Indirect immunofluorescent antibody diagnosis of herpes simplex with upper tarsal and corneal scrapings

Indirect immunofluorescent techniques were used to diagnose active herpes simplex virus ocular infections in 84 patient observations (41 with ocular lesions suspicious clinically for herpes simplex and 43 with lesions suspicious clinically for other ocular inflammatory conditions). We found indirect immunofluorescent antibody techniques to have a high sensitivity (97%) and specificity (73%) when compared to herpes simplex virus cultures. Similarly, we found the sensitivity (98%) and specificity (77%) of indirect immunofluorescent antibody techniques to be high when compared to the clinical diagnosis of herpes simplex viral infection. Significantly, there were no false negative tests by indirect immunofluorescent techniques. Both corneal and upper tarsal scrapings by indirect immunofluorescence were used and the upper tarsal scrapings were an excellent source of cells exhibiting herpes simplex virus antigens. All cases in which corneal scrapings were positive by indirect immunofluorescence for herpes simplex ere also positive by upper tarsal scrapings, although the converse was not true.     

Herpes simplex keratitis following excimer laser application

PURPOSE: To report two cases of herpes simplex keratitis following excimer laser application. METHODS: Two immunocompetent patients with no history of ocular viral infection developed ulcers after LASIK and phototherapeutic keratectomy (PTK), respectively. RESULTS: Antiviral treatment was administered, and the lesions healed within 14 days. CONCLUSIONS: These two cases suggest that herpes simplex virus was associated with the use of the excimer laser.     

Secretory IgA specific for herpes simplex virus in lacrimal fluid from patients with herpes keratitis--a possible diagnostic parameter.

In the present study a solid-phase radioimmune assay was used for the demonstration of herpes simplex virus-specific IgG and secretory IgA antibodies in the lacrimal fluid from patients with active recurrent herpes keratitis. The method was quantitative and made it possible to test specifically for the production of secretory IgA antibodies produced during an active herpes simplex virus infection. The production of secretory IgA was followed in 2 patients with fresh recurrent lesions. The HSV-specific secretory IgA could be demonstrated during the first 10 days of infection, where the maximal concentration was reached 3-5 days after the first symptoms occurred. The secretory antibodies were locally produced, and it is shown for the first time that herpes virus-specific secretory antibodies were of diagnostic value.     

Effects of topical unoprostone and latanoprost on acute and recurrent herpetic keratitis in the rabbit

PURPOSE: To determine the effect of the topical ocular hypotensive drug, isopropyl unoprostone, a docosanoid molecule with very weak prostaglandin activity, on herpes keratitis in the rabbit eye. METHODS: For acute disease, rabbit corneas inoculated with the corticosteroid-sensitive F(MP)E strain of herpes simplex virus type 1 were treated with various combinations of 0.12% isopropyl unoprostone, latanoprost, trifluridine, benzalkonium chloride 0.02%, dexamethasone sodium phosphate, ketorolac tromethamine, or saline solution beginning 1 day after infection. Severity of keratitis was evaluated in a masked manner. For recurrent disease, rabbit corneas infected with McKrae strain herpes simplex virus type 1 were treated with unoprostone or saline solution on postinfection days 25 to 42, and the presence or absence of lesions was recorded. RESULTS: Eyes treated with unoprostone showed significantly less severe disease than saline-treated or latanoprost-treated eyes during acute infection. Unoprostone-treated and saline-treated eyes showed no significant difference in the frequency of recurrent lesions. Eyes treated with latanoprost and/or dexamethasone, separately or in combination, showed increased severity of acute herpes simplex virus keratitis, whereas benzalkonium chloride 0.02%--treated eyes showed no significant difference, compared with saline treatment. Trifluridine resulted in rapid healing. CONCLUSIONS: Unoprostone did not increase the severity or recurrence rate of herpes simplex virus keratitis. Unoprostone requires twice-a-day administration, compared with once-a-day for latanoprost, and unoprostone lowers intraocular pressure less than latanoprost. Nevertheless, unoprostone's superior safety profile may make its use advantageous. Benzalkonium chloride alone did not make the keratitis worse.     

Herpes simplex virus DNA identification from aqueous fluid in Fuchs heterochromic iridocyclitis

PURPOSE: To report the presence of herpes simplex virus DNA in the aqueous humor of an eye with Fuchs heterochromic iridocyclitis. METHODS: In an eye with a clinical diagnosis of Fuchs heterochromic iridocyclitis, samples of aqueous humor and anterior capsule of the lens were obtained during cataract surgery. Polymerase chain reaction was performed on the samples to detect the presence of viral DNA including herpes simplex virus, varicella-zoster virus, and cytomegalovirus. Serologic analysis was also performed for antiviral immunoglobulins. RESULTS: Herpes simplex virus DNA was identified in the aqueous humor but not in the anterior capsule. Serum immunoglobulin G was positive for herpes simplex virus, varicella-zoster virus, and cytomegalovirus. CONCLUSIONS: The presence of herpes simplex virus DNA in the aqueous humor of an eye with Fuchs heterochromic iridocyclitis suggests that herpes simplex virus infection may play a role in the pathogenesis of Fuchs heterochromic iridocyclitis.     

Ocular herpes simplex: changing epidemiology, emerging disease patterns, and the potential of vaccine prevention and therapy

PURPOSE: To review the changing epidemiology of herpes simplex virus infection, emerging patterns of herpetic ocular disease, and the challenges and promise of herpes simplex virus vaccine therapy. DESIGN: Perspective. METHODS: Literature review. RESULTS: An epidemic increase in genital herpes simplex type 2 infection is reflected in a 30% increase in HSV-2 antibodies in the United States since 1976. Approximately one in four people in the United States over age 30 is infected with HSV-2. Primary acquisition of herpes simplex type 1 is becoming progressively delayed in many industrialized countries, in contrast to developing nations where the virus is acquired early in life and is ubiquitous. Changes in sexual behavior among young adults have been associated with a recent increase in genital HSV-1 infection, resulting from oral-genital rather than genital-genital contact. Clinical trials of HSV vaccines using selected herpes simplex virus type 2 proteins mixed in adjuvant have shown limited efficacy in seronegative women, but not in men. CONCLUSIONS: The recent epidemic of genital herpes simplex type 2 infection is likely to result in an increase in neonatal ocular herpes and in delayed cases of acute retinal necrosis syndrome. The increase in genital HSV-1 may lead to industry production of vaccines that contain components of both HSV-1 and HSV-2 targeted toward limiting genital disease and transmission. As newer herpes simplex vaccines become available, ophthalmologists must be vigilant that a boost in immunity against HSV does not have a paradoxical effect in exacerbating break-through cases that develop immune-mediated herpes simplex stromal keratitis.     

Inflammatory eye changes in the mouse caused by herpesvirus. Changes caused by the cytopathogenic effect. An animal model

The reproducible inflammatory changes caused by infection with herpes simplex virus (Eidolon-Virus) in the anterior segment in mice represent a useful model. They are very similar to severe inflammation of the eye, as seen in herpes simplex infection. The method used by the authors to damage the corneal epithelium with a local anesthetic is similar to human pathology, in which a disturbance of the protective function of the corneal epithelium also facilitates infection by herpes simplex virus as well. The changes described are a starting point for further investigations.     

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。     

MANAGEMENT OF HERPES SIMPLEX KERATITIS: PROBLEMS ASSOCIATED WITH EPITHELIAL DISEASE

The management of active viral replication in the corneal epithelium is not always straightforward despite the availability of effective topical antiviral agents The list of lesions that may mimic epithelial infection with herpes simplex virus is long and now includes Acanthamoeba infection Problems with antiviral agent toxicity and corticosteroid administration may also at times obscure the diagnosis while at the same time making management difficult     

Herpes simplex virus epidemiology and ocular importance

PURPOSE: To review the changing epidemiology of herpes simplex disease and correlate it with the epidemiology of ocular herpes simplex disease. METHOD: A review of pertinent reports in the world literature about the epidemiology of herpes simplex and specifically about ocular herpes simplex. RESULTS: In developed countries, many individuals are reaching adolescence and adulthood without prior herpesvirus infection. Herpes simplex genital infection is increasing at a rapid rate in sexually active adolescents and adults, with about one in six adults now infected in the United States. Similar statistics are confirmatory worldwide in developed countries. Active herpes simplex infection is a risk factor for acquisition of human immunodeficiency virus. The Herpetic Eye Disease Study, as well as prior studies from Moorfields Eye Hospital and the Mayo Clinic in Rochester, Minnesota, provides us with the epidemiology of ocular herpes simplex. Recent studies suggest an older age of onset and perhaps overall more severe ocular disease as compared with the older literature. CONCLUSIONS: Herpes simplex is a significant health concern at present with genital infections increasing in epidemic proportions. This is also reflected in a rise in the incidence of neonatal herpes. Herpes simplex virus type 1 (HSV-1) infection is being acquired for the first time in an older age group. A significant and increasing proportion of genital herpes is caused by HSV-1. Serologic studies are no longer as useful in distinguishing orofacial herpes from genital herpes. More acute retinal necrosis syndrome cases are associated with HSV-2. Speculation about the future of ocular herpes is made based on this changing epidemiology.     

Management of herpes simplex keratitis: problems associated with epithelial disease

The management of active viral replication in the corneal epithelium is not always straightforward despite the availability of effective topical antiviral agents. The list of lesions that may mimic epithelial infection with herpes simplex virus is long and now includes Acanthamoeba infection. Problems with antiviral agent toxicity and corticosteroid administration may also at times obscure the diagnosis while at the same time making management difficult.     

慢性结膜炎患者泪液中腺病毒与单纯疱疹病毒的检测

目的 探讨慢性结膜炎患者泪液标本中腺病毒和单纯疱疹病毒的表达情况.方法 实验研究.2008年11月至2009年6月期间,在北京大学第三医院、北京大学眼科中心门诊采集81例临床确诊为慢性结膜炎(成人组66例、儿童组15例)、9例急性病毒性结膜炎及30例健康者的双眼泪液标本,采用聚合酶链反应(PCR)法特异性检测腺病毒及单纯疱疹病毒核酸的存在情况,并对PCR阳性结果结合临床症状和体征进行分析.采用两个样本例数的卡方检验.结果 在慢性结膜炎患者中,腺病毒阳性率为32.1%(26/81),单纯疱疹病毒阳性率为30.9%(25/81).在慢性结膜炎的儿童组患者中腺病毒阳性率为33.3%(5/15),单纯疱疹病毒阳性率为13.3%(2/15).成人组中腺病毒的阳性率为31.8%(21/66),单纯疱疹病毒阳性率为34.8%(23/66).在既往有急性结膜炎病史的患者中腺病毒的阳性率为61.5%(16/26),与既往无急性结膜炎病史的患者比较,差异有统计学意义(χ2=16.884,P＜0.01).单纯疱疹病毒阳性率为42.3%(11/26),与既往无急性结膜炎病史的患者比较,差异有统计学意义(χ2=5.351,P=0.021).正常阴性对照组病毒检测阳性率均为0%(0/30),阳性对照组即急性病毒性结膜炎组腺病毒阳性率为100.0%(9/9).81例慢性结膜炎患者中腺病毒和(或)单纯疱疹病毒阳性者为37例.病毒检测阳性的患者中64.9%(24/37)的患者出现眼红症状,56.8%(21/37)的患者出现眼痒症状,32.4%(12/37)的患者兼有眼红和眼痒,73.0%(27/37)的患者临床体征表现有下睑滤泡.结论 慢性结膜炎患者中腺病毒和单纯疱疹病毒的表达占有相当的比例,既往有明确感染史的患者病毒阳性率明显高于无既往感染史患者.     

Recurrent herpes simplex virus ocular infection: epidemiological and clinical features.

The epidemiological and clinical features of recurrent herpes simplex virus ocular infection (RHSV) were studied. Of 108 patients with primary herpes simplex virus ocular infection (PHSV) who were followed up for two to 15 years 35 (32%) suffered one or more recurrent attacks. The recurrence rate was significantly higher in patients under 20 years of age, but there was no significant difference between recurrence rates in males and females. Of 35 patients with RHSV 17 (49%) had one recurrent attack, 14 (40%) had between two and five, and four (11%) had between six and 15 attacks. The mean time interval between PHSV and the first four RHSV attacks was 10 months, and was shorter in subsequent attacks. The duration and severity of RHSV were reduced in successive recurrences. Patients with more severe conjunctivitis and lid lesions during PHSV ocular infection had a higher incidence of recurrent infection. The severity of the corneal signs in PHSV had no influence on the incidence of recurrent infection. Several clinical forms of RHSV were observed. Conjunctivitis associated with lid lesions was observed in 29 (83%) patients. In six (17%) patients the disease presented as an acute follicular conjunctivitis without characteristic lid or corneal lesions. Dendritic ulcer was found in three (9%) patients, and in one of them it was associated with a disciform keratitis. A chronic blepharoconjunctivitis developed in eight (23%) patients. The epidemiological and clinical features of RHSV were compared with those of PHSV.     

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.     

The ultrastructure of corneal epithelium after co-cultivation with herpes simplex virus

To elucidate the ultrastructural change of corneal epithelium co-cultured with herpes simplex virus (HSV), the corneal epithelium of 3 rabbits was excised and cultivated in culture media. After 7 days, the Kos strain of herpes simplex virus was inoculated in the cultured cornea epithelium until cytopathic effect was occurred. It was fixed in the solution of 3% glutaraldehyde and examined with electronmicroscope. In co-cultured cells, the intercellular spaces had increased and microvilli were seen prominently. The virus particles that initiated the infection by fusing the viral envelope with the plasma membrane were also seen. The nuclear degeneration in an infected cell was prominent. The nuclear membrane was folded markedly, and the chromatin was degraded, condensed and displaced toward the nuclear membrane. Numerous viral particles and inclusion bodies were present in the nuclei. These findings suggest that the infectious process of herpes simplex virus in the human corneal epithelium may occur in a similar way. This result would be helpful in understanding the pathogenesis of herpes simplex epithelial keratitis.     

High prevalence of herpes simplex virus type 2 in acute retinal necrosis syndrome associated with herpes simplex virus in Japan

PURPOSE: To determine the type of herpes simplex virus in acute retinal necrosis syndrome associated with herpes simplex virus. METHODS: Herpes simplex virus type 1, herpes simplex virus type 2, varicella-zoster virus, Epstein-Barr virus, and cytomegalovirus were examined by polymerase chain reaction in intraocular specimens from 16 patients with acute retinal necrosis syndrome. Anti-herpes simplex virus type 1 and anti-herpes simplex virus type 2 type-specific antibodies in serum from the patients were detected by enzyme immunoassay. RESULTS: Of 16 patients with acute retinal necrosis syndrome, seven were polymerase chain reaction positive for herpes simplex virus type 2 and nine were positive for varicella-zoster virus. Anti-herpes simplex virus type 2 antibody was positive and anti-herpes simplex virus type 1 antibody was negative in the sera of the seven patients with herpes simplex virus type 2 DNA-positive acute retinal necrosis syndrome. In contrast, anti-herpes simplex virus type 2 antibody was absent in all nine varicella-zoster virus DNA-positive acute retinal necrosis syndrome patients. CONCLUSION: Herpes simplex virus type 2 has been demonstrated to be the major causative agent in acute retinal necrosis syndrome associated with herpes simplex virus by molecular biological and serological methods. Negative preexisting anti-herpes simplex virus type 1 antibody may play an important role in acute retinal necrosis syndrome associated with herpes simplex virus type 2.     

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。     

Latanoprost-associated recurrent herpes simplex keratitis

PURPOSE/METHOD: We present a case of a patient who developed recurrent epithelial herpes simplex keratitis after starting treatment with latanoprost. Her ophthalmic history was only remarkable for a past episode of herpetic keratitis 21 years previously. RESULTS/CONCLUSIONS: Episodes of herpetic keratitis were under remission only when latanoprost was discontinued. No recurrences of herpes simplex keratitis have been observed since then. Latanoprost usage might be associated with recurrent episodes of herpes simplex keratitis in patients with previous history of ocular herpes simplex virus infection.     

Herpes simplex keratitis after ophthalmic surgery

PURPOSE: We report 6 cases of herpes simplex keratitis after ophthalmic surgery, in eyes without clinical history of herpes simplex keratitis. CASES: These cases comprised 6 patients examined at our hospital between April 1992 and November 2001. Past operations were keratoplasty in 5 eyes and cataract surgery in 1 eye. Clinical findings and predisposing factors were evaluated retrospectively. The period between herpetic epithelial keratitis onset and ophthalmic surgery ranged from 1.5 to 79 months. Predisposing factors included corticosteroid therapy and operative wound. The herpetic epithelial lesions were dendritic ulcers in 2 eyes, geographic ulcer in 1 eye, and atypical epithelial lesions in 3 eyes; in all cases, herpes simplex virus (HSV)-DNA was detected by polymerase chain reaction (PCR) in tear fluid. All herpetic epithelial lesions healed with oral and topical acyclovir. CONCLUSIONS: When corticosteroids are used following ophthalmic surgery, physicians should be alert to the possibility of herpetic epithelial keratitis, even in patients with no clinical history of herpes simplex keratitis. PCR detection in tear fluid is helpful in diagnosing this disease.