急性高眼压引起视神经纤维层厚度改变的规律

目的在体测量兔眼不同眼压水平以及急性高眼压形成后不同时刻的视神经纤维层厚度,获取急性高眼压作用所致的兔眼视神经纤维层厚度改变规律。方法向兔眼前房注射生理盐水使眼压不断升高,形成4组急性高眼压动物模型。利用相干断层扫描仪,采用以视神经乳头为中心、直径为6 mm的辐射状扫描模式,分别扫描并测量不同眼压状态的兔眼视神经纤维层厚度。结果 4组模型的急性高眼压为(4.50±0.35)、(6.07±0.31)、(7.74±0.26)、(10.71±0.07)kPa,视神经纤维层厚度绝对改变量分别为(-27.16±14.24)、(-33.33±6.74)、(-48.75±5.24)、(-67.29±3.89)μm,而且视神经纤维层厚度的相对改变量与眼压成线性关系,高眼压后2天兔眼眼压可以恢复正常,视神经纤维层厚度2周时基本恢复,急性高眼压低于6.65 kPa时视神经纤维层厚度更易于恢复。结论急性高眼压导致视神经纤维层变薄,且随眼压的升高视神经纤维层厚度变薄加重;一定时间后视神经纤维层厚度能恢复正常。     

急性高眼压下猫眼视乳头形态变化

目的:研究随着眼压增高,视乳头各形态学参数的变化趋势,以及视乳头形态学参数对压力的敏感性。方法:1选择12只健康家猫,排除各种眼疾,利用光学相干断层扫描成像技术获得正常眼压下猫视乳头形态学参数;2通过前房灌注的方法制造急性高眼压动物模型,利用光学相干断层扫描成像技术获得在40、60、80 mm Hg眼压下猫视乳头形态学参数;3利用均值和标准差分析随着眼压增高,视乳头各形态学参数的变化趋势,利用Spearman相关性分析视乳头形态学参数对压力的敏感性。结果与结论:Bruch膜开口距离与筛板深度对压力的敏感性最强,随着眼压的升高,Bruch膜开口距离逐渐增大,筛板深度逐渐减小。Bruch膜开口距离变大与筛板深度变浅对研究青光眼病程的发展有一定的指导意义。     

急性高眼压作用下视神经轴浆运输与视网膜光学功能的关系

目的:研究急性高眼压下视神经轴浆运输与视网膜光学功能之间的关系。方法:通过前房灌注的方法制造急性高眼压动物模型;利用罗兰电生理仪进行闪光视网膜电图和视觉诱发电位的测量。在玻璃体注射荧光染料后,利用激光共聚焦显微镜观察视神经轴浆运输,并利用苏木素-伊红染色,观察视乳头的形态变化。结果:当眼压为60 mm Hg并维持2 h,闪光视网膜电图的a波幅值明显降低,视网膜外层功能可能发生变化。当眼压为100 mm Hg并维持4 h,闪光视网膜电图的a波、b波和Ops的幅值以及闪光视觉诱发电位的幅值明显降低,视网膜内外层光学功能出现损伤,此时视神经的轴浆运输明显改变,视乳头形态也发生了变化。结论:急性高眼压下视神经轴浆运输与视网膜光学功能之间可能存在一定的关系。     

高眼压动物模型的造模时间

背景：急性高眼压动物模型为研究青光眼提供了简单有效的途径,模型成功与否直接影响研究结果,目前对造模成功的判据多为观察性指标。 目的：为前房穿刺所致的急性高眼压动物模型提供准确、可行的造模成功判定方法,观察特定高眼压下急性高眼压动物模型的成模时间。 方法：利用连通器原理,将加压装置与内充2 mm水银球的玻璃管相连,通过读取水银球的流动,计算眼内液体流入量。采用前房灌注法,成功建立10只兔眼眼内压为4.9 kPa的急性高眼压动物模型,监测眼内液体流入量随造模时间的变化至液体不再流动30 min后结束实验。拟合眼内压液体流入量随造模时间的变化规律,计算急性高眼压动物模型造模成功的时间。 结果与结论：兔眼眼球进水量(y)与加压时间(t)呈Logistic变化规律,即         ,其中参数U,b0和b1分别为957.44±313.22,0.023±0.008和0.980±0.003。当注水时间达到(282.93±42.68) min后,眼内压等于外界施加的高压,兔急性高眼压模型造模成功。     

视乳头的结构和力学特性对筛板变形的影响

目的:建立包含筛板的全眼球轴对称模型,分析视乳头的结构和力学特性对青光眼患者筛板变形的影响。方法:基于青光眼患者和正常对照组的视乳头结构参数数据,并参考文献结果,建立包含筛板的全眼球轴对称有限元模型;分析视乳头的力学特性和结构参数对筛板变形的影响。结果:眼压升高会导致筛板后移,且随着眼压的升高,筛板变形程度增大。巩膜、筛板和硬脑膜的弹性模量对筛板变形的影响程度较大;且筛板厚度、视杯深度、视杯宽度均对筛板变形有影响。青光眼患者的眼底结构参数、力学特性会使其筛板对眼压和颅压的作用更敏感。结论:有限元方法可用于筛板变形影响因素的研究,为青光眼早期诊断提供参考。     

视神经三维结构可视化及定量测量

目的:定量分析眼底视神经的损伤用于青光眼的早期诊断。通过青光眼患者和正常对照组眼底视神经乳头可视化三维结构对比,研究青光眼患者眼球内部筛板、视神经束等框内视神经结构的定量形态学变化,分析青光眼下框内视神经损伤的定量评价。方法:采集正常对照组6例,青光眼组6例。利用光学相干断层成像获得青光眼组和对照组的视神经乳头的断层容积图像,采用三维可视化和多平面绘制对视神经乳头进行三维重建,并对可见筛板区域面积、可视筛孔数量、平均面积和总面积及可视视神经束的长度、宽度进行定量测量,并进行数据对比分析,用SPSS 19.0软件进行统计分析。结果:青光眼患者组和正常对照组在可视筛板面积、可视筛孔的面积及个数有明显差异,可视视神经束的长度及宽度无明显差异。结论:通过对青光眼患者的视神经乳头可视化结构的定量测定,获得青光眼视神经乳头部分结构的形态变化,青光眼患者筛板及筛板前组织明显变形,筛孔的可见面积和数量明显增加,视神经形态无明显差异。分析青光眼致病过程,有助于青光眼致病机理的研究,帮助获得青光眼早期诊断的依据和方法,具有一定的临床价值。     

持续高眼压对大鼠视网膜神经节细胞的损伤

目的 观察持续高眼压对大鼠视网膜神经节细胞（RGCs）的损害。方法 烙闭大鼠上巩膜静脉,制作大鼠持续性高眼压模型,分时点摘取眼球,光镜及TUNEL法观察大鼠视网膜各层厚度变化和RGCs凋亡率,电镜观察RGCs超微结构变化。结果 随着高眼压时间持续,视网膜神经节细胞及纤维层逐渐变薄,节细胞及轴突的超微结构呈进行性损害,神经节细胞的细胞凋亡率增加。结论 持续高眼压导致大鼠RGCs的病理改变过程及其结果符合青光眼视神经损伤的病理特点。     

急性高眼压后大鼠视网膜葡萄糖转运因子-1的表达

目的:观察急性高眼压后大鼠视网膜葡萄糖转运因子-1(GLUT-1)的表达变化及其对视网膜损伤的影响.方法:利用急性高眼压大鼠模型,通过免疫组织化学和免疫印迹检测急性高眼压后大鼠视网膜GLUT-1蛋白的表达变化;Nissl染色观察视网膜神经细胞层次改变及节细胞数的变化.结果:正常视网膜血管内皮细胞有GLUT-1表达,急性高眼压后3h开始下调,6h达最低值,之后1d、3d、7d逐渐恢复至正常水平.Nissl染色结果显示急性高眼压后3h、6h和12 h视网膜节细胞数减少不明显,到1、3d,视网膜层次紊乱、变薄,节细胞数明显减少.结论:急性高眼压后早期大鼠视网膜GLUT-1表达下调,影响了视网膜葡萄糖的转运,这可能是视网膜结构紊乱,节细胞丢失的重要原因.     

Müller细胞反应性胶质化在急性高眼压致大鼠视网膜损伤中作用

 目的 观察Müller细胞反应性胶质化在急性高眼压(AOH)大鼠视网膜中变化及其抑制对视网膜损伤的影响。方法 建立大鼠AOH青光眼模型,分为正常对照(Ctrl)、AOH和AOH+玻璃体内注射胶质毒素α-氨基己二酸(AAA)后再灌注1、3和5d组,以及单纯AAA和AOH+PBS对照组。TUNEL染色检测细胞凋亡,GFAP免疫荧光染色反应Müller细胞反应性胶质化程度,Thy-1染色标记视网膜神经节细胞(RGCs)。结果 AOH可致大鼠视网膜内丛状层和内核层明显变薄、神经节细胞层内细胞排列紊乱和数量减少,并诱发Müller细胞反应性胶质化(GFAP表达增加)。同时,AAA抑制Müller细胞反应性胶质化可明显缓解AOH所致RGCs丢失和凋亡发生。结论 Müller细胞反应性胶质化参与AOH所致视网膜损伤,抑制其反应性胶质化可能是改善高眼压性青光眼视网膜病变的一种有效治疗方法。     

一种基于SFS的视乳头三维形貌重建方法

视乳头形貌的确定有助于眼底类病变的准确诊断,例如视杯和视盘尺寸的相对大小是青光眼疾病病程诊断的重要依据。通常视盘和视杯的大小是通过眼底照片分离视乳头区域并进行测量,这种方法对视乳头的三维形变缺乏全面的描述。为了更加方便准确地获取视杯视盘大小的比值和视乳头的三维形貌,采用明暗恢复形状的计算机视觉方法,通过眼底图像来重建眼底结构的三维形貌。具体步骤包括:通过眼底照相机,得到二维眼底数字图像;采用图像分割方法,得到视杯和视盘区域;估计视盘视杯图像区域的光源照射方向;利用Tsai线性化方法,根据二维数字眼底图像的明暗信息,重建眼底三维结构形貌图。对初步实验结果中视杯和视盘的比计算可得,青光眼患者的杯盘比的比值大于0.6,与临床上对青光眼的判断相吻合。此方法提供新的眼底形貌变形可视化方法,能够清晰、准确地重建出眼底视盘和视杯的三维结构形貌图;可以对视盘视杯几何尺寸和结构进行更全面的描述,为眼底疾病方便和准确地诊断提供新的线索。     

Minimum distance mapping using three-dimensional optical coherence tomography for glaucoma diagnosis

Objective imaging of the optic nerve structure has become central to the management of patients with glaucoma. There is an urgent need in diagnosis and staging for reliable objective precursors and markers. Three-dimensional ultrahigh-resolution frequency domain optical coherence tomography (3D UHR OCT) holds particular promise in this respect since it enables volumetric assessment of intraretinal layers including tomographic data for the retinal nerve fiber layer (RNFL) and optic nerve head. The integrated analysis of this information and the resolution advantage has enabled the development of more informative indices of axonal damage in glaucoma compared with measurements of RNFL thickness and cup-to-disc ratio provided by commercial OCT devices. The potential for UHR OCT in enabling the combined analysis of tomographic and volumetric data on retinal structure is explored. A novel parameter was developed; the three-dimensional minimal distance as the optical correlate of true retinal nerve fiber layer thickness around the optic nerve head region. For the purposes of this pilot study, we present data from a normal subject and from two patients with characteristic optic nerve and retinal nerve fiber layer changes secondary to glaucoma.     

Scleral edge, not optic disc or retina, is the primary site of injury in chronic glaucoma

In chronic glaucoma, there is a gradual painless loss of vision, early manifestation of arcuate field defect and typical atrophy of the optic disc known as 'cupping'. Chronic glaucoma is classified into high-tension glaucoma (HTG) and normal-tension glaucoma (NTG). Although both types manifest with the same typical visual field defect and cupping of the optic disc, high-tension glaucoma has elevated intraocular pressure whereas in normal-tension glaucoma the intraocular pressure (IOP) is within the normal range (10-21 mmHg). There are several theories about the pathogenesis of chronic glaucoma ranging from high intraocular pressure directly damaging the optic disc to programmed death(apoptosis) of the ganglion cells of the retina. But none of them satisfactorily explain the manifestation of the early arcuate field defect which is a pathognomonic feature of both types of chronic glaucoma. This article focuses on two main issues. First, how and why the arcuate field defects are produced in the early stages of glaucoma and secondly to find out the common ground in the pathogenesis of both high and normal tension glaucoma. The early arcuate field defects are an important lead in discovering the pathogenesis of glaucoma, therefore if any factor or site which could not possibly produce initial sharply defined arcuate field defects was ruled out. This article presents an unconventional approach to the pathogenesis of glaucoma. Instead of looking for various factors causing glaucoma, emphasis was placed on determining the primary site of injury which could produce the initial arcuate field defects. Keeping the arcuate visual field defects in mind, the primary site of injury appears to be at the scleral edge and not the optic disc or the retina in chronic glaucoma. The border tissue which separates the sclera and choroid from the nerve fibers would atrophy due to chronic ischemia as a result of high intraocular pressure in HTG, whereas due to poor systemic circulation in NTG. In both types of chronic glaucoma, the ciliary circulation supplying the prelaminar and border tissue is compromised. As a result of atrophy of the border tissue, the optic disc sinks as a whole beginning temporally due to its tilted position and causing nerve fibers to stretch, kink, and cut at the scleral edge. This process of optic disc sinking would accelerate due to loss of nerve fibers which also provides anchorage to the optic disc. This cycle would continue until all the nerve fibers are cut at the scleral edge and the optic disc is destroyed.     

Transplanted olfactory ensheathing cells incorporated into the optic nerve head ensheathe retinal ganglion cell axons: possible relevance to glaucoma

A mixture of olfactory ensheathing cells and fibroblasts cultured from the adult rat olfactory mucosa was transplanted through a scleral incision into the retina. A major stream of transplanted cells migrated through the stratum opticum and penetrated for up to about 0.5mm into the optic nerve head. This stream of transplanted cells consisted of a mixture of bipolar olfactory ensheathing cells with long processes which give rise to a non-myelinating ensheathment of single retinal ganglion cell axons, and olfactory nerve fibroblasts embedded in a dense fibronectin-positive extracellular matrix. A second stream of ovoid olfactory ensheathing cells with tufted processes and unaccompanied by fibroblasts or matrix migrate into the internal plexiform layer. The incorporation of olfactory ensheathing cells in the optic nerve head may suggest future possibilities for protection of the axons in this vulnerable region from mechanical damage, as in the raised intraocular pressure of glaucoma.     

Therapeutic potentials of aspirin in glaucomatous optic neuropathy

Glaucoma is a common blinding disease worldwide. Although traditionally considered as a disease of elevated intraocular pressure, it is now clear that glaucoma is primarily a distinctive optic neuropathy with many proposed pathogenic mechanisms. Impaired blood flow resulting in ischemia has been proposed to be involved in the retinal ganglion cell loss seen in glaucoma. Aspirin might improve optic nerve head perfusion by stabilizing microcirculatory flow. Evidence also indicates that apoptosis may be the final common pathway for ganglion cell death in glaucoma. Aspirin has been shown to exhibit neuroprotective properties. Prostaglandins play an important role in the regulation of intraocular pressure. Aspirin is well known to inhibit cyclooxygenase mediated prostaglandin synthesis. The NSAID-inhibition of PGs synthesis up-regulates the concentration prostaglandin receptors in retinovascular tissues. Based on the body of evidence implicating ocular blood flow disturbances, apoptotic cell death, and also the role of prostaglandins in the pathogenesis of glaucoma we hypothesize that aspirin could be potentially useful drugs in the treatment of glaucoma. Hypothetical pathophysiologic mechanisms explaining potential beneficial effects of aspirin on glaucomatous optic neuropathy include: increasing optic nerve blood flow, preventing retinal ganglion cell death through neuroprotective mechanisms, and upregulating prostaglandin receptors.     

猫视乳头三维模型重建及有限元分析

BACKGROUND: Glaucoma is a kind of eye disease that can cause irreversible blindness which is characterized by visual field loss. Clinical research shows that the optic nerve head has changed before the visual field loss. The morphological changes of the optic nerve head have become the key to determine the early diagnosis of glaucoma and disease development. So it has important significance for us to study the morphological changes of the tissues of optic nerve head under the high intraocular pressure.     

The Oxygen Supply to the Retina,II. Effects of High Intraocular Pressure and of Increased Arterial Carbon Dioxide Tension on Uveal and Retinal Blood Flow in Cats

Alm , A. and A. Bill . The oxygen supply to the retina, II. Effects of high intraocular pressure and of increased arterial carbon dioxide tension on uveal and retinal blood flow in cats. A study with radioactively labelled microspheres including flow determinations in brain and some other tissues. Acta physiol. scand. 1972. 84. 306–319. 15 μ and 35 μ microspheres labelled with ^8SSr and ¹⁶⁹Yb were used to determine the rate of blood flow through various intraocular tissues, optic nerve, brain, kidney cortex and small intestine in cats at normal and increased Paco2- One eye had its spontaneous intraocular pressure, the other eye had its pressure stabilized at a higher level. At normal P_aco2 a reduction in perfusion pressure resulted in decreased vascular resistance in the iris, the ciliary body and the retina, but not in the choroid. In the retina the eye with reduced perfusion pressure had a significantly higher blood flow than the control eye. Increased PaCO₂ resulted in increased blood flow in all ocular tissues and all extraocular tissues studied except the kidney cortex. Reductions in perfusion pressure at high Paco₂ resulted in further decreases in vascular resistance in two eyes of seven only. The results suggest that about 21 % of the O₂ consumed by the retina is delivered by the retinal blood vessels, the rest by the choroid. Both myogenic and metabolic mechanisms seem to contribute to the adjustment of retinal vascular resistance after a change in perfusion pressure.     

Central corneal thickness as a risk factor for glaucoma

Glaucoma is the second leading cause of blindness worldwide. It has many risk factors such as age, race, sex, intraocular pressure, optic nerve changes, corneal thickness, refractive error, systemic diseases, family history and trauma. Central corneal thickness plays an important role in risk stratification among patients in whom glaucoma was of concern. Scleral thickness and central corneal thickness have a moderately positive correlation. Stress is responsible for glaucoma and causes deformations of the retinal layers and the consequent high levels of neural tissue strain. Stress and scleral thickness have inverse relation together and since scleral thickness is related to central corneal thickness positively, stress is related to central corneal thickness inversely. Risk of progression of glaucoma damage has an inverse relation with the central corneal thickness. This hypothesis is provable via two ways: (1) Based on formula of stress, when central corneal thickness decreases, the amount of stress increases inversely. This leads to more interruption of retinal layers and consequent higher levels of neural tissue strain that increases the risk of suffering glaucoma. (2) Variations of central corneal thickness lead to misestimation of intraocular pressure with Goldmann applanation tonometry. Underestimation of intraocular pressure may lead to underdiagnosis and consequently undertreatment of glaucoma. In conclusion central corneal thickness is a powerful predictor for risk of progression of glaucoma in population. So it should be added to routine clinical examinations for screening of glaucoma. Our hypothesis answers the question about relationship between increased susceptibility to glaucoma damage in patients with thinner corneas.     

Retinal nerve fiber layer structure abnormalities in early Alzheimer's disease: Evidence in optical coherence tomography

Alzheimer's disease (AD) patients often have visual disorders which may be due to retinal nerve degenerative changes. The aim of the current study was to determine the thickness changes of retina nerve fibers with optical coherence tomography (OCT) in AD patients. The OCT was used to assess the thickness of retinal nerve fiber layer (RNFL) from 22 AD patients and 22 healthy age-matched controls. The corrected visual acuity and intraocular pressure were measured and the dilated fundus examination and fundus image acquisition were also performed in those subjects. Compared with healthy age-matched controls, the RNFL thickness of AD patients were much thinner (p < 0.05), especially in supra-retina and infra-retina, while no difference was found in the other retinal area. These changes were also confirmed by the fundus images. In conclusion, retinal nerve degeneration is present in the retina of AD patients and this degeneration is likely localized preferentially to the superior and inferior quadrant.     

Are intracranial pressure fluctuations important in glaucoma?

Glaucoma is one of the leading causes of irreversible blindness. Primary open-angle glaucoma (POAG), the most common type, is a progressive optic neuropathy with characteristic structural changes in the optic nerve head and functional changes in the visual field. Mechanical and vascular theories for the pathogenesis of glaucomatous optic neuropathy have been proposed. Elevated intraocular pressure (IOP) is a strong risk factor, although a subset of POAG patients has normal IOP and is designated normal tension glaucoma (NTG). Clearly, factors other than IOP are likely to be involved in retinal ganglion cell death in glaucoma. An intriguing finding of recent studies is that intracranial pressure (ICP) is lower in patients with POAG and NTG when compared with nonglaucomatous control subjects. It has been suggested that the relationship between IOP and ICP may play a fundamental role in the development of glaucoma. A decreased ICP could result in an increased trans-lamina cribrosa pressure difference (IOP minus ICP) and lead to glaucomatous damage. In the present paper, we raise the question of whether ICP fluctuations also may be important in glaucoma. The effect of ICP fluctuation might be comparable to that of IOP fluctuation, which has been recognized as an independent risk factor for glaucoma progression.