Conjunctival flap covering combined with antiviral and steroid therapy for severe herpes simplex virus necrotizing stromal keratitis.
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ABSTRACT:
SUBMITTER: Gao H
PROVIDER: S-EPMC4345056 | biostudies-other | 2015
REPOSITORIES: biostudies-other
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| S-EPMC4443501 | biostudies-literature
Project description:BACKGROUND:Eye disease due to herpes simplex virus (HSV) commonly presents as epithelial keratitis. OBJECTIVES:To compare the relative effectiveness of antiviral agents, interferon, and corneal débridement in the treatment of acute HSV epithelial keratitis. SEARCH STRATEGY:We searched CENTRAL (The Cochrane Library 2010, Issue 4), MEDLINE (January 1950 to October 2010), EMBASE (January 1980 to October 2010), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to October 2010), Zetoc (British Library's Electronic Table of Contents), System for Information on Grey Literature in Europe (openSIGLE), Biosciences Information Service (BIOSIS), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov), Japan Information Center of Science and Technology (JICST-EPlus), and China Academic Journals database (CAJ) via China National Knowledge Infrastructure (CNKI) with citations confirmed using China/Asia On Demand (COAD). There were no language or date restrictions in the search for trials. All databases except CNKI and COAD were last searched on 27 October 2010, CNKI and COAD were searched on 1 April 2010. We also searched literature digests, conference proceedings and reference lists. SELECTION CRITERIA:Of 152 eligible studies,106 comparative treatment trials involving 5872 eyes with dendritic or geographic epithelial keratitis were analysed for corneal healing over two weeks. DATA COLLECTION AND ANALYSIS:Interventions were compared at 14 days after trial enrolment by calculating a risk ratio (RR) that was adjusted with indirect RR, assessed by an inconsistency index (I(2) ) and supplemented by a seven-day RR and a hazard ratio (HR). MAIN RESULTS:Idoxuridine, though uncertainly better in healing outcome than control because of few trials with 14-day follow up, allowed earlier corneal re-epithelialisation. Vidarabine resulted in a significantly better outcome than placebo in one trial (RR 1.96; 95% CI 1.10 to 3.49). Compared to idoxuridine, in combined direct and indirect analyses, vidarabine (RR 1.11; 95% CI 1.03 to 1.19), trifluridine (RR 1.31; 95% CI 1.20 to 1.42), acyclovir (RR 1.23; 95% CI 1.16 to 1.31), brivudine (RR 1.38; 95% CI 1.18 to 1.61), and ganciclovir (RR 1.40; 95% CI 1.25 to 1.57) were significantly more effective. Trifluridine (RR 1.12; 95% CI 1.04 to 1.21) and acyclovir (RR 1.11; 95% CI 1.05 to 1.19) appeared more effective than vidarabine. No significant differences were found in comparisons between acyclovir, trifluridine and brivudine. The comparison of ganciclovir to acyclovir was limited by heterogeneity and possible publication bias. The joint use of two topical antivirals (RR 1.00; 95% CI 0.89 to 1.12) and the use of oral acyclovir alone (RR 0.92; 95% CI 0.79 to 1.07) or combined with a topical antiviral (RR 1.08; 95% CI 0.99 to 1.17) appeared as effective as topical antiviral therapy. Compared to antiviral monotherapy, the combination of an antiviral with interferon (RR 1.03; 95% CI 0.99 to 1.07) or with débridement (RR 1.04; 95% CI 0.95 to 1.14) did not yield significantly better outcomes but may have accelerated healing. The corneal epithelial healing outcome was improved when antiviral therapy was added to débridement (RR 1.21; 95% CI 1.04 to 1.42). AUTHORS' CONCLUSIONS:Trifluridine and acyclovir are more effective than idoxuridine or vidarabine, and similar in therapeutic effectiveness. Brivudine and ganciclovir are at least as effective as acyclovir. While not improving outcome, the combination of interferon and an antiviral agent may speed healing. The effectiveness of corneal epithelial débridement is improved by an antiviral agent.
| S-EPMC4739528 | biostudies-other
Project description:Herpes simplex virus type 1 (HSV-1) is a leading cause of infectious blindness. Current treatments for HSV-1 do not eliminate the virus from the site of infection or latent reservoirs in the trigeminal ganglia. Here, we target HSV-1 genomes directly using mRNA-carrying lentiviral particles that simultaneously deliver SpCas9 mRNA and viral-gene-targeting guide RNAs (designated HSV-1-erasing lentiviral particles, termed HELP). We show that HELP efficiently blocks HSV-1 replication and the occurrence of herpetic stromal keratitis (HSK) in three different infection models. HELP was capable of eliminating the viral reservoir via retrograde transport from corneas to trigeminal ganglia. Additionally, HELP inhibited viral replication in human-derived corneas without causing off-target effects, as determined by whole-genome sequencing. These results support the potential clinical utility of HELP for treating refractory HSK.
| S-EPMC7611178 | biostudies-literature
Project description:Herpes simplex virus mutants lacking the vhs gene are severely attenuated in animal models of pathogenesis and exhibit reduced growth in primary cell culture. As a result of these properties vhs-deleted virus have been proposed as live-attenuated viruses. Despite these findings and their implications for vacccines, the mechanisms by which vhs promotes infection in cell culture and in vivo are not understood. In this study we demonstrate that vhs-deficent viruses replicate to reduced levels in interferon(IFN)- primed cells. Furthermore, vhs-defective viruses induce increased levels of IFN? and IFN?-stimulated genes, and increased levels of eIF2? phosphorylation in infected cells. In addition, we demonstrate a generalized over-expression of viral RNAs following infection with a vhs-deficient virus. This suggests increased expression of IFN pathway inducing double stranded RNA, a potent pathogen-associated molecular pattern (PAMP). Together these data show that vhs likely functions to reduce innate immune responses and thereby acts as critical determinant of viral pathogenesis. Keywords: time course, genetic modification Time course (1,3,6,9 & 12h) of HSV infected mouse embryo fibroblasts. Wild type (KOS) virus is co-hybridized with vhs null virus (NHB). Each time-point is hybridized in quadruplicate.
2008-04-03 | E-GEOD-10962 | biostudies-arrayexpress
Project description:Herpetic stromal keratitis (HSK) is a blinding ocular disease that is initiated by HSV-1 and characterized by chronic inflammation in the cornea. Although HSK immunopathology of the cornea is well documented in animal models, events preceding this abnormal inflammatory cascade are poorly understood. In this study, we have examined the activation of pathological CD4(+) T cells in the development of HSK. Dendritic cell autophagy (DC-autophagy) is an important pathway regulating major histocompatibility complex class II (MHCII)-dependent antigen presentation and proper CD4(+) T cell activation during infectious diseases. Using DC-autophagy-deficient mice, we found that DC-autophagy significantly and specifically contributes to HSK disease without impacting early innate immune infiltration, viral clearance, or host survival. Instead, the observed phenotype was attributable to the abrogated activation of CD4(+) T cells and reduced inflammation in HSK lesions. We conclude that DC-autophagy is an important contributor to primary HSK immunopathology upstream of CD4(+) T cell activation.Herpetic stromal keratitis (HSK) is the leading cause of infectious blindness in the United States and a rising cause worldwide. HSK is induced by herpes simplex virus 1 but is considered a disease of inappropriately sustained inflammation driven by CD4(+) T cells. In this study, we investigated whether pathways preceding CD4(+) T cell activation affect disease outcome. We found that autophagy in dendritic cells significantly contributed to the incidence of HSK. Dendritic cell autophagy did not alter immune control of the virus or neurological disease but specifically augmented CD4(+) T cell activation and pathological corneal inflammation. This study broadens our understanding of the immunopathology that drives HSK and implicates the autophagy pathway as a new target for therapeutic intervention against this incurable form of infectious blindness.
| S-EPMC4626854 | biostudies-other
Project description:Herpes simplex virus mutants lacking the vhs gene are severely attenuated in animal models of pathogenesis and exhibit reduced growth in primary cell culture. As a result of these properties vhs-deleted virus have been proposed as live-attenuated viruses. Despite these findings and their implications for vacccines, the mechanisms by which vhs promotes infection in cell culture and in vivo are not understood. In this study we demonstrate that vhs-deficent viruses replicate to reduced levels in interferon(IFN)- primed cells. Furthermore, vhs-defective viruses induce increased levels of IFNβ and IFNβ-stimulated genes, and increased levels of eIF2α phosphorylation in infected cells. In addition, we demonstrate a generalized over-expression of viral RNAs following infection with a vhs-deficient virus. This suggests increased expression of IFN pathway inducing double stranded RNA, a potent pathogen-associated molecular pattern (PAMP). Together these data show that vhs likely functions to reduce innate immune responses and thereby acts as critical determinant of viral pathogenesis. Keywords: time course, genetic modification
2008-04-03 | GSE10962 | GEO
Project description:Purpose:To describe four cases of concomitant herpes simplex keratitis (HSK) and autoimmune-associated ulcerative keratitis (UK) in patients with rheumatoid arthritis (RA). Observations:All patients developed HSK and UK while undergoing treatment for RA. The average age of onset for RA, UK and HSK was 49.3, 69.5 and 70.5 years, respectively. UK preceded HSK in three cases and followed HSK in one case. Two patients had bilateral UK and two had unilateral UK. HSK was unilateral in all cases. All the cases had been treated with immunosuppressive agents including steroid, methotrexate, calcineurin inhibitors, etanercept and tocilizumab at the onset of HSK. Every patient was treated for HSK with topical acyclovir ointment combined with oral valacyclovir. The final visual outcome was extremely poor despite intensive therapy. Conclusions and Importance:These cases raise the possibility that RA patients have an increased risk of HSK, and that HSK may tend to be severe in these patients because of their immunocompromised condition. Furthermore, the complication of HSK and UK in RA patients is difficult to treat because of the atypical clinical manifestation. Thus, the emergence of corneal ulcer, especially in patients with a long clinical history of RA, calls for careful follow-up.
| S-EPMC7136173 | biostudies-literature
Project description:Background and Objectives: This paper aims to describe the single nucleotide polymorphisms (SNPs) of C21orf91 rs1062202 and rs10446073 in patients with herpetic keratitis by evaluating corneal sub-basal nerves, as well as the density of Langerhans cells (LC) and endothelium cells (EC) during the acute phase of the disease. Materials and Methods: A prospective clinical study included 260 subjects: 70 with herpetic eye disease, 101 with previous history of herpes labialis-but no history of herpetic eye disease-and 89 with no history of any herpes simplex virus (HSV) diseases. All subjects underwent a complete ophthalmological examination including in vivo laser scanning confocal microscopy (LSCM) of the central cornea. C21orf91 rs1062202 and rs10446073 were genotyped using the real-time polymerase chain reaction (PCR) method with the Rotor-Gene Q real-time PCR quantification system. SNPs were determined using TaqMan genotyping assay, according to the manufacturer's manual. Results: The C21orf91 rs10446073 genotype GT was more frequent in the HSV keratitis group, compared with healthy controls (20.0% vs. 7.9%), OR 2.929[1.11-7.716] (p <0.05). The rs10446073 genotype TT was more frequent in healthy controls (12.4% vs. 1.4%), OR 22.0[2.344-260.48] (p <0.05). The rs10446073 genotype GT increased the risk of EC density being less than 2551.5 cell/mm2, OR 2.852[1.248-6.515] (p <0.05). None of the SNPs and their genotypes influenced the LC density and corneal sub-basal nerve parameters (p >0.05). Conclusions: Our study reports a new association between herpetic keratitis and human gene C21orf91, with the rs10446073 genotype GT being more common in herpetic keratitis patients and increasing the risk for the disease by a factor of 2.9.
| S-EPMC6956000 | biostudies-literature
Project description:Background and objectives: Recurrent herpes simplex keratitis (HSK) is the most common cause of corneal blindness in the developed world. A relationship between host gene polymorphisms and the recurrence of herpes simplex virus (HSV) infection has previously been proposed. Thus, the aim of this study was to investigate a potential association between the IL28B host genotype and recurrent HSK. Materials and Methods: Eighty patients older than 18 years of age of both genders with a history of recurrent herpes simplex labialis (HSL) were considered for inclusion. Seventy-five of these patients were found to be seropositive for HSV-1 and were subsequently enrolled in the study. Twenty-four of the enrolled patients also had a history of recurrent HSK associated with severe corneal scarring and visual acuity deterioration. Total DNA was isolated from whole blood samples. A single-nucleotide polymorphism (SNP) rs12979860 near the IL28B gene on chromosome 19 was genotyped. Results: A significant association was observed between recurrent HSK and two SNPs of the IL28B genotype (CCrs12979860 and CTrs12979860, p < 0.01). The variation CCrs12979860 showed a significantly greater association with HSK (16 out of 26 patients) compared with CTrs12979860 (8 out of 34 patients). Conclusion: Seropositive individuals with a history of recurrent HSK are likely to have the CC IL28B genotype. This genotype may be related to incomplete control of the infection and more frequent periodical viral shedding along the first nerve branch of the trigeminal ganglion, which clinically manifests as recurrent herpes keratitis. The clinical manifestation of recurrent HSV-1 infection seems to be influenced by polymorphism of the IL28B genotype.
| S-EPMC6843532 | biostudies-literature
Project description:The aim of the present study was to investigate the use and effectiveness of a selective, partial, pedunculated (tongue-shaped) conjunctival flap (CF) for the treatment of refractory fungal keratitis (FK) with or without perforation. A total of 31 cases of corneal diseases treated by CF surgery between April 2014 and October 2015 were evaluated. Among the 31 cases, 16 cases (male:female, 11:5) with FK were selected. Logistic regression analysis was used to investigate factors associated with complications of CF surgery. A higher prevalence of FK was identified among male farmers compared with female farmers, in which plant trauma was the most prevalent cause of the disease. Only 4 patients had experienced corneal perforation prior to CF surgery. Patients aged 61-80 years had a higher prevalence of FK (50%) compared with other age groups; however, there was no statistically significant correlation between the prevalence of FK and sex or age. It was also demonstrated that age, sex, combined surgery and surgery duration were not significantly associated with post-surgical complications. All CF surgeries were performed following corneal ulcer scraping; however, 4 patients (12.5%) required additional surgery. The visual acuity of participants post-surgery decreased in 4 cases and remained unchanged in 12 cases. A total of 3 study patients experienced post-surgical complications of corneal perforation (1 patient) and purulent exudate spreading (2 patients). The post-surgical outcome was good for all study participants as the surgeries were able to control infection and preserve the eyeball, with the potential of future corneal transplant. These results suggest that CF surgery may be a useful alternative treatment for refractory FK in countries such as China where there is lack of cornea donors.
| S-EPMC5525570 | biostudies-other