抗VEGF药物玻璃体内注射治疗对早产儿视网膜病变神经系统发育的影响

Effect of anti-VEGF intravitreal injections on the development of nervous system in retinopathy of prematurity

早产儿视网膜病变(ROP)是以视网膜血管异常增生为主要病理特征的儿童致盲眼病。血管内皮生长因子(VEGF)是一种特异性刺激血管内皮细胞增生及新生血管形成的生长因子。早产儿视网膜局部缺血、缺氧环境促使眼内VEGF表达代偿性升高,进而诱导视网膜血管病理性生长。玻璃体内注射抗VEGF药物可抑制眼内VEGF的生物活性,从而延缓视网膜新生血管形成,可有效治疗ROP。然而,ROP患者常伴有血-视网膜屏障损伤,导致视网膜微环境稳态失衡,抗VEGF药物易透过血-视网膜屏障及血-脑屏障进入全身血液循环,可能导致ROP患儿神经系统发育异常。目前抗VEGF药物玻璃体内注射是否影响患儿神经系统发育仍是眼科研究的热点。本文就VEGF在ROP发病机制和神经发育中的作用以及抗VEGF药物玻璃体内注射对ROP患儿神经系统发育的影响进行综述,以期为临床合理、安全应用抗VEGF药物提供依据。

Retinopathy of prematurity(ROP)is a blinding eye disease characterized by abnormal proliferation of retinal blood vessels in children.Vascular endothelial growth factor(VEGF)can specifically stimulate retinal vascular endothelial cell proliferation and neovascularization.Retinal ischemia and hypoxia in preterm infants promote the compensatory increase of intraocular VEGF expression,and then induce the pathological growth of retinal vessels.The intravitreal injection of anti-VEGF drugs provides a new therapeutic way for ROP by inhibiting the biological activity of VEGF and delaying retinal neovascularization.However,the blood-retina barrier of children with ROP is likely to be destructed,which can cause the imbalanced homeostasis of the retinal microenvironment.The anti-VEGF drugs can cause irreversible damage to nerve cells through the blood-retina barrier and blood-brain barrier,which affects the development of the nervous system in children with ROP.At present,whether anti-VEGF drugs result in the abnormal development and functional changes of nervous system in premature infants remains unknown and attracts much attention.In this paper,the role of VEGF in the pathogenesis of ROP and neurodevelopment,as well as the effects of anti-VEGF drug intravitreal injections on the neurological development of children with ROP were reviewed to provide the clinical basis for the rational and safe application of anti-VEGF drugs.