Wykoff Charles C, Eichenbaum David A, Roth Daniel B, Hill Lauren, Fung Anne E, Haskova Zdenka
Retina Consultants of Houston, Blanton Eye Institute, Houston Methodist Hospital and Weill Cornell Medical College, Houston, Texas.
Morsani College of Medicine, University of South Florida, Tampa, Florida.
Ophthalmol Retina. 2018 Oct;2(10):997-1009. doi: 10.1016/j.oret.2018.06.005. Epub 2018 Aug 1.
To evaluate diabetic retinopathy (DR) outcomes with ranibizumab (Lucentis, Genentech, Inc., South San Francisco, CA) treatment in patients with DR and diabetic macular edema (DME) at high risk of progression to proliferative disease.
Post hoc analysis of the phase 3 RIDE (ClinicalTrials.gov identifier, NCT00473382) and RISE (ClinicalTrials.gov identifier, NCT00473330) clinical trials of ranibizumab for the treatment of DME.
Seven hundred forty-six patients with baseline fundus photographs and randomized for treatment.
Diabetic retinopathy outcomes were assessed through month 36 by baseline DR severity level. Diabetic retinopathy severity was quantified using the Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS).
Two-step or more or 3-step or more improvement or worsening on the ETDRS DRSS and time to new proliferative event (composite end point).
At baseline, most patients were distributed evenly among mild or moderate nonproliferative DR (NPDR; ETDRS DRSS, 35/43), moderately severe or severe NPDR (ETDRS DRSS, 47/53), and proliferative DR (ETDRS DRSS, 60-75; 28.8%, 33.2%, and 31.1%, respectively). At month 24, rates of 2-step or more improvement with ranibizumab 0.3 mg, ranibizumab 0.5 mg, and sham treatment were highest among patients with baseline DR levels 47/53 (78.4%, 81.1%, and 11.6%, respectively) compared with patients with baseline DR levels 35/43 (10.3%, 15.8%, and 1.4%, respectively) or 60 through 75 without panretinal photocoagulation (31.0%, 36.4%, and 6.7%, respectively; all ranibizumab vs. sham comparisons, P < 0.05). In patients with baseline DR levels 47/53, ranibizumab treatment reduced the probability of patients experiencing a new proliferative event at month 36 by 3 times compared with sham treatment (12.4% and 11.9% vs. 35.2% for ranibizumab 0.3 mg, ranibizumab 0.5 mg, and sham, respectively). In patients with baseline DR levels 47/53 who achieved 2-step or more DR improvement, improvements were independent of all assessed baseline characteristics (P > 0.4).
Ranibizumab treatment resulted in DR improvements in all 3 baseline DR severity subsets examined. The greatest benefits in DR improvement occurred in patients with baseline moderately severe to severe NPDR (DR levels 47/53). Diabetic retinopathy improvements were rapid, clinically meaningful, and sustained through month 36.
评估雷珠单抗（Lucentis，基因泰克公司，加利福尼亚州南旧金山）治疗糖尿病性视网膜病变（DR）和有进展为增殖性疾病高风险的糖尿病性黄斑水肿（DME）患者的DR结局。
雷珠单抗治疗DME的3期RIDE（ClinicalTrials.gov标识符，NCT00473382）和RISE（ClinicalTrials.gov标识符，NCT00473330）临床试验的事后分析。
746例有基线眼底照片并随机接受治疗的患者。
根据基线DR严重程度水平评估至36个月时的DR结局。使用早期糖尿病性视网膜病变治疗研究（ETDRS）糖尿病性视网膜病变严重程度量表（DRSS）对DR严重程度进行量化。
ETDRS DRSS上两步或更多步或三步或更多步的改善或恶化以及新的增殖性事件发生时间（复合终点）。
在基线时，大多数患者均匀分布在轻度或中度非增殖性DR（NPDR；ETDRS DRSS，35/43）、中度严重或重度NPDR（ETDRS DRSS，47/53）以及增殖性DR（ETDRS DRSS，60 - 75；分别为28.8%、33.2%和31.1%）患者中。在第24个月时，与基线DR水平为35/43的患者（分别为10.3%、15.8%和1.4%）或60至75且未进行全视网膜光凝的患者（分别为31.0%、36.4%和6.7%；所有雷珠单抗与假治疗比较，P < 0.05）相比，雷珠单抗0.3 mg、雷珠单抗0.5 mg和假治疗组中基线DR水平为47/53的患者两步或更多步改善的发生率最高。在基线DR水平为47/53的患者中，与假治疗相比，雷珠单抗治疗使第36个月时发生新的增殖性事件的患者概率降低了3倍（雷珠单抗0.3 mg、雷珠单抗0.5 mg和假治疗组分别为12.4%、11.9%和35.2%）。在基线DR水平为47/53且实现两步或更多步DR改善的患者中，改善与所有评估的基线特征无关（P > 0.4）。
雷珠单抗治疗使所检查的所有3个基线DR严重程度亚组的DR均有改善。DR改善最大的益处出现在基线中度严重至重度NPDR（DR水平47/53）的患者中。DR改善迅速、具有临床意义且持续至36个月。
