Feltgen Nicolas, Ogura Yuichiro, Boscia Francesco, Holz Frank G, Korobelnik Jean-Francois, Brown David M, Heier Jeffrey S, Stemper Brigitte, Rittenhouse Kay D, Asmus Friedrich, Ahlers Christiane, Vitti Robert, Saroj Namrata, Mitchell Paul
Department of Ophthalmology, University of Göttingen, Göttingen, Germany.
Department of Ophthalmology and Visual Science, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
Ophthalmol Retina. 2019 Jul;3(7):553-560. doi: 10.1016/j.oret.2019.02.010. Epub 2019 Feb 27.
To evaluate the impact of baseline retinal capillary nonperfusion (RNP) and macular retinal capillary nonperfusion (MNP) status on outcomes at week 24 (W24).
Post hoc analyses of 2 phase 3, randomized, double-masked, multicenter, sham-controlled studies.
Three hundred sixty-six patients with macular edema secondary to central retinal vein occlusion randomized in COPERNICUS and GALILEO.
We randomized patients 3:2 to receive intravitreal aflibercept 2 mg every 4 weeks or sham injections until W24. RNP and MNP were assessed by a masked independent reading center.
Proportion of patients with 10 disc areas (DA) or more of RNP and any degree of MNP at W24, relative risks of 10 DA or more of RNP or any degree of MNP at W24 developing, change from baseline in best-corrected visual acuity (BCVA) and central retinal thickness (CRT) by baseline RNP and MNP status, and relationship between baseline RNP and MNP status.
At baseline, 24.6% of patients showed 10 DA or more of RNP and 72.6% showed MNP, regardless of baseline RNP status. At W24, the pooled proportions of patients in the intravitreal aflibercept and sham groups with 10 DA or more of RNP were 11.6% and 29.0%, respectively (P = 0.0001); the respective proportions with any degree of MNP were 61.2% and 79.5% (P = 0.0008). Relative risks and 95% confidence intervals for intravitreal aflibercept versus sham were 0.4 (0.25-0.62) for 10 DA or more of RNP and 0.8 (0.68-0.90) for MNP, indicating a lower risk for these outcomes with intravitreal aflibercept than with sham. Mean BCVA change was greater in intravitreal aflibercept- versus sham-treated eyes, with less than 10 DA and 10 DA or more of RNP at baseline (+17.5 vs. +0.8 letters and +18.3 vs. -4.1 letters, respectively) and with and without baseline MNP (+15.7 vs. +0.3 letters and +17.1 vs. +0.4 letters, respectively). Agreement between baseline RNP and MNP status was low (κ = 0.12). The proportions of patients with 1 or more ocular serious adverse event in the intravitreal aflibercept- and sham-treated groups, respectively, were 3.2% and 11.3%.
At W24, visual and anatomic improvements, including perfusion status, were greater in eyes treated with intravitreal aflibercept than in eyes treated with sham, regardless of baseline RNP or MNP status.
评估基线视网膜毛细血管无灌注（RNP）和黄斑视网膜毛细血管无灌注（MNP）状态对第24周（W24）结局的影响。
对两项3期随机、双盲、多中心、假手术对照研究进行事后分析。
366例继发于视网膜中央静脉阻塞的黄斑水肿患者，这些患者在哥白尼（COPERNICUS）和伽利略（GALILEO）研究中被随机分组。
我们按3:2将患者随机分组，每4周接受一次玻璃体内注射阿柏西普2mg或假注射，直至W24。RNP和MNP由一个独立的盲态阅读中心进行评估。
在W24时，RNP达到10个视盘面积（DA）或更多且存在任何程度MNP的患者比例；在W24时出现10 DA或更多RNP或任何程度MNP的相对风险；根据基线RNP和MNP状态，最佳矫正视力（BCVA）和视网膜中央厚度（CRT）相对于基线的变化；以及基线RNP和MNP状态之间的关系。
在基线时，无论基线RNP状态如何，24.6%的患者RNP达到10 DA或更多，72.6%的患者存在MNP。在W24时，玻璃体内注射阿柏西普组和假注射组中RNP达到10 DA或更多的患者合并比例分别为11.6%和29.0%（P = 0.0001）；存在任何程度MNP的相应比例分别为61.2%和79.5%（P = 0.0008）。玻璃体内注射阿柏西普与假注射相比，RNP达到10 DA或更多的相对风险及95%置信区间为0.4（0.25 - 0.62），MNP为0.8（0.68 - 0.90），表明玻璃体内注射阿柏西普出现这些结局的风险低于假注射。在基线时RNP少于10 DA和RNP达到10 DA或更多的情况下，玻璃体内注射阿柏西普治疗的眼睛与假注射治疗的眼睛相比，平均BCVA变化更大（分别为+17.5对 +0.8字母和+18.3对 -4.1字母），以及在有和无基线MNP的情况下（分别为+15.7对 +0.3字母和+17.1对 +0.4字母）。基线RNP和MNP状态之间的一致性较低（κ = 0.12）。玻璃体内注射阿柏西普治疗组和假注射治疗组中发生1次或更多眼部严重不良事件的患者比例分别为3.2%和11.3%。
在W24时，无论基线RNP或MNP状态如何，玻璃体内注射阿柏西普治疗的眼睛在视力和解剖结构改善方面，包括灌注状态，均优于假注射治疗的眼睛。
