Valverde-Megías Alicia, Veganzones-de-Castro Silvia, Donate-López Juan, Maestro-de-Las-Casas Maria Luisa, Megías-Fresno Alicia, García-Feijoo Julián
Retina Service, Ophthalmology Department, San Carlos Clinical Hospital, Sanitary Research Institute of the San Carlos Clinical Hospital (IdISSC), c/ Profesor Martin Lagos s/n, 28040, Madrid, Spain.
Department of Clinical Analysis, San Carlos Clinical Hospital, Madrid, Spain.
Graefes Arch Clin Exp Ophthalmol. 2017 Nov;255(11):2091-2098. doi: 10.1007/s00417-017-3748-0. Epub 2017 Jul 25.
To investigate whether single-nucleotide polymorphisms (SNPs) known to be strongly associated with the development of age-related macular degeneration (AMD) have an influence on recurrence rate of choroidal neovascularization (CNV) activity during 4-year ranibizumab treatment for exudative AMD.
This prospective study included 103 treatment-naïve patients (103 eyes) that received initially a loading dose of 3 monthly ranibizumab injections and thereafter, were treated according to an as-needed regimen for a 4-year follow-up period. Baseline values, visual outcome, and recurrence rate were examined. CFH Y402H and ARMS2 A69S polymorphisms were determined and their association with lesion recurrence and visual outcome was analyzed using a one-way analysis of variance (ANOVA) with post hoc comparison tested by Fisher's LSD method. Multivariate linear regression analysis was then used to identify factors associated with recurrence rate.
The cumulative total mean number of ranibizumab injections at the end of each year of the follow-up was 5.3 ± 1.8, 9.2 ± 2.9, 12.6 ± 4.6, and 15.7 ± 6.1. There was great inter-patient variability. Nineteen eyes (18.5%) did not experience recurrence during the first year, and five (4.8%) still displayed inactive CNV after 4 years of follow-up. No significant association was found between the number of injections and mean best corrected visual acuity (BCVA) change or final BCVA at the end of the study period. Genotypes had no influence on baseline characteristics or visual outcome but a significant association was found between the A69S polymorphism and the number of injections needed by the patients. Homozygous for the T risk allele required more retreatments over the 48-month follow-up.
The ARMS2 A69S polymorphism was associated with CNV recurrence rate in our patient cohort. Prediction of a greater risk of recurrence could help to design more appropriate follow-up treatment strategies for patients with neovascular AMD.
研究已知与年龄相关性黄斑变性（AMD）发生密切相关的单核苷酸多态性（SNP）是否会对雷珠单抗治疗渗出性AMD 4年期间脉络膜新生血管（CNV）活性的复发率产生影响。
这项前瞻性研究纳入了103例初治患者（103只眼），这些患者最初接受每月3次雷珠单抗注射的负荷剂量，此后根据按需治疗方案进行4年的随访。检查基线值、视力结果和复发率。确定CFH Y402H和ARMS2 A69S多态性，并使用单因素方差分析（ANOVA）及事后比较（采用Fisher最小显著差异法检验）分析它们与病变复发和视力结果的关联。然后使用多元线性回归分析来确定与复发率相关的因素。
随访各年末雷珠单抗注射的累积总平均数分别为5.3±1.8、9.2±2.9、12.6±4.6和15.7±6.1。患者间存在很大差异。19只眼（18.5%）在第一年未复发，5只眼（4.8%）在随访4年后仍显示CNV无活性。在研究期末，注射次数与平均最佳矫正视力（BCVA）变化或最终BCVA之间未发现显著关联。基因型对基线特征或视力结果无影响，但发现A69S多态性与患者所需注射次数之间存在显著关联。在48个月的随访中，T风险等位基因纯合子需要更多的再次治疗。
在我们的患者队列中，ARMS2 A69S多态性与CNV复发率相关。预测更高的复发风险有助于为新生血管性AMD患者设计更合适的随访治疗策略。
