Outcomes With As-Needed Aflibercept and Macular Laser Following the Phase III VISTA DME Trial: ENDURANCE 12-Month Extension Study.
Outcomes With As-Needed Aflibercept and Macular Laser Following the Phase III VISTA DME Trial: ENDURANCE 12-Month Extension Study.
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III 期 VISTA DME 试验后按需使用阿柏西普和黄斑激光的结果：ENDURANCE 12 个月扩展研究。
DOI：
10.1016/j.ajo.2017.02.025
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发表时间：
2017
影响因子：
4.2
通讯作者：
M. Călugăru
中科院分区：
文献类型：
--
作者：
D. Călugăru;M. Călugăru
我们想解决Wykoff及其同事的研究中出现的几个挑战，具体总结如下。Endurance扩展研究中的60例患者是从3个原始VISTA糖尿病黄斑水肿（DME）随机化组（即接受玻璃体内注射阿柏西普的眼睛）中选择的，因此存在选择偏倚（Eylea; Regeneron，Tarrytown，纽约，美国）注射（IAI）每4周2 mg（Q4），在5次初始每月剂量后每8周IAI 2 mg（Q8），和黄斑焦点/网格激光治疗。没有说明选择的标准。因此，在入组Endurance研究前对60例患者进行的异质性既往治疗可能导致结果偏倚。此外，在当前视力、光谱域光学相干断层扫描（SDOCT）、散瞳检眼镜检查结果和荧光素血管造影的背景下，研究者自行决定是否重新开始治疗存在差异。Endurance扩展研究中患者的基线中央视网膜厚度（CRT）属于正常值，因为它低于正常中心凹厚度（270 ± 22.5 mm）上限的临界值（315.2 mm）加上2个标准差。2然而，没有关于入组前和Endurance扩展研究结束时DME的OCT结果（例如，单纯DME/囊样DME [轻度、中度和重度]/浆液性黄斑脱离）以及研究结束时被认为“干”的眼睛比例的数据。在进入研究前和治疗12个月后，没有关于临床相关DME（CR-DME）患者的详细信息。在Endurance期间，仅CR-DME患者根据需要接受2.0 mg IAI治疗。值得注意的是，18例患者（30%）没有CR-DME，因此不需要额外的IAI;但他们被纳入按需阿柏西普和黄斑激光的疗效最终评价中，以维持Vista DME期间获得的收益。如果排除了18例无临床显著DME和临床相关疾病活动的患者，研究结局可能会有所不同。没有关于患者在进入研究时和治疗结束时的荧光素血管造影结果的数据，即微动脉瘤或扩张毛细血管的局灶性渗漏、涉及中央凹整个周边的渗漏以及血管造影后期黄斑囊性区域内的染料蓄积。没有关于这些变化的质量状况和规模的数据视网膜外层（破裂/缺失）（例如，外界膜、椭圆体区、指状交错区，和视网膜色素上皮）作为按需阿柏西普和黄斑激光治疗后视力变化的潜在预测因素。（例如，玻璃体黄斑粘连/牵引和视网膜前膜）及其变化，作为受CR-DME影响的眼睛按需接受阿柏西普和黄斑激光治疗后解剖和视力结果的潜在预测因素。总之，研究作者证实，在3年Vista DME试验期间获得的视觉和解剖学增益可维持至Endurance扩展研究的第12个月，并根据临床相关疾病活动的证据进行个性化的按需治疗。值得注意的是，视觉上的好处可能已经获得的患者...
WE WOULD LIKE TO ADDRESS SEVERAL CHALLENGES THAT have arisen from the study by Wykoff and associates, 1 which can be specifically summarized below. There was a selection bias attributable to the way in which the 60 patients in the Endurance extension study were selected from the 3 original VISTA diabetic macular edema (DME) randomized arms, namely, eyes that had received intravitreal aflibercept (Eylea; Regeneron, Tarrytown, New York, USA) injection (IAI) 2 mg every 4 weeks (Q4), IAI 2 mg every 8 weeks after 5 initial monthly doses (Q8), and macular focal/grid laser treatment. Nothing was stated regarding the criteria used for this selection. Therefore, the heterogeneous prior treatments administered to the 60 patients before enrolment in the Endurance study may have biased the results. In addition, there was a variability in determining retreatment attributable to investigator discretion in the context of the current visual acuity, spectral-domain optical coherence tomography (SDOCT), dilated ophthalmoscopic examination findings, and fluorescein angiography. The baseline central retinal thickness (CRT) of the patients in the Endurance extension study was among the normal values because it was below the cutoff (315.2 mm) for the upper level of the normal foveal thickness (270 6 22.5 mm) plus 2 standard deviations. 2 However, there were no data on the OCT findings of the DME before enrolment and at the end of the Endurance extension study (eg, simple DME/cystoid DME [mild, intermediate, and severe]/serous macular detachment) as well as the proportion of eyes considered ‘‘dry’’at the end of the study. There were no details regarding the patients with clinically relevant DME (CR-DME) before entering the study and after 12 months of treatment. During Endurance, only patients with CR-DME were treated with 2.0 mg IAIs as needed. Of note, 18 patients (30%) did not have CR-DME and therefore did not require additional IAIs; and yet they were included in the final evaluation of the efficacy of as-needed aflibercept and macular laser to maintain the gains achieved during Vista DME. Possibly, the outcomes of the study would have been different if the 18 patients without clinically significant DME and clinically relevant disease activity had been excluded. There were no data referring to the fluorescein angiographic findings of the patients at the entry into the study and at the end of the treatment applied, namely, focal leakage from microaneurysms or dilated capillaries, leakage involving the entire circumference of the fovea, and accumulation of the dye within the cystic areas of the macula during the late phase of the angiogram. There are no data on the qualitative status, as well as the magnitude, of the changes (disruption/absence) in the outer retinal layers (eg, the external limiting membrane, the ellipsoid zone, the interdigitation zone, and the retinal pigment epithelium) as potential predictors of vision changes after treatment with as-needed aflibercept and macular laser.Nothing was stated referring to the prevalence of the vitreoretinal interface abnormalities (eg, vitreomacular adhesion/traction and epiretinal membranes) and their changes, as potential predictive factors on anatomic and visual outcomes after as-needed aflibercept and macular laser in eyes affected by CR-DME. Altogether, the authors of the study substantiated that the visual and anatomic gains achieved during the 3-year Vista DME trial were maintained through month 12 of the Endurance extension study with individualized, as-needed treatment based on evidence of clinically relevant disease activity. Notably, visual benefits might have obtained in the patients of …