Herpes simplex keratitis:A brief clinical overview

The aim of our minireview is to provide a brief overview of the diagnosis,clinical aspects,treatment options,management,and current literature available regarding herpes simplex keratitis(HSK).This type of corneal viral infection is caused by the herpes simplex virus(HSV),which can affect several tissues,including the cornea.One significant aspect of HSK is its potential to cause recurrent episodes of inflammation and damage to the cornea.After the initial infection,the HSV can establish a latent infection in the trigeminal ganglion,a nerve cluster near the eye.The virus may remain dormant for extended periods.Periodic reactivation of the virus can occur,leading to recurrent episodes of HSK.Factors triggering reactivation include stress,illness,immunosuppression,or trauma.Recurrent episodes can manifest in different clinical patterns,ranging from mild epithelial involvement to more severe stromal or endothelial disease.The severity and frequency of recurrences vary among individuals.Severe cases of HSK,especially those involving the stroma and leading to scarring,can result in vision impairment or even blindness in extreme cases.The cornea's clarity is crucial for good vision,and scarring can compromise this,potentially leading to visual impairment.The management of HSK involves not only treating acute episodes but also implementing long-term strategies to prevent recurrences and attempt repairs of corneal nerve endings via neurotization.Antiviral medications,such as oral Acyclovir or topical Ganciclovir,may be prescribed for prophylaxis.The immune response to the virus can contribute to corneal damage.Inflammation,caused by the body's attempt to control the infection,may inadvertently harm the corneal tissues.Clinicians should be informed about triggers and advised on measures to minimize the risk of reactivation.In summary,the recurrent nature of HSK underscores the importance of both acute and long-term management strategies to preserve corneal health and maintain optimal visual function.

Virus DNA Detection of Herpes Simplex Keratitis by PCR

HSV-DNA of seven corneal lesions suspected with herpessimplex keratitis (HSK) and nine normal human donor corneas weredetected by PCR,Five out of seven diseased corneas showed positiveresults,and the other two diseased corneas and nine.normal corneasnegative.The results suggest the PCR may be useful as a rapid andsensitive method for diagnosing HSK.Eye Science 1993;9:126-128.

Effects of integrated traditional Chinese and western medicine on the vision recovery and serum trace elements of patients with herpes simplex keratitis

Objective:To explore the effects of integrated traditional Chinese and western Medicine on the vision recovery and serum trace elements in patients with herpes simplex keratitis.Methods:A total of 86 cases of HSK patients admitted in Baogang Hospital of Inner Mongolia from January 2015 to October 2016 were selected and divided randomly into the observation group(n=43)and the control group(n=43)according to the random number table.The control group was treated with ganciclovir eye drops and chondroitin sulfate eye drops,and the observation group was treated with Qinggan Mingmu Decoction on the basis of the control group.The 2 groups were treated for 4 weeks continuously.The clinical efficacy was compared between two groups.The vision recovery,serum trace elements and tear immune factor levels were also compared between two groups before and after treatment.Results:After treatment,the effective rate of treatment in the observation group was significantly higher than that in the control group(p<0.05);in the observation group of patients,visual analogue scale(VAS)score and visual acuity after treatment were obviously higher than those before treatment,and also remarkably higher than those in the control group of patients(p<0.05);after treatment,the levels of Fe,Ca and Cu ions in the observation group were significantly lower than those in the control group and before treatment(p<0.05);after treatment,the level of zinc ions in the serum in the observation group was significantly higher than that before treatment and in the control group(p<0.05);after treatment,the levels of tear IgA,IgG and C3 in the observation group were prominently higher than those before treatment and in the control group(p<0.05).Conclusions:In the treatment of HSK,integrated traditional Chinese and western medicine can promote effectively the vision recovery,regulate the level of trace elements in the serum and enhance the level of tear immune factors,with the clinical efficacy better than the treatment of western medicine alone.

The role of adhesion molecules ICAM-1 and VCAM-1 in herpes simplex keratitis

Purpose:To elucidate the role of adhesion molecules in the pathogenesis of herpes simplex keratitis. Methods:Fifty female Balb/c mice (4-6 weeks old, 14-22 g weight) were divided into two groups randomly. Forty were infected by herpes simplex virus and the other 10 were used as normal controls.All mice were fed under the same conditions.Corneas of these mice were collected for immunohistochemical testing on day 14 and 21 after infection. Results:ICAM-1 was mainly expressed in the basal cells of the corneal epithelia and vascular endothelia of the infected mice. A substantial amount of VCAM-1 was also expressed in the corneal vascular endothelial cells of infected mice,and was also found in inflammatory cells in the epithelial and stromal layers of the corneas. Conclusion:Adhesion molecules ICAM-1 and VCAM-1 were involved in the progression of herpex simplex keratitis.They may accelerate the progress of inflammation by mediating the extravsation of inflammatory cells from vessels into the infected sites.

DNA vaccine expressing herpes simplex virus 1 glycoprotein C and D protects mice against herpes simplex keratitis

AIM： To investigate whether DNA vaccine encoding herpes simplex virus 1（HSV-1） glycoprotein C（g C） and glycoprotein D（g D） will achieve better protective effect against herpes simplex keratitis（HSK） than DNA vaccine encoding gD alone. METHODS： DNA vaccine expressing gD or gC combined g D（g D.g C） were constructed and carried by chitosan nanoparticle. The expression of fusion protein gD and gC were detected in DNA/nanoparticle transfected 293 T cells by Western-blot. For immunization, mice were inoculated with DNA/nanoparticle for 3 times with 2 wk interval, and two weeks after the final immunization, the specific immune responses and clinical degrees of primary HSK were evaluated. RESULTS： Fusion protein g D.g C could be expressed successfully in cultured 293 T cells. And, p RSC-g C.g DIL21 DNA/chitosan nanoparticle could effectively elicit strongest humoral and cellular immune response in primary HSK mice evidenced by higher levels of specific neutralizing antibody and s Ig A production, enhanced cytotoxicities of splenocytes and nature killer cells（NK）,when compared with those of gD alone or mocked vaccine immunized mice. As a result, gC-based vaccine immunized mice showed least HSK disease. CONCLUSION： gC-based DNA vaccine could effectively prevent the progress of primary HSK, suggesting that this DNA vaccine could be a promising vaccine for HSK treatment in the future.

Systemic IL-1β production as a consequence of corneal HSV-1 infection-contribution to the development of herpes simplex keratitis

This study sought to identify potential therapeutic targets in herpes simplex keratitis(HSK) patients with active and inactive infection by investigating peripheral cytokine production. Peripheral blood mononuclear cells(PBMCs) and serum were prepared from healthy controls and HSK patients during active infection or following treatment(inactive infection). Serum antibody titres were determined by ELISA. Protein expression levels were analysed by Western blot. Cytokine levels were determined by multiplex ELISA. Active corneal herpes simplex virus type 1(HSV-1) infection resulted in significantly elevated peripheral levels of IL-1β in HSK patients compared to healthy controls, and remained significantly increased following treatment. Elevated production of IL-1β in inactive patients was associated with significantly increased levels of IRF3 and STAT1, key proteins involved in promoting anti-viral immune responses. Our data suggest that inflammation persists beyond the period that it is clinically evident and that enhanced peripheral production of IL-1β may have implications for HSV-1 viral clearance in active and inactive HSK patients.

A Comparison of the Clinical and Molecular Diagnosis of Herpes Simplex Keratitis

Purpose: To compare the clinical and molecular diagnoses of Herpes Simplex Keratitis (HSK). Materials and Methods: Conjunctival swabs (after fluorescein and anaesthetic wash out) and detailed questionnaire data were obtained from 146 participants. Corneal rims and conjunctival epithelial cells were infected with Herpes Simplex Virus (HSV) type 1 or HSV2 and supernatant collected. HSV1;HSV2;Varicella Zoster Virus (VZV) and Adenovirus (ADV) DNA was assessed using two real time Polymerase Chain Reaction (PCR) methods. Results: Of the 146 participants recruited, 54 were clinically diagnosed with typical epithelial lesions and 38 with atypical epithelial lesions, 17 with old inactive HSK and 37 healthy volunteers. HSV1 DNA was detected in 28 (30%) of the 92 participants with clinically suspect HSK. Patients who presented with typical epithelial lesions had a higher positive rate (46%) than those who presented with atypical type lesions (8%), when using primers against the Glycoprotein (Gp) G region of the virus. When the same samples were retested with primers against the GpB region, the positive rate for the typical and atypical cases increased to 52% and 11% respectively. Antiviral use at the time of sampling reduced the rate of PCR positivity by 20% (p < 0.05). ADV DNA was detected in 6% of the typical cases and 8% of the atypical cases. All control participants with no history of HSK were negative for HSV1 DNA. Sample quantity was confirmed by testing for housekeeping control genes, beta-actin and beta-2 macroglobulin. PCR results from in vitro control investigations of HSV1 and 2 infected corneal rims and conjunctival epithelial cells were 100% positive for infected and 100% negative for uninfected samples when assessed using both PCR methods. Conclusions: Clinical diagnosis of typical HSK is not always confirmed by PCR. Concomitant use of an antiviral reduces levels of PCR positivity. Given this and the findings that other ocular surface pathogens may mimic HSK pathology, and that choice of gene amplification region can also affect accurate detection of HSV1 by PCR, we propose the use of a multiplex assay. This would perform PCR using primers spanning a number of different regions within one gene and would also target a number of different viral genes to ensure potentially different HSV1 viral strains or other viruses do not affect the test and lead to disagreements between the clinical and molecular diagnosis of HSK. From these findings, this paper proposes a clinical supportive algorithmic guide to manage such disagreements.

复发HSK病人泪液中K、Na、Ca、Mg、Zn、Fe、Cu、Mn元素含量测定与临床意义

本文应用原子吸收光谱法测定了25例(25眼)复发HSK病人及53侈4(64眼)无眼病的健康人泪液中K、Na、Ca、Mg、Zn、Fe、Cu、Mn元素含量。结果显示:复发HSK病人泪液Zn、Fe、Mg、Ca 4种元素含量明显低于对照组(P<0.001)。提示HSK复发可能与这些元素含量不足有关。认为局部补充锌剂在预防和治疗HSK复发上是非常必要的。

现代医学和传统医学对复发性HSK的研究进展

从近年来大量的研究文献可以看出,复发性单纯疱疹病毒性角膜炎一直是眼科学研究的一个热点,其发病机制及治疗药物的探索早已成为研究的焦点。随着医学研究的深入,我们对单纯疱疹性角膜炎有了新的认识,但目前对其具体发病机制和治疗手段尚不一致,还需进一步研究。

多重聚合酶链反应快速诊断HSK和真菌性角膜炎的研究

目的:探讨多重聚合酶链反应(multiplexPCR,MPCR)技术快速诊断单纯疱疹病毒性角膜炎(HSK)和真菌性角膜炎的价值。方法:建立单纯疱疹病毒(HSV)和致病性真菌菌株的MPCR检测方法,检测49例患者54眼角膜刮片或泪液标本,对怀疑为真菌和混合感染的与涂片镜检和真菌培养比较。结果:MPCR5h可检测出标本中微量HSV和真菌,54份标本MPCR检测阳性43份(80%),其中怀疑有真菌感染的25份标本中17份真菌检测阳性(68%),阳性率明显高于真菌培养(χ2=11.57,P<0.005)和涂片镜检(χ2=13.33,P<0.005)。结论:MPCR速度快、敏感性和特异性高,有助于HSK和真菌性角膜炎的快速明确诊断。

HSK合并白内障行超声乳化术后的疗效及临床用药观察

目的:观察单纯疱疹病毒性角膜炎(Herpes simplex keratitis,HSK)合并白内障患者行白内障超声乳化术后视力变化及术后应用抗病毒药物预防单纯疱疹病毒性角膜炎复发的疗效。方法:单纯疱疹病毒性角膜炎合并白内障22例22眼行白内障超声乳化+人工晶状体植入术,术后随机分为两组,治疗组给予口服阿昔洛韦及滴用更昔洛韦凝胶;对照组仅给予滴用更昔洛韦凝胶。观察术后视力变化情况;分析单纯疱疹病毒性角膜炎复发的情况。结果:术后6mo随访,治疗组和对照组视力均获得提高;治疗组无1例出现单纯疱疹病毒性角膜炎的复发;对照组也仅有1例于术后6mo复发,差异无显著性。结论:在抗病毒药物的保护下,>6mo未复发的单纯疱疹病毒性角膜炎不是白内障的手术禁忌,白内障手术能有效改善HSK合并白内障患者的视力;仅滴用更昔洛韦凝胶亦能有效预防白内障术后单纯疱疹病毒性角膜炎的复发。

羊膜移植对实验性HSK中基质金属蛋白酶表达的影响

目的研究羊膜移植(AMT)对单纯疱疹性角膜炎(HSK)中基质金属蛋白酶(MMP-2,-9)表达的影响。方法40只BALB/c小鼠角膜感染Ⅰ型单纯疱疹病毒(HSV-1),实验组角膜行AMT。术后第0、2、7、14 d取出角膜。常规病理切片、免疫组化染色和计算机图像分析检测角膜中MMP-2及-9的表达及平均光度值的变化。结果对照组20只鼠眼中17只发生HSK;AMT组仅有9只眼发生,差异有显著统计学意义(P<0.01)。AMT组角膜上皮、基质病变程度及新生血管发生率明显低于对照组(P<0.05)。免疫组化及图像分析显示对照组角膜细胞和浸润炎性细胞中表达的MMP-2及-9在第2 d增加,14 d时达高峰。AMT组各时间点MMP-2及-9表达低于对照组,差异有显著统计学意义(P<0.05)。结论羊膜移植可能通过抑制角膜细胞及浸润的炎症细胞产生MMPs,从而抑制HSK的发生和发展。

抗HSV单克隆抗体－阿糖胞苷特异性导向药物的制备及对实验性HSK的疗效观察

本文报道了抗ＨＳＶＭｃＡｂ与抗病毒药物阿糖胞苷偶联物的制备及鉴定。首先用高碘酸钠氧化葡聚糖为多醛基葡聚糖，使之作为中间载体将阿箱胞苷与ＭｃＡｈ偶联，经鉴定偶联物中ＭｃＡｂ含量为１０ｍｇ／ｍｌ，阿糖胞苷含量为１．０５ｍｇ／ｍｌ，阿糖胞苷与ＭｃＡｂ的充分子比为１：６０，偶联物的ＥＬＩＳＡ效价为１：２５６与偶联前效价相同。应用偶联物和阿糖胞苷分别结膜下注射治疗免眼ＨＳＫ模型共３６只眼，表明偶联物的疗效优于阿糖胞苷。

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。

HSK的包膜糖蛋白gB和gD与疫苗的研究新进展

包膜糖蛋白gB,gD是参与单纯疱疹病毒(herpes simplex virus,HSV)感染的基本结构蛋白,具有重要的抗原表位,参与病毒穿膜过程,介导了病毒的细胞间扩散,在病毒感染和宿主免疫过程中起着重要作用,其分子和功能特性的研究对HSV作用机制及预防的研究有着重要意义。近年来,该领域的研究取得一定进展,针对HSVgB,HSVgD的抗原表位已研究出相应疫苗,本文将对与单纯疱疹病毒性角膜炎(herpes simples keratitis,HSK)有关的糖蛋白gB,gD与疫苗的研究进展做一简要综述。

DNA疫苗pRSC-gD.gC-IL-21的构建及其预防HSK的动物实验初步研究

目的:构建DNA疫苗pRSC-gD.gC-IL-21,探讨其是否能诱导动物免疫应答及抵抗眼角膜单纯疱疹病毒Ⅰ型(HSV-1)的感染。方法:提取HSV-1基因组DNA,PCR扩增获得gC基因。以pRSC-gD-IL-21质粒为模板(本实验室2011年构建),构建重组质粒pRSC-gD.gC-IL-21,用纳米材料壳聚糖(chitosan)包裹,采用黏膜接种的方式分别以pRSC-gD.gC-IL-21+chitosan、pRSC-gD-IL-21+chitosan、pRSC+chitosan及chitosan免疫小鼠3次,间隔2周,末次免疫2周后检测各项免疫学指标,同时评价小鼠对病毒攻击角膜的免疫保护作用。结果:经测序、酶切及Westernblot鉴定,重组质粒pRSC-gD.gC-IL-21构建成功,chitosan包裹率高。与对照鼠相比,该疫苗在鼠体内产生了更强的特异性中和抗体、细胞毒性T淋巴细胞(CTL)及自然杀伤细胞(NK)杀伤活性增强、泪液中特异性sIgA水平增高,同时使小鼠产生了较强的针对眼角膜HSV-1感染的免疫保护作用。结论:DNA疫苗pRSC-gD.gC-IL-21构建成功,能诱导小鼠产生较强的免疫应答及针对HSV-1眼部感染的免疫保护作用,能够预防单纯疱疹病毒性角膜炎(HSK)的发生、发展。

氟米龙配合更昔洛韦治疗HSK疗效与安全性观察

目的探析氟米龙配合更昔洛韦治疗单纯疱疹病毒性角膜炎(HSK)疗效与安全性。方法选取2015年6月至2018年1月本院收治的HSK患者110例,采用随机抽签法分为观察组与对照组,各55例,对照组采用更昔洛韦眼凝胶治疗,观察组在对照组基础上加用氟米龙滴眼液联合治疗,观察两组患者治疗有效率、症状缓解时间、不良反应发生率及复发率。结果两组患者治疗有效率分别为94.55%、80.00%,观察组明显高于对照组(P<0.05);两组患者治疗后视力较治疗前均明显升高(P<0.05),观察组治疗后视力明显高于对照组(P<0.05),眼部疼痛缓解时间及角膜愈合时间均显著短于对照组(P<0.05);两组患者不良反应发生率分别为5.45%、9.09%,差异无统计学意义,复发率分别为9.09%、25.45%,观察组明显低于对照组(P<0.05)。结论 HSK患者采用氟米龙配合更昔洛韦治疗可显著提高治疗效果,明显缓解临床症状,促进角膜修复愈合,复发率低,安全性高。

CBSC结膜下注射对HSK患者血T-LC亚群IL-2及SIL-2R水平的影响

目的 探讨脐血干细胞结膜下注射对单纯疱疹性角膜炎 (herpessimplexkeratitis,HSK)患者血T淋巴细胞 (T LC)亚群、白细胞介素 2 (IL 2 )及可溶性IL 2受体 (SIL 2R)水平含量的影响 ,并观察其临床疗效程度。方法 将患者随机分为 2组 ,治疗组 5 0例 5 1眼 ,以脐血干细胞 (CBSC)结膜下注射治疗为主 ,共注射 3次 ;对照组 5 0例 5 2眼 ,以干扰素(IF)结膜下注射治疗为主 ;2周后评价疗效 ,检测 2组患者血T LC亚群、IL 2及SIL 2R水平含量 ,并与 5 0例健康者作正常对照。结果 2组患者治疗前血T LC亚群CD4 (39.7±6 6 ) %、CD8(2 9.6± 5 .4 ) %、CD4 /CD8(1.34± 0 .6 1)及IL 2((16 5 8.2 )± 312 .8)ng·L-1、SIL 2R(378.6± 5 7.8U·mL-1)水平含量均明显不同于正常者 (P <0 .0 5 ) ;治疗后治疗组上述指标均明显较治疗前改善 (P <0 .0 5 ) ,基本接近正常者 (P>0 0 5 ) ,而对照组治疗前后上述指标均无明显差异 (P >0 0 5 ) ,仍与正常者有一定差异 (P <0 .0 5 ) ;2组治疗后上述指标间比较均有显著性差异 (P <0 .0 5 ) ;临床观察显示 :治疗组疗效明显优于对照组 (P <0 0 5 ) ,且平均痊愈时间缩短 (P<0 0 1)、复发率降低 (P <0 0 5 )。结论 脐血干细胞结膜下注射治疗HSK疗效可靠 ,且有明显调节患者血T LC?

Clinical Efficacy of Oral Ganciclovir for Prophylaxis and Treatment of Recurrent Herpes Simplex Keratitis

Background：Herpes simplex keratitis （HSK） caused by herpes simplex virus 1 （HSV-1）,which has high recurrent rate and incidence of severe vision loss,is the leading cause of infectious blindness in the world.The aim was to explore the clinical efficacy of oral ganciclovir （GCV） in the prevention of recurrent HSK.Methods：A multicenter,prospective,randomized,single-blind,and controlled clinical trial was conducted from April 2010 to June 2013.One hundred seventy-three patients （173 eyes involved） who were diagnosed as recurrent HSK definitely,including stromal keratitis and corneal endotheliitis,were divided into three groups randomly：negative control （placebo） group was topically administered with 0.15% GCV ophthalmic gel,4 times per day and 0.1% fluorometholone eye drops,3 times per day until resolution of HSK; positive control acyclovir （ACV） group was topically adopted the same ophthalmic gel and eye drops and additionally received oral ACV 400 mg 5 times a day for 10 weeks and followed by 400 mg 2 times per day for 6 months; test GCV group was topically adopted the same treatment as negative control group and additionally received oral GCV 1000 mg 3 times per day for 8 weeks.The symptoms and signs were evaluated before and after the therapy 1^st week,2^nd week and then followed up every 2 weeks until recovery.Furthermore,we followed up recurrence of HSK for every 3 months after recovery and then assessed the cure time,recurrent rate and adverse reactions.Results：One hundred and seventy-three patients were followed up 7-48 months （mean 32.1 ± 12.3 months）,but 34 patients were failed to follow-up.The cure time was 12.1± 4.3,11.9 ± 4.0 weeks in negative control （placebo） group and positive control ACV group respectively （P =0.991）,which was longer than that in test GCV group （8.6 ± 2.8 weeks） and there was a significant difference between test GCV group and negative control （placebo） group or positive control ACV group （P =0.000）.Furthermore,the recurrent rate was higher in negative control （placebo） group （47.3%） than that in positive control group ACV （26.7%） and test GCV group （17.2%）,and there was a great significant difference among the three groups （P =0.007）,but there was no significant difference between positive control ACV group and test GCV group （P =0.358）.In addition,there was no obvious adverse reaction expect neutropenia （only one patient in test GCV group）.Conclusion：Short-term oral GCV could cure recurrent HSK and endotheliitis,shorten the course,reduce recurrent rate of HSK and have confirmed safety.

Corneal esthesiometry and sub-basal nerves morphological changes in herpes simplex virus keratitis/uveitis patients

AIM: To describe and compare corneal sensation and morphological changes of sub-basal corneal nerves by in vivo laser scanning confocal microscopy(LSCM) in herpes simplex virus(HSV) keratitis/uveitis and contralateral, clinically unaffected eyes. METHODS: A prospective clinical study included 30 HSV eyes and 30 contralateral eyes of 30 patients, diagnosed with unilateral HSV keratitis/uveitis. Both eyes underwent a complete ophthalmological examination, Cochet-Bonnet aesthesiometry and LSCM of the central cornea, using the Heidelberg Retina Tomograph III Rostock Cornea Module. After 6 mo, the same examination of the HSV affected and contralateral, clinically unaffected eyes was performed.RESULTS: HSV eyes, as compared to contralateral eyes, demonstrated a significant decrease in mean corneal sensation(3.1±1.6 vs 5.3±0.8 cm), total nerve fibres number(5.7±4.4 vs 15.1±5.4), nerve branches(3.4±3.0 vs 8.4±4.7), main nerve trunks(2.3±1.6 vs 5.8±2.2), and nerve fibres density(7.5±5.6 vs 18.1±5.3 mm/mm2, P<0.05). There was no significant difference between keratitis and uveitis eyes in mean corneal sensation and nerve fibres parameters. After 6 mo, corneal sensation and sub-basal nerve fibres parameters were increased significantly, but did not reach the parameters of contralateral, clinically unaffected eyes.CONCLUSION: Corneal aesthesiometry and LSCM in HSV affected eyes reveals a significant decrease of corneal sensation and sub-basal nerve fibres which recovers at6 mo but does not reach the normal level.