原发性开角型青光眼与近视的关系

目的 :在人群为基础的眼病调查中评价原发性开角型青光眼 (POAG)与近视的关系。方法 :调查北京市南部 3个自然村及 4个城区社区 4 0岁以上居民 4 4 5 1例。进行问卷及视力、屈光、倍频视野检查、非接触眼压测量、裂隙灯眼前节数码照相、晶状体后照明数码照相、散瞳眼底照相等检查。采用电脑验光结合插片法确定屈光状态。近视的定义为等效球镜度≤- 1 0D。近视又分为轻度近视及中、高度近视。根据存在典型的青光眼性视神经与视野改变、前房角开放诊断POAG。结果 :近视者与无近视者的POAG患病率分别为 3 31%、1 4 3% (校正性别与年龄的OR =2 16 ,P =0 0 0 1)。轻度近视者与中高度近视者POAG患病率分别为 2 4 6 %、4 4 9% (OR =0 5 0 9,P =0 0 74 )。与无近视者相比 ,轻度近视者POAG患病率校正性别、年龄因素的OR值为 1 5 2 (P =0 188) ;中高度近视者POAG患病率校正OR值为 3 17(P =0 0 0 0 )。 4 0～ 5 9岁组有、无近视者POAG患病率分别为 1 39%、0 5 6 % (OR =2 5 6 ,P =0 0 5 ) ;>6 0岁组有、无近视者POAG患病率分别为 5 72 %、2 77% (OR =2 0 4 ,P =0 0 0 8)。近视者的平均眼压较无近视者高 0 5 3mmHg(P =0 0 0 2 )。结论 :近视是POAG的重要危险因素。近视程度越高 ,年龄越大 ,POAG患     

高度近视与原发性开角型青光眼关系的研究进展

近年来,在青光眼及近视发病机制研究中发现,高度近视与原发性开角型青光眼的发病有明显相关性.高度近视眼底病理改变是开角型青光眼的高危因素,且高度近视眼底改变与早期开角型青光眼眼底改变容易混淆,造成青光眼早期诊断困难.如何从高度近视患者中早期发现青光眼,并进行早期干预治疗成为难点.本文回顾分析近年文献,对高度近视与原发性开角型青光眼的关系做一综述.     

一原发性开角型青光眼家系相关致病基因的筛查

目的探索一原发性开角型青光眼(POAG)家系的遗传学致病机制。方法按照POAG诊断标准对该家系所有成员进行患病状况调查和家系图绘制。抽取家系成员外周静脉血,提取基因组DNA,并对DNA样本进行全外显子测序和Sanger测序。结果通过筛查发现,GNAT1基因c.G819T.p.K273N突变在POAG家系6例患者中,5例发生突变;8例正常人中,7例未发生突变。结论GNAT1基因c.G819T.p.K273N突变与POAG家系青光眼患病相关性较高,可能为POAG的潜在致病基因。     

原发性开角型青光眼和阿尔茨海默氏病相关性的研究进展

原发性开角型青光眼（primary open-angle glaueoma,POAG）是临床上常见的一种不可逆性致盲眼病。阿尔茨海默氏病（Alzheimer＇s disease，AD）是一种以记忆、智力和识别功能的不同程度减退或丧失为表现的常见中枢神经系统退行性病变。两者的病因均与神经元的损伤有着密切的关系。目前流行病学、组织病理学资料的研究以及两者交叉的临床表现提示两者可能有相似的发病机理。本文从流行病学、功能学和形态学、基因学研究等多个角度简述了近年来有关青光眼与AD之间相关性的研究进展。     

开角型青光眼患者外周血中IL-4、IL-6、IL-12含量的研究

目的　观察开角型青光眼患者与正常人外周血中IL 4、IL 6、IL 12的水平差异。方法　青光眼组 15例 ,正常对照组 15例。 2组年龄无显著性差异。分别取外周血 3mL ,采用双抗体夹心酶联免疫吸附法 (ABC ELISA)方法分别测定IL 4、IL 6、IL 12含量。结果　IL 4含量 :正常对照组为 (2 4 .0 85± 6 .0 88)pg·mL-1;青光眼组为 (2 8.348± 2 0 .131)pg·mL-1,P =0 .4 93,2组间无显著性差异。IL 6含量 :正常对照组为 (7.131± 8.4 15 ) pg·mL-1,青光眼组为 (1.383± 2 30 3)pg·mL-1,P =0 .0 2 1,具有显著性差异。IL 12含量 :正常对照组为 (19.4 0 0± 4 .85 0 )pg·mL-1;青光眼组为 (12 2 15± 4 .12 1) pg·mL-1,P =0 .0 0 0 ,2组相比具有高度统计学差异。结论　开角型青光眼患者外周血中IL 6 ,IL 12的含量显著低于正常人。开角型青光眼患者机体内的细胞免疫水平不同于正常人 ,提示免疫因素可能在视神经损害机制中起重要作用。     

Agreement between event-based and trend-based glaucoma progression analyses

Purpose

To evaluate the agreement between event- and trend-based analyses to determine visual field (VF) progression in glaucoma.

Methods

VFs of 175 glaucoma eyes with ≥5 VFs were analyzed by proprietary software of VF analyzer to determine progression. Agreement (κ) between trend-based analysis of VF index (VFI) and event-based analysis (glaucoma progression analysis, GPA) was evaluated. For eyes progressing by event- and trend-based methods, time to progression by two methods was calculated.

Results

Median number of VFs per eye was 7 and follow-up 7.5 years. GPA classified 101 eyes (57.7%) as stable, 30 eyes (17.1%) as possible and 44 eyes (25.2%) as likely progression. Trend-based analysis classified 122 eyes (69.7%) as stable (slope >−1% per year or any slope magnitude with P>0.05), 53 eyes (30.3%) as progressing with slope <−1% per year, P≤0.05 (sensitive criteria), and 37 eyes (21.1%) as progressing with slope <−1% per year, P≤0.01 (specific criteria). κ between sensitive criteria of GPA (possible combined with likely progression) and trend-based analysis was 0.48, and between specific criteria of GPA (possible clubbed with no progression) and trend-based analysis was 0.50. In eyes progressing by sensitive criteria of both methods (42 eyes), median time to progression by GPA (4.9 years) was similar (P=0.30) to trend-based method (5.0 years). This was also similar in eyes progressing by specific criteria of both methods (25 eyes; 5.6 years versus 5.9 years, P=0.23).

Conclusion

Agreement between event- and trend-based progression analysis was moderate. GPA seemed to detect progression earlier than trend-based analysis, but this wasn''t statistically significant.     

高度近视与原发性开角型青光眼

目的:从流行病学、临床特征及诊断、遗传学说及机制等方面对高度近视与原发性开角型青光眼的关系及研究进展进行综述。方法:仔细分析了28篇原文,总结出高度近视与原发性开角型青光眼的可能机理。结果:高度近视与原发性开角型青光眼密切相关,其可能的机制有:①升压基因学说。②胶原基因学说。结论:高度近视与原发性开角型青光眼密切相关,根据TIGR基因理论和胶原基因理论,高度近视与原发性开角型青光眼都与TIGR基因突变和胶原疾病有关。     

MicroRNA-related polymorphisms in pseudoexfoliation syndrome,pseudoexfoliative glaucoma,and primary open-angle glaucoma

Background: Pseudoexfoliation syndrome (PEX) and glaucoma (pseudoexfoliative glaucoma; PEXG, primary open-angle glaucoma; POAG) have mainly been studied for their associations with genes’ polymorphisms. The purpose of this exploratory study was to investigate the role of polymorphisms in genes encoding for micro RNAs (miRNAs) and in genes related to miRNA biogenesis.

Material and Methods: In the present genetic association study, ninety-two polymorphisms were investigated for their contribution to PEX (n = 203), PEXG (n = 38), and POAG (n = 40) pathogenesis compared to a control group (n = 188). The next generation sequencing (NGS) genotypic analysis revealed data for additional 28 variants.

Results: A protective association was found between PEX and polymorphism 11382316 (mir-3161) [odds ratio (OR) = 0.64, 95% confidence interval (CI): 0.47–0.86, p = 0.003], rs2155248 (mir-1304) [OR = 0.66, 95%CI: 0.47–0.94, p = 0.019], and rs28635903 (mir-1268a) [OR = 0.30, 95%CI: 0.10–0.94, p = 0.029]. Polymorphism rs113297757 (mir-3196) was associated with an increased risk of POAG [OR = 7.75, 95%CI: 2.13–28.76, p = 3 × 10^?4]. Polymorphism rs1057035 (DICER) and rs55671916 (XPO5) in the 3?-UTR of genes related to miRNA biogenesis was associated with decreased risk of PEX [OR = 0.65, 95%CI: 0.46–0.92, p = 0.014] and increased risk of PEXG [OR = 2.84, 95%CI: 1.02–7.94, p = 0.038], respectively. The aforementioned associations according to the allelic model were further supported by the genotypic models of statistical analyses.

Conclusions: This is the first study to report distinct associations of PEX, PEXG, and POAG in the same population with variants of genes involved in miRNA biogenesis and with miRNA genes’ polymorphisms. Further studies in larger groups of patients of various origins are needed to confirm the reported preliminary results.     

原发性开角型及慢性闭角型青光眼患者视盘毛细血管密度和视野缺损的关联性研究

目的 本研究旨在通过分析原发性开角型青光眼(POAG)患者和慢性原发性闭角型青光眼(PACG)患者的视盘毛细血管密度与视野缺损的相关性,探讨视盘毛细血管密度在青光眼诊断和病情评估中的价值。方法 纳入2017年9月2018年9月我院收治的POAG患者90例(90眼)作为POAG组,慢性PACG患者75例(75眼)作为PACG组,2组的年龄、性别和视野平均缺损(MD)值进行了匹配。此外,纳入同期性别、年龄匹配的60位健康体检者60眼作为对照组。检测所有参与者的视盘毛细血管密度、视网膜神经纤维层(RNFL)厚度及视野缺损情况。结果 POAG和PACG患者的平均RNFL厚度和平均毛细血管密度均显著低于正常人(P<0.05),而POAG患者和PACG患者的平均RNFL厚度和平均毛细血管密度差异没有统计学意义(P>0.05)。对于POAG患者,其视盘上方、下方、颞侧和全区的RNFL厚度与视野MD值呈负相关(r=-0.525,-0.462,-0.246,-0.453,P均<0.05),但是鼻侧的RNFL厚度与视野MD值无相关性(r=-0.198,P>0.05)。4个区域和全区的毛细血管密度与视野MD值均呈显著负相关(r=-0.341,-0.426,-0.285,-0.298,-0.557,P均<0.05)。对于PACG患者,仅上方、下方和全区的RNFL厚度与视野MD值相关(r=-0.543,-0.604,-0.448,P均<0.05),但是4个区域及全区的毛细血管密度均与视野MD值显著相关(r=-0.613,-0.494,-0.179,-0.413,-0.589,P均<0.05)。结论 视盘毛细血管密度与POAG和PACG患者的视野缺损相关,视盘毛细血管密度的变化对于青光眼的诊断和病情评估有重要的参考价值。     

高度近视合并原发性开角型青光眼诊断中的几个问题

高度近视是一种复杂的眼病，其眼底改变与原发性开角型青光眼（POAG）有相似之处。重视高度近视合并POAG的早期诊断，避免或降低误诊、漏诊率，首先应重视对二者视盘改变相似性与差异性的了解。现代眼底检查设备先进，但有其局限性。其更主要的目的是为随诊建立量化标准。视野分析要结合眼底情况，排除高度近视的影响因素，并注意初检者的学习曲线及视野的短期、长期波动特点。门诊常规项目的检查不可忽视，不能用设备代替临床经验以及医生的综合分析能力。（跟科，2007,16：17-19）     

Screening glaucoma genes in adult glaucoma suggests a multiallelic contribution of CYP1B1 to open-angle glaucoma phenotypes

Background: Despite increasing knowledge of the genetic pathophysiology of glaucoma, mutations in known genes account for less than 15% of disease. Gene screening predominantly remains a research tool rather than an essential part of the clinical work‐up. We aimed to determine the mutational spectrum and frequency in the genes implicated in glaucoma, in a range of glaucoma and ‘glaucoma suspect’ (GS) participants, with a positive family history. Methods: Observational large case series. One hundred fifteen patients recruited from public hospital and private clinics had diagnoses of GS, ocular hypertension, pseudoexfoliative glaucoma (PXG) or primary open‐angle glaucoma (POAG), and at least one affected family member. In a university laboratory, DNA samples were screened for mutations in all coding exons of MYOC and CYP1B1, and OPTN (exons 4, 5 and 16). WDR36 (exons 1, 4, 5, 8, 11, 13 and 17) was screened in those with CYP1B1 changes. LOXL1 risk variants were screened in PXG pedigrees. Cascade screening of family members was undertaken. Results: Seven out of one hundred fifteen (6.1%) individuals had at least one pathogenic or hypomorphic CYP1B1 allele associated with GS, POAG (5) and PXG phenotypes, including two novel sequence variations (p.Ser6Gly, p.Val243Leu). No pathogenic MYOC change was detected. Five individuals (4.3%) carried an OPTN sequence variation. Three of the seven with CYP1B1 changes had polygenic changes. Conclusions: Mutational analysis of known glaucoma genes in a mixed glaucoma population replicates the reported frequency of pathogenic CYP1B1 changes. Heterozygous CYP1B1 changes occurred at a greater frequency than other genes. Glaucoma pathogenesis in the clinic setting is genetically heterogeneous and may be polygenic.     

选择性激光小梁成形术治疗原发性青光眼

目的评价选择性激光小梁成形术治疗原发性开角型青光眼(primaryopenangleglaucome,POAG)及原发性闭角型青光眼(prionaryangleclosureglaucome,PACG)虹膜周切术后残余青光眼的疗效和安全性。方法前瞻性、非随机性选择局部用药眼压不能控制的原发性开角型青光眼患者(13例16眼),或已行周边虹膜切除或激光虹膜打孔术,房角大部开放而眼压高的原发性闭角型青光眼患者(22例32眼)。应用选择性激光小梁成形术治疗。观察患者术后6个月眼压的变化。结果两组患者的眼压在激光治疗后均有显著下降:POAG组由术前的(25.3±3.9)mmHg降低至术后6个月的(18.0±4.2)mmHg;PACG组由术前的(23.9±3.0)mmHg,降低至术后6个月的(18.8±3.8)mmHg(1kPa=7.5mmHg)。术后暂时的眼压升高为最常见的并发症。结论选择性激光小梁成形术不仅可用于原发性开角型青光眼的治疗,也可以作为治疗残余闭角型青光眼的一种安全有效的方法。     

血液中一氧化氮和内皮素与开角型青光眼的关系

目的 探讨一氧化氮(NO),内皮素(ET-1)与开角型青光眼(POAG)的关系。方法测定POAG及对照组血清中的亚硝酸盐／硝酸盐(NO;／N03^-3),一氧化氮合酶(NOS)和血浆中的ET-1,并测量POAG患者的沿盘面积比,将其与相应的NO;／NO^-3,NOS,ET-1进行相关性分析。结果 (1)POAG中NO减少,ET-1升高。(2)在POAG早期视野损害阶段,N0减低,ET-1升高较中晚期视野损害阶段明显。(3)POAG的沿盘面积比与NO^-2／N0^-3呈负相关,与ET-1呈正相关。结论在POAG患者,可能有某些因素使NO减少,ET-1增加,造成了青光眼性视神经损害。     

The occurrence of primary open-angle glaucoma in the fellow eye of patients with unilateral angle-cleavage glaucoma

The late onset of glaucoma occurs in approximately 7% of eyes with traumatic angle cleavage. We studied 13 patients who developed glaucoma in the angle-cleavage eye at an average of 34 years following trauma. Ten of the 13 patients had 270 degrees or more of angle cleavage. At the time of the initial diagnosis of angle cleavage glaucoma, there were no optic disc or visual field abnormalities in the fellow eyes. After a mean follow-up of 7.7 years, all 13 patients were reevaluated. In addition to standard examination techniques, all underwent disc photos, goniophotos, and Octopus perimetry. Seven of 13 patients (55%) had either frank glaucomatous or suspicious Octopus visual field abnormalities in the fellow eyes. Patients with angle-cleavage glaucoma appear to have at least a 50% chance of developing open-angle glaucoma in the non-traumatized fellow eyes.     

SIRT1、PGC-1α在原发性开角型青光眼患者小梁网组织中的表达及意义

目的　检测原发性开角型青光眼（primary open-angle glaucoma，POAG）患者小梁网组织中沉默信息调节因子2相关酶1（silent information regulator factor 2 related enzyme 1，SIRT1）和过氧化物酶体增殖物激活受体γ辅激活因子1α（peroxisome proliferator-activated receptor γ coactivator-1α，PGC-1α）表达水平，探讨其与POAG小梁网组织功能损伤的关系。方法　收集2017年1月至2018年4月在海南医学院第一附属医院手术切除确诊为POAG 40例（40眼）患者的小梁网组织为POAG组样本，另取30例眼球供体的小梁网组织为对照组样本，采用RT-PCR法检测2组小梁网组织中SIRT1、PGC-1α mRNA表达，免疫组织化学染色法检测SIRT1、PGC-1α蛋白表达，同时检测过氧化物酶（peroxidase dismutase，POD）和超氧化物歧化酶（superoxide dismutase，SOD）水平。结果　POAG组小梁网组织中SIRT1、PGC-1α mRNA表达水平（0.11±0.03、0.32±0.10）均低于对照组（0.24±0.07、0.67±0.21）（均为P＜0.05）；POAG组小梁组织中SIRT1表达与PGC-1α表达呈正相关关系（r=0.759，P＜0.05）；POAG组小梁网组织中POD水平［（102.59±22.37）×10³ U·L^-1］高于对照组［（73.46±15.81）×10³U·L^-1］（P＜0.05），SOD水平［（347.62±50.73）U·L^-1］低于对照组［（412.57±61.25）U·L^-1］（P＜0.05）；POAG组小梁网组织中SIRT1、PGC-1α表达与POD水平均呈负相关关系（r=-0.636、-0.737，均为P＜0.05），与SOD水平均呈正相关关系（r=0.662、0.614，均为P＜0.05）。结论　POAG患者小梁网组织中SIRT1和PGC-1α表达水平降低，可能在线粒体功能失调和氧化应激对小梁网的损伤中发挥重要调控作用。     

Analysis of risk factors that may be associated with progression from ocular hypertension to primary open angle glaucoma

Background: As a multifactorial disease, glaucoma may be associated with pressure‐dependent and pressure‐independent factors. Ocular hypertension (OHT) may develop into primary open angle glaucoma (POAG) for many patients. Groups with OHT and POAG were compared for pressure‐dependent and independent risk factors. A high prevalence of any factor(s) could indicate a contribution to progression from OHT to POAG. Methods: A sample of patients with POAG (n = 438) and with OHT (n = 301) were selected from those attending a tertiary referral private glaucoma practice, and data were collected regarding age and intraocular pressure at the time of diagnosis, sex, family history of glaucoma, systemic hypertension, diabetes, Raynaud's phenomenon, migraine and myopia. Results: After multivariate analysis, older age at time of diagnosis (χ²₅ = 73.89, P < 0.001), myopia (odds ratio [OR] = 1.5, 95% confidence interval [CI] 1.0?2.2; P < 0.05), a family history of glaucoma (OR = 1.6, 95% CI 1.1?2.3; P < 0.01) and a high intraocular pressure (χ²₄ = 16.96; P = 0.002) were found to be more prevalent among those with POAG. No other significant differences could be found between the two groups. Conclusion: Patients who have OHT may be at higher risk of developing POAG if they also have myopia, a family history of glaucoma or are of older age.     

外路小梁切开联合切除术治疗开角型青光眼

目的确定外路小梁切开联合切除术治疗开角型青光眼的效果。方法对21例（36眼）相对年轻的开角型青光眼患者行小梁切开联合切除术，并与20例（33眼）单行小梁切除术的患者进行比较。结果治疗组随访14例（24眼），平均随访22．5mo，眼压控制率为87．5％（不用药），局部用抗青光眼药物达95．7％。对照组随访16例26眼，平均随访19．3mo，眼压控制率为53．8％（不用药），局部用药为73．1％，两组比较有显著差异。结论外路小梁切开联合切除术治疗相对年轻的开角型青光眼患者比单纯小梁切除术成功率明显提高。     

Autonomic nervous system, circadian rhythms, and primary open-angle glaucoma

The etiology of primary open-angle glaucoma (POAG) remains the subject of continuing investigation. Despite the many known risk factors and mechanism of damage, the principal treatment objectives in POAG still consist of reduction of intraocular pressure, which although straightforward in many cases, often leaves the clinician with the question of how far to pursue a sufficiently low pressure to prevent further damage. Other risk factors such as hemodynamic insufficiency due to vascular dysregulation and abnormal blood pressure are often overlooked in the day-to-day practice; their harmful effects for glaucoma are, it seems, more potent at night while the patient sleeps and when clinical investigation is most difficult. Although the status of autonomic nervous system is an important determinant of the systemic hemodynamic parameters, this issue is usually ignored by the clinician in the process of glaucoma diagnosis. Consequently, there is a lack of alternative therapies tailored to address associated systemic risk factors for POAG on a case and chronological basis; this approach could be more effective in preventing the progression and visual loss in selected glaucoma cases.     

Relationship between parapapillary atrophy and visual field abnormality in primary open-angle glaucoma

PURPOSE: To investigate the relationship of parapapillary atrophy measured by confocal scanning laser ophthalmoscopy to visual field sensitivity measured with standard automated perimetry and short-wavelength automated perimetry in patients with primary open-angle glaucoma. METHODS: Forty-seven eyes of 47 primary open-angle glaucoma patients with increased intraocular pressure (> or = 22 mm Hg) were enrolled. Optic nerve head topography and parapapillary atrophy (beta and alpha zones) were assessed by confocal scanning laser ophthalmoscopy. Mean deviation and corrected pattern SD were assessed with standard automated perimetry and short-wavelength automated perimetry. RESULTS: Beta and alpha zones were found in 23 (49%) and 47 (100%) eyes with primary open-angle glaucoma, respectively. The area of beta zone showed significant correlations with MD of standard automated perimetry, corrected pattern SD of standard automated perimetry, and corrected pattern SD of short-wavelength automated perimetry (Spearman r = -0.366, P = .012; r = 0.327, P = .025; and r = 0.436, P = .002, respectively). The area of alpha zone showed a significant correlation with mean deviation of standard automated perimetry (r = -0.378, P = .009). Mean MD of standard automated perimetry, mean corrected pattern SD of standard automated perimetry, and mean corrected pattern SD of short-wavelength automated perimetry were significantly worse in eyes with beta zone than in eyes without beta zone. CONCLUSIONS: Parapapillary atrophy measured by confocal scanning laser ophthalmoscopy, especially beta zone, is associated with glaucomatous visual field loss demonstrated by standard automated perimetry and short-wavelength automated perimetry.