Department of Ophthalmology, School of Medicine, University of California, San Francisco, San Francisco, California.
Ophthalmology. 2013 Nov;120(11):2292-9. doi: 10.1016/j.ophtha.2013.03.046. Epub 2013 May 3.
To assess long-term outcomes 7 to 8 years after initiation of intensive ranibizumab therapy in exudative age-related macular degeneration (AMD) patients.
Multicenter, noninterventional cohort study.
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).
Fourteen clinical trial sites recruited their original subjects for a return evaluation. Individual subject comparisons were obtained from the ANCHOR, MARINA, and HORIZON databases.
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).
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. Thirty-seven 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 mm(2); the area of atrophy correlated significantly with poor visual outcome (P<0.0001).
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.
评估接受密集型雷珠单抗治疗后 7 至 8 年渗出性年龄相关性黄斑变性（AMD）患者的长期结局。
多中心、非干预性队列研究。
65 名 AMD 患者最初在抗血管内皮生长因子抗体治疗湿性年龄相关性黄斑变性（AMD）的 3 期临床试验（抗 VEGF 抗体治疗 AMD 的主要经典脉络膜新生血管形成的 ANCHOR 试验、最小经典/隐匿性脉络膜新生血管形成的抗 VEGF 抗体雷珠单抗治疗 AMD 的 MARINA 试验和雷珠单抗治疗年龄相关性黄斑变性继发脉络膜新生血管的开放性标签扩展试验（HORIZON）中接受雷珠单抗治疗。
14 个临床试验地点招募了他们的原始受试者进行回归评估。个体受试者比较来自 ANCHOR、MARINA 和 HORIZON 数据库。
主要终点为最佳矫正视力（BCVA）为 20/70 或更好的比例；次要结局包括与前一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）和眼底自发荧光（FAF）的解剖结果。
在进入 ANCHOR 或 MARINA 平均 7.3 年（范围 6.3-8.5 年）后，37%的研究眼达到了 20/70 或更好的 BCVA 主要终点，其中 23%的研究眼达到了 20/40 或更好的 BCVA。37%的研究眼的 BCVA 为 20/200 或更差。与 ANCHOR 或 MARINA 基线测量值相比，43%的研究眼的字母评分稳定或提高（≥0 个字母的提高），而 34%的研究眼下降了 15 个字母或更多，总体平均下降了 8.6 个字母（P<0.005）。自退出 HORIZON 研究以来，研究眼在平均 3.4 年的间隔内平均接受了 6.8 次抗血管内皮生长因子（VEGF）注射；接受 11 次或更多抗 VEGF 注射的患者亚组自退出 HORIZON 以来字母评分的平均提高明显更好（P<0.05）。68%的研究眼通过光谱域 OCT 检测到活动性渗出性疾病，46%的研究眼正在接受持续的眼部抗 VEGF 治疗。通过 FAF 在 98%的眼中检测到黄斑萎缩，平均面积为 9.4mm2；萎缩面积与视力不良结果显著相关（P<0.0001）。
在 ANCHOR 或 MARINA 试验中接受雷珠单抗治疗约 7 年后，三分之一的患者表现出良好的视力结果，而三分之一的患者则表现出较差的结果。与基线相比，近一半的眼睛稳定，而三分之一的眼睛下降了 15 个字母或更多。即使在治疗过程的这个晚期阶段，渗出性 AMD 患者仍然有发生严重视力下降的风险。
