Seven-Year Outcomes in Ranibizumab-Treated Patients in ANCHOR, MARINA, and HORIZON
Seven-Year Outcomes in Ranibizumab-Treated Patients in ANCHOR, MARINA, and HORIZON
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DOI：
10.1016/j.ophtha.2013.03.046
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发表时间：
2013-11-01
期刊：
影响因子：
13.7
通讯作者：
Zhang, Kang
中科院分区：
文献类型：
--
作者：
Rofagha, Soraya;Bhisitkul, Robert B.;Zhang, Kang
目的：评估开始强化雷尼单抗治疗渗出性年龄相关性黄斑变性（AMD）患者7 - 8年后的长期结果。设计：多中心、非干预性队列研究。参与者：65名最初接受雷尼单抗治疗的AMD患者在3期抗vegf抗体治疗AMD主要经典脉络膜新生血管（ANCHOR）试验，抗vegf抗体雷尼单抗治疗新生血管性AMD的最低经典/隐匿试验（MARINA）试验，以及雷尼单抗治疗继发于年龄相关性黄斑变性脉络膜新生血管的开放标签扩展试验（HORIZON）。方法：14个临床试验点招募原始受试者进行回归评估。个体受试者比较数据来自ANCHOR、MARINA和HORIZON数据库。主要结局指标：主要终点为最佳矫正视力（BCVA）达到20/70或更高的百分比；次要结果包括与先前时间点相比字母评分的平均变化以及荧光素血管造影、光谱域眼相干断层扫描（OCT）和眼底自身荧光（FAF）的解剖结果。结果：在进入ANCHOR或MARINA后平均7.3年（范围6.3-8.5年），37%的研究眼睛达到了20/70或更好的BCVA的主要终点，23%达到了20/40或更好的BCVA。研究中37%的眼睛BCVA为20/200或更差。与ANCHOR或MARINA基线测量值相比，43%的研究眼睛的字母评分稳定或改善（>= 0个字母增加），而34%的眼睛下降了15个字母或更多，总体平均下降了8.6个字母（P< 0.005）。自HORIZON研究退出以来，研究对象的眼睛在平均3.4年的时间间隔内平均接受了6.8次抗血管内皮生长因子（VEGF）注射；自HORIZON退出后，接受11次及以上抗vegf注射的亚组患者的字母评分平均增加明显更好（P< 0.05）。在68%的研究眼睛中，光谱域OCT检测到活动性渗出性疾病，46%正在接受眼部抗vegf治疗。FAF检出黄斑萎缩率为98%，平均面积为9.4 mm2；萎缩面积与视力差显著相关（P< 0.0001）。结论：在ANCHOR或MARINA试验中，雷尼单抗治疗约7年后，三分之一的患者表现出良好的视力结果，而另外三分之一的患者预后较差。与基线相比，几乎一半的眼睛是稳定的，而三分之一的眼睛下降了15个字母或更多。即使在治疗过程的晚期，渗出性AMD患者仍有明显视力下降的风险。
Purpose: To assess long-term outcomes 7 to 8 years after initiation of intensive ranibizumab therapy in exudative age-related macular degeneration (AMD) patients.Design: Multicenter, noninterventional cohort study.Participants: Sixty-five AMD patients originally treated with ranibizumab in the phase 3 Anti-VEGF Antibody for the Treatment of Predominantly Classic Choroidal Neovascularization in AMD (ANCHOR) trial, Minimally Classic/Occult Trial of the Anti-VEGF Antibody Ranibizumab in the Treatment of Neovascular AMD (MARINA) trial, and Open-Label Extension Trial of Ranibizumab for Choroidal Neovascularization Secondary to Age-Related Macular Degeneration (HORIZON).Methods: Fourteen clinical trial sites recruited their original subjects for a return evaluation. Individual subject comparisons were obtained from the ANCHOR, MARINA, and HORIZON databases.Main Outcome Measures: The primary end point was percentage with best-corrected visual acuity (BCVA) of 20/70 or better; secondary outcomes included mean change in letter score compared with previous time points and anatomic results on fluorescein angiography, spectral-domain ocular coherence tomography (OCT), and fundus autofluorescence (FAF).Results: At a mean of 7.3 years (range, 6.3-8.5 years) after entry into ANCHOR or MARINA, 37% of study eyes met the primary end point of 20/70 or better BCVA, with 23% achieving a BCVA of 20/40 or better. Thirtyseven percent of study eyes had BCVA of 20/200 or worse. Forty-three percent of study eyes had a stable or improved letter score (>= 0-letter gain) compared with ANCHOR or MARINA baseline measurements, whereas 34% declined by 15 letters or more, with overall a mean decline of 8.6 letters (P< 0.005). Since exit from the HORIZON study, study eyes had received a mean of 6.8 anti-vascular endothelial growth factor (VEGF) injections during the mean 3.4-year interval; a subgroup of patients who received 11 or more anti-VEGF injections had a significantly better mean gain in letter score since HORIZON exit (P< 0.05). Active exudative disease was detected by spectral-domain OCT in 68% of study eyes, and 46% were receiving ongoing ocular anti-VEGF treatments. Macular atrophy was detected by FAF in 98% of eyes, with a mean area of 9.4 mm2; the area of atrophy correlated significantly with poor visual outcome (P< 0.0001).Conclusions: Approximately 7 years after ranibizumab therapy in the ANCHOR or MARINA trials, one third of patients demonstrated good visual outcomes, whereas another third had poor outcomes. Compared with baseline, almost half of eyes were stable, whereas one third declined by 15 letters or more. Even at this late stage in the therapeutic course, exudative AMD patients remain at risk for substantial visual decline.