Macular Atrophy in the HARBOR Study for Neovascular Age-Related Macular Degeneration
Macular Atrophy in the HARBOR Study for Neovascular Age-Related Macular Degeneration
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DOI：
10.1016/j.ophtha.2017.12.026
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发表时间：
2018-06-01
期刊：
影响因子：
13.7
通讯作者：
Hopkins, J. Jill
中科院分区：
文献类型：
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作者：
Sadda, SriniVas R.;Tuomi, Lisa L.;Hopkins, J. Jill
目的：在为期24个月的HARBOR研究中评价黄斑萎缩（MA）的存在（NCT 00891735）用于新生血管性年龄相关性黄斑变性（AMD）。设计：3期多中心、前瞻性、随机、双盲、活性治疗对照临床试验的事后分析。参与者：可评价受试者（N = 1095）继发于新生血管性AMD的中心凹下脉络膜新生血管（CNV），接受雷珠单抗0.5 mg或2.0 mg每月一次或临产（PRN）治疗方法：由设盲的分级者对基线和第3、12和24个月的血管造影（FA）和彩色眼底照片进行MA回顾性分级：边界清晰的色素脱失区域，脉络膜血管可见度增加，直径≥ 250 mm，对应于FA上边界清晰的染色平坦区域，不包括与视网膜色素上皮撕裂相关的萎缩。包括CNV病变内、邻近和不邻近的萎缩。主要结局指标：结果：在基线时，11.2%（123/1095）的研究眼检测到MA。在第24个月时，29.4%（229/778）基线无萎缩的眼睛可检测到MA。第24个月时，有和无基线MA的眼睛的平均BCVA较基线显著增加（字母[95%置信区间]：分别为+6.7 [4.1-9.3]; +9.1 [8.0-10.2]）。在第24个月时有MA和无MA的患眼中，第24个月的平均BCVA分别为62.0 [60.3-63.7]和64.7 [63.2-66.3]个字母。第24个月MA存在的基线风险因素包括视网膜内囊肿（风险比[HR]，2.45 [1.76-3.42]）和对侧眼萎缩（HR，2.02 [1.42-2.87]）;视网膜下液与较低的MA风险相关（HR，0.50 [0.33-0.74]）。雷珠单抗剂量与MA发生无关。每月与PRN治疗的趋势与MA（HR，1.29 [0.99-1.68]），但没有统计学意义。结论：新MA检测在29%的研究眼睛后，24个月的治疗。在24个月内，MA存在时获得了临床显著的BCVA增益。基线视网膜下液缺乏、视网膜内囊肿存在和对侧眼萎缩存在与第24个月MA存在相关。根据现有数据，在HARBOR研究中，雷珠单抗治疗新生血管性AMD的获益超过了24个月内MA发展的风险，尽管没有评估> 2年的结局。(C)2018年美国眼科学会。
Purpose: To evaluate macular atrophy (MA) presence in the 24-month HARBOR study (NCT00891735) for neovascular age-related macular degeneration (AMD).Design: Post hoc analysis of a phase 3 multicenter, prospective, randomized, double-masked, active treatment-controlled clinical trial.Participants: Evaluable subjects (N = 1095) with subfoveal choroidal neovascularization (CNV) secondary to neovascular AMD treated with ranibizumab 0.5 mg or 2.0 mg monthly or pro re nata (PRN).Methods: Fluorescein angiograms (FAs) and color fundus photographs at baseline and months 3, 12, and 24 were retrospectively graded by masked graders for MA: well-defined areas of depigmentation with increased choroidal vessel visibility, diameter >= 250 mm, corresponding to flat areas of well-demarcated staining on FA, excluding atrophy associated with retinal pigment epithelium tears. Atrophy immediately within, adjacent, and nonadjacent to CNV lesions was included. Main Outcome Measures: Macular atrophy incidence, best-corrected visual acuity (BCVA).Results: At baseline, MA was detected in 11.2% (123/1095) of study eyes. At month 24, 29.4% (229/778) of eyes without baseline atrophy had detectable MA. Eyes with and without baseline MA had significant mean BCVA gains from baseline at month 24 (letters [95% confidence interval]: +6.7 [4.1-9.3]; +9.1 [8.0-10.2], respectively). Among eyes with and without MA at month 24, mean month 24 BCVA was 62.0 [60.3-63.7] and 64.7 [63.2-66.3] letters, respectively. Baseline risk factors for month 24 MA presence included intraretinal cysts (hazard ratio [HR], 2.45 [1.76-3.42]) and fellow eye atrophy (HR, 2.02 [1.42-2.87]); subretinal fluid was associated with a lower MA risk (HR, 0.50 [0.33-0.74]). Ranibizumab dose was not associated with MA development. Monthly versus PRN treatment trended toward an association with MA (HR, 1.29 [0.99-1.68]), but was not statistically significant.Conclusions: New MA was detected in 29% of study eyes after 24 months of treatment. Clinically significant BCVA gains were achieved with MA present over 24 months. Baseline subretinal fluid absence, intraretinal cyst presence, and fellow eye atrophy presence were associated with month 24 MA presence. With existing data, the benefits of ranibizumab for neovascular AMD outweighed the risk of MA development over 24 months in HARBOR, although outcomes > 2 years were not evaluated. (C) 2018 by the American Academy of Ophthalmology.