Aqueous proteins help predict the response of patients with neovascular age-related macular degeneration to anti-VEGF therapy.
Aqueous proteins help predict the response of patients with neovascular age-related macular degeneration to anti-VEGF therapy.
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含水蛋白有助于预测新生血管性年龄相关性黄斑变性患者对抗vegf治疗的反应。
DOI：
10.1172/jci144469
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发表时间：
2022-01-18
期刊：
影响因子：
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通讯作者：
Sodhi A
中科院分区：
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作者：
Cao X;Sanchez JC;Dinabandhu A;Guo C;Patel TP;Yang Z;Hu MW;Chen L;Wang Y;Malik D;Jee K;Daoud YJ;Handa JT;Zhang H;Qian J;Montaner S;Sodhi A
为了减轻新生血管性年龄相关性黄斑变性（nvAMD）患者的治疗负担，针对血管内皮生长因子（VEGF）的新疗法正在设计中，以延长治疗间隔，从而最大限度地减少眼内注射次数。然而，哪些患者将受益于长效药物尚不清楚。患有nvAMD的眼睛（n = 122）连续3个月接受目前可用的抗vegf疗法的注射，随后进行治疗和延长方案。从之前的治疗中保持静止状态12周的患者进入治疗暂停期，并切换到恢复原状（PRN）治疗（基于视力、临床检查和/或影像学检查）。对含水液体进行蛋白质组学分析，以确定与患者对治疗反应相关的蛋白质。1年后，122只眼中有38只（31%）进入治疗暂停期（≥30周）。相反，122只眼中有21只（17%）的延长治疗失败，在第一年末需要每月治疗。蛋白质组学分析确定了与患者对治疗反应相关的蛋白质，包括先前与AMD发病机制有关的蛋白质。有趣的是，载脂蛋白b100 （ApoB100）是与非新生血管性AMD进展有关的drusen的主要成分，在需要较少注射次数的治疗患者中增加。与对照组相比，ApoB100在AMD眼睛中的表达较高，但在发生脉络膜新生血管（CNV）的眼睛中表达较低，与保护作用一致。因此，过表达ApoB100的小鼠部分免受激光诱导的CNV。这项工作得到了国家眼科研究所、国家卫生研究院资助R01EY029750、R01EY025705和R01 EY27961的支持；预防失明研究公司；爱尔康研究所；约翰霍普金斯大学通过罗伯特·邦德·韦尔奇，布兰娜和欧文·西森韦恩的眼科学教授。含水生物标志物可以帮助识别可能不需要或不受益于长期抗vegf治疗的nvAMD患者。
To reduce the treatment burden for patients with neovascular age-related macular degeneration (nvAMD), emerging therapies targeting vascular endothelial growth factor (VEGF) are being designed to extend the interval between treatments, thereby minimizing the number of intraocular injections. However, which patients will benefit from longer-acting agents is not clear. Eyes with nvAMD (n = 122) underwent 3 consecutive monthly injections with currently available anti-VEGF therapies, followed by a treat-and-extend protocol. Patients who remained quiescent 12 weeks from their prior treatment entered a treatment pause and were switched to pro re nata (PRN) treatment (based on vision, clinical exam, and/or imaging studies). Proteomic analysis was performed on aqueous fluid to identify proteins that correlate with patients’ response to treatment. At the end of 1 year, 38 of 122 eyes (31%) entered a treatment pause (≥30 weeks). Conversely, 21 of 122 eyes (17%) failed extension and required monthly treatment at the end of year 1. Proteomic analysis of aqueous fluid identified proteins that correlated with patients’ response to treatment, including proteins previously implicated in AMD pathogenesis. Interestingly, apolipoprotein-B100 (ApoB100), a principal component of drusen implicated in the progression of nonneovascular AMD, was increased in treated patients who required less frequent injections. ApoB100 expression was higher in AMD eyes compared with controls but was lower in eyes that develop choroidal neovascularization (CNV), consistent with a protective role. Accordingly, mice overexpressing ApoB100 were partially protected from laser-induced CNV. This work was supported by the National Eye Institute, National Institutes of Health grants R01EY029750, R01EY025705, and R01 EY27961; the Research to Prevent Blindness, Inc.; the Alcon Research Institute; and Johns Hopkins University through the Robert Bond Welch and Branna and Irving Sisenwein professorships in ophthalmology. Aqueous biomarkers could help identify patients with nvAMD who may not require or benefit from long-term treatment with anti-VEGF therapy.