青光眼视神经保护的治疗现状及进展

青光眼是以视网膜神经节细胞及视神经轴突的丢失为特征的神经变性疾病。现有证据表明眼压升高仅仅是青光眼的许多危险因素之一,很多患者虽然已有效地降低了眼压但疾病仍然处于进展中。本文对青光眼视神经保护相关的药理学方法、基因治疗、免疫调节代谢物和接种疫苗、干细胞疗法和生物能疗法,以及目前相关的药物疗法进行综述,展望青光眼视神经保护治疗新前景。     

第三届国际青光眼会议及21世纪青光眼会议概况

第三届国际青光眼会议于 2 0 0 1年 3月 2 1～ 2 5日在捷克布拉格召开。共有 50个国家 1 0 0 0余名代表参会。 2 1世纪青光眼学术会议于 2 0 0 1年 5月 2 4～ 2 7日在西班牙马略卡岛举行 ,有 47个国家 90 0余名代表出席。现将两会的学术内容简要介绍如下。一、青光眼视神经保护的研究青光眼视神经保护问题是当前国内外研究的热点。学者们一致认为眼压升高是最常见的危险因素 ,但有些患者在眼压正常后 ,病情仍有进展 ,需阐明潜在的病理生理机制 ,如神经营养因子被剥夺、谷氨酸兴奋性毒、氧化性应激反应、氮氧化物及微循环障碍等。最简要的视…     

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。     

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     

青光眼视神经保护的研究进展

青光眼是眼科临床中最常见的致盲眼病之一,目前的治疗方法主要是药物和手术控制眼压,单纯的降低眼压并不能有效地防止视网膜神经节细胞程序性死亡所引起的视神经进行性损害.自视网膜神经保护概念提出以来,对视网膜神经节细胞的损伤和保护研究取得了长足进展.文中就视网膜神经节细胞的损伤、死亡机制及对视网膜神经保护措施的研究进展加以综述.     

青光眼视神经保护治疗的研究进展

青光眼是由于眼压升高引起视乳头损害和视野缺损的一种致盲性眼病,其病理基础是视网膜神经节细胞及其轴突的进行性丢失。过去大量的研究都集中在降低眼压方面,现在视神经保护治疗作为一种通过阻止神经元死亡治疗青光眼的新策略已被普遍接受。我们从NMDA受体拮抗剂、神经营养因子、热休克蛋白、免疫系统等方面,总结了目前青光眼视神经保护治疗的研究进展。     

青光眼视神经保护研究进展

青光眼是以视网膜神经节细胞进行性死亡为特征的一类疾病,其病理学机制包括慢性缺血、氧自由基损害、谷氨酸兴奋性毒素导致神经变性、轴突运输障碍、神经营养因子缺乏、电活动消失等。临床上主要通过降眼压治疗青光眼,但往往有一部分患者控制眼压后仍不能有效减少视网膜神经节细胞的死亡。因此,合理的青光眼治疗应包括视神经保护,本文就近几年青光眼视神经保护治疗的研究进展作一综述。     

青光眼的药物治疗

青光眼是全球第二位致盲眼病，其病因尚未完全明了，目前的有效治疗是降低眼压，因眼压是导致青光眼患者视野丧失的最危险因素，一旦确诊需长期治疗。青光眼的降眼压药物有多种，可根据用药后的降眼压效果正确选择。除了降眼压外，还应注意保护视网膜神经节细胞或增强视神经对高眼压的抵抗力。由于目前尚无有效“神经保护的治疗”方案，因此只能应用降眼压药物以减少或预防视网膜神经节细胞的丧失。     

青光眼视神经保护相关研究进展

Tian Yuan;Zhang Yinjian(Department of Ophthalmology, Longhua Hospital affiliated to Shanghai university of traditional Chinese medicine,Shanghai 200030,China)     

Axon deviation in the human lamina cribrosa

AIMS—To examine the course taken by individual retinal ganglion cell axons through the human lamina cribrosa.
METHODS—Retinal ganglion cell axons were labelled using the retrograde tracer horseradish peroxidase applied directly to the optic nerve in two normal human eyes removed during the course of treatment for extraocular disease.
RESULTS—A majority of axons took a direct course through the lamina cribrosa but a significant minority, in the range 8-12%, deviated to pass between the cribrosal plates in both central and peripheral parts of the optic disc.
CONCLUSIONS—It is postulated that these axons would be selectively vulnerable to compression of the lamina cribrosa in diseases such as glaucoma in which the intraocular pressure is increased.

Keywords: retina; optic nerve; glaucoma; lamina cribrosa     

Heidelberg retinal flowmetry: factors affecting blood flow measurement

AIMS—To evaluate factors affecting Heidelberg retinal flowmeter (HRF) measurements of retinal and optic nerve head blood flow in human subjects.
METHODS—The angle of incidence between laser beam and fundus, and camera distance from the eye, were evaluated for their effect upon measures of blood volume, velocity, and flow in a single 100 × 100 × 400 µm volume of temporal peripapillary retinal tissue in normal volunteers. Both intra and intersession reproducibility of these measures were studied. Intersession data were obtained by taking one image per week for 4 weeks. Finally, the intersession haemodynamic data were examined in the entire image (640 × 2560 × 400 µm), using histograms of pixel by pixel blood flow.
RESULTS—Measures of blood volume, velocity, and flow from a single anatomical site were unaffected by laser beam to fundus angle of incidence (n = 12). As camera distance from the eye was increased (from 2 to 5 to 7 cm), flow measurements showed increasing individual changes, despite unaltered measured vessel lengths and constant overall mean flow (n = 14). The coefficient of variation for two intrasession images of optic nerve head blood flow averaged 7% (n = 20); in contrast, the 4 week intersession coefficient of variation averaged 30% (n = 15). Intersession reproducibility was increased by using flow histograms from the entire image: the coefficients of variation averaged 16% for total flow and 17% for flow in the pixel of median flow.
CONCLUSION—HRF measures of flow are independent of the laser beam to fundus angle of the incidence and dependent upon camera distance from the eye. Intersession reproducibility is best using pixel by pixel analysis of the entire image.

Keywords: retina; optic nerve head; glaucoma; diabetic retinopathy     

神经营养素在视网膜及视神经疾病方面的研究

神经营养素是一类结构和功能相近的多肽类家族,广泛分布于人体各种组织细胞中,有着重要的生物学特性,在临床已广泛应用,在眼科方面也有研究。对神经营养素及其受体在视网膜组织的分布作了描述和分析,并对神经营养素在视网膜及神经疾病方面的基础及临床研究作了综述。     

慢性高眼压青光眼动物模型的构建和鉴定

目的:建立大鼠慢性高眼压模型,观察眼压、病理和视功能改变.方法:SD大鼠45只,麻醉后使用532二极管激光行右眼角膜缘360°光凝,角膜缘激光斑为80～100个,大鼠角膜缘颞侧、颞上及颞下巩膜浅层静脉3条,每条静脉光凝3～4个斑点,功率0.45W/0.7s.左眼为对照眼,3d后测量眼压,部分眼压升高不明显者,进行同样的二次光凝.Tono-penXL眼压计监测3,7,30,60,90,180d麻醉状态下的眼压.激光术后60,180d取大鼠各5只,40g/L多聚甲醛灌注固定,摘取双侧眼球和视神经,分别进行冰冻和石蜡切片,采用HE染色、尼氏染色、甲苯胺蓝染色,光镜下观察房角变化,不同时间视网膜节细胞计数,比较视神经髓鞘密度的变化.60,180d大鼠10只,使用TEC-350V视觉电生理仪行F-VEP检查;然后6mo大鼠5只,进行逆行荧光金标记RGCs,7d后40g/L多聚甲醛灌注固定,全视网膜铺片,荧光显微镜下比较视网膜节细胞数量变化.结果:大鼠高眼压模型成功38只,平均最高眼压在激光后30d,平均值为25.0±4.1mmHg,对照眼17.1±3.2mmHg,180d时眼压基本恢复正常.病理改变:实验眼前房角明显变窄,小梁网间隙压缩、变窄,甚至部分闭锁,消失,少量梭形成纤维细胞聚集,组织致密、硬化,而小梁细胞减少,虹膜部分卷曲,水肿、肥厚出现明显异常.逆行荧光金视网膜铺片和视网膜切片尼氏染色见实验眼视网膜节细胞数量有明显的减少;尼氏染色切片每400倍视野总平均数,60d组对照眼为41±10.6个,实验眼为35±11.2个,180d组对照眼为40±9.8个,实验眼为34±11.0个,周边视网膜平均值减少最为显著,均值相差可达8个神经节细胞;180d时模型眼视神经甲苯胺蓝染色显示的髓鞘密度明显降低;视功能检查:高眼压大鼠模型60,180d的实验眼和对照眼均可引出典型的和重复性好的NPN波形,60d时实验眼AP1(N1-P1振幅)均值降低,为13.03±3.11ms,对照眼为21.14±3.10ms,两者具有显著性差异(P＜0.05),波幅值降低持续至180d仍未恢复;LP1(P1峰潜伏期)60d时无明显变化,180d时则明显延迟,实验眼为74.47±8.05μV,对照眼为59.73±4.16μV,与对照组比较有显著性差异(P＜0.05).结论:使用532-二极管激光角巩膜缘小梁网及巩膜浅层静脉光凝能成功升高眼内压,眼压升高近8mmHg;病理显示视网膜神经节细胞数显著减少,以周边视网膜为著;视神经髓鞘密度亦显著地减少;视觉电生理检测,F-VEP的AP1振幅降低,LP1波峰潜伏期延迟非常显著.     

原发性开角型青光眼正常眼压时共焦扫描激光多普勒视网膜血流图

目的　探讨中国人中原发性开角型青光眼患者眼压在正常范围时视乳头和视网膜的血流动力学。方法　应用共焦扫描激光多普勒视网膜血流图检测 82例原发性开角型青光眼 15 0眼眼压控制在 2 2mmHg以下时视乳头和视网膜血流。结果　视乳头平均血容量、血流速和红细胞移动速率分别是 10 4 3 5± 49 2 4,3 2 43 93± 15 89 72 ,8 3 8±3 0 7;筛板处平均血容量、血流速和红细胞移动速率分别是 7 2 8± 4 18,10 8 5 5± 80 5 1,0 3 9± 0 2 5。盘沿处平均血容量、血流速和红细胞移动速率分别是 2 0 2 1± 16 86,5 2 9 91± 5 2 0 74,1 68± 1 3 2 ;盘缘外视网膜平均血容量、血流速和红细胞移动速率分别是 13 5 6± 5 97,2 5 7 90± 13 8 11,0 92± 0 46;视网膜平均血容量、血流速和红细胞移动速率分别是 17 96±6 2 3 ,3 5 0 3 9± 179 82 ,1 2 3± 0 5 7;血管、筛板和视网膜的血容量、流速和红细胞移动速率和正常眼比较都有明显下降。结论　原发性开角型青光眼患者存在着血流动力学障碍。     

Pattern reversal retinal potentials in ocular hypertensives at high and low risk of developing glaucoma

The human pattern-reversal retinal potential (PRRP) is a bioelectrical response which reflects neural activity generated in the proximal retina. Visual diseases which affect the retinal ganglion cells and the optic nerve often produce significant reductions in the amplitude of the PRRP. PRRP amplitude reductions are frequently observed in patients with primary open-angle glaucoma. This investigation was designed to determine whether patients with ocular hypertension who are at risk of developing glaucoma also exhibit PRRP amplitude reductions. The results indicate that PRRP amplitude reductions do occur in some ocular hyptertensives, but many other ocular hypertensives do not exhibit PRRP abnormalities.Supported in part by Research Grant EY 04464 from the National Eye Institute.     

Heidelberg retina tomograph parameters of the optic disc in eyes with progressive retinal nerve fibre layer defects

Purpose: To determine the Heidelberg retina tomograph (HRT) parameters that identify glaucomatous changes in optic nerve head (ONH) topography associated with progression of retinal nerve fibre layer (RNFL) defects. Methods: A total of 68 eyes with open‐angle glaucoma were included in this retrospective study: 34 eyes showed progression of an RNFL defect during the follow‐up period and 34 eyes did not. Successful RNFL photographs and scanning laser tomography examinations with the HRT were taken in all patients at each of three visits. The change in HRT parameter values during follow‐up was calculated. Results: Progression of the RNFL defect was statistically significantly correlated (p = 0.049) with only one topographic ONH parameter, the cup shape measure. The best combination of two parameters (p = 0.009) included the maximum cup depth and the linear cup : disc area ratio; the best combination of three parameters (p = 0.007) included the maximum cup depth, the linear cup : disc area ratio and the horizontal cup : disc area ratio. Sensitivity and specificity values were 52.9% and 73.5%, respectively, for the cup shape measure, 70.6% and 73.5%, respectively, for the two‐parameter combination, and 76.5% and 79.4%, respectively, for the three‐parameter combination. The areas under the receiver operating characteristic curve were 0.617, 0.724 and 0.753, respectively. Conclusions: The results indicate that the HRT parameters may be used to detect small ONH changes associated with progression of the RNFL defect. With the exception of the cup shape measure, the parameters which provide the best correlation with progression differ from those considered optimal for recognizing the presence or absence of glaucoma.