原发性开角型青光眼中枢视觉通路的改变

原发性开角型青光眼是临床上常见的一种不可逆性致盲眼病,对于青光眼所造成的视网膜神经节细胞水平及视神经水平的损害已得到广泛研究.最近研究表明,青光眼患者的上行视路部分,如外侧膝状体及枕叶视皮质等,存在损伤,提示青光眼可能同时也是一种中枢神经退行性疾病,早期对青光眼进行视神经保护治疗有助于减缓视神经节细胞的凋亡并阻止视功能的进一步损害.本文将从青光眼中枢损伤的发病机制、临床诊断及青光眼视神经保护治疗方面的研究进展进行综述,并对青光眼的研究前景进行展望.     

TLR4在青光眼视神经损伤机制中的作用

青光眼是一种以视乳头萎缩凹陷、视野缺损及视力下降为共同特征的不可逆的致盲性疾病,其视神经损伤的本质为视神经节细胞的凋亡。尽管通过药物干预和手术控制眼压可以对青光眼起到一定的治疗作用,但如何从根本上阻止青光眼的进一步发展仍处于探索阶段。因此,研究青光眼视神经损伤机制,通过阻断视神经损伤而治疗青光眼至关重要。近几年,免疫机制对青光眼视神经损伤的影响成为研究热点,本文中主要对Toll样受体4(TLR4)通过不同免疫通路并与神经胶质细胞相互作用引起青光眼患者视神经损伤进行综述。     

青光眼的中枢神经系统改变

青光眼是一组以进行性视网膜神经节细胞(RGCs)凋亡、视神经纤维层丢失为特征的神经退行性疾病.大量研究证明,青光眼患者在RGCs、视神经、视交叉、视束、外侧膝状体、视放射、大脑枕叶视皮质整个视觉通路上均出现了病理改变,青光眼是整个视觉通路在多层次、多因素损害的基础上出现的复杂综合症群.从视觉通路多级神经元水平更深入地研究青光眼视觉通路损害的特征,及时发现青光眼患者整个视觉通路的早期微小变化,重新认识疾病,开发新的临床诊治方法,早诊断、早治疗,有效延缓青光眼致盲进程,日益成为眼科学界和神经科学界关注的焦点.本文将从青光眼性中枢神经系统损害的表现、青光眼中枢神经系统损伤可能存在的机制、研究青光眼中枢神经损伤的意义几个方面就青光眼的中枢神经系统改变研究进展进行综述.     

再论青光眼是否属于中枢神经系统疾病

青光眼是一种以眼压为主要危险因素的视神经疾病.近年来,随着对青光眼和视觉科学的深入研究以及眼科神经科交叉学科的发展,同时借助于神经影像技术的不断提高,关于青光眼本质的一些新问题随即产生,即青光眼仅仅是一种眼部疾病吗?它是原发于眼部但累及全视路的疾病吗?或者它是某种特殊中枢神经系统疾病在眼部的表现?这些问题在眼科界引起了争论.已有许多证据表明青光眼不仅仅累及视神经,而且引起外侧膝状体、视放射和视觉中枢的损伤,它是整个视路多层次损害的综合征群,其机制复杂.我们认为青光眼是一种中枢神经系统疾病.最近,有学者通过实验发现青光眼的首发损害在中枢神经系统而非眼部.将青光眼归为一种中枢神经系统疾病对认识青光眼的发病机制、建立系统全面的治疗策略、挽救患者视力具有一定意义.     

巩膜生物力学改变与青光眼性视神经损伤

青光眼的主要病理特征是视网膜神经节细胞(RGC)的丧失,从而导致进行性、不可逆性的视力丧失。目前已有研究表明,巩膜的生物力学性质会影响视神经的生物力学变化,并且在RGC损伤和视力丧失的病理过程中起重要作用。因此,巩膜生物力学与青光眼关系的研究对深入了解青光眼的发病机制有着重要的意义。本文就巩膜的生物力学特性、巩膜胶原纤维结构、巩膜重塑、巩膜刚度及通透性与青光眼性视神经损伤的关系进行综述,以利于更深入地了解青光眼性视神经损害的机制,为青光眼的预防和治疗提供新思路。     

局灶性筛板缺损对青光眼进展的影响

筛板一直被认为是青光眼视网膜神经节细胞和轴突发生损伤的初始部位,观察筛板的形态学改变有助于认识青光眼的病理机制。以往研究结果显示局灶性筛板缺损与青光眼进展相关,但两者的因果关系和作用机制并不清楚。本文指出相干光层析成像术发展,首次揭示了青光眼局灶性筛板缺损可以平衡跨筛板压力梯度,从而起到延缓或终止青光眼视神经损伤进展的作用,该发现为跨筛板压力梯度学说在青光眼发病机制中的作用提供了直接的临床依据,深化了临床对局灶性筛板缺损与青光眼进展的认识,从另一角度阐述了原发性开角型青光眼的发病机制,为该疾病的治疗和预后判断提供了新的思路。     

青光眼视神经损伤机制的研究进展

青光眼是目前全球范围内致盲性最高的疾病之一,是以进行性视网膜神经节细胞丧失、不可逆的视野损害等病理性改变为特征,最终导致视神经萎缩及视功能丧失的疾病。目前青光眼的发病机制并不完全清楚,其中视神经损伤的机制有多种学说,包括眼压因素及非眼压因素,非眼压因素包括血管因素、免疫作用、远端轴突病变、氧化应激作用、细胞因子的变化及自噬等机制。本文综述了有关青光眼视神经损伤机制的研究进展,为进一步研究青光眼视神经病变提供依据。     

人类青光眼和青光眼动物模型中神经胶质细胞的改变

青光眼是主要的致盲眼病之一,其特征性表现为视乳头的凹陷性萎缩和视野的特征性缩小.青光眼的病因复杂,但却有共同的病理结局即视网膜神经节细胞的进行性凋亡.因此对青光眼的研究多集中在视网膜神经节细胞的改变及其机制上.但近年来的研究结果表明,作为神经系统另一大类细胞即神经胶质细胞在青光眼的病理过程中也发生了活化,并且其活化与视网膜神经节细胞的改变及疾病的发生、发展密切相关.所以对青光眼中神经胶质细胞的研究也越来越深入.笔者就目前对神经胶质细胞在人类青光眼及青光眼动物模型中的改变进行综述,以供同道参考.     

DDLS视乳头损伤分期法与青光眼视野损害的相关性研究

目的:研究 DDLS(disk damage likelihood scale)视乳头损伤分期法与开角型青光眼视野损害的相关性,探讨开角型青光眼的早期诊断方法.方法:利用Discam早期青光眼诊断仪彩色视乳头立体成像系统在Screen Vu立体观察镜下确定31例(58眼)开角型青光眼及29例(58眼)可疑青光眼患者视乳头的DDLS分期.所选患者均为中等大小视乳头(2.0～3.0mm).利用 Humphrey 自动电脑视野分析仪30-2程序对上述患者进行视野检测,研究DDLS分期与视野指数平均缺损(MD,mean defect)、视野模式标准差(PSD,pattern standard deviation)及视野损害分期(HPASS,Hodapp-Parrish-Anderson staging system)的相关性.结果:对116眼中等大小视乳头(2.0～3.0mm)开角型青光眼及可疑青光眼患者研究发现,青光眼组DDLS分期与MD(Pearson,r=-0.664,P＜0.000)、PSD(Pearson.r=0.554.P＜0.000)及HPASS(Spearman,r=0.603,P＜0.000)有相关性,相关系数具有统计学意义.可疑青光眼组DDLS分期与MD、PSD及HPASS分期无明显相关性.结论:DDLS视乳头损伤分期法与开角型青光眼视野损害的程度相关,DDLS视乳头损伤分期法有助于开角型青光眼的早期诊断.     

生物信息法推算青光眼小鼠视乳头及视网膜功能变化

目的：本研究运用生物信息学软件,利用数据库资料,推测青光眼早期小鼠视乳头及视网膜可能的信号路径及基因生物功能模块,为研究青光眼发病机制提供新的途径。方法：本研究的数据是从美国生物技术信息中心GEO基因表达数据库获得。利用美国昂飞公司 Expression Console软件对原始的CEL数据进行标准化及对数化转换处理。利用以t检验为基础的基因表达差异显著性分析方法SAM对基因芯片数据进行显著性差异分析,分析后筛选显著性差异表达基因,采用GNRInfer软件构建了小鼠视乳头及视网膜前50个有显著差异表达基因的调控网络,同时我们利用 MAS3.0分子注释系统软件及DAVID软件这两种在线分析平台中进一步富集基因信号通路。
　　结果：青光眼各组视乳头和视网膜及其相对应组的显著性差异基因分析表明,在青光眼早期视乳头组及视网膜组较之正常组相比视乳头组显著性差异基因数量明显增多,青光眼视乳头及视网膜网络构建显示,视乳头基因网络中主要调控节点基因包括 Unc13 c、Kif5 a、TRPM1、PANX;视网膜基因网络中主要调控节点基因包括POU4 F1、NEFL、BC03870、CALB2。 MAS在线信号通路分析显示,视乳头组织中主要的信号代谢通路包括肌萎缩侧索硬化代谢通路、神经退行性紊乱、白细胞穿内皮性迁移及前列腺癌信号通路。视网膜组织主要代谢通路包括肌萎缩侧索硬化代谢、酪氨酸代谢、黑色素生成、氮代谢、缝隙连接、白细胞穿内皮迁移。
　　结论：早期青光眼阶段视乳头较视网膜对眼压更为敏感,特别是Tyrp1基因在早期高眼压的表达能否作为青光眼早期生物学指标有待进一步探讨。在青光眼高眼压压力下,节点分子生物学功能显示在视乳头组织中,细胞骨架的重排、生物驱动马达动力、物质代谢及运输力均为增强;而在视网膜组织中,最突出的表现在细胞的再生、分化及修复作用,此结果提示我们在青光眼的研究中应重视哺乳动物视网膜损伤后自身修复的研究。代谢通路富集分析显示,炎性反应在视乳头及视网膜的病理反应中均起到非常重要的作用,而在视乳头中由于其狭窄而拥挤的解剖结构在青光眼发病中存在营养代谢及物质转运障碍。     

Glaucoma screening--justified or not justified?

In explaining the damages of primary open-angle glaucoma, the elevated eye pressure was assumed to be the central causative factor. But epidemiological research found high proportions of the following clinical entities: only elevated pressure without further damages (called ocular hypertension), and only glaucomatous damages without high pressure (called normal- or low-pressure glaucoma). These facts made the pressure-theory doubtful, and therefore it had to be modified. Some authors, though, doubt the general validity of the pressure-theory, and postulate other models for the etiology of glaucomatous damages. According to current knowledge, for the diagnosis and screening of primary open angle glaucoma, emphasis should be put rather on the visual fields and the appearance of the optic disc, while pressure measurements supply further clues.     

青光眼视网膜中央动脉和眼动脉的血流动力学改变

本文应用彩色多普勒成像(CDI)技术,检测了50例100只正常眼,和39例61只青光眼的眼动脉(OA),视网膜中央动脉(CRA)血流动力学参数.表明正常眼和青光眼的血流动力学特点.首次提出青光眼的血流动力学分型.提出CRA缺血性改变是青光眼性视功能掼害的高危因素.提出监测CRA缺血性改变的临床应用及意义.本文还首次提出用血管动压强来计算视网膜血管灌注压;引入血流速度及血流阻力,血液粘滞度等物理量来判断视网膜灌注压,从而解释了眼压升高、血流速度减慢的机理;高粘滞血症、全身血管病对青光眼的作用机理;低压性青光眼的部分高危因素.提出了青光眼研究的新途径.     

非青光眼性大视杯临床分析

目的 探讨非青光眼性疾病引起视杯扩大的病因以及鉴别要点,为临床识别非青光眼性大视杯提供依据。设计 回顾性病例系列。研究对象 12例（19眼）非青光眼大视杯患者。方法 分析比较这些患者的病因、视盘形态学特征以及相关影像资料。主要指标 病因、视盘形态特征以及视功能改变。结果 12例患者中,4例为视神经炎,1例视神经脊髓炎,1例Leber遗传性视神经病变,2例垂体瘤,1例基底节脑出血,1例睫状视网膜动脉阻塞合并视网膜中央静脉阻塞,1例视网膜中央动脉阻塞,1例视神经损伤。所有患者视杯呈弥漫性或局限性扩大,盘沿苍白。视野表现为与原发病相应的缺损。结论 各种视神经疾病和视网膜疾病均有可能导致大视杯,它与青光眼性大视杯的鉴别点在于盘沿色泽、有无盘沿局限性缺失以及视功能异常和视盘改变的相关性。（眼科, 2012, 21: 306-309）     

The Competer automatic campimeter II. Clinical experience

The Competer automatic campimeter was tested in 98 patients. The results of 31 visual fields with glaucomatous defects and 11 (para) central defects due to maculopathies are reported. The examination with the Competer will miss a certain amount of early glaucomatous visual field defects. The percentage depends on the selection of the visual fields. Any substantial glaucomatous visual field defect will be detected. The indication of typical configuration is not ideal. The examination with the Competer is not suitable for the detection of small (para) central defects, due to lack of stimuluspositions in the (para) central visual field. The Competer's meridional static perimetry device was not used in this study. The Competer has a large dynamic range and a good detection strategy. The stimulus distribution over the visual field could be improved.     

Central corneal thickness correlated with glaucoma damage and rate of progression

PURPOSE: To evaluate whether the amount of glaucomatous optic nerve damage at presentation of the patient and the rate of progression of glaucoma during follow-up are related to central corneal thickness. METHODS: The prospective observational clinical study included 861 eyes of 454 white subjects (239 normal eyes of 121 subjects, 250 ocular hypertensive eyes of 118 patients, 372 eyes of 215 patients with chronic open-angle glaucoma). For 567 eyes (304 patients) with ocular hypertension or chronic open-angle glaucoma, follow-up examinations were performed, with a mean follow-up time of 62.7 +/- 33.2 months (median, 60.8; range, 6.2-124.9). All patients underwent qualitative and morphometric evaluation of color stereo optic disc photographs and white-on-white visual field examination. Central corneal thickness was measured by corneal pachymetry. RESULTS: Central corneal thickness correlated significantly (P < 0.001) and positively with the area of the neuroretinal rim and negatively with the loss of visual field. Development or progression of glaucomatous visual field defects detected in 119 (21.0%) eyes was statistically independent of central corneal thickness, in univariate (P = 0.99) and multivariate Cox regression analyses (P = 0.19). CONCLUSIONS: At the time of patient referral, the amount of glaucomatous optic nerve damage correlated significantly with a thin central cornea. Progression of glaucomatous optic nerve neuropathy was independent of central corneal thickness, suggesting that central corneal thickness may not play a major role in the pathogenesis of progressive glaucomatous optic nerve damage.     

Clinical classification of glaucomatous visual field loss by frequency doubling perimetry

Purpose: To determine whether the frequency doubling perimeter (FDP) can grade glaucomatous visual function loss in a clinically relevant manner. Sinusoidal gratings <1 cpd that undergo counterphase flicker >15 Hz appear to have twice as many bands of light, a phenomenon referred to as the “frequency doubling illusion.” Evidence suggests that this psychophysical effect is mediated in part by large-diameter ganglion cells, which are reported to be lost early in the glaucomatous disease process. A portable, commercially available FDP has already demonstrated high diagnostic potential for glaucoma screening.Methods: Sixty-four eyes of 42 glaucomatous patients and 22 eyes of 14 normal subjects were evaluated by means of both frequency doubling perimetry and Humphrey perimetry. A clinical scoring algorithm modeled after the Hodapp-Parrish-Anderson criteria for scoring Humphrey visual field defects was derived for the FDP at the halfway point of the study, and all participants were reassessed with this algorithm upon its completion.Results: FDP mean and pattern deviation showed strong linear correlations with Humphrey 30-2 mean deviation (R = 0.75; P < .0001) and corrected pattern standard deviation values (R = 0.64; P < .0001). Despite this, neither global index could consistently categorize the graded glaucomatous visual fields in a manner consistent with the Hodapp-Parrish-Anderson criteria. The new FDP scoring algorithm did provide good segregation (73% precise parity, 93% parity within one Humphrey grade).Conclusions: Sixteen-zone frequency doubling perimetry can segregate glaucomatous visual field loss into pathologic categories approximating those obtained with Humphrey 30-2 perimetry by means of a formula modeled after the Hodapp-Parrish-Anderson criteria.     

Paying attention to the cerebrovascular system in glaucoma

In glaucoma, damage to vision pathways in the brain may contribute to vision dysfunction and loss. A large part of the central visual system is located within a watershed area of increased susceptibility to ischemic injury. In addition to glaucomatous central visual neuron injury, glaucoma patients may suffer silent vascular insults from cerebral small blood vessel disease. We hypothesize that "double-hit" mechanisms of injury, such as glaucoma and comorbid cerebrovascular conditions, play a role in glaucomatous susceptibility and disease manifestations in young and aging populations at risk.     

Glaucomatous versus nonglaucomatous optic disc cupping: clinical differentiation

Cupping of the optic nerve head associated with normal intraocular pressure (IOP) is a common clinical presentation for which clearly defined management guidelines have not been established. The clinical approach represents a diagnostic challenge because the mechanism of optic nerve injury is often difficult to objectively establish. Of paramount importance is the primary distinction between physiologic cupping and pathologic cupping, and the accurate subclassification of eyes with pathologic cupping. Therefore, it is essential for clinicians to differentiate glaucomatous from nonglaucomatous disc damage. This article reviews the clinical differentiation of eyes with glaucomatous and nonglaucomatous optic disc cupping.