【作者】 邸岩；

【导师】 张岩；

【作者基本信息】 吉林大学 ， 临床医学， 2012， 硕士

【摘要】 角膜感染为准分子激光上皮下角膜磨镶术（laser subepithelial kerato-mileusis, LASEK）术后最严重的并发症之一，常可引起视力的严重损害。导致LASEK术后疱疹病毒感染的主要原因有：手术刺激和准分子激光照射诱发潜伏的疱疹病毒活化；术后局部长期应用皮质类固醇激素；也可能是上述因素综合作用的结果。及时诊断和有效的抗病毒治疗是避免视力严重损害的关键。病毒分离培养曾被公认为诊断病毒感染的金标准，但其存在一定限制，不适合快速诊断，而多重PCR通过一次反应，检测多个目的基因，可能会成为眼部病毒感染有效的诊断方法。LASEK术后疱疹病毒感染性角膜炎的治疗方法主要是根据病情局部及全身联合应用抗病毒药物治疗。目的：本研究应用病毒分离培养和多重PCR方法检测LASEK术后疱疹病毒感染，比较不同方法检测的敏感性和精确性，探讨其发病相关因素及药物联合治疗效果，为临床诊治提供参考。方法：对2006年1月至2009年7月于我院行LASEK手术896例（1782眼）中，术后疑为疱疹病毒性角膜炎的9例（15眼）患者进行分析。记录所有患者临床表现，采集泪液和角、结膜拭子，应用病毒分离培养和多重PCR法进一步明确诊断同时确定感染病毒种类。局部及全身联合应用抗病毒药物治疗。结果：LASEK术后单纯疱疹病毒性角膜炎（herpes simplex keratitis, HSK）病变形态不典型，呈单个或多个散在的点片状浸润，角膜上皮水肿明显，边界不清，容易形成瘢痕。病毒分离培养6眼结果阳性，为单纯疱疹病毒1型(herpes simplex virus type1, HSV-1)感染，9眼结果阴性。多重PCR检测13眼结果阳性，其中12眼HSV-1感染，1眼水痘带状疱疹病毒（varicella-zoster virus，VZV）感染。多重PCR方法比病毒分离培养法敏感，病毒检出率高。经抗病毒治疗后，8例（13眼）角膜恢复透明，1例（2眼）残留Ⅰ级和Ⅱ级角膜上皮下混浊（Haze）。结论：(1)LASEK术后角膜病毒感染以HSV-1常见，伴皮肤疱疹时高度怀疑VZV感染。(2)术中准分子激光消融前弹力层和前部角膜基质层，发生疱疹病毒感染时病变形态不典型。(3)应用多重PCR方法诊断，省时省力，阳性率高，可确定感染病毒种类，是适合眼部疱疹病毒感染的诊断方法。(4)联合应用抗病毒药物可加快病变愈合，缩短病程。(5)术前详细询问病毒感染既往史也很重要。更多还原

【Abstract】 Infectious keratitis is one of the most serious complications after lasersubepithelial keratomileusis(LASEK). Herpes virus infection followingLASEK often leads to serious damage of vision, the main causes of virusinfection including: stimulation of corneal by surgery and the recurrence oflatent herpes virus irradiated by excimer laser; long-term topical administrationof steroids eye drops, or the interaction of all above factors. Once the herpetickeratitis appears, early and correct diagnosis and management are critical forrescuing the visual acuity. Viral culture has been recognized as the goldstandard for diagnosing herpes virus infection. But it has limitation, it’s notsuitable for rapid diagnosis. Multiplex PCR was used to amplify several targetgenetic segments and was regarded as a sensitive method to detect virus.Treatment consist of topical and systemic antiviral therapy.Objective:Viral culture and multiplex PCR was used to detect herpes virus. Thesensitivity and accuracy of Multiplex PCR was compared to that of viral culture.The etiology and the effect of combination of antiviral therapy on herpetickeratitis after LASEK were investigated.Methods:A retrospective study was carried out on9patients (15eyes) whodeveloped viral keratitis at one to three months postoperative from2008to2010in our cohort. The diagnosis was evaluated primarily according to theclinical findings and then the multiplex PCR and viral culture were used tofurther determine the diagnosis and identify the categories of viruses. The tears,corneal or conjunctival swabs were used as specimens. Furthermore, the effect of combining antiviral therapy on herpetic keratitis was testified.Results:Herpes simplex virus type1(HSV-1) was identified by viral culture in6eyes (6/15,40%). Thirteen of15eyes were positive by multiplex PCR, amongthem HSV-1was identified in12eyes while varicella-zoster virus (VZV) wasidentified in one eye. The results indicate that multiplex PCR was moresensitive than viral culture. The cornea clarity was restored in8patients（13eyes）after antiviral therapy. Only one patient（2eyes）remained Haze (grade Iand II respectively).Conclusions:(1) Our study indicates that HSV-1is the most common reason of viralinfection after LASEK. VZV should be considered when skin eruptiondeveloped.(2) Because the Bowman’s layer and anterior stroma were ablatedby excimer laser after LASEK, the typical dendritic ulcer or geographic ulcer inthe cornea were not observed in our study. The clinical observations of thesepatients showed a mild irritation with atypical single or diffused lesions, easilyto develop Haze. So it is difficult to make diagnosis on the basis of the atypicalclinical findings.(3) Multiplex PCR is an accurate and rapid method todetermine the diagnosis and identify the categories of various viruses using aminute amount of specimen.(4)The combination of therapy is effective toherpetic keratitis after LASEK and could be shorten the duration of active viraldisease.更多还原