Wykoff Charles C, Nittala Muneeswar G, Zhou Brenda, Fan Wenying, Velaga Swetha Bindu, Lampen Shaun I R, Rusakevich Alexander M, Ehlers Justis P, Babiuch Amy, Brown David M, Ip Michael S, Sadda SriniVas R
Retina Consultants of Houston, Houston, Texas; Blanton Eye Institute, Houston Methodist Hospital & Weill Cornell Medical College, Houston, Texas.
Doheny Image Reading Center, Doheny Eye Institute, Los Angeles, California.
Ophthalmol Retina. 2019 Dec;3(12):1076-1086. doi: 10.1016/j.oret.2019.07.011. Epub 2019 Jul 24.
Evaluate the impact of intravitreal aflibercept (Eylea; Regeneron, Tarrytown, NY) on retinal nonperfusion (RNP) in eyes with proliferative diabetic retinopathy (PDR).
Prospective, randomized clinical trial.
Eyes with treatment-naïve PDR and extensive RNP without diabetic macular edema.
Patients were randomized 1:1 to intravitreal 2 mg aflibercept every 4 weeks (monthly) or every 12 weeks (quarterly).
The primary outcome measure was change in total RNP area (in square millimeters) from baseline to year 1. Secondary outcomes included ischemic index (ISI), diabetic retinopathy severity scale (DRSS) scores, visual acuity, central retinal thickness, and adverse events. The mean and 95% confidence interval were calculated for each outcome.
Through 1 year, the monthly (n = 20) and quarterly (n = 20) cohorts received 11.0 and 3.95 mean aflibercept injections, and DRSS scores improved 2 steps or more in 74% and 67% of patients, respectively. Among all patients through 1 year, mean total area of RNP increased from 235 mm to 266 mm (P = 0.18) and ISI increased from 25.8% to 31.9% (P = 0.004). Retinal nonperfusion outcomes favored monthly dosing. Mean total RNP increased from 207 mm at baseline to 268 mm (P = 0.01) at 1 year in the quarterly cohort and remained stable at 264 mm at baseline and 1 year (P = 0.70) in the monthly cohort (P = 0.05, monthly vs. quarterly cohorts). Although many eyes demonstrated increased areas of RNP longitudinally (n = 24 [66.7%]), this was more common with quarterly dosing (n = 14 [77.8%]), and a proportion of eyes (n = 12 [33.3%]) demonstrated localized areas of apparent reperfusion of nonperfused retina, more commonly in the monthly cohort (n = 8 [44.4%]).
Widespread evidence of retinal reperfusion with aflibercept dosing of PDR eyes with extensive RNP was not identified, and therefore the primary outcome of the current study was not met. Nevertheless, zones of apparent reperfusion were detected in some patients, and a dose response was identified with a reduction of RNP progression with monthly compared to quarterly dosing.
评估玻璃体内注射阿柏西普（Eylea；Regeneron公司，纽约州塔里敦）对增殖性糖尿病视网膜病变（PDR）患者视网膜无灌注（RNP）的影响。
前瞻性随机临床试验。
初治PDR且有广泛RNP但无糖尿病性黄斑水肿的眼睛。
患者按1:1随机分为每4周（每月）或每12周（每季度）玻璃体内注射2mg阿柏西普。
主要观察指标为从基线到第1年总RNP面积（平方毫米）的变化。次要观察指标包括缺血指数（ISI）、糖尿病视网膜病变严重程度量表（DRSS）评分、视力、中心视网膜厚度和不良事件。计算每个观察指标的均值和95%置信区间。
在1年的时间里，每月治疗组（n = 20）和每季度治疗组（n = 20）平均接受阿柏西普注射的次数分别为11.0次和3.95次，DRSS评分分别在74%和67%的患者中改善了2级或更多。在所有患者中，经过1年，RNP的平均总面积从235平方毫米增加到266平方毫米（P = 0.18），ISI从25.8%增加到31.9%（P = 0.004）。视网膜无灌注结果显示每月给药更有利。在每季度治疗组中，RNP的平均总面积从基线时的207平方毫米增加到1年时的268平方毫米（P = 0.01），而在每月治疗组中，基线时和1年时均稳定在264平方毫米（P = 0.70）（每月治疗组与每季度治疗组相比，P = 0.05）。尽管许多眼睛纵向显示RNP面积增加（n = 24 [66.7%]），但这在每季度给药时更常见（n = 14 [77.8%]），并且一部分眼睛（n = 12 [33.3%]）显示出无灌注视网膜的局部明显再灌注区域，更常见于每月治疗组（n = 8 [44.4%]）。
未发现广泛证据表明阿柏西普给药对有广泛RNP的PDR眼睛有视网膜再灌注作用，因此本研究的主要结果未达到。然而，在一些患者中检测到了明显的再灌注区域，并且确定了剂量反应，与每季度给药相比，每月给药可减少RNP进展。
