颅内压与青光眼及其无创测量技术的研究进展

青光眼是世界上第二位致盲性眼病,第一位不可复性致盲性眼病。尽管眼压增高被认为是青光眼性视神经损害的主要危险因素,但是50%的原发性开角型青光眼患者的日常眼压正常,还有一些患者尽管眼压控制良好,但青光眼性视神经损害仍继续发展。这些现象无法用高眼压理论来解释,青光眼患者视神经损害的发病机制仍待探讨。目前国内外的一些研究表明：（1）视神经周围的生物力学的解剖结构包括眼内压,筛板和球后的脑脊液压力在原发性开角型青光眼的发病机制中发挥重要的作用;（2）正常眼压性青光眼患者的脑脊液压力比正常人低,而跨筛板压力差比正常人高;（3）高眼压症患者的脑脊液压力比正常人群高,而跨筛板压力差和正常人之间没有统计学意义。基于以上研究,本文就颅内压与青光眼性视神经损害之间关系的相关研究进展及临床上可行的无创颅内压测量方法作一综述。     

谁动了我的视神经？ -正常眼压性青光眼视神经损害探因

正常眼压性青光眼和高眼压原发性开角型青光眼是一个“连续体”。本文基于病理生理学,探讨了正常眼压性青光眼中眼压与视神经损害的关系,认为视盘筛板是上述关系及其“连续体”概念的中间环节,眼压和筛板共同构成青光眼视神经损害的始动因素。（眼科,2020, 29： 87-89）     

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。     

低颅压与正常眼压性青光眼的关系

青光眼作为导致人类不可逆性盲的头号杀手,是一组慢性进行性视神经病变疾病。虽然病理性眼压增高是青光眼发展的主要危险因素,但是其视神经病变机制始终不明。而且有部分患者眼压处于正常值范围内,却依然发生了青光眼性视神经损害,被称为“正常眼压性青光眼”。因此,我们不得不考虑,除眼压外还有其他因素参与青光眼视神经的损害。近年来有研究表明:颅内压与眼压的失衡有可能是正常眼压性青光眼的原因之一,本文就颅内压与正常眼压性青光眼的关系做一综述。     

关于青光眼定义之商榷

试图提出一个与目前研究及认识水平相适应的青光眼定义，即“青光眼是由于病理性高眼压以及其他相关因素，引起进行性视神经损害，导致视乳头进行性凹陷性萎缩和视功能、特别是视野损害的一类眼病”。定义强调4点：①视神经对眼压的耐受性有较大的个体差异；②眼压升高的机械压迫和血供障碍共同参与了青光眼的视神经损害，病理性高眼压是主要因素；③青光眼性视神经损害，导致眼底改变的特点是视乳头进行性凹陷性萎缩；④在青光眼性视功能损害方面，视野改变是主要的且具有特征性。本文从眼压、眼底、视野、青光眼视神经损害机制以及视神经保护五个方面对青光眼定义进行了阐述。用比较简明的语言揭示了青光眼的内涵，提出较为全面、科学的青光眼定义。     

青光眼性视神经损害的成因及其防治（二）

第二部分:保护青光眼视神经功能的研究,一、保护青光眼患者视功能的根本方法——降低眼压从青光眼性视神经损害的成因方面考虑,眼压是重要的因素。临床发现,青光     

青光眼发病机制:从临床复杂表型剖析到基本科学问题探索

青光眼是一类复杂疾病综合征,其共同临床表现为"特征性视神经病变",实际病因则千差万别。青光眼的发病机制亟待剖析,重点在于梳理其错综复杂的临床表型,围绕眼压改变、视网膜神经节细胞(RGCs)/轴突损伤、非眼压因素等进行合理分型,还原为基础研究手段可以系统探索的基本科学问题。本文将青光眼分为两大类型:Ⅰ型:真实眼压显著升高,直接导致大量RGCs/轴突原发性损害,并在继发性神经免疫炎症参与下造成青光眼视神经病变(GON)。Ⅱ型:检测到的眼压不能或者不足以直接导致大量RGCs/轴突损害和GON,此时神经免疫炎症可能在青光眼的起始发病机制中起到更重要的作用。根据病因机制不同,本文又将前者进一步细分为5型,后者进一步细分为4型。     

原发性开角型青光眼与24h眼压及眼灌注压的研究进展

原发性开角型青光眼是一类早期无明显临床症状,但随病情进展将导致不可逆的视神经损害及视野缺损的致盲性眼病。眼压是原发性开角型青光眼诊断及评定治疗效果的简单而又重要的指标。临床上,一些治疗中的原发性开角型青光眼患者白天就诊时间所测眼压已达靶眼压,但视神经损害却仍在进展,研究表明可能与夜间眼压的升高、24 h较大的眼压波动及夜间眼灌注压的降低有关。因此,我们对原发性开角型青光眼与眼压及眼灌注压波动的相关文献予以综述,以更好的理解三者之间的关系。     

正常眼压性青光眼

正常眼压性青光眼患者的眼压在统计学眼压的正常范围之内,却有典型的青光眼性视野缺损及与之相关的视盘改变。故发病隐匿,常造成不可逆的视神经损害。现代研究认为其发病机制是机械因素、血管因素、自身免疫因素等多种因素的共同作用。降眼压是必要的措施,眼压降低30%以上对其病变有利。与此同时,改善视神经血流供应和保护视神经的药物正被关注。     

正常眼压青光眼的基本问题及其认识方法

正常眼压青光眼在临床和研究上存在的诸多困惑,既出自疾病本身,更多地源于我们临床型思维和认识方法的局限性。正常眼压青光眼临床表现与病理本质关系复杂并相距甚远,基于临床思维的各种研究难以真正解决发病机制问题。正常眼压青光眼的基本问题和特殊性恰在“正常眼压”及其与视神经损害的关系上。正常群体眼压范围不等于正常个体眼压区间;眼压高低不是质的差异,仅是量的差别;眼压即使正常,对眼组织也有“生理性”压迫作用。因此,要从病因、病理生理、病理,到临床表现,全面合理地解释正常眼压青光眼的眼压与视神经损害的关系。     

New directions in the treatment of normal tension glaucoma

Glaucoma is a progressive optic neuropathy that causes characteristic changes of the optic nerve and visual field in relation to intraocular pressure (IOP). It is now known that glaucoma can occur at statistically normal IOPs and prevalence studies have shown that normal tension glaucoma (NTG) is more common than previously thought. While IOP is believed to be the predominant risk factor in primary open angle glaucoma (POAG), IOP-independent risk factors, such as vascular dysregulation, are believed to play an important part in the pathogenesis of NTG. Though certain distinguishing phenotypic features of NTG have been reported, such as an increased frequency of disc hemorrhages, acquired pits of the optic nerve and characteristic patterns of disc cupping and visual field loss, there is much overlap of the clinical findings in NTG with POAG, suggesting that NTG is likely part of a continuum of open angle glaucomas. However, IOP modification is still the mainstay of treatment in NTG. As in traditional POAG, reduction of IOP can be achieved with the use of medications, laser trabeculoplasty or surgery. Studies now show that the choice of medication may also be important in determining the outcomes of these patients. Though it is likely that future treatment of NTG will involve modification of both IOP and IOP-independent risk factors, current efforts to develop IOP-independent neuroprotective treatments have not yet proven to be effective in humans.     

Biomechanics of the sclera and effects on intraocular pressure

Accumulating evidence indicates that glaucoma is a multifactorial neurodegenerative disease characterized by the loss of retinal ganglion cells (RGC), resulting in gradual and progressive permanent loss of vision. Reducing intraocular pressure (IOP) remains the only proven method for preventing and delaying the progression of glaucomatous visual impairment. However, the specific role of IOP in optic nerve injury remains controversial, and little is known about the biomechanical mechanism by which elevated IOP leads to the loss of RGC. Published studies suggest that the biomechanical properties of the sclera and scleral lamina cribrosa determine the biomechanical changes of optic nerve head, and play an important role in the pathologic process of loss of RGC and optic nerve damage. This review focuses on the current understanding of biomechanics of sclera in glaucoma and provides an overview of the possible interactions between the sclera and IOP. Treatments and interventions aimed at the sclera are also discussed.     

The role of blood pressure in glaucoma

Although intraocular pressure (IOP) remains an important risk factor for glaucoma, it is clear that other factors can also influence disease development and progression. More recently, the role that blood pressure (BP) has in the genesis of glaucoma has attracted attention, as it represents a clinically modifiable risk factor and thus provides the potential for new treatment strategies beyond IOP reduction. The interplay between blood pressure and IOP determines the ocular perfusion pressure (OPP), which regulates blood flow to the optic nerve. If OPP is a more important determinant of ganglion cell injury than IOP, then hypotension should exacerbate the detrimental effects of IOP elevation, whereas hypertension should provide protection against IOP elevation. Epidemiological evidence provides some conflicting outcomes of the role of systemic hypertension in the development and progression of glaucoma. The most recent study showed that patients at both extremes of the blood pressure spectrum show an increased prevalence of glaucoma. Those with low blood pressure would have low OPP and thus reduced blood flow; however, that people with hypertension also show increased risk is more difficult to reconcile. This finding may reflect an inherent blood flow dysregulation secondary to chronic hypertension that would render retinal blood flow less able to resist changes in ocular perfusion pressure. Here we review both clinical and experimental studies that have attempted to clarify the relationships among blood pressure, OPP and blood flow autoregulation in the pathogenesis of glaucoma.     

Pathophysiology of human glaucomatous optic nerve damage: Insights from rodent models of glaucoma

Understanding mechanisms of glaucomatous optic nerve damage is essential for developing effective therapies to augment conventional pressure-lowering treatments. This requires that we understand not only the physical forces in play, but the cellular responses that translate these forces into axonal injury. The former are best understood by using primate models, in which a well-developed lamina cribrosa, peripapillary sclera and blood supply are most like that of the human optic nerve head. However, determining cellular responses to elevated intraocular pressure (IOP) and relating their contribution to axonal injury require cell biology techniques, using animals in numbers sufficient to perform reliable statistical analyses and draw meaningful conclusions. Over the years, models of chronically elevated IOP in laboratory rats and mice have proven increasingly useful for these purposes. While lacking a distinct collagenous lamina cribrosa, the rodent optic nerve head (ONH) possesses a cellular arrangement of astrocytes, or glial lamina, that ultrastructurally closely resembles that of the primate. Using these tools, major insights have been gained into ONH and the retinal cellular responses to elevated IOP that, in time, can be applied to the primate model and, ultimately, human glaucoma.     

青光眼的治疗目标与评估

降低眼压是目前惟一经证实可控且有效的青光眼治疗方式,对眼压的控制已成为检验或评估青光眼治疗是否有效的标志,目标眼压即靶眼压的设定,是实现个体化治疗的主要指标。在降低眼压达到目标眼压的同时,还应注意眼压的波动以及潜在的视神经保护治疗。应根据视神经及视野损害进展情况不断调整或再评估目标眼压。阻止视功能损害进一步加重、保存有用视力、提高生活质量是青光眼治疗的目标。（眼科,2013,22：220-223）     

角膜屈光手术与青光眼(英文)

角膜屈光手术改变了角膜厚度及曲率,影响术后眼压(in-trocular pressure,IOP)的测量,但动态轮廓眼压计(dynamiccontour tonometer ,DCT)不受此影响。激光原位角膜磨镶术(LASIK)中一过性的IOP升高,增加了视神经损害的风险。同时,功能性滤过泡的存在,影响屈光手术的选择和效果,甚至可能成为手术的禁忌。术后患者使用激素点眼,还可能导致激素性青光眼,故应严密监测术后眼压,并且注意角膜瓣层间积液可能掩盖高眼压。对于已接受屈光手术的青光眼患者,药物治疗方案与其他青光眼患者基本相同。本文就角膜屈光手术对眼压测量、青光眼相关特殊检查的影响、屈光手术并发症及其治疗、手术安全性等问题进行了详细综述。     

原发性急性闭角型青光眼患者房水蛋白质组学分析

目的：探究不同眼压的原发性急性闭角型青光眼（PAACG）患者房水蛋白的差异性表达,寻找青光眼性视神经损伤的可能机制,为青光眼性视神经保护的可能作用靶点提供实验依据。方法：病例对照研究。通过简单随机抽样选取2019年3月至2020年9月期间于吉林大学第二医院眼科中心入院治疗的PAACG患者共88例（88眼）。根据PAACG患者的眼压将88个选定的样本分为2组：A组36个样本,眼压≥50 mmHg（1 mmHg=0.133 kPa）;B组52个样本,眼压≤21 mmHg。以上样本被分为2个队列：发现队列（A组26个样本;B组37个样本）和验证队列（A组10个样本;B组15个样本）。分别通过数据独立采集（DIA）方法和平行反应监测（PRM）方法分析房水蛋白。采用独立样本t检验分析蛋白表达差异。结果：本研究从发现队列的A、B组中63个房水样本中共检测出636个蛋白,去除默认蛋白后得到506个蛋白用于后续分析,其中51个蛋白在发现队列A、B组间差异有统计学意义（P=0.020）在这51个差异蛋白中,A组存在17个蛋白表达上调,B组存在34个蛋白表达上调。抽取上述51个差异蛋白中APOA2、TIMP1、LRP2和VASN进行PRM验证,结果显示这4个差异蛋白在发现队列及验证队列中保持一致。结论：PAACG患者房水中差异蛋白的表达与炎症反应以及小梁网细胞外基质重塑、神经损伤相关,可能是导致青光眼患者眼压升高以及视神经损伤的重要原因。