青光眼视神经保护性治疗的进展

青光眼是一种致盲率高且不可逆转的严重性眼病,严重影响患者的生活质量,随着对青光眼诊治水平的提高和青光眼视神经损害机制的研究,青光眼视神经的保护越来越受到人们的高度重视。本文主要就青光眼视神经损害的机制和视神经保护性治疗等方面进行综述,以其阻止视神经进一步损害,保护视功能,使治疗达到最佳效果。     

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     

青光眼神经保护治疗研究进展

目前认为青光眼是一种由眼压升高在内的多重危险因素诱导的视神经变性疾病 ,其病理基础是视网膜神经节细胞及其轴突的进行性丢失。神经保护治疗是一种通过阻止神经元死亡治疗神经系统病变的新策略。本文从实验技术、理论基础、治疗手段等方面 ,总结了目前神经保护治疗青光眼的研究进展。     

青光眼视神经保护的相关分析及研究进展

青光眼(glaucoma)是一组具有特征性视神经损害和视野缺损的眼病,在临床上常常表现为视力减退、眼部胀痛伴头痛等症状,是一种致盲率居第二位的不可逆性眼病.青光眼视神经损伤有一定的遗传倾向,造成视神经凹陷性萎缩及视野不同程度缺损这两种结局的危险因素有多种,其中致盲的主要原因包括进行性视神经节损害、病理性眼压升高等.所以在青光眼的治疗中一方面要考虑降低眼压,另一方面还要保护好视神经.本文将从视神经损害的机制、影响因素、分级方法、视神经相关检测指标及其在临床上相关仪器应用、治疗等方面进行综述.     

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     

OCT测量视网膜神经纤维层厚度及视盘参数在青光眼早期诊断中的应用

青光眼是一种进行性视神经疾病,它能引起视神经结构改变,最终导致不可逆的视功能损害。青光眼的早期诊断对保护视功能有重要意义。光学相干断层扫描仪是一种准确性和可重复性高的视网膜神经纤维层厚度和视盘参数检测技术,为早期诊断青光眼,监测视神经损害及指导青光眼的治疗提供了新的思路。我们主要阐述该技术在青光眼早期诊断中的应用。     

中药单体治疗青光眼的研究进展

青光眼(glaucoma)是一组进行性视神经损害,导致视力损伤的疾病,是人类首要不可逆致盲性眼病,病理性眼压升高是其危险因素。临床上常用降眼压类与保护视神经类药物治疗,以对症治疗为主,疗效不理想。中药单体兼有中药与化药双重优势,我国传统中药与中药单体在青光眼治疗,特别是视神经保护方面具有独特优势,可供研发的空间很大。本文综述了代表性组方与单味中药,尤其是代表性中药单体在青光眼治疗中的应用与机制,以期为青光眼临床治疗与新药研发提供参考。     

青光眼视神经保护治疗的实验研究

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，阻断或延缓神经节细胞原发性和（或）继发性损伤的治疗方法称为青光眼视神经保护治疗。目前这一领域的研究包括谷氨酸拮抗剂、钙通道阻滞剂、抗氧化剂、NO合成酶抑制剂、神经营养、凋亡抑制剂、疫苗等。在未来的青光眼治疗中视神经保护治疗很可能成为一种重要的辅助治疗措施，将和包括降眼压药在内的其他手段一起来减少各种原发性和（或）继发性致病因素对视网膜神经节细胞的损伤。     

青光眼的视神经保护治疗

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,阻断或延缓神经节细胞原发性和(或)继发性损伤的治疗方法称为青光眼视神经保护治疗。目前这一领域的研究包括基因治疗、谷氨酸拮抗剂、钙通道阻滞剂、自由基清除剂、NO合成酶抑制剂、β受体阻滞剂、α2-肾上腺素能受体激动剂、疫苗接种等。在未来的青光眼治疗中视神经保护治疗很可能成为一种重要的辅助治疗措施,将和包括降眼压药在内的其他手段一起来减少各种原发性和(或)继发性致病因素对视网膜神经节细胞的损伤。     

改良前房穿刺术在急性闭角型青光眼持续高眼压中的应用

目的:探讨改良前房穿刺术处理急性闭角型青光眼持续高眼压状态下的疗效。方法:对33例33眼急性闭角型青光眼急性发作患者(术前眼压均>60mmHg)在应用常规降眼压药物治疗未能有效降低眼压后,采用改良前房穿刺术,放出房水。结果:所有患者经改良前房穿刺放液后高眼压及眼痛迅速缓解,视力有不同程度的提高,术后眼压平均为15mmHg,未发生与前房穿刺有关的并发症。结论:改良前房穿刺术处理急性闭角型青光眼持续高眼压,损伤小、反应轻、简便高效,可以避免长期大量应用降眼压药物引起的副作用,迅速降低眼压,可以缓解患者痛苦,减轻因高眼压造成的视功能损害。     

Time Course of Age-dependent Changes in Intraocular Pressure and Retinal Ganglion Cell Death in DBA/2J Mouse

Glaucoma is a major cause of irreversible blindness and is characterized by the death of retinal ganglion cells (RGCs) [1]. This death of RGCs is frequently associated with an elevation in intraocular pressure (IOP) [2].However, the understanding of how elevated IOP leads to cell death is hampered by the lack of an animal model that emulates the clinical time course for decades. Mouse studies have proven helpful for investigating human complex diseases. The DBA/2J mouse, which is inheri…     

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。     

The pig eye as a novel model of glaucoma

We validated the pig eye as a model of glaucoma, based on chronic elevation of intraocular pressure (IOP). IOP was elevated by cauterising three episcleral veins in each of the left eyes of five adult pigs. Right eyes were used as controls. Measurement of IOP was performed during the experiment with an applanation tonometer (Tono-Pen). Five months after episcleral vein occlusion, retinal ganglion cells (RGCs) from both cauterised and control eyes were retrogradely backfilled with Fluoro-Gold. Analysis of RGC loss and morphometric as characterization of surviving RGCs was performed using whole-mounted retinas. Elevation of IOP was apparent after three weeks of episcleral vein cauterisation and it remained elevated for at least 21 weeks (duration of the experiments). Analysis of RGC loss after chronic elevation of IOP revealed that RGC death was significant in the mid-peripheral and peripheral retina, mainly in the temporal quadrants of both retinal regions. Moreover the mean soma area of remaining RGCs was observed to increase and we found a greater loss of large RGCs in the mid-peripheral and peripheral retina. We conclude that the pattern of RGC death induced in the pig retina by episcleral vein cauterisation resembles that found in human glaucoma. On the basis of this study, the pig retina may be considered as a suitable model for glaucoma-related studies, based on its similarity with human and on its affordability.     

Detection of early neuron degeneration and accompanying microglial responses in the retina of a rat model of glaucoma

PURPOSE: To characterize the early reaction of retinal ganglion cells (RGCs) in a rat model of glaucoma using in vivo imaging and to examine the involvement of retinal microglia in glaucomatous neuropathy. METHODS: Glaucoma was induced in adult female Sprague-Dawley rats by cauterizing two episcleral veins, which resulted in a 1.6-fold increase in intraocular pressure (IOP). Retinal ganglion cells were retrogradely labeled with the fluorescent dye, 4-[didecylaminostyryl]-N-methyl-pyridinium-iodide (4-Di-10ASP) and monitored in vivo after elevation of IOP using fluorescence microscopy imaging. The number of RGCs was quantified on retinal flatmounts. Dying RGCs were surrounded by activated microglia that became visible after taking up the fluorescent debris. Immunocytochemistry was conducted to characterize further the ganglion cells and microglia. RESULTS: Cauterizing two of the four episcleral veins resulted in a consistent increase of IOP to 25.3 +/- 2.0 mm Hg, as measured with a handheld tonometer. IOP remained high for at least 3 months in glaucomatous eyes. The earliest sign of RGC death was detected in anesthetized animals 20 hours after induction of glaucoma. RGCs continued to decrease in number over time, with 40% of RGCs having degenerated after 2.5 months. Fundoscopic examination of the optic nerve head revealed cupping 2 months after induction of glaucoma. In addition, microglia were detected on retinal flatmounts as early as 72 hours after induction. Activated microglia and RGCs were also identified immunocytochemically, with an antibody against ionized calcium-binding adaptor molecule (Iba)-1 and an antibody specific to the 200-kDa subunit of the neurofilament protein, respectively. CONCLUSIONS: Occlusion of episcleral veins is a reproducible method that mimics human glaucoma, with chronically elevated IOP-induced RGC loss. This study shows that in vivo imaging permits the detection of ganglion cells in the living animal in the early stages of the disease and highlights the importance of in vivo imaging in understanding ophthalmic disorders such as glaucoma. Secondly, activation of intraretinal microglia coincides with degeneration of RGCs in glaucoma.     

难治性青光眼睫状体光凝疗效观察

目的:评价激光经巩膜睫状体光凝术(transscleral cyclo-photocoagulation,TSCPC)治疗难治性青光眼的临床疗效。方法:对36眼难治性青光眼采用低能量1.5~2.1W,多点数10~32的TSCPC,术后随访观察并记录眼压,视力,眼部自觉症状以及并发症,随访时间约3mo。结果:术前平均眼压62.89±17.36mmHg,最后随访平均眼压为21.13±7.06mmHg,经配对资料t检验,术前眼压与术后眼压相比,差别具有统计学意义(P<0.05)。手术有效率83%。指数以上视力10眼中术后6眼视力无变化,4眼视力提高。6眼眼压控制欠佳,行睫状体冷冻手术。术前所有眼痛的患者眼痛均消失或缓解,并发症少,程度轻,主要有色素膜炎,前房出血等,无眼球萎缩发生。结论:TSCPC是难治性青光眼的一种简单安全有效的治疗方法。     

Comparison of latanoprost monotherapy to dorzolamide combined with timolol in patients with glaucoma and ocular hypertension — A 3-month randomised study

· Background: The purpose of the study was to compare the effects on intraocular pressure (IOP) of adding dorzolamide to timolol or of switching from timolol to latanoprost monotherapy in glaucoma patients inadequately controlled on timolol. · Methods: The study was designed as a 3-month randomised, open-label, multicentre study comprising 183 patients with primary open-angle glaucoma, capsular glaucoma with IOP above 22 mmHg on treatment with one or two ocular hypotensive drugs, or ocular hypertension with IOP above 27 mmHg. After a 2- to 4-week run-in period on timolol, 0.5% twice daily, the patients were randomised to treatment with either latanoprost, 0.005% once daily, or the combination of timolol, 0.5% twice daily, and dorzolamide, 2% twice daily. The mean diurnal IOP after 3 months of treatment was compared with baseline. · Results: Switching from timolol to latanoprost reduced mean diurnal IOP by 4.5±0.2 mmHg (mean±SEM, ANCOVA; 20%), and adding dorzolamide to timolol reduced mean diurnal by 4.4±0.2 mmHg (mean±SEM, ANCOVA; 20%). No serious side effects were observed with either treatment. · Conclusion: Latanoprost monotherapy can be an alternative to combined treatment with two aqueous flow suppressors in patients whose IOP is insufficiently controlled by timolol alone. Received: 30 March 1999 Revised version received: 27 May 1999 Accepted: 7 June 1999     

穿透性角膜移植术后继发性青光眼的临床研究

目的:探讨穿透性角膜移植术(penetrating keratoplasty,PK)后继发性青光眼(post-penetrating keratoplasty glaucoma,PPKG)的病因、分类及防治措施。方法:对197例206眼穿透性角膜移植进行回顾性分析。结果:其中52例52眼(25.2%)诊断为PPKG;34例34眼经联合药物治疗后眼压得到控制;18例18眼行手术或激光治疗后眼压控制良好。结论:PK围手术期的正确处理能够降低继发性青光眼的发生率。根据PPKG的不同病因进行不同治疗,疗效满意。     

Rat chronic glaucoma model induced by intracameral injection of microbeads suspended in sodium sulfate–sodium hyaluronate

Purpose

To establish a rat glaucoma model with chronic intraocular pressure (IOP) elevation induced by microbeads suspended in sodium sulfate–sodium hyaluronate.

Methods

Chronic elevation of IOP was induced unilaterally by injecting polystyrene microbeads, suspended in 4 % sodium sulfate and 3 % sodium hyaluronate, into the anterior chamber. The microbead suspension was injected through either the clear corneal (CC) or sclerocorneal (SC) tunnel. IOP changes were monitored up to 8 weeks after injection. The loss of retinal ganglion cells (RGCs) was assessed using fluorogold retrograde labeling of RGCs. RGC axons were evaluated by immunohistochemistry and immunoblotting.

Results

The resulting IOP elevation was maintained up to 3 weeks after the intracameral injection of microbeads through the CC route and up to 4 weeks after injection through the SC route. The density of RGCs was significantly reduced at 4 weeks after injection, with the SC route leading to more RGC loss than the CC route (p = 0.037). The neurofilament immunoreactivity and protein levels in the optic nerve were also significantly reduced at 4 weeks after injection. Some eyes in the SC route cohort received re-injection of the microbead suspension at 4 weeks after the initial injection, which led to an elevated IOP more than 8 weeks after the initial injection, and eventually a 27.5 % loss of RGC density compared with the control eyes.

Conclusion

The intracameral injection of microbeads suspended in hyaluronate effectively produced chronic IOP elevation and subsequent RGC degeneration in rat eyes. The sclerocorneal tunnel approach yielded a longer period of IOP elevation than the clear corneal approach. Our modified microbead injection offers a reliable high-pressure glaucoma model.