本文選題：非動(dòng)脈炎性前部缺血性視神經(jīng)病變 + 臨床特征�。� 參考：《北京協(xié)和醫(yī)學(xué)院》2016年博士論文

【摘要】：目的探討非動(dòng)脈炎性前部缺血性視神經(jīng)病變(nonarteritic anterior ischemic optic neuropathy, NAION)的臨床特征,初步分析結(jié)構(gòu)-功能關(guān)系在預(yù)測(cè)NAION嚴(yán)重程度中的作用,探討環(huán)境、遺傳(ATOH7、ET-1、ACE基因多態(tài)性)危險(xiǎn)因素以及NAION中可能存在的基因-基因、基因-環(huán)境交互作用。方法1.病例系列研究。收集73例NAION患者眼科檢查、動(dòng)態(tài)視野(visual field, VF)、視網(wǎng)膜神經(jīng)纖維層(retinal nerve fiber layer, RNFL)厚度、視盤(pán)參數(shù)以及神經(jīng)節(jié)細(xì)胞復(fù)合體(ganglion cell complex, GCC)結(jié)果,進(jìn)行描述性分析,非參數(shù)檢驗(yàn)分析NAION患者以上測(cè)量指標(biāo)的差異,Spearman相關(guān)分析分析VF、 RNFL、視盤(pán)參數(shù)以及GCC間的相關(guān)性,受試者工作特征曲線(receiver operating characteristic curves, ROC)的曲線下面積(area under the curve, AUROC)評(píng)價(jià)鑒別NAION眼與正常眼的最佳指標(biāo)。2.前瞻性病例對(duì)照研究。73例NAION患者與年齡、性別匹配正常對(duì)照146例納入研究。記錄所有研究對(duì)象年齡、性別、糖尿病、高血壓等信息資料。聚合酶鏈?zhǔn)椒磻?yīng)(polymerase chain reaction, PCR)對(duì)ATOH7 (rs1900004)、ET-1 (rs5370)、ACE (rs1799752)基因擴(kuò)增并進(jìn)行Sanger測(cè)序。多因素logistic回歸分析NAION環(huán)境危險(xiǎn)因素及基因關(guān)聯(lián)性,相乘模型和相加模型分析基因-基因、基因-環(huán)境交互作用。結(jié)果1.單眼NAION患者31.58%表現(xiàn)為與生理盲點(diǎn)相連弓形缺損,8.93%對(duì)側(cè)健眼視盤(pán)形態(tài)異常；雙眼患者40.63%表現(xiàn)視野向心性縮小。NAION患眼與對(duì)側(cè)健眼視盤(pán)參數(shù)間差異無(wú)統(tǒng)計(jì)學(xué)意義(P均0.05),雙眼C/D面積比、垂直C/D、水平C/D、視杯容積明顯相關(guān)(P均0.05)；顳側(cè)RNFL減少明顯(P=0.004)；NAION患眼上半VF MD與下半GCC、上半VF MS與下半GCC明顯相關(guān)。GCC FLV能最好的鑒別NAION眼與正常眼(AUROC = 0.93),最適宜臨界值為3.331%,雙眼NAION患者視野缺損程度、GCC FLV及GLV在兩眼間具有強(qiáng)相關(guān)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)與NAION顯著相關(guān)；攜帶ATOH7 TT基因型者是CC或CT基因型攜帶者發(fā)生NAION風(fēng)險(xiǎn)的2.95倍(95% CI=1.19-7.30,P=0.02);ATOH7與ET-1基因?qū)AION的發(fā)病有乘法交互作用(OR=27.31,95% CI=2.96.251.84, P=0.004)和協(xié)同作用：協(xié)同指數(shù)(synergy index,SI)=35.73(95%CI=32.21-39.24),交互作用歸因比例(attributable proportion of interaction,AP)=0.93(95%CI=0.78-1.09):ET-1基因與糖尿病(SI=4.03(95%CI=2.09-5.98),AP=0.68(95%CI= 0.17-1.18))及高血壓(SI=4.51(95%CI=2.43-6.59),AP=0.65(95%CI=0.17-1.12))對(duì)NAION的發(fā)病具有協(xié)同作用。結(jié)論NAION中應(yīng)注意對(duì)側(cè)健眼中的初發(fā)期NAION患者；NAION患者兩眼視盤(pán)結(jié)構(gòu)具有相關(guān)性,發(fā)病后視盤(pán)形態(tài)較為穩(wěn)定；GCC測(cè)量指標(biāo)可作為NAION診斷及鑒別診斷的輔助檢查；NAION患者雙眼發(fā)病嚴(yán)重程度具有強(qiáng)相關(guān)性；糖尿病、肥胖以及ATOH7獨(dú)立增加了NAION的發(fā)病風(fēng)險(xiǎn)；NAION中存在ATOH7基因與ET-1基因,ET-1基因與糖尿病、高血壓的交互作用。
[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.
【學(xué)位授予單位】：北京協(xié)和醫(yī)學(xué)院
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2016
【分類(lèi)號(hào)】：R774.6

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