青光眼的中枢损伤

青光眼性损伤的形态学特征及病理机制 ,在视网膜节细胞水平及视神经水平已得到广泛研究 ;最近研究表明 ,青光眼对外侧膝状体、视皮质等中枢视路也存在相应损伤 ,并且提示青光眼的中枢损伤可能参与视功能状态的进一步恶化。我们对近年来青光眼中枢损伤的病理形态学及病理机制研究作一综述。     

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。     

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.     

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.     

斑马鱼视觉损伤和视神经再生的研究进展

斑马鱼因其视觉系统与人类的相似性和其视网膜再生的巨大潜能,成为目前研究眼变性疾病的热门模型。眼变性疾病特别是视网膜变性、视神经变性会严重影响视力,并且病变后再生修复十分有限,严重者甚至导致失明。与哺乳动物相反,斑马鱼能修复视神经轴突损伤,刺激视网膜Müller胶质细胞去分化为多能祖细胞,从而实现视网膜神经元及神经轴突再生,恢复正常视功能。本文主要从斑马鱼模型在眼病方面的应用,斑马鱼视网膜神经元和Müller胶质细胞响应损伤启动再生修复的关键信号通路方面作一综述。     

视觉电生理技术在青光眼早期诊断中的意义

青光眼是一组威胁和损害视神经及其视觉通路,最终导致视觉功能损害的疾病。青光眼视神经损害以视网膜神经节细胞( retinal ganglion cells,RGCs)及其轴突数目进行性丢失、视盘凹陷、视野缺损为特征。静态自动视野计检查是评估青光眼病程进展的金标准,但其结果往往受到患者主观因素的限制。近年来视觉电生理技术飞速发展,虽还不能代替传统的视野检查,但作为补充,其能在青光眼视野缺损前即出现振幅及潜伏期的改变,为早期青光眼的诊断提供了新的参考思路。本文主要对三种特殊类型的视网膜电图以及多焦视觉诱发电位在青光眼早期诊断中的意义进行综述。     

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。     

青光眼视神经保护的研究进展

视网膜神经节细胞死亡是青光眼视神经损伤的最终共同通路,阻断视神经损伤通路和增强视神经存活机制的方法称为视神经保护。目前这一研究领域主要包括抗凋亡途径,促红细胞生成素,谷氨酸拮抗剂,钙离子拮抗剂,一氧化氮合酶抑制剂,神经营养因子,自身保护性免疫,抗青光眼药物等方面。将来视神经保护将成为一种重要的青光眼辅助治疗措施     

视神经损伤的基因治疗研究进展

视神经损伤后,所处的微环境发生了较大改变,如何通过基因治疗的手段调整这些变化,使其更好地发挥对损伤视神经的保护作用是近期研究的热点。视神经及视网膜神经节细胞（RGCs）与相关的视觉通路作为一种成熟的中枢神经系统研究模型,其研究结果对中枢神经系统疾病的治疗有积极的意义。拟从视神经损伤后RGCs死亡的特点、所处微环境的改变、基因治疗工具及治疗损伤常见的基因干预等方面进行综述。     

静息态功能磁共振成像在青光眼疾病中的应用研究进展

青光眼是全球第一大不可逆致盲性眼病,是一组以特征性视神经损伤和视野缺损为共同特征的神经眼科疾病。已有多项研究表明,青光眼的损害不仅局限于眼球局部视神经节细胞的凋亡,而且会累及大脑视皮层整个视觉通路,是一种全脑神经退行性疾病。近年来,功能性磁共振成像(functional magnetic resonance imaging,fMRI)技术飞速发展,将神经系统的解剖和功能相结合,使局部脑组织的损伤与脑功能的缺失对应起来,可以实现在无创条件下观察中枢神经系统解剖结构及功能变化,为青光眼病理机制的研究提供了有效证据。而静息态功能磁共振成像(resting-state functional magnetic resonance imaging, rs-fMRI)作为神经影像学的热点研究技术,为探讨青光眼患者视觉相关脑区的解剖结构、代谢以及功能改变提供了影像学支持。本综述主要讨论了rs-fMRI的基本原理以及低频振幅(amplitude of low-frequency fluctuation, ALFF)、局部一致性(regional homogeneity, ReHo)、度中心度(degree centrality, DC)、功能连接(functional connectivity, FC)等几种较为常用的分析方法在青光眼中应用的研究进展。     

Diffusion tensor magnetic resonance imaging reveals visual pathway damage that correlates with clinical severity in glaucoma

Background: To investigate nerve fibre damage of the visual pathway in patients with primary open‐angle glaucoma using tract‐based spatial statistical analysis of diffusion tensor imaging and correlate these measures with the clinical severity of glaucoma. Design: Cross‐sectional study. Participants: Twenty‐five individuals with primary open‐angle glaucoma and 24 healthy controls were recruited. Methods: All subjects underwent detailed ophthalmological examinations, including the cup‐to‐disc ratio, retinal nerve fibre layer thickness and visual fields test. Diffusion tensor imaging of the visual pathway was performed using a 3.0‐T magnetic resonance scanner. Main Outcome Measures: Diffusivity changes of the nerve fibres in the visual pathway were calculated through tract‐based spatial statistical analysis. The mean diffusivity and fractional anisotropy were assessed and compared with ophthalmological measurements. Results: Compared with controls, bilateral optic tracts and optic radiations in primary open‐angle glaucoma patients showed significantly decreased fractional anisotropy and increased mean diffusivity (P < 0.05). In the glaucoma group, the fractional anisotropy of the optic tracts and optic radiations varied consistently with the cup‐to‐disc ratio, retinal nerve fibre layer thickness and visual function analysis, respectively (P < 0.05). The mean diffusivity of the optic tracts correlated with these ophthalmological measurements (P < 0.05). However, no significant correlation was observed between the mean diffusivity of the optic radiations and the ophthalmological measurements (P > 0.05). Conclusions: The optic tracts and optic radiations of primary open‐angle glaucoma patients demonstrated radiological evidence of neurodegeneration. This varied with damage to the optic disc and with the loss of visual function. Tract‐based spatial statistical analysis of diffusion tensor imaging is an objective and effective tool for detecting the loss of cortical nerve fibres in primary open‐angle glaucoma.     

原发性开角型青光眼的中医分型与RNFL厚度改变及视野损害关系

目的:探讨原发性开角型青光眼(青风内障)中医辨证分型与视网膜神经纤维层厚度的改变及视野损害之间关系的临床研究。方法:对72例144眼原发性开角型青光眼患者,采用光学相干断层成像术对144眼作围绕视盘3.4mm的环形扫描,记录各个象限视网膜神经纤维层厚度,并采用进口Humphry视野分析仪作中30°全定量视野检测检查,同时根据中医理论对患者作中医辨证分型,观察二者之间的关系。结果:中医的证型与视网膜神经纤维层厚度改变类型有统计学意义,中医证型与视野损害的类型有统计学意义(P<0.05)。结论:视神经损害较严重多见于青风内障的虚证,视神经损害早期多见于实证,因此视神经损害的程度在一定的程度上给予中医辨证治疗一定的指导作用。     

Association of magnetic resonance imaging of anterior optic pathway with glaucomatous visual field damage and optic disc cupping

PURPOSE: To investigate the association of magnetic resonance imaging (MRI) of anterior optic pathway with glaucomatous visual field damage and optic disc cupping. SUBJECTS AND METHODS: Twenty-three healthy volunteers (controls) and 31 glaucoma patients (14 with primary open angle glaucoma and 17 with normal tension glaucoma) were enrolled. All the participants showed no abnormal signs in their intracranial space and optic tract causing optic nerve atrophy and visual field defect, as confirmed by MRI. Multislice T1-weighted spin-echo imaging was performed in the sagittal plane followed by the coronal plane. MRI enabled the evaluation of the diameter of the optic nerve located in the retro-bulb space and the height of the optic chiasm in an observer-masked fashion. The MRI data were compared with the mean deviation (MD) score of the full threshold static visual field test and the optic cup-disc ratio (C/D ratio). RESULTS: The optic nerve diameter was significantly smaller in glaucoma patients (2.25 +/- 0.33 mm) than in controls (2.47 +/- 0.24 mm) and the height of the optic chiasm was significantly shorter in glaucoma patients (2.12 +/- 0.37 mm) than in controls (2.77 +/- 0.36 mm). The optic nerve diameter showed significant correlation with MD score (r = 0.547, P = 0.001) and C/D ratio (r = 0.407, P = 0.009). These correlations are similar to that between MD score and C/D ratio (r = 0.490, P = 0.001). The height of the optic chiasm showed significant correlation with MD score (r = 0.503, P = 0.01) and low correlation with C/D ratio (r = 0.339, P = 0.113). CONCLUSION: Glaucoma affects the anterior visual pathway anterogradely at least up to the optic chiasm, and these morphologic changes in the anterior visual pathway are correlated with glaucomatous optic nerve damage. MRI of the anterior visual pathway may be a good tool for evaluating glaucomatous damage objectively.     

Cupping of the optic disc with compressive lesions of the anterior visual pathway

Cupping of the optic nerve, classically a sign of glaucoma, was demonstrated in 16 patients with lesions compressing the anterior visual pathway. Color contrast determinations of the cup/disc ratio demonstrated a ratio greater than 0.49 in 31 eyes. Further evaluation by stereobiomicroscopy showed cavernous degeneration by contour changes in 25 of the optic nerves. None of the patients had intraocular pressures greater than 22, and seven had normal tonography. Visual fields demonstrated bitemporal field defects in most patients and none were typical of glaucoma. Snellen acuity loss, out of proportion to the extent of optic disc cupping was found in 12 patients. This study indicates that diseases other than glaucoma can cause significant cupping of the optic nerves. Detailed evaluation of the disc changes and the visual fields will prevent confusion between compressive lesions of the optic nerves or chiasm and glaucoma.     

Contrast sensitivity and pattern visual evoked potential in patients with glaucoma

Contrast sensitivity and pattern visual evoked potential (VEP) were measured in cases of ocular hypertension and primary open-angle glaucoma at various stages. The visual field of each eye was examined quantitatively and the retinal nerve fiber layer and optic disc were precisely assessed with magnified stereoscope fundus photography.This study revealed that contrast sensitivity of the eyes with glaucoma was within the normal range in the very early stage of the disease. As optic nerve damage advanced, high-or low-frequency loss developed. Further optic nerve damage produced a level type of loss.Pattern VEPs also showed increasing abnormalities as glaucomatous optic nerve damage progressed. Measurements of contrast sensitivity and pattern VEP were found not to be as sensitive as quantified precise visual field measurment or color stereosopic fundus photography for detection of minor optic nerve damage in cases of early glaucoma. These methods may be useful, however, as an objective and subjective monitor of progression of optic nerve damage in glaucoma.     

Longitudinal changes in the visual field and optic disc in glaucoma

The nature and mode of functional and structural progression in open-angle glaucoma is a subject of considerable debate in the literature. While there is a traditionally held viewpoint that optic disc and/or nerve fibre layer changes precede visual field changes, there is surprisingly little published evidence from well-controlled prospective studies in this area, specifically with modern perimetric and imaging techniques. In this paper, we report on clinical data from both glaucoma patients and normal controls collected prospectively over several years, to address the relationship between visual field and optic disc changes in glaucoma using standard automated perimetry (SAP), high-pass resolution perimetry (HRP) and confocal scanning laser tomography (CSLT). We use several methods of analysis of longitudinal data and describe a new technique called "evidence of change" analysis which facilitates comparison between different tests. We demonstrate that current clinical indicators of visual function (SAP and HRP) and measures of optic disc structure (CSLT) provide largely independent measures of progression. We discuss the reasons for these findings as well as several methodological issues that pose challenges to elucidating the true structure-function relationship in glaucoma.     

青光眼是一种中枢神经系统疾病吗？

长期以来,人们对青光眼的理解均局限在房水循环障碍和视神经损害方面。近年来,随着对青光眼和视觉科学的深入研究及眼科神经科交叉学科的发展,跨学科的新问题被提了出来,即青光眼仅仅是一种视神经疾病吗？它是原发于眼部但累及全视路的疾病吗？抑或是某种特殊中枢神经系统疾病在眼部的表现？这些问题迄今尚无定论,但有理由认为,青光眼是整个视路在多方面、多层次、多因素损害基础上形成的综合征群;其机制复杂,涉及跨突触损害、视路供血紊乱、血一脑屏障异常等。将青光眼归为眼部和脑部神经变性性疾病对认识青光眼的发病机制、建立系统全面的治疗策略、挽救患者视力具有十分重大的意义。