PURPOSE To report the natural history of untreated neovascular age-related macular degeneration (nAMD) regarding subsequent macular atrophy. DESIGN Prospective cohort within a randomized, controlled trial of oral micronutrient supplements. PARTICIPANTS Age-Related Eye Disease Study (AREDS) participants (55-80 years) who demonstrated nAMD during follow-up (1992-2005), prior to anti-vascular endothelial growth factor (VEGF) therapy. METHODS Color fundus photographs were collected at annual study visits and graded centrally for late age-related macular degeneration (AMD). Incident macular atrophy after nAMD was examined by Kaplan-Meier analysis and proportional hazards regression. MAIN OUTCOME MEASURES Incident macular atrophy after nAMD. RESULTS Of the 4757 AREDS participants, 708 eyes (627 participants) demonstrated nAMD during follow-up and were eligible. The cumulative risks of incident macular atrophy after untreated nAMD were 9.6% (standard error, 1.2%), 31.4% (standard error, 2.2%), 43.1% (standard error, 2.6%), and 61.5% (standard error, 4.3%) at 2, 5, 7, and 10 years, respectively. This corresponded to a linear risk of 6.5% per year. The cumulative risk of central involvement was 30.4% (standard error, 3.2%), 43.4% (standard error, 3.8%), and 57.0% (standard error, 4.8%) at first appearance of atrophy, 2 years, and 5 years, respectively. Geographic atrophy (GA) in the fellow eye was associated with increased risk of macular atrophy (hazard ratio [HR], 1.70; 95% confidence interval [CI], 1.17-2.49; P = 0.006). However, higher 52-single nucleotide polymorphism AMD genetic risk score was not associated with increased risk of macular atrophy (HR, 1.03; 95% CI, 0.90-1.17; P = 0.67). Similarly, no significant differences were observed according to SNPs at CFH, ARMS2, or C3. CONCLUSIONS The rate of incident macular atrophy after untreated nAMD is relatively high, increasing linearly over time and affecting half of eyes by 8 years. Hence, factors other than anti-VEGF therapy are involved in atrophy development, including natural progression to GA. Comparison with studies of treated nAMD suggests it may not be necessary to invoke a large effect of anti-VEGF therapy on inciting macular atrophy, although a contribution remains possible. Central involvement is present in one third of eyes at the outset (similar to pure GA) and increases linearly to half at 3 years.

中文翻译：

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未经治疗的新血管性年龄相关性黄斑变性后黄斑萎缩的发生率：年龄相关性眼病研究报告40。

目的报告未经治疗的新血管性年龄相关性黄斑变性（nAMD）有关随后的黄斑萎缩的自然史。设计口服微量营养素补充剂的随机对照试验中的前瞻性队列。参与者年龄相关的眼病研究（AREDS）参与者（55-80岁）在抗血管内皮生长因子（VEGF）治疗之前的随访期间（1992-2005年）证实了nAMD。方法每年一次的研究访问中收集彩色眼底照片，并对晚期老年性黄斑变性（AMD）进行中央分级。通过Kaplan-Meier分析和比例风险回归分析了nAMD之后的事件性黄斑萎缩。主要观察指标nAMD后发生黄斑萎缩。结果在4757名AREDS参与者中，708眼（627名参与者）在随访期间表现出nAMD并符合条件。未经治疗的nAMD引起的黄斑萎缩的累积风险分别为9.6％（标准误，1.2％），31.4％（标准误，2.2％），43.1％（标准误，2.6％）和61.5％（标准误，4.3％）。 ）分别在2、5、7和10年。这对应于每年6.5％的线性风险。首次出现萎缩，2年和5年时，中枢累及的累积风险分别为30.4％（标准误，3.2％），43.4％（标准误，3.8％）和57.0％（标准误，4.8％），分别。另一只眼睛的地理萎缩（GA）与黄斑萎缩的风险增加相关（危险比[HR]为1.70； 95％置信区间[CI]为1.17-2.49； P = 0.006）。然而，较高的52个单核苷酸多态性AMD遗传风险评分与黄斑萎缩风险增加无关（HR，1.03； 95％CI，0.90-1.17； P = 0.67）。同样，根据CFH，ARMS2或C3上的SNP，也没有观察到显着差异。结论未治疗的nAMD后黄斑萎缩的发生率相对较高，随时间呈线性增加，影响了一半的眼睛，持续了8年。因此，抗VEGF疗法以外的因素也参与了萎缩的发展，包括自然发展为GA。与已治疗的nAMD的研究比较表明，尽管仍有可能做出贡献，但可能没有必要对诱发黄斑萎缩的抗VEGF治疗产生巨大影响。一开始，中心性受累出现在三分之一的眼睛中（类似于纯GA），并在3年​​时线性增加至一半。