The aim of this thesis is to elucidate pathogenic mechanisms of different forms of human HSV keratitis. HSV infection of the corneal epithelium causes a classical dendritic shaped lesion. Many studies could explain the development and growth in dendritic keratitis, but none of these found the anatomical substrate for the linear branching pattern. The most obvious explanation would be, that the shape of dendritic ulcers corresponds with the anatomical pattern of innervating nerves of the cornea. In chapter 2 a relationship between the shape of dendritic ulcers in infectious epithelial keratitis and the subbasal nerve plexus of the corneal epithelium is postulated. Recurrence of HSV keratitis is a common complication after PKP for corneal opacities resulting from HSV infection. After PKP, for reasons unrelated to HSV keratitis, epithelial defects may still be caused by HSV. In chapter 3 the incidence of newly acquired HSV keratitis after PKP is determined and possible contributing factors are assessed. Several possibilities as to the origin of the infecting HSV exist. These include reactivation oflatent virus in the trigeminal ganglion, horizontal spread, or transmission through the donor cornea. To test the assumption of graft-to-host transmission of HSV by PKP, surplus corneal material was examined for the presence of HSV DNA. Because the amount of viral DNA available could be very limited, a new method independent of viral culture, was developed to allow distinction between different virus strains. The newly developed technique was used to test our hypothesis that graft-to-host transmission of HSV is possible. This new method was used to determine the incidence of HSV-1 superinfection in patients with recurrent HSV keratitis. Although HSK has been studied extensively in the mouse model, it is not clear what triggers the immune response and to what extent the mouse data correlate with findings in human keratitis. The most logical idea, that virus-derived proteins are the eliciting factor for the immune response, has been ruled out in the experimental HSK mouse model. Alternative sources of the keratogenic antigens, like auto-antigens, have been suggested. Data on the pathogenesis of human HSK are limited. Therefore, in chapter 4 the antigenspecificity of corneal T cells in HSK patients was investigated. Besides this, corneas of patients with HSK were examined for the presence of corneal antigen reactive T cells (auto-reactive T cells). Chapter 5 provides a concise summary of the data generated in the framework of this thesis, and concludes with an overall discussion of the data and their possible impact on current ophthalmologic practice.

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A.D.M.E. Osterhaus (Albert)
Erasmus University Rotterdam
THE STUDIES IN THIS THESIS WERE FINANCIALLY SUPPORTED BY: Rotterdamse Vereniging Blindenbelangen, Stichting Wetenschappelijk Onderzoek Oogziekenhuis Rotterdam, Hoornvlies Stichting Nederland, Stichting OOG, De Flierenga·Houet Stichting, Dr. F.P.Fischer Stichting
Erasmus MC: University Medical Center Rotterdam

Remeijer, L. (2002, June 20). Human herpes simplex virus keratitis: the pathogenesis revisted. Erasmus University Rotterdam. Retrieved from