深板层角膜移植联合抗病毒药物治疗严重基质坏死型单纯疱疹病毒性角膜炎的临床观察

Deep anterior lamellar keratoplasty combined with antiviral therapy in the treatment of severe herpes necrotizing stromal keratitis

目的探讨改良深板层角膜移植术（DLKP）联合抗病毒药物治疗严重基质坏死型单纯疱疹病毒性角膜炎（HSK）的临床效果。方法回顾性病例系列研究。收集山东省眼科医院2007年4月至2015年4月收治的应用抗病毒药物治疗1周无效的严重基质坏死型HSK患者50例（50只眼），其中男性33例，女性17例；年龄（49±13）岁。术前应用角膜刮片、激光共聚焦显微镜检查排除真菌、细菌、棘阿米巴等其他感染，并检查角膜内皮细胞密度〉1 500个/mm2；眼前节相干光层析成像术（AS-OCT）检查角膜浸润深度及剩余角膜厚度。患者接受改良的DLKP术治疗，术后给予抗病毒药物和低剂量的糖皮质激素，定期随访。观察术中及术后角膜植片愈合情况，免疫排斥及病毒复发等并发症出现。结果50例患者病史均超过4个月，主要表现为持续性角膜深部溃疡，直径平均5 mm，入院抗病毒治疗无效或者溃疡加重。其中23例（46%）患者溃疡达深基质层，剩余角膜组织厚度仅为角膜厚度的1/5，9例（18%）发生后弹力层膨出，濒于穿孔。AS-OCT检测浸润累及角膜深度（265±84）μm，其中36例（72%）患者角膜溃疡浸润深度大于2/3角膜。角膜刮片均未见真菌、细菌及阿米巴包囊，微生物培养阴性。通过改良的DLKP手术，所有基质坏死型HSK患者炎性反应均得到控制，术中无一例植床穿孔，其中6例（12%）患者术后因角膜植片上皮愈合缓慢，再次行羊膜移植治疗后愈合，2例（4%）活动期患者术后2 d发生单纯疱疹病毒活化复发，及时停用糖皮质激素，应用抗病毒药物治疗后得以控制，42例（84%）患者术后1~2周角膜植片恢复透明。术后2年随访期间，10例（20%）患者发生病毒复发；2例（4%）出现免疫排斥反应。结论严重基质坏死型HSK应用DLKP术联合抗病毒药物治疗可以达到治愈溃疡的目的。

ObjectiveTo evaluate the efficacy of modified deep lamellar keratoplasty （DLKP） combined with antiviral medications for severe herpes necrotizing stromal keratitis.MethodsRetrospective case series study. Modified DLKP was performed in combination with antiviral medications in fifty patients （50 eyes） with severe necrotizing stromal keratitis, which was unresponsive to systemic and topical antiviral treatment for 1 week, at Shandong Eye Hospital. Before surgery, the operated eyes were examined using slit-lamp microscopy. The size of corneal ulceration and inflammatory infiltration and the depth of ulceration were observed in all of the patients. Corneal scraping and microbial culture and confocal laser scanning microscopy were used to exclude fungal, bacterial, Acanthamoeba, or other infections, and check the number of corneal endothelial cells. Anterior segment optical coherence tomography was used to examine the depth of infiltration, especially the thickness of the remaining cornea below the deepest ulceration. Antiviral drugs were used topically and systemically to control the infection and inflammation. Postoperatively, both antiviral drugs and low-dose corticosteroids were used. The ocular inflammation, corneal graft status and viral recurrence were monitored intraoperatively and postoperatively.ResultsAll of the fifty patients showed obvious inflammatory infiltration and stromal ulcers, and the corneal stroma in 23 patients （46%） remained less than 1/5 of the corneal thickness. Nine （18%） of the patients presented with descemetocele. The depth of infiltration ranged from 128 μm to 519 μm [mean, （265±84） μm]. The depth of corneal ulcers was deeper than 2/3 of the corneal thickness in 36 eyes （72%）. The endothelial cells were visible in 26 eyes. The density of endothelial cells ranged from 1 275 cells/mm2 to 2 994 cells/mm2 [mean, （2 053±507） cells/mm2]. No fungal or bacterial infection was detected by corneal scraping. The microbial culture results were negative. All the inflammations in patients with severe herpes necrotizing stromal keratitis were under control by DLKP. No intraoperative corneal perforation occurred, and 6 eyes （12%） healed following amniotic membrane transplantation due to slow corneal epithelial healing. The infection was exacerbated two days following the surgery in two eyes （4%）. These infections were controlled with enhanced antiviral medications in addition to the immediate withdrawal of corticosteroids. The corneal grafts returned to transparency at 1-2 weeks in 42 eyes （84%）. Ten eyes （20%） exhibited recurrence due to medication withdrawal without the doctors＇ advice and a lack of regular visit during 2-year follow-up. Two patients （4%） developed stromal graft rejection for the same reasons.ConclusionsDLKP can achieve the results of ulcer healing for severe herpes necrotizing stromal keratitis. Combined antiviral therapy and close follow-up can reduce the viral recurrence.