Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria.
Ophthalmology. 2012 Aug;119(8):1615-20. doi: 10.1016/j.ophtha.2012.02.001. Epub 2012 Apr 21.
Along with environmental risk factors such as smoking, hypertension, and atherosclerosis, genetic susceptibility is a primary contributor to the development and progression of exudative age-related macular degeneration (AMD). Vascular endothelial growth factor (VEGF) is a central angiogenic regulator and there has been general agreement now that it is an important trigger for the progression of exudative AMD. In the present study, we tested the hypothesis that VEGF gene polymorphisms play a role in the treatment success with VEGF inhibitors in patients with exudative AMD.
Prospective cohort study.
We included 185 eyes of 141 patients with exudative AMD who were scheduled for their first treatment with intravitreally administered bevacizumab in this trial.
All patients were aged >50 years and had angiographically verified exudative AMD. Blood from the finger pad was collected on blood cards for genotyping for the VEGF polymorphisms rs1413711, rs3025039, rs2010963, rs833061, rs699947, rs3024997, and rs1005230. At each follow-up visit, visual acuity was reassessed and an ophthalmic examination was carried out. Visual acuity outcome, number of retreatments, and overall time of treatment were analyzed in dependence of the VEGF polymorphisms.
Mean change in visual acuity at the end of the treatment period.
The included patients were reinjected with bevacizumab 1 to 15 times, resulting in a total treatment period of 42 to 1182 days. In univariate analysis only the G/G genotypes of rs3024997 and rs2010963 compared with all other 5 single nucleotide polymorphisms (SNPs) showed a significantly lower visual acuity at the end of treatment. In multivariate analysis including parameters such as time, baseline visual acuity, and number of reinjections, none of the SNPs showed a significant correlation.
The current study indicates that VEGF polymorphisms are not major predictors of anti-VEGF treatment success in patients with exudative AMD.
除了吸烟、高血压和动脉粥样硬化等环境危险因素外,遗传易感性也是渗出性年龄相关性黄斑变性(AMD)发生和发展的主要原因。血管内皮生长因子(VEGF)是一种重要的血管生成调节剂,目前普遍认为它是渗出性 AMD 进展的重要触发因素。在本研究中,我们检验了这样一个假设,即 VEGF 基因多态性在接受抗 VEGF 治疗的渗出性 AMD 患者的治疗效果中发挥作用。
前瞻性队列研究。
本试验纳入了 141 例年龄大于 50 岁且经血管造影证实为渗出性 AMD 的患者的 185 只眼,这些患者均计划首次接受玻璃体内注射贝伐单抗治疗。
所有患者均采集指垫血样,用血液卡进行 VEGF 多态性 rs1413711、rs3025039、rs2010963、rs833061、rs699947、rs3024997 和 rs1005230 的基因分型。每次随访时,均重新评估视力,并进行眼科检查。根据 VEGF 多态性分析视力结果、治疗次数和总治疗时间。
治疗期末视力的平均变化。
纳入的患者接受贝伐单抗注射 115 次,治疗总时间为 421182 天。单变量分析仅 rs3024997 和 rs2010963 的 G/G 基因型与其他 5 个单核苷酸多态性(SNP)相比,治疗期末视力明显较低。在包括时间、基线视力和再注射次数等参数的多变量分析中,没有一个 SNP 显示出与治疗效果有显著相关性。
本研究表明,VEGF 多态性不是渗出性 AMD 患者抗 VEGF 治疗效果的主要预测因子。