准分子激光角膜屈光手术后疱疹病毒性角膜炎的研究进展

准分子激光角膜屈光手术后并发单纯疱疹病毒（HSV）感染常可引起视力的严重损害。导致准分子激光角膜屈光手术后并发疱疹病毒感染的主要原因有：准分子激光照射和手术刺激诱发潜伏的HSV活化;术后局部长期应用糖皮质激素类滴眼液,也可是上述因素综合作用的结果。及时诊断及有效的抗病毒治疗是恢复视力的关键,血清抗体检测、病毒培养、角膜上皮刮片、组织细胞切片和Negative染色、聚合酶链反应（PCR）等实验室检测均存在一定的限制,而多重PCR可能会成为有效的实验室诊断方法。准分子激光角膜屈光手术后并发HSV感染的治疗方法主要是根据病情局部或全身应用抗病毒药物,对于术前曾有单纯疱疹病毒性角膜炎（HSK）病史的患者围手术期局部给予抗病毒药物可显著降低准分子激光角膜屈光手术后疱疹病毒感染的发生率。根据近年来国内外相关的临床研究及基础研究,对准分子激光角膜屈光手术后合并HSK的病因、诊断、治疗及预防进行综述。     

眼科手术后继发单纯疱疹性角膜炎的研究进展

眼科手术后继发单纯疱疹病毒性角膜炎是影响手术效果的重要因素。眼科手术往往在一个健康的角膜上进行,个别地方医疗纠纷时有发生,应当引起广大医务工作者的足够重视!现将术后继发单纯疱疹病毒性角膜炎的原因、临床表现、诊断及治疗的研究进展做一综述。     

The differential regulation of nitric oxide by Herpes simplex virus-1 and -2 in a corneal epithelial cell line

Herpes simplex keratitis s a significant cause of blindness worldwide. Nitric oxide (NO) has been shown to play a role in non-specific defence mechanisms and cell signalling in bacterial and parasitic infections. We investigated if Herpes simplex virus (HSV) isolated from keratitis could induce NO production. Human corneal epithelial cells were infected with high (multiplicity of infection; MOI 0.4) and low (MOI 0.04) HSV-1 and HSV-2 concentrations. Culture supernatants were collected at 1 h, 4 h, 8 h, 12 h and 24 h postchallenge. Samples were prepared by removal of proteins by ultrafiltration. Production of NO was measured using nitrite and nitrate assays. Herpes simplex virus-1 downregulated the production of NO, while HSV-2 upregulated NO production. Downregulation of NO could be a survival strategy against the cytotoxic action of NO, to eliminate infected cells. Upregulation of NO production may be associated with the presence of glycoproteins on the viral coat, which have been shown to induce NO in other disease conditions. Further studies are required to confirm the role of NO in viral keratitis.     

板层角膜移植术治疗基质型活动期单纯疱疹性角膜炎的临床价值

客观评估板层角膜移植术 (Lamellarkeratoplasty ,LKP)治疗基质型活动期单纯疱疹性角膜炎 (herpessimplexkeratitis ,HSK)的临床价值。方法 :对 71例 ( 71只眼 )HSK基质型活动期患者分两组 ,一组 ( 33例 )行LKP ,另一组 ( 38例 )行穿透性角膜移植术 (pene tratingkeratoplasty ,PKP) ,比较两组病人术后的疗效与并发症。结果 :LKP组术后在视力、角膜移植片排斥反应发生率、原发病复发率与内眼手术并发症发生率等方面均明显优于PKP组 (P <0 0 1)。结论 :在适应症范围内 ,成功的LKP具有清除病灶彻底、排斥反应发生率低、无内眼手术并发症等优点 ,是治疗基质型活动期HSK的理想方法。     

单纯疱疹病毒性角膜炎动物模型制备

单纯疱疹病毒性角膜炎(herpes simplex keratitis,HSK)是由单纯疱疹病毒Ⅰ型(herpessimplex virus type Ⅰ,HSV-1)感染引起的具有高复发率、高致盲率及难根治性特点的疾病,可导致角膜溶解、新生血管形成及溃疡穿孔,是目前角膜病中最常见的致盲眼病之一.本文参考目前国内外实验研究时使用的各种HSK动物模型建模方法来进行综述,如建立原发感染模型的划痕法、环钻法、外植体培养法以及潜伏感染模型和诱导复发模型的建立方法.力求探索如何建立一种可靠的HSK动物模型,在为研究人类HSK发病机制、药物治疗和对比以及角膜移植等方面均有重要意义.     

单疱病毒性角膜炎新分类指导临床实践

目的评价Holland等(1999)提出的单疱病毒性角膜炎(HSK)新分类法在指导临床诊治HSK的意义。方法应用Holland等的新分类法,诊断及治疗门诊各类型HSK患者204例,观察这些患者的诊断及治疗效果。本组未包括神经营养性角膜病。结果本组204例HSK中,属于感染性上皮角膜炎86例,其中角膜小泡13例,树枝状溃疡33例,地图状溃疡38例,缘部溃疡2例,全部治愈。属于基质性角膜炎91例,其中坏死性基质角膜炎2例,药物治疗无效,行穿透性角膜移植术。免疫性基质角膜炎89例,全部治愈。属于角膜内皮炎27例,其中中央型13例,周边型8例,弥漫型6例,全部治愈。结论Holland等的新分类法可指导临床诊治HSK,提高HSK临床诊治质量,改善HSK患者预后。     

单纯疱疹性角膜炎发病机制的研究进展

单纯疱疹性角膜炎(HSK)是一种全球高发的严重感染性致盲眼病,视力的慢性损害常与感染的复发、角膜瘢痕、角膜白斑、新生血管以及新生淋巴管等相关.根据目前的研究,角膜的损伤是免疫系统对单纯疱疹病毒(HSV)抗原反应的结果.由于HSK发病机制尚不明确,治疗效果不满意,因此全面了解其初次感染、潜伏、复发的机制是有效治疗的前提.本文分别阐述自噬、免疫系统、细胞因子和微小RNA等几个方面在HSK感染与发病中的作用机制,以了解HSK的发生和发展过程,在一定程度上为HSK的诊断提供参考,并为HSK的治疗及药物研制等研究带来新的启发.     

多聚酶链反应在单疱角膜炎诊断中的应用

目的：寻找一种快速有效的临床诊断单疱角膜炎（ＨＳＫ）的客观依据。方法：应用多聚酶链反应（ＰＣＲ）技术,分别以多聚酶基因、胸腺嘧啶激酶基因和糖蛋白Ｄ基因引物,检测正常人和各种角膜炎病人的泪液及角膜上皮中单纯疱疹病毒（ＨＳＶ）ＤＮＡ。结果：正常人全部为阴性,树枝状和地图状角膜炎２６例中２４例阳性;盘状角膜炎１６例中１４例为阴性;浅层点状角膜炎３２例中１９例阳性,其他未定性角膜炎３３例中１４例阳性,同时对ＨＳＫ病变过程进行监测,显示在发病２～１５天ＨＳＶＤＮＡ的检出阳性率最高;发病４０天或用药３０天左右转阴,并对泪液和角膜上皮不同取材方法进行比较。二者间无显著差异。可优选泪液。结论：ＰＣＲ可以作为ＨＳＫ病原学的诊断方法。     

Pathogenesis of herpes simplex keratitis: The host cell response and ocular surface sequelae to infection and inflammation

Herpes simplex virus type 1 (HSV) keratitis is a leading cause of infectious blindness. Clinical disease occurs variably throughout the cornea from epithelium to endothelium and recurrent HSV stromal keratitis is associated with corneal scarring and neovascularization. HSV keratitis can be associated with ocular pain and subsequent neutrophic keratopathy. Host cell interactions with HSV trigger an inflammatory cascade responsible not only for clearance of virus but also for progressive corneal opacification due to inflammatory cell infiltrate, angiogenesis, and corneal nerve loss. Current antiviral therapies target viral replication to decrease disease duration, severity and recurrence, but there are limitations to these agents. Therapies directed towards viral entry into cells, protein synthesis, inflammatory cytokines and vascular endothelial growth factor pathways in animal models represent promising new approaches to the treatment of recurrent HSV keratitis.     

Management of Herpes Simplex Virus Stromal Keratitis: An Evidence-based Review

Herpes simplex virus (HSV) stromal keratitis is a leading cause of corneal opacification and an important indication for penetrating keratoplasty. Based on several observational studies and clinical trials, the current standard of care includes topical corticosteroids and antivirals. However, corticosteroids have significant side effects, and antivirals are only beneficial if replicating virus is present. High-quality clinical trials investigating therapies for HSV stromal keratitis beyond corticosteroids and antivirals are lacking. Immune regulatory drugs, such as cyclosporine A, present attractive alternatives to managing HSV stromal keratitis, given the immune-mediated pathogenesis of stromal disease. Also, inhibiting viral reactivation in the latently infected ganglia through therapeutic vaccination will likely be the most efficient avenue to reduce recurrent HSV ocular disease. Our present aim is to review the current evidence-based treatment options for HSV stromal keratitis including and beyond the use of corticosteroids and antivirals and to cultivate insights into developing therapeutic vaccination strategies to inhibit HSV stromal keratitis recurrences.     

深板层角膜移植术治疗单纯疱疹病毒性角膜炎的临床研究

目的评价深板层角膜移植术治疗单纯疱疹性角膜炎的临床效果。方法对临床确诊为单疱病毒性角膜炎且经抗病毒药物治疗无效的患者,根据角膜炎累及角膜范围及深度选择深板层角膜移植术,共18例18眼。术后随访时间为12～36个月。观察术后视力、植片的透明度、复发率及术中术后并发症情况。结果18例中17例视力均有不同程度的恢复,矫正视力0．1～0．8,其中12例植片透明,5例植片轻度浑浊,1例角膜炎复发。结论深板层角膜移植是治疗单疱病毒性角膜炎的有效手术方法。     

单纯疱疹病毒性角膜炎的发病机制

单纯疱疹病毒性角膜炎(herpes simplex keratitis,HSK)是一种常见的眼部疾病,由单纯疱疹病毒(herpes simplex virus,HSV)感染引起。人群中超过90%的人曾经感染过HSV。HSV可以在神经组织及角膜组织长期潜伏。在适宜的刺激下,如紫外线照射、发热、精神压力、高温、低温、手术等,病毒活化增殖导致HSK。HSV感染引起的免疫反应是造成角膜组织损害的主要机制。HSK的免疫反应主要是由CD4+细胞介导的,而CD8+细胞对病毒感染具有保护作用。     

A systematic review on advances in diagnostics for herpes simplex keratitis

Herpes simplex keratitis (HSK) is a significant cause of vision impairment worldwide. Currently, there are no set diagnostic criteria, and popular diagnostic methods, including clinical examination of the eye via slit lamp examination, could lead to false-negatives and misdiagnoses. Molecular testing with polymerase chain reaction (PCR) may lack concordance with clinical findings, posing a great challenge to ophthalmologists. We evaluate recent studies on techniques for the diagnosis of HSK. We included a total of 23 studies published between 2010 and 2020 in English on diagnostic techniques, including in vivo confocal microscopy, polymerase PCR testing, protein detection in tear film with enzyme-linked immunosorbent assay, and various other protein assays. Although PCR has been widely used as one of the current diagnostic methods for HSK, most studies evaluated its efficacy after including alterations to its normal protocol. Tear sample analysis was performed using multiple tools, although corneal scrapings demonstrated a higher positive detection rate. Diagnostic tools identified were able to detect HSK with varying accuracy. Newer diagnostic techniques like multiplex dot hybridization assay and immunochromatographic assays may be considered as the point-of-care preliminary diagnostic tools. More reliable results may be generated by developing a standardized diagnostic protocol.     

单纯疱疹病毒性角膜炎复发及治疗的研究进展

单纯疱疹病毒性角膜炎(herpes simplex keratitis,HSK)是由单纯疱疹病毒(HSV)引起的一种严重的感染性角膜疾病。HSV的感染有两种形式：原发性感染和复发性感染。其中,复发性HSV感染的相关机制和干预方式是近些年来的研究焦点。本文介绍了几种常见的HSK的复发免疫机制及治疗,分析了最新研究发现的各种抗HSV复发的药物,希望能尽早开发出新型的干预方式,开发出具有较强疗效和较小毒性的化合物,使其减少潜在的副作用,提供更好的治疗效果。     

Recurrence rate of herpetic uveitis in patients on long-term oral acyclovir

We examined the recurrence rate of herpetic uveitis (HU) in 13 patients (group A) treated prophylactically with long-term systemic acyclovir (600–800 mg/day) and compared it with that of 7 patients with no prophylactic therapy (group B). HU was diagnosed on the basis of a history of dendritic or disciform keratitis accompanied by iridocyclitis and iris atrophy. The study population consisted of 12 men and 8 women with a mean age at onset of uveitis of 52.9 years (range 19 – 78 years). All patients were followed for at least 8 months. The mean follow-up time of patients on long-term oral acyclovir was 26.0 months. In this group, only one patient experienced a single recurrent episode of uveitis while on 600–800 mg/day of acyclovir therapy; two additional patients had recurrence of HU within 16.2 months after the acyclovir dose was tapered below 600 mg/day. In striking contrast, 16 recurrences occurred in the 7 patients of group B (p<0.05). Of these, the initial recurrence occurred within an average of 4.3 months following cessation of therapy. There was a significant difference (p<0.05) in the mean recurrence-free interval between patients in group A (24.6 months) and those in group B (3.4 months). Herpetic uveitis is a serious ocular disease in which recurrence of inflammation results in severe ocular complications. The long-term use of oral acyclovir may be of benefit in the prevention of recurrences, and hence may reduce the blinding complications of this disease. Efforts at completing a randomized, placebo-controlled trial on this matter by the Herpes Epithelial Disease Study Group were unsuccessful due to insufficient patient recruitment.Abbreviations ACV acyclovir - HSV herpes simplex virus - AIDS acquired immunodeficiency syndrome - KPs keratic precipitates     

球结膜下注射转移因子在治疗单纯疱疹病毒性角膜炎的临床应用

目的观察球结膜下注射转移因子对治疗单纯疱疹病毒性角膜炎（ HSK）的疗效。方法86例（92只眼）HSK患者随机分成两组。 A组（45例49只眼）予球结膜下注射转移因子,B组（41例43只眼）予球结膜下注射α-干扰素及α-干扰素滴眼,两组均常规滴用阿昔洛韦滴眼液。结果 A组疗效优于B组（ P ＜0．05）。结论球结膜下注射转移因子可以提高患眼局部免疫力,配合抗病毒治疗HSK效果好,操作简单,无明显副作用。     

荧光定量PCR技术检测HSK房水中HSV-Ⅰ型DNA

目的探讨荧光定量聚合酶链反应（FQ-PCR）技术对I型单纯疱疹病毒性角膜炎（HSK）的病原学诊断价值。方法应用FQ-PCR技术对HSK患眼房水中的I型单纯疱疹病毒（HSV-I）DNA进行扩增,并对PCR产物进行定量检测,同时以老年性白内障患者房水作为对照,并作统计学分析。结果 16例（16只眼）HSK患眼房水中有5例阳性,阳性率31.25%,20例（20只眼）单纯老年性白内障患者房水无1例阳性,阳性率0%,差异有统计学意义（P〈0.05）。结论 FQ-PCR法可以作为HSK的病原学快速诊断的实验室方法之一。     

T淋巴细胞因子与单纯疱疹病毒性角膜炎的研究进展

单纯疱疹病毒性角膜炎(herpes simplex keratitis,HSK)是由病毒抗原引起的T淋巴细胞介导的迟发型变态反应。T淋巴细胞如何介导HSK免疫反应的详细机制目前仍不清楚,但从目前研究可总结:T淋巴细胞的细胞因子如IL-2,IL-10,IL-17,IFN-γ等促炎性因子在HSK的复发过程中起重要作用。本文将对T淋巴细胞及其细胞因子与HSK的研究进展做简要综述。     

The treatment of HSV1 ocular infections using quantitative real‐time PCR results

Purpose: Herpes stromal keratitis is a serious condition and the most frequent cause of unilateral blindness. The real‐time PCR is an accurate and fast diagnostic method for an analysis of infectious agents causing keratitis and keratouveitis. The aim of the study was to assess the relationship between clinical symptoms, treatment efficacy monitoring and viral quantity in corneal swabs determined by quantitative real‐time PCR method. The real‐time PCR method was used as well for the detection of other viral eye pathogens. Methods: A total of 212 patients (136 men and 76 women) suspect of having herpes simplex virus (HSV) keratitis or keratouveitis were included in the study. The detection and quantitative analysis of the viral DNA were performed using the EliGene HSV1 RT kit, and the result was correlated with the clinical picture of the disease. The patients were routinely treated with acyclovir applied locally or, alternatively, in systemic administration. In a case of acyclovir treatment resistant keratitis, the patients were treated with local ganciclovir (Virgan gel ophth 0.15%). Results: A total of 636 analyses of the viral DNA were performed; 85 patients were positive for HSV1 (198 detected). There were 16 acyclovir resistant cases of keratitis (14%). Conclusions: The real‐time PCR appears as a fast and accurate method for an exact identification of the viral DNA in patients with herpes stromal keratitis. The introduction of the quantification is important for the treatment evaluation and for the specification of a so‐called acyclovir resistant keratitis. A long‐term systemic administration in maintenance doses may lead to the resistance and repeated, frequent relapses of the disease.     

Herpes simplex virus keratitis: an update of the pathogenesis and current treatment with oral and topical antiviral agents

Ophthalmic herpes simplex viral keratitis is responsible for a range of ocular manifestations from superficial epithelial disease to stromal keratitis and endotheliitis. The Herpetic Eye Disease Study has guided the management of herpetic eye disease for almost twenty years, but newer medications such as valacyclovir are now available and are considered to have better bioavailability than acyclovir. In this review, we examine the existing evidence on the pathogenesis of different ophthalmic herpes simplex viral keratitis disease modalities and the role of oral and topically administered antiviral drugs in the treatment of herpes simplex viral keratitis.