Neurodevelopmental Outcomes after Intravitreal Bevacizumab Therapy for Retinopathy of Prematurity

Abstract

Purpose: To evaluate the neurodevelopmental and ocular developmental outcomes in premature children who have undergone intravitreal bevacizumab injection (IVB) for treatment of type 1 retinopathy of prematurity (ROP).Design: Prospective case-control study.Participants: We enrolled 3 groups of premature patients: premature children who had no history of ROP (group 0), premature children with history of ROP without treatment (group 1), and premature children with ROP who had received a single IVB (0.625 mg; group 2).Methods: Ocular developmental assessment, including cycloplegic refractometry, axial length, Cardiff acuity, and neurodevelopmental assessment via the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley III), were performed at 1 to 3 years of age and were compared between groups.Main Outcome Measures: Ocular developmental outcomes and Bayley III scores.Results: A total of 148 patients (85 boys and 63 girls) were included. The mean age at assessment was 1.49AE0.59 years. Group 0 patients demonstrated significantly higher gestational age (GA), birth weight, and Apgar scores compared with group 1 and 2 patients. There were no significant differences between groups 1 and 2 in demographics or systemic risk factors except for lower GA in group 2. The cylindrical power was significantly larger in groups 1 and 2 compared with group 0. The spherical equivalent was significantly more myopic and the Cardiff acuity was significantly poorer in group 2 than in group 0. There were no significant differences between groups 1 and 2 in refractive status, axial length, or Cardiff acuity. Neurodevelopmental assessment using Bayley III showed no significant difference among the 3 groups in any aspect after adjusting for GA and other systemic risk factors. The risks for poor neurodevelopmental outcomes also were not significantly different.Conclusions: At the mean age of 1.5 years, children with prior history of IVB (group 2) showed similar refractive and visual outcomes and similar neurodevelopmental outcomes compared with premature patients with ROP without requirement of treatment (group 1), although there is a possibility that a small but clinically significant difference may not have been detected in the current study.

The systemic antiangiogenic effect of intravitreal aflibercept injection in a mouse model of retinopathy of prematurity

“…Therefore, the use of anti‐VEGF agents in infants potentially has adverse systemic effects on development because VEGF is one of the molecules needed for development 7,8 . Among clinical studies focused on the systemic adverse effects of intravitreal anti‐VEGF injection in ROP infants, 9‐14 some studies reported systemic adverse effects 9‐11 and others did not 12‐14 . Systemic adverse effects of intravitreal anti‐VEGF injection in ROP are difficult to assess from clinical data because: (1) the general status of ROP infants vary widely due to variation in their birth weights or gestational age, (2) the number of ROP infants requiring treatment is small, and (3) ROP infants in the control groups of clinical trials are treated with laser therapy or cryotherapy, which is highly invasive.…”

Translational Research in Retinopathy of Prematurity: From Bedside to Bench and Back Again

“…There are also concerns that anti-VEGF therapy, particularly IVB, may cause neurodevelopmental delay [ 39 , 40 , 159 ]. Although no consensus has been established because some reports indicate that IVB does not affect neurodevelopment [ 38 , 160 , 161 ], it is known that serum VEGF levels are significantly reduced for approximately 2 months after IVB [ 36 , 37 ]. VEGF is an essential molecule in brain homeostasis, as well as angiogenesis [ 162 , 163 ].…”

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

“…The fact that IVB can seep into the systemic circulation and may potentially affect brain development of the preterm infant is concerning. 7,8 Several retrospective studies [9][10][11][12][13] have assessed the risk of neurodevelopmental impairment (NDI) related to IVB therapy in preterm infants but reported conflicting results. In addition, the population of periviable infants who are at highest risk for posteriorly located ROP disease, and who could be the most vulnerable subjects for the adverse effects of anti-VEGF therapy, was adequately represented in only one study that showed higher death and developmental impairment in the bevacizumab-treated group.…”