Characteristics of Patients Losing Vision after 2 Years of Monthly Dosing in the Phase III Ranibizumab Clinical Trials
Characteristics of Patients Losing Vision after 2 Years of Monthly Dosing in the Phase III Ranibizumab Clinical Trials
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DOI：
10.1016/j.ophtha.2010.07.011
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发表时间：
2011-03-01
期刊：
影响因子：
13.7
通讯作者：
Blodi, Barbara
中科院分区：
文献类型：
--
作者：
Rosenfeld, Philip J.;Shapiro, Howard;Blodi, Barbara
目的：在关键的雷尼单抗III期试验中，研究每月接受雷尼单抗注射的新生血管性年龄相关性黄斑变性（AMD）患者视力（VA）下降的原因。设计：回顾性分析。参与者：抗vegf抗体雷尼单抗治疗新生血管性AMD （MARINA）的最小经典/隐匿试验和抗vegf抗体治疗AMD中主要经典脉络膜新生血管（ANCHOR）试验。方法：比较基线至24个月>= 15个字母VA丧失患者和>= 15个字母VA增加患者在基线和24个月的人口统计学和病变特征。对这些患者的眼底照片进行额外的评估，以评估非渗出性AMD的特征，如地理萎缩（GA）和视网膜色素上皮（RPE）异常。主要结局指标：从基线到第24个月，>= 15个字母VA减少与增加的患者之间病变特征的差异。结果：在第24个月，9%的MARINA患者接受雷尼单抗治疗，10%的ANCHOR患者接受雷尼单抗治疗，>= 15个字母VA消失；来自MARINA的30%接受雷尼单抗治疗的患者和来自ANCHOR的38%接受雷尼单抗治疗的患者获得了>= 15个字母的VA。在第24个月时，与VA丧失相关的基线特征包括年龄更大、VA更好和病变更大。在第24个月，MARINA （P = 0.0008）和ANCHOR （P = 0.0046）试验中，RPE异常面积的增加与VA损失相关。在两项试验中，24个月时总病变面积增加与VA损失有关。在MARINA中，总病变面积的增加是由于VA失败者中萎缩瘢痕的血管造影标记的增加（P = 0.0043），但在ANCHOR中，这是由于脉络膜新生血管（CNV）面积的增加（P = 0.039），而不是由于渗漏面积的增加（P = 0.17）。GA、纤维化和出血面积的增加与VA损失无关。结论：每月接受雷尼单抗治疗2年后的视力下降与CNV抑制相关的病变特征相关，如色素异常、萎缩性疤痕和无渗漏。未来接受雷尼单抗治疗的患者的VA改善可能需要保留光感受器和RPE功能，而不是针对CNV的策略。
Purpose: To investigate the cause of visual acuity (VA) loss in patients with neovascular age-related macular degeneration (AMD) receiving monthly ranibizumab injections in the pivotal ranibizumab phase III trials.Design: Retrospective analysis.Participants: The Minimally Classic/Occult Trial of the Anti-VEGF Antibody Ranibizumab In the treatment of Neovascular AMD (MARINA) and Anti-VEGF Antibody for the Treatment of Predominantly Classic Choroidal Neovascularization in AMD (ANCHOR) trials.Methods: Demographics and lesion characteristics at baseline and month 24 were compared in patients with >= 15 letters VA loss and patients with >= 15 letters VA gain from baseline to month 24. Additional evaluations of fundus photographs from these patients were performed to assess features of non-exudative AMD, such as geographic atrophy (GA) and retinal pigment epithelium (RPE) abnormalities.Main Outcome Measures: Differences in lesion characteristics between patients who lost versus gained >= 15 letters of VA from baseline to month 24.Results: At month 24, 9% of ranibizumab-treated patients from MARINA and 10% of ranibizumab-treated patients from ANCHOR had lost >= 15 letters VA; 30% of ranibizumab-treated patients from MARINA and 38% of ranibizumab-treated patients from ANCHOR had gained >= 15 letters VA. Baseline characteristics associated with VA loss at month 24 included older age, better VA, and larger lesions. At month 24, an increased area of RPE abnormality was associated with VA loss in both the MARINA (P = 0.0008) and ANCHOR (P = 0.0046) trials. Increased total lesion area at month 24 was associated with VA loss in both trials. In MARINA, the increase in total lesion area was attributable to an increase in the angiographic designation of atrophic scar among VA losers (P = 0.0043), but in ANCHOR it was attributable to an increased area of choroidal neovascularization (CNV) (P = 0.039) but not an increased area of leakage (P = 0.17). Increased areas of GA, fibrosis, and hemorrhage were not associated with VA loss.Conclusions: Vision loss after 2 years of monthly ranibizumab therapy was associated with lesion characteristics commonly associated with suppressed CNV, such as pigmentary abnormalities, atrophic scar, and the absence of leakage. Future VA improvements in patients receiving ranibizumab therapy may require preservation of photoreceptor and RPE function rather than strategies that target CNV.