Department of Ophthalmology, St. Michael's Hospital/Unity Health Toronto, Toronto, Ontario, Canada.
Department of Ophthalmology & Vision Sciences, University of Toronto, Toronto, Ontario, Canada.
Acta Ophthalmol. 2021 Mar;99(2):134-155. doi: 10.1111/aos.14537. Epub 2020 Jun 29.
Inflammatory cytokines are involved in the pathogenesis of neovascular age-related macular degeneration (nAMD) and have been shown to be useful as diagnostic and predictive biomarkers. Given the heterogeneity of data within the literature, we aimed to quantitatively summarize data related to inflammatory cytokines in nAMD. A systematic search without year limitation was performed up to 13 April 2020. Studies were included if they provided data on aqueous or vitreous cytokine concentrations in patients with nAMD. Data were extracted from 95 studies that encompassed 3105 study eyes with nAMD and 1209 control eyes. Effect sizes were generated as standardized mean differences (SMDs) of cytokine concentrations between patients with nAMD and controls. Among the 4314 eyes in 95 studies, aqueous concentrations (standard mean difference, 95% confidence interval and p-value) of MCP-1 (0.43, 0.09 to 0.77 and p = 0.01), MIG (0.63, 0.31 to 0.94 and p = 0.0001), TGF-β (0.45, 0.07 to 0.82 and p = 0.02) and VEGF (0.64, 0.31 to 0.98 and p = 0.0001) were significantly higher in patients with nAMD compared to healthy controls. No differences, failed sensitivity analyses or insufficient data were found between patients with nAMD and healthy controls for the concentrations of the remaining cytokines and with all vitreous samples. Previous studies had shown conflicting associations with nAMD for all 27 cytokines assessed. Our analysis indicates multiple candidate cytokines other than VEGF that are implicated in nAMD and adds clarity to the previous literature. This will help focus translational research in nAMD investigating biomarkers and therapeutic targets.
炎症细胞因子参与新生血管性年龄相关性黄斑变性（nAMD）的发病机制，已被证明可用作诊断和预测生物标志物。鉴于文献中数据的异质性，我们旨在定量总结与 nAMD 相关的炎症细胞因子数据。系统检索无年限限制，截至 2020 年 4 月 13 日。如果研究提供了 nAMD 患者房水或玻璃体内细胞因子浓度的数据，则纳入研究。从 95 项研究中提取数据，这些研究包括 3105 只 nAMD 研究眼和 1209 只对照眼。效应大小以细胞因子浓度在 nAMD 患者和对照组之间的标准化均数差（SMD）表示。在 95 项研究的 4314 只眼中，MCP-1（0.43，0.09 至 0.77 和 p=0.01）、MIG（0.63，0.31 至 0.94 和 p=0.0001）、TGF-β（0.45，0.07 至 0.82 和 p=0.02）和 VEGF（0.64，0.31 至 0.98 和 p=0.0001）的房水浓度在 nAMD 患者中明显高于健康对照组。在 nAMD 患者和健康对照组之间，其余细胞因子的浓度以及所有玻璃体样本均未发现差异、敏感性分析失败或数据不足。先前的研究表明，评估的 27 种细胞因子与 nAMD 均存在相互矛盾的关联。我们的分析表明，除了 VEGF 之外，还有多种候选细胞因子与 nAMD 有关，并为之前的文献提供了更清晰的认识。这将有助于集中研究 nAMD 的转化研究，以探索生物标志物和治疗靶点。
