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Am J Perinatol 2021; 38(11): 1158-1166
DOI: 10.1055/s-0040-1710556
Original Article

Bevacizumab for Retinopathy of Prematurity: 2-Year Neurodevelopmental Follow-up

Michael Zayek
1   Division of Neonatology, Department of Pediatrics, University of South Alabama, Mobile, Alabama
,
Kaitlyn Parker
1   Division of Neonatology, Department of Pediatrics, University of South Alabama, Mobile, Alabama
,
Monika Rydzewska
2   Department of Pediatrics, Neonatal Medicine, Crozer-Keystone Health System, Upland, Pennsylvania
,
Aref Rifai
3   Retina Center of Pensacola, Pensacola, Florida
,
Ramachandra Bhat
1   Division of Neonatology, Department of Pediatrics, University of South Alabama, Mobile, Alabama
,
Fabien Eyal
1   Division of Neonatology, Department of Pediatrics, University of South Alabama, Mobile, Alabama
› Author Affiliations Funding None.
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Abstract

Objective This study aimed to determine whether infants who were treated with intravitreal bevacizumab (IVB) for retinopathy of prematurity (ROP) were at higher risk of death or neurodevelopmental impairment (NDI) when compared with infants who were not treated with IVB (Laser only).

Study Design This retrospective study included 146 infants born from 2009 through 2016 with a birth weight (BW) <1,000 g, gestational age <27 weeks, and required ROP therapy. Death and NDI rates were assessed at 18 to 24 months' corrected age.

Results Rates of death or severe NDI were 62 and 53% in the IVB (n = 61) and Laser only (n = 85) groups, respectively. This difference was not statistically different despite sample selection bias in treating growth-restricted infants with IVB, BW (median [IQR]) was 481 (420–583) versus 547 (473–640) g in IVB and Laser only groups, respectively, p = 0.003. The adjusted odds ratio and 95% confidence interval of death or severe NDI was 0.86 (0.33–2.20).

Conclusion Bevacizumab therapy for ROP did not affect survival and neurodevelopment of extremely preterm infants.

Key Points

  • Intravitreal bevacizumab therapy for retinopathy of prematurity may be safe in periviable preterm infants.

  • Intravitreal bevacizumab therapy does not increase mortality rate in periviable preterm infants.

  • Intravitreal bevacizumab therapy does not increase adverse neurodevelopmental outcome in periviable infants.

Keywords

preterm infants - extremely low birth weight - neurodevelopmental outcome - laser photocoagulation - Bevacizumab and retinopathy of prematurity


Publication History

Received: 20 January 2020

Accepted: 09 April 2020

Article published online:
23 May 2020

© 2020. Thieme. All rights reserved.

Thieme Medical Publishers, Inc.
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  • References

  • 1 Mintz-Hittner HA. Treatment of retinopathy of prematurity with vascular endothelial growth factor inhibitors. Early Hum Dev 2012; 88 (12) 937-941
    CrossrefPubMedGoogle Scholar
  • 2 Cryotherapy for Retinopathy of Prematurity Cooperative Group. Multicenter trial of cryotherapy for retinopathy of prematurity. Preliminary results. Arch Ophthalmol 1988; 106 (04) 471-479
    CrossrefPubMedGoogle Scholar
  • 3 Early Treatment For Retinopathy Of Prematurity Cooperative Group. Revised indications for the treatment of retinopathy of prematurity: results of the early treatment for retinopathy of prematurity randomized trial. Arch Ophthalmol 2003; 121 (12) 1684-1694
    CrossrefPubMedGoogle Scholar
  • 4 Flynn JT, Chan-Ling T. Retinopathy of prematurity: two distinct mechanisms that underlie zone 1 and zone 2 disease. Am J Ophthalmol 2006; 142 (01) 46-59
    CrossrefPubMedGoogle Scholar
  • 5 Naug HL, Browning J, Gole GA, Gobé G. Vitreal macrophages express vascular endothelial growth factor in oxygen-induced retinopathy. Clin Exp Ophthalmol 2000; 28 (01) 48-52
    CrossrefPubMedGoogle Scholar
  • 6 Mintz-Hittner HA, Kennedy KA, Chuang AZ. BEAT-ROP Cooperative Group. Efficacy of intravitreal bevacizumab for stage 3+ retinopathy of prematurity. N Engl J Med 2011; 364 (07) 603-615
    CrossrefPubMedGoogle Scholar
  • 7 Wu W-C, Shih C-P, Lien R. et al. Serum vascular endothelialgrowth factor after bevacizumab or ranibizumab treatment for retinopathy of prematurity. Retina 2017; 37 (04) 694-701
    CrossrefPubMedGoogle Scholar
  • 8 Malik S, Vinukonda G, Vose LR. et al. Neurogenesis continues in the third trimester of pregnancy and is suppressed by premature birth. J Neurosci 2013; 33 (02) 411-423
    CrossrefPubMedGoogle Scholar
  • 9 Fan YY, Huang YS, Huang CY. et al. Neurodevelopmental outcomes after intravitreal bevacizumab therapy for petinopathy of prematurity: a prospective case-control study. Ophthalmology 2019; 126 (11) 1567-1577
    CrossrefPubMedGoogle Scholar
  • 10 Morin J, Luu TM, Superstein R. et al; Canadian Neonatal Network and the Canadian Neonatal Follow-Up Network Investigators. Neurodevelopmental outcomes following bevacizumab injections for retinopathy of prematurity. Pediatrics 2016; 137 (04) e20153218
    CrossrefPubMedGoogle Scholar
  • 11 Lien R, Yu MH, Hsu KH. et al. Neurodevelopmental outcomes in infants with retinopathy of prematurity and bevacizumab treatment. PLoS One 2016; 11 (01) e0148019
    CrossrefPubMedGoogle Scholar
  • 12 Natarajan G, Shankaran S, Nolen TL. et al. Neurodevelopmental outcomes of preterm infants with retinopathy of prematurity by treatment. Pediatrics 2019; 144 (02) e20183537
    CrossrefPubMedGoogle Scholar
  • 13 Raghuram K, Isaac M, Yang J. et al. Neurodevelopmental outcomes in infants treated with intravitreal bevacizumab versus laser. J Perinatol 2019; 39 (09) 1300-1308
    CrossrefPubMedGoogle Scholar
  • 14 Zayek MM, Trimm RF, Hamm CR, Peevy KJ, Benjamin JT, Eyal FG. The limit of viability: a single regional unit's experience. Arch Pediatr Adolesc Med 2011; 165 (02) 126-133
    CrossrefPubMedGoogle Scholar
  • 15 Alexander GR, Himes JH, Kaufman RB, Mor J, Kogan M. A United States national reference for fetal growth. Obstet Gynecol 1996; 87 (02) 163-168
    CrossrefPubMedGoogle Scholar
  • 16 American College of Obstetricians and Gynecologists; Society for Maternal-Fetal Medicine. Obstetric Care consensus No. 6: Periviable Birth. Obstet Gynecol 2017;130(4):e187–e199
    PubMed
  • 17 Papile LA, Burstein J, Burstein R, Koffler H. Incidence and evolution of subependymal and intraventricular hemorrhage: a study of infants with birth weights less than 1,500 gm. J Pediatr 1978; 92 (04) 529-534
    CrossrefPubMedGoogle Scholar
  • 18 Rosenbaum P, Paneth N, Leviton A. et al. A report: the definition and classification of cerebral palsy April 2006. Dev Med Child Neurol Suppl 2007; 109 (suppl): 8-14
    PubMedGoogle Scholar
  • 19 Tyson JE, Parikh NA, Langer J, Green C, Higgins RD. National Institute of Child Health and Human Development Neonatal Research Network. Intensive care for extreme prematurity--moving beyond gestational age. N Engl J Med 2008; 358 (16) 1672-1681
    CrossrefPubMedGoogle Scholar
  • 20 Scott JS, Freese J. Regression Models for Categorical Dependent Variables Using Stata, 2nd ed. College Station, TX: Stata Press Corp; 2006: 112-113
    Google Scholar
  • 21 Kennedy KA, Mintz-Hittner HA. BEAT-ROP Cooperative Group. Medical and developmental outcomes of bevacizumab versus laser for retinopathy of prematurity. J AAPOS 2018; 22 (01) 61-65.e1
    CrossrefPubMedGoogle Scholar
  • 22 Rysavy MA, Li L, Bell EF. et al; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Between-hospital variation in treatment and outcomes in extremely preterm infants. N Engl J Med 2015; 372 (19) 1801-1811
    CrossrefPubMedGoogle Scholar
  • 23 Gschließer A, Stifter E, Neumayer T. et al. Inter-expert and intra-expert agreement on the diagnosis and treatment of retinopathy of prematurity. Am J Ophthalmol 2015; 160 (03) 553-560.e3
    CrossrefPubMedGoogle Scholar
  • 24 Mourani PM, Sontag MK, Younoszai A. et al. Early pulmonary vascular disease in preterm infants at risk for bronchopulmonary dysplasia. Am J Respir Crit Care Med 2015; 191 (01) 87-95
    CrossrefPubMedGoogle Scholar
  • 25 Check J, Gotteiner N, Liu X. et al. Fetal growth restriction and pulmonary hypertension in premature infants with bronchopulmonary dysplasia. J Perinatol 2013; 33 (07) 553-557
    CrossrefPubMedGoogle Scholar
  • 26 Whyte RK, Kirpalani H, Asztalos EV. et al; PINTOS Study Group. Neurodevelopmental outcome of extremely low birth weight infants randomly assigned to restrictive or liberal hemoglobin thresholds for blood transfusion. Pediatrics 2009; 123 (01) 207-213
    CrossrefPubMedGoogle Scholar
  • 27 Geloneck MM, Chuang AZ, Clark WL. et al; BEAT-ROP Cooperative Group. Refractive outcomes following bevacizumab monotherapy compared with conventional laser treatment: a randomized clinical trial. JAMA Ophthalmol 2014; 132 (11) 1327-1333
    CrossrefPubMedGoogle Scholar
  • 28 Chen YC, Chen SN, Yang BC, Lee KH, Chuang CC, Cheng CY. 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; 2018: 4565216
    PubMedGoogle Scholar
  • 29 Han J, Kim SE, Lee SC, Lee CS. Low dose versus conventional dose of intravitreal bevacizumab injection for retinopathy of prematurity: a case series with paired-eye comparison. Acta Ophthalmol 2018; 96 (04) e475-e478
    CrossrefPubMedGoogle Scholar
  • 30 Hu J, Blair MP, Shapiro MJ, Lichtenstein SJ, Galasso JM, Kapur R. Reactivation of retinopathy of prematurity after bevacizumab injection. Arch Ophthalmol 2012; 130 (08) 1000-1006
    CrossrefPubMedGoogle Scholar
  • 31 Mireskandari K, Adams GG, Tehrani NN. Recurrence of retinopathy of prematurity following bevacizumab monotherapy: is it only the tip of the iceberg?. JAMA Ophthalmol 2013; 131 (04) 544-545
    CrossrefPubMedGoogle Scholar
  • 32 Mintz-Hittner HA, Kretzer FL. Postnatal retinal vascularization in former preterm infants with retinopathy of prematurity. Ophthalmology 1994; 101 (03) 548-558
    CrossrefPubMedGoogle Scholar
  • 33 Toy BC, Schachar IH, Tan GSW, Moshfeghi DM. Chronic vascular arrest as a predictor of bevacizumab treatment failure in retinopathy of prematurity. Ophthalmology 2016; 123 (10) 2166-2175
    CrossrefPubMedGoogle Scholar
  • 34 Fierson WM. American Academy of Pediatrics Section on Ophthalmology; American Academy of Ophthalmology; American Association for Pediatric Ophthalmology and Strabismus; American Association of Certified Orthoptists. Screening examination of premature infants for retinopathy of prematurity. Pediatrics 2018; 142 (06) e20183061
    CrossrefPubMedGoogle Scholar