Department of Ophthalmology and Visual Sciences, University of Wisconsin Medical School, Madison, Wisconsin.
Department of Ophthalmology and Visual Sciences, University of Wisconsin Medical School, Madison, Wisconsin.
Ophthalmology. 2015 Feb;122(2):367-74. doi: 10.1016/j.ophtha.2014.08.048. Epub 2014 Nov 18.
To assess the effects of intravitreal ranibizumab on diabetic retinopathy (DR) severity when administered for up to 3 years, evaluate the effect of delayed initiation of ranibizumab therapy on DR severity, and identify baseline patient characteristics associated with the development of proliferative DR (PDR).
Exploratory analyses of phase III, randomized, double-masked, sham-controlled multicenter clinical trials.
Adults with diabetic macular edema (DME) (N = 759), baseline best-corrected visual acuity 20/40 to 20/320 Snellen equivalent, and central foveal thickness ≥275 μm.
Patients were randomized to monthly 0.3 or 0.5 mg ranibizumab or sham injections. Sham participants could switch to 0.5 mg ranibizumab during the third year (sham/0.5 mg crossover). Baseline risk factors were evaluated to explore potential associations with development of PDR. Time to first development of PDR was analyzed by Kaplan-Meier methods to calculate cumulative probabilities by group.
Study eye change on the Early Treatment Diabetic Retinopathy Study severity scale and a composite clinical outcome evaluating progression to PDR based on photographic changes plus clinically important events defining PDR.
At month 36, a greater proportion of ranibizumab-treated eyes had ≥2- or ≥3-step DR improvement compared with sham/0.5 mg crossover. A ≥3-step improvement was achieved at 36 months by 3.3%, 15.0%, and 13.2% of sham/0.5 mg, 0.3 mg, and 0.5 mg ranibizumab-treated eyes, respectively (P < 0.0001). Through 36 months, 39.1% of eyes in the sham/0.5 mg group developed PDR, as measured by composite outcome, compared with 18.3% and 17.1% of eyes treated with 0.3 or 0.5 mg ranibizumab, respectively. The presence of macular capillary nonperfusion at baseline seems to be associated with progression to PDR in ranibizumab-treated eyes but did not meaningfully influence visual acuity improvement in eyes with DME after ranibizumab therapy.
Ranibizumab, as administered to patients with DME for 12 to 36 months in these studies, can both improve DR severity and prevent worsening. Prolonged delays in initiation of ranibizumab therapy may limit this therapeutic effect. Although uncommon, the development of PDR still occurs in a small percentage of eyes undergoing anti-vascular endothelial growth factor therapy and may be related to the presence of macular nonperfusion.
评估玻璃体内雷珠单抗治疗长达 3 年对糖尿病视网膜病变（DR）严重程度的影响，评估延迟开始雷珠单抗治疗对 DR 严重程度的影响，并确定与增殖性 DR（PDR）发展相关的基线患者特征。
III 期、随机、双盲、假对照多中心临床试验的探索性分析。
患有糖尿病性黄斑水肿（DME）的成年人（N=759），基线最佳矫正视力为 20/40 至 20/320 等效 Snellen，中央视网膜厚度≥275μm。
患者被随机分配到每月接受 0.3 或 0.5mg 雷珠单抗或假注射。假注射组可以在第三年转为 0.5mg 雷珠单抗（假/0.5mg 交叉）。评估基线风险因素，以探索与 PDR 发展相关的潜在关联。通过 Kaplan-Meier 方法分析首次发生 PDR 的时间，以计算按组计算的累积概率。
早期治疗糖尿病视网膜病变研究严重程度量表上的研究眼变化和基于摄影变化加临床上定义 PDR 的重要事件的综合临床结局，评估进展为 PDR。
在 36 个月时，与假/0.5mg 交叉组相比，接受雷珠单抗治疗的眼有更多比例达到≥2 级或≥3 级 DR 改善。在 36 个月时，假/0.5mg、0.3mg 和 0.5mg 雷珠单抗治疗的眼分别有 3.3%、15.0%和 13.2%达到≥3 级改善（P<0.0001）。通过 36 个月，复合结局测量时，假/0.5mg 组有 39.1%的眼发生 PDR，而接受 0.3 或 0.5mg 雷珠单抗治疗的眼分别为 18.3%和 17.1%。基线时存在黄斑毛细血管无灌注似乎与雷珠单抗治疗眼的 PDR 进展相关，但对雷珠单抗治疗后 DME 眼的视力改善没有明显影响。
在这些研究中，雷珠单抗治疗糖尿病性黄斑水肿 12 至 36 个月，既能改善 DR 严重程度，又能预防病情恶化。延迟开始雷珠单抗治疗可能会限制这种治疗效果。尽管很少见，但接受抗血管内皮生长因子治疗的眼仍会发生少量 PDR，可能与黄斑无灌注有关。
