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暴露性角膜炎的现代治疗策略

Modern treatment strategies for exposure keratitis

来源期刊: 眼科学报 | 2021年5月 第36卷 第5期 364-370 发布时间: 收稿时间:2023/5/19 15:08:13 阅读量:3508
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暴露性角膜炎治疗方法研究进展
exposure keratitis therapy research prog
DOI:
10.3978/j.issn.1000-4432.2021.03.09
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暴露性角膜炎是角膜失去眼睑保护而暴露在空气中,引起角膜干燥、上皮细胞脱落进而继发感染的角膜炎症,多见于眼睑缺损、眼球突出、睑外翻、面神经麻痹、手术麻醉等。泪液的缺失、眼睑闭合不全、眼表暴露等因素皆会影响角膜健康,使其处于炎症、溃疡及穿孔的危险中。暴露性角膜炎治疗目的是去除暴露因素、保护角膜上皮和维持眼表湿润,目前常用的治疗手段有手术治疗与药物治疗,有些是暂时性的,有些是永久性的。
Exposure keratitis is an inflammation of the cornea that occurs when the cornea loses the protection of the eyelid and is exposed to air, resulting in dryness, epithelial exfoliation, and secondary infection. Most of them are found in eyelid defect, protopsis, eyelid ectropion, facial palsy, and anesthesia. Loss of tears, lagophthalmos and exposed ocular surface all affect the health of the cornea, putting it at risk of inflammation, ulceration, and perforation. The purpose of treatment is to remove exposure factors, protect the corneal epithelium and keep ocular surface moist.Currently, the commonly used treatments are surgical treatment and medical treatment, and some of them are temporary while others are permanent.
暴露性角膜炎是角膜失去眼睑保护而暴露在空气中,引起角膜干燥、上皮细胞脱落进而继发感染的角膜炎症。引起暴露的常见原因有眼睑缺损、眼球突出、睑外翻、手术源性上睑滞留或睑闭合不全。此外也可见于面神经麻痹、深度麻醉或昏迷。各种原因引起眼表的暴露和/或瞬目功能的损害,导致泪液过度蒸发及泪液流体动力分布异常,引起眼表上皮损害。病变多位于下1/3的角膜,初期角膜、结膜上皮干燥、粗糙,暴露部位的结膜充血、肥厚,角膜上皮逐渐由点状糜烂融合成大片的上皮缺损,新生血管形成,继发感染时则出现化脓性角膜溃疡的症状及体征。但不是所有的暴露性角膜炎都会继发感染,如眼睑关闭不全引起的暴露性角膜炎一般无继发感染,仅呈灰白色调,不会有急剧的改变,也无化脓现象。
暴露性角膜炎发生率较高,眼部并发症严重。Lehpamer等[1]对一所医院18岁及以上的暴露性角膜炎住院患者进行回顾性研究发现:暴露性角膜炎是一种可避免的并发症,但在住院患者中并不少见,几种最常见的危险因素是插管(36%)、面神经麻痹(16%)、夜间眼睑闭合不全(11%)和瘢痕性眼睑改变(8%)。本文将对暴露性角膜炎的现代治疗策略进行综述,旨在为临床治疗暴露性角膜炎提供参考。

1 治疗方法

暴露性角膜炎是威胁视力的疾病,可引起角膜严重的浸润和溃疡,若不及时治疗可导致视力下降甚至失明。根据角膜暴露的原因制定治疗方案,包括手术治疗与药物治疗,同时要考虑美观问题,选择对患者最有益、负面影响最小的治疗方式。

1.1 药物治疗

泪液分泌不足或泪液不够稳定都会导致眼表因缺乏泪液而干燥,影响角膜正常功能。人工泪液是人体泪液的替代品,可缓解角膜干燥。泪液补充剂配方中使用的增黏剂包括聚丙烯酸、羧甲基纤维素、右旋糖酐、透明质酸、HP-瓜尔胶、羟丙基甲基纤维素、聚乙烯醇、聚乙烯吡咯烷酮和聚乙二醇[2]。高黏度的眼药水在眼表的滞留时间长,但也可能造成一过性的视力障碍,并导致眼睑和睫毛上不必要的碎片以及耐受性和顺应性降低[2]。通常推荐夜间使用黏度很高的眼药水,白天使用低黏度的眼药水[2]。需注意的是,需长期使用人工泪液的患者应选用不含防腐剂的剂型,以避免防腐剂的毒性作用加重眼表和泪膜的损害。研究[3]表明:羟丙基纤维素植入物可持续润滑眼表并减少高达75%的人工泪液的使用,但有相当大比例的患者因出现视力模糊症状而停止使用。
睑板腺分泌的油脂物对维持泪液质量起关键性作用,睑板腺功能丧失,分泌异常会破坏泪膜的稳定性,进而导致眼表疾病,因此治疗睑缘炎是改善泪液质量的关键。睑缘炎的治疗方法多样,一项从1956年至2011年的关于治疗睑缘炎的研究[4]表明:没有充分的证据证实有哪种治疗方法是有效的。美国眼科学会[5]认为:尽管目前的证据水平不足,但口服强力霉素、阿奇霉素和米诺环素可能有效治疗睑板腺功能障碍。此外,使用抗生素治疗睑板腺功能障碍必须考虑其可能发生的不良反应,包括胃肠道不适,华法林使用者国际标准化比值(international normalized ratio,INR)升高和罕见不良反应如史提芬强生症候群(Stevens-Johnson syndrome)[5]

1.2 手术治疗

1.2.1 闭合眼睑
眼睑是角膜的屏障,眼睑闭合不全导致角膜暴露,影响眼表健康。
1.2.1.1 面神经麻痹
发生眼睑闭合不全最主要的原因是面神经麻痹。美国耳鼻喉科学会和美国神经病学学会强烈建议16岁及以上人群在Bell麻痹症状出现后在72 h内口服类固醇以增加面部功能恢复的可能性[6]。此外,MIME疗法(一种物理疗法)在改善面部功能方面也有成效,包括自我按摩、放松、呼吸、面部表情运动和字母、单词的发音[7]
对于面神经受损的患者,面神经修复或移植手术对恢复对称性的效果可能十分显著,但手术结果难以预测[8]。舌下神经移植和跨面神经移植都已被运用,相较而言后者能有更多自发和自然的面部运动[9]。在跨面神经移植中,使用的腓肠神经跨过面部,将健康一侧的冲动传导到对侧。咬肌神经-面神经吻合和跨面神经移植联合手术有助于恢复肌肉运动,预防肌肉萎缩[9]。已有使用尸体提供的腓肠神经进行脱细胞同种异体移植的案例,术后不会产生排斥反应[10]。对于已出现肌肉萎缩的患者还需要进行肌肉移植,目前有不需神经移植的颞肌转移和需要神经移植的股薄肌移植[11]。颞肌转移成功率高,转移后产生类似括约肌的运动使眼睑闭合,阻止角膜暴露,大部分患者能将咀嚼与眨眼分开,但可能影响面部骨骼发育,故不建议儿童患者使用[12]。股薄肌移植在跨面神经移植后几个月进行,需要10~18个月实现眼睑闭合,并且更可能产生联动[13]
1.2.1.2 面部烧伤
对于面部严重烧伤伴有瘢痕性眼睑闭合不全的患者,眼睑或面部移植可能成为一种选择。广泛的面部移植也包括眼睑移植,研究显示移植后眼睑功能正常,外观和眼睑闭合不全的症状也得到改善,但眼表恢复的细节未被描述。移植后,患者需终生接受免疫移植治疗,因为有排异的风险[14]。为避免排斥风险,使用自身移植物和人造肌肉治疗眼睑闭合不全已被提议[15]
1.2.1.3 眼睑闭合不全
肉毒杆菌毒素注射可使上睑下垂,但它有使上直肌麻痹,减弱贝尔反射的可能性。Naik等[16]建议使用更短的针头,在上睑提肌和上直肌连接不那么紧密接触的眼眶更前部注射肉毒杆菌毒素,在这种操作下未出现上直肌麻痹的现象,并且更短的针头眼球穿刺的风险也更低。但这只能暂时诱导上睑下垂,平均持续6.5~9周[8]
透明质酸注射于上眼睑以增加上睑重量可使上睑下垂,注射于下眼睑可起到支撑作用,治疗下睑退缩和外翻,利于眼睑闭合[17]。这种治疗方式简单安全,但价格昂贵,具有可逆性,当不再需要这种效果时,可注射透明质酸酶消除[17]
金种植体植入也是通过增加上睑重量将眼睑闭合,但在仰卧位时会恶化眼睑闭合不全,并可能发生过敏、炎症、移位甚至脱出的不良反应[18]。Lessa等[19]报告了一种用上睑提肌腱膜覆盖金种植体的技术,使得上眼睑更加美观,金种植体拥有足够的空间避免被挤出。距眼睑边缘2 mm和5 mm植入比较,较高位置的植入能获得更好的效果也更加美观[20]。与金相比,铂的密度更小,铂种植体植入的鼓起较小,挤压更少,可见度更低。铂植入物可制为链状或段状,可部分添加或移除,以方便后期手术的重量调整[21]
A?ik等[22]在家兔身上进行了一项实验,他将铁磁钢板附着于家兔眼睑,检测到健康一侧的眨眼而诱导麻痹一侧的眨眼,解决了增加上睑重量、重力作用下的眨眼延迟的问题,但此项技术暂时不适合用于人体。
眼睑弹簧不受重力影响,仰卧位时也能有效闭合眼睑[23]。上睑提肌和弹簧对抗打开眼睑,肌肉放松时(如睡觉)在弹簧作用下眼睑闭合[23]。但眼睑弹簧需要耐心调整以适应患者自身的情况,此外可能有弹簧挤压与感染的不良反应,金属疲劳可能会导致弹簧失效进而需要后续手术进行移除与更换[23-24]。最近使用的镍钴金属合金MP35N弹簧材料允许植入眼睑弹簧的患者安全地进行磁共振成像检查[23]。目前此项手术并不多见。
眼睑磁体的植入也已尝试,肌肉放松时磁体作用闭合眼睑,但发生不良反应与磁体挤压的概率很大[25]。用于检测健康一侧的电信号并迅速传递至患病一侧,诱导产生眨眼动作的电刺激器也正在研发中[26]
对于下睑退缩或松弛的患者,同样可以实行睑缘缝合术和外眦或内眦缩短术,但术后眼睑缝隙变小影响美观,可能加重眼睑瘢痕。外侧睑板条悬吊术是收紧下眼睑的常用方法,修正睑板条位置以及外侧睑板条悬吊联合下睑缩肌的技术也有被报道[27]。瘢痕性眼睑外翻则常需要皮肤、睑板移植以延长下眼睑[8]。有许多支撑下眼睑的方法用于改善眼睑闭合不全。d'Alcontres等[28]将上眼睑的眼轮匝肌肌瓣使用到下眼睑,有效改善眼睑闭合不全且具有良好的对称性。有研究[29]使用掌长肌腱或阔筋膜,通过睑板前固定在上颌骨额突和眶外骨外侧部支撑下眼睑。自体硬腭黏膜移植也是治疗下睑退缩的理想方法[30]。同种异体移植物的使用可避免进行手术以取得自体硬腭黏膜,但相比而言,自体移植的失败率更低,抬高下眼睑的效果更好[31]。在下眼睑下方添加支撑组织或抬高下眼睑下方的组织用于抬高下睑,可采用自体脂肪移植抬高面中部以支撑下眼睑减小向下拉力[32]。研究[33]表明:硬腭黏膜移植可优化面中部抬高手术的效果,并进行硬腭移植+外眦悬吊术+面中部提升复合手术和骨膜下安多泰植入面中部提升下眼睑,都达到令人满意的效果[34]
1.2.1.4 暂时性睑缘闭合
暂时性睑缘闭合也常用于治疗暴露性角膜炎。使用氰基丙烯酸酯胶黏合眼睑可使眼睑快速闭合,但粘合后难以进行眼表检查,干后的氰基丙烯酸酯胶可能摩擦眼表,划伤角膜,其持续时间也不可控[35]。氰基丙烯酸酯胶也可用于将2颗空心小珠子或小管黏至上下眼睑,通过珠子或小管带动眼睑闭合与打开[36]
暂时性睑缘缝合术在施行后通过调节垫片或小管仍可对眼表进行检查,一些学者[37]认为垫片会导致皮肤破坏,眼睑边缘不整及炎症等不良反应而不使用垫片。将缝线穿过缝合在皮肤上的小管可以避免打开眼睑时拉扯眼睑缝线的疼痛[38]。通过松解缝合在眼睑皮肤上垫片的缝线使开关眼睑更加方便,无须松紧眼睑缝线[39]
为延长、降低上眼睑,可使用全厚或分层眼睑切开术[40]。上睑提肌延长术和Müller肌切除术也可用于延长上睑,但手术并未改善眼轮匝肌功能,无和上睑提肌相拮抗的力作用,因此眼睑闭合不全并未完全改善[41]
1.2.2 其他手术
闭合泪点、泪小管可阻止泪液排出,保持眼表泪量。泪点栓塞、泪小管栓塞最常见的并发症是栓子脱出,其发生率约为40%,其次是溢泪、刺激症状和泪小管炎[42]。有一新型栓子,中间细,两头粗,栓塞到位后中间细的部分会膨胀,从而降低脱出率[43]。泪点灼烧术和泪小管切除术也可用于阻断泪道,达到维持眼表泪量的目的[44]
另一仅推荐用于严重干眼患者的治疗方式为植入连续输送人工泪液的机械泪管。贮液器植入腹前部皮下,导管经皮下引至上结膜穹,以1 mL/min (1.5 mL/d)的速度连续递送人工泪液,每40 d对贮液器进行补充,但可能有皮肤溃疡与感染的并发症[45]
以上方法不能增加自身泪液分泌量,而唾液腺移植可从根源解决泪液缺乏的问题。其中,腮腺管异位移植失败率约为50%,因分泌液体过多有溢泪的并发症,就餐时味觉刺激移植的唾液腺分泌,溢泪更为严重[46]。舌下腺移植坏死率高,二者都不建议使用[47]。颌下腺移植于1986年首次实行,颌下腺被切除移植至颞部并进行血管吻合,颌下腺导管引入上穹窿结膜囊内[48]。手术成功率为70%~80%,5年内存活率为66%~72%,效果良好[47-48]
颌下腺导管引至结膜上穹,分泌液体可由重力作用扩散至眼表,无须眨眼辅助,移植腺体切除了神经,味觉不会刺激分泌[48-49]。术后仍会出现溢泪问题,有建议进行部分颌下腺移植以避免溢泪[49]。研究[50]显示:移植后颌下腺所分泌液体的渗透压和蛋白质浓度高于正常颌下腺液但低于正常泪液。分泌液体的低渗透压易导致角膜微囊状水肿,有视力恶化的情况出现,目前仅推荐用于Schirmer<1 mm的严重干眼患者[47]

1.3 人工眼表覆盖物

除眼睑闭合覆盖眼表外,人工覆盖物也可用于覆盖眼表,对眼表疾病的控制起重要作用。目前较为常用的有眼用润滑剂和凝胶,特别是在重症监护环境中[8]。一项研究[51]表明眼睑贴合的患者发生角膜擦伤的可能性是仅接受眼部润滑患者的2倍。
营造水分室(即湿房)也可达到湿润眼表、治疗疾病的效果,可用带有湿润纱布或覆盖聚乙烯薄膜的泳镜制成[52]。一项比较眼部润滑剂、软膏与水分室的试验[52]发现:水分室并发症较少,所需护理时间更少,能够更好地保护眼表。市售或定制的湿房镜通过紧贴眼睛,延缓泪液蒸发,有助于维持泪膜稳定,改善干眼症状[53]。有报道定制3 D打印的湿房镜比市售的更有效[54]。电刺激泪腺以产生泪液与泪腺的移植和再生也正在研究当中[6]
使用巩膜镜可起到矫正不规则角膜,改善屈光不正和保护眼表的作用。商业制造和定制的高透氧透气性的巩膜镜均可供选择[8]。巩膜镜的使用需要训练,研究[55]表明持续佩戴有促进角膜上皮再生和提高视力的作用。持续佩戴巩膜镜时可通过每天向流体室内注入不含防腐剂的莫西沙星降低角膜感染率,可安全的持续佩戴[56]
绷带镜是一种治疗性角膜接触镜,起减轻眼部疼痛、机械性保护角膜上皮和促进角膜愈合等作用[57]。目前,角膜绷带镜已广泛运用于临床,在治疗眼表疾病中起重要作用。硅胶水凝胶绷带隐形眼镜材料本身含有许多微小的硅氧通道,使分子氧可以自由透过绷带镜[58]。此外,硅材料还表现出良好的吸水能力[58]。因此,硅可以帮助锁住水分,模仿脂肪层,从而减少泪水蒸发、改善干眼症状,并有促进角膜伤口愈合和增加泪膜稳定性的次要作用[58]。但对于接受绷带隐形眼镜的患者,强烈建议进行严格的随访程序[59]。交联巯基羧甲基透明质酸液体凝胶是一种眼绷带凝胶,同样能起机械性屏障、加速角膜缺损愈合的作用,但缺点是在眼表面滞留时间短[60]。放置冷冻保存羊膜(cryopreserved amniotic membrane,CAM)不但可以起到绷带镜的保湿和屏障作用,还有控制眼表炎症作用,CAM已被证明可促进眼表健康的恢复,减轻眼部不适症状和体征[61-62]

2 结语

治疗暴露性角膜炎的方法有很多,目前很多治疗方式如植入眼睑弹簧等均具有一定局限性,难度大而难以普遍施行;还有很多治疗方式如电刺激器正在研究中,尚未使用于人体。传统的睑缘缝合术需要患者经历手术缝线、拆线,给美观带来影响,可能加重眼睑瘢痕,其他很多更有效,对外观影响更小的治疗方法正在研究中。选择一种或多种最适合患者的治疗方法是医生的责任,这需要医生考虑患者的身体因素、病例情况、术后可能产生的并发症以及患者诉求。在治疗疾病的同时,也应尽量保证患者的美观要求。
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1、汤书仪.适用于全麻手术的新型眼部护理装置的研制与应用效果[J].医学理论与实践,2022,35(16):2879-2880+2876.
2、李梵英.全麻手术后暴露性角膜炎治疗的研究进展[J].湖北职业技术学院学报,2022,25(3):103-107.
3、程熠,宋金妹,冯毅承等.全身麻醉术后患者视物模糊的研究进展[J].中国乡村医药,2023,30(18):77-78.
1、国家自然科学基金 (81660158);江西省重点研发项目 (20181BBG70004);江西省杰出青年人才计划 (20192BCBL23020); 江西省基层卫生适宜技术“星火推广计划”项目(20188003);江西省卫计委科技计划面上项目 (20175116, 20201032);江西省卫计委中医药科技计划项目 (2018A060)。
This work was supported by the National Natural Science Foundation (81660158), Key Research Foundation of Jiangxi Province (20181BBG70004), Excellent Talents Development Project of Jiangxi Province (20192BCBL23020), Grassroots Health Appropriate Technology “Spark Promotion Plan” Project of Jiangxi Province (20188003), Health Development Planning Commission Science Foundation of Jiangxi Province (20175116, 20201032), and Health Development Planning Commission Science TCM Foundation of Jiangxi Province (2018A060), China.()
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    主办:中山大学
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    主办:中山大学
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