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Refractive status and retinal morphology in children with a history of intravitreal ranibizumab for retinopathy of prematurity

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Abstract

This study investigated the characteristics of refractive status, visual acuity, and retinal morphology in children with a history of receiving intravitreal ranibizumab for retinopathy of prematurity (ROP). Children 4–6 years of age were enrolled and divided into the following four groups: group 1, children with a history of ROP who had been treated with intravitreal ranibizumab; group 2, children with a history of ROP who had not received any treatment; group 3, premature children without ROP; and group 4, full-term children. Refractive status, peripapillary retinal nerve fiber layer (RNFL), and macular thickness were measured. A total of 204 children were enrolled. In group 1, myopic shift was not noted, but poorer best corrected visual acuity (BCVA) and shorter axial length were observed. Significantly lower peripapillary RNFL thickness in the average total and superior quadrant, higher central subfield thickness, lower parafoveal retinal thickness in average total, superior, and nasal and temporal quadrants were observed in group 1 than in the other groups. The poor BCVA in patients with ROP was correlated with the lower RNFL thickness in the superior quadrant.

   Conclusion: Children with a history of type 1 ROP treated with ranibizumab did not show a myopic shift but did show abnormal retinal morphology and the poorest BCVA among all groups. We suggest that pediatric ophthalmologists should always pay attention to visual development in patients with ROP with a history of intravitreal ranibizumab.

What is Known:

• Anti-VEGF is efficiently and widely used in the treatment of type 1 retinopathy of prematurity (ROP), and different anti-VEGF agents are associated with different prevalence of myopia.

• Patients with ROP who receive treatment such as laser therapy or cryotherapy have abnormal macular development and retinal nerve fiber layer (RNFL) thickness.

What is New:

• Children with a history of ROP treated with intravitreal ranibizumab did not show a myopic shift but did show poor BCVA at 4–6 years of age.

• Abnormal macular morphology and lower peripapillary RNFL thickness were found in these children.

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Data availability

The data that support the findings of this study are available from the authors but restrictions apply to the availability of these data, which were used under license from the Children's Hospital of Nanjing Medical University for the current study, and so are not publicly available. Data are, however, available from the authors upon reasonable request and with permission from the Ethics Committee at the Children's Hospital of Nanjing Medical University.

References

  1. Hellstrom A, Smith LE, Dammann O (2013) Retinopathy of prematurity. Lancet 382:1445–1457

    Article  PubMed  PubMed Central  Google Scholar 

  2. Hartnett ME (2020) Retinopathy of prematurity: evolving treatment with anti-vascular endothelial growth factor. Am J Ophthalmol 218:208–213

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Lei C, Duan J, Ge G, Zhang M (2021) Association between neonatal hyperglycemia and retinopathy of prematurity: a meta-analysis. Eur J Pediatr 180:3433–3442

    Article  CAS  PubMed  Google Scholar 

  4. Agrawal G, Dutta S, Prasad R, Dogra MR (2021) Fetal oxidative stress, micronutrient deficiency and risk of retinopathy of prematurity: a nested case-control study. Eur J Pediatr 180:1487–1496

    Article  CAS  PubMed  Google Scholar 

  5. Mintz-Hittner HA, Geloneck MM (2016) Review of effects of anti-VEGF treatment on refractive error. Eye Brain 8:135–140

    PubMed  PubMed Central  Google Scholar 

  6. Hwang CK, Hubbard GB, Hutchinson AK, Lambert SR (2015) Outcomes after intravitreal bevacizumab versus laser photocoagulation for retinopathy of prematurity: a 5-year retrospective analysis. Ophthalmology 122:1008–1015

    Article  PubMed  Google Scholar 

  7. Wu WC, Lin RI, Shih CP, Wang NK, Chen YP, Chao AN, Chen KJ, Chen TL, Hwang YS, Lai CC, Huang CY, Tsai S (2012) Visual acuity, optical components, and macular abnormalities in patients with a history of retinopathy of prematurity. Ophthalmology 119:1907–1916

    Article  PubMed  Google Scholar 

  8. Fiess A, Janz J, Schuster AK, Kolb-Keerl R, Knuf M, Kirchhof B, Muether PS, Bauer J (2017) Macular morphology in former preterm and full-term infants aged 4 to 10 years. Graefes Arch Clin Exp Ophthalmol 255:1433–1442

    Article  CAS  PubMed  Google Scholar 

  9. Wang J, Spencer R, Leffler JN, Birch EE (2012) Characteristics of peripapillary retinal nerve fiber layer in preterm children. Am J Ophthalmol 153(850–855):e851

    Google Scholar 

  10. Park KA, Oh SY (2015) Retinal nerve fiber layer thickness in prematurity is correlated with stage of retinopathy of prematurity. Eye (Lond) 29:1594–1602

    Article  PubMed  Google Scholar 

  11. Quinn GE, Dobson V, Davitt BV, Hardy RJ, Tung B, Pedroza C, Good WV, Treatment E, for Retinopathy of Prematurity Cooperative G (2008) Progression of myopia and high myopia in the early treatment for retinopathy of prematurity study: findings to 3 years of age. Ophthalmology 115(1058–1064):e1051

    Google Scholar 

  12. Sen P, Wu WC, Chandra P, Vinekar A, Manchegowda PT, Bhende P (2020) Retinopathy of prematurity treatment: Asian perspectives. Eye (Lond) 34:632–642

    Article  PubMed  Google Scholar 

  13. Stahl A, Lepore D, Fielder A, Fleck B, Reynolds JD, Chiang MF, Li J, Liew M, Maier R, Zhu Q, Marlow N (2019) Ranibizumab versus laser therapy for the treatment of very low birthweight infants with retinopathy of prematurity (RAINBOW): an open-label randomised controlled trial. Lancet 394:1551–1559

    Article  CAS  PubMed  Google Scholar 

  14. Chen SN, Lian I, Hwang YC, Chen YH, Chang YC, Lee KH, Chuang CC, Wu WC (2015) Intravitreal anti-vascular endothelial growth factor treatment for retinopathy of prematurity: comparison between Ranibizumab and Bevacizumab. Retina 35:667–674

    Article  CAS  PubMed  Google Scholar 

  15. Lin CJ, Tsai YY (2016) Axial length, refraction, and retinal vascularization 1 year after ranibizumab or bevacizumab treatment for retinopathy of prematurity. Clin Ophthalmol 10:1323–1327

    Article  PubMed  PubMed Central  Google Scholar 

  16. Chen YC, Chen SN, Yang BC, Lee KH, Chuang CC, Cheng CY (2018) Refractive and biometric outcomes in patients with retinopathy of prematurity treated with intravitreal injection of ranibizumab as compared with bevacizumab: a clinical study of correction at three years of age. J Ophthalmol 2018:4565216

    Article  PubMed  PubMed Central  Google Scholar 

  17. Kimyon S, Mete A (2018) Comparison of Bevacizumab and Ranibizumab in the Treatment of Type 1 Retinopathy of Prematurity Affecting Zone 1. Ophthalmologica 240:99–105

    Article  CAS  PubMed  Google Scholar 

  18. Ecsedy M, Szamosi A, Karko C, Zubovics L, Varsanyi B, Nemeth J, Recsan Z (2007) A comparison of macular structure imaged by optical coherence tomography in preterm and full-term children. Invest Ophthalmol Vis Sci 48:5207–5211

    Article  PubMed  Google Scholar 

  19. Early treatment diabetic retinopathy study research group (1991) Early Treatment Diabetic Retinopathy Study design and baseline patient characteristics. ETDRS report number 7. Ophthalmology 98:741–756

  20. Laws F, Laws D, Clark D (1997) Cryotherapy and laser treatment for acute retinopathy of prematurity: refractive outcomes, a longitudinal study. Br J Ophthalmol 81:12–15

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Mueller B, Salchow DJ, Waffenschmidt E, Joussen AM, Schmalisch G, Czernik C, Buhrer C, Schunk KU, Girschick HJ, Winterhalter S (2017) Treatment of type I ROP with intravitreal bevacizumab or laser photocoagulation according to retinal zone. Br J Ophthalmol 101:365–370

    CAS  PubMed  Google Scholar 

  22. Marlow N, Stahl A, Lepore D, Fielder A, Reynolds JD, Zhu Q, Weisberger A, Stiehl DP, Fleck B, group Ri, (2021) 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. Lancet Child Adolesc Health 5:698–707

    Article  CAS  PubMed  Google Scholar 

  23. Meng Q, Cheng Y, Wu X, Zhao D, Zhao M, Liang J (2020) Refractive error outcomes after intravitreal ranibizumab for retinopathy of prematurity. Clin Exp Optom 103:495–500

    Article  PubMed  Google Scholar 

  24. Wang J, Ren X, Shen L, Yanni SE, Leffler JN, Birch EE (2013) Development of refractive error in individual children with regressed retinopathy of prematurity. Invest Ophthalmol Vis Sci 54:6018–6024

    Article  PubMed  PubMed Central  Google Scholar 

  25. Mao J, Lao J, Liu C, Wu M, Yu X, Shao Y, Zhu L, Chen Y, Shen L (2019) Factors that influence refractive changes in the first year of myopia development in premature infants. J Ophthalmol 2019:7683749

    Article  PubMed  PubMed Central  Google Scholar 

  26. Wang Y, Pi LH, Zhao RL, Zhu XH, Ke N (2020) Refractive status and optical components of premature babies with or without retinopathy of prematurity at 7 years old. Transl Pediatr 9:108–116

    Article  PubMed  PubMed Central  Google Scholar 

  27. Pueyo V, Gonzalez I, Altemir I, Perez T, Gomez G, Prieto E, Oros D (2015) Microstructural changes in the retina related to prematurity. Am J Ophthalmol 159:797–802

    Article  PubMed  Google Scholar 

  28. Cheung N, Tong L, Tikellis G, Saw SM, Mitchell P, Wang JJ, Wong TY (2007) Relationship of retinal vascular caliber with optic disc diameter in children. Invest Ophthalmol Vis Sci 48:4945–4948

    Article  PubMed  Google Scholar 

  29. Lim LS, Saw SM, Cheung N, Mitchell P, Wong TY (2009) Relationship of retinal vascular caliber with optic disc and macular structure. Am J Ophthalmol 148:368–375

    Article  PubMed  Google Scholar 

  30. Duggan TJ, Cai CL, Aranda JV, Beharry KD (2021) Acute and chronic effects of intravitreal bevacizumab on lung biomarkers of angiogenesis in the rat exposed to neonatal intermittent hypoxia. Exp Lung Res 47:121–135

    CAS  PubMed  Google Scholar 

  31. Morin J, Luu TM, Superstein R, Ospina LH, Lefebvre F, Simard MN, Shah V, Shah PS, Kelly EN, Canadian Neonatal N, the Canadian Neonatal Follow-Up Network I (2016) Neurodevelopmental outcomes following bevacizumab injections for retinopathy of prematurity. Pediatrics 137

  32. Liang L, Yang Y, Bu S, Lu F (2021) Case report: a case of cotton-wool spots after intravitreal injection of Conbercept in an infant with Incontinentia pigmenti. Front Med (Lausanne) 8:761398

    Article  PubMed  Google Scholar 

  33. Calzetti G, Mora P, Borrelli E, Sacconi R, Ricciotti G, Carta A, Gandolfi S, Querques G (2021) Short-term changes in retinal and choroidal relative flow volume after anti-VEGF treatment for neovascular age-related macular degeneration. Sci Rep 11:23723

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Lee YS, Chang SHL, Wu SC, See LC, Chang SH, Yang ML, Wu WC (2018) The inner retinal structures of the eyes of children with a history of retinopathy of prematurity. Eye (Lond) 32:104–112

    Article  PubMed  Google Scholar 

  35. Hansen RM, Moskowitz A, Akula JD, Fulton AB (2017) The neural retina in retinopathy of prematurity. Prog Retin Eye Res 56:32–57

    Article  CAS  PubMed  Google Scholar 

  36. Yuodelis C, Hendrickson A (1986) A qualitative and quantitative analysis of the human fovea during development. Vision Res 26:847–855

    Article  CAS  PubMed  Google Scholar 

  37. Maldonado RS, O’Connell RV, Sarin N, Freedman SF, Wallace DK, Cotten CM, Winter KP, Stinnett S, Chiu SJ, Izatt JA, Farsiu S, Toth CA (2011) Dynamics of human foveal development after premature birth. Ophthalmology 118:2315–2325

    Article  PubMed  Google Scholar 

  38. Dong L, Kang YK, Li Y, Wei WB, Jonas JB (2020) Prevalence and time trends of myopia in children and adolescents in China: A Systemic Review and Meta-Analysis. Retina 40:399–411

    Article  PubMed  Google Scholar 

  39. Fiess A, Christian L, Janz J, Kolb-Keerl R, Knuf M, Kirchhof B, Muether PS, Bauer J, Prematurity Eye Study G (2017) Functional analysis and associated factors of the peripapillary retinal nerve fibre layer in former preterm and full-term infants. Br J Ophthalmol 101:1405–1411

    Article  Google Scholar 

  40. Fu Z, Hong H, Su Z, Lou B, Pan CW, Liu H (2020) Global prevalence of amblyopia and disease burden projections through 2040: a systematic review and meta-analysis. Br J Ophthalmol 104:1164–1170

    Article  PubMed  Google Scholar 

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Funding

This study was supported by the National Key R&D Program of China (2019YFC0840607), the National Science and Technology Major Project of China (2017ZX09304010), and the Program of the National Natural Science Foundation of China (82000908).

Author information

Author notes

  1. Haixia Cheng, Di Cao and Jing Qian have contributed equally to this work.

Authors and Affiliations

  1. Department of Ophthalmology, Children’s Hospital of Nanjing Medical University, Nanjing, Jiangsu, China

    Haixia Cheng & Jing Qian

  2. Department of Ophthalmology, Shanghai General Hospital of Nanjing Medical University, Shanghai, China

    Haixia Cheng, Di Cao & Zhi Zheng

  3. Department of Quality Management, Children’s Hospital of Nanjing Medical University, Nanjing, Jiangsu, China

    Wei Gu

  4. Department of Ophthalmology, Shanghai General Hospital; National Clinical Research Center for Eye Diseases; Shanghai Key Laboratory of Ocular Fundus Diseases; Shanghai Engineering Center for Visual Science and Photomedicine; Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, No. 85, Wujin Road, Hongkou District, Shanghai, China

    Zhi Zheng & Mingming Ma

  5. Department of Ophthalmology, Wuxi Maternity and Child Health Care Hospital, Women’s Hospital of Jiangnan University, Jiangnan University, Wuxi, Jiangsu, China

    Di Cao

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  1. Haixia Cheng
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Contributions

All authors listed above have met at least one of the requirements for authorship. Zhi Zheng and Mingming Ma had final responsibility for the decision to submit for publication. Haixia Cheng was the leading study investigator.

Corresponding authors

Correspondence to Zhi Zheng or Mingming Ma.

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Ethics approval

This study was conducted in accordance with the Declaration of Helsinki and was approved by the institutional review board of the Children’s Hospital of Nanjing Medical University. Informed consent was obtained from a parent or guardian of each participant.

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The authors declare no competing interests.

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Communicated by Piet Leroy.

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Cheng, H., Cao, D., Qian, J. et al. Refractive status and retinal morphology in children with a history of intravitreal ranibizumab for retinopathy of prematurity. Eur J Pediatr 182, 3121–3128 (2023). https://doi.org/10.1007/s00431-023-04965-7

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