Teper Slawomir J, Nowinska Anna, Pilat Jaroslaw, Palucha Andrzej, Wylegala Edward
Department of Ophthalmology, Okregowy Szpital Kolejowy, Katowice, Poland.
Mol Vis. 2010 Dec 7;16:2598-604.
To determine whether gene polymorphisms of the major genetic risk factor for age-related macular susceptibility 2 (ARMS2 A69S) and the complement factor H Y402H influence the response to a variable-dosing treatment regimen with ranibizumab for age-related macular degeneration.
This prospective cohort study included 90 patients (90 eyes) with exudative age related macular degeneration (AMD) treated with ranibizumab. Patients underwent a 1-year treatment as in the Study of Ranibizumab in Patients with Subfoveal Choroidal Neovascularization Secondary to Age-Related Macular Degeneration (Mitchell et al.). Injections were administered monthly when a patient lost five letters on the Early Treatment Diabetic Retinopathy Study chart or gained 100 μm in central subfield retinal thickness (CSRT). Genotypes (rs10490924 and rs1061170) were analyzed using gene sequence analysis. Best-corrected visual acuity (BCVA) and CSRT values were compared between ARMS2 and complement factor H genotypes. Multiple regression analysis was used to assess the statistical significance.
Mean increase in visual acuity was 4.44±8.12 letters with a 103.63±94.7 µm decrease in CSRT. BCVA improvement was statistically significant in all genotype groups except in homozygous 69S in the AMRS2 gene. CSRT and BCVA changes were correlated (r=0.2521; 95% CI: 0.04746-0.4364, p=0.0165). Multiple regression analysis revealed a significant impact of 69S (p=0.015) on the change in BCVA.
Visual acuity did not improve during the study in patients homozygous for ARMS2 69S, despite a decrease in CSRT. Further investigation is needed to confirm our findings and understand the mechanisms involved.
确定年龄相关性黄斑易感性2（ARMS2 A69S）的主要遗传风险因素及补体因子H Y402H的基因多态性是否影响雷珠单抗可变剂量治疗方案对年龄相关性黄斑变性的疗效。
这项前瞻性队列研究纳入了90例接受雷珠单抗治疗的渗出性年龄相关性黄斑变性（AMD）患者（90只眼）。患者接受了为期1年的治疗，治疗方式同年龄相关性黄斑变性继发中心凹下脉络膜新生血管患者的雷珠单抗研究（米切尔等人）。当患者在早期糖尿病视网膜病变研究图表上视力下降5行或中心子野视网膜厚度（CSRT）增加100μm时，每月进行一次注射。使用基因序列分析对基因型（rs10490924和rs1061170）进行分析。比较ARMS2和补体因子H基因型之间的最佳矫正视力（BCVA）和CSRT值。采用多元回归分析评估统计学意义。
平均视力提高4.44±8.12行，CSRT下降103.63±94.7μm。除ARMS2基因纯合69S外，所有基因型组的BCVA改善均具有统计学意义。CSRT和BCVA变化具有相关性（r=0.2521；95%CI：0.04746-0.4364，p=0.0165）。多元回归分析显示69S对BCVA变化有显著影响（p=0.015）。
尽管CSRT有所下降，但在研究期间，ARMS2 69S纯合患者的视力并未改善。需要进一步研究以证实我们的发现并了解其中涉及的机制。
