrics, 2011, 128(4): e848-e855.
[5] Li L, Gao Y L, Chen W, et al. Screening for retinopathy of prematurity in North China[J]. BMC Ophthalmol, 2022, 22(1): 251.
[6] Lyon J, Gagrani M, Hiasat J G, et al. Retrospective evaluation of Postnatal Growth and Retinopathy of Prematurity (G-ROP) and Colorado Retinopathy of Prematurity (CO-ROP) screening algorithms in University of Pittsburgh Medical Centers cohort[J]. J AAPOS, 2023, 27(5): 289-291.
[7] Zhou H P, Hashimoto Y, Araki F, et al. Recent trends in the cumulative incidence and intervention patterns of retinopathy of prematurity in Japan: a multicenter analysis, 2011?2020[J]. Retina, 2024, 44(2): 295-305.
[8] Wang S F, Liu J, Zhang X R, et al. Global, regional and national burden of retinopathy of prematurity among childhood and adolescent: a spatiotemporal analysis based on the Global Burden of Disease Study 2019[J]. BMJ Paediatr Open, 2024, 8(1): e002267.
[9] 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.
[10] Sabri K, Ells A L, Lee E Y, et al. Retinopathy of prematurity: a global perspective and recent developments[J]. Pediatrics, 2022, 150(3): e2021053924.
[11] Chen J, Stahl A, Hellstrom A, et al. Current update on retinopathy of prematurity: screening and treatment[J]. Curr Opin Pediatr, 2011, 23(2): 173-178.
[12] Lee A, Shirley M. Ranibizumab: a review in retinopathy of prematurity[J]. Paediatr Drugs, 2021, 23(1): 111-117.
[13] Jang J H. Characteristics of retinal vascularization in reactivated retinopathy of prematurity requiring treatment and clinical outcome after reinjection of ranibizumab[J]. Sci Rep, 2024, 14(1): 15647.
[14] Stahl A, Lepore D, Fielder A, et al. Ranibizumab versus laser therapy for the treatment of very low birthweight infants with retinopathy of prematurity (RAINBOW): an open-label randomised controlled trial[J]. Lancet, 2019, 394(10208): 1551-1559.
[15] Prajapati V, Choudhary T, Chauhan W, et al. Efficacy of a biosimilar ranibizumab monotherapy for the treatment of retinopathy of prematurity[J]. Indian J Ophthalmol, 2023, 71(2): 411-415.
[16] Zou Q, Zhu Y Q, Zhang F J, et al. Efficacy evaluation of intravitreal ranibizumab therapy for three types of retinopathy of prematurity[J]. Int J Ophthalmol, 2022, 15(5): 753-759.
[17] Aldebasi T, Guma M A, Bashir R, et al. Intravitreal ranibizumab injection for the treatment of retinopathy of prematurity[J]. Med Princ Pract, 2019, 28(6): 526-532.
[18] Strawbridge J, Cheng J Y, Gundlach B S, et al. Short-term reactivation of retinopathy of prematurity after primary ranibizumab treatment[J]. Retina, 2024, 44(11): 1945-1951.
[19] Sahinoglu-Keskek N, Akkoyun I, Torer B, et al. Predictive factors of early reactivation after ?ntravitreal ranibizumab in agressive retinopathy of prematurity[J]. J Fr Ophtalmol, 2025, 48(1): 104348.
[20] Zhang G M, Yang M M, Zeng J, et al. Comparison of intravitreal injection of ranibizumab versus laser therapy for zone Ⅱ treatment-requiring retinopathy of prematurity[J]. Retina, 2017, 37(4): 710-717.
[21] Sukgen E A, Ko?luk Y. Comparison of clinical outcomes of intravitreal ranibizumab and aflibercept treatment for retinopathy of prematurity[J]. Graefes Arch Clin Exp Ophthalmol, 2019, 257(1): 49-55.
[22] Patel N A, Acaba-Berrocal L A, Hoyek S, et al. Comparison in retreatments between bevacizumab and ranibizumab intravitreal injections for retinopathy of prematurity: a multicenter study[J]. Ophthalmology, 2023, 130(4): 373-378.
[23] Karkhaneh R, Khodabande A, Riazi-Eafahani M, et al. Efficacy of intravitreal bevacizumab for zone-Ⅱ retinopathy of prematurity[J]. Acta Ophthalmol, 2016, 94(6): e417-e420.
[24] Alyama? Sukgen E, ??mez A, Ko?luk Y, et al. The process of retinal vascularization after anti-VEGF treatment in retinopathy of prematurity: a comparison study between ranibizumab and bevacizumab[J]. Ophthalmologica, 2016, 236(3): 139-147.
[25] Meng Q Y, Cheng Y, Zhao M W, et al. The process of retinal vascularization in retinopathy of prematurity after ranibizumab treatment in China[J]. Int J Ophthalmol, 2019, 12(7): 1146-1150.
[26] Harper C A 3rd, Wright L M, Young R C, et al. Fluorescein angiographic evaluation of peripheral retinal vasculature after primary intravitreal ranibizumab for retinopathy of prematurity[J]. Retina, 2019, 39(4): 700-705.
[27] Xia F J, Lyu J, Peng J, et al. Repeated intravitreal ranibizumab for reactivated retinopathy of prematurity after intravitreal ranibizumab monotherapy: vascular development analysis[J]. Graefes Arch Clin Exp Ophthalmol, 2022, 260(9): 2837-2846.
[28] Zhang X R, Peng J, Yang Y, et al. Vascular development analysis: a study for tertiary anti-vascular endothelial growth factor therapy after second reactivation of retinopathy of prematurity[J]. Front Med, 2024, 11: 1421894.
[29] Cheng H X, Cao D, Qian J, et al. Refractive status and retinal morphology in children with a history of intravitreal ranibizumab for retinopathy of prematurity[J]. Eur J Pediatr, 2023, 182(7): 3121-3128.
[30] Hoppe C, Holt D G, Arnold B F, et al. Structural and refractive outcomes of intravitreal ranibizumab followed by laser photocoagulation for type 1 retinopathy of prematurity[J]. J Am Assoc Pediatr Ophthalmol Strabismus, 2022, 26(6): 305.e1-305.e6.
[31] Kubota H, Fukushima Y, Nandinanti A B, et al. Retinal blood vessel formation in the macula following intravitreal ranibizumab injection for aggressive retinopathy of prematurity[J]. Cureus, 2024, 16(5): e60005.
[32] 海峡两岸医药卫生交流协会眼科专业委员会小儿视网膜学组, 中华医学会眼科学分会眼底病学组. 早产儿视网膜病变玻璃体腔注射抗血管内皮生长因子药物治疗的专家共识[J]. 中华眼底病杂志, 2021, 37(11): 836-840.
  Pediatric Retinology Group of Ophthalmology Professional Committee of Cross Strait Medical and Health Exchange Association, Fundus Disease Group of Chinese Medical Association Ophthalmology Branch. Expert consensus on intravitreal injection of anti-vascular endothelial growth factor drugs for retinopathy of prematurity[J]. Chinese Journal of Ocular Fundus Diseases, 2021, 37(11): 836-840.
[33] Stahl A, Krohne T U, Eter N, et al. Comparing alternative ranibizumab dosages for safety and efficacy in retinopathy of prematurity: a randomized clinical trial[J]. JAMA Pediatr, 2018, 172(3): 278-286.
[34] Stahl A, Bründer M C, Lagrèze W A, et al. Ranibizumab in retinopathy of prematurity-one-year follow-up of ophthalmic outcomes and two-year follow-up of neurodevelopmental outcomes from the CARE-ROP study[J]. Acta Ophthalmol, 2022, 100(1): e91-e99.
[35] Marlow N, Stahl A, Lepore D, et al. 2-year outcomes of ranibizumab versus laser therapy for the treatment of very low birthweight infants with retinopathy of prematurity (RAINBOW extension study): prospective follow-up of an open label, randomised controlled trial[J]. Lancet Child Adolesc Health, 2021, 5(10): 698-707.
[36] Chen J, Hao Q F, Zhang J, et al. The efficacy and ocular safety following aflibercept, conbercept, ranibizumab, bevacizumab, and laser for retinopathy of prematurity: a systematic review and meta-analysis[J]. Ital J Pediatr, 2023, 49(1): 136.
[37] Wardati H J, Khadijah M, Nurul-Farhana M, et al. Comparison of intravitreal ranibizumab and laser photocoagulation in the treatment of type Ⅰ retinopathy of prematurity in Malaysia: a one-year follow-up study[J]. Cureus, 2024, 16(7): e63712.
[38] Kang H G, Choi E Y, Byeon S H, et al. Intravitreal ranibizumab versus laser photocoagulation for retinopathy of prematurity: efficacy, anatomical outcomes and safety[J]. Br J Ophthalmol, 2019, 103(9): 1332-1336.
[39] Zhang H T, Yang X, Zheng F F, et al. Changes in serum concentrations of vascular endothelial growth factors-A and B after intravitreal injection of ranibizumab and conbercept for retinopathy of prematurity[J]. Ophthalmologica, 2023, 246(2): 81-89.
[40] Tian Y, Fan Z X, Zeng X L, et al. Long-term follow-up of the cognitive function in children after intravitreal ranibizumab for retinopathy of prematurity[J]. Graefes Arch Clin Exp Ophthalmol, 2024, 262(10): 3117-3124.
[41] Chiang M C, Chen Y T, Kang E Y, et al. Neurodevelopmental outcomes for retinopathy of prematurity: a Taiwan premature infant follow-up network database study[J]. Am J Ophthalmol, 2023, 247: 170-180.
[42] Modrzejewska M, Nazwalska M. The long-term observation of the beneficial effects of treatment: 0.12 mg anti-VEGF monotherapy or anti-VEGF combined therapy and diode-laser in various stages of retinopathy of prematurity-series of cases[J]. J Clin Med, 2023, 12(17): 5644.
[43] Gangwe A B, Agrawal D, Gangrade A K, et al. Outcomes of early versus deferred laser after intravitreal ranibizumab in aggressive posterior retinopathy of prematurity[J]. Indian J Ophthalmol, 2021, 69(8): 2171-2176.
[44] Yoon J M, Shin D H, Kim S J, et al. Outcomes after laser versus combined laser and bevacizumab treatment for type 1 retinopathy of prematurity in zone Ⅰ[J]. Retina, 2017, 37(1): 88-96.
[45] Marlow N, Reynolds J D, Lepore D, et al. Ranibizumab versus laser therapy for the treatment of very low birthweight infants with retinopathy of prematurity (RAINBOW): five-year outcomes of a randomised trial[J]. EClinicalMedicine, 2024, 71:102567.
[46] Zhang W T, Liu H Y, Chen Y Y, et al. Intra-anterior chamber injection of ranibizumab in advanced pediatric vitreoretinal diseases[J]. JAMA Ophthalmol, 2024, 142(2): 133-139.
[47] Yaylaci S, Din? E, Ayd?n B, et al. Peptide nanofiber system for sustained delivery of anti-VEGF proteins to the eye vitreous[J]. Pharmaceutics, 2023, 15(4): 1264.
[48] Ranade S V, Wieland M R, Tam T, et al. The port delivery system with ranibizumab: a new paradigm for long-acting retinal drug delivery[J]. Drug Deliv, 2022, 29(1): 1326-1334.
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