EPSTEIN-BARR VIRUS ACUTE RETINAL NECROSIS IN AN IMMUNOCOMPETENT HOST.

PURPOSE: To describe a case of Epstein-Barr virus (EBV)-associated acute retinal necrosis (ARN) in an immunocompetent patient and to summarize the clinical features of published molecularly confirmed EBV-ARN cases. METHODS: Case report and literature review. RESULTS: An 83-year-old immunocompetent woman with unilateral ARN presented with visual acuity of light perception. Oral valacyclovir was started. One week later, vitrectomy was conducted for worsening inflammation. Intraoperatively, a severe confluent necrotizing retinitis and occlusive vasculitis involving all four quadrants of posterior and peripheral retina were noted. Vitreous polymerase chain reaction was exclusively positive for EBV. Other autoimmune, infective, and hematological work-up was negative. The retinitis resolved 3 months later, but with significant macular and generalized retinal atrophy, visual acuity remained light perception. From the literature, there are four EBV-ARN cases (six eyes) diagnosed based on polymerase chain reaction or fluorescence in-situ hybridization of vitreous or retinal samples. All patients were immunocompromised or on immunosuppressive treatment. Presenting visual acuity was light perception or worse in 3/6 eyes. Three patients received systemic acyclovir-based therapy. Vitrectomy was performed in 4/6 eyes between 4 and 8 weeks from disease onset. All cases had involvement of the posterior and peripheral retina. Retinal detachment occurred in 2/6 eyes, and final visual acuity was no light perception in 3/6 eyes. CONCLUSION: This case expands the clinical spectrum of EBV-ARN to include infection in immunocompetent hosts. Epstein-Barr virus-ARN seems to be characterized by a global peripheral and posterior fulminant retinitis, with adverse visual acuity outcomes despite systemic acyclovir-based therapy. The benefits of adjunctive intravitreal foscarnet, systemic steroids, and early vitrectomy may warrant further investigation.

Immune Cell Status and Cytokines Profiles in Patients with Acute Retinal Necrosis.

Purpose: To assess the immune status of acute retinal necrosis (ARN) patients and to investigate the immune cell types involved in the immunopathogenesis.Methods: Peripheral blood and intraocular fluid were collected from 17 ARN patients and 9 control subjects. The Percentage of immune cells was measured using flow cytometry, levels of complement and antibodies were determined by rate nephelometry, and cytokine levels in the serum and aqueous humor (AH) were detected using cytokine quantitative chips. Data were analyzed using SPSS 23.0. p < .05 was considered statistically significant.Results: Proportion of T-helper 17 cells (p = .034) in serum and concentrations of multiple cytokines associated with Th17 cells (IL-6, IL-17, IL-17 F, IL-21, IL-22) in AH and serum were elevated of ARN patients.Conclusion: Th17 cells appeared to participate in the development of ARN. We found inflammatory cytokines and cells were elevated in the serum and AH of ARN patients.

Varicella zoster virus (VZV) oculomeningoencephalomyeloradiculitis: a previously undescribed constellation.

A 53-year-old immunocompromised woman developed acute left eye blindness and paraparesis suspected to be due to neuromyelitis optica (NMO). During treatment for NMO, right eye blindness and progressive multiple cranial neuropathies developed. Cerebrospinal fluid polymerase chain reaction (PCR) revealed Varicella zoster virus (VZV). This case emphasizes the importance of considering VZV in individuals, particularly the immunocompromised, presenting with a constellation of neurological signs and symptoms, even in the absence of rash.

Bilateral acute retinal necrosis after bilateral cataract surgery in an immunocompromised patient: a case report.

PURPOSE: To report a case of bilateral varicella zoster virus (VZV)-associated acute retinal necrosis (ARN) occurring after both eyes sequential cataract surgery in an elderly immunocompromised patient. METHODS: Medical records and investigation results of the patient were reviewed. RESULTS: Patient experienced floaters and blurring of vision in both eyes 4 weeks after her second uncomplicated cataract surgery. Clinical signs of granulomatous keratic precipitates, prominent vitritis, retinitis and vascular thrombosis were noted in both eyes. Aqueous samples from both eyes were positive for VZV. Disease was treated with intravitreal foscarnet bilaterally and 10 days of systemic intravenous acyclovir (10 mg/kg) followed by oral valaciclovir 1 g three times daily. Final visual acuity at 4 months after initial presentation was 20/60 in both eyes with no retinal detachment noted. CONCLUSIONS: Cataract surgery may have been the trigger for bilateral VZV-associated ARN. Immunocompromised patients can develop ARN and require close observation after cataract surgery. This is, to our knowledge, the first report of bilateral ARN following routine cataract surgery.

Cytokines and Chemokines Involved in Acute Retinal Necrosis.

Purpose: To investigate which cytokines and chemokines are involved in the immunopathogenesis of acute retinal necrosis (ARN), and whether cytokine profiles are associated with clinical manifestations, such as visual outcome. Methods: Serum and aqueous humor (AH) samples of 19 patients with ARN were analyzed by multiplex immunoassay. Infectious controls consisted of 18 patients with rubella virus-associated Fuchs' uveitis and 20 patients with ocular toxoplasmosis all confirmed by intraocular fluid analyses. The control group consisted of seven paired AH and serum samples from seven noninflammatory control patients with age-related cataract. In each sample, 4 anti-inflammatory, 12 proinflammatory, 2 vascular, and 4 other immune mediators were measured. In addition, various clinical characteristics were assessed. Results: In ARN, 10 of the 22 mediators, including most proinflammatory and vascular mediators such as IL-6, IL-8, IL-18, MIF, MCP-1, Eotaxin, IP-10, IL-15, sICAM-1, and sVCAM-1, were significantly elevated when compared to all controls. In addition, one anti-inflammatory mediator (IL-10) was significantly elevated in ARN as compared to the controls. No association was found between the time of sampling and the extent and levels of immune mediator expression. Conclusions: The pathogenesis of ARN is characterized by the presence of predominantly proinflammatory cytokines and chemokines with high expression levels as compared to other infectious causes of uveitis. There are no indications for an obvious Th-1 or Th-17 pathway. The combined data suggest that immune mediator expression is related to severity of disease, which is more fulminant in ARN, rather than to a specific uveitis entity.

[Analysis of Cytokines Related to Helper T and Regulatory T Cells in the Vitreous of Uveitis Patients].

PURPOSE: To investigate helper T (Th) cell-related cytokines elevated in the vitreous of endogenous uveitis (EU), and to compare these with those of acute retinal necrosis (ARN). METHODS: Vitreous fluids were obtained from 23 eyes of EU patients, 4 eyes of ARN patients, and 14 eyes of patients with epiretinal membrane (ERM) who had had vitrectomy surgery. The vitreous levels of interleukin (IL)-1, IL-4, IL-6, IL-10, IL-17A, IL-17F, IL-21, IL-22, IL-23, IL-25, IL-31, IL-33, interferon (IFN)-γ, soluble CD40 ligand (sCD40L) and tumor necrosis factor (TNF)-α were measured. RESULTS: The vitreous cytokine levels of IL-6, IL-10, IL-31, IFN-γ and TNF-α in the EU patients were significantly higher than in the ERM patients. On the other hand, the levels of IL-1ß, IL-6, IL-10, IL-31, IFN-γ, sCD40L and TNF-α were significantly higher in the ARN patients than in the EU patients, while those of IL-4, IL-17A and IL-22 were higher in the EU patients than in the ARN patients although they were not significant. CONCLUSIONS: It is suggested that Th1-, Th2- and Th17 cells are related to the development of EU, and Th1- and regulatory T cells to that of ARN, and that the severity of ocular inflammation may be associated with the activity of Th1 cells.

Subconjunctival antisense oligonucleotides targeting TNF-alpha influence immunopathology and viral replication in murine HSV-1 retinitis.

BACKGROUND: To investigate the role of tumor necrosis factor-alpha (TNF-alpha) in immunopathology and viral replication in the contralateral eye in the von Szily model of herpes simplex virus (HSV)-1 acute retinitis. METHODS: In vivo distribution was analyzed after subconjunctival injection of FITC-labeled antisense oligonucleotides (ASON). After HSV-1 (KOS) was injected in the right anterior chamber (AC) in BALB/c mice, the course of the contralateral retinitis was evaluated. The left eyes were treated with either TNF-alpha ASON, sequence-unspecific control (CON), or buffer. The ocular TNF-alpha content was quantified by ELISA. The delayed-type hypersensitivity (DTH) reaction, uptake of [3H]thymidine from regional lymph nodes (rln)- and spleen cells, serum-neutralizing antibodies, and viral titer in the eyes were evaluated. RESULTS: After subconjunctival injection, FITC-labeled ASON were found in the choroid and retina. In the TNF-alpha ASON-treated eyes, TNF-alpha expression and the incidence and severity of retinitis were reduced on day 8 postinfection (PI) (p < 0.05). On day 10 PI, higher viral titers were only seen in the eyes of the TNF-alpha ASON group (p < 0.05), and retinitis was slightly more severe on day 12 PI. While the HSV-1 specific [3H]thymidine uptake from rln cells was higher in the TNF-alpha ASON mice (p < 0.05), the [3H]thymidine uptake from spleen cells, the DTH response, and the neutralizing-antibody titers did not differ between the groups. CONCLUSIONS: After regional blockade of TNF-alpha in experimental HSV-1 retinitis TNF-alpha seems to possess an antiviral capacity against HSV-1 in the contralateral eye and participates in the immunopathology of HSV-1-induced acute retinitis.

[Atypical ocular toxoplasmosis with concomitant ocular reactivation of varicella-zoster virus and cytomegalovirus in an immunocompromised host]. / Atypische Toxoplasmose-Chorioretinitis mit begleitender Varizella-Zoster-Virus und Zytomegalovirus-Reaktivierung bei einem immunsupprimierten Patienten.

BACKGROUND: Necrotising retinopathy in immunocompromised hosts is characterised by an unfavourable course often with unspecific clinical features. Therefore, differential diagnosis can be critical. HISTORY AND SIGNS: A case of an initially therapy-resistant, necrotizing retinopathy is presented in a 65-year-old immunocompromised male patient suffering from chronic B-cell leukemia. THERAPY AND OUTCOME: Despite demonstration of cytomegalovirus and Varicella-Zoster-Virus DNA by polymerase chain reaction in vitreous, aqueous humour samples and from retinal biopsy with specific antiviral therapy, a progression of retinal necrosis was noted. Finally Toxoplasma gondii DNA was detected and retinal necrosis resolved after specific treatment. However, visual acuity remains poor because of optic nerve atrophy. CONCLUSIONS: The polymerase chain reaction is an important diagnostic tool for differential diagnosis in immunocompromised patients suffering from necrotising retinopathy. If resistance to therapy is noted atypical ocular toxoplasmosis should be considered. The presented case report shows that even multiple infections are possible in the same host.

Antibody-mediated retinopathies in canine patients: mechanism, diagnosis, and treatment modalities.

Antibody-mediated retinopathies may be widely present among the canine population. Early diagnosis and appropriate treatment are essential for visual preservation and reversal of blindness in these patients. The principal purpose of this review is to describe the mechanistic basis, clinical signs, diagnostic methods, and treatment options for retinal diseases causing sudden onset of blindness with absence of typical signs of intraocular inflammation or retinal degeneration-sudden acquired retinal degeneration syndrome and immune-mediated retinitis.

Impaired plasmacytoid dendritic cell innate immune responses in patients with herpes virus-associated acute retinal necrosis.

Plasmacytoid dendritic cells (PDC), the main producers of type I IFNs in the blood, are important for the recognition and control of viral and bacterial infections. Because several viruses induce IFN-alpha production, severe courses of herpes virus infections in nonimmunocompromised patients may be related to numerical or functional PDC deficits. To evaluate this hypothesis, PBMC and PDC were repeatedly isolated from nine patients with acute retinal necrosis (ARN), caused by herpes simplex or varicella zoster virus. The patients experienced meningitis/encephalitis and frequent infections in childhood (n = 2), recurrent herpes virus infections at unusual localizations (n = 2), ocular surgery (n = 1), infections (n = 4), and stress around ARN (n = 6). The median percentage of isolated PDC was significantly lower in patients compared with 18 age-matched healthy controls (p < 0.001), confirmed by FACS analysis using peripheral blood, and was extremely low during acute disease. PDC counts dropped in five controls suffering from respiratory infections or diarrhea. IFN-alpha production in PDC and PBMC exposed to different stimuli was significantly lower in patients than in controls (p < 0.05). Anergy to these stimuli was observed on four occasions, in particular during acute disease. PDC of patients showed up-regulated IFN regulatory factor-7 mRNA levels and evidence of in vivo activation (CD80) and maturation (CD83) (p < 0.05). CD8+ cell responses were significantly lower in patients vs controls (p = 0.04). These data support a risk factor model in which numerical and functional deficits in PDC-mediated innate immune responses contribute to an impaired control of latent herpes virus infections and subsequent development of ARN.

[Acute retinal necrosis]. / Akute Retinanekrose.

Acute retinal necrosis (ARN) is a rare entity caused by Herpes viruses. An immunocompromised background and the complications of ARN mostly lead to a poor visual outcome. Confirmation of the early diagnosis through polymerase chain reaction and antibody detection from aqueous or vitreous taps is recommended to improve the medical management and prevent disease progression with an increased risk of complications. Favourable outcomes are possible by means of combined antiviral systemic and intravitreal strategies with Acyclovir, Foscarnet and Ganciclovir. We report on the relevant literature recommendations and our own experience.

Acute retinal necrosis.

Acute retinal necrosis (ARN) is a rare disease that is usually caused by one of the three neurotropic human herpesviruses - herpes simplex virus type 1(HSV-1), HSV-2 and varicella-zoster virus (VZV). Although much is known about the clinical course of the disease and its treatment and about the viruses that cause it, comparatively little is known about its pathogenesis. This article will review the history of ARN, the typical clinical findings, and methods of diagnosis. Information from studies of the mouse model of ARN including development of anterior chamber-associated immune deviation (ACAID) and routes of spread will be reconsidered, and the combined information from human and mouse studies will be discussed to suggest mechanisms that contribute to the pathogenesis of ARN in human patients. Finally, puzzles and questions about the disease will be considered.