Department of Ophthalmology, Seoul St Mary's Hospital, The Catholic University of Korea, Seoul, Korea.
Department of Ophthalmology, Tokyo Women's Medical University, Tokyo, Japan.
JAMA Ophthalmol. 2018 Jul 1;136(7):786-793. doi: 10.1001/jamaophthalmol.2018.1804.
Polypoidal choroidal vasculopathy (PCV) is common in Asian populations, but an optimal treatment approach remains to be confirmed.
To evaluate intravitreal aflibercept injection (IAI) in participants with PCV and compare IAI monotherapy with IAI plus rescue photodynamic therapy (PDT).
DESIGN, SETTING, AND PARTICIPANTS: This 96-week, double-masked, sham-controlled phase 3b/4 randomized clinical trial was conducted at multiple centers in Australia, Germany, Hong Kong, Hungary, Japan, Singapore, South Korea, and Taiwan from May 2014 to August 2016, and included adults 50 years or older with symptomatic macular PCV and a best-corrected visual acuity of 73 to 24 Early Treatment Diabetic Retinopathy Study letters (20/40-20/320 Snellen equivalent).
Participants received 2 mg of IAI at weeks 0, 4, and 8. At week 12, participants with a suboptimal response were randomized 1:1 to receive IAI plus sham PDT (IAI monotherapy) or a "rescue" of IAI plus rescue PDT (IAI/PDT). Participants who did not qualify for rescue received IAI every 8 weeks; those qualifying for rescue received IAI every 4 weeks plus sham/active PDT. When the rescue criteria were no longer met, injection intervals were gradually extended to 8 weeks.
Noninferiority of IAI monotherapy to IAI/PDT for mean change in best-corrected visual acuity from baseline to week 52 (95% CI of the difference entirely above -5 letters).
Of the 318 participants, the mean (SD) age was 70.6 (8.2) years, 96 (30.2%) were women, and 152 (47.8%) were Japanese. Monotherapy with IAI was noninferior to IAI/PDT for the primary end point (+10.7 vs +10.8 letters, respectively; 95% CI, -2.9 to 1.6; P = .55), with few participants requiring rescue therapy (19 [12.1%] vs 23 [14.3%], respectively). Participants in both treatment groups had similar reductions in central subfield thickness from baseline to week 52 (-137.7 [IAI monotherapy] vs -143.5 μm [IAI/PDT]). At week 52, 49 (38.9%) and 60 participants (44.8%) had no polypoidal lesions observed on indocyanine green angiography in the IAI monotherapy and IAI/PDT groups, respectively. Furthermore, 116 (81.7%) and 136 (88.9%), respectively, had no polypoidal lesions with leakage. The most frequent ocular adverse events were conjunctival hemorrhage (IAI monotherapy, 8 [5.1%]) and dry eye (IAI/PDT, 9 [5.6%]).
Improvement in visual and/or functional outcomes was achieved in more than 85% of participants who were treated with IAI monotherapy, with no signs of leakage from polypoidal lesions in more than 80%. As fewer than 15% met the criteria of a suboptimal response to receive PDT, the potential benefit of adding PDT cannot be determined.
ClinicalTrials.gov Identifier: NCT02120950.
息肉样脉络膜血管病变（PCV）在亚洲人群中很常见，但仍需确定最佳治疗方法。
评估玻璃体内阿柏西普注射（IAI）在 PCV 患者中的疗效，并比较 IAI 单药治疗与 IAI 联合挽救性光动力疗法（PDT）。
设计、地点和参与者：这是一项 96 周、双盲、假对照的 3b/4 期随机临床试验，于 2014 年 5 月至 2016 年 8 月在澳大利亚、德国、中国香港、匈牙利、日本、新加坡、韩国和中国台湾的多个中心进行，纳入年龄 50 岁及以上、有症状的黄斑 PCV 和最佳矫正视力为 73 至 24 个早期治疗糖尿病视网膜病变研究字母（20/40-20/320 斯耐伦等价物）的成年人。
参与者在 0、4 和 8 周时接受 2mg IAI。在第 12 周，对反应不佳的参与者进行 1:1 随机分组，接受 IAI 联合假性 PDT（IAI 单药治疗）或“挽救”IAI 联合挽救性 PDT（IAI/PDT）。未符合挽救标准的参与者每 8 周接受一次 IAI；符合挽救标准的参与者每 4 周接受一次 IAI 联合假性/活性 PDT。当挽救标准不再满足时，注射间隔逐渐延长至 8 周。
从基线到第 52 周，最佳矫正视力的平均变化，IAI 单药治疗与 IAI/PDT 的非劣效性（差异的 95%置信区间完全在-5 个字母以上）。
在 318 名参与者中，平均（SD）年龄为 70.6（8.2）岁，96（30.2%）为女性，152（47.8%）为日本人。IAI 单药治疗与 IAI/PDT 的主要终点相似（分别增加 10.7 比 10.8 个字母，95%CI，-2.9 至 1.6；P=0.55），需要挽救治疗的参与者较少（19 [12.1%] 比 23 [14.3%]）。两组参与者的中央视网膜下厚度均从基线到第 52 周有相似的降低（IAI 单药治疗组减少 137.7μm[IAI 单药治疗]比 IAI/PDT 组减少 143.5μm）。在第 52 周时，IAI 单药治疗组和 IAI/PDT 组分别有 49（38.9%）和 60 名参与者（44.8%）在吲哚青绿血管造影上没有观察到息肉样病变。此外，IAI 单药治疗组和 IAI/PDT 组分别有 116（81.7%）和 136（88.9%）名参与者没有息肉样病变伴有渗漏。最常见的眼部不良事件是结膜下出血（IAI 单药治疗组 8[5.1%]）和干眼症（IAI/PDT 组 9[5.6%]）。
超过 85%接受 IAI 单药治疗的参与者的视力和/或功能结果得到改善，超过 80%的参与者没有息肉样病变伴有渗漏。由于不到 15%的参与者符合接受 PDT 的反应不佳标准，因此无法确定添加 PDT 的潜在益处。
ClinicalTrials.gov 标识符：NCT02120950。
