Classification of Herpes Simplex Virus Keratitis

Holland, Edward J.; Schwartz, Gary S.

doi:10.1097/00003226-199903000-00002

Cited by 166 publications

(115 citation statements)

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“…The complex nomenclature of HSV corneal syndromes (25,37) emphasizes division by the anatomical layer(s) involved and the extent of active viral replication. Most cases begin as superficial epithelial infections.…”

Section: Discussionmentioning

confidence: 99%

Tegument-Specific, Virus-Reactive CD4 T Cells Localize to the Cornea in Herpes Simplex Virus Interstitial Keratitis in Humans

Koelle

Reymond

Chen

et al. 2000

J Virol

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Herpes stromal keratitis (HSK) is a prevalent and frequently vision-threatening disease associated with herpes simplex virus type 1 (HSV-1) infection. In mice, HSK progression occurs after viral clearance and requires T cells and neutrophils. One model implicates Th1-like CD4 T cells with cross-reactivity between the HSV-1 protein UL6 and a corneal autoantigen. HSK can be prevented by establishing specific immunological tolerance. However, HSK can also occur in T-cell receptor-transgenic X SCID mice lacking HSV-specific T cells. To study the pathogenesis of HSK in the natural host species, we measured local HSV-specific T-cell responses in HSK corneas removed at transplant surgery (n ‫؍‬ 5) or control corneas (n ‫؍‬ 2). HSV-1 DNA was detected by PCR in two specimens. HSV-specific CD4 T cells were enriched in three of the five HSK specimens and were not detectable in the control specimens. Reactivity with peptide epitopes within the tegument proteins UL21 and UL49 was documented. Responses to HSV-1 UL6 were not detected. Diverse HLA DR and DP alleles restricted these local responses. Most clones secreted gamma interferon, but not interleukin-5, in response to antigen. HSV-specific CD8 cells were also recovered. Some clones had cytotoxic-T-lymphocyte activity. The diverse specificities and HLA-restricting alleles of local virus-specific T cells in HSK are consistent with their contribution to HSK by a proinflammatory effect.Herpes simplex keratitis (HSK) is a common and frequently vision-threatening disease. In the natural human host, interstitial inflammation leading to opacification of the light path occurs in 28 to 40% of persons with herpes simplex virus (HSV) infection of the corneal epithelium. Recovery of live virus from the corneal stroma, in the absence of epithelial ulceration, is uncommon, and antiviral therapy does little to prevent the progression from epithelial to stromal disease. In contrast, corticosteroids and cyclosporin A, compounds with antileukocyte effects, are therapeutic. These clinical observations and murine models have recently been reviewed (21, 37). Despite the lack of spontaneous HSV reactivation in mice, these models partially replicate human HSK in that initial productive viral infection is followed by leukocyte infiltration, virus clearance, and an interval of normal histology. A second phase of leukocyte infiltration and chronic inflammation then occurs in the absence of live virus. Hypotheses developed in these models are addressed here using human corneal specimens.Murine models show that both virus and host factors are involved in the pathogenesis of HSK. Live virus scarification into the cornea is required. Inoculation into the anterior chamber leads to antigen-specific tolerance rather than immunopathology (18, 45). The conclusions from various murine models are widely disparate, however. In the congenic mouse strains C.AL-20 and C.B-17, which differ in susceptibility to HSK, an elegant three-way molecular mimicry has been shown to explain both susceptibility and resistance ...

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Section: Discussionmentioning

confidence: 99%

Tegument-Specific, Virus-Reactive CD4 T Cells Localize to the Cornea in Herpes Simplex Virus Interstitial Keratitis in Humans

Koelle

Reymond

Chen

et al. 2000

J Virol

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“…The cornea buttons analyzed were obtained from three patients with a fulminant HSV-induced necrotizing stromal keratitis after therapeutic penetrating keratoplasty. HSK classification and disease status were defined on the basis of clinical criteria (33). None of the patients were treated with steroids.…”

Section: Rna Isolation and Rt-pcr Analysesmentioning

confidence: 99%

IL-17 Expression in Human Herpetic Stromal Keratitis: Modulatory Effects on Chemokine Production by Corneal Fibroblasts

Maertzdorf

Osterhaus

Verjans

2002

The Journal of Immunology

118

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Herpetic stromal keratitis (HSK) is an immunopathologic disease triggered by infection of the cornea with HSV. Key events in HSK involve the interaction between cornea-infiltrating inflammatory cells and resident cells. This interaction, in which macrophages, producing IL-1 and TNF-α, and IFN-γ-producing Th1 cells play a crucial role, results in the local secretion of immune-modulatory factors and a major influx of neutrophils causing corneal lesions and blindness. The Th1-derived cytokine IL-17 has been shown to play an important role in several inflammatory diseases characterized by a massive infiltration of neutrophils into inflamed tissue. Here we show that IL-17 is expressed in corneas from patients with HSK and that the IL-17R is constitutively expressed by human corneal fibroblasts (HCF). IL-17 exhibited a strong synergistic effect with TNF-α on the induction of IL-6 and IL-8 secretion by cultured HCF. Secreted IL-8 in these cultures had a strong chemotactic effect on neutrophils. IL-17 also enhanced TNF-α- and IFN-γ-induced secretion of macrophage-inflammatory proteins 1α and 3α, while inhibiting the induced secretion of RANTES. Furthermore, considerable levels of IFN-γ-inducible protein 10 and matrix metalloproteinase 1 were measured in stimulated HCF cultures, while the constitutive secretion of monocyte chemotactic protein 1 remained unaffected. The data presented suggest that IL-17 may play an important role in the induction and/or perpetuation of the immunopathologic processes in human HSK by modulating the secretion of proinflammatory and neutrophil chemotactic factors by corneal resident fibroblasts.

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“…Corneal endothelium plays an important role in maintaining corneal transparency and its abnormality or dysfunction results in corneal edema. Ocular trauma, surgeries, Fuchs endothelial dystrophy, iridocorneal endothelial syndromes (ICE), stromal keratitis, and endotheliitis should be considered in the differential diagnosis of corneal edema [2,[4][5][6][7][8]. In our case, the absence of any ocular trauma or surgery, no signs of cornea guttae, and a normal specular microscopic examination in the fellow eye, and the lack of iris findings and typical specular findings for ICE syndrome in the left eye, led us to the diagnosis of endotheliitis of viral origin.…”

Section: Discussionmentioning

confidence: 99%

Atypical Herpetic Corneal Endotheliitis: A Case Report

Karalezlı¹

2016

Ann Clin Anal Med

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ÖzetKorneal endotelit, sıklıkla viral orijinli olan ve primer olarak kornea endotelinin iflamasyonunun gözlendiği bir hastalıktır. Bu olgu sunumunda ön kamara reaksiyonunun gözlenmediği sadece tek taraflı yaygın korneal ödem ile giden atipik herpetik korneal endotelitli bir olguyu sunuyoruz. Anahtar KelimelerKorneal Ödem; Endotelitis; HSV Abstract Corneal endotheliitis; frequently caused by viruses, is a disorder in which corneal endothelium is the primary site of the inflammation. We discuss a case of atypical herpetic endotheliitis presented with unilateral diffuse corneal edema with no signs of anterior chamber reaction.

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Classification of Herpes Simplex Virus Keratitis

Cited by 166 publications

References 0 publications

Tegument-Specific, Virus-Reactive CD4 T Cells Localize to the Cornea in Herpes Simplex Virus Interstitial Keratitis in Humans

Tegument-Specific, Virus-Reactive CD4 T Cells Localize to the Cornea in Herpes Simplex Virus Interstitial Keratitis in Humans

IL-17 Expression in Human Herpetic Stromal Keratitis: Modulatory Effects on Chemokine Production by Corneal Fibroblasts

Atypical Herpetic Corneal Endotheliitis: A Case Report

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