Management of varicella zoster virus retinitis in AIDS

Moorthy, Ramana S.; Weinberg, David V.; Teich, Steven; Berger, Brian B.; Minturn, John; Kumar, Sanjiv; Rao, Narsing A.; Fowell, Susan M.; Loose, Isaac A.; Jampol, Lee M.

doi:10.1136/bjo.81.3.189

Cited by 74 publications

(70 citation statements)

References 11 publications

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“…VZV retinitis (VZVR) is a clinically distinct necrotizing retinitis syndrome caused by VZV that occurs often in immunocompromised patients. The pathological features of VZVR include progressive outer retinal necrosis causing retinal detachment and blindness in most patients (6). However, the mechanisms of VZVR are rarely investigated due to the lack of reliable in vitro models.…”

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confidence: 99%

In Vitro Replication of Varicella-Zoster Virus in Human Retinal Pigment Epithelial Cells

et al. 2008

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Here we describe for the first time the productive in vitro infection of human retinal pigment epithelial cells by varicella-zoster virus (VZV), resulting in a typical cytopathic effect (CPE) that is characterized by enlarged cells with increased granularity. Depending on the CPE dissemination, high titers of up to 1.6 ؋ 10 6 PFU of cell-free and cryostable VZV/ml can be recovered.Varicella-zoster virus (VZV) is a human alphaherpesvirus (human herpesvirus 3) that causes chickenpox (varicella) during primary infection, whereas its reactivation from latency may result in shingles (zoster). VZV retinitis (VZVR) is a clinically distinct necrotizing retinitis syndrome caused by VZV that occurs often in immunocompromised patients. The pathological features of VZVR include progressive outer retinal necrosis causing retinal detachment and blindness in most patients (6). However, the mechanisms of VZVR are rarely investigated due to the lack of reliable in vitro models. Due to the difficulties to obtain cell-free infectious VZV (5), current in vitro investigations are usually based on freshly prepared, nontitrated or cell-associated VZV. However, cell-associated VZV cannot be used in neutralization assays because the virus is not accessible for the binding of antibodies present in samples to be investigated. Moreover, in antiviral susceptibility assays the use of cell-associated VZV resulted in a variable and significantly lower inhibition of plaque formation by the drugs assayed (5). Therefore, the objective of the present study was to establish a reliable reproductive in vitro infection system for generating high-titer and cryostable cell-free VZV stocks for subsequent use in different in vitro applications.Human retinal pigment epithelial (RPE) cells were isolated from freshly enucleated bulbi for corneal transplantation according to the tenets of the Declaration of Helsinki. RPE cell isolation and culture were performed as described previously (2), with slight modifications (1). The homogeneity of cultured RPE cells was confirmed by positive immunostaining with monoclonal antibodies (MAbs) directed against cytokeratins (pan) and cellular retinaldehyde-binding protein (MAbs were donated by J. Saari, Department of Ophthalomology, University of Washington, School of Medicine, Seattle). Cells were routinely monitored for potential mycoplasma contamination and were used only until passage 5. Cells producing VZVspecific antigens were detected by biotin-streptavidin staining using MAb directed against immediate-early antigen 62 (IE62; Chemicon, Billerica, MA). Viral DNA was isolated, sequenced, and typed as described recently (10, 11). Preparation of cell-free VZV, titration of virus stocks, and antiviral susceptibility assays were performed as described elsewhere (5). Briefly, cell-free VZV was prepared as follows. The overlay medium was removed from a 75-cm 2 tissue culture flask, and the cell monolayer (1 ϫ 10 7 to 2 ϫ 10 7 cells) was rinsed with phosphate-buffered saline (PBS). The cell monolayer was scraped into 3 ml o...

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confidence: 99%

In Vitro Replication of Varicella-Zoster Virus in Human Retinal Pigment Epithelial Cells

et al. 2008

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“…Progressive outer retinal necrosis (PORN) is described as a distinct form of VZV necrotizing chorioretinitis and is found almost exclusively in patients with acquired immunodeficiency syndrome (AIDS). [1][2][3][4] However, a few cases in non-AIDS patients have been reported. These patients were immunocompromised due to therapy for idiopathic thrombocytopenic purpura (ITP), cutaneous non-Hodgkin's lymphoma, rheumatoid arthritis and renal transplantation.…”

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Varicella zoster virus (VZV)-related progressive outer retinal necrosis (PORN) after allogeneic stem cell transplantation

Kalpoe

Dehn

Bollemeijer

et al. 2005

Bone Marrow Transplant

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“…3,4 Quantitative PCR of VZV DNA from aqueous fluid has been used successfully to monitor a patient's clinical course and may also be beneficial in these challenging cases. 5 Therapies utilized for PORN traditionally have included long-term systemic antivirals; 2,3, 6 Moorthy et al 6 previously described more favorable outcomes with intravenous foscarnet and/or ganciclovir compared with acyclovir monotherapy. More recently, the addition of intravitreal ganciclovir and foscarnet to systemic antiviral therapy has been associated with preservation of visual acuity, albeit infrequently.…”

Section: Commentmentioning

confidence: 99%

A therapeutic challenge in AIDS-associated viral retinitis

Yeh

Lombardi

Fahle

et al. 2011

Eye

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'The initial VA acuity is a good predictor of the final VA acuity'Fthis is unquestionable. Hence, by relying on the initial VA acuity, instead of dismissing it from the scoring system, we preferred to downscale the amount of points scored for initial VA. We halved the effect of initial VA on prognosis by means of using additional factors such as the age and the zone of injury. We developed POTS in order to obtain information on prognosis immediately after the trauma in patients whose initial VA could not be obtained. The replacement of the OTS by POTS is a too ambitious expectation at present. Multicentered, prospective studies with larger patient groups are required to obtain the objective evidence to replace the OTS by another scoring system. We think that there is an exact need for a new ocular trauma score for preverbal pediatric patients, whether ours or of another study. Our study is an attempt to fill in the missing aspect of the scoring system; we appreciate any suggestion to improve it.

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Management of varicella zoster virus retinitis in AIDS

Cited by 74 publications

References 11 publications

In Vitro Replication of Varicella-Zoster Virus in Human Retinal Pigment Epithelial Cells

In Vitro Replication of Varicella-Zoster Virus in Human Retinal Pigment Epithelial Cells

Varicella zoster virus (VZV)-related progressive outer retinal necrosis (PORN) after allogeneic stem cell transplantation

A therapeutic challenge in AIDS-associated viral retinitis

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