Chang Woohyok, Noh Dong Hyoun, Sagong Min, Kim In Taek
Department of Ophthalmology, Yeungnam University College of Medicine, Daegu, South Korea.
Mol Vis. 2013;19:702-9. Epub 2013 Mar 21.
To determine whether genetic factors that influence age-related macular degeneration (AMD) have an early pharmacogenetic effect on treating exudative AMD with ranibizumab in a Korean population.
A retrospective study of 102 patients (70 with typical neovascular AMD and 32 with polypoidal choroidal vasculopathy) with exudative AMD treated with intravitreal ranibizumab monotherapy was conducted. Optical coherence tomography, fluorescein, and indocyanine green angiography were taken at the baseline. The best-corrected visual acuity (BCVA) and the central subfield macular thickness (CSMT) were recorded at the baseline and at each monthly visit. The genotypes of the polymorphisms in the known AMD susceptibility loci (CFH, AMRS2, HTRA1, VEGFA, and KDR) were determined, and association between their frequencies and the changes in the BCVA and the CSMT were evaluated.
The mean baseline visual acuity was 0.96 ± 0.59 logMAR (approximately 20/200 in the Snellen equivalent), and the mean number of injections was 3.87 before the month 6 visit. No association was observed between the change in BCVA and each genotype. For the changes in the CSMT, a significant difference was observed only with the VEGF-A (rs833069) gene. The decrease in the CSMT at month 3 for the major allele homozygote AA genotype, the heterozygote AG genotype, and the risk allele homozygote GG genotype was 25.66 ± 85.40, 86.93 ± 92.31, and 85.30 ± 105.30 μm, respectively (p=0.012, p=0.044, and p=0.002 for AG, GG, and combined AG or GG genotype, respectively, compared to the AA genotype). This trend was maintained until month 6.
The VEGF-A (rs833069) polymorphism showed a significant association with the anatomic response to intravitreal ranibizumab. No significant difference was found between the genotype of the potential risk polymorphism for development of AMD and the early visual improvement after intravitreal ranibizumab.
确定影响年龄相关性黄斑变性（AMD）的遗传因素是否对韩国人群中使用雷珠单抗治疗渗出性AMD具有早期药物遗传学效应。
对102例接受玻璃体内雷珠单抗单药治疗的渗出性AMD患者（70例典型新生血管性AMD患者和32例息肉状脉络膜血管病变患者）进行回顾性研究。在基线时进行光学相干断层扫描、荧光素和吲哚菁绿血管造影。在基线时以及每月随访时记录最佳矫正视力（BCVA）和黄斑中心子野厚度（CSMT）。确定已知AMD易感基因座（CFH、AMRS2、HTRA1、VEGFA和KDR）中多态性的基因型，并评估其频率与BCVA和CSMT变化之间的关联。
平均基线视力为0.96±0.59 logMAR（相当于Snellen视力表约20/200），在第6个月就诊前平均注射次数为3.87次。未观察到BCVA变化与各基因型之间存在关联。对于CSMT的变化，仅在VEGF-A（rs833069）基因上观察到显著差异。主要等位基因纯合子AA基因型、杂合子AG基因型和风险等位基因纯合子GG基因型在第3个月时CSMT的降低分别为25.66±85.40、86.93±92.31和85.30±105.30μm（与AA基因型相比，AG、GG以及联合AG或GG基因型的p值分别为0.012、0.044和0.002）。这一趋势持续到第6个月。
VEGF-A（rs833069）多态性与玻璃体内雷珠单抗的解剖学反应显著相关。在AMD发生的潜在风险多态性基因型与玻璃体内雷珠单抗治疗后的早期视力改善之间未发现显著差异。
