Purpose

To determine whether there are baseline characteristics that distinguish patients with diabetic macular edema (DME) with coexisting macular nonperfusion (MNP) at baseline and assess these patients’ potential to achieve favorable visual acuity (VA), anatomic, and diabetic retinopathy (DR) outcomes over 24 months.

Design

Post hoc analysis of RIDE/RISE, 2 phase 3, parallel, randomized, multicenter, double-masked trials (ClinicalTrials.gov: NCT00473382; NCT00473330).

Participants

Study eyes with best-corrected VA (BCVA)/fluorescein angiogram (FA) data at baseline.

Methods

To measure MNP, the Early Treatment for Diabetic Retinopathy Study (ETDRS) grid was overlaid on FAs of the macula. The MNP area was calculated by estimating the percentage of capillary loss in the central, inner, and outer subfields and converting into disc areas (DAs) using a software algorithm. Summary statistics and P values, respectively, were provided for all outcomes and comparisons of interest.

Main Outcome Measures

Baseline characteristics; MNP area, BCVA, and central subfield thickness (CST) at months 12 and 24; and incidence of study eyes with ≥2-step DR improvement at months 3, 6, 12, 18, and 24.

Results

Baseline MNP was detected in 28.2%, 25.8%, and 26.3% of study eyes in the ranibizumab 0.3 mg (n = 213), ranibizumab 0.5 mg (n = 225), and sham (n = 228) arms, respectively. At baseline, patients with MNP were younger and had shorter diabetes duration, worse vision, increased CST, and worse DR severity (P values < 0.01 vs. those without MNP). In the ranibizumab 0.3 mg arm, eyes with baseline MNP had lower mean baseline BCVA (53.4 vs. 57.2 ETDRS letters for those without baseline MNP; P = 0.05), but mean BCVA gain at month 24 was comparable (+15.6 vs. +13.4 ETDRS letters, respectively; P = 0.2). Eyes with baseline MNP had increased CST at baseline, but experienced a greater decrease in CST by month 24. The proportion of eyes with ≥2-step DR improvement was greater for eyes with versus without baseline MNP in each ranibizumab arm.

Conclusions

Despite having worse vision/increased CST versus those without baseline MNP, eyes with concurrent DME and baseline MNP entering RIDE/RISE experienced robust VA and anatomic improvement with ranibizumab and therefore should not be excluded from therapy.

中文翻译：

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雷尼珠单抗在糖尿病性黄斑水肿和黄斑非灌注性眼病中的疗效

目的

为了确定是否存在基线特征来区分糖尿病性黄斑水肿（DME）和基线并存的黄斑非灌注（MNP）患者，并评估这些患者获得良好视力（VA），解剖学和糖尿病性视网膜病（DR）结果的潜力超过24个月。

设计

对RIDE / RISE的事后分析，第2阶段，第3期，平行，随机，多中心，双掩蔽试验（ClinicalTrials.gov：NCT00473382; NCT00473330）。

参加者

在基线时用最佳校正的VA（BCVA）/荧光素血管造影（FA）数据研究眼睛。

方法

为了测量MNP，将糖尿病视网膜病变研究的早期治疗（ETDRS）网格覆盖在黄斑的FA上。MNP面积是通过估算中央，内部和外部子区域中毛细血管损失的百分比并使用软件算法转换为椎间盘区域（DA）来计算的。为所有结果和感兴趣的比较分别提供了摘要统计量和P值。

主要观察指标

基线特征；第12个月和第24个月的MNP面积，BCVA和中心子域厚度（CST）；在第3、6、12、18和24个月内，≥2步DR改善的研究眼睛的发生率。

结果

在兰尼单抗0.3 mg（n = 213），兰尼单抗0.5 mg（n = 225）和假（n = 228）的研究眼中分别检测到28.2％，25.8％和26.3％的基线MNP。基线时，MNP患者较年轻，糖尿病病程较短，视力较差，CST升高，DR严重程度较差（与无MNP的患者相比，P值<0.01）。在兰尼单抗0.3 mg组中，基线为MNP的眼睛的平均基线BCVA较低（对于没有基线MNP的那些，ETDRS字母为53.4 vs. 57.2；P  = 0.05），但在第24个月的平均BCVA增益是可比较的（+15.6 vs. +13.4） ETDRS字母分别；P = 0.2）。具有基线MNP的眼睛在基线时CST升高，但是到24个月时CST降低更大。在每个雷珠单抗组中，具有≥2步DR改善的眼睛比例比没有基线MNP的眼睛更大。

结论

尽管与未使用基线MNP的患者相比，视力/ CST升高较差，但同时使用DME和基线MNP进入RIDE / RISE的眼睛，使用兰尼单抗的VA增强且解剖学改善，因此不应将其排除在治疗范围之外。