Purpose

Comparison of the efficacy of ranibizumab (RBZ) 0.5 mg intravitreal injections plus panretinal photocoagulation (PRP) versus PRP alone in the regression of the neovascularization (NV) area in subjects with high-risk proliferative diabetic retinopathy (HR-PDR) over a 12-month period.

Design

Prospective, randomized, multicenter, open-label, phase II/III study.

Participants

Eighty-seven participants (aged ≥18 years) with type 1/2 diabetes and HR-PDR (mean age, 55.2 years; 37% were female).

Methods

Participants were randomized (1:1) to receive RBZ+PRP (n = 41) or PRP monotherapy (n = 46). The RBZ+PRP group received 3 monthly RBZ injections along with standard PRP. The PRP monotherapy group received standard PRP between day 1 and month 2; thereafter, re-treatments in both groups were at the investigators' discretion.

Main Outcome Measures

The primary outcome was regression of NV total, on the disc (NVD) plus elsewhere (NVE), defined as any decrease in the area of NV from the baseline to month 12. Secondary outcomes included best-corrected visual acuity (BCVA) changes from baseline to month 12, time to complete NV regression, recurrence of NV, macular retinal thickness changes from baseline to month 12, need for treatment for diabetic macular edema, need for vitrectomy because of occurrence of vitreous hemorrhage, tractional retinal detachment or other complications of DR, and adverse events (AEs) related to treatments.

Results

Seventy-seven participants (88.5%) completed the study. Overall baseline demographics were similar for both groups, except for age. At month 12, 92.7% of participants in the RBZ+PRP group presented NV total reduction versus 70.5% of the PRP monotherapy participants (P = 0.009). The number of participants with NVD and NVE reductions was higher with RBZ+PRP (93.3% and 91.4%, respectively) versus PRP (68.8% and 73.7%, respectively), significant only for NVE (P = 0.048). Complete NV total regression was observed in 43.9% in the RBZ+PRP group versus 25.0% in the PRP monotherapy group (P = 0.066). At month 12, the mean BCVA was 75.2 letters (20/32) in the RBZ+PRP group versus 69.2 letters (20/40) in the PRP monotherapy group (P = 0.104). In the RBZ+PRP group, the mean number of PRP treatments over month 12 was 3.5±1.3, whereas in the PRP monotherapy group, it was 4.6±1.5 (P = 0.001). No deaths or unexpected AEs were reported.

Conclusions

Treatment with RBZ+PRP was more effective than PRP monotherapy for NV regression in HR-PDR participants over 12 months.

中文翻译：

---

雷尼珠单抗加全视网膜光凝与单独全视网膜光凝治疗高风险增生性糖尿病性视网膜病（PROTEUS研究）

目的

兰尼单抗（RBZ）0.5 mg玻璃体内注射加全视网膜光凝（PRP）与单独PRP在高危增生性糖尿病视网膜病变（HR-PDR）12岁以上的受试者新血管形成（NV）区域回归中的疗效比较一个月的时间。

设计

前瞻性，随机，多中心，开放标签的II / III期研究。

参加者

患有1/2型糖尿病和HR-PDR（平均年龄55.2岁；女性占37％）的八十七名参与者（年龄≥18岁）。

方法

参与者被随机分配（1：1）接受RBZ + PRP（n = 41）或PRP单药治疗（n = 46）。RBZ + PRP组每月接受3次RBZ注射以及标准PRP。PRP单药治疗组在第1天到第2个月之间接受标准PRP；之后，两组的再治疗由研究者决定。

主要观察指标

主要结局是椎间盘上NV总数（NVD）加上其他部位（NVE）的消退，定义为从基线到第12个月NV面积的任何减少。次要结局包括最佳矫正视力（BCVA）的变化。基线到第12个月，需要完成NV消退，NV复发，从基线到第12个月的黄斑视网膜厚度改变。由于玻璃体出血，牵引性视网膜脱离或其他并发症的发生，需要对糖尿病性黄斑水肿进行治疗，进行玻璃体切除术DR和与治疗相关的不良事件（AE）。

结果

77名参与者（88.5％）完成了研究。除年龄外，两组的总体基线人口统计数据均相似。在第12个月，RBZ + PRP组的92.7％的患者呈现NV总量减少，而PRP单药治疗的70.5％的患者表现为NV（P  = 0.009）。使用RBZ + PRP的NVD和NVE降低的参与者数量（分别为93.3％和91.4％）高于PRP（分别为68.8％和73.7％），仅对于NVE显着（P  = 0.048）。RBZ + PRP组的完全NV总消退率为43.9％，而PRP单药治疗组为25.0％（P  = 0.066）。在第12个月，RBZ + PRP组的平均BCVA为75.2个字母（20/32），而PRP单药治疗组的平均BCVA为69.2个字母（20/40）（P = 0.104）。在RBZ + PRP组中，第12个月的PRP平均治疗次数为3.5±1.3，而在PRP单药治疗组中，平均治疗次数为4.6±1.5（P  = 0.001）。没有死亡或意外的不良事件的报道。

结论

对于HR-PDR参与者，在12个月内，对于NV消退，RBZ + PRP治疗比PRP单药治疗更有效。