青光眼周边部视神经纤维损伤机制探讨

目的:比较正常人和青光眼患者视盘周围巩膜纵切面形态(经过视神经中轴)以及神经纤维变化,结合生物力学原理,探讨青光眼周边部视神经损伤机制。方法:对捐献的12个正常人眼和12个青光眼绝对期患者的视神经及其周围组织标本进行固定、切片、格利染色,比较视盘周围巩膜纵切面(经过视神经中心)形态,观察毗邻的周边部视神经纤维走行特点。结果:视盘周围巩膜孔的纵切面为一锐角(平均角度为73.3°),青光眼绝对期患者残留的视盘周围巩膜纵切面也是锐角(平均角度为75.6°),两者差异无显著性(t=1.44,P>0.05)。正常人视神经纤维从视网膜到筛板的走行变化急剧,青光眼绝对期患者该段视神经纤维消失。结论:视盘周围的巩膜前缘和内侧缘夹角为锐角。青光眼绝对期视神经纤维消失的原因可能与高眼压和视盘周围巩膜的形态、巩膜和视神经纤维的剪切模量、以及"折曲损伤"机制有关。     

跨筛板压力差与青光眼发病机制的关系

原发性开角型青光眼及正常眼压青光眼患者脑脊液压力较正常人低,而高眼压症患者脑脊液压力较正常人高.跨筛板压力差增大可能导致青光眼损害,脑脊液压力升高是青光眼的保护因素.跨筛板压力差增大导致筛板向后弯曲变形变薄,视盘凹陷加深,杯盘比增大,导致青光眼病变发生发展.本文就跨筛板压力差的概念、测量方法、影响因素及其与青光眼的关系等方面综述.     

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     

角膜滞后量在青光眼中的作用

青光眼是全球首位不可逆致盲性眼病,其具体发病机制尚不清楚,但颇受重视的是眼压和房水流出通道等方面。近年,研究人员开始越来越多地关注非压力依赖因素如角膜滞后量(CH)在青光眼中的作用。CH是角膜的生物力学参数,它反映了角膜的黏性阻力,即吸收和分散能量的能力。CH在临床上很容易获得,可作为眼后部组织生物力学特性的替代标志物,如筛板和乳头周围巩膜,这些组织可能与青光眼损伤的易感性有关。有研究提供了CH与青光眼临床相关结果之间的联系的证据。本文综述了CH在青光眼中的作用的最新发现,从CH的测量方法、CH与中央角膜厚度、青光眼性视野进展、视盘损害、视网膜神经纤维层缺失等方面进行了归纳和总结。     

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...     

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）     

青光眼患者的角膜生物力学研究

临床上部分眼压控制理想的青光眼患者视野缺损仍持续进展,而部分患者通过治疗即使眼压不能显著降低仍可延缓病情进展。因此患者对眼压的个体敏感性差异决定了青光眼病情的发展。角膜、巩膜的胶原纤维互相连接且成分相似,角膜Descemet前层延伸形成小梁网胶原蛋白的核心,因此角膜生物力学特性是眼球整体生物力学特性的首要表现。当眼压升高时角膜等弹性组织承受形变的能力较弱,导致筛板受压,进一步发生视野损害。个体角膜生物力学属性的差异或许可解释视神经对眼压变化敏感性的不同。本文就角膜生物力学与青光眼诊断、进展、治疗的相互关系进行综述,以期为临床工作提供指导。（国际眼科纵览, 2018,  42:  83-88）     

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...     

兔慢性高眼压模型的眼部表现

目的:观察慢性高眼压状态对兔眼及其视盘的影响.方法:新西兰白兔,10眼前房内抽出0.2mL房水后注射0.2mL复方卡波姆溶液,使眼压慢性升高,10眼为对照组.每天测眼压1次,4wk后,眼底照相,并取出视盘周围视网膜及球后视神经制片,镜下观察.结果:对照组眼前节、视盘、筛板等正常;高眼压组眼部有明显的变化,视盘加深、筛板处形态显著凹陷.结论:高眼压模型眼部改变明显,尤其是视盘筛板更接近临床慢性青光眼的改变.     

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。     

光相干断层扫描检测筛板结构的临床应用及新进展

筛板是位于视旁深部,由胶原纤维构成的筛束和穿行有神经、血管及神经胶质细胞的筛孔组成的复杂结构,为视网膜神经节细胞轴突穿出眼球时提供结构和营养支持。眼压引起机械应力的直接作用以及筛板变形和重塑导致轴浆运输、血运障碍,共同导致视网膜神经节细胞轴突损伤进而死亡。因此,筛板被认为是青光眼病变的始发部位。光相干断层扫描技术的发展...     

Primary open angle glaucoma and low tension glaucoma--pathogenesis and mechanism of optic nerve damage]

The etiology, pathogenesis and mechanism of optic nerve damage in primary open angle glaucoma (POAG) and low tension glaucoma (LTG) were investigated by experimental glaucoma in monkey and by follow-up studies of many patients over 15 years, by pathohistological and immunohistochemical analysis. 1) LTG was proved to be a real glaucoma, showing pressure-dependent optic nerve damage. The pathological entity was a primary weakness of the lamina cribrosa (LC), and therefore even normal pressure could deform the LC. Due to backward distortion of LC the channels were disarranged and twisted, inducing mechanical optic nerve damage. There was no active vascular damage or vascular constriction at the site of the optic nerve damage. The filling defects of the advanced glaucomatous optic disc were not the cause of optic nerve damage, but the result of regressive vascular change after axon bundle loss. Splinter hemorrhage of the optic disc might be the result of the same process. 2) The weakness of LC might be induced by the abnormal metabolism of the extracellular matrix of the LC. 3) To arrest the progressive optic nerve damage in LTG, the intraocular pressure (IOP) should be maintained under 12, or ideally, 10 mmHg. 4) The optic nerve damage in POAG was not only pressure-dependent, but also dependent on the weakness of the LC, as in the case of LTG. In the early stage the IOP should be under 19 mmHg, in the advanced stage under 14 mmHg in order to arrest progression for over 15 years. 5) In advanced experimental glaucoma of monkeys, the LC showed reduction of elastin, fragmentation of collagen, and change of proteoglycans. 6) As in the LC, the trabecular meshwork also showed abnormal metabolism and abnormal deposits on the extracellular matrix in POAG, and LTG as well. 7) POAG and LTG might belong to the same family in which common abnormal metabolism of LC and trabecular meshwork induce various clinical features.     

Alterations in the morphology of lamina cribrosa pores in glaucomatous eyes

AIMS: To determine alterations which occur in the size and shape of lamina cribrosa (LC) pores in glaucomatous eyes over a period of time. METHODS: Baseline and follow up optic disc photographs were retrospectively studied in 39 eyes of 39 patients with glaucoma. Only eyes with a vertical cup to disc ratio equal to or greater than 0.6 were included in the study. In addition, all selected eyes had to have serial optic disc photographs obtained at least 3 years apart allowing clear visualisation of LC surface. The association of the alterations in LC surface morphology with patient specific and eye specific characteristics was statistically analysed. RESULTS: During a mean study period of 3.90 (SD 0.7) years, individual pore size (mean pore area to disc area ratio) exhibited a significant decrease between baseline and follow up measurements of each eye (p<0.0001). However, during the study period, total pore area to disc area ratio did not change (p>0.05), and the change in pore shape in some eyes (from circular to more oval and elongated) was statistically insignificant (p = 0.12). Although a relation was detectable between the optic disc and lamina cribrosa parameters at a given time, which reflects cumulative effects, during the study period, there was no significant association between the changes of the LC parameters and neural tissue damage. The rate and the magnitude of the changes in individual pore size during the study period were not significantly different among the eyes exhibiting progressive neural rim damage and those staying stable (p>0.05). CONCLUSION: These findings demonstrate that the LC surface morphology exhibits changes along with the glaucomatous optic disc damage. However, the clinical appearance of LC surface in glaucomatous eyes may continue to change, even when the neural rim damage is clinically stable. These findings are probably associated with the chronic cellular events of tissue remodelling that occur in the glaucomatous optic nerve head.     

Optic nerve damage in highly myopic eyes with chronic open-angle glaucoma

PURPOSE: To compare the amount of optic nerve damage in relation to intraocular pressure in highly myopic eyes with chronic open-angle glaucoma versus non-highly myopic eyes with chronic open-angle glaucoma. METHODS: The comparative clinical observational study included 1841 eyes of 1100 patients with chronic open-angle glaucoma. The highly myopic study group consisted of 25 eyes with a myopic refractive error equal to or higher than -8 diopters. It was subdivided into eyes with an optic disc size larger than 2.7 mm2 and eyes with an optic disc smaller than 2.7 mm2. The control group included the remaining, non-highly myopic eyes (n=1816). For all patients, a morphometric analysis of color stereo optic disc photographs was performed. Main outcome measures were morphometric optic disc measurements and intraocular pressure. RESULTS: In the highly myopic, large-optic-disc study group compared with the control group, maximal and minimal intraocular pressure readings were significantly (p<0.05) lower and neuroretinal rim area corrected for optic disc size was slightly (p=0.16) smaller. Comparing the total highly myopic study group with a control group adjusted for optic disc area, neuroretinal rim area was significantly (p=0.039) smaller in the study group with no significant difference in intraocular pressure measurements between the groups. CONCLUSIONS: At a given intraocular pressure in chronic open-angle glaucoma, optic nerve damage may be more pronounced in highly myopic eyes with large optic discs than in non-highly myopic eyes. This may suggest a higher susceptibility for glaucomatous optic nerve fiber loss in highly myopic eyes than in non-highly myopic eyes.     

Intraocular pressure-dependent dynamic changes of optic disc cupping in adult glaucoma patients.

The authors performed a study of intraocular pressure-dependent changes in optic disc cupping in 17 adults with chronic open-angle glaucoma. Analyses with the Rodenstock Optic Nerve Head Analyzer were performed at baseline low intraocular pressure during therapy, after elevation of intraocular pressure (from therapeutic failure or noncompliance), and after reduction of intraocular pressure with successful therapy. Optic disc cupping increased significantly upon short-term increase of intraocular pressure from baseline of 20.4 +/- 2.5 mmHg to 31.1 +/- 5.9 mmHg. Optic disc cupping reverted to baseline after persistent intraocular pressure reduction to 19.3 +/- 4.8 mmHg. These data demonstrate intraocular pressure-dependent dynamic changes of optic disc cupping in patients with demonstrable glaucomatous optic nerve damage. They underscore the detrimental effect of elevated intraocular pressure and the beneficial effect of intraocular pressure reduction on optic disc cup changes.     

Increase in dephosphorylation of the heavy neurofilament subunit in the monkey chronic glaucoma model

PURPOSE: To investigate the phosphorylation of the heavy neurofilament subunit (NF-H), which could be deeply involved in axonal transport of retinal ganglion cells (RGCs), in an experimental glaucoma model of chronic elevation of intraocular pressure (IOP) in monkeys. METHODS: One eye in adult monkeys was randomly selected for laser treatment, and IOP was maintained between 30 and 40 mm Hg throughout the experiment. The eyeballs with the optic nerve and optic chiasm were enucleated as one tissue and were subject to immunocytochemical observation, using two NF-H-specific antibodies, NF-200 and SMI31. NF-200 reacts with both phosphorylated and dephosphorylated NF-H, whereas SMI reacts only with phosphorylated NF-H. Ratios of SMI31-positive to NF-200-positive areas were calculated for quantitative evaluation of phosphorylation status. Specimens from the retina, lamina cribrosa (LC), post-LC, and optic chiasm were evaluated separately. Phosphorylation of NF-H at the retina and optic nerve head was compared between specimens from temporal retina and nasal retina, or between temporal and nasal regions of the optic disc. The status of phosphorylation was confirmed by Western blot analysis. RESULTS: An enlargement of the disc cup was observed on the temporal side, and the superior and inferior poles were preferentially involved in the neuronal damage in laser-treated eyes. Most NF-Hs in the control eyes were phosphorylated in all investigated regions, whereas those in the glaucomatous eyes were significantly dephosphorylated, and NF-Hs in the temporal region were significantly dephosphorylated compared with those in the nasal region. At the optic chiasm, NF-Hs in axons traveling from laser-treated eyes were highly dephosphorylated, and the extent of NF-H dephosphorylation corresponded to the degree of glaucoma-induced axonal damage. Western blot analysis showed the change in the phosphorylation of NF-Hs. CONCLUSIONS: NF-Hs in RGC axons are dephosphorylated by elevated IOP, which may be deeply involved in glaucoma-induced damage to axonal transport.     

The pathogenic role of transforming growth factor-β2 in glaucomatous damage to the optic nerve head

In patients with primary open angle glaucoma (POAG), the optic nerve head (ONH) shows characteristic cupping correlated with visual field defects. The progressive optic neuropathy is characterized by irreversible loss of retinal ganglion cells (RGC). The critical risk factor for axonal damage at the ONH is an elevated intraocular pressure (IOP). The increase in IOP correlates with axonal loss in the ONH, which might be due to an impaired axoplasmatic flow leading to the loss of RGCs. Damage to the optic nerve is thought to occur in the lamina cribrosa (LC) region of the ONH, which is composed of characteristic sieve-like connective tissue cribriform plates through which RGC axons exit the eye. The cupping of the optic disc, and the compression and excavation of LC are characteristic signs of glaucomatous ONH remodelling. In ONH of POAG patients a disorganized distribution and deposition of elastic fibers and a typical pronounced thickening of the connective tissue septae surrounding the optic nerve fibers is found.Transforming growth factor (TGF)-β2 could be one of the pathogenic factors responsible for the structural alterations in POAG patients as the TGF-β2 levels in the ONH of glaucomatous eyes are elevated as well as in the aqueous homour. TGF-β2 leads to an increased synthesis of extracellular matrix (ECM) molecules mediated by connective tissue growth factor and to an impaired ECM degradation in cultured ONH astrocytes. Bone morphogenetic protein (BMP)-4 effectively antagonizes the effects of TGF-β2 on matrix deposition. The BMP antagonist gremlin blocks this inhibition, allowing TGF-β2 stimulation of ECM synthesis. Overall, the ECM in the ONH is kept in balance in the OHN by factors that augment or block the activity of TGF-β2.     

Morphology of the optic papilla in glaucoma. I. Primary open-angle glaucoma

BACKGROUND: Previous studies have shown that the chronic open-angle glaucomas form a heterogeneous spectrum of diseases which have in common an open anterior chamber angle and glaucomatous optic nerve damage. Purpose of this study was to evaluate whether the appearance of the optic disc differs among the various types of primary open-angle glaucoma. METHODS: Color stereo optic disc photographs of 683 patients with primary open-angle glaucoma (POAG), and 481 normal eyes were morphometrically evaluated. RESULTS: Morphologic characteristics of the glaucoma types were as follows: Highly myopic POAG: secondary macrodiscs with abnormal shape; shallow, flat, concentric disc cupping; low frequency of disc hemorrhages; large parapapillary atrophy or myopic crescent; medium to low intraocular pressure. Juvenile-onset POAG: Optic disc of normal size and shape; deep and steep disc cupping; low frequency of broad rim notches or large disc hemorrhages; small parapapillary atrophy; high minimal and maximal intraocular pressure measurements. Age-related atrophic POAG: Optic disc of normal size and shape; shallow, flat and concentric disc cupping; medium to low frequency of disc hemorrhages; large parapapillary atrophy; medium to low intraocular pressure. Eyes with normal-pressure glaucoma: Optic disc of normal size and shape; deep and steep cupping; relatively small parapapillary atrophy; high frequency of disc hemorrhages and rim notches. CONCLUSIONS: These characteristics in the appearance of the optic disc may be helpful for clinical diagnosis and therapy and may give pathogenetic hints.     

Mucopolysaccharidosis Type I and Bilateral Optic Disc Edema

ABSTRACT

Mucopolysaccharidosis type I (MPS I or Hurler syndrome) is a multisystem genetic disorder caused by α-L-iduronidase (IDUA) deficiency, which leads to widespread accumulation of glycosaminoglycans triggering tissue damage and organ dysfunction. A variety of ocular manifestations have been described in Hurler Syndrome. We present the case of an 11-year-old boy with Hurler Syndrome and optic disc edema related to ocular glycosaminoglycan deposition. This report advances the idea that the optic nerve swelling seen in MPS I is likely influenced as much by biomechanical changes at the optic nerve head as by increased intracranial pressure.     

Can frequency-doubling technology and short-wavelength automated perimetries detect visual field defects before standard automated perimetry in patients with preperimetric glaucoma?

PURPOSE: To assess the ability of frequency-doubling technology (FDT) perimetry and short-wavelength automated perimetry (SWAP) to detect glaucomatous damage in preperimetric glaucoma subjects. PARTICIPANTS: Two hundred seventy-eight eyes of 278 subjects categorized as normal eyes [n=98; intraocular pressure <20 mm Hg, normal optic disc appearance, and standard automated perimetry (SAP)]; preperimetric glaucoma eyes (n=109; normal SAP and retinal nerve fiber layer defects or localized optic disc notching and thinning); and glaucoma patients (n=71; intraocular pressure >21 mm Hg, optic disc compatible with glaucoma, and abnormal SAP). METHODS: The preperimetric glaucoma group underwent at least 2 reliable full-threshold 24-2 Humphrey SAPs, full-threshold C-20 FDT, full-threshold 24-2 SWAP, optic disc topography using the Heidelberg Retina Tomograph II, laser polarimetry using the GDx VCC, and Optical Coherence Tomography (Zeiss Stratus OCT 3000). Receiver operating characteristic curves were plotted for the main Heidelberg Retina Tomograph, Optical Coherence Tomography, and GDx VCC parameters for the normal and glaucoma patients. The area under the receiver operating characteristic curve was used to determine the parameters indicating glaucomatous damage in the optic disc or retinal nerve fiber layer, which were used to establish additional subgroups of patients with preperimetric glaucoma. FDT and SWAP sensitivities were calculated for the patient subsets with structural damage and normal SAP. RESULTS: At least 20% of the patients with preperimetric glaucoma demonstrated functional losses in FDT and SWAP. The more severe the structural damage, the greater the sensitivity for detecting glaucomatous visual field losses. CONCLUSIONS: FDT and SWAP detect functional losses in cases of suspected glaucoma before glaucomatous losses detected by SAP.