Department of Ophthalmology, University of Pennsylvania, Philadelphia.
Department of Ophthalmology, Duke University, Durham, North Carolina.
JAMA Ophthalmol. 2020 May 1;138(5):510-518. doi: 10.1001/jamaophthalmol.2020.0437.
Retinal hypopigmentation and hyperpigmentation are precursors of geographic atrophy (GA). Incidence and progression to GA in eyes treated with anti-vascular endothelial growth factor for neovascular age-related macular degeneration (nAMD) have not been investigated.
To determine the incidence and progression of non-GA (NGA) and associated risk factors.
DESIGN, SETTING, AND PARTICIPANTS: This study is a post hoc analysis of a cohort study within the Comparison of Age-Related Treatments Trials (CATT) clinical trial. Participants were recruited February 20, 2008, through December 9, 2009; released from protocol follow-up and treatment after 2 years; and recalled from March 14, 2014, through March 31, 2015. Data analyses were conducted from January 11, 2019, through November 27, 2019.
Participants were randomized to ranibizumab or bevacizumab for (1) 2 years of monthly or as-needed injections or (2) monthly injections for 1 year and as-needed injections the following year. Participants were treated according to best medical judgement thereafter.
Incidence of nAMD-associated NGA (hypopigmentation and hyperpigmentation in color images) and progression; adjusted risk ratios (aRR) for baseline characteristics.
Among 1107 participants, risk of NGA was 35% (391 eyes), 59% (246 eyes), and 81% (122 eyes) at 1, 2, and 5 years, respectively. Risk factors for NGA included worse visual acuity (20/200-20/320: aRR, 1.74 [95% CI, 1.24-2.43], compared with ≤20/40; P = .006), larger neovascularization area (>4 disc areas: aRR, 1.31 [95% CI, 1.01-1.71], compared with ≤1 disc areas; P = .007), switched drug regimen (aRR, 1.28 [95% CI, 1.06-1.54], compared with as-needed injections; P = .02), and single-nucleotide variants Age-Related Maculopathy Susceptibility 2 (ARMS2) (TT variant: relative risk [RR], 1.53 [95% CI, 1.22-1.93]; P = .001) and HtrA Serine Peptidase 1 (HTRA1) (AG variant: RR, 1.23 [95% CI, 1.01-1.48]; AA variant: RR, 1.51 [95% CI, 1.20-1.91]; P = .002). Sub-retinal pigment epithelium thickness was protective (>275 μm: aRR, 0.59 [95% CI, 0.46-0.75], compared with ≤75 μm; P < .001). Among 389 eyes with NGA by 2 years and subsequent color images, risk of progression to GA was 29%, 43%, and 50% at 1, 3, and 4 years, respectively. Risk factors for progression to GA included worse visual acuity (20/200-20/320: aRR, 2.75 [95% CI, 1.54-4.93], compared with ≤20/40; P < .001), worse fellow-eye visual acuity (<20/40: aRR, 1.77 [95% CI, 1.12-2.79], compared with ≥20/40; P = .01), fellow-eye GA (aRR, 1.71 [95% CI, 1.06-2.75]; P = .03), and pseudodrusen in either eye (aRR, 1.65 [95% CI, 1.17-2.34]; P = .005). Subretinal fluid was associated with a decreased risk of progression (aRR, 0.42 [95% CI, 0.28-0.63]; P < .001).
In this study, after 2 years of protocol-guided anti-vascular endothelial growth factor treatment for nAMD, more than half of the eyes in the study developed NGA in the location of nAMD. After 3 additional years of regular care, half of them progressed to GA.
ClinicalTrials.gov Identifier: NCT00593450.
视网膜色素减退和色素沉着是地理萎缩（GA）的前兆。抗血管内皮生长因子治疗新生血管性年龄相关性黄斑变性（nAMD）的眼部病变未发生非 GA（NGA）的发生率和进展情况尚不清楚。
确定非 GA（NGA）的发生率和进展情况及其相关危险因素。
设计、地点和参与者：本研究是 CATT 临床试验队列研究的事后分析。参与者于 2008 年 2 月 20 日至 2009 年 12 月 9 日招募；在 2 年后从协议随访和治疗中释放；并于 2014 年 3 月 14 日至 2015 年 3 月 31 日召回。数据分析于 2019 年 1 月 11 日至 2019 年 11 月 27 日进行。
参与者被随机分配接受雷珠单抗或贝伐单抗治疗（1）2 年的每月或按需注射或（2）1 年的每月注射和下一年的按需注射。此后，根据最佳医疗判断对参与者进行治疗。
nAMD 相关 NGA（彩色图像中的色素减退和色素沉着）的发生率和进展；调整基线特征的风险比（aRR）。
在 1107 名参与者中，分别有 35%（391 只眼）、59%（246 只眼）和 81%（122 只眼）在 1、2 和 5 年内出现 NGA。NGA 的危险因素包括视力更差（20/200-20/320：aRR，1.74[95%CI，1.24-2.43]，与≤20/40 相比；P=0.006）、新生血管面积更大（>4 个盘区：aRR，1.31[95%CI，1.01-1.71]，与≤1 个盘区相比；P=0.007）、药物治疗方案改变（aRR，1.28[95%CI，1.06-1.54]，与按需注射相比；P=0.02）和单核苷酸变异体年龄相关性黄斑病变易感性 2（ARMS2）（TT 变异体：相对风险[RR]，1.53[95%CI，1.22-1.93]；P=0.001）和 HtrA 丝氨酸肽酶 1（HTRA1）（AG 变异体：RR，1.23[95%CI，1.01-1.48]；AA 变异体：RR，1.51[95%CI，1.20-1.91]；P=0.002）。视网膜下色素上皮厚度是保护性的（>275μm：aRR，0.59[95%CI，0.46-0.75]，与≤75μm 相比；P<0.001）。在 2 年内出现 NGA 并随后进行彩色图像检查的 389 只眼中，分别有 29%、43%和 50%在 1、3 和 4 年内进展为 GA。进展为 GA 的危险因素包括视力更差（20/200-20/320：aRR，2.75[95%CI，1.54-4.93]，与≤20/40 相比；P<0.001）、对侧眼视力更差（<20/40：aRR，1.77[95%CI，1.12-2.79]，与≥20/40 相比；P=0.01）、对侧眼 GA（aRR，1.71[95%CI，1.06-2.75]；P=0.03）和双眼假性血管翳（aRR，1.65[95%CI，1.17-2.34]；P=0.005）。视网膜下液与进展风险降低相关（aRR，0.42[95%CI，0.28-0.63]；P<0.001）。
在这项研究中，在 2 年的抗血管内皮生长因子治疗 nAMD 协议指导治疗后，研究中一半以上的眼在 nAMD 的位置出现 NGA。在随后的 3 年常规治疗后，其中一半进展为 GA。
ClinicalTrials.gov 标识符：NCT00593450。
