Retinopathy of prematurity (ROP) is a vasoproliferative disorder that occurs in the developing retina of preterm infants. It is the leading cause of blindness in children,
1 with an incidence rate of approximately 30% in preterm infants born at or earlier than 32 weeks gestation.
2 Normal retinal vascularization begins during the 14th week of gestation. This process consists of two stages: vasculogenesis followed by angiogenesis. In the vasculogenesis stage, precursor cells of mesenchymal origin enter the retina through the optic disc. These cells are responsible for the growth of the main retinal vessels. In the angiogenesis stage, capillary vessels increase in number and extend out from the optic disc into the peripheral retina.
3 This process is tightly regulated by a complex network of angiogenic cytokines, extracellular matrix components, and growth factors. Vascular endothelial growth factor (VEGF) is an important component in this network and a major factor for the pathogenesis of ROP.
4 Therefore, the goals of treatment are to reduce the production of VEGF by the immature retina and to eliminate the abnormal growth of new vessels. Laser photocoagulation of the peripheral avascularized retina is the treatment standard for type I ROP, with a failure rate of approximately 9.1%.
5 Recently, intravitreal injection of the anti-VEGF antibody bevacizumab has been used as an off-label alternative therapy.
6–11 However, there are concerns regarding the pharmacokinetics and the short- and long-term safety to ocular and neurologic development. Vascular endothelial growth factor is necessary for the development of systemic neurons and blood vessels in premature infants,
12,13 and blockage of VEGF could potentially inhibit these processes. In adults, dose-dependent adverse effects from systemic bevacizumab-induced VEGF blockade have been reported, which include gastrointestinal perforations, wound-healing complications, hemorrhage, stroke or myocardial infarction, hypertension, proteinuria, and congestive heart failure.
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