Shimura Masahiko, Sasaki Shotaro, Nonaka Ryota, Kashiwagi Ikumi, Yasuda Kanako, Noma Hidetaka, Takagi Hitoshi
Department of Ophthalmology, Tokyo Medical University Hachioji Medical Center, Hachioji, Tokyo, Japan.
Kawasaki-Tama Eye Clinic, Kawasaki, Kanagawa, Japan.
Transl Vis Sci Technol. 2024 Dec 2;13(12):35. doi: 10.1167/tvst.13.12.35.
The purpose of this study was to investigate the dynamic changes in aqueous concentrations of angiopoietin (Ang)-1/2 and vascular endothelial growth factor (VEGF) during injection in treatment-naïve patients with diabetic macular edema (DME) receiving faricimab during the induction phase (3 consecutive monthly doses) and retrospectively analyze the data.
Thirty-five eyes of 26 patients (age = 63.1 ± 12.9 years) with treatment-naïve DME received faricimab injections monthly, 3 consecutive times. Additionally, 59 eyes of 59 patients (age = 63.9 ± 8.8 years) who underwent cataract surgery were recruited as controls. Aqueous humor samples were collected from each injection or surgery and stored at -80°C, and the concentration of each cytokine was quantified using a multiple enzyme-linked immunosorbent assay (Luminex). The clinical parameters of best-corrected visual acuity (BCVA) and central foveal thickness (CFT) at each visit were also recorded.
Three induction phases of faricimab significantly suppressed each aqueous cytokine, rapidly for VEGF, gradually for Ang-2, and slightly for Ang-1. The Ang-1/2 ratio was lower (<1.0) at baseline and gradually increased, but did not reach a control ratio of 1.58. The baseline CFT correlated with VEGF, but not with the Ang-2, Ang-1, or Ang-1/2 ratios. After three injections, CFT did not correlate with VEGF, but it positively correlated with Ang-2 and negatively correlated with Ang-1, and it strongly negatively correlated with the Ang-1/2 ratio.
The Ang-1/2 ratio in the aqueous humor significantly negatively correlated with the degree of residual edema after faricimab treatment for DME.
The Ang-1/2 ratio in aqueous humor is thus a useful biomarker of the treatment response for DME.
本研究旨在调查初治糖尿病性黄斑水肿(DME)患者在诱导期(连续3个每月一次的剂量)接受法西单抗注射期间房水中血管生成素(Ang)-1/2和血管内皮生长因子(VEGF)浓度的动态变化,并对数据进行回顾性分析。
26例(年龄=63.1±12.9岁)初治DME患者的35只眼每月接受一次法西单抗注射,连续3次。此外,招募59例(年龄=63.9±8.8岁)接受白内障手术的患者的59只眼作为对照。在每次注射或手术后采集房水样本,储存在-80°C,使用多重酶联免疫吸附测定(Luminex)对每种细胞因子的浓度进行定量。每次就诊时还记录最佳矫正视力(BCVA)和中心凹厚度(CFT)的临床参数。
法西单抗的三个诱导期显著抑制了每种房水细胞因子,对VEGF的抑制迅速,对Ang-2的抑制逐渐,对Ang-1的抑制轻微。Ang-1/2比值在基线时较低(<1.0),并逐渐升高,但未达到对照比值1.58。基线CFT与VEGF相关,但与Ang-2、Ang-1或Ang-1/2比值无关。三次注射后,CFT与VEGF不相关,但与Ang-2呈正相关,与Ang-1呈负相关,与Ang-1/2比值呈强烈负相关。
DME患者接受法西单抗治疗后,房水中的Ang-1/2比值与残余水肿程度显著负相关。
因此,房水中的Ang-1/2比值是DME治疗反应的有用生物标志物。