视神经筛板的生物力学研究

视神经筛板是一个生物力学结构,其受力应变引起青光眼视神经损伤.眼压被认为是引起筛板应变的主要因素,眼压升高引起筛板应变增加.相应的在青光眼用药或术后眼压下降的患者中,筛板会发生应变的消除.脑脊液压力作为跨筛板压力差的组成部分同样影响筛板,脑脊液压力降低增加了跨筛板压力差从而导致筛板应变增加.此外,眼球水平运动引起视神经...     

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。     

适用于大样本人群的无创脑脊液压力估算方法的标准与规范

最近的研究资料显示:视盘筛板前的眼压与筛板后的脑脊液压之间的差值(跨筛板压力梯度),而非眼压,是导致青光眼视神经损害的主要危险因素[1-2]。且已在单纯颅内脑脊液压力降低的动物模型发现了类似于青光眼视神经损害的结构性改变[3],提示脑脊液压力降低所致的跨筛板压力梯度增大与视神经损害之间存在因果关系。跨筛板压力梯度在原发性开角型青光眼     

正常眼压性青光眼的研究现状

正常眼压性青光眼(normal tension glaucoma,NTG)长期以来是一备受争议的话题.关于其发病机制,各学说均提出了有利证据,如NTG患者跨筛板压增大;筛板较为薄弱,对眼压的耐受力较差;氧化应激反应导致小梁网退行性改变及视网膜神经节细胞凋亡;眼部血流动力学异常;颈内动脉对视神经的机械压迫等.各因素之间既...     

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）     

视盘生物力学的研究进展

生物力学因素与青光眼视神经病变有关,筛板处的缺血和作用于该处的机械压力,在青光眼的轴浆流损害中起着重要作用。根据生物力学的基本原理,分析视盘的几何形状、材料特性、周边环境和机械负荷等生物力学环境,建立计算机辅助的视盘3-维有限元素模型,观察在不同眼压下视盘周围巩膜的结缔组织,筛板前后的神经组织,筛板,巩膜管壁的张力、压力和变形;研究视盘生物力学特点与青光眼视功能丧失的关系,探讨青光眼的病因及不同个体对眼压的易感性。     

应用OCT探究眼压与筛板参数的关系

筛板的变形与血流减少一直被视作青光眼视神经轴突损伤的首发因素.病理性眼压升高与青光眼的发生发展间有紧密关系.通过OCT技术衡量筛板及周边参数随眼压变化来研究青光眼发病机制受到了广泛关注.研究表明筛板深度(LCD)、筛板前表面厚度(PTT)、筛板曲率指数(LCCI)以及视盘血管密度等参数均与眼压具有相关性.眼压升高可对筛...     

青光眼昼夜眼压波动

病理性高眼压和较大的昼夜眼压波动是青光眼视神经损害进展的重要危险因素.眼压具有波动性,正常人眼压波动的峰值多出现于凌晨,这种波动与体位、眼灌注压、眼轴等有关.正常眼压性青光眼患者眼压波动是视野进展的重要危险因素,且经24小时眼压监测发现大部分眼压是存在异常的,因此需根据其昼夜眼压曲线明确诊断和针对性治疗;原发性开角型青光眼患者昼夜眼压波动规律与正常人相似,眼压高峰多在夜间,但波动范围可能比正常人大,且双眼的波动呈明显的一致性;激光周边虹膜切开术后的慢性闭角型青光眼患者的昼夜眼压波动较大,其眼压波动与基线眼压和房角粘连程度呈正相关.与激光和药物相比,小梁切除术更有利于控制长期和昼夜的眼压波动.抗青光眼药物中前列腺素类药物是控制昼夜眼压波动效果最好的滴眼剂.     

原发性青光眼及高眼压症患者中央角膜厚度的比较研究

目的 探讨用超声角膜测厚仪测量的急性原发性闭角型青光眼、慢性原发性闭角型青光眼、原发性开角型青光眼、高眼压症及正常人中央角膜厚度(central corneal thickness,CCT)的差异.方法 临床病例对照研究.对2010年2月至2011年11月在承德医学院附属医院眼科应用超声角膜测厚仪测量62例(107只眼)的CCT值.急性原发性闭角型青光眼16例(18只眼)、慢性原发性闭角型青光眼14例(26只眼)、原发性开角型青光眼10例(19只眼)、高眼压症6例(12只眼)及正常人16例(32只眼).采用单因素方差分析及SNK-q检验行统计分析.结果 各组CCT值:急性原发性闭角型青光眼(548.44±30.46)μm、慢性原发性闭角型青光眼(522.70±50.39)μm、原发性开角型青光眼(546.32±22.85) μm、高眼压症(585.67±21.22) μm、正常人(536.38±26.53)μm.组间比较差异有统计学意义(F=7.661,P＜0.01).两两比较显示:高眼压症与原发性青光眼组及正常人比较,差异有统计学意义;原发性青光眼各组及正常人两两比较,差异无统计学意义.结论 与正常人及原发性青光眼相比,高眼压症CCT较厚;原发性青光眼CCT与正常人相比差异无统计学意义;CCT与原发性青光眼类型无相关性.     

筛板前组织的OCT影像检测及其与眼病的关系

筛板前组织是位于视乳头筛板前区的结构性组织,其与筛板组织一样均为青光眼性视神经损害中不可缺少的部分.筛板前组织厚度可通过OCT观察,其在眼压增高及缺血时会变薄,在青光眼术后眼压降低时会增厚.所以探索筛板前组织的变化可能有利于揭示青光眼的发病机制,并为青光眼随诊提供临床生物学指标.此外,也有些研究发现筛板前组织变化与缺血性视神经病变、糖尿病视神经病变、视网膜色素变性相关.     

Einfluss des Liquordrucks auf die glaukomatöse Schädigung des Nervus opticus

Eyes with normal pressure glaucoma and eyes with high pressure glaucoma show a similar optic disc appearance with marked differences to eyes with vascular optic neuropathy. Non-vascular, potentially barotraumatic factors in addition to intraocular pressure (IOP) may thus play a role in glaucoma. Recent studies have shown that cerebrospinal fluid pressure (CSFP), arterial blood pressure and IOP are correlated with each other, higher CSFP is associated with younger age, higher blood pressure and higher body mass index, some patients with normal (IOP) pressure glaucoma have abnormally low CSFP and thus an abnormally high trans-lamina cribrosa pressure difference and a small orbital CSF space, the orbital CSF space width is associated with CSFP and the estimated CSFP correlated better with open-angle glaucoma-related parameters than IOP. The orbital CSFP as counter-pressure against IOP may play a role in the pathogenesis of glaucoma.     

Role of cerebrospinal fluid pressure in the pathogenesis of glaucoma

The pathogenesis of normal (intraocular) pressure glaucoma has remained unclear so far. As hospital‐based studies showed an association of normal‐pressure glaucoma with low systemic blood pressure, particularly at night, and with vasospastic symptoms, it has been hypothesized that a vascular factor may play a primary role in the pathogenesis of normal‐pressure glaucoma. That assumption may, however, be contradicted by the morphology of the optic nerve head. Eyes with normal‐pressure glaucoma and glaucomatous eyes with high‐intraocular pressure can show a strikingly similar appearance of the optic nerve head, including a loss of neuroretinal rim, a deepening of the optic cup, and an enlargement of parapapillary atrophy. These features, however, are not found in any (other) vascular optic neuropathy, with the exception of an enlargement and deepening of the optic cup in arteritic anterior ischaemic optic neuropathy. One may additionally take into account (i) that it is the trans‐lamina cribrosa pressure difference (and not the trans‐corneal pressure difference, i.e. the so‐called intraocular pressure) which is of importance for the physiology and pathophysiology of the optic nerve head; (ii) that studies have shown that the anatomy of the optic nerve head including the intraocular pressure, the anatomy and biomechanics of the lamina cribrosa and peripapillary sclera, retrobulbar orbital cerebrospinal fluid pressure and the retrobulbar optic nerve tissue pressure may be of importance for the pathogenesis of the highly myopic type of chronic open‐angle glaucoma; (iii) that studies have suggested a physiological association between the pressure in all three fluid filled compartments, i.e. the systemic arterial blood pressure, the cerebrospinal fluid pressure and the intraocular pressure; (iv) that an experimental investigation suggested that a low cerebrospinal fluid pressure may play a role in the pathogenesis of normal (intraocular) pressure glaucoma; and (v) that recent clinical studies reported that patients with normal (intraocular) pressure glaucoma had significantly lower cerebrospinal fluid pressure and a higher trans‐lamina cribrosa pressure difference when compared to normal subjects. One may, therefore, postulate that a low cerebrospinal fluid pressure may be associated with normal (intraocular) pressure glaucoma. A low systemic blood pressure, particularly at night, could physiologically be associated with a low cerebrospinal fluid pressure, which leads to an abnormally high trans‐lamina cribrosa pressure difference and as such to a similar situation as if the cerebrospinal fluid pressure is normal and the intraocular pressure is elevated. This model could explain why patients with normal (intraocular) pressure glaucoma tend to have a low systemic blood pressure, and why eyes with normal (intraocular) pressure glaucoma and eyes with high‐pressure glaucoma, in contrast to eyes with a direct vascular optic neuropathy, show profound similarities in the appearance of the optic nerve head.     

Facts and myths of cerebrospinal fluid pressure for the physiology of the eye

The orbital cerebrospinal fluid pressure (CSFP) represents the true counter-pressure against the intraocular pressure (IOP) across the lamina cribrosa and is, therefore, one of the two determinants of the trans-lamina cribrosa pressure difference (TLPD). From this anatomic point of view, an elevated TLPD could be due to elevated IOP or abnormally low orbital CSFP. Both experimental and clinical studies have suggested that a low CSFP could be associated with glaucomatous optic neuropathy in normal-pressure glaucoma. These included monkey studies with an experimental long-term reduction in CSFP, and clinical retrospective and prospective studies on patients with normal-pressure glaucoma. Since the choroidal blood drains via the vortex veins through the superior ophthalmic vein into the intracranial cavernous sinus, anatomy suggests that the CSFP could influence choroidal thickness. A population-based study revealed that thicker subfoveal choroidal thickness was associated with higher CSFP. Since the central retinal vein passes through the orbital CSF space, anatomy suggests that the retinal venous pressure should be at least as high as the orbital CSFP. Other experimental, clinical or population-based studies suggested an association between higher CSFP and higher retinal venous pressure and wider retinal veins. Consequently, a higher estimated CSFP was associated with arterial hypertensive retinopathy (with respect to the dilated retinal vein diameter and higher arterial-to-venous diameter) and with the prevalence, severity and incidence of diabetic retinopathy. Physiologically, CSFP was related with higher IOP. The influence of the CSFP on the episcleral venous pressure and/or a regulation of both CSFP and IOP by a center in the dorsomedial/perifornical hypothalamus may be responsible for this. In summary, the CSFP may be an overlooked parameter in ocular physiology and pathology. Abnormal changes in the CSFP, in particular in relationship to the IOP, may have pathophysiologic importance.     

Glymphatic stasis at the site of the lamina cribrosa as a potential mechanism underlying open‐angle glaucoma

The underlying pathophysiology of primary open‐angle glaucoma remains unclear, but the lamina cribrosa seems to be the primary site of injury, and raised intraocular pressure is a major risk factor. In recent years, a decreased intracranial pressure, leading to an abnormally high trans‐lamina cribrosa pressure difference, has gained interest as a new risk factor for glaucoma. New research now lends support to the hypothesis that a paravascular transport system is present in the eye analogous to the recently discovered ‘glymphatic system’ in the brain, which is a functional waste clearance pathway that promotes elimination of interstitial solutes, including β‐amyloid, from the brain along paravascular channels. Given that β‐amyloid has been reported to increase by chronic elevation of intraocular pressure in glaucomatous animal models and to cause retinal ganglion cell death, the discovery of a paravascular clearance system in the eye may provide powerful new insights into the pathophysiology of primary open‐angle glaucoma. In this review, we provide a new conceptual framework for understanding the pathogenesis of primary open‐angle glaucoma, present supporting preliminary data from our own post‐mortem study and hypothesize that the disease may result from restriction of normal glymphatic flow at the level of the lamina cribrosa owing to a low intracranial pressure and/or a high trans‐lamina cribrosa pressure gradient. If confirmed, this viewpoint could offer new perspectives for the development of novel diagnostic and therapeutic strategies for this devastating disorder.     

The interaction between intracranial pressure,intraocular pressure and lamina cribrosal compression in glaucoma

This review examines some of the biomechanical consequences associated with the opposing intraocular and intracranial forces. These forces compress the lamina cribrosa and are a potential source of glaucomatous pathology. A difference between them creates a displacement force on the lamina cribrosa. Increasing intraocular pressure and/or decreasing intracranial pressure will increase the trans‐lamina cribrosa pressure difference and the risk of its posterior displacement, canal expansion and the formation of pathological cupping. Both intraocular pressure and intracranial pressure can be elevated during a Valsalva manoeuvre with associated increases in both anterior and posterior lamina cribrosa loading as well as its compression. Any resulting thinning of or damage to the lamina cribrosa and/or retinal ganglion cell axons and/or astrocyte and glial cells attached to the matrix of the lamina cribrosa and/or reduction in blood flow to the lamina cribrosa may contribute to glaucomatous neuropathy. Thinning of the lamina cribrosa reduces its stiffness and increases the risk of its posterior displacement. Optic nerve head posterior displacement warrants medical or surgical lowering of intraocular pressure; however, compared to intraocular pressure, the trans‐lamina cribrosa pressure difference may be more important in pressure‐related pathology of the optic nerve head region. Similarly important could be increased compression loading of the lamina cribrosa. Reducing participation in activities which elevate intraocular and intracranial pressure will decrease lamina cribrosa compression exposure and may contribute to glaucoma management and may have prognostic significance for glaucoma suspects.     

Fast circulation of cerebrospinal fluid: an alternative perspective on the protective role of high intracranial pressure in ocular hypertension

As ocular hypertension refers to a condition in which the intraocular pressure is consistently elevated but without development of glaucoma, study of it may provide important clues to factors that may play a protective role in glaucoma. β‐amyloid, one of the key histopathological findings in Alzheimer's disease, has been reported to increase by chronic elevation of intraocular pressure in animals with experimentally induced ocular hypertension and to cause retinal ganglion cell death, pointing to similarities in molecular cell death mechanisms between glaucoma and Alzheimer's disease. On the other hand, recent studies have reported that intracranial pressure is higher in patients with ocular hypertension compared with controls, giving rise to the idea that elevated intracranial pressure may provide a protective effect for the optic nerve by decreasing the trans‐lamina cribrosa pressure difference. The speculation that the higher intracranial pressure reported in ocular hypertension patients may protect against glaucoma mainly through a lower trans‐lamina cribrosa pressure difference remains at least questionable. Here, we present an alternative viewpoint, according to which the protective effect of higher intracranial pressure could be due, at least in part, to a pressure‐independent mechanism, namely faster cerebrospinal fluid production leading to increased cerebrospinal fluid turnover with enhanced removal of potentially neurotoxic waste products that accumulate in the optic nerve. This suggests a new hypothesis for glaucoma, which, just like Alzheimer's disease, may be considered then as an imbalance between production and clearance of neurotoxins, including β‐amyloid. If confirmed, then strategies to improve cerebrospinal fluid flow are reasonable and could provide a new therapeutic approach for stopping the neurotoxic β‐amyloid pathway in glaucoma.     

Cerebrospinal fluid pressure in ocular hypertension

Background: To assess the lumbar cerebrospinal fluid pressure (CSF‐P) in ocular hypertensive subjects with elevated intraocular pressure (IOP) but without development of glaucomatous optic nerve damage. Methods: The prospective interventional study included 17 patients with ocular hypertension and 71 subjects of a nonglaucomatous control group. All patients underwent a standardized ophthalmologic and neurological examination including measurement of lumbar CSF‐P. In the ocular hypertensive group, the IOP was corrected for its dependence on central corneal thickness (IOP_corrected). The trans‐lamina cribrosa pressure difference (Trans‐LCPD) was calculated as IOP_corrected ? CSF‐P. Results: CSF‐P was significantly (p < 0.001) higher in the ocular hypertensive group (16.0 ± 2.5 mmHg) than in the control group (12.9 ± 1.9 mmHg). CSF‐P was significantly associated with IOP_corrected (p < 0.001; r = 0.82). In multivariate analysis, CSF‐P was significantly correlated with IOP_corrected (p < 0.001) and marginally significantly with mean blood pressure (p = 0.05). Trans‐LCPD was not associated significantly with blood pressure (p = 0.69). Conclusion: Some ocular hypertensive subjects with increased intraocular pressure measurements (after correction for their dependence on central corneal thickness) had an abnormally high lumbar cerebrospinal fluid pressure. Assuming that lumbar cerebrospinal fluid pressure correlated with orbital cerebrospinal fluid pressure, one may postulate that the elevated retro‐lamina cribrosa pressure compensated for an increased intraocular pressure. The elevated retro‐lamina cribrosa pressure may have led to a normal trans‐laminar pressure difference in the eyes with elevated intraocular pressure, so that glaucomatous optic nerve damage did not develop. Intraocular pressure, cerebrospinal fluid pressure and arterial blood pressure were correlated with each other.     

Anatomic relationship between lamina cribrosa, intraocular space, and cerebrospinal fluid space

PURPOSE: The lamina cribrosa, as the main structural element of the optic nerve head, forms a pressure barrier between the intraocular space and the retrobulbar space. The function as a pressure barrier may have importance for the pathogenesis of ocular diseases related to intraocular pressure and/or cerebrospinal fluid (CSF) pressure, such as the glaucomas. The purpose of the present study was to examine the anatomic relationship between the lamina cribrosa, the intraocular pressure space, and the retrobulbar cerebrospinal pressure space in eyes with glaucoma. METHODS: The study included 53 globes enucleated because of malignant choroidal melanoma (n = 42) without involvement of the optic nerve (control group) or because of painful absolute secondary angle-closure glaucoma (n = 11; glaucoma group). Anterior-posterior histologic sections through the pupil and the optic disc were morphometrically evaluated. RESULTS: In the glaucoma group compared with the control group, the lamina cribrosa was significantly (P < 0.001) thinner, the part of the outer lamina cribrosa surface directly exposed to the pia mater and indirectly exposed to the CSF space was significantly (P = 0.001) wider, and the shortest distance between the intraocular space and the CSF space was significantly (P < 0.001) shorter. The posterior lamina cribrosa surface in direct contact with the pia mater was located close to the optic disc border. CONCLUSIONS: The thickness of the lamina cribrosa and the anatomic relationships between the intraocular space and the CSF space differ significantly between normal and glaucomatous eyes. The findings may be of importance for the pathogenesis of glaucomatous optic neuropathy.     

Lamina cribrosa thickness and spatial relationships between intraocular space and cerebrospinal fluid space in highly myopic eyes

PURPOSE: To evaluate the spatial relationships of the intraocular space, the cerebrospinal fluid space, and the lamina cribrosa in highly myopic eyes. METHODS: The study included 36 human globes with an axial length of more than 26.5 mm that showed marked glaucomatous optic nerve damage (n = 29; highly myopic glaucomatous group) or in which the optic nerve was affected by neither glaucoma nor any other disease (n = 7; highly myopic normal group). Two non-highly myopic control groups included 53 globes enucleated because of malignant choroidal melanoma (n = 42; non-highly myopic normal group) or because of painful absolute secondary angle-closure glaucoma (n = 11; non-highly myopic glaucomatous group). Anterior-posterior histologic sections through the pupil and the optic disc were morphometrically evaluated. RESULTS: In both highly myopic groups compared with both non-highly myopic groups and in the highly myopic glaucomatous group compared with the highly myopic normal group, the lamina cribrosa was significantly (P < 0.001) thinner. Correspondingly, the distance between the intraocular space and the cerebrospinal fluid space was significantly (P < 0.05) shorter in the highly myopic normal group than in the non-highly myopic normal group and in the highly myopic glaucomatous group than in the highly myopic normal group. CONCLUSIONS: In highly myopic eyes, the lamina cribrosa is significantly thinner than in non-highly myopic eyes, which decreases the distance between the intraocular space and the cerebrospinal fluid space and steepens the translaminar pressure gradient at a given intraocular pressure, which may explain the increased susceptibility to glaucoma in highly myopic eyes. As in non-highly myopic eyes, thinning of the lamina cribrosa gets more pronounced in highly myopic eyes if glaucoma is also present.