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 μm, 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.

中文翻译：

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黄斑萎缩在新生血管年龄相关性黄斑变性的HARBOR研究中

目的

为了评估新血管性年龄相关性黄斑变性（AMD）在24个月的HARBOR研究（NCT00891735）中的黄斑萎缩（MA）的存在。

设计

对3期多中心，前瞻性，随机，双盲，积极治疗控制的临床试验进行事后分析。

参加者

可评估的受试者（N = 1095），继发于新生血管性AMD的小凹下脉络膜脉络膜新生血管（CNV），每月接受雷珠单抗0.5 mg或2.0 mg或前列腺素（PRN）治疗。

方法

蒙面分级师对基线，第3、12和24个月的荧光素血管造影照片（FAs）和彩色眼底照片进行了回顾性分级：明确的色素脱失区域，脉络膜血管可见度增加，直径≥250μm，对应于FA上划定的染色，不包括与视网膜色素上皮撕裂相关的萎缩。包括在CNV病变内，相邻且不相邻的萎缩。

主要观察指标

黄斑萎缩发生率，最佳矫正视力（BCVA）。

结果

基线时，在研究眼的11.2％（123/1095）中检测到了MA。在第24个月，没有基线萎缩的眼睛有29.4％（229/778）有可检出的MA。有和没有基线MA的眼睛在第24个月时均具有比基线明显的平均BCVA增高（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个月有或没有MA的眼睛中，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。24个月MA存在的基线危险因素包括视网膜内囊肿（危险比[HR]，2.45 [1.76-3.42]）和同伴眼萎缩（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]）。雷尼单抗剂量与MA发展无关。每月与PRN的治疗趋向于与MA相关（HR，1.29 [0.99–1.68]），

结论

治疗24个月后，在29％的研究眼睛中发现了新的MA。在过去的24个月中，MA的使用可实现临床上显着的BCVA增益。基线视网膜下积液缺乏，视网膜内囊肿存在和同伴眼萎缩与24个月MA的存在有关。根据现有数据，兰尼单抗对新生血管性AMD的益处超过了HABOR治疗24个月内发生MA的风险，尽管未评估> 2年的结局。