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中华眼科医学杂志(电子版) ›› 2024, Vol. 14 ›› Issue (02) : 95 -101. doi: 10.3877/cma.j.issn.2095-2007.2024.02.006

病例报告

眼部移植物抗宿主病角膜穿孔合并真菌性角膜炎1例
沈重成1, 李方烃2,()   
  1. 1. 100730 北京医院 国家老年医学中心 中国医学科学院老年医学研究院眼科
    2. 10044 北京大学人民医院眼科、眼视光中心 眼病与视光医学研究所 视网膜脉络膜疾病诊治研究北京市重点实验室 北京大学医学部眼视光学院
  • 收稿日期:2024-04-14 出版日期:2024-04-28
  • 通信作者: 李方烃
  • 基金资助:
    国家重点研发计划资助项目(2020YFC2008200); 北京大学人民医院研究与发展基金项目(RDY2020-03)

One case of eye graft-versus-host disease with corneal perforation and fungal keratitis

Zhongcheng Shen, Fanghan Li()   

  • Received:2024-04-14 Published:2024-04-28
  • Corresponding author: Fanghan Li
引用本文:

沈重成, 李方烃. 眼部移植物抗宿主病角膜穿孔合并真菌性角膜炎1例[J]. 中华眼科医学杂志(电子版), 2024, 14(02): 95-101.

Zhongcheng Shen, Fanghan Li. One case of eye graft-versus-host disease with corneal perforation and fungal keratitis[J]. Chinese Journal of Ophthalmologic Medicine(Electronic Edition), 2024, 14(02): 95-101.

患者,女性,47岁。2022年9月患者因左眼眼痛和眼干1年余病史,近1个月余症状加重并伴视力下降,遂就诊于北京大学人民医院眼科。主诉1年前因左眼眼痛、眼干及雾状遮档,伴视力下降,就诊于外院,诊断为左眼角膜炎,行左眼羊膜覆盖术治疗与药物治疗(药品治疗与方法不详),术后症状有所好转。9个月前出现左眼眼前白色雾状遮挡,药物治疗后轻微缓解。1个月前再次出现左眼眼痛和眼干,症状逐渐加重,伴视力显著下降。既往2018年诊断为急性淋巴白血病后行异基因造血干细胞移植,曾出现肝脏、肺部、关节及口腔等多器官排异反应,目前全身排异反应控制良好,已停用全身激素及免疫抑制剂治疗。结合病史,遂给予左眼配戴角膜绷带镜,左氧氟沙星滴眼液(日本参天制药株式会社生产)点眼,4次/d;妥布霉素地塞米松滴眼液(美国爱尔康公司生产)点眼,2次/d;玻璃酸钠滴眼液(日本参天制药株式会社生产)点眼,6次/d;小牛血去蛋白提取物眼用凝胶(沈阳兴齐眼药公司生产),3次/d;更昔洛韦眼用凝胶(湖北科益药业公司生产),3次/d。患者右眼视力0.3,最佳矫正视力0.6;左眼视力眼前手动,矫正不提高,光感光定位正常;右眼眼压21 mmHg(1 mmHg=0.133 kPa),左眼眼压23 mmHg。右眼睑结膜瘢痕化,角膜透明,角膜上皮点状染色,前房中等深度,虹膜纹理清,晶状体介质清,视网膜在位,左眼睑结膜瘢痕化,结膜轻度充血,绷带镜在位,角膜多个浸润病灶,边界稍模糊,角膜浅层新生血管,中央角膜明显变薄,角膜后白色色素沉着,前房积脓1 mm,眼底窥视不清。见图1A。结合病史及查体结果诊断为右眼角膜炎原因待查,双眼移植物抗宿主病。鉴于不除外感染性角膜炎,除去患者绷带镜,更改治疗为给予患者左氧氟沙星滴眼液点眼,4次/d;更昔洛韦眼用凝胶,3次/d;左氧氟沙星眼膏(日本参天制药株式会社生产),右眼每晚滴眼;更昔洛韦片(湖北科益药业),1000 mg口服,3次/d。患者2周后复诊,左眼中央角膜溶解明显,下方浸润灶明显扩大,前房积脓加重。见图1B。角膜刮片可见真菌,角膜刮片培养结果提示近平滑念珠菌阳性。修正诊断为左眼真菌性角膜炎,双眼移植物抗宿主病。给予左眼1%伏立康唑滴眼液(医院自制)点眼,1次/h;伏立康唑(北京博康健基因科技有限公司生产),200 mg口服,2次/d;治疗2 d后角膜浸润灶减小,同时角膜基质溶解明显,后弹力层膨出,前房积脓减少。见图1C。治疗3 d后,左眼角膜穿孔,为患者行左眼穿孔修补联合结膜瓣遮盖术,术中可见角膜中央偏下方1.5 mm左右穿孔,取下方球结膜做4 mm宽度桥状结膜瓣,取少量tenon囊组织使用10-0不可吸收缝线将其填塞缝合于穿孔处角膜,10-0不可吸收缝线间断缝合将桥状结膜瓣缝合于角膜,将线结转入角膜基质,10:00时钟位角膜缘做侧切口,注入眼内冲洗液建立前房检查穿孔处水密封,前房形成良好。术后继续给予左眼1%伏立康唑滴眼液点眼,1次/h;伏立康唑,200 mg口服,2次/d,术后2周左眼角膜上皮愈合良好,结膜瓣在位,前房存在。见图2A。术后6周左眼前房消失,溪流征阳性。见图2B。再次行角膜穿孔修补,术中取约150 μm厚度微小切口基质透镜取出术基质微透镜片,裁剪至1.5 mm×1.5 mm,将2针10-0不可吸收缝线穿过基质片后,2针呈90°,缝合固定于穿孔处角膜基质,10:00时钟位侧切口注入眼内冲洗液建立前房检查穿孔处水密封,前房形成良好。见图2C。术后2周复查,再次发现前房消失,溪流征阳性。第三次行角膜穿孔修补,术中采用多层4层羊膜,填塞于角膜穿孔处,10-0不可吸收缝线间断缝合8针于角膜基质,10:00时钟位侧切口注入眼内冲洗液建立前房检查穿孔处水密封,前房形成欠佳,前房注入无菌空气,术毕。术后1周,患者左眼前房偏浅,溪流征仍阳性。见图2D。为进一步控制病情,患者行第四次角膜穿孔修补。术中使用3 mm角膜环钻环切至约1/2角膜剩余厚度基质,手动剖切角膜基质接近后弹力层,使用3.25 mm角膜环钻冲切2片厚度约120 μm微小切口基质透镜取出术角膜基质微透镜片,使用10-0不可吸收缝线将2片角膜基质重叠间断缝合8针于角膜植床,10:00时钟位侧切口注入眼内冲洗液建立前房检查穿孔处水密封,前房形成欠佳,前房注入无菌空气,术毕。术后左眼使用重组牛碱性成纤维细胞生长因子滴眼液(珠海亿胜生物公司生产)点眼,6次/d,左眼他克莫司滴眼液(日本千寿制药株式会社生产)点眼,2次/d;左眼1%伏立康唑滴眼液点眼,6次/d,逐渐减量。术后3个月,左眼视力眼前手动,角膜表层新生血管,中央植片在位,角膜缝线在位,角膜植片及部分基质白斑,前房不浅,角膜荧光素钠染色溪流征阴性。见图2E。前节光学相干断层扫描成像显示角膜植片愈合良好。见图3。患者继续使用无防腐剂人工泪液,左眼按需给予他克莫司滴眼液点眼,2次/d。此后患者长期眼科门诊随访,病情稳定。左眼使用重组牛碱性成纤维细胞生长因子滴眼液点眼,6次/d,左眼他克莫司滴眼液点眼,2次/d;左眼1%伏立康唑滴眼液点眼,6次/d,逐渐减量。术后3个月,左眼视力眼前手动,角膜表层新生血管,中央植片在位,角膜缝线在位,角膜植片及部分基质白斑,前房不浅,角膜荧光素钠染色溪流征阴性。见图2E。前节光学相干断层扫描成像显示角膜植片愈合良好。见图3。患者继续使用无防腐剂人工泪液,左眼按需给予他克莫司滴眼液点眼,2次/d。此后患者长期眼科门诊随访,病情稳定。

图1 裂隙灯显微镜下双眼移植物抗宿主病患者药物治疗前后的眼前节彩色照相(×10) 图1A示患者初诊眼前节彩色照相,可见左眼绷带镜在位,角膜多个浸润病灶,边界稍模糊,角膜浅层新生血管,中央角膜明显变薄,角膜后白色色素沉着,前房积脓;图1B示药物治疗2周后眼前节彩色照相,可见左眼中央角膜溶解明显,下方浸润灶明显扩大,前房积脓加重;图1C示抗真菌治疗2 d后眼前节彩色照相,可见角膜浸润灶减小,角膜基质溶解明显,后弹力层膨出,前房积脓减少  图2 裂隙灯显微镜下双眼移植物抗宿主病患者角膜穿孔术后的眼前节彩色照相(×10) 图2A和图2B分别示患者角膜穿孔结膜瓣覆盖术后2周和术后6周的眼前节彩色照相,2周时结膜瓣在位,前房存在;6周时角膜表层新生血管化,前房消失;图2C示患者第二次角膜穿孔修补后1 d的眼前节彩色照相,可见角膜修补片及缝线在位;图2D示患者第三次羊膜移植穿孔修补术后1周的眼前节彩色照相,可见羊膜植片及缝线在位,前房浅;图2E示患者第四次角膜移植穿孔修补术后3个月的眼前节彩色照相,可见角膜表层新生血管,中央植片在位,角膜缝线在位,角膜植片及部分基质白斑  图3 双眼移植物抗宿主病患者角膜移植术后3个月的前节光学相干断层成像 可见角膜植片愈合良好
表1 移植物抗宿主病临床表现的分级
表2 慢性移植物抗宿主病结膜病变的分级
表3 眼部移植物抗宿主病患者发生角膜穿孔的文献汇总表
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