Double Trouble: An Unusual Keratitis Case of Herpes Simplex Virus and Varicella-Zoster Virus Co-infection.

PURPOSE: The aim of this study was to describe a case of herpes simplex virus (HSV) and varicella-zoster virus (VZV) corneal co-infection in a patient with systemic immunosuppression. METHODS: A 77-year-old White man who was recently administered pembrolizumab present with reduction in visual acuity in his left eye from 20/25 to 20/50. There was a known history of ocular HSV keratitis. Slit-lamp examination showed superficial dendritic lesions suggestive of VZV. RESULTS: Viral polymerase chain reaction testing was positive for both HSV and VZV, confirming clinical diagnosis of VZV keratitis in the setting of recurrent HSV keratitis. The infection responded to treatment with topical trifluridine. Two months later, he had another episode of keratitis based on his symptoms reported through telephone encounter which resolved with trifluridine. Unfortunately, the patient committed suicide 4 months after onset. CONCLUSIONS: This is the first case of keratitis with HSV and VZV co-infection likely related to systemic immunosuppression. Clinicians should have a high suspicion for viral co-infections in the setting of systemic immunosuppression.

AmpliVue Is a Practical and Timely Test for the Detection of HSV From Keratitis Specimens.

OBJECTIVE: The laboratory diagnostic detection of herpes simplex virus (HSV) from eye samples must be practical, timely, and definitive for appropriate therapy. Although polymerase chain reaction (PCR) and/or cell culture can be definitive, HSV results can be delayed. Enzyme Linked Virus Inducible System (ELVIS) is a test that can provide results within 24 to 48 hr. We evaluated "AmpliVue HSV 1+2 Assay" as a molecular colorimetric test that can detect HSV (1 or 2) DNA within 1 hr. METHODS: Cornea/conjunctival samples were tested retrospectively with AmpliVue against 53 true-positive and 20 true-negative specimens collected in chlamydial transport medium. All clinical specimens were tested by cell culture isolation, PCR, and ELVIS for routine patient care. RESULTS: The sensitivity of AmpliVue against ocular samples that were both culture-positive and PCR-positive was 84%. The specificity of AmpliVue was 100%. Only one clinical sample was HSV-2 positive, whereas all others tested positive for HSV-1. Based on PCR-positive and cell culture-negative samples, AmpliVue (11 of 17) tested more positive than ELVIS (0 of 17) (P=0.003, Fisher Exact). CONCLUSIONS: AmpliVue is moderately sensitive and highly specific as a practical and timely diagnostic test for detecting ocular HSV. Expertise is readily achieved and the test is straightforward with easy interpretation. Negative AmpliVue testing must be confirmed with PCR. AmpliVue has potential as an office-based diagnostic test.

Long-term Outcomes of Pediatric Penetrating Keratoplasty for Herpes Simplex Virus Keratitis.

PURPOSE: To analyze the characteristics and long-term outcomes of patients that underwent pediatric penetrating keratoplasty (PPK) for herpes simplex virus (HSV) keratitis. DESIGN: Retrospective, interventional, consecutive case series. METHODS: Observational report of outcomes and findings for 9 patients with history of HSV keratitis that underwent PPK and were followed in a single institution. Difference between the median preoperative and final best-corrected visual acuity (BCVA) was assessed and the outcomes are reported. RESULTS: We included 9 eyes; median age at the moment of the PPK was 14 years. The median initial BCVA was 20/400 (range 20/60 to hand motion) and final was 20/50 (range 20/30 to 20/400) (P < .05). Follow-up was a median of 94 months. Complications in these patients included glaucoma (1), graft rejection (1), recurrence of disease (1), and amblyopia (3). No graft failures were present. CONCLUSION: The long-term outcomes with PPK for HSV keratitis in children provide improvement in BCVA when not compromised by amblyopia.

Herpes Simplex Virus Disease of the Anterior Segment in Children.

PURPOSE: To analyze the clinical presentation, characteristics, treatment, recurrences, and final outcomes and complications of herpes simplex virus (HSV) disease of the anterior segment in patients aged 17 years or younger. METHODS: This is an observational and retrospective study with review of the medical records of all the children diagnosed with herpes simplex infection of the anterior segment at an ophthalmologic referral center, from 2002 to 2012. The diagnosis was made on the basis of the history and examination of patients and in specific cases by viral culture and the polymerase chain reaction. Main outcome measurements included final visual acuity, bilateral disease, and recurrence. Recurrent disease was analyzed with Kaplan-Meier curves. RESULTS: A total of 103 patients were included with a median age at presentation of 9 years. Of them, 6 had bilateral and simultaneous disease. The median follow-up time was 18 months (range, 18 days-12 years). The most common clinical manifestations were epithelial dendritic keratitis in 42 eyes (38.5%) and interstitial keratitis in 39 eyes (35.7%), with 15 patients presenting multiple forms of HSV disease. The median final visual acuity in the group of patients was 20/40. Recurrent disease was evident in 42 (38.5%) of the eyes, with a median recurrence time of 15 months (95% confidence interval, 8.1-26.2 months). CONCLUSIONS: In this study, epithelial dendritic and interstitial keratitis were the most frequent forms of disease in the pediatric population with HSV of the anterior segment. A high rate of recurrent disease was present.

Incidence of Alpha-Herpes virus induced ocular disease in Suriname.

Herpes simplex virus (HSV) infection of the corneal stroma is the most prominent cause of scar formation impairing visual acuity and HSV keratitis is the leading cause of corneal opacity throughout the world. Suriname lacked test systems for microbial causes of ocular disease, therefore a polymerase chain reaction-based Herpes virus assay was introduced, enabling prompt recognition, and timely treatment, preventing progressive eye damage. The incidence and epidemiology of Herpes simplex virus type 1 (HSV-1), type 2 (HSV-2), and varicella zoster virus (VZV) in ocular disease in Suriname was assessed. In a cross-sectional prospective study, ocular swabs were collected from 91 patients with a presumptive α-Herpes virus ocular infection attending the Academic Hospital between November 2008 and August 2010 and were tested by a PCR-based α-Herpes virus assay. Alpha-Herpes virus ophthalmic infections were caused predominantly by HSV-1 with a prevalence of 31%. The prevalences of VZV, HSV-2, and a mixed HSV-1/HSV-2 infection were 4%, 3%, and 2%, respectively. The first reported annual incidence of herpetic induced ocular disease in Suriname was estimated at 11.4 per 100,000 person-years (95% CI, 4.8-18.1). No clear age, ethnic or gender dependent difference in incidence was observed. The information obtained on α-Herpes virus positive ocular infections and the distribution of subtypes provided the first insight in the South American situation of α-Herpes virus induced ocular disease.

Detecção do vírus herpes simples por reação em cadeia da polimerase em pacientes com ceratite herpética típica ou atípica / Molecular detection of herpes simplex virus by polymerase chain reaction in patients with typical and atypical herpetic keratitis

OBJETIVO: Avaliação dos pacientes com o quadro clínico de ceratite herpética (CH) típicas e atípicas, pela reação em cadeia da polimerase (PCR) correlacionando com o diagnóstico clínico. MÉTODOS: Foi realizada a PCR em 28 pacientes com ceratite herpética típica e atípica. RESULTADOS: A PCR foi positiva em 57,14 por cento (n=16) do total (n=28). Nos casos de CH típica a positividade foi de 60,00 por cento (n=12) em 20 casos. Para CH epitelial a positividade foi de 69,23 por cento (n=9), sendo 77,78 por cento (n=7) apenas para as lesões epiteliais dendríticas. Os casos de CH atípica apresentaram positividade de 50 por cento (n=4) em oito casos. CONCLUSÃO: Quadro clínico típico de CH teve boa correlação com o resultado positivo observado na PCR. Entretanto, metade dos pacientes com o quadro de CH atípica apresentou PCR positivo, portanto, o exame do PCR é teste importante para o auxílio e diagnóstico da CH. No caso de CH estromal, foi demonstrado que a técnica da PCR conseguiu identificar o vírus HSV.

PURPOSE: To evaluate patients with clinically typical and atypical herpetic keratitis (HK) by means of polymerase chain reaction (PCR) as compared with the clinical diagnosis. METHODS: PCR in 28 patients with clinical symptoms of typical and atypical HK was performed. RESULTS: PCR was positive in 57.14 percent (n=16) of the total cases (n=28). The test was positive in 60.0 percent (n=12) of the 20 typical HK cases. For epithelial HK, the test was positive in 69.23 percent (n=9), and 77.78 percent (n=7) only for dendritic injuries. Atypical HK presented a positive test in 50 percent (n=4) of eight cases. CONCLUSION: Clinical typical picture of HK had a good correlation with the positive result of PCR, mainly for epithelial injury of the dendritic type. However, 50 percent of the patients with atypical HK presented positive PCR. This result showed that PCR test can provide an effective HK diagnosis. In the stromal case of HK, PCR was a useful technique to identify HSV virus.

[Molecular detection of herpes simplex virus by polymerase chain reaction in patients with typical and atypical herpetic keratitis]. / Detecção do vírus herpes simples por reação em cadeia da polimerase em pacientes com ceratite herpética típica ou atípica.

PURPOSE: To evaluate patients with clinically typical and atypical herpetic keratitis (HK) by means of polymerase chain reaction (PCR) as compared with the clinical diagnosis. METHODS: PCR in 28 patients with clinical symptoms of typical and atypical HK was performed. RESULTS: PCR was positive in 57.14% (n=16) of the total cases (n=28). The test was positive in 60.0% (n=12) of the 20 typical HK cases. For epithelial HK, the test was positive in 69.23% (n=9), and 77.78% (n=7) only for dendritic injuries. Atypical HK presented a positive test in 50% (n=4) of eight cases. CONCLUSION: Clinical typical picture of HK had a good correlation with the positive result of PCR, mainly for epithelial injury of the dendritic type. However, 50% of the patients with atypical HK presented positive PCR. This result showed that PCR test can provide an effective HK diagnosis. In the stromal case of HK, PCR was a useful technique to identify HSV virus.

An immunofluorescence test for diagnosis of ophthalmic herpes in a mouse corneal model.

Herpes simplex virus type 1 (HSV-1) ophthalmic disease is the most common cause of corneal blindness in humans world-wide. Current culture techniques for HSV take several days and commercially available HSV laboratory based diagnostic techniques vary in sensitivity. Our study was conducted to evaluate the use of a quicker and simpler method to herpes ophthalmic diagnosis. Corneal smears were made by firm imprints of infected mouse eyes to glass slides, after smears were fixated with cold acetone, and an indirect immunofluorescence (IIF) method was performed using monoclonal antibodies in a murine model of ophthalmic herpes. Eye swabs from infected mice were inoculated in Vero cells for virus isolation. Cytology and histology of the eye were also performed, using hematoxylin-eosin routine. Mouse eyes were examined by slit-lamp biomicroscopy for evidence of herpetic disease at various times postinoculation. We made a comparative evaluation of sensitivity, specificity and speed of methods for laboratory detection of HSV. Our results indicate that this IIF method is quick, sensitive, specific and can be useful in the diagnosis of ophthalmic herpes as demonstrated in an animal model.

An immunofluorescence test for diagnosis of ophthalmic herpes in a mouse corneal model

Herpes simplex virus type 1 (HSV-1) ophthalmic disease is the most common cause of corneal blindness in humans world-wide. Current culture techniques for HSV take several days and commercially available HSV laboratory based diagnostic techniques vary in sensitivity. Our study was conducted to evaluate the use of a quicker and simpler method to herpes ophthalmic diagnosis. Corneal smears were made by firm imprints of infected mouse eyes to glass slides, after smears were fixated with cold acetone, and an indirect immunofluorescence (IIF) method was performed using monoclonal antibodies in a murine model of ophthalmic herpes. Eye swabs from infected mice were inoculated in Vero cells for virus isolation. Cytology and histology of the eye were also performed, using hematoxylin-eosin routine. Mouse eyes were examined by slit-lamp biomicroscopy for evidence of herpetic disease at various times postinoculation. We made a comparative evaluation of sensitivity, specificity and speed of methods for laboratory detection of HSV. Our results indicate that this IIF method is quick, sensitive, specific and can be useful in the diagnosis of ophthalmic herpes as demonstrated in an animal model.

A doença oftálmica do vírus herpes simplex do tipo 1 (HSV-1) é a causa mais comum de cegueira córnea em humanos mundialmente. Técnicas de cultura atuais para HSV levam vários dias e laboratórios de HSV comercialmente disponíveis estabelecem que as técnicas diagnósticas variam em sensibilidade. Nosso estudo foi conduzido para avaliar a aplicação prática de um método mais rápido e simples para diagnosticar o herpes oftálmico. Decalques córneos foram feitos por impressões firmes de olhos de camundongos a lâminas de vidro, depois os decalques foram fixados com acetona fria, e um método de imunofluorescência indireta (IIF) foi executado empregando anticorpos monoclonais no modelo murino de herpes oftálmico. Swabs de córnea foram inoculados em células Vero para o isolamento de vírus a partir de camundongos infectados. A citologia e a histologia do olho foi feita pela rotina de hematoxilina e eosina. Os olhos de camundongos foram examinados através de oftalmomicroscopia para evidência de doença herpética em vários tempos pós-inoculação. A avaliação comparativa da sensibilidade, especificidade e velocidade de métodos para detecção laboratorial de HSV foi feita. Nossos resultados indicam que este método de IIF é rápido, sensível, específico e pode ser útil no diagnóstico de herpes oftálmico como demonstrado no modelo animal.

Herpes simplex uveitis.

BACKGROUND: Uveitis in herpes simplex virus (HSV) ocular disease is usually associated with corneal stromal disease. It has generally been believed that herpetic uveitis in the absence of corneal disease is very rare. When seen it is usually attributed to varicella zoster virus (VZV) infections. The diagnosis of uveitis caused by herpes simplex is often not diagnosed resulting in inadequate treatment and a poor visual result. METHODS: Seven patients from a large uveitis practice who presented with a clinical picture of: anterior uveitis and sectoral iris atrophy without keratitis, a syndrome highly suggestive of herpetic infection, are reported. Polymerase chain reaction (PCR) was done in the aqueous of four of them and was positive for HSV. One patient had bilateral disease. Most of the patients also had severe secondary glaucoma. RESULTS: Of the seven patients presented five had no history of any previous corneal disease. Two had a history of previous dendritic keratitis which was not active at the time of uveitis development. One patient with bilateral disease was immunosuppressed at the time when the uveitis developed. Six of the seven patients had elevated intraocular pressures at the time of uveitis and five required glaucoma surgery. Intractable glaucoma developed in two patients leading to rapid and severe visual loss despite aggressive management. CONCLUSION: Findings suggest that uveitis without corneal involvement may be a more frequent manifestation of ocular herpes simplex disease than previously thought. Absence of corneal involvement delays a correct diagnosis and may worsen visual outcome. Primary herpetic uveitis (when there is no history of previous corneal disease) seems to be more severe than the uveitis in patients with previous corneal recurrences. The associated glaucoma may be a devastating complication.

Herpes simplex uveitis

BACKGROUND: Uveitis in herpes simplex virus (HSV) ocular disease is usually associated with corneal stromal disease. It has generally been believed that herpetic uveitis in the absence of corneal disease is very rare. When seen it is usually attributed to varicella zoster virus (VZV) infections. The diagnosis of uveitis caused by herpes simplex is often not diagnosed resulting in inadequate treatment and a poor visual result. METHODS: Seven patients from a large uveitis practice who presented with a clinical picture of: anterior uveitis and sectoral iris atrophy without keratitis, a syndrome highly suggestive of herpetic infection, are reported. Polymerase chain reaction (PCR) was done in the aqueous of four of them and was positive for HSV. One patient had bilateral disease. Most of the patients also had severe secondary glaucoma. RESULTS: Of the seven patients presented five had no history of any previous corneal disease. Two had a history of previous dendritic keratitis which was not active at the time of uveitis development. One patient with bilateral disease was immunosuppressed at the time when the uveitis developed. Six of the seven patients had elevated intraocular pressures at the time of uveitis and five required glaucoma surgery. Intractable glaucoma developed in two patients leading to rapid and severe visual loss despite aggressive management. CONCLUSION: Findings suggest that uveitis without corneal involvement may be a more frequent manifestation of ocular herpes simplex disease than previously thought. Absence of corneal involvement delays a correct diagnosis and may worsen visual outcome. Primary herpetic uveitis (when there is no history of previous corneal disease) seems to be more severe than the uveitis in patients with previous corneal recurrences. The associated glaucoma may be a devastating complication

Estudio clínico y virológico en un grupo de niños chilenos con herpes ocular: análisis genómico de las cepas / Clinical-virological study in chilean children with ocular herpes: genomic analysis of strains

Objetivo: Caracterizar el diagnóstico de infección ocular por virus herpes simples (HSV) en un grupo de niños chilenos, mediante el estudio clínico y de laboratorio virológico. Métodos: La población estudiada comprendió niños menores de 15 años, con diagnóstico clínico de herpes ocular, que fueron atendidos por los autores y un grupo de oftalmólogos entrenados especialmente para el estudio. Junto con detallar el tipo de infección herpética, a todos los pacientes se les tomaron muestra para estudio virológico que incluyó estudio de cultivos celulares y posteriormente técnica de reacción en cadena de polimerasa (PCR), con el fin de tipificar las cepas y características genómicas del virus infectante. Resultados: El estudio enroló 18 niños, cuyas edades fluctuaron entre los 40 días y 13 años, con una media de 6 años. De las formas clínicas observadas, la más frecuentes fueron la blefaritis y la queratitis dendrítica constituyendo en 27 y 22 por ciento de los casos, respectivamente. El diagnóstico de HSV fue confirmado en 15 de 18 pacientes, constituyendo un 83 por ciento de positividad. 14 de 15 casos correspondieron a HSV tipo 1, y en un niño se diagnóstico infección por HSV tipo 2. Los antecedentes clínicos de este caso confirmaron que se trataba de una infección perinatal, lo que permitió instaurar el tratamiento en forma oportuna. El estudio permitió identificar un caso de excreción ocular viral asintomática, lo que sumando a un cuadro de recurrencias múltiples obligó a indicar terapia profiláctica permanente con aciclovir. Conclusiones: La blefaritis y queratitis herpética constituyeron en conjunto el 70 por ciento de los casos. El rendimiento celular y PCR fue elevado en los casos con alto índice de replicación viral, como la queratitis y blefaritis. En los casos con menor replicación, como queratitis estromal o conjuntivitis, el estudio PCR demostró una mayor sensibilidad que el estudio en cultivo celular. La presencia de un caso de infección perinatal por HSV-2 pudiera ser indicativo de un aumento en la frecuencia de esta forma de presentación.

Ceratite herpética em transplante de córnea por causas não ligadas ao Herpes / Herpetic keratitis after penetrating keratoplasty for cases not related to herpes simplex infection

Objetivo: Alertar para a possibilidade do desenvolvimento de ceratite causada pelo HSV (Herpes Simplex Virus) no pós-operatório de ceratoplastia por causas não ligadas ao herpes. Local: Instituto de Oftalmologia Tadeu Cvintal - São Paulo - SP - Brasil. Método: Relato de casos e revisão de literatura. Resultado: Foi comprovado, através de exames complementares, a presença do HSV no transplante de córnea por causas não ligadas ao herpes Conclusão: A ceratite herpética deve constar no diagnóstico diferencial de casos de epiteliopatia persistente, úlceras de aspecto linear, dendrítico ou geográfico no pós-operatório de transplante de córnea, mesmo que a causa inicial da ceratoplastia não tenha relação com o HSV.

Detección del virus herpes simple tipo I por inmunofluorescencias directa en córneas nativas y transplantadas con leucomas postherpéticos / Detection of herpes simplex virus type 1 by direct immunofluorescence in native and transplanted corneas with postherpetic leukomas

Por muchos años se ha sabido que el virus HVS-1 se perpetúa en el ganglio trigeminal, una vez ocurrida su colonización; asimismo es ampliamente conocida la facilidad con que recidivan los cuadros herpéticos corneales. Algunos trabajos previos han demostrado la persistencia de partículas virales en córnea. En el presente trabajo se incluyeron pacientes con diagnóstico clínico de leucomas corneales (postherpéticos) inactivos y se estudiaron por técnicas de inmunofluorescencia directa bajo estrictas normas de seguridad. Se encontró 90 por ciento de positividad independientemente del tiempo transcurrido desde el último cuadro activo. El 10 por ciento de negatividad nos lo explicamos por errores en el diagnóstico inicial o por lesiones corneales secundarias a HVS-2.

Secuelas oculares debidas a infección herpética en un grupo de niños chilenos / Ocular sequels caused by herpetic infection in chilean children

Estudio prospectivo, multicéntrico, en el cual investigadores entrenados seleccionaron y siguieron clínica y virológicamente (aislamiento viral, anticuerpos monoclonales y PCR) pacientes de 0 a 18 años de edad con diagnóstico clínico de infección ocular por HSV. Se efectuó determinación de la agudeza visual (AV) por el Test de Mirada Preferencial, HOTV, E Snellen u optotipos de Snellen, con la mejor corrección óptica, examen refractivo bajo cicloplegia, estudio completo de estrabismo, topografía, paquimetría y fotografía. Se enrolaron entre 1993 a 1997 16 niños, dos de ellos con compromiso bilateral (18 ojos). En todos salvo un niño, se identificó HSV tipo I. Mediana de edad 5 años. El diagnóstico de ingreso fue el edema disciforme en 45 por ciento y en 33 por ciento de los casos una queratitis epitelial dendrítica. El 87,5 por ciento de los pacientes con edema disciforme presentó al menos una recurrencia por año. Los pacientes con compromiso epiteliar presentaron en todos los casos AV > 20/40, a diferencia de los pacientes con edema disciforme en que 71,4 por ciento presentaron AV final < de 20/50. El leucoma corneal fue severo en 62,5 por ciento de los ojos con edema disciforme y desarrollaron estrabismo 50 por ciento de los casos. En tres casos se requiere trasplante corneal. La enfermedad ocular herpética afecta principalmente a población joven y sana. El diagnóstico más frecuente fue el edema disciforme que presentó evolución crónica, requirió un gran número de consultas médicas y de tratamiento prolongado (entre 3 y 6 meses) y presentaron la mayor frecuencia de secualas. En general, el 78 por ciento de los pacientes estudiados desarrolló algún tipo de secuela visual

Utilidad del examen oftalmológico en el diagnóstico del herpes neonatal / Ophthalmologic exam is useful in the diagnosis of neonatal herpes virus infection

Con el propósito de mostrar la importancia del examen oftalmológico en niños con afecciones sistémicas y manifestaciones oculares se describe el caso de un lactante de 41 días, con antecedentes de meningoencefalitis, neumopatía, microcefalia y opacidad corneal, en cuyo examen oftalmológico con biomicroscopio se comprobó una extensa úlcera de la córnea, de la cual se identificó mediante cultivo, reacción de polimerasa en cadena y anticuerpos monoclonales, un virus herpes simplex tipo 2. El examen oftalmológico completo en niños, con alteraciones o malformaciones oculares, asociados a manifestaciones sistémicas, posiblemente causadas por infección congénita a perinatal puede ser de gran utilidad para orientar el diagnóstico y el tratamiento