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      Necrotizing Keratitis Caused by Acyclovir-Resistant Herpes Simplex Virus


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          Background: We report a case of necrotizing keratitis caused by acyclovir (ACV)-resistant herpes simplex virus (HSV) with a clinical appearance similar to a previous fungal keratitis infection. Methods: Observational case report. Results: Penetrating keratoplasty was performed in the left eye with a history of herpetic keratitis that resolved with periodic treatment with ACV ointment and a topical steroid. The left eye was painful and red with an abscess and corneal erosion in the peripheral donor cornea. Examination of the scraped corneal epithelium by light microscopy and culturing identified Candida albicans; polymerase chain reaction (PCR) was negative for human herpes viruses. After antifungal treatment, the ocular pain gradually decreased and the lesions slowly improved but recurred with a similar clinical appearance. A second light microscopy examination and cultures were negative for pathogens including C. albicans. PCR was positive for HSV-1 DNA; treatment with 3% topical ACV ointment was unsuccessful. A third examination showed only HSV-1 DNA. Despite antiviral ACV ointment, no clinical improvement occurred based on the HSV DNA copy numbers, which were the same before and after treatment, indicating a possible ACV-resistant strain. When topical trifluorothymidine was substituted for ACV, clinical improvement occurred and the HSV DNA copy numbers decreased. Conclusion: Necrotizing keratitis induced by ACV-resistant HSV occurred independently after fungal keratitis, with a similar clinical appearance in this case, making diagnosis and treatment difficult. Monitoring the HSV DNA load by real-time PCR could be useful for refractory cases even with atypical clinical appearances.

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          Most cited references6

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          Corneal Endotheliitis With Quantitative Polymerase Chain Reaction Positive for Human Herpesvirus 7

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            Immunopathogenesis of corneal inflammation in herpes simplex virus stromal keratitis: role of the polymorphonuclear leukocyte.

            The present studies suggest that polymorphonuclear leukocytes (PMNs) play an essential role in the development of corneal infiltrates in stromal herpes virus (HSV) keratitis. Corneal infiltration was seen rarely in herpes-infected animals treated with anti-PMN serum or with chemotherapy to reduce the numbers of circulating PMNs. By contrast, at least two thirds of the control animals with intact PMNs and infected with herpes virus developed stromal infiltrates. Host complement was localized with HSV antigen and rabbit gamma globulin along with inflammatory cells in the corneas of animals with stromal infiltrates. In the absence of PMN infiltrates, neither complement nor a significant amount of gamma globulin was localized in the corneal stroma. In the PMN-depleted animals, only viral antigen was detected in the stromal keratocytes.
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              Dendritic keratitis caused by an acyclovir-resistant herpes simplex virus with frameshift mutation.

              To report a case of acyclovir-resistant herpes simplex virus (HSV) keratitis after long-term, inconsistent use of topical acyclovir and fluorometholone.

                Author and article information

                Case Reports in Ophthalmology
                S. Karger AG
                September – December 2014
                10 October 2014
                : 5
                : 3
                : 325-328
                Department of Ophthalmology, Ehime University School of Medicine, Toon, Japan
                Author notes
                *Tomoyuki Inoue, MD, Department of Ophthalmology, Ehime University School of Medicine, Shitsukawa, Toon, Ehime 791-0295 (Japan), E-Mail tomonoue@m.ehime-u.ac.jp
                368297 PMC4241636 Case Rep Ophthalmol 2014;5:325-328
                © 2014 S. Karger AG, Basel

                Open Access License: This is an Open Access article licensed under the terms of the Creative Commons Attribution-NonCommercial 3.0 Unported license (CC BY-NC) ( http://www.karger.com/OA-license), applicable to the online version of the article only. Distribution permitted for non-commercial purposes only. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                Page count
                Figures: 1, Pages: 4
                Published: October 2014

                Vision sciences,Ophthalmology & Optometry,Pathology
                Real-time polymerase chain reaction,Necrotizing keratitis,Herpes simplex virus,Fungal infection,Acyclovir-resistant herpes simplex virus


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