青光眼临床基础研究要览课件

青光眼临床与基础研究要览 葛 坚 中山眼科中心 眼科学国家重点实验室 中山大学 Zhongshan Ophthalmic Center 原发性开角型青光眼的诊断 （中华医学会眼科学会青光眼学组，1987) n眼压超过21mmHg，卧位测量暂定 23mmHg（Goldmann); n眼底有青光眼的特异性变化（RNFL缺损 或视乳头改变）或视野出现青光眼性损害 ， Zhongshan Ophthalmic Center 高眼压症（可疑青光眼） n眼压多次测量超过正常上限，但无眼底 及视野改变，房角为宽角， n排除继发性青光眼 Zhongshan Ophthalmic Center 低眼压性青光眼 n眼压峰值不超过正常上限，但有青光眼 的眼底及视野的变化，并排除其它疾病 n可能伴有体位性低血压、血液动力学危 象、角膜厚度偏薄、玻璃体腔偏大、近视 等 Zhongshan Ophthalmic Center n原发性慢性闭角型青光眼患者尚无任何 体征的另眼，可成为慢性闭角型青光眼前 期，最好做预防性虹膜周切 Zhongshan Ophthalmic Center 美国眼科临床指南(PPP） n原发性开角型青光眼疑似者 n定义：具有发生POAG可能性增高的临 床表现和/或一些危险因素的人。 Zhongshan Ophthalmic Center POAG疑似者的临床表现： n前房角镜检查为开放，并具有下列多个特征： n视乳头或视网膜神经纤维层的形态提示有青光 眼性损害。 n视野检查怀疑为早期青光眼性改变。 n眼压持续升高，但视乳头和RNFL形态正常， 视野检查结果正常。 Zhongshan Ophthalmic Center 青光眼性视乳头损伤的 重要危险因素 n测量眼压值增高 n高龄 n有青光眼家族史 n非洲裔或西班牙裔/拉丁美洲裔 n中央角膜厚度薄 注：对已有明确的继发性原因可能导致OAG的情 况，被排除在POAG疑似者之外。 Zhongshan Ophthalmic Center 原发性开角型青光眼 n定义 是成人中一种进行性、慢性的视神经病变，眼 压和其他目前尚不清楚的因素促成了损伤，在缺 少其他可确定的原因的情况下，出现特征性获得 性视神经萎缩和视网膜神经节细胞及其轴索的丢 失。前房角镜下房角开放。 Zhongshan Ophthalmic Center 原发性开角型的临床特征 nPOAG是慢性的眼部病变过程，通常是进行性 的，双眼发病，但常常并不对称。它具有以下特 征： n具有下列之一或两者的视神经损伤的证据 视乳头或视网膜神经纤维层的结构异常 确实代表患者视功能状态的视野异常 n成年发病 n前房角开放 n没有其他已知原因（如继发性青光眼） Zhongshan Ophthalmic Center 目标眼压 n定义 可阻止视神经进一步损伤的稳定的眼压范围的上限 n目标眼压因人而异。即使对于同一患者，在疾病的不 同发展阶段，目标眼压也会有所不同。 n根据患者的临床表现，首次选择的目标眼压应至少降 低20%. n目标眼压是否恰当和可靠应当通过定期地比较目前和 以前的视神经状况来判断。 Zhongshan Ophthalmic Center primary open-angle glaucoma (European glaucoma society) nEtiology: Unknown nPathomechanism: Unknown nFeatures: Onset: from the 35th year of age onwards Signs and symptoms: asymptomatic until field loss advanced IOP21 mmHg without treatment(diurnal tension curve) Optic nerve head: acquired charactristic glaucomatous damage and /or RNFL changes Visual field: usually detectable glaucomatous defects corresponding to the optic disc damage may be present Gonioscopy: open anterior chamber angle (not occludable, no goniodysgenesis) Zhongshan Ophthalmic Center primary open-angle glaucoma suspect (European glaucoma society) nEtiology: Unknown nPathomechanism: Unknown nFeatures: visual field and/or optic disc and/or RNFL normal or suspiciaous, with at least one being suspicious Peak IOP 21 mmHg 4 mmHg between the two eyes peak IOP value any other vascular risk factors for glaucomatous optic neuropathy POAG in fellow eye AION in fellow eye Zhongshan Ophthalmic Center TARGET IOP nDefinition: an estimate of the IOP obtained with treatment that is expected to prevent further glaucomatous damage. Zhongshan Ophthalmic Center POAG (Asia pacific glaucoma guidelines) nDefinition: Chronic progressive optic neuropathy with characteristic changes in the optic nerve head and/or visual field in the absence of secondary causes Zhongshan Ophthalmic Center POAG suspect (Asia pacific glaucoma guidelines) nDefinition: significant risk factors for glaucoma( e.g., ocular hepertension, family history) and/ or glaucoma suspect disc in the absence of frank glaucomatous optic neuropathy or visual field loss Zhongshan Ophthalmic Center Target IOP nBased on the pressure required to slow or halt disease progression nWhen target is achieved, the patient needs continued monitoring for structural and functional changes nNeeds to be individualized nThe benefits of further pressure reduction need to be weighted against risks Zhongshan Ophthalmic Center Global Data on Visual Impairment in 2002, bulletin of the WHO, 2004 n160 million people are vision disabled n40 million people are blind n9/10 in developing countries n60% resides in sub-Saharan Africa, China, and India. nDiseases: AMD, glaucoma, corneal opacities, DR, trachoma, river blindness nGlaucoma is the second leading cause of blindness globally 青光眼前景展望 Zhongshan Ophthalmic Center 世界青光眼会议 7月6-9, 2005, Vienna 青光眼研究热点 背景背景 Zhongshan Ophthalmic Center n靶眼压 眼压波动 (压力敏感探测器) nFMR, 2PELGN, 视皮层 n影像学 (OCT UBM HRT GDX SLO CDI ） n房水流出通道及循环 n基因筛查及功能研究 Zhongshan Ophthalmic Center n自然动物模型 n药效及副作用 n节细胞神经保护 n滤过泡疤痕调控 n患病率与生活方式、预期寿命 Zhongshan Ophthalmic Center 世界青光眼峰会 Mar 23-25, 2006, Beijing 关键性共识 背景背景 Zhongshan Ophthalmic Center n单纯用神经保护药物 ( 0/56 专家 ) n眼内压降低加神经保护药物 ( 56/56 specialists) n 缺乏24小时持续检测眼内压的设备 (46/56专家) n缺乏精确检测视功能进行性丧失的设备 (34/56专家) Zhongshan Ophthalmic Center 背景 2006 AAO, Nov 11-14 Glaucoma 2006: Beating the Odds Zhongshan Ophthalmic Center 观点及进展 n眼压控制在平均眼压水平（10mmHg） ， 视功能损害持续进展，是否需要手术？ n青光眼治疗是否需要靶眼压？ Zhongshan Ophthalmic Center 观点及进展 n青光眼手术临床研究热点： n脉络膜上腔分流术 n小梁旁路分流术 nSchlemn管切开术 n房角手术 避免滤过术区瘢痕化 Zhongshan Ophthalmic Center New Surgery is the Greatest ! Why Trabs are still with us? Zhongshan Ophthalmic Center Trabs n控制巩膜瓣的厚度及大小 n术中应用MMC等抗代谢药物 n调整缝线 n滤过泡瘢痕化的手术处理 Zhongshan Ophthalmic Center 观点及进展 n视神经保护 目前没有一种视神经保护疗法得到美国FDA批准 潜在的视神经保护药物： nMemamtineNMDA受体抑制剂 nAmyloid抑制淀粉样物质沉着 nCalcinerin抑制Ca 2+超负荷 抑制钙调蛋白，从而抑制FK506活性， 减少节细胞损害 Zhongshan Ophthalmic Center 观点及进展 n视神经保护 nStatins减少胆固醇沉积 nEPO直接减少节细胞损害 nMMPs抑制金属巯蛋白的产生，减少节细胞损 害 nIL-6 直接增加房水排出流量，减少节细胞损害 Zhongshan Ophthalmic Center ARVO 2006 摘要 47(7): 2782-2787 Zhongshan Ophthalmic Center 眼压: 视力丧失的始动因素? nCCT 50(7):823839 FMR, 2PEFMR, 2PE检测青光眼检测青光眼LGN, LGN, 视皮层改变视皮层改变 Zhongshan Ophthalmic Center 干细胞途径构建自然动物模型 Culture for 0.5d after injection 猴鼠嵌合体6w 1w Zhongshan Ophthalmic Center 嵌合体筛查 1：positive2：negative3：E13.54：E10.5 5：E7.56：E16.5a7：E16.5b8：E16.5c marker 100bp 将青光眼致病基因转入猴表皮干细胞进行鼠 囊胚显微注射可能制备青光眼自然动物模型 恒河猴表皮干细胞检测（Y染色体SRY基因） Zhongshan Ophthalmic Center 人工视觉/视网膜假体 Zhongshan Ophthalmic Center 青光眼流行病学 调查与早期干预 Zhongshan Ophthalmic Center TrialsTrialsMajor findingsMajor findings MPPTMPPT MoorfieldsMoorfields primary primary treatment trialtreatment trial Initial treatment withInitial treatment with trabeculectomy trabeculectomy works better than ALT or medicinesworks better than ALT or medicines GLTGLT Glaucoma laser trialGlaucoma laser trial ALT works at least as effective as ALT works at least as effective as medicine as an initial treatmentmedicine as an initial treatment FFSSFFSS FluorouracilFluorouracil filtering filtering surgery studysurgery study 5-5-FU improves success ofFU improves success of trabeculectomytrabeculectomy in eye at high risk for in eye at high risk for failurefailure AGISAGIS AdvancedAdvanced glaucomaglaucoma intervention studyintervention study A dose-response relation of lower IOP A dose-response relation of lower IOP and reduced progression of VF defect. and reduced progression of VF defect. Lower IOP after surgery protects Lower IOP after surgery protects against VF loss more effectively in against VF loss more effectively in whites than blackswhites than blacks Zhongshan Ophthalmic Center TrialsTrialsMajorMajor findingsfindings NTGSNTGS Normal tensionNormal tension glaucoma studyglaucoma study Aggressive IOP reduction (30%) Aggressive IOP reduction (30%) reduced VF progression from 30% to reduced VF progression from 30% to 10% in normal tension glaucoma 10% in normal tension glaucoma patientspatients OHTSOHTS Ocular hypertensionOcular hypertension treatment studytreatment study Treatment reduced risk of developing Treatment reduced risk of developing glaucomatous damage from 10% to 5% glaucomatous damage from 10% to 5% over 5 years in ocular hypertension over 5 years in ocular hypertension patientspatients CIGTSCIGTS Collaborative initial Collaborative initial glaucoma treatment trialglaucoma treatment trial Medicine Medicine works works as as well well as as surgery surgery as as initial treatmentinitial treatment EMGTEMGT Early manifest glaucoma Early manifest glaucoma treatment trialtreatment trial Treatment reduces progression of Treatment reduces progression of glaucomatous damage from 62% to glaucomatous damage from 62% to 45%45% OHTSOHTS CIGTSCIGTS AGISAGIS OcularOcular HypertensionHypertension EarlyEarly GlaucomaGlaucoma AdvancedAdvanced GlaucomaGlaucoma EMGTEMGT FFSSFFSS GLTGLT ongoing trialsongoing trials interim resultsinterim results completed trialscompleted trials NEI clinical trials across the spectrum of glaucoma Zhongshan Ophthalmic Center Cumulative Probability of Developing POAG (OHTS) EMGT Progression rate of vision loss at varying IOPs mean IOP 20.2 mm Hg 16.9 mm Hg 14.7 mm Hg 12.3 mm Hg AGIS Am J Ophthalmol 2000;130:429-440 associative analyses rate of vision loss at varying IOPs predictive analyses: (mean IOP over first three 6-month visits) AGIS Am J Ophthalmol 2000;130:429-440 3x CIGTS: Medical Management and Surgery both Lower IOP Lichter et al, 2001 Lichter et al, 2001 CIGTS: Aggressive IOP Reduction n = 307 n = 300 Lichter et al, 2001 CIGTS: aggressive IOP reduction 10.7%* 13.5%* *cataract 11.6% versus 2.7% (p=0.0001) Zhongshan Ophthalmic Center v 全国非选择性人群：1 45岁：1.122.12 全球全球70007000万万 中国约中国约10001000万万 青光眼患病率 Zhongshan Ophthalmic Center 传统的患病率比较 中 国 西方国家 POAG 80% 5-15% Zhongshan Ophthalmic Center 青光眼谱系变化 总数： 9,774例 n1977-1982 1,432 n1990-1996 2,579 n1997-2002 4,152 n2003-2004.6 1,611 中山眼科中心原发性青光眼住院患者中山眼科中心原发性青光眼住院患者 Zhongshan Ophthalmic Center 青光眼构成比变化青光眼构成比变化 PACG POAG CG PACG POAG CG 77-8277-82 84.36% 8.59% 7.05%84.36% 8.59% 7.05% 90-9690-96 68.55% 23.61% 7.83%68.55% 23.61% 7.83% 97-0297-02 68.4568.45% 27.34% 4.22% 27.34% 4.22% 03- 03- 55.7455.74% 29.11% 15.15% 29.11% 15.15% （中山眼科中心原发性青光眼住院患者）（中山眼科中心原发性青光眼住院患者） Epidemiological Data in Liwan District ，Guangzhou (Cluster Sampling) n1405 cases successfully examined UBM, gonioscopy, fundus photography, IOP, visual field n Prevalence of glaucoma: 3.8(53 patients) n POAG(29) : PACG(21)1.38 : 1 He M, Foster PJ, Ge J: Prevalence of glaucoma in adult Chinese: a population-based study in Liwan district, Guangzhou. Invest Ophthalmol Vis Sci, 2006; 47(7): 2782-2787 Zhongshan Ophthalmic Center PACG新的分类标准？ nPACS (primary angle closure suspect) 存在双眼浅前房、窄房角的解剖结构，静态房角镜下大于三个象 限的功能小梁结构不可见，除外继发因素 nPAC (primary angle closure) 存在浅前房、窄房角的解剖特征，有证据曾经发生过周边虹膜与 功能小梁接触并导致房水外流受阻（周边边虹膜前粘连连、眼压压高于统 计学范围、虹膜纹理的改变、青光眼斑导致的晶状体混浊以及功能 小梁上异常色素沉积等），尚未发生青光眼性视神经病变 nPACG (primary angle closure glaucoma) PAC基础上出现青光眼性视神经病变 Zhongshan Ophthalmic Center 角膜厚度对眼压测量的影响 眼压26mmHg者视神经损害的发生： 正常或薄角膜（ 588m）： 588m 1 555-588m 1.7 0.05 P21mmHg,视力0.4，可先行Phaco n房角关闭 180 时，伴有视功能损害，可行 Phaco-trab，或先行Phaco，观察眼压变化 n 认真细致的前房角镜观察！ Zhongshan Ophthalmic Center v 葡萄膜炎活动期，先行Phaco v葡萄膜炎静止期，再行二期 IOL 植 入 葡萄膜炎继发青光眼 Zhongshan Ophthalmic Center 合并白内障的巨大薄壁滤过泡 n经典处理：修补法 n行Phaco， 自动修复 Zhongshan Ophthalmic Center 结论 nPhaco是治疗闭角型青光眼有效、有益的 补充手段 n争议原因：闭角型青光眼诊断标准不同 Phaco手术指征不同 n需要多中心随机临床对照研究 玻璃体放液前房形成术 恶性青光眼超声乳化术 手术录像手术录像 Zhongshan Ophthalmic Center 联合手术 手术录像手术录像 Zhongshan Ophthalmic Center 内窥镜睫状体光凝术 手术录像手术录像 Zhongshan Ophthalmic Center 内窥镜睫状体光凝手术适应症 1、各种无晶体眼和人工晶体眼继发青光眼 ； 2、外伤性青光眼； 3、葡萄膜炎性青光眼； 4、新生血管性青光眼； 5、恶性青光眼； Zhongshan Ophthalmic Center 内窥镜睫状体光凝手术适应症 6、合并PVR或视网膜玻璃体手术后继 发青光眼； 7、多次手术失败的原发性开角型青光 眼和先天性青光眼； 8、联合白内障或玻璃体视网膜手术。 Zhongshan Ophthalmic Center 现代前房引流物-难治性青光眼 White MoltenoBaerveldt Krupin AhmedJosephOptimed 新型引流管：无缝合、软性硅胶管（HOOD） White前房引流物 v硅胶引流管 外径0.64mm 内径0.3mm v硅胶圆形引流盘 表面积为280mm2 v单向阀门 常用的现代前房引流物 Molteno前房引流 物 长管单盘 长管双盘 长管双房单盘和双盘 v硅胶引流管 外径0.63mm 内径0.3mm 长 21mm v丙烯酸甲酯引流盘 直径为13mm(儿童8mm) 表面积为135mm2 v无活瓣单元 常用的现代前房引流物 Baerveldt前房引流物 v硅胶管 外径0.64mm 内径0.3mm v三种大小储液盘： 250mm2、350mm2 、 425mm2 v外植盘体 含钡硅胶 v术后易发生复视 常用的现代前房引流物 Krupin前房引流物 v具有单向压力敏感阀 管的远端具有水平和垂 直裂隙，活瓣的开放压力为 1lmmHg，关闭压力为 9mmHg vv硅胶管硅胶管 外径外径0.580.58mm mm 内径内径0.380.38mmmm、长长2