氦氖激光血管内照射治疗单纯型糖尿病视网膜病变的临床研究

目的 探讨低能量氦氖激光血管内照射疗法（ＩＬＩＢ）治疗单纯型糖尿病视网膜病变（ＤＲ）的临床价值。方法 用ＩＬＩＢ治疗单纯型ＤＲ患者３８例，设对照组３２例不用ＩＬＩＢ。共治疗３个疗程，每个疗程１０天，疗程间隔１０天。观察治疗前后的血液流变学和眼底变化。结果 与对照组相比，治疗组的显效率（１３．１６％）和总有效率（５７．８９％）均显著高于对照组（分别为０％，Ｐ〈０．０５，９．４％Ｐ〈０．０１），治疗前后血流变学指标较治疗前明显下降（Ｐ〈０．０１）。结论 ＩＬＩＢ能明显降低ＤＲ患者的血液粘度，改善和稳定其眼底病变。     

hrIL—2治疗单疱病毒性角膜炎临床研究

目的研究人重组白细胞介素Ⅱ（ｈｒＩＬ－２）与无环鸟苷联合治疗单纯疱疹病毒性角膜炎（ｈｅｒｐｅｓｓｉｍｐｌｅｘｋｅｒ－ａｔｉｔｉｓ，ＨＳＫ）疗效与预防复发。方法应用ｈｒＩＬ－２与０．１％无环鸟苷联合治疗ＨＳＫ５０例，对照组３０例单用０．１％无环鸟苷治疗。结果联合用药治疗组疗效明显高于对照组。随访１ａ观察复发率明显低于对照组。结论应用ｈｒＩＬ－２与０．１％无环鸟苷联合治疗ＨＳＫ疗效明显，复发率低，临床观察眼部无不良反应。     

UL48基因反义寡聚核苷酸对实验性单疱病毒角膜炎的治疗作用

为了观察硫修饰和未修饰的反义寡聚核苷酸对小鼠实验性单疱病毒角膜炎的治疗作用，将ＴＣＤ５０为１０－６．５的ＨＳＶ－１病毒稀释１０倍，种植于小鼠角膜上，用０．１％硫代反义寡聚核苷酸、０．１％反义寡聚核苷酸和０．１％无环鸟苷进行治疗，以生理盐水为对照，观察角膜上皮和实质病变。小鼠角膜上皮病变：硫代反义寡聚核苷酸组在第３、４、５天，反义寡聚核苷酸组在第４、５天，无环鸟苷组在第３、４、５、６天显著轻于对照组。角膜实质病变：硫代反义寡聚核苷酸组在第５天，无环鸟苷组在第３、４、５天显著轻于对照组。硫代反义寡聚核苷酸对小鼠实验性单疱病毒性角膜炎有一定的治疗作用     

复明Ⅱ号抑制HSV—1再活的实验研究

通过已建立ＨＳＶ—１潜伏感染的动物模型，比较了复明Ⅱ号和无环鸟苷治疗后ＨＳＶ—１的激活率。结果表明：在ＨＳＶ—１角膜感染及给予复明Ⅱ号和无环鸟苷（ＡＣＶ）三十天的全身治疗后，经角膜肾上腺素电离子导入激活潜伏于三叉神经节中的ＨＳＶ—１，复明Ⅱ号组三叉神经节中抗原阳性率和泪液中病毒释放率均低于无环鸟苷组。证明了复明Ⅱ号对潜伏感染之后的再活具有较好的抑制作用，应于临床进一步观察     

微量皮质类固醇联合抗病毒药物治疗单纯疱疹病毒性角膜炎

目的观察微量皮质类固醇与抗病毒药物合用对单纯疱疹病毒性角膜炎（ＨＳＫ）的疗效。方法将１６０例ＨＳＫ患者随机分为治疗组和对照组,治疗组用５ｇ·Ｌ－１可的松、１ｇ·Ｌ－１无环鸟苷（ＡＣＶ）和２５ｇ·Ｌ－１三氮唑核苷（ＲＢＶ）３种眼液,对照组用１ｇ·Ｌ－１ＡＣＶ和２５ｇ·Ｌ－１ＲＢＶ２种眼液交替滴眼治疗。结果治疗组治愈率、有效率明显高于对照组（Ｐ＜０．０１）,治愈时间明显短于对照组（Ｐ＜０．０１）,随访１４～２４ｍｏ复发率明显低于对照组（Ｐ＜０．０１）。结论在临床上用微量皮质类固醇联合足量有效的抗病毒药物,对上皮型和实质层型ＨＳＫ都能促进其痊愈过程,并可降低复发率。     

葡萄膜炎患者血清中抗EB病毒抗体的测定及意义

为了解我国葡萄膜炎的发生与ＥＢ病毒感染的关系，我们用免疫酶标法对４２例活动期不同类型葡萄膜炎患者作抗ＥＢ病毒壳抗原（ＶＣＡ）抗体的检测，并以３３例正常人作为对照组。结果发现葡萄膜炎患者血清中抗ＥＢ病毒ＶＣＡ－ＩｇＧ抗体的阳性率及抗体滴度与正常对照组无显著性差异（Ｐ＞０．０５），而患者血清中ＶＣＡ－ＩｇＭ抗体阳性率及抗体滴度明显高于对照（Ｐ＜０．０１）。表明葡萄膜炎患者和对照组以往均感染过ＥＢ病毒，而葡萄膜炎患者新近又重复感染ＥＢ病毒或潜伏感染状态被激活。提示葡萄膜炎的发生与ＥＢ病毒感染可能有关。     

普拉洛芬滴眼液不同用药时间对干眼症疗效的影响

目的　探讨普拉洛芬滴眼液不同用药时间对干眼症疗效的影响。方法　选取我院眼科门诊诊断为双眼干眼症的患者１１７例,按照随机数字表法将患者分成普拉洛芬１４ｄ组（３９例）、普拉洛芬３０ｄ组（４０例）和对照组（３８例）。普拉洛芬１４ｄ组给予１ｇ·Ｌ－１普拉洛芬滴眼液（１４ｄ）联合１ｇ·Ｌ－１玻璃酸钠滴眼液（３０ｄ）;普拉洛芬３０ｄ组给予１ｇ·Ｌ－１普拉洛芬滴眼液（３０ｄ）联合１ｇ·Ｌ－１玻璃酸钠滴眼液（３０ｄ）,对照组仅给予１ｇ·Ｌ－１玻璃酸钠滴眼液（３０ｄ）。给药方法均为局部滴双眼,每次１滴,每天４次。分别于治疗前后检测３组患者的泪液分泌试验Ｉ（ＳｃｈｉｒｍｅｒＩｔｅｓｔ,ＳＩｔ）、泪膜破裂时间（ｔｅａｒｂｒｅａｋ-ｕｐｔｉｍｅ,ＢＵＴ）和角膜荧光素染色（ｃｏｒｎｅａｌｆｌｕｏｒｅｓｃｅｎｔｓｔａｉｎｉｎｇ,ＦＬ）评分。结果　治疗前３组患者人口基线特征比较差异均无统计学意义（均为Ｐ＞０．０５）。治疗后普拉洛芬１４ｄ组ＳＩｔ（７．１１±１．３６）ｍｍ和ＢＵＴ（８．４２±０．７９）ｓ均高于对照组ＳＩｔ（５．１９±０．８５）ｍｍ和ＢＵＴ（５．９２±１．２４）ｓ;ＦＬ评分（０．７３±０．７２）显著低于对照组（１．８８±０．７１）,差异均有统计学意义（ｔＳＩｔ＝８．０００,Ｐ＜０．００１;ｔＢＵＴ ＝１０．８７０,Ｐ＜０．００１;ｔＦＬ＝－７．６６７,Ｐ＜０．００１）;治疗后普拉洛芬３０ｄ组ＳＩｔ（７．３８±１．０１）ｍｍ和ＢＵＴ（８．１２±１．００）ｓ均高于对照组,ＦＬ评分（０．８８±０．６８）显著低于对照组,差异均有统计学意义（ｔＳＩｔ＝９．１２５,Ｐ＜０．００１;ｔＢＵＴ＝９．５６５,Ｐ＜０．００１;ｔＦＬ ＝－６．６６７,Ｐ＜０．００１）;但治疗后普拉洛芬１４ｄ组与普拉洛芬３０ｄ组的ＳＩｔ、ＢＵＴ和ＦＬ评分差异均无统计学意义（ｔＳＩｔ＝－１．１２５,０．４＞Ｐ＞０．２;ｔＢＵＴ＝１．３０４,０．２＞Ｐ＞０．１;ｔＦＬ＝－１．０００,０．４＞Ｐ＞０．２）。结论　短期应用１ｇ·Ｌ－１普拉洛芬滴眼液治疗干眼症即可达到较好的疗效,它是辅助治疗干眼症的有效药物。     

枸杞多糖对高压诱导凋亡的视网膜神经节细胞延迟整流钾电流的影响

目的　观察枸杞多糖（ｌｙｃｉｕｍｂａｒａｒｕｍｐｏｌｙｓａｃｃｈａｒｉｄｅｓ,ＬＢＰ）对体外高压诱导调亡的视网膜神经节细胞（ｒｅｔｉｎａｌｇａｎｇｌｉｏｎｃｅｌｌｓ,ＲＧＣｓ）钾电流的影响。方法　生后２～３ｄ的ＳＤ乳大鼠ＲＧＣｓ原代培养,分为对照组、加压组和ＬＢＰ组,对照组为常规培养６ｄ;加压组为常规培养６ｄ后用自行设计的加压装置加压１ｈ８０ｍｍＨｇ（１ｋＰａ＝７．５ｍｍＨｇ）;ＬＢＰ组为常规培养５ｄ后,加入ＬＢＰ共培养２４ｈ后,再加压８０ｍｍＨｇ１ｈ。通过全细胞膜片钳技术观察各组钾电流、半数最大激活电压（Ｖ１／２）、斜率（Ｋ）、最大电导（Ｇｍａｘ）的变化。结果　加压能使电流幅度显著增加,ＬＢＰ能抑制加压引起的电流增加。在刺激电位为－１０～６０ｍＶ时,加压组的电流密度明显大于对照组,差异有统计学意义（均为Ｐ＜０．０１,ｎ＝５／６）;ＬＢＰ组电流密度明显小于加压组,差异有统计学意义（均为Ｐ＜０．０１,ｎ＝６／８）。三组钾电流Ｖ１／２总体差异有统计学意义（Ｆ＝５５．６０,Ｐ＜０．０１）,加压组Ｖ１／２（１１．６５±１．３０）ｍＶ与对照组（２１．４２±１．３３）ｍＶ、ＬＢＰ组（１９．３３±１３．７５）ｍＶ比较,差异均有统计学意义（均为Ｐ＜０．０１）;ＬＢＰ组Ｖ１／２与对照组Ｖ１／２比较,差异无统计学意义（Ｐ＞０．０５）。三组Ｋ值分别是１７．０９±１．２４、１６．５８±１．１８、１８．１３±１．２９,总体差异无统计学意义（Ｆ＝１．３９,Ｐ＞０．０５）。三组Ｇｍａｘ总体差异有统计学意义（Ｆ＝３．７７,Ｐ＜０．０５）,加压组Ｇｍａｘ（０．５９±０．１３）与对照组Ｇｍａｘ（０．４６±０．０６）、ＬＢＰ组Ｇｍａｘ（０．４６±０．０７）比较,差异均有统计学意义（均为Ｐ＜０．０５）;ＬＢＰ组Ｇｍａｘ与对照组Ｇｍａｘ比较,差异无统计学意义（Ｐ＞０．０５）。结论　ＬＢＰ能抑制加压引起的ＲＧＣｓ钾电流增加,对ＲＧＣｓ具有保护作用。     

用“红细胞免疫检测法”研究单疱病毒性角膜炎病人细胞免疫功能的变化

用先进的“红细胞免疫检测法”测定正常人及单疱病毒性角膜炎患者应用单疱病毒特异性转移因子（ＨＳＶ－１ＴＦ）治疗前后红细胞免疫功能，其结果：１０例正常人与５０例治疗前病人比较（Ｐ〈０．０１），两组有显著性差异。５０例治疗前与２０例治疗后病人比较（Ｐ〈０．０１），两组有显著性差异。表明ＨＳＫ病人治疗前免疫功能明显低下，用ＨＳＶ０１ＴＦ治疗后，红细胞免疫功能显著提高。     

氩激光对玻璃体积血吸收的影响

目的 从动物实验角度评价氩激光对玻璃体积血吸收的影响。方法 氩激光照射兔眼玻璃体内血块，动态测定玻璃体内＾５１Ｃｒ标记ＲＢＣ的放射性强度变化，计算出ＲＢＣ吸收率，并用检眼镜观察玻璃体混浊的吸收情况。结果 氩激光照射组ＲＢＣ吸收率明显较对照组块（Ｐ〈０．０５）。玻璃体完全透明时间对照组１１２．７天，氩激光组５１．２天。（Ｐ〈０．０１）。结论 氩激光能加速兔眼玻璃体出血及其混浊的吸收。     

Cyclaradine的抗单纯疱疹病毒作用:在体和离体实验研究

目的 探讨(十)—Cyclaradine在体外及动物模型中抗HSV—1及其耐药株的作用。方法 应用VER0细胞培养和实验性单纯疱疹病毒性角膜炎动物模型，观察(十)—Cyclaradine对HSV—1KOS株、F株、HFTC株、dPyK株、7—2667ACVr株和LeBleu株的抑制效果，并与无环鸟苷(acyclovir，ACV)和三氟胸苷(trif1uorothymidine，TFT)作比较。结果 (十)—Cyclaradine在体外及动物模型中有确切的抗HSV—1作用，而且对ACV和TFT的耐药株也同样有效。结论 (十)—Cyclaradine是一种值得进一步研究的治疗单纯疱疹病毒性角膜灸的药物。     

流式细胞技术测定Ⅰ型单纯疱疹病毒的药物敏感性

目的探讨应用流式细胞技术（FMC）测定Ⅰ型单纯疱疹病毒（HSV-1）对抗病毒药物敏感性的可行性。方法分别应用流式细胞技术和空斑减数试验（PRA）测定对无环鸟苷（ACV）敏感的HSV-1病毒株（SM44）和对ACV耐药的病毒株（ACVr）对常用抗病毒药物ACV、更昔洛韦（GCV）、膦甲酸（PFA）和阿糖腺苷（Ara-A）的敏感性。结果两种检测方法均显示ACVr对ACV和GCV的IC50明显高于SM44（P〈0．05），而对PFA和Ara—A的IC50。两株病毒差异无统计学意义（P〉0．05），FCM法和PRA法的结果具有良好的相关性（r=0．9774，P〈0．01）。结论FCM可以用于抗病毒药物敏感性的测定。     

Effects of anti herpetic drugs on mice with herpetic epithelial keratitis after reactivation of herpes simplex virus type 1

To compare the efficacies of valacyclovir (VCV) and acyclovir (ACV) on murine herpetic epithelial keratitis, mice inoculated with herpes simplex virus type 1(HSV-1) strain McKrae were divided into 6 treatment groups: oral VCV 50 mg/kg and 100 mg/kg, oral ACV 50 mg/kg, ACV eye ointment (EO), ACV eye drops (ED), and placebo. Keratitis scores showed that oral VCV 50 mg/kg, oral ACV, and ACV ED had equivalent efficacies, while oral VCV 100 mg/kg was as efficacious as ACV EO during acute infection. Each treatment group was further divided into the stimulated group with HSV-1 reactivation by immunosuppressant drugs and hyperthermia, and the non-stimulated group without reactivation. We assessed the virus titers in tissues by plaque assay and HSV DNA copy number in the trigeminal ganglia (TG) by real time polymerase chain reaction (PCR). Results showed that the virus titers in the tissues were lowered after reactivation, and the oral VCV group with reactivation had significantly reduced DNA copy number in the TG than the same treatment group without reactivation. In conclusion, oral VCV is as efficacious as ACV EO and significantly suppresses HSV-1 reactivation.     

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。     

Oral Acyclovir in the Management of Herpes Simplex Ocular Infections

Acyclovir, an oral antiviral agent that inhibits viral DNA replication, was used to treat 27 patients (16 males, 11 females) (mean age, 50 years) with vision-threatening herpes simplex virus (HSV) infections. Twenty patients had active stromal keratitis or keratouveitis, four had controlled nonnecrotizing stromal keratitis but could not taper topical medications, and four eczema patients with previous HSV infections had intraocular surgery (1 of these patients also is included in the 20 with active stromal keratitis). All 20 patients with active stromal keratitis or keratouveitis improved on acyclovir, all four patients using acyclovir postoperatively were disease-free while on the drug, but only two of the four patients using acyclovir to assist tapering topical medications were successful. There has been only one recurrence during a cumulative 194 months while on acyclovir. Thirteen patients have remained on acyclovir, and three who stopped acyclovir had prompt recurrences. Acyclovir seems to be a promising adjunct antiviral agent for the treatment of recalcitrant epithelial, stromal, or uveal disease secondary to HSV.     

单纯疱疹病毒性角膜炎小鼠模型的建立及鉴定

目的：探讨建立不同感染时期HSK小鼠动物模型,为HSK的深入研究建立基础。方法：Balb/c小鼠125只麻醉后在显微镜下用刀片背面尖端于角膜＂#＂字划痕,其中100只小鼠接种HSV-Ⅰ病毒,另25只小鼠不接种病毒作为正常对照组。术后每天用10g/L荧光素钠染色后裂隙灯显微镜下观察角膜病变发生情况,并取角膜表面泪液进行HEK293T细胞检测以确定裂隙灯显微镜下有无病毒复制。对潜伏感染期小鼠模型采用紫外线B光照射以诱导HSK复发。结果：接种HSV-Ⅰ病毒的小鼠模型眼于接种后3d内全部出现急性上皮性角膜炎表现。经阿昔洛韦滴眼液治疗1wk后角膜炎症消失,但角膜和三叉神经节中PCR检测病毒仍为阳性。潜伏感染期小鼠模型经紫外线B光照射后也都在1wk内复发,并表现为以基质型角膜炎为主要临床表现的角膜病变。结论：采用角膜划痕法对Balb/c小鼠接种HSV-Ⅰ病毒和紫外线B光照射可以成功地制作出原发感染期、潜伏感染期和复发感染期等不同感染时期的HSK模型,而且操作相对简单、方便易行。     

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.     

Geldanamycin is effective in the treatment of herpes simplex virus epithelial keratitis in a rabbit model

Background: To evaluate the efficacy of geldanamycin eye drops against herpes simplex virus epithelial keratitis in a rabbit model. Methods: New Zealand white rabbits were randomized into four groups and infected with herpes simplex virus type 1; geldanamycin topical eye drops was initiated 24 h after the infection and maintained for 12 consecutive days. Four groups of rabbits received 5 µg/mL geldanamycin, 10 µg/mL geldanamycin, 0.1% acyclovir and escipient (a kind of artificial tears), respectively. The severity of herpes simplex virus type 1 epithelial keratitis was measured by slit‐lamp and scored for statistics analysis. The virus shedding in eye swabs was isolated, and tissue culture infective dose (TCID₅₀) was determined. Results: Geldanamycin (10 µg/mL) treatment reduced significantly the severity of herpes simplex virus type 1 epithelial keratitis than the other three groups. Geldanamycin (5 µg/mL) was as effective as acyclovir (0.1%) treatment. The effect of geldanamycin against herpes simplex virus type 1 epithelial keratitis correlated with accelerated clearance of virus of the rabbits. Conclusion: Geldanamycin is a promising treatment option against herpes simplex virus type 1 epithelial keratitis. Geldanamycin (10 µg/mL) is better than acyclovir and geldanamycin (5 µg/mL) in the rabbit model. The optimal concentration of this drug in human is still to be determined.     

Treatment of Refractory Acute Retinal Necrosis with Intravenous Foscarnet or Cidofovir

Purpose: To report use of intravenous foscarnet or cidofovir for the treatment of refractory acute retinal necrosis (ARN).

Methods: Retrospective chart review.

Results: Four immunocompetent men aged 45–90 years presented with ARN from 2008–2014. One patient with two prior episodes of herpes simplex virus (HSV) ARN developed ARN after 6 years of antiviral prophylaxis. His condition worsened on acyclovir followed by intravenous foscarnet but responded to intravenous cidofovir (final VA in involved eye 20/20). Another patient with HSV ARN had received prolonged acyclovir prophylaxis for HSV keratitis; ARN improved after switching from acyclovir to intravenous foscarnet (final VA 20/125). Two patients with varicella zoster virus (VZV) ARN initially responded to acyclovir but developed fellow eye involvement 2–8 weeks later that worsened on acyclovir but responded to intravenous foscarnet (fellow eye final VA 20/20, 20/40).

Conclusions: Cases of HSV or VZV ARN that worsen despite intravenous acyclovir treatment may respond to intravenous foscarnet or cidofovir.     

单纯疱疹性角膜炎的免疫发病机制

相关的动物模型研究表明，单纯疱疹性角膜炎（HSK）的转归取决于3种相互作用的因素，即宿主固有免疫的基因组成、适应性免疫、病毒的种属。HSK的发病依赖于病毒复制。眼内自身抗原的分子模拟机制可引起自身免疫反应。此外，炎性分子可能通过旁活化的方式激活T细胞，Toll样受体对病毒抗原的免疫识别在炎症反应中发挥重要作用。不同种属的特定病毒基因组成也是影响角膜病变的重要因素。就单纯疱疹性角膜炎的多种免疫机制学说做一综述。