The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Retina Consultants Houston, Houston, Texas.
Ophthalmology. 2014 Sep;121(9):1783-9. doi: 10.1016/j.ophtha.2014.03.021. Epub 2014 Apr 24.
To determine the effect of suppression of vascular endothelial growth factor (VEGF) by monthly injection of ranibizumab on posterior retinal nonperfusion (RNP) in patients with diabetic macular edema (DME).
Unplanned retrospective analysis of prospectively collected data from 2 randomized, sham injection-controlled, double-masked, multicenter clinical trials.
Six hundred sixty-six patients with DME.
An independent reading center measured the area of RNP on fluorescein angiograms obtained in the phase 3 RISE and RIDE trials.
The percentage of patients with no posterior RNP.
The percentage of patients with no posterior RNP decreased in the sham group between baseline and month 24, but remained relatively stable in the 2 ranibizumab groups. After month 24, the sham group crossed over to receive monthly injections of ranibizumab 0.5 mg, and the differences between the sham and ranibizumab groups were reduced. The percentage of patients who showed an increase in posterior RNP from baseline increased over time in all 3 groups, but at a faster rate in the sham group, resulting in statistically significant differences at every time point between months 3 (9.6% vs. 18.5%; P = 0.016) and 24 (16.1% vs. 37.6%; P<0.0001) for ranibizumab 0.5 mg versus sham and from months 6 (12.3% vs. 23.0%; P = 0.013) through 24 (15.0% vs. 37.6%; P<0.0001) for ranibizumab 0.3 mg. Initiation of ranibizumab in the sham group at month 24 was followed by reduction in the percentage of patients with an increase in posterior RNP from baseline at months 30 and 36, whereas the 2 ranibizumab groups continued their gradual rise.
Just as high VEGF levels contribute to progression of retinal nonperfusion in retinal vein occlusion, the same is true in patients with DME, suggesting that regardless of the underlying disease process, high levels of VEGF can cause closure of retinal vessels. However, our data also suggest that VEGF-induced worsening of retinal perfusion in DME is superimposed on another cause of more gradually worsening perfusion, possibly glucotoxicity. Thus, monthly injections of ranibizumab can slow, but not completely prevent, retinal capillary closure in patients with DME.
评估每月注射雷珠单抗抑制血管内皮生长因子（VEGF）对糖尿病黄斑水肿（DME）患者后极部视网膜无灌注（RNP）的影响。
对 2 项随机、假注射对照、双盲、多中心临床试验前瞻性收集的数据进行计划外回顾性分析。
666 例 DME 患者。
由独立的阅读中心在 RISE 和 RIDE 试验的 3 期荧光素眼底血管造影中测量 RNP 面积。
无后极部 RNP 的患者比例。
假治疗组患者的后极部 RNP 比例在基线至 24 个月时逐渐下降，但在 2 个雷珠单抗组中相对稳定。24 个月后，假治疗组交叉接受每月 0.5mg 雷珠单抗注射，假治疗组与雷珠单抗组之间的差异减小。所有 3 组患者的后极部 RNP 从基线开始的增加比例随时间逐渐增加，但假治疗组增加速度更快，导致在第 3 个月（9.6%比 18.5%；P=0.016）和第 24 个月（16.1%比 37.6%；P<0.0001）时雷珠单抗 0.5mg 与假治疗组之间以及在第 6 个月（12.3%比 23.0%；P=0.013）至第 24 个月（15.0%比 37.6%；P<0.0001）时雷珠单抗 0.3mg 与假治疗组之间存在统计学显著差异。假治疗组在第 24 个月开始使用雷珠单抗后，第 30 个月和第 36 个月时基线后极部 RNP 增加的患者比例减少，而 2 个雷珠单抗组继续逐渐增加。
正如高 VEGF 水平导致视网膜静脉阻塞的视网膜无灌注进展一样，在 DME 患者中也是如此，这表明无论潜在的疾病过程如何，高 VEGF 水平均可导致视网膜血管闭塞。然而，我们的数据还表明，DME 中 VEGF 诱导的视网膜灌注恶化叠加了另一种导致灌注逐渐恶化的原因，可能是糖毒性。因此，每月注射雷珠单抗可减缓，但不能完全阻止 DME 患者的视网膜毛细血管闭塞。
