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先天性晶状体脱位的治疗及预后研究进展

Recent advances in research onthe treatment and prognosis of congenital ectopia lentis

来源期刊: 眼科学报 | 2024年8月 第39卷 第8期 424-430 发布时间:2024-08-28 收稿时间:2024/9/30 9:53:06 阅读量:525
作者:
关键词:
先天性晶状体脱位视力预后屈光变化术后并发症
congenital ectopia lentis visual prognosis refractive changes postoperative complications
DOI:
10.12419/24072304
收稿时间:
2024-07-01 
修订日期:
2024-07-28 
接收日期:
2024-08-13 
先天性晶状体脱位(congenital ectopia lentis, CEL)是一种罕见的遗传相关性疾病,其主要临床特征是晶状体悬韧带先天性发育异常,导致晶状体偏离正常解剖位置。随着病情的进展,CEL可引起高度屈光不正甚至弱视外,还可能导致继发性青光眼和视网膜脱离等严重的并发症。目前,手术仍是改善CEL患儿视觉质量及防治并发症的主要手段。常用的手术方式包括晶状体摘除术、前房型人工晶状体(intraocular lens, IOL)植入术、囊袋支撑装置联合IOL植入术及经巩膜IOL固定术等,这些手术方式各具特点,但目前最佳手术方式仍未有定论。既往大量文献表明,手术能够显著改善CEL患儿视力,但随着眼球的生长发育,CEL患儿术后屈光状态常出现近视漂移。此外,术后并发症如缝线暴露,IOL瞳孔夹持、IOL脱位、视网膜脱离等仍有可能发生,需要长期的严密随访。这些因素都使得CEL的治疗具有挑战性。为此,文章就CEL的手术方式、视力预后、术后屈光变化及术后并发症进行综述,旨在为该疾病的临床诊断及治疗提供更为全面和深入的理解。

Congenital ectopia lentis (CEL) is a rare genetic disorder characterized by the displacement of the lens from its normal anatomical position due to abnormalities in the lens zonular. As the progression of the disease, CEL can lead to high refractive error, even amblyopia, as well as other serious complications such as secondary glaucoma and retinal detachment. Currently, surgical intervention remains the primary method to improve the visual quality and prevent complications in children with CEL.Common surgical options include lens extraction, anterior chamber intraocular lens (IOL) implantation, IOL implantation combined with capsular tension devices, and transcleral fixation of IOL. Each surgical approach has its own characteristics, but there is currently no consensus on the best surgical method. Previous literature has shown that surgery can significantly improve vision in children with CEL; however, due to the growth of the eye, postoperative refractive status often experiences myopic shift. Additionally, complications such as suture exposure, IOL pupil capture, IOL dislocation, and retinal detachment may still occur, necessitating long-term close follow-up. These factors make the treatment of CEL challenging. This article reviews the surgical approaches, visual prognosis, postoperative refractive changes, and postoperative complications associated with CEL, aiming to provide a more comprehensive and in-depth understanding for the clinical diagnosis and treatment of this disease.

文章亮点

1. 关键发现

• 文章系统性总结了先天性晶状体脱位的手术方式、视力预后、术后屈光变化及术后并发症,为临床医生提供参考。

2. 已知与发现

• 多种手术方法被应用于治疗先天性晶状体脱位,手术能够改善先天性晶状体脱位患儿的视力,然而,术后可能出现的并发症亦不可轻视。

3. 意义与改变

• 文章对先天性晶状体脱位的治疗及预后进行总结,强调了术后长期严密随访的重要性,并提出未来研究的新方向。

  先天性晶状体脱位
(congenital ectopia lentis, CEL)是由于晶状体悬韧带先天性发育异常导致晶状体偏离正常解剖位置的一种罕见的遗传相关性疾病[1]CEL除引起严重的屈光不正,甚至弱视外,还可能引起继发性青光眼和视网膜脱离(retinal detachment, RD)等严重的并发症。手术仍是目前改善患儿视觉质量及防治并发症的主要方法。然而,儿童眼球仍处于生长发育阶段,虽然手术可以去除晶状体脱位对视觉发育的干扰,但手术相关并发症仍有可能出现,使得最终手术效果和预后大不相同。因此,本文就CEL的手术方式、视力预后、术后屈光变化及术后并发症的研究进展进行综述,以期为提高该病的防治水平提供翔实依据。

1 先天性晶状体脱位概述

  CEL的患病率约为6.4/100 000[2],多于儿童及青少年时期发病,常累及双眼。该病可单独发生,也可伴随其他眼部异常如球形晶状体、先天性无虹膜等,或与其他全身性综合征如马方综合征(Marfan syndrome, MFS)、威尔-马切山尼综合征(WeillMarchesani syndrome)、同型半胱氨酸尿症等有关。CEL具有明显的遗传倾向,基因突变是其最主要的病因,多数为常染色体显性遗传,少数为常染色体隐性遗传。研究表明,CEL的致病基因种类繁多,其中FBN1基因突变占比最高,为83%~85%[3-5],其他基因包括LTBP2(1.71%~2.76%)[4,6]ADAMTSL4(2.88%~3.94%)[4,7-8]ADAMTSL17(2.16%)[9]CBS(2.29%)[4]等。

2 先天性晶状体脱位的治疗

  在疾病的早期阶段,轻度的晶状体脱位可通过观察、配戴框架眼镜或角膜接触镜矫正屈光不正[10]。然而,随着疾病的进展,晶状体脱位程度会不断加重,这可能引起高度屈光不正、屈光参差,甚至导致弱视的发生[11]。此外,晶状体脱位还可能并发白内障、角膜内皮失代偿、继发性青光眼、RD等并发症。对于严重的晶状体脱位,手术是提高视觉质量及预防和治疗并发症的主要手段。目前,多种治疗CEL的手术方式已在临床广泛应用,但关于最佳术式的选择,尚未达成共识。

2.1 无晶状体眼的保守治疗

  一旦CEL患儿的晶状体被移除,无晶状体眼和囊袋支撑不足的儿童在光学矫正方面将面临挑战。在摘除脱位的晶状体后,可以通过佩戴框架眼镜或角膜接触镜矫正残余的屈光不正。但是,对于无晶状体眼的高度远视患儿而言,佩戴框架眼镜矫正时的镜片较厚,这可能给患儿日常生活带来不便,同时佩戴眼镜时所带来的外观上的改变,可能会对患儿的心理健康造成一定影响。角膜接触镜作为一种非侵入性的治疗方式,具有放大率小、影像畸变小等优点,但其使用需要患儿及家长有较高的依从性。此外,长期佩戴角膜接触镜可能会增加角膜内皮的多形性,并且存在一定的感染风险,特别是在儿童患者中[12-13]
  对于囊袋支撑不足的CEL患儿,IOL植入与固定方式主要分为三类:前房型人工晶状体(intraocular lens,IOL)植入、联合囊袋支撑装置的IOL植入、经巩膜IOL固定术。

2.2 前房型人工晶状体

  以虹膜夹持型IOL或房角支撑型IOL为代表的前房型IOL植入术,虽然操作简便,但在年轻患者中因可能引发较多较严重的术后并发症,如角膜内皮失代偿、IOL脱位、青光眼、虹膜色素播散及慢性炎症等,因此在临床上已较少使用[14-15]

2.3 囊袋支撑装置联合人工晶状体植入术

  联合标准囊袋张力环的IOL植入术能够使晶状体囊袋张力均匀地分布在残余晶状体悬韧带上,适用于悬韧带离断范围小于120°的患者[14]。然而,由于CEL是一种进展性疾病,晶状体悬韧带进行性离断,在长期随访中存在IOL-张力环-囊袋复合体脱位的风险[16]。改良带钩囊袋张力环(modified capsular tension ring, MCTR)联合IOL植入术能够在保留后囊膜的同时,通过缝线将MCTR固定于巩膜,实现IOL的原位植入,尤其适用于悬韧带离断范围超过120°的患者[14]。MCTR的应用能够最大限度地保留和重塑晶状体囊袋悬韧带隔的完整性,减少术中对眼后段的扰动,显著提高了术后IOL的长期稳定性,因此受到广泛关注[17-18]。然而,由于囊袋尺寸、广泛的悬韧带病变或术中囊袋撕裂等原因,部分患者无法进行MCTR植入[18]。此外,由于复杂的手术技术和MCTR来源的限制,使得该手术方式难以在我国普及。近年来,有学者采用5-0聚丙烯缝线制成的囊袋拉钩联合标准囊袋张力环代替MCTR,并应用于CEL患者中,在中短期随访研究中取得了良好的疗效[19]

2.4 经巩膜人工晶状体固定术

  经巩膜IOL固定术的发展历程可划分为三个主要阶段:传统的经巩膜IOL缝线固定术、无线结IOL缝线固定术以及无缝线的IOL巩膜层间固定术。传统的经巩膜IOL缝线固定术作为经巩膜IOL固定术的经典术式,广泛地应用于CEL患儿中,其核心特点是通过缝线打结固定IOL,并将线结埋藏于巩膜瓣下。然而,随着时间的推移,即使采用巩膜瓣埋藏线结,线结仍可能对局部组织造成摩擦和刺激,导致巩膜瓣逐渐萎缩,进而引发线结侵蚀、暴露等问题,严重者甚至导致感染性眼内炎的发生[20-22]。Szurman等[23]首次提出了“Z”形无线结经巩膜IOL缝线固定术,其核心特点在于采用缝线在巩膜层间“Z”形穿行,取代缝线打结,从而避免了巩膜瓣的制作及线结相关并发症的发生,如巩膜萎缩、缝线侵蚀和感染。但该术式仍需使用缝线固定IOL,因此无法完全避免缝线降解、断裂和继发的IOL脱位等并发症。近年来,以Yamane术式为代表的无缝线的IOL巩膜层间固定术也用于儿童患者中[24]。然而,由于儿童患者前房相对较小、巩膜相对较软,术中操作难度较大。尽管IOL巩膜层间固定术展现出了良好的前景,然而,其在儿童群体中的应用尚未得到推广,因此需要对其长期疗效进行深入研究。

3 先天性晶状体脱位的预后

3.1 先天性晶状体脱位的视力预后

  CEL在0~6岁儿童中的发病率较高[25],鉴于大多数患儿仍处于视觉发育的关键时期,脱位的晶状体不仅严重影响患儿的视功能发育,还对患儿的视觉相关生活质量和心理健康造成持久的影响[26]。因此,对CEL患儿进行及时和恰当的手术干预显得尤为重要。既往的研究显示,大部分CEL患儿手术后能够实现最佳矫正视力(best-corrected visual acuity, BCVA)的提高。Sen等[27]对43例(73眼)接受手术治疗的CEL儿童进行了(47.05±48.11)个月的随访,发现91.7%的患眼末次随访时BCVA较术前得到改善或保持稳定,其中61.64%的患眼(45/73眼)BCVA可以达到0.5以上。Chen等[28]的研究发现首诊年龄与术前BCVA是CEL患儿术后早期视力预后的预测因子,首诊年龄越大、术前BCVA越好的患儿术后视力预后越好。尽管如此,关于CEL患儿手术时机的选择,目前尚无统一的结论。由于儿童视觉系统的可塑性,早期手术可能有助于避免或减少晶状体脱位对视功能发育的损害,同时手术后也面临着晶状体调节能力的丧失、近视漂移和其他并发症风险。因此,未来还需要进一步研究CEL患儿手术时机选择的准则,为该类患儿的治疗提供更好的指导和支持。

3.2 先天性晶状体脱位术后屈光状态的变化

  晶状体作为眼球的主要屈光介质之一,其位置的改变往往导致严重的屈光不正,包括高度离焦、散光、屈光参差和单眼复视等,极大地影响患儿的视觉质量[29-30]。手术治疗对于改善CEL患儿的屈光状况具有显著效果。Meng等[31]的研究结果显示,虽然术后柱镜绝对值未见明显变化,但术后球镜绝对值下降幅度超过92%,从术前的9.50(2.50,18.00) D降至末次随访时的0.75(0.00,3.25) D。此外,Sen等[32]的研究发现接受经巩膜IOL缝线固定术的患儿术后的屈光变化呈现向近视漂移趋势,由术后6周的(–1.40±2.10) D显著增长至末次随访时的(–2.90±3.68) D。我们的前期研究纳入接受手术的学龄前CEL患儿42例42眼,手术年龄为(5.02±0.81)岁,术后每月近视漂移为(–0.05±0.09)D[33]。这些数据均表明,CEL患儿术后的屈光状态存在近视漂移趋势。这可能是由于CEL患儿仍处于生长发育阶段,随着年龄的增长,眼轴会继续增长,进而导致屈光状态向近视化进展[34]

3.3 先天性晶状体脱位的术后并发症

  随着现代显微手术技术的不断革新,CEL手术治疗的有效性和安全性得到了大幅度提高,然而,手术相关并发症依然存在,需要术后长期密切随访。CEL患者术后常见的并发症有线结暴露、IOL瞳孔夹持、IOL脱位、RD、眼内炎等。

3.3.1 线结暴露

  Solomon等[20]的回顾性研究报道了经巩膜 IOL缝线固定术后2年随访期间内,线结侵蚀的发生率高达73%。而在另一项大样本研究中,Uthoff 等[21]报告称,在接受经巩膜 IOL 缝襻固定术的患者术后1年的随访期间,线结暴露的发生率达到了17.9%。此外,Schechter[22]报道了因 10-0 聚丙烯缝线侵蚀结膜并暴露,病原菌通过暴露的缝线进入眼睛引起感染性眼内炎的病例。改良的无线结经巩膜 IOL缝线固定术能有效规避线结相关并发症[23,35],然而,未来仍需进行更为长期的大样本、多中心的随访观察来评估该术式的优势。

3.3.2 人工晶状体瞳孔夹持

  CEL 术 后 IOL 瞳孔夹持的发生率约为 9 % ~43.8%[27,31,36],其发生可能与术前晶状体脱位程度、IOL的类型、IOL光学面大小、IOL固定位置(距角膜缘位置)、术后前房深度、玻璃体的完整性等因素有关[24,31,36]。Jin等[36]观察了39例CEL术后发生IOL瞳孔夹持患者,发现这种并发症并未导致明显的视力下降,也没有引发明显的炎症反应,同时也没有观察到出血或继发性青光眼等其他并发症的出现。因此,IOL瞳孔夹持若对视力的影响不大及无其他严重并发症,可以不进行额外的干预处理。联合MCTR植入可以稳定和固定虹膜后方的IOL位置,降低IOL的移动度,从而降低CEL术后IOL瞳孔夹持的发生风险[36]。此外,采用襻更宽、光学面积更大的IOL,也可能是降低CEL患儿术后瞳孔夹持风险的一个很好的选择[36]

3.3.3 人工晶状体脱位

  IOL 脱位是CEL患儿术后严重并发症之一,这一问题在临床实践中备受关注。由于脱位的 IOL 可能导致视力下降、葡萄膜炎、玻璃体视网膜疾病等,因此,许多患者需要进行二次手术以复位或置换脱位的IOL。CEL术后IOL脱位发生率为3.9%~9.0%[27,31,37],发生时间从术后6个月至10余年不等,常见的原因包括IOL襻断裂、缝线断裂、术后眼部外伤等[31,37]。为了降低缝线断裂的风险,采用较粗的缝线进行IOL固定逐渐成为一种新的趋势,譬如用8-0或9-0缝线代替10-0缝线。然而,其优势还需要大样本的前瞻性随机对照研究的长期随访结果证实。Wang等[37]研究揭示了眼外伤是CEL术后IOL脱位的危险因素。同时,儿童患者的眼部仍在发育过程中,以及其活泼好动的生活方式,都可能增加CEL术后IOL脱位的风险。然而,目前关于CEL术后IOL脱位相关危险因素的研究还比较有限,这为未来的研究提供了方向。

3.3.4 视网膜脱离

  RD是CEL术后的严重并发症,可导致永久性视力损害,其发生率为3.4%~17.2%[38-40]。晶状体异位和悬韧带缺损会对玻璃体基底部产生持续牵拉,从而导致视网膜周边出现小的撕裂或裂孔,同时眼轴长度增加也会引起视网膜变薄,这些因素均容易引发RD[38]。此外,手术中对玻璃体的扰动会导致玻璃体视网膜牵引力增加和新的视网膜裂孔形成,这也被认为是术后RD的主要原因之一[40]。另外,针头在穿过巩膜时可能会扰乱玻璃体基底部的解剖结构,并容易在周围区域发生牵拉和断裂[40]。除此之外,年龄、严重晶状体脱位、高度轴型近视、完全的玻璃体切除以及术后眼部创伤史均被认为是CEL术后RD的危险因素[37-38,41-42]

4 总结与展望

  虽然CEL是一种罕见疾病,但其已经成为导致儿童视力损害的主要原因之一。随着公众健康意识的提高,人们对于CEL的关注日益增多。因此,在临床工作中,不断加深对CEL的认识,提高手术的安全性和疗效,防止术后并发症的发生,仍是当前CEL诊疗中面临的挑战。文章总结和探讨了CEL的手术方式及其预后,强调了术后长期严密随访的重要性,以便医患双方对疾病进行更好的管理,最终使患者获得最佳的临床转归。

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1、国家自然科学基金(81873673, 81900841);广东省自然科学基金(2021A1515011673, 2022A1515011181);广州市基础研究计划市校(院)联合资助项目(SL2023A03J00514)。
This work was supported by the National Natural Science Foundation of China (81873673, 81900841), Guangdong Basic and Applied Basic Research Foundation (2021A1515011673, 2022A1515011181), and the Guangzhou Basic Research Program, City & University (Institute) Joint Funding Project (SL2023A03J00514), China.()
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