Intravitreal Foscarnet for the Treatment of Acyclovir-resistant Acute Retinal Necrosis Caused by Varicella Zoster Virus

Lee, Mee Yon; Kim, Kyu Seop; Lee, Won Ki

doi:10.3109/09273948.2010.544857

Cited by 26 publications

(27 citation statements)

References 3 publications

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“…Foscarnet injected intravitreally has been used to treat ARN caused by both HSV and VZV in adults,13 55 in children55 56 and in ARN associated acyclovir-resistant VZV 57 58. Intravitreal foscarnet can be administered at a dose of 2.4 mg/0.1 ml, which requires no dilution from the commercially available intravenous solution, and may be administered immediately following diagnostic sampling of aqueous or vitreous fluid.…”

Section: Medical Treatment Of Arnmentioning

confidence: 99%

Emerging concepts in the management of acute retinal necrosis

et al. 2012

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Acute retinal necrosis (ARN), also known as Kirisawa-type uveitis, is an uncommon condition caused by infection of the retina by one of the herpes family of viruses, most typically varicella zoster virus or herpes simplex virus and less commonly cytomegalovirus. Clinical diagnosis can be challenging and is often aided by PCR-based analysis of ocular fluids. Treatment typically involves extended use of one or more antiviral agents. Long term retinal detachment risk is high. We review the literature on ARN and present an approach to the diagnosis and management of this serious condition.

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Section: Medical Treatment Of Arnmentioning

confidence: 99%

Emerging concepts in the management of acute retinal necrosis

et al. 2012

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“…Because most ACV r VZV strains have alterations in the viral TK (31,33,41,47,49,53), foscarnet (PFA) (a direct inhibitor of viral DNA Pol) is the drug of choice to treat ACV r VZV infections (1,11,21,32,48). A few reports have described VZV mutants with alterations at the level of DNA Pol associated with resistance to PFA (26,66,67).…”

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confidence: 99%

In Vitro -Selected Drug-Resistant Varicella-Zoster Virus Mutants in the Thymidine Kinase and DNA Polymerase Genes Yield Novel Phenotype-Genotype Associations and Highlight Differences between Antiherpesvirus Drugs

Andrei

Topalis

Fiten

et al. 2012

J Virol

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Varicella zoster virus (VZV) is usually associated with mild to moderate illness in immunocompetent patients. However, older age and immune deficiency are the most important risk factors linked with virus reactivation and severe complications. Treatment of VZV infections is based on nucleoside analogues, such as acyclovir (ACV) and its valyl prodrug valacyclovir, penciclovir (PCV) as its prodrug famciclovir, and bromovinyldeoxyuridine (BVDU; brivudin) in some areas. The use of the pyrophosphate analogue foscarnet (PFA) is restricted to ACV-resistant (ACV r ) VZV infections. Since antiviral drug resistance is an emerging problem, we attempt to describe the contributions of specific mutations in the viral thymidine kinase (TK) gene identified following selection with ACV, BVDU and its derivative BVaraU (sorivudine), and the bicyclic pyrimidine nucleoside analogues (BCNAs), a new class of potent and specific anti-VZV agents. The string of 6 Cs at nucleotides 493 to 498 of the VZV TK gene appeared to function as a hot spot for nucleotide insertions or deletions. Novel amino acid substitutions (G24R and T86A) in VZV TK were also linked to drug resistance. Six mutations were identified in the "palm domain" of VZV DNA polymerase in viruses selected for resistance to PFA, PCV, and the 2-phophonylmethoxyethyl (PME) purine derivatives. The investigation of the contributions of specific mutations in VZV TK or DNA polymerase to antiviral drug resistance and their impacts on the structures of the viral proteins indicated specific patterns of cross-resistance and highlighted important differences, not only between distinct classes of antivirals, but also between ACV and PCV.

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“…Further supporting this theory, the VZVassociated ARN in this same patient only improved with supplemental intravitreal foscarnet, indicating there may have been a component of resistance to the valacyclovir molecule. Other case reports of patients with acyclovir resistant varicella zoster that required treatment of foscarnet have been reported [7]. It should be noted that in this scenario, the standard lifelong prophylactic treatment of oral acyclovir to prevent contralateral involvement would be insufficient [8].…”

Section: Discussionmentioning

confidence: 96%