Avastin (Bevacizumab) in Neonates: Treatment of Retinopathy of Prematurity
Avastin (bevacizumab) is given to neonatal babies specifically for the treatment of severe retinopathy of prematurity (ROP), particularly Type 1 ROP in Zone I or posterior Zone II, though it should be reserved for exceptional circumstances and compassionate use as it remains investigational with significant safety concerns. 1
Primary Indication
Retinopathy of prematurity (ROP) is the sole indication for bevacizumab use in neonates, specifically targeting:
- Stage 3 ROP in Zone I or posterior Zone II with plus disease 2, 3
- Type 1 ROP as defined by the Early Treatment for Retinopathy of Prematurity (ET-ROP) criteria 3
- Typically affects extremely premature infants weighing 515-1,100 grams at birth with gestational ages of 23-28 weeks 2, 3
Mechanism and Rationale
- Bevacizumab is a recombinant humanized monoclonal antibody that inhibits vascular endothelial growth factor (VEGF), blocking pathological neovascularization in the retina 4
- The typical intravitreal dose is 0.625 mg (0.025 mL) per eye, administered as a single bilateral injection 2, 3
- Treatment is usually given at 9-15 weeks of postnatal age (mean 11 weeks) 2
Critical Safety Concerns and Limitations
Why Extreme Caution Is Warranted
Bevacizumab should NOT be considered standard first-line therapy for the following reasons:
- Systemic absorption occurs: Intravitreal bevacizumab leaks into systemic circulation in animals and adult humans, raising serious concerns about effects on developing preterm infants 1
- Vascular growth factors are critical for organogenesis: VEGF plays essential roles in normal organ development, and systemic suppression could cause harm to multiple developing organ systems 1
- No visual outcomes reported: The landmark BEAT-ROP study did not report actual visual outcomes, only anatomical success 1
- Underpowered for safety assessment: Studies lack adequate power to assess longer-term safety in this vulnerable population 1
- Maternal-fetal transfer demonstrated: Animal studies show bevacizumab crosses placental barriers and transfers to developing fetuses in a dose-dependent manner via FcRn receptor binding 5
Current Evidence Quality
- Available studies are small case series (7-12 patients) without adequate long-term follow-up 2, 3
- The BEAT-ROP study had significant design issues and interpretation problems 1
- No randomized controlled trials with adequate power have established safety in neonates 1
When Bevacizumab Might Be Considered
Reserve for exceptional circumstances only:
- Failure of laser photocoagulation (the proven first-line therapy) 1, 3
- Anatomical situations where laser is technically impossible or extremely difficult 1
- Compassionate use situations with informed parental consent acknowledging investigational status 1
Standard of Care Remains Laser Therapy
Laser photocoagulation is the proven effective first-line treatment for all forms of ROP with:
- Established efficacy for preventing retinal detachment and vision loss 1
- Minimal systemic morbidity compared to anti-VEGF agents 1
- Decades of safety data in premature infants 1
Common Pitfalls to Avoid
- Do not use bevacizumab as routine first-line therapy: Despite promising short-term anatomical results, the lack of long-term safety data and potential for systemic harm makes this inappropriate 1
- Do not assume local injection means no systemic effects: Systemic absorption is documented and concerning in this population 1, 5
- Do not proceed without ophthalmology consultation: All ROP treatment decisions should involve specialists experienced in neonatal retinal disease 1
- Do not neglect informed consent discussions: Parents must understand the investigational nature and potential unknown risks 1