非动脉炎性前部缺血性视神经病变临床特征及危险因素分析

发布时间：2018-06-04 13:35

本文选题：非动脉炎性前部缺血性视神经病变 + 临床特征　；参考：《北京协和医学院》2016年博士论文

【摘要】：目的探讨非动脉炎性前部缺血性视神经病变(nonarteritic anterior ischemic optic neuropathy, NAION)的临床特征,初步分析结构-功能关系在预测NAION严重程度中的作用,探讨环境、遗传(ATOH7、ET-1、ACE基因多态性)危险因素以及NAION中可能存在的基因-基因、基因-环境交互作用。方法1.病例系列研究。收集73例NAION患者眼科检查、动态视野(visual field, VF)、视网膜神经纤维层(retinal nerve fiber layer, RNFL)厚度、视盘参数以及神经节细胞复合体(ganglion cell complex, GCC)结果,进行描述性分析,非参数检验分析NAION患者以上测量指标的差异,Spearman相关分析分析VF、 RNFL、视盘参数以及GCC间的相关性,受试者工作特征曲线(receiver operating characteristic curves, ROC)的曲线下面积(area under the curve, AUROC)评价鉴别NAION眼与正常眼的最佳指标。2.前瞻性病例对照研究。73例NAION患者与年龄、性别匹配正常对照146例纳入研究。记录所有研究对象年龄、性别、糖尿病、高血压等信息资料。聚合酶链式反应(polymerase chain reaction, PCR)对ATOH7 (rs1900004)、ET-1 (rs5370)、ACE (rs1799752)基因扩增并进行Sanger测序。多因素logistic回归分析NAION环境危险因素及基因关联性,相乘模型和相加模型分析基因-基因、基因-环境交互作用。结果1.单眼NAION患者31.58%表现为与生理盲点相连弓形缺损,8.93%对侧健眼视盘形态异常；双眼患者40.63%表现视野向心性缩小。NAION患眼与对侧健眼视盘参数间差异无统计学意义(P均0.05),双眼C/D面积比、垂直C/D、水平C/D、视杯容积明显相关(P均0.05)；颞侧RNFL减少明显(P=0.004)；NAION患眼上半VF MD与下半GCC、上半VF MS与下半GCC明显相关。GCC FLV能最好的鉴别NAION眼与正常眼(AUROC = 0.93),最适宜临界值为3.331%,双眼NAION患者视野缺损程度、GCC FLV及GLV在两眼间具有强相关性。2.肥胖(OR=8.09,95% CI=2.94-22.23,P0.001)和糖尿病(OR=4.72,95%CI=1.57-14.25,P=0.006)与NAION显著相关；携带ATOH7 TT基因型者是CC或CT基因型携带者发生NAION风险的2.95倍(95% CI=1.19-7.30,P=0.02);ATOH7与ET-1基因对NAION的发病有乘法交互作用(OR=27.31,95% CI=2.96.251.84, P=0.004)和协同作用：协同指数(synergy index,SI)=35.73(95%CI=32.21-39.24),交互作用归因比例(attributable proportion of interaction,AP)=0.93(95%CI=0.78-1.09):ET-1基因与糖尿病(SI=4.03(95%CI=2.09-5.98),AP=0.68(95%CI= 0.17-1.18))及高血压(SI=4.51(95%CI=2.43-6.59),AP=0.65(95%CI=0.17-1.12))对NAION的发病具有协同作用。结论NAION中应注意对侧健眼中的初发期NAION患者；NAION患者两眼视盘结构具有相关性,发病后视盘形态较为稳定；GCC测量指标可作为NAION诊断及鉴别诊断的辅助检查；NAION患者双眼发病严重程度具有强相关性；糖尿病、肥胖以及ATOH7独立增加了NAION的发病风险；NAION中存在ATOH7基因与ET-1基因,ET-1基因与糖尿病、高血压的交互作用。
[Abstract]:Objective to investigate the clinical features of nonarteritic anterior ischemic optic neuropathy, NAION) in anterior ischemic optic neuropathy of non-arteritis, to analyze the role of structure-functional relationship in predicting the severity of NAION, and to explore the environment. Genetic polymorphism of ATOH7ET-1ACE gene and possible gene-gene, gene-environment interaction in NAION. Method 1. Case series study. The visual field, retinal nerve fiber layer, RNFL) thickness, optic disc parameters and ganglion cell complex, GCC) were collected from 73 patients with NAION. Spearman correlation analysis of NAION patients the correlation between VF, RNFL, disc parameters and GCC was analyzed by non-parametric test. The area under the receiver operating characteristic curves, ROC) curve area under the curve, AUROC) was used to evaluate the best index of differentiating NAION eyes from normal eyes. Prospective Case-control study. 146 normal controls with age and gender matched with NAION were included in the study. All subjects' age, sex, diabetes, hypertension and other information were recorded. Polymerase chain reaction (chain reaction, PCR) was used to amplify the ATOH7 rs19004, ET-1, rs53701, ACE-rs1799752 gene and sequence it by Sanger. Multivariate logistic regression analysis of NAION environmental risk factors and gene association, multiplication model and additive model analysis of gene-gene, gene-environment interaction. Result 1. 31.58% of monocular NAION patients showed arcuate defect associated with physiological blind spot, 8.93% of contralateral healthy eyes had abnormal optic disc shape, 40.63% of binocular patients showed that the visual field was concentrically narrowed. There was no significant difference in visual disc parameters between eye and contralateral healthy eyes (P < 0.05), and the area ratio of C / D in both eyes was not significant (P > 0.05). Vertical C / D, horizontal C / D, cup-volume correlation (P = 0.05), temporal RNFL decreased significantly (P 0.004) in the affected eye, VF MD in the upper half of the eye and GCCin in the lower half of the eye, FLV in the upper half of the eye and GCC in the lower half of the eye. FLV was the best way to distinguish NAION eyes from normal eyes, and the most suitable critical value was 0.93%. The degree of visual field defect in bilateral NAION patients was 3.331.GCC FLV and GLV had a strong correlation between the two eyes. 2.94-22.23P0.001) and 4.72c95% CI 1.57-14.25P0. 006) were significantly correlated with NAION. The risk of developing NAION was 2.95 times as high as that of CC or CT carriers with ATOH7 TT genotype. 95% of CIOH7 and ET-1 gene had a multiplicative interaction with ET-1 gene on the pathogenesis of NAION. OR27.31% 95% CI 2.96.251.84, P0. 004) and synergistic effect: synergistic index Synergy Synergy index Synergy SI 35.7395CIT 32.21-39.24, interaction attributive ratio attributable proportion of NAION. There is a synergistic effect on the pathogenesis of NAION with the ratio of 0.93-1.09% ET-1 gene and the diabetes mellitus (SIX4.033.95) and hypertension (SI4.51C95CII 2.43-6.59A 0.6595CI0.17-1.12). Conclusion in NAION, we should pay attention to the correlation between the optic disc structure of two eyes in the initial stage of NAION in contralateral healthy eyes. The morphology of optic disc is relatively stable after onset. The measurement index can be used as an auxiliary examination for the diagnosis and differential diagnosis of NAION, which has a strong correlation with the severity of binocular disease in patients with diabetes, diabetes, Obesity and ATOH7 increased the risk of NAION. There was interaction between ATOH7 gene and ET-1 gene, ET-1 gene, diabetes mellitus and hypertension.
【学位授予单位】：北京协和医学院
【学位级别】：博士
【学位授予年份】：2016
【分类号】：R774.6

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