Background/Objectives

Systemic levels of pro-inflammatory cytokines and activated complement components affect the risk and/or progression of neovascular age-related macular degeneration (AMD). This study investigated the effect of serum pro-inflammatory cytokine levels and complement pathway activity on the clinical response to vascular endothelial growth factor (VEGF) inhibition in neovascular AMD.

Methods

Sixty-five patients with a new diagnosis of neovascular AMD were observed over a six-month period in a single-centre, longitudinal cohort study. At each visit, the visual acuity score (VAS), central macular thickness (CMT), serum levels of CRP, pro-inflammatory cytokines (TNF-α, IL-1β, IL-2, IL-6 and IL-8), and complement pathway activity were measured. Participant DNA samples were sequenced for six complement pathway single nucleotide polymorphisms (SNPs) associated with AMD.

Results

A statistically significant difference in VAS was observed for serum levels of TNF-α only: there was a gain in VAS (from baseline) of 1.37 for participants below the 1st quartile of mean concentration compared to a reduction of 2.71 for those above the 3rd quartile. Statistical significance was maintained after Bonferroni correction (P value set at <0.006). No significant differences in CMT were observed. In addition, statistically significant differences, maintained after Bonferroni correction, were observed in serum complement activity for participants with the following SNPs: CFH region (rs1061170), SERPING1 (rs2511989) and CFB (rs641153). Serum complement pathway components did not significantly affect VAS.

Conclusions

Lower serum TNF-α levels were associated with an increase in visual acuity after anti-VEGF therapy. This suggests that targeting pro-inflammatory cytokines may augment treatment for neovascular AMD.

中文翻译：

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TNF-α的全身水平和补体通路活性对新生血管性AMD中VEGF抑制结果的影响

背景/目标

促炎细胞因子和活化补体成分的全身水平影响新生血管性年龄相关性黄斑变性 (AMD) 的风险和/或进展。本研究调查了血清促炎细胞因子水平和补体通路活性对新生血管性 AMD 中血管内皮生长因子 (VEGF) 抑制的临床反应的影响。

方法

在一项单中心纵向队列研究中，在六个月的时间里观察了 65 名新诊断为新生血管性 AMD 的患者。每次就诊时，视力评分 (VAS)、中央黄斑厚度 (CMT)、血清 CRP 水平、促炎细胞因子 (TNF-α、IL-1β、IL-2、IL-6 和 IL-8)、和补体途径活性进行了测量。参与者 DNA 样本被测序，以确定与 AMD 相关的六种补体途径单核苷酸多态性 (SNP)。

结果

仅观察到 TNF-α 血清水平的 VAS 有统计学显着差异：平均浓度低于第 1 个四分位数的参与者的 VAS（从基线）增加 1.37，而高于第 3 个四分位数的参与者减少 2.71 . Bonferroni 校正后保持统计学显着性（P值设置为 <0.006）。没有观察到 CMT 的显着差异。此外，在具有以下 SNP 的参与者的血清补体活性中观察到 Bonferroni 校正后保持的统计学显着差异：CFH区域 (rs1061170)、SERPING1 (rs2511989) 和CFB (rs641153)。血清补体途径成分对 VAS 没有显着影响。

结论

较低的血清 TNF - α 水平与抗 VEGF 治疗后视力的增加有关。这表明靶向促炎细胞因子可能会增加对新生血管性 AMD 的治疗。