单纯疱疹病毒性角膜炎内皮型药物治疗转归的动态观察

发布时间：2018-09-08 10:34

【摘要】：目的：应用共焦显微镜观察单纯疱疹病毒性角膜炎(Herpes simplex virus endothelitis; HSK)内皮型发病时角膜上皮细胞、角膜基质、内皮细胞及局部树突状细胞等的变化联合眼前段OCT对角膜的形态学变化进行动态观察,记录药物治疗转归,并为调整临床用药提供依据。方法：选择与我院就诊的HSK内皮型患者30例(30眼),其中男性21例,女性9例,平均年龄55岁(17-69岁)。发病时间最短1周,最长2月,平均为20天。根据HSK内皮型的分型,6例患者为扇形,其中4例有复发病史。17例为盘状,其中8例为既往有单疱病毒性角膜炎反复发作史,3例患者伴有继发性青光眼,2例患者伴有前房积脓。7例为弥散性,其中4例既往有单疱病毒性角膜炎反复发作史。入院后常规给予入院后常规给予抗病毒及抗免疫治疗,眼压升高者加用降眼压药物。裂隙灯显微镜常规检查,记录角膜水肿的范围、内皮面KP及皱褶等的变化。共焦显微镜检查,分别于药物治疗前、治疗7-14天、1月、3月时进行观察,分析角膜上皮细胞、角膜基质细胞、内皮细胞及KP、树突状细胞(Dendritic cells, DCs)、炎性细胞的变化,并根据情况调整用药。同时应用眼前段OCT观察角膜的形态变化。结果：裂隙灯显微镜检查：扇形及盘状HSK内皮型患者恢复速度较快,一般于用药7天角膜水肿基本消退,但可见到明显的KP,连续治疗2周后角膜可恢复透明,内皮面KP明显减少或消退。3例合并继发性青光眼的患者均于7天内眼压降至正常范围,停用降压药物后未见升高。2例伴有前房积脓的患者,与用药3-5后积脓消失,未再次出现。弥散性HSK内皮型患者恢复速度较慢,一般于用药后10-14天角膜水肿基本消退,连续治疗20-30天后角膜可恢复透明,内皮面KP明显减少或消退。30例患者随访期内均无再次复发。共焦显微镜检查：上皮细胞层：细胞水肿,体积增大,排列疏松,细胞核呈高反光,有时见大量体积较小、强反光的炎症细胞浸润。药物治疗7-14天,上皮细胞排列规则,体积恢复正常,细胞核呈低反光,炎症细胞明显减少或消失。树突状细胞：分布于角膜上皮细胞层、基底膜区、浅基质层约44μm范围内。药物治疗前与治疗后7-14天DCs无明显变化：角膜水肿区可见大量DCs聚集,呈特征性的树枝状高亮反光结构,并可见迁移的DCs；周边透明区DCs数量较多但树突不明显。随病情好转,药物治疗后1月、3月观察：树突状细胞数量减少,胞体及树突状反光逐渐降低,树突缩小。各时期DC细胞的密度,药物治疗前、治疗后7-14天、1月、3月分别为：(137±46)、(148±33)、(100±25)、(53±15)个/mm2,20例患者对侧健眼DCs的密度为：29±5个/mm2。HSK发病组DC数量大于对照组,两组之间的差异有统计学意义。药物治疗后DC数量减少,药物治疗后7-10天与药物治疗后1月、3月两两比较有统计学意义。基质层：基质细胞普遍体积增大,胞体变形,细胞质增多,胞内大量高反光颗粒普遍体积增大,而胞质反光较强,胞核与胞质不易区分,部分患者浅基质层难以分辨细胞形态。药物治疗1月,基质层结构规则,细胞核清晰可见,部分患者浅基质形成瘢痕呈现无结构状态。内皮细胞层：药物治疗前水肿角膜区内皮细胞无法成像,仅可见大量强反光团。透明区内皮细胞呈激活状态,细胞核可见,。药物治疗7-14天可获得较为清晰的角膜内皮图像：内皮细胞水肿,六边形结构改变,内皮细胞核可见并呈高反光,炎性细胞浸润,点空样改变等表现。药物治疗1月时：内皮细胞水肿减轻,不规则六边形细胞所占比例降低,炎细胞明显减少,并可见赘疣形成。药物治疗3月时,内皮细胞恢复六边形结构,排列规则,部分患者仍可见少量赘疣及KP存在,角膜内皮细胞密度2009.3±200个/mm2,对侧健眼2456.00±382个/mm2,差异有统计学意义。前段OCT检查：治疗前,角膜基质层厚度明显增加,反射强度较低且不均匀,内皮面可见高反光团及皱褶形成,角膜测厚为：686.31±167.54μm。。药物治疗7-14天后,角膜基质厚度降低,内皮面高反光团消失或变小,无皱褶形成。1月时角膜内皮面无高反光团,部分患者可见浅基质残留高密度的强反射带,瘢痕形成,角膜测厚为：516.69±59.58μm。结论：应用共聚焦显微镜联合眼前段OCT对HSK内皮型患者角膜各层进行活体的动态观察,对进一步了解其药物治疗过程中的病理变化及指导治疗,有效提高HSK内皮型的诊治水平,具有重要的临床意义。
[Abstract]:AIM: To observe the changes of corneal epithelial cells, corneal stroma, endothelial cells and local dendritic cells during the onset of herpes simplex virus endothelitis (HSK) with confocal microscope, and to observe the morphological changes of cornea with OCT in the anterior segment of the eye. Provide basis for adjusting clinical medication.
Methods: Thirty patients (30 eyes) with HSK endothelial type were selected, including 21 males and 9 females, with an average age of 55 years (17-69 years). There were 3 cases with secondary glaucoma and 2 cases with empyema in the anterior chamber. 7 cases were diffuse, of which 4 cases had a history of recurrent herpes simplex keratitis. Confocal microscopy was used to observe the changes of corneal epithelial cells, corneal stromal cells, endothelial cells and KP, dendritic cells (DCs), inflammatory cells before treatment, 7-14 days, 1 month and 3 months after treatment. At the same time, anterior segment OCT was used to observe corneal morphological changes.
Results: Slit lamp microscopy showed that the recovery rate of the patients with HSK endothelial type was faster than that of the patients with HSK endothelial type. Generally, the corneal edema subsided after 7 days of treatment, but obvious KP could be seen. After 2 weeks of continuous treatment, the cornea became transparent and the KP on the endothelial surface decreased or subsided significantly. The recovery rate of diffuse HSK endothelial type patients was slow, and the corneal edema basically subsided after 10-14 days of treatment. After 20-30 days of continuous treatment, the cornea could be restored to transparency, and the endothelial KP significantly decreased or subsided. No recurrence occurred during the follow-up period.
Confocal microscopy showed that the epithelial cell layer was edema, enlarged, loosely arranged, high reflective nucleus, and sometimes a large number of small, strongly reflective inflammatory cells infiltrated.
Dendritic cells were distributed in the epithelial layer, basement membrane area and superficial stroma of cornea within 44 microns. There was no significant change in DCs before and after treatment 7-14 days. There were a large number of DCs in the edema area of cornea with characteristic dendritic high reflective structure and migrating DCs. With the improvement of the disease, the number of dendritic cells decreased, the body and dendritic reflex gradually decreased, and the dendrites shrank. The density of DC cells in different periods before treatment, 7-14 days after treatment, 1 month and 3 months after treatment were (137 65507 The number of DCs in the group with (+5/mm2.HSK) was higher than that in the control group, and the difference between the two groups was statistically significant.
Stromal layer: the general volume of stromal cells increased, the body deformation, cytoplasm increased, a large number of high-reflective particles in the cell generally increased volume, and the cytoplasm was strong, the nucleus and cytoplasm were difficult to distinguish, some patients with superficial stroma difficult to distinguish cell morphology. Scar formation presents no structural state.
Endothelial cell layer: Before drug treatment, edema of corneal endothelial cells can not be imaged, only a large number of strong reflective masses can be seen. Inflammatory cell infiltration, dot-like changes and other manifestations. 1 month after treatment: endothelial cell edema reduced, irregular hexagonal cells decreased, inflammatory cells significantly reduced, and verrucous formation. 3 months after treatment, endothelial cells restored to hexagonal structure, regular arrangement, some patients still see a small number of verrucous and KP presence in the cornea. The density of skin cells was 2009.3 + 200 /mm2, and the contralateral healthy eyes were 2456 + 382 /mm2, the difference was statistically significant.
Before treatment, corneal stroma thickness was significantly increased, reflective intensity was low and inhomogeneous, high reflectors and folds were observed on the endothelial surface. Corneal thickness was 686.31 [167.54] micron. After 7-14 days of treatment, corneal stroma thickness decreased, high reflectors on the endothelial surface disappeared or diminished, and no folds formed. High reflective mass, some patients can see the residual high-density superficial stroma of strong reflex zone, scar formation, corneal thickness: 516.69 + 59.58 micron.
Conclusion: The dynamic observation of corneal layers in HSK patients by confocal microscope combined with ocular anterior segment OCT has important clinical significance for further understanding the pathological changes and guiding treatment in the course of drug therapy, and effectively improving the diagnosis and treatment of HSK endothelial type.
【学位授予单位】：济南大学
【学位级别】：硕士
【学位授予年份】：2011
【分类号】：R772.21

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