Department of Ophthalmology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
Graefes Arch Clin Exp Ophthalmol. 2019 Nov;257(11):2559-2569. doi: 10.1007/s00417-019-04456-2. Epub 2019 Sep 3.
At present, the standard treatment of neovascular age-related macular degeneration (AMD) is the repeated administration of antivascular endothelial growth factor (VEGF) agents. However, we often encounter patients who develop tachyphylaxis for anti-VEGF agents. In this study, we investigated the characteristics of patients who developed tachyphylaxis on repeated intravitreal aflibercept (IVA) injections for neovascular AMD and the frequency of tachyphylaxis.
Three hundred thirteen eyes (313 patients) with treatment-naïve AMD who achieved resolution soon after starting IVA and were followed up for ≥ 12 months were enrolled in this retrospective, interventional, consecutive case series. The eyes were investigated for tachyphylaxis to aflibercept. Tachyphylaxis was defined as absence of any improvement (more than 100 μm) in or worsening of CRT within 1 month after more than two repeated monthly IVA injections when the exudative change remained.
Twenty-eight (8.9%) of the 313 eyes developed tachyphylaxis (occult with no classic, n = 14; polypoidal choroidal vasculopathy, n = 14) at an annual rate of about 3%. The mean number of IVA injections was 10.5 ± 7.8, and the mean interval until tachyphylaxis was 20.9 ± 14.0 months. There was a significant difference in the AMD subtypes between the group with tachyphylaxis and the group without it (p = 0.0029). Occult with no classic type and polypoidal choroidal vasculopathy were the only AMD subtypes in the eyes with tachyphylaxis. In the analysis of the eyes that had occult with no classic or polypoidal choroidal vasculopathy, only intraretinal edema was significantly less common (p = 0.042). A combination of photodynamic therapy and aflibercept was effective in 13 (87%) of 15 eyes with tachyphylaxis, and switching to intravitreal ranibizumab was effective in 5 (56%) of 9 eyes.
Tachyphylaxis occurs after repeated IVA injections in a minority of patients with AMD for a long term and is more likely to occur in eyes with lesions beneath the retinal pigment epithelium and no intraretinal edema. Treatment of AMD should be performed keeping this fact in mind, while considering the consecutive treatment.
目前，新生血管性年龄相关性黄斑变性（AMD）的标准治疗方法是反复给予抗血管内皮生长因子（VEGF）药物。但是，我们经常遇到对抗 VEGF 药物产生快速耐受的患者。在本研究中，我们研究了在反复玻璃体内注射阿柏西普（IVA）治疗新生血管性 AMD 时出现快速耐受的患者的特征和快速耐受的频率。
本回顾性、干预性、连续病例系列研究纳入了 313 只眼（313 例）初治 AMD 患者，这些患者在开始 IVA 治疗后很快得到缓解，并且随访时间≥12 个月。对这些眼进行阿柏西普快速耐受的研究。快速耐受定义为在超过两次每月重复 IVA 注射后 1 个月内 CRT 没有任何改善（超过 100 μm）或恶化，同时渗出性改变仍然存在。
28 只眼（8.9%）出现快速耐受（隐匿型，无典型型，n=14；息肉状脉络膜血管病变型，n=14），年发生率约为 3%。IVA 注射的平均次数为 10.5±7.8 次，快速耐受的平均间隔时间为 20.9±14.0 个月。快速耐受组和无快速耐受组的 AMD 亚型有显著差异（p=0.0029）。隐匿型，无典型型和息肉状脉络膜血管病变型是快速耐受眼的唯一 AMD 亚型。在隐匿型或息肉状脉络膜血管病变型眼的分析中，仅视网膜内水肿明显较少见（p=0.042）。光动力疗法联合阿柏西普治疗对 15 只快速耐受眼中的 13 只（87%）有效，玻璃体腔内雷珠单抗治疗对 9 只快速耐受眼中的 5 只（56%）有效。
在长期接受阿柏西普重复玻璃体内注射的 AMD 患者中，少数患者会出现快速耐受，并且在有视网膜色素上皮下病变和无视网膜内水肿的眼中更有可能出现。在考虑连续治疗的同时，应牢记这一事实，进行 AMD 的治疗。
