[In Press] Genes of tumor necrosis factors and their receptors and the primary open-angle glaucoma in the population of Central Russia

AIM: To examine the association of genetic polymorphisms (-308)G/A TNFα, (+250)A/G Ltα, (+36)A/G TNFR1, (+1663)G/A TNFR2 with the development of primary open-angle glaucoma (POAG) among people in Central Russia. METHODS: The study sample included 443 individuals, of which 252 patients with POAG and 191 individuals in the control group. Genotyping of (-308)G/A TNFα, (+250)A/G Ltα, (+36)A/G TNFR1, (+1663)G/A TNFR2 was performed using polymerase chain reaction. The distribution of alleles and genotypes of the studied DNA markers in the groups was examined by 2×2 contingency tables and ?2 with the Yates’s correction for continuity and odds ratios (OR) with 95% confidence intervals (CI). RESULTS: Allele (-308)G TNFα (Р=0.01, OR=1.78, 95%CI 1.12-2.85) was identified as a risk factor for POAG. Homozygotes (-308) AA TNFα are at a lowest risk for development of the disease (Р=0.01, OR=0.0005). The following combination of genetic variants of cytokines were associated with a reduced risk of POAG: (+1663)A TNFR2 and (+250)G Ltα (OR=0.34) CONCLUSION: Genetic polymorphisms (-308)G/A TNFα, (+250)A/G Ltα, (+1663)G/A TNFR2 associated with the development of POAG in the population of Central Russia.     

Estrogen receptor gene polymorphisms and their influence on clinical status of Caucasian patients with primary open angle glaucoma

ABSTRACT

Purpose: The aim of this study was to evaluate the frequency of single nucleotide polymorphisms (SNP) of estrogen receptor genes (ESR1: rs12154178, rs1884054 and ESR2: rs1268656, rs7159462) and to assess their possible influence on the clinical phenotype of primary open angle glaucoma (POAG).

Methods: The study included 235 patients with POAG (143 patients with normal-tension glaucoma [NTG] and 92 patients with high-tension glaucoma [HTG]), and 165 healthy controls. DNA was isolated from peripheral blood, and SNP genotyping was performed using the Real-Time Polymerase Chain Reaction method to analyze the frequency of selected polymorphic variants of estrogen receptor genes. The clinical phenotype (best-corrected visual acuity, intraocular pressure [IOP], mean deviation [MD], cup to disc ratio, disc hemorrhages, notches, peripapillary atrophy, cold extremities) of participants were examined for association with the polymorphisms.

Results: A similar frequency of the polymorphic variants of the studied genes was observed in patients with NTG, HTG and control group. Initial intraocular pressure was the lowest in NTG patients with GG variant of rs1268656 (p = 0.044). The lowest maximal IOP in HTG patients was observed in CC variant of rs12154178 (p = 0.039). Patients with HTG and CC variant of ESR1 polymorphism rs1884054 had the best visual acuity (p = 0.009), similar tendency was also observed in the NTG group. This polymorphic variant of ESR1 gene in HTG was also related to earlier damage in visual field assessed according to MD values and higher percentage of notches. For rs12154178, homozygotic variant CC was related to earlier glaucoma damage according to MD in HTG patients (p = 0.006). For polymorphism rs12154178, disc hemorrhages were found only for those with the AC variant. Cold extremities were most frequent in NTG patients with TT variant of rs1268656 comparing to other variants (p = 0.021). Notches on optic disc were less frequent in patients with CC variant of rs12154178 of ERS-1 gene (p = 0.022).

Conclusions: The studied polymorphic variants of ESR1 and ESR2 genes may have an influence on the clinical phenotype of patients with POAG.     

近视人群原发性开角型青光眼相关因素研究

目的:分析眼轴长度、中央角膜厚度与眼压的关系,探讨它们对原发性开角型青光眼(POAG)的诊断意义。方法:对118例210眼早期原发性开角型青光眼患者以及58例116眼对照组(根据屈光度的不同分为正视组,低中度近视组和高度近视组3组)进行中央角膜厚度,眼轴长度,眼压测量,并用统计学的方法对其结果进行比较。结果:正常组中央角膜厚度,眼轴长度与眼压呈正相关关系(r1=0.351,r2=0.883)。两组人群比较,中央角膜厚度、眼轴长度均有极显著性差异(P<0.01);而在同一组内不同屈光度比较,中央角膜厚度随着屈光度的增加而降低;眼轴长度随着屈光度的增加而增加。结论:了解近视人群的特点,有利于提高临床医师对近视合并POAG的早期诊断水平。     

Long-term evaluation of trabeculectomy in primary open angle glaucoma and chronic primary angle closure glaucoma in an Asian population

Purpose: A retrospective cohort study was undertaken to evaluate and compare the long‐term results of trabeculectomy in primary open angle glaucoma (POAG) and chronic primary angle closure glaucoma (CPACG) in an Asian population. Methods: Yearly diurnal measurements of intraocular pressure (IOP), best‐corrected visual acuity, optic disc and visual field records of patients having primary adult glaucomas who had undergone trabeculectomy, without anti­mitotic agents, with a minimum of 5 years follow up were evaluated. Only one eye of each patient was studied. The success rates for IOP control in POAG and CPACG were statistically analysed. Results: Sixty‐four eyes of 64 patients were studied. The overall probability of success of trabeculectomy in controlling IOP to ≤21 mmHg with or without additional topical antiglaucoma medication was 0.94 and 0.88 at 5 and 10 years, respectively. There was no statistically significant difference in the qualified and absolute success rates for IOP control between POAG and CPACG eyes (log rank test P= 0.6, 0.88, respectively). Twelve of 38 CPACG eyes had a two‐line decrease in visual acuity as compared to four of 26 POAG eyes (P = 0.17). Progression or development of a cataract was the most common cause of visual decline. Conclusions: Trabeculectomy without antimetabolite use appears to be efficacious in lowering IOP and in visual field preservation over a period of 10 years in both POAG and CPACG. Development/progression of cataract especially in eyes with chronic angle closure glaucoma after trabeculectomy must be considered an important issue.     

正常眼压青光眼与原发性开角型青光眼的比较

正常眼压青光眼（ＮＴＧ）的发病率逐渐增加,日益受到眼科工作者的重视。ＮＴＧ发病隐蔽,早期诊断较其它青光眼显得更为困难和复杂,其发病机制、诊断标准及其与原发性开角型青光眼（ＰＯＡＧ）的异同等一系列问题仍无统一意见。就ＮＴＧ与ＰＯＡＧ的诊断标准,发病机制,临床表现,治疗原则以及相互关系等问题的研究进展等进行综述。     

原发性开角型青光眼的早期诊断

青光眼是全世界成人致盲的主要眼病。原发性开角型青光眼做为青光眼的一种类型,其特点是病程进展较为缓慢,多数没有明显症状,不易早期发现。许多患者就诊时已经出现了较严重的视功能障碍,且近年来该病患病率在临床上所占的比例有所上升。而对原发性开角型青光眼的早期诊断,是延缓或停止视功能进行性损害的关键。因此,综合国内外近年来相关文献,对原发性开角型青光眼的早期诊断做以下综述。     

High myopia as a risk factor in primary open angle glaucoma

Glaucoma, one of the leading causes of irreversible blindness in the adult population worldwide, is a progressive optic neuropathy. Primary open angle glaucoma (POAG) is the most commonly reported type of glaucoma in population based prevalence studies worldwide. Elevated intraocular pressure is a well-known major risk factor for POAG. In addition, there is growing evidence that other risk factors like age, gender, race, refractive error, heredity and systemic factors may play a role in glaucoma pathogenesis. Many studies found that high myopia has been associated with POAG, however, direct and convincing evidences are still lacking. The aim of this review is to summarize the evidences implicating high myopia as a risk factor in the pathogenesis of POAG.     

原发性开角型青光眼患者焦虑症伴随状况及特征分析

目的:了解原发性开角型青光眼(primary open angle glau-coma,POAG)患者焦虑症伴随状况及其影响因素。方法:用Hamilton焦虑量表(HAMD)对82例POAG患者及82例非青光眼患者进行焦虑测试,对比两组患者焦虑症伴随比率,并对82例POAG患者以不同性别、年龄、文化程度等进行分组比较,分析焦虑症发生的影响因素。结果:POAG组与对照组伴发焦虑者分别为13例(16%)和5例(6%),经χ2检验,差异有统计学意义(P=0.046)。对82例POAG患者内部分组比较显示:性别、年龄、文化水平、病程、视野为POAG伴发焦虑的相关因素。结论:POAG患者心理健康状况应予以关注,尤其对病程长、年龄大、文化程度低、视功能损害严重的女性患者,应同时给予心理评估及干预,以改善POAG患者的生活质量及预后。     

原发性开角型青光眼三个致病基因的研究进展

原发性开角型青光眼（primary open angle glaucoma，POAG）是一种损伤视力及致盲性眼病。近年来越来越多的研究表明基因变异及遗传在POAG的发病中起重要作用。目前已知的POAG相关基因有20余种．包括3种明确的POAG致病基因：myocilin（MYOC），optineurin（OPTN）和WD repeat domain 36（WDR36）．本文就这3种POAG致病基因研究作一综述。     

原发性开角型青光眼的代谢综合征相关基因单核苷酸多态性

目的：检测原发性开角型青光眼（POAG）和代谢综合征相关基因的单核苷酸多态性（SNP）,分析代谢综合征作为危险因素在POAG发生发展中所起的可能作用。方法：应用ABI Prism 7500HT型荧光定量PCR仪结合TaqMan SNP Genotyping试剂盒荧光探针技术检测POAG37和正常对照100例白介素6（IL-6）、白介素6受体（IL-6R）、多巴胺受体-D2（DRD2）、β-纤维蛋白原（FGB）、过氧化物酶体增殖物激活受体-γ2（PPARG）、转化生长因子-β1（TGF—β1）、E-选择素（E—Sel）、脂蛋白A-5（APOA5）、C反应蛋白（CRP）、外核苷酸焦磷酸酶／磷酸二酯酶1（ENPP1）、肝脂肪酶（LIPC）、脂联素（ADIPOQ）、对氧磷酯酶-1（PON1）和丝氨酸蛋白酶抑制剂E（SERPINE1）基因的基因型,计算并比较其等位基因频率。结果：POAG组IL-6R,IL-6,FGB,CRP,ENPP1,LIPC,ADIPOQ,PON1和SERPINE1的基因型和等位基因频率与正常对照组差异有显著性统计学意义。其中OR值〉2．5的有IL-6,FGB,CRP,ENPP1,LIPC和ADIPOQ。结论：代谢综合征作为POAG的危险因素,可能与其相关基因的基因型和等位基因频率有关。其相应的基因表达及其功能可影响POAG的发生和发展,包括SERPINE1作用于小梁网细胞外基质;ENPP1抑制胰岛素样因子活性,影响小梁网细胞生长;IL-6的内源性视神经保护作用;IL-6,IL-6R,E—Sel参与的自身免疫反应;FGB和LIPC在高粘滞血症中作用;ADIPOQ促进NOS／NO生成;PON1的血管内皮保护作用。     

Single nucleotide polymorphisms of metabolic syndrome-related genes in primary open angle glaucoma

AIM: To analyze single nucleotide polymorphisms (SNP) of primary open angle glaucoma- and metabolic syndrome-related genes in primary open angle glaucoma (POAG), in order to elucidate the roles of metabolic syndrome as a risk factor in POAG progress. · METHODS: SNP genotypes and alleles of interleukin-6 (IL-6), IL-6 receptor (IL-6R), dopamine D2 receptor (DRD2), beta-fibrinogen (FGB), peroxisome proliferator-activated receptor-γ2 (PPARG), transforming growth factor-β1 (TGF-β1), E-selectin (E-Sel), apolipoprotein A-5 (APOA5), C-reactive protein (CRP), ectonueleotide pyrophosphatase/ phosphodiesterase 1 (ENPP1), hepatic lipase (LIPC), adiponectin (ADIPOQ), paraoxonase 1 (PON1) and serine protease inhibitor E (SERPINE1) genes in POAG (n =37) and normal control (n =100) groups were measured with ABI Prism 7900HT Fluorescence Quantitative PCR and TaqMan SNP Genotyping fluorescence probe kit. · RESULTS: Genotypes and allele frequencies of IL-6R, IL-6, FGB, CRP, ENPP1, LIPC, ADIPOQ, PON1, and SERPINE1 in total POAG group were significantly different compared to the control group. · CONCLUSION: Metabolic syndrome as a risk factor for POAG may be associated with genotypes and allele frequencies of the related genes. The corresponding gene expression and function can affect POAG progress, including roles of SERPINE1 in extracellular matrix, ENPP1 in insulin inhibition, IL-6 in endogenous neuroprotection, IL-6, IL-6R and E-Sel in autoimmune response, LIPC and FGB in blood hyperviscosity syndrome, ADIPOQ in NOS/NO production, PON1 in vascular endothelial protection.     

Comparison of ocular response analyzer parameters in primary open angle glaucoma and exfoliative glaucoma patients

Aim:

We sought to identify differences in the following measures of the ocular response analyser (ORA) between primary open angle glaucoma (POAG) and exfoliative glaucoma (EXG) patients: Corneal hysteresis (CH), corneal resistance factor (CRF), corneal-compensated intraocular pressure (IOPcc) and Goldmann-correlated intraocular pressure (IOPg). We also sought to relate these ORA measures with central corneal thickness (CCT).

Materials and Methods:

This cross-sectional study was conducted on a total of 162 individuals (46 EXG patients, 66 POAG patients and 50 healthy subjects without any ocular and systemic disease). ORA measurements were performed, and a minimum of three readings were obtained from each test subject. Groups were compared according to their ORA parameters.

Results:

The mean CH levels of the EXG, POAG and healthy subjects were 7.6 ± 2.1, 9.1 ± 1.9 and 9.6 ± 1.7 mmHg, respectively. CH was significantly lower in the EXG patients compared to the other groups (P < 0.001). The mean CRF levels of the EXG, POAG and healthy subjects were 9.0 ± 2.0, 10.1 ± 1.7 and 9.8 ± 1.8mmHg, respectively. CRF levels in the eyes of the EXG patients were significantly lower compared to those of either the POAG patients (P = 0.005) or the healthy subjects (P = 0.03), but there was no significant difference in CRF levels between the POAG patients and the healthy subjects (P = 0.59). There was a significant positive correlation between CH and CCT in the EXG patients and healthy subjects (P < 0.001), but this correlation was not present in the POAG patients (P = 0.70).

Conclusions:

In this study, CH and CRF were found to be significantly reduced in the eyes of EXG patients compared to both the POAG patients and healthy subjects. Reduced CH in EXG patients might result in decreased support of peripapillary scleral structure and increased damage to the optic nerve during IOP increase.     

原发性开角型青光眼的代谢综合征相关基因单核苷酸多态性

目的:检测原发性开角型青光眼(POAG)和代谢综合征相关基因的单核苷酸多态性(SNP),分析代谢综合征作为危险因素在POAG发生发展中所起的可能作用。方法:应用ABI Prism 7500HT型荧光定量PCR仪结合TaqMan SNP Genotyping试剂盒荧光探针技术检测POAG37和正常对照100例白介素6(IL-6)、白介素6受体(IL-6R)、多巴胺受体-D2(DRD2)、β-纤维蛋白原(FGB)、过氧化物酶体增殖物激活受体-γ2(PPARG)、转化生长因子-β1(TGF-β1)、E-选择素(E-Sel)、脂蛋白A-5(APOA5)、C反应蛋白(CRP)、外核苷酸焦磷酸酶/磷酸二酯酶1(ENPP1)、肝脂肪酶(LIPC)、脂联素(ADIPOQ)、对氧磷酯酶-1(PON1)和丝氨酸蛋白酶抑制剂E(SERPINE1)基因的基因型,计算并比较其等位基因频率。结果:POAG组IL-6R,IL-6,FGB,CRP,ENPP1,LIPC,ADIPOQ,PON1和SERPINE1的基因型和等位基因频率与正常对照组差异有显著性统计学意义。其中OR值>2.5的有IL-6,FGB,CRP,ENPP1,LIPC和ADIPOQ。结论:代谢综合征作为POAG的危险因素,可能与其相关基因的基因型和等位基因频率有关。其相应的基因表达及其功能可影响POAG的发生和发展,包括SERPINE1作用于小梁网细胞外基质;ENPP1抑制胰岛素样因子活性,影响小梁网细胞生长;IL-6的内源性视神经保护作用;IL-6,IL-6R,E-Sel参与的自身免疫反应;FGB和LIPC在高粘滞血症中作用;ADIPOQ促进NOS/NO生成;PON1的血管内皮保护作用。     

原发性开角型青光眼发病机制的研究进展

原发性开角型青光眼作为全球第二大致盲性眼病，其发病机制的研究一直备受关注。本文对传统的机械学说和血管学说，以及近年来发展的跨筛板压力学说、基因研究、免疫机制、线粒体动力学等研究结果和各种危险因素进行综述，为眼科工作者提供参考资料。     

Ex-PRESS引流器植入治疗原发性开角型青光眼的疗效

目的：观察Ex-PRESS青光眼引流器植入治疗原发性开角型青光眼的临床疗效。

方法：原发性开角型青光眼患者41例54眼分为研究组和对照组。研究组19例25眼,行Ex-PRESS青光眼引流器植入; 对照组22例29眼,行小梁切除术。比较两组患者平均手术时间、术后视力、浅前房、眼压、滤过泡及其他并发症的情况。

结果：研究组手术时间34.60±4.43min,术后1d浅前房1眼、前房出血1眼; 术后1wk高眼压2眼; 术后3mo视力下降1眼、功能性滤过泡24眼、眼压11.5±5.8mmHg。对照组手术时间44.37±3.00min,术后1d浅前房13眼、前房出血渗出12眼; 术后1wk高眼压8眼; 术后3mo视力下降6眼、功能性滤过泡25眼、眼压13.6±6.7mmHg。研究组术后并发症较少,眼压控制更低,术后视力影响、功能性滤过泡与对照组相当。

结论：Ex-PRESS青光眼引流器植入治疗原发性开角型青光眼手术时间缩短,术后浅前房、前房出血渗出并发症少,安全性高,疗效好。     

Association between interleukin-10 genetic polymorphisms and risk of primary open angle glaucoma in a Chinese Han population: a case-control study

AIM: To investigate the association between interleukin-10 (IL-10) genetic polymorphisms and risk of POAG through a case-control study in a Han population of China. METHODS: A total of 210 patients with POAG and 420 normal subjects were recruited during the period from Dec. 2013 to Dec. 2016. The IL-10 -1082A>G (rs1800870), -819T>C (rs1800871) and -592C>A (rs1800872) polymorphisms were determined using iPlex GOLD SNP genotyping analysis (the SequenomMassARRAY® System, Sequenom, San Diego, USA). The association between IL-10 -1082A>G (rs1800870), -819T>C (rs1800871), and -592C>A (rs1800872) polymorphisms and risk of POAG was assessed by singlelogistic regression analysis. RESULTS: We observed that those carrying the CC genotype of rs1800871 was associated with an increased risk of POAG when compared with those harboring the TT genotype (OR=1.84, 95%CI=1.01-3.38). Those with AA genotype of rs1800872 had a 10.62 fold risk of POAG in comparison to the CC genotype (OR=10.62, 95%CI, 3.41-33.09). A completely linkage disequilibrium was found between IL-10 rs1800871-rs1800872 (D’=1.00, r2=0.16). The A-C-A (OR=2.60, 95%CI, 1.48-4.58) and G-T-A (OR=2.34, 95%CI, 1.42-3.86) haplotypes were associated with an increased risk of POAG, while the A-T-C haplotype showed a decreased risk of POAG (OR=0.63, 95%CI, 0.49-0.81). CONCLUSION: Our data suggest that IL-10 rs1800871 and rs1800872 can be predictive factors for the pathogenesis of POAG in the Chinese population.     

Association of apolipoprotein E-219T>G promoter polymorphism with primary open angle glaucoma in Turkish population

AIM: To investigate the association between apolipoprotein E (APOE) -219 T>G promoter polymorphism and primary open angle glaucoma (POAG).METHODS: Patients and healthy subjects were genotyped with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Genotype/allele frequencies were compared between 122 healthy subjects and in 75 POAG patients using Chi-square test.RESULTS:Although the frequency of APOE -219 GG genotype was higher in POAG group (13.3%) than in control group (6.6%), this finding was not statistically significant (P=0.09). In glaucoma patients carrying GG genotype, mean linear C/D ratio was higher and progression was more compared to glaucoma patients with GT genotype.CONCLUSION: APOE -219 T>G polymorphism does not seem to be a risk factor for the presence of glaucoma, but might play a role in deterioration of the disease, which needs further evaluation.     

Ex-PRESS引流钉植入治疗原发性开角型青光眼的临床观察

目的：观察Ex－PRESS引流钉植入联合调整缝线治疗原发性开角型青光眼的临床效果。方法：回顾2013－01／2015－05在我院就诊的确诊为原发性开角型青光眼患者23例29眼。患者年龄23～42岁,术前最佳矫正视力：指数／50cm～0．5,眼压16～52mmHg。给予降眼压药物效果不理想,行Ex－PRESS引流钉植入联合调整缝线手术。术后进行眼压、滤过泡形成观察及超声生物显微镜（ ultrasound biomicroscope,UBM）观察引流钉开口是否通畅。结果：术后视力0．06～0．5;术后1 wk 平均眼压为10±3mmHg,与术前比较明显降低（ P＜0．05）;手术后有1眼出现术后浅前房,1眼术后第2 d出现前房积血;所有患者（29眼）在术后至术后1wk拆除调整缝线期间滤过泡形成好,有1眼术后3mo复查滤过泡包裹,UBM检查巩膜内口有高密度强回声阻塞物,而无巩膜瓣下通道,其他患者（28眼）术后3mo UBM观察滤过通道通畅。结论：Ex－PRESS青光眼引流钉植入术联合调整缝线治疗开角型青光眼是安全有效的,术中及术后风险低、并发症少。     

原发性开角型青光眼的相关基因研究进展

原发性开角型青光眼(POAG)是以视野缺损和视神经损害为特征的致盲性眼病。最近几年越来越多学者的研究结果表明基因的变异及遗传在原发性开角型青光眼的发生发展中起非常重要的作用。现在已知的原发性开角型青光眼致病基因有20余种,现在就目前较为确定的原发性开角型青光眼的相关基因,尤其是已确认的MYOC、OPTN、WDR36及CAV1/CAV2基因的定位、结构及相关研究等方面进行综述,为在原发性开角型青光眼的遗传基因研究方面提供一点参考。     

中国陕西省农村原发性开角型青光眼流行病学调查

目的：调查陕西省农村人群原发性开角型青光眼的患病率及相关影响因素。方法：2003—07／12，采用按比例随机整群抽样的方法在陕南、陕北及关中3个地区农村调查8500人，所有受检人员均进行标准问卷调查，包括询问青光眼确诊史、家族史、发作史及手术史，并进行了相关的眼科检查，包括视力、外眼、眼前节、眼底检查。≥50岁人群及怀疑有高眼压者对其应用压平式眼压计测量眼压。对可疑青光眼者进行进一步检查，包括复查眼压、前房角镜检查、视野检查。结果：8500人中共有6815人完成了青光眼的相关检查，受检率为80．18％。原发性开角型青光眼患者共有9例，年龄为38-80（平均62．0）岁，患病率为0．13％，≥30岁、≥40岁和≥50岁人群患病率分别为0．23％、0．28％和0．39％。可疑原发性开角型青光眼患者有12例（0．18％），年龄为35-77（平均54.7）岁，比原发性开角型青光眼患者平均年龄约小7岁。多因素logistic回归分析显示患病率随着年龄的增长而增加（P=0．023）。除年龄外，高度近视也是该人群开角型青光眼发生的危险因素。有青光眼确诊史的患者占22．22％，其中无1例接受过药物或手术治疗。66．67％（6例）原发性开角型青光眼患者存在不同程度的视力损伤，其中盲目占33．33％。结论：原发性开角型青光眼的患病率与国内其他报道相近，且随着年龄的增长而增加。绝大部分患者无青光眼确诊史，并且从未接受过任何相关治疗。