Mintz-Hittner研究了玻璃体内注射贝伐单抗（Bevacizumab）对早产儿3+期视网膜病变的疗效。结果发现，贝伐单抗与传统激光疗法相比，能减少此类患儿视网膜病变的复发率，同时尽可能保留了视网膜本身的结构，宜于患儿日后的视力发育，是ROP治疗上的一大突破。Reynolds从有效性、安全性及实用性等方面对该研究做了较高的评价。
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早产儿视网膜病变（retinopathy of prematurity, ROP）是视网膜新生血管生长异常导致视网膜发育的异常。毛细血管床的血管提前收缩甚至闭塞可导致新生血管长入玻璃体，视网膜水肿、出血、纤维化，甚至牵拉而导致视网膜脱离。病变的最终阶段可致盲。ROP是世界范围内婴幼儿致盲的首要原因，患儿多为妊娠31周以下，出生体重不足1250g。早产、出生低体重和吸高浓度氧为已知的发病因素。
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人胚视网膜血管在16周时开始从视神经处向前生长，40周时达视网膜颞缘。早产儿视网膜血管尚未发育完全，出生后继续发育，由于其眼球发育尚未臻完善，中央存在过大的无血管区，正常情况下该血管仍需继续生长，并分化为毛细血管。这些血管对高浓度氧气和缺氧都高度敏感，可引起血管闭塞和收缩，并形成(病理性的)新生血管，即可导致早产儿视网膜病变(ROP)的发生。不同病程ROP表现各异，国际ROP会议制定的分类标准如下——
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1．定位
I区：以视盘为中心，以视盘至黄斑中心凹的两倍距离为半径划圆，圆内区域为I区。
II区：从I区向外直到鼻侧视网膜周边部划圆，此环形区域为II区。
III 区： II区以外剩下的颞侧半月形区为III区，该区域最常发生ROP。
2．范围
以累计眼底的钟点数计。 canada pharmacy cheap viagra cialis dosage
3．病程分期
1期：视网膜的有血管区和无血管区之间产生一条细的分界线。
2期：分界线发展成凸入玻璃体的嵴。
3期：嵴上视网膜外纤维血管增生伸向玻璃体。
4期：纤维血管膜牵拉部分视网膜脱离，以累及黄斑与否分别称4A及4B期。
5期：全视网膜脱离，不同程度的漏斗状。
“附加病变”(Plus diseases)：后极部视网膜血管发生扩张迂曲，如3+期，意味3期的基础上加上后极部视网膜动静脉血管发生扩张迂曲，提示病变向严重进展。
不同时期的ROP对应不同的氧浓度、血管内皮生长因子（VEGF）和新生血管活动。详情点击原图查看。
冷冻疗法、激光疗法先后用于治疗ROP，但由于前者导致整层眼睛结构的瘢痕增厚，后者导致视网膜的瘢痕增厚，均未达理想效果。随后抗VEGF剂开始被尝试用于治疗ROP，主要是对3+、4、5期患儿玻璃体内注射贝伐单抗（一种抗VEGF剂）。贝伐单抗起到抑制纤维血管增生的作用，并且，只在患儿角膜缘留下针眼的疤痕，不会遗留视野缺损，看似优于传统疗法。那么，这种疗法是否真的见效呢？Mintz-Hittner进行了临床随机对照试验，对比玻璃体内注射贝伐单抗和传统激光疗法对早产儿3+期视网膜病变的疗效。
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研究结果发现，3+期ROP患儿中使用贝伐单抗的实验组比对照组较少复发视网膜病变，其中病变在I区的患儿发病率具有统计学差异，而II区的患儿没有。同时该疗法尽可能的保留了视网膜本身的结构，见原图，宜于患儿日后的视力发育，是ROP治疗上的一大突破。Reynolds从有效性、安全性及实用性等方面对该研究做了评价。
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Reynolds肯定了贝伐单抗治疗ROP的有效性，复发率低且几乎不遗留眼部结构异常。另外，玻璃体内注射贝伐单抗费用便宜，对操作人员技术要求低，便于推广，具有很高的实用性。至于贝伐单抗对于眼睛局部的副作用，我们基本上可以放心，它至少和传统的激光治疗一样安全。但是，对于安全性，我们需要警惕贝伐单抗对于全身系统的作用，毕竟这种抗肿瘤药是可以进入循环系统的，这有待于大规模、长期的进一步研究。另外，仍要注意选择注射药物的时机，过早会干涉视网膜必要的血管生成，过晚可能导致早期视网膜脱离，因此该法对治疗时机把握的要求较高，并且有复发的可能，需要长期随访。
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玻璃体内注射贝伐单抗为早产视网膜病变患儿提供了新的选择，目前尚需研究的是针对不同时期病变选择合适的药物浓度，还需要制定规范的随访和复发处理制度。正是科学家的一步步努力让早产儿视网膜病变患儿拥抱光明。
来源 Efficacy of Intravitreal Bevacizumab for Stage 3+ Retinopathy of Prematurity, Helen A. Mintz-Hittner, M.D., N Engl J Med 2011; 364:603-615February 17, 2011
Bevacizumab for Retinopathy of Prematurity, James D. Reynolds, M.D. N Engl J Med 2011; 364:677-678February 17, 2011