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晶状体诱导性青光眼的诊治进展

Progress in diagnosis and treatment of lens-induced glaucoma

来源期刊: 眼科学报 | 2022年10月 第37卷 第10期 827-834 发布时间: 收稿时间:2022/11/22 11:47:56 阅读量:4587
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关键词:
晶状体诱导性青光眼继发性青光眼晶状体蛋白晶状体颗粒瞳孔阻滞
lens-induced glaucoma secondary glaucoma lens protein lens particles pupillary block
DOI:
10.3978/j.issn.1000-4432.2022.10.03
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晶状体诱导性青光眼(lens-induced glaucoma,LIG)是因晶状体蛋白相关或解剖学异常引起的一类继发性青光眼。基于发病机制,分为晶状体溶解性青光眼、晶状体颗粒性青光眼、晶状体过敏性青光眼、晶体膨胀性青光眼、瞳孔阻滞性青光眼等几类,房角可能是开放或关闭的。高分子量晶状体蛋白、晶状体颗粒释放、瞳孔阻滞、晶体体积增大是引起青光眼的机制。其病因包括膨胀期、成熟期或过熟期白内障,眼部手术和外伤,各种晶体脱位等。流行病学在发达国家和发展中国家各不相同。以视力下降、眼红、单侧眼痛等为主要临床表现,可产生青光眼性不可逆视功能损害。眼部超声检查对其诊断有帮助。需要和急性闭角型青光眼、睫状环阻滞性青光眼、脉络膜上腔出血、外伤或术后眼内炎等疾病相鉴别。治疗方法是去除晶体刺激物质,从而控制眼压。
Lens-induced glaucoma (LIG) is a kind of secondary glaucoma caused by lens proteins or anatomic abnormality of the lens. Based on the pathogenesis, LIG is classified as phacolytic glaucoma, lens-particle induced glaucoma, phacoanaphylactic glaucoma, phacomorphic glaucoma, pupillary block glaucoma. The angle may be open or closed. High-molecular-weight lens protein, release of lens particles, and pupillary block, increase in the volume of the cataractous lens are the mechanisms of glaucoma. Its pathogensis includes intumescent cataracts, mature senile cataract, hyper-mature senile cataracts, surgery and trauma in eyes, and dislocation of lens. The epidemiology varies across developed and developing countries. The common symptom includes diminution of vision, redness of the eye, and unilateral eye pain. It can cause glaucomatous irreversible visual impairment. Ocular ultrasonography is helpful for its diagnosis. Differential diagnosis includes acute angle-closure glaucoma, ciliary block glaucoma, supra-choroidal hemorrhage, post-traumatic or postoperative endophthalmitis. The management is the removal of inciting lenticular matter to control intraocular pressure
     晶状体诱导性青光眼(lens-induced glaucoma, LIG)也称晶体源性青光眼,即由晶体引起的青光眼。该病在最初被描述为因过熟期老年性白内障引起的青光眼,在后面的研究中发现,晶体位置异常、形态异常和晶体蛋白自身改变都会导致该类青光眼。近年来,对LIG的认识逐渐深入。现就LIG的分类、流行病学、病因、病理生理、症状、 体征、辅助检查、鉴别诊断、治疗、预后等进行综述。

1 分类

      根据发病机制的不同,LIG可分为3类:1)晶状体蛋白相关。晶状体蛋白通过完整或破裂的晶状体囊泄漏,包括晶状体溶解性青光眼(phacolytic glaucoma,PLG)、晶状体颗粒性青光眼(lens-particle glaucoma,LPG)、晶状体过敏性青光眼 (phacoanaphylactic glaucoma,PAG),该疾病在不同文献有不同的名称,如晶状体抗原性青光眼、晶状体抗原性葡萄膜炎、晶状体毒性葡萄膜炎及晶状体过敏性眼内炎,这些不同的名称都是基于其发病机制、病理特点来描述该疾病。2 )由晶体位置或形态异常引起的青光眼,包括晶体膨胀性青光眼(phacomorphic glaucoma,PMG)和瞳孔阻滞性青光眼(pupillary block glaucoma,PBG)。3)将假性剥脱性青光眼和睫状体阻滞性青光眼归类为LIG 是有争议的[1-2]

2 流行病学

      该病的流行病学在发达国家和发展中国家各不相同,不同类型的发病率报道也不尽相同。 有研究[3]发现大多数患者发病年龄在 70~79 岁 (44.30%),其次是60~69岁(34.18%)、50~59岁 (11.39%)、80~89岁(7.59%)、40~49岁和90~99岁 (1.27%),且在白内障患者中,LIG整体患病率 1.08%。女性占多数[4-6],男女比例为1:1.4[7]

3 病因

3.1 白内障

      成熟期或过熟期白内障:晶体囊膜完整,但晶状体蛋白渗出,这些物质被巨噬细胞吞噬,和其他炎症介质一起导致前房炎症并阻塞小梁网,导致PLG。是一种继发性开角型青光眼,又称晶状体蛋白性青光眼,常单眼急性发病[8]。 膨胀期白内障晶状体皮质吸水膨胀导致其体积增大,引起瞳孔阻滞或虹膜前移使前房变浅,继发闭角型青光眼。

3.2 眼部手术和外伤

      眼部手术和外伤导致晶体物质释放,可导致急性LPG或慢性PAG,晶体物质释放到前房,引起继发性青光眼,且随着前房内晶体颗粒浓度的增加,房水排出呈线性下降[9]。此外,外伤可导致晶状体脱位引起PBG。

3.3 各种晶体脱位引起 PBG

      先天性晶状体异位:Marfan综合征,Weill-Marchesani综合征等[10]。自发性晶体脱位:高度近视自发晶体脱位等。外伤性晶体脱位,如前所述。

4 病理生理

4.1 PLG

      Epstein曾描述了高分子量晶状体蛋白在PLG发病机制中的作用,白内障晶状体囊中的微缺陷导致可溶性晶状体蛋白逐渐泄漏到房水。巨噬细胞吞噬这些蛋白质并阻断小梁网,导致急性继发性开角型青光眼[11]。有理论[12]表明:高分子量晶状体蛋白直接阻碍小梁网阻止房水流出,并导致 PLG,随着年龄的增长,人类晶状体中高分子量晶状体蛋白含量的增加支持了这一理论。最近研究[8]表明:在成熟期或过熟期白内障,晶体囊膜完整,但晶状体蛋白渗出,这些物质被巨噬细胞吞噬,导致其肿胀变大,和其他炎症介质一起聚集在前房、小梁网,导致前房炎症和小梁网的阻塞,最终引起PLG,是一种继发性开角型青光眼, 又称晶状体蛋白性青光眼,常单眼急性发病。用电子显微镜检查患者晶体囊膜,尽管在宏观和组织学上看起来都完整,但仍有多个非常细小的全 层裂开的裂孔[13]

4.2 LPG

     囊外白内障摘除术或外伤性晶体破裂后晶体颗粒释放,晶状体颗粒直接沉积到小梁网中,阻碍房水流出,导致开角型青光眼。但在LPG中几乎没有炎症,既往误称为晶体诱导性葡萄膜炎[14]

4.3 PAG

      晶体颗粒的释放类似于LPG,但其释放到青光眼发病之间有一个1~14d的致敏期。小梁网的炎症由IgG和补体系统介导的III型超敏反应中的Arthus型反应介导。晶体蛋白是自身隐蔽抗原,体内存在对晶体蛋白的主动免疫,但正常情况下是耐受的,不引起免疫炎症反应,当这种免疫耐受遭到破坏后,患者血清中晶体抗原的抗体效价增加,淋巴细胞对晶体抗原有活跃的增殖反应,用晶体渗出液皮试时,可出现迟发性皮肤过敏反应,甚至有报道[15]患者发生双侧的晶体过敏性葡萄膜炎。晶状体蛋白的泄漏被认为会引起异物反应或免疫排斥反应,是自身免疫反应的一种形式从而导致晶状体诱发的葡萄膜炎,晶体物质阻塞房角,造成小梁网炎症,炎症又导致虹膜前粘连或虹膜后粘连,导致青光眼。

4.4 PBG

      典型的PBG的发病机制是瞳孔中度扩张时房水流动受阻,眼内压力异常,主要体现于虹膜后与虹膜前压力差的增加。晶状体异位、晶状体脱位同样会阻碍房水流动,加重瞳孔阻滞,但并非所有晶体脱位都会继发青光眼,如晶体全脱位至玻璃体腔,患者可无任何眼压升高的症状。晶体全脱位或不全脱位引起的青光眼机制是复杂的,可以分为1 )虹膜后方的晶体半脱位:松弛的晶体悬韧带使晶体向前移动,增加了其与虹膜的接触, 虹膜膨隆,发生继发性闭角型青光眼;2 )对于小而球形的脱位的晶体直接嵌顿在瞳孔区,直接导致后房和前房的压力差;3 )晶体完全脱位进入前房时,晶体的后表面与虹膜接触,导致前部瞳孔阻滞;4 )晶体向玻璃体腔全脱位时发生玻璃体疝,是一种继发性开角型青光眼[16-17]

4.5 PMG

      膨胀期白内障,晶体前后径增大致其体积增大,晶体虹膜隔前移,瞳孔阻滞,前房变浅,房角变窄直至关闭[18]

5 症状

      由于起病前的晶体位置、形态、本身结构的异常,在起病之前就有视力下降、近视、散光、单眼复视,或因晶体全脱位至玻璃体腔出现的高度远视的症状。 
      LIG患者常见的眼部症状是:1 )突然发作的眼红;2 )突然发作的单侧眼痛,可能伴有同侧头痛、恶心和呕吐;3 )视力减退,白内障患者逐渐进行性减退,青光眼发作时可有急性的视力下降;4)虹视、畏光和溢泪。

6 体征

      除开青光眼特有的结膜充血、巩膜上腔静脉迂曲扩张、瞳孔呈散大光反射消失以外,LIG各亚型也有独特的表现。 
      LPG中房水可以看到前房内晶状体颗粒,晶体表面晶状体囊膜破裂伴白内障。 
      在PLG和PAG中,由于炎症细胞的存在而显示前房炎症反应,可见角膜后表面有新鲜的沉着物,PLG可出现前房明显混浊,甚至假性前房积脓,类似眼内炎的表现[19],长期炎症刺激可出现虹膜后粘连和房角粘连,但很少发现炎性结节, 由于炎症刺激,可出现小瞳孔或花瓣样瞳孔,甚至在炎症较重的情况下表现为瞳孔扩张不良,术中角膜内皮可能受损,导致术后角膜水肿[20]。PLG还可见成熟期或过熟期白内障,晶体呈灰白色或完全液化呈乳白色,前囊表面可见白色小钙化点或黄色小斑点,PMG和PBG的前房深度变浅,且患眼与健眼相比,前房深度、房角开放程度不一 致。PMG可见膨胀的老年性白内障。PBG可见向不同位置、方向脱位的晶状体[14]

7 辅助检查

      压平眼压计测眼压:Goldmann眼压计是测量眼压的金标准。 
      房角镜检查:在角膜透明的情况下,必须进行房角检查。PMG患者受累眼的房角关闭或狭窄,对侧眼房角的开发或关闭与否取决于该眼白内障的阶段。LPG患者房角开放,可见晶体颗粒沉积。长时间的PLG和PAG可能有粘连角闭合伴粘连形成。 
      眼部超声检查:在没有眼底的情况下,超声检查可以提供后段的图像。晶体溶解型青光眼因晶体皮质溶解,其声像图有别于成熟期白内障, 超声表示为晶状体周边呈环形斑片状分布、表面粗糙且边界不规整,中央部透声差,内见较多大 小不一的点状强回声[21]。 
      眼前段光学相干断层扫描:PMG可见前房深度变浅和房角狭窄,晶状体直径及厚度增加。
      房水或玻璃体液检测有助于区分PAG或PLG与 感染性疾病,但很少需要房水细胞学检测来帮助诊断和明确病因[22]。 
      超声生物显微镜检查(ultrasound biomicroscopy,UBM)能准确发现晶状体半脱位和晶状体韧带断裂,可为临床诊断继发于晶状体脱位的急性房角 关闭、瞳孔阻滞提供新的思路和提示,有助于做出准确的诊断[19,23]。UBM可以提供更详细的眼睛前段图像,评估晶状体在疾病病理生理学中的作用,并可以预判手术的难度以及可能的并发症, 同时还可以与B超互补[24],发现前房内的晶状体颗粒,对LPG、PLG有一定的诊断价值[25]。有研究[26]表明:通过UBM发现虹膜包裹晶状体是可能诱发青光眼的隐藏机制。

8 鉴别诊断

8.1 急性闭角型青光眼

      该病可与PMG或PLG相混淆,青光眼的阳性家族史和过去类似发作史有助于区分它们,对侧眼的房角镜检查有助于区分确切的机制。在PLG 中,房角开放,但在虹膜根部、巩膜突和小梁表面,可见散在的灰白色或褐黄色片状沉着物,是与急性闭角型青光眼相鉴别的重要体征[27]

8.2 睫状环阻滞性青光眼 ( 恶性青光眼 )

      该病是由于晶体、睫状突、玻璃体前界膜等解剖关系异常引起,常发生在青光眼滤过术后, 缩瞳治疗后病情加重,而睫状肌麻痹治疗可获得良好的效果,与PBG经常混淆。可诊断性行虹膜周边激光切开术,因为它可以缓解PBG发作,而睫状体阻滞性青光眼不能降低眼压[28]

8.3 脉络膜上腔出血

      类似PBG,也可出现在白内障术中或术后迟发性,其前房变浅,眼压升高。眼底可见显示典型的深红色隆起,或者在眼底视野不佳的情况下, 可以进行B超扫描以帮助诊断[24]

8.4 外伤或术后眼内炎

      存在房水细胞、眼压升高、角膜水肿或外伤后伴有晶状体破裂的前房房水闪辉、下方积脓可与LPG、PAG相似或共存。B超检查、房水或玻璃体的微生物学检查有助于排除眼内炎[29]

9 治疗

      治疗的主要目标是充分控制眼内压。最终的治疗方法是去除刺激性晶体物质或脱位的晶体。

9.1 药物治疗

      局部抗青光眼药物:一线治疗包括β受体阻滞剂、α受体激动剂和碳酸酐酶抑制剂。前列腺素类药可能会增加眼内炎症[30]。 全身降眼压药物:高渗药物(即甘露醇)和碳酸酐酶抑制剂(乙酰唑胺)可增强局部药物的效果。对于PBG,全身药物可促使晶体向后移位,减轻瞳孔 阻滞[31]。 皮质类固醇:在白内障术前,局部和全身皮质类固醇可降低PLG和PAG的炎症反应。 谨慎使用缩瞳或散瞳药剂:在明确患者是闭角型青光眼的患者中,可使用缩瞳剂,缩瞳剂可以增加虹膜张力,减少或避免周边虹膜前粘连,为手术治疗和术式选择提供良好的条件。晶体全脱位至前房的患者术前可予缩瞳剂收缩瞳孔,挡住晶状体向后移位,以便前路取出。在部分PBG 中,对于使用缩瞳剂后前房更浅、房角更窄、眼压升高时,可试用散瞳药剂,这是因为在向后不全脱位的晶体病例中,缩瞳药刺激睫状肌收缩使悬韧带进一步松弛,晶体更向前移位,加重瞳孔阻滞,散瞳使悬韧带拉紧,缓解病情。晶体向前部分脱位的患者可予仰卧位散瞳,甚至棉签按压角膜中央行晶状体复位。对眼内炎症较明显的患者,可以使用睫状肌麻痹,以防止虹膜后粘连、稳定血-房水屏障、缓解睫状肌痉挛和减轻疼痛[14]

9.2 手术治疗

      理想情况下,可在充分控制眼压后进行晶体摘除术或彻底清除眼内晶体蛋白。在青光眼急性期或药物难以控制的LIG,可考虑前房穿刺降低眼压,缓解症状,保护视神经。对于PBG和PMG, 激光周边虹膜切开术可以缓解瞳孔阻滞,但可能不足以控制眼压。白内障摘除术,根据医生的经 验或治疗条件,传统的白内障囊外摘除术、小切口白内障手术或超声乳化技术都可以用来摘除晶状体,该方式可去除晶体因素导致的青光眼,是 LIG的主要治疗方式,同时能提高可见度,大大增强了医生诊断和跟踪青光眼进展的能力,并具有提高患者视力的额外好处[32]。 
      对于高度成熟或膨胀性白内障,如果前房空间不足,无法安全地进行白内障手术,需要在白内障手术前进行平坦部玻璃体切除术。对于 LPG和PAG患者,应彻底抽吸出晶体囊膜及皮质颗粒[33]。对于先天性晶体位置异常的患者,可根据晶体脱位的程度采用各种技术。对于轻度至中度半脱位,超声乳化联合囊袋张力环植入或缝合囊袋是首选[34]。对于严重或向玻璃体腔的晶体脱位,可能需要囊内白内障摘除术或平坦部入路的玻璃体切除联合晶状体切除术[35]。在晶状体半脱位的情况下,单纯的小梁切除术前应谨慎,因为可能发生浅前房或恶性青光眼[36]。对于PLG, 如果之前的病史少于1周,仅立即取出晶状体可使眼压得到良好控制。对于2周以上的病史,初次手术白内障手术联合小梁切除术显示出更好的眼压控制。因既往曾有过眼内手术的患者前房内炎症因子浓度更高,二次行小梁切除术的患者失败率高[37]。对于无光感因而预估不太可能改善视力的患者,白内障手术仍然可以用来控制炎症和疼痛。

9.3 恢复视力的治疗

      后囊膜完整且囊袋稳定性好的患者可一期植入后房型人工晶状体。对于晶体半脱位,囊膜张力环等装置可稳定囊袋并有助于植入后房型人 工晶状体。对于晶体囊内摘除和晶状体切除术病例,一期或二期巩膜固定人工晶状体或前房人工晶状体的成功率各不相同[38]。白内障摘除联合房角粘连松解术、房角成形术是LIG患者房角粘连形成的一种治疗选择。对于PMG,若病程小于4周, 行白内障手术,控制眼压和视力康复是有用的,如PMG时间较长,房角广泛粘连,则进行晶状体摘除联合小梁切除术[39]

10 预后

      LIG及时处理可获得良好的视觉预后[40]。在 适当的眼压控制下进行早期晶状体摘除是治疗的 基础。在加尔各答国立医学院2012至2013年进行 的一项前瞻性观察研究[41]中,大部分患者(72.2%) 在完成随访后,术后最佳矫正视力超过20/125。 有研究[42]发现LIG症状持续时间较短与术后视力增加呈正相关,青光眼损害在眼压约35mmHg时表现出平台效应,决定视力丧失程度的不是眼压水平,而是持续时间,白内障摘除联合小梁切除术在术后即刻有良好的眼压控制效果,若房角粘连、关闭,或因其他原因延迟手术时间,则术后眼压控制多较差,房角粘连是一个不良的预后指标,需要定期监测眼压[43]

11 并发症

      并发症类似于青光眼发作、白内障术后等并发症,如持续性炎症、人工晶状体上的色素和/或蛋白质沉积,房角粘连形成闭角型青光眼,视力低下,持续的高眼压最终引起青光眼性视神经萎缩、感染性眼内炎、驱逐性脉络膜上腔出血、永久视力丧失及眼球萎缩伴疼痛等。LIG术后可出现眼内炎症、继发性青光眼、黄斑囊样水肿,严重 眼内炎还会引起视网膜血管炎[44]。 
      值得强调的是,术后持续高眼压,其原因可能是:1 )手术时间较长,加重手术创伤,引发更多的炎症,使炎症细胞及炎性渗出物增多,堵塞房水排出管道[45];2)手术过程对房水排出系统如巩膜层血管或房水静脉血管等造成破坏[46];3)手术器械损伤房角组织,小梁网水肿,房水排出困难[47];4)炎症、手术操作或植入的人工晶体刺激睫状突上皮细胞,导致分泌房水量增加。5 )青光眼滤过手术失败;6 )其他一些影响房水排出的疾病,如糖尿病和糖代谢异常,血管性病变影响其通透性,高度近视眼球壁变薄,抗张能力下降, 陈旧性葡萄膜炎,眼外伤等[48]

12 结语

      随着对疾病的不断认识,诊疗技术的不断发展,LIG的诊治已不再是眼科难题,期望今后能不断提高白内障手术率、尽早诊治晶体脱位、避免眼外伤等来降低LIG发病率,也期望在将来对LIG有统一的认识,尽早得出流行病学数据。

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1、李婷, 胡红梅, 刘含军, 等. 超声乳化与小梁切除术联合治疗闭角型青光眼并白内障疗效及对术后视力水平、房角结构变化的影响[J]. 湖南师范大学学报(医学版), 2023, 20(2): 126-129.LI Ting, HU Hongmei, LIU Hanjun, et al. Effect of phacoemulsification and trabeculectomy in the treatment of angle-closure glaucoma and cataract and the changes of postoperative visual acuity and angular structure[J]. J Hunan Norm Univ Med Sci, 2023, 20(2): 126-129.
2、李婷,胡红梅,刘含军等.超声乳化与小梁切除术联合治疗闭角型青光眼并白内障疗效及对术后视力水平、房角结构变化的影响[J].湖南师范大学学报(医学版),2023,20(02):126-129+148.LI Ting, HU Hongmei, LIU Hanjun, et al. Effect of phacoemulsification and trabeculectomy in the treatment of angle-closure glaucoma and cataract and the changes of postoperative visual acuity and angular structure[J]. J Hunan Norm Univ Med Sci, 2023, 20(2): 126-129.
1、重庆市自然科学基金 (cstc2020.jcyj-msxmX0698)。This work was supported by the Chongqing Natural Science Foundation, China (cstc2020.jcyj-msxmX0698)()
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