Lee A Y, Raya A K, Kymes S M, Shiels A, Brantley M A
Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St Louis, MO 63110, USA.
Br J Ophthalmol. 2009 May;93(5):610-3. doi: 10.1136/bjo.2008.150995. Epub 2008 Dec 17.
To determine whether complement factor H (CFH) genotypes have a pharmacogenetic effect on the treatment of exudative age-related macular degeneration (AMD) with ranibizumab.
A retrospective study of 156 patients with exudative AMD treated with intravitreal ranibizumab monotherapy was conducted. AMD phenotypes were characterised by clinical examination, visual acuity, fundus photography, fluorescein angiography and injection timing. Patients received intravitreal ranibizumab injections as part of routine ophthalmological care and were followed for a minimum of 9 months. Each patient was genotyped for the single nucleotide polymorphism rs1061170 (Y402H) in the CFH gene.
Baseline lesion size and angiographic type, as well as mean visual acuities at baseline, 6 months, and 9 months were similar among the three CFH genotypes. Over 9 months, patients with both risk alleles received approximately one more injection (p = 0.09). In a recurrent event analysis, patients homozygous for the CFH Y402H risk allele had a 37% significantly higher risk of requiring additional ranibizumab injections (p = 0.04).
In this study cohort, the response to treatment of AMD with ranibizumab differed according to CFH genotype, suggesting that determining patients' CFH genotype may be helpful in the future in tailoring treatment for exudative AMD with intravitreal ranibizumab.
确定补体因子H(CFH)基因型对雷珠单抗治疗渗出性年龄相关性黄斑变性(AMD)是否具有药物遗传学效应。
对156例接受玻璃体内雷珠单抗单药治疗的渗出性AMD患者进行回顾性研究。通过临床检查、视力、眼底照相、荧光素血管造影和注射时间来表征AMD的表型。患者接受玻璃体内雷珠单抗注射作为常规眼科护理的一部分,并随访至少9个月。对每位患者的CFH基因中的单核苷酸多态性rs1061170(Y402H)进行基因分型。
三种CFH基因型之间的基线病变大小和血管造影类型,以及基线、6个月和9个月时的平均视力相似。在9个月的时间里,具有两个风险等位基因的患者多接受了约一次注射(p = 0.09)。在复发事件分析中,CFH Y402H风险等位基因纯合的患者需要额外注射雷珠单抗的风险显著高37%(p = 0.04)。
在本研究队列中,雷珠单抗治疗AMD的反应因CFH基因型而异,这表明确定患者的CFH基因型可能在未来有助于为玻璃体内注射雷珠单抗治疗渗出性AMD量身定制治疗方案。