Herpes simplex virus type 1 related acute retinal necrosis following an encephalitis illness: a case report.

BACKGROUND: Virus encephalitis is found to be a risk factor for acute retinal necrosis (ARN). CASE PRESENTATION: We herein presented a case of a 20-year-old teenage boy who suffered from encephalitis of unknown etiology with early negative pathologic results, and was primarily treated with systemic administration of high-dose steroids without antiviral therapy. He later had sudden vision loss in his right eye. Intravitreal and intravenous antiviral treatments were immediately started due to suspected ARN. Herpes simplex virus (HSV)-1 was identified later in the vitreous humor of the patient. After the surgery of retinal detachment (RD), obvious improvements in vision were observed. However, the patient had recurrent RD and vision declination 5 weeks later. CONCLUSIONS: The case with suspected viral encephalitis should be treated with antiviral therapy regardless of early virologic results in order to avoid complications of a missed viral encephalitis diagnosis, especially if systemic steroid treatment is being considered.

Case Report: Acute Retinal Necrosis after Intravitreal Ranibizumab for Exudative Macular Degeneration.

SIGNIFICANCE: Acute retinal necrosis (ARN) may occur after intravitreal ranibizumab (IVR) treatment for patients with exudative age-related macular degeneration (AMD). Awareness of this unusual but devastating complication after IVR is needed. Early identification may help provide timely antiviral treatment and prevent irreversible visual loss. PURPOSE: This study aimed to report a case of ARN after IVR in a patient with exudative AMD. CASE REPORT: A 67-year-old male patient complained of blurred vision in his left eye for 1 month. The patient was diagnosed with exudative AMD after detailed ophthalmic clinical evaluations. He received IVR once in his left eye. Three days after IVR, he developed varicella-zoster virus-associated ARN, which was treated with systemic and intravitreal antiviral therapy. Because of progressive inflammation, the patient underwent 25G pars plana vitrectomy with silicone oil tamponade. Seven months later, the patient was administered intravitreal aflibercept once in his left eye. Three months after intravitreal aflibercept, he underwent removal of silicone oil, and retinal detachment occurred 2 weeks after the surgery because of low IOP, and the patient eventually discontinued treatment. CONCLUSIONS: This study reports the first case of varicella-zoster virus-associated ARN after IVR. Early ARN may be very difficult to distinguish from intraocular inflammation after IVR. Therefore, early detection of viral DNA in the intraocular fluid using polymerase chain reaction is recommended. Immediate antiviral treatment may be beneficial to prevent severe visual loss.

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: A Case Series.

PURPOSE: To investigate the clinical characteristics and visual outcome of bilateral acute retinal necrosis. METHODS: The study included 30 patients (60 eyes) who were diagnosed with bilateral acute retinal necrosis. The medical records were reviewed. RESULTS: Twenty-five patients developed the disease in the contralateral eye within 5 months and 5 patients at >2 years after the initial onset. At presentation, 14 of 21 eyes suffered from retinal necrosis of more than 180° in the initially affected eye, whereas 3 of 22 eyes suffered it in the later-affected eye. Retinal detachment occurred in 23 of the 27 initially affected eyes and in 5 of the 27 later-affected eyes. The mean logarithm of the minimum angle of resolution best-corrected visual acuity decreased from 2.0 ± 1.1 (Snellen equivalent counting fingers) to 2.2 ± 1.0 (Snellen equivalent counting fingers) in the initially affected eyes after a follow-up of 34.1 ± 48.2 months (P = 0.529), and improved from 0.5 ± 0.4 (Snellen equivalent 20/66) to 0.3 ± 0.4 (Snellen equivalent 20/40) in the later-affected eyes after a follow-up of 21.2 ± 23.3 months (P = 0.005). CONCLUSION: Bilateral acute retinal necrosis usually occurs in the contralateral eye within a few months, but sometimes after several years. Inflammation and retinal necrosis are less severe in the later-affected eye, with less retinal detachment and a better visual outcome.

Case Report: Varicella-zoster Encephalitis with Acute Retinal Necrosis and Oculomotor Nerve Palsy.

SIGNIFICANCE: Varicella-zoster virus is a common cause of morbidity and vision loss in patients worldwide. It can affect any structure of the eye, from keratitis to acute retinal necrosis. Rapid diagnosis and treatment significantly improve clinical outcomes and quality of life. PURPOSE: The purpose of this study was to demonstrate a case where urgent referral to the emergency department was required to treat a patient with disseminated herpes zoster infection. CASE REPORT: This is a rare case of varicella-zoster virus encephalitis in a 70-year-old immunocompetent white man who initially presented to the eye clinic for vertical diplopia and floaters. He also had prior thoracic dermatomal rash, followed by new-onset headaches and cerebellar ataxia. Examination revealed a partial oculomotor nerve palsy in the right eye with bilateral optic disc edema and areas of retinitis consistent with acute retinal necrosis in both eyes. Polymerase chain reaction analysis of his aqueous humor and cerebrospinal fluid confirmed an active zoster infection. He received combination systemic and intravitreal antiviral medication until his retinitis resolved but required adjustments for recalcitrant disease and drug-induced nephrotoxicity. While on maintenance dosing of oral valacyclovir, he experienced reactivation in the form of bilateral vasculitis, which was successfully managed once restarting therapeutic oral dosing. CONCLUSIONS: This case describes a successful clinical course of acute retinal necrosis with strategies for its treatment in the setting of varicella-zoster encephalitis. Antiviral medication should be given as soon as possible, as prompt treatment has been shown to improve patient outcomes, although prognosis is typically poor in these cases. Multiple specialists are often needed to address different clinical challenges, including central nervous system involvement, viral strain resistance, disease reactivation, and drug toxicity.

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.

Acute Retinal Necrosis Caused by the Zoster Vaccine Virus.

We report acute retinal necrosis caused by the vaccine Oka strain following immunization of a 78-year-old woman with live zoster vaccine. Whole genome sequencing confirmed the ocular vOka strain to be derived from the vaccine and excluded the presence of new mutations or recombination with wild-type Varicella zoster virus.

Diagnosis and Treatment of Acute Retinal Necrosis: A Report by the American Academy of Ophthalmology.

PURPOSE: To evaluate the available evidence in peer-reviewed publications about the diagnosis and treatment of acute retinal necrosis (ARN). METHODS: Literature searches of the PubMed and Cochrane Library databases were last conducted on July 27, 2016. The searches identified 216 unique citations, and 49 articles of possible clinical relevance were reviewed in full text. Of these 49 articles, 27 were deemed sufficiently relevant or of interest, and they were rated according to strength of evidence. An additional 6 articles were identified from the reference lists of these articles and included. All 33 studies were retrospective. RESULTS: Polymerase chain reaction (PCR) testing of aqueous or vitreous humor was positive for herpes simplex virus (HSV) or varicella zoster virus (VZV) in 79% to 100% of cases of suspected ARN. Aqueous and vitreous specimens are both sensitive and specific. There is level II and III evidence supporting the use of intravenous and oral antiviral therapy for the treatment of ARN. Data suggest that equivalent plasma drug levels of acyclovir can be achieved after administration of oral valacyclovir or intravenous acyclovir. There is level II and III evidence suggesting that the combination of intravitreal foscarnet and systemic antiviral therapy may have greater therapeutic efficacy than systemic therapy alone. The effectiveness of prophylactic laser or early pars plana vitrectomy (PPV) in preventing retinal detachment (RD) remains unclear. CONCLUSIONS: Polymerase chain reaction testing of ocular fluid is useful in supporting a clinical diagnosis of ARN, but treatment should not be delayed while awaiting PCR results. Initial oral or intravenous antiviral therapy is effective in treating ARN. The adjunctive use of intravitreal foscarnet may be more effective than systemic therapy alone. The role of prophylactic laser retinopexy or early PPV is unknown at this time.

Progressive outer retinal necrosis associated with occlusive vasculitis in acquired immunodeficiency syndrome.

A 45-year-old man, a case of acquired immunodeficiency syndrome, received a highly active antiretroviral therapy at the outpatient service for 4 years without regular follow-up. He experienced progressively blurred vision for 6 months and a cutaneous zoster on his back 3 months ago. He was diagnosed with progressive outer retinal necrosis by polymerase chain reaction-restriction fragment length polymorphism using an aqueous humor sample, which revealed an existence of varicella zoster virus. He was given a combination of systemic, intravitreal antiviral and a highly active antiretroviral therapy. Occlusive vasculitis, an unusual finding for progressive outer retinal necrosis, developed in both eyes 1 week after the secondary intravitreal injection. Unfortunately, his vision deteriorated to no light perception in both eyes within 2 weeks. Progressive outer retinal necrosis is characterized clinically as showing minimal or no inflammation in the aqueous and vitreous humors, absence of retinal vasculitis, and patches of yellowish spots located deep in the retina. Physicians should pay attention to this rare case of progressive outer retinal necrosis associated occlusive vasculitis with very poor prognosis in spite of aggressive treatment.

Acute retinal necrosis--a case report.

Acute retinal necrosis (ARN) is a rare but very severe form of retinitis. In contrast to progressive outer retinal necrosis acute retinal necrosis typically affects immunocompetent individuals. Herpes Simplex and Varicella-zoster viruses play the main role in the development of the disease. We report a case study of a healthy, young male who presented to the ophthalmologist with unilateral visual acuity decrease and eye irritation. The acute retinal necrosis was diagnosed and a therapy was started including both systemic and local anti-viral agents, as well as an oral anticoagulant. Additional systemic steroid therapy was introduced a week later. The regression of retinal inflammatory changes and the improvement of visual acuity were observed. The polymerase chain reaction assay for the presence of viral DNA in serum was negative. The IgM antibody assay for potential causal pathogens was negative, but the level of Varicella-zoster virus IgG antibodies was markedly elevated. During the follow-up, the patient developed retinal detachment and pars plana vitrectomy with silicone oil endotamponade was performed. Although the surgery resulted in the successful retinal reattachment, the final visual acuity remained decreased. Six months after the surgery, the eye was free of the intraocular inflammation and the visual acuity slightly improved.

Diagnostic and therapeutic challenges in acute retinal necrosis; an update.

Acute retinal necrosis (ARN) is a rare but severe ophthalmic pathology defined by panuveitis, retinal necrosis, and high rates of retinal detachment. ARN may lead to poor visual outcomes even if promptly diagnosed and treated. ARN may present with a wide spectrum of clinical findings compatible with panuveitis including anterior uveitis, scleritis, vitritis, necrotizing retinitis, occlusive vasculitis, and optic disc edema. The American Uveitis Society introduced clinical criteria in 1994 for the diagnosis of ARN, while more recent criteria have been proposed by the Standardization of Uveitis Nomenclature (SUN) Working Group and the Japanese ARN Study Group. Multimodal imaging is a valuable tool in evaluating patients with ARN, particularly in unusual cases, while utilizing retinal imaging and applying AI algorithms in these areas of clinical research could be highly beneficial. Over the last few years, significant progress has been made in achieving timely diagnosis and treatment. The precise identification of the viral cause in suspected ARN cases has been greatly enhanced by the advancements in PCR techniques and flow cytometry used for intraocular fluids. systemic (intravenous or oral) antivirals with adjunctive intravitreal antiviral therapy are recommended as first-line therapy to reduce disease severity, the risk of vision loss, and retinal detachment incidence. Although aciclovir was the first existing antiviral agent, at present many clinicians prefer high-dose valaciclovir orally or intravenous aciclovir combined with intravitreal foscarnet. Despite significant progress in diagnosing and treating ARN, further research is needed to improve visual outcomes in this challenging clinical condition.

Time profile of viral DNA in aqueous humor samples of patients treated for varicella-zoster virus acute retinal necrosis by use of quantitative real-time PCR.

The objective of this study was to evaluate the kinetics of varicella-zoster virus (VZV) loads using quantitative PCR (qPCR) in patients treated for acute retinal necrosis (ARN). Six patients (52 ± 13 years old) with ARN syndrome were consecutively studied. Aqueous humor (AH) was sampled from both eyes of all patients for qPCR evaluation. The patients were treated with intravenous acyclovir and intravitreal injections of antiviral drugs. The mean follow-up time was 17.6 ± 16.4 months. Main outcome measures were the numbers of viral genome copies in the AH, assessed using real-time qPCR with hydrolysis probe technology with a threshold of detection of 200 copies/ml. Two main portions of the viral load curves were observed for each patient: a plateau phase (27.8 ± 24.9 days) and a decrease in the number of viral genome copies. The mean baseline viral load was 3.4 × 10(7) ± 4.45 × 10(7) copies/ml (6 × 10(6) to 1.2 × 10(8) copies/ml). The viral load decreased according to a logarithmic model, with a 50% reduction obtained in 3 ± 0.7 days. There was a significant viral load (>102 copies/ml) at 50 days after the onset of treatment, despite antiviral drugs. qPCR use demonstrated reproducible VZV DNA kinetics with a two-phase evolution: a plateau followed by a logarithmic decrease. These data suggest that high-dosage antiviral therapy administered for the conventional 10-day duration is insufficient for most patients. This series of patients responded with a similar decrease in viral load once treatment was initiated, and the data from these patients may be used to predict the responses of future patients.

Herpes simplex virus type 2 mediated acute retinal necrosis in a pediatric population: case series and review.

BACKGROUND: We report 15 eyes with herpes simples virus type 2 (HSV-2) mediated acute retinal necrosis (ARN) in order to better characterize pathogenesis, clinical course, diagnosis, and outcomes of the disease. METHODS: Retrospective observational case series of 14 patients (15 eyes) all aged 21 years or younger with acute retinal necrosis resulting from HSV-2 and examined between 1995 and 2009. Patients were diagnosed by various techniques, including polymerase chain reaction (PCR) of aqueous, vitreous, and serum, antibody determination of serum and intraocular fluids, fundoscopic exam, a therapeutic trial of antivirals active against HSV-2, or a combination thereof. RESULTS: Mean age of presentation was 11.7 years (range, newborn to 21.0 years) with a standard deviation of 7.0 years. Mean initial vision was 20/200 (median, 20/400; range, 20/20 to LP). Eleven patients (73.3 %) had received oral, injectable, or topical corticosteroids, and 14 (93.3 %) had received antiviral therapy. All patients were diagnosed based on evaluation of intraocular fluids and tissue by antibody determinations, culture, PCR, histopathologic examination, or a combination thereof. Mean final visual acuity was 20/400 (median, CF; range, 20/25 to LP) with worsened visual acuity in five eyes (33.3 %). Anatomically, 14 of 15 eyes had healed or improved retinal appearance. CONCLUSIONS: In a pediatric population with acute retinal necrosis, HSV-2 should be considered as the prime candidate virus. Diagnosis of HSV-2 acute retinal necrosis is accomplished mainly by PCR of ocular specimens. Prompt diagnosis may lead to appropriate anti-viral therapy.

Intravitreal treatment with antisense oligonucleotides targeting tumor necrosis factor-α in murine herpes simplex virus type 1 retinitis.

BACKGROUND: Tumor necrosis factor alpha (TNF-α) is a proinflammatory cytokine known to participate in intraocular inflammatory disease. This study investigated whether treatment with intravitreal antisense-oligonucleotides (ASON) targeting TNF-α mRNA affects the progression of herpes simplex virus 1 (HSV-1) retinitis in mice. METHODS: The in vivo uptake of the oligonucleotid after intravitreal injection was determined with FITC-labeled TNF-α ASON. HSV-retinitis was induced on day 0 by the injection of HSV-1 (KOS strain) into the anterior chamber (AC) of the right eyes of BALB/c mice (von Szily model). The left contralateral eyes were injected intravitreally on day 7 with TNF-α ASON, sequence-unspecific control ASON (CON), or buffer. The clinical course of retinitis, ocular inflammatory cell-infiltration, TNF-α expression in the eye by ELISA, delayed-type hypersensitivity (DTH) reaction, virus-neutralizing antibody titers in the serum, uptake of [3H]thymidine from regional lymph node (rln) cells, and viral content in the eyes were determined. RESULTS: In vivo, strong fluorescence of FITC- TNF-α ASON was detected in the choroid and retina up to 3 days after intravitreal injection, but none in the rln. After treatment of eyes with ASON, decreased expression of TNF-α in the eye, and reduced incidence and severity of retinitis on day 10 after infection (P < 0.05) could be found. The other parameters were not significantly influenced after TNF-α ASON treatment. CONCLUSIONS: TNF-α participates in the pathology of HSV-1 retinitis. Local inhibition of TNF-α mRNA by intraocular TNF-α ASON injection did not influence the systemic HSV-specific immune response or the antiviral response in the eye, but reduced ocular inflammatory bystander damage.

[Treatment results for acute retinal necrosis].

PURPOSE: To investigate the clinical course of patients with acute retinal necrosis (ARN) in order to evaluate the efficacy of treatment. METHODS: Clinical characteristics, causative virus, treatment and clinical course were analyzed in 14 eyes of 14 patients with ARN who presented between December 2000 and April 2008. RESULTS: All patients were treated with systemic anti-viral agents. Four eyes (29%) did not develop retinal detachment nor did they undergo prophylactic vitreous surgery; 3 of these eyes were of patients with baseline systemic diseases and were in a state of relative immunosuppression. Rhegmatogenous retinal detachment occurred in 6 eyes (43%) for which vitreous surgery with silicone oil tamponade was performed. Successful retinal reattachment was obtained in 5 of these eyes, although the silicone oil could not be removed in 3 eyes judged to be at high risk for recurrent detachment. Prophylactic vitreous surgery was performed in 3 eyes (21%) that had no retinal detachment. The indication for surgery in these eyes was an acute worsening of vitreous haze obscuring view of the fundus. Two of these eyes required a second surgical procedure, but all 3 eyes maintained useful vision with final attachment of the retina. CONCLUSIONS: Good outcomes were obtained in ARN patients who at baseline were in a state of relative immunosuppression, suggesting a role for strong immune reactions in the development of retinal detachment in ARN. Silicone oil could not be removed in most eyes that had undergone vitreous surgery after the onset of retinal detachment. Indications for the use of prophylactic vitreous surgery for ARN eyes without retinal detachment require further evaluation.

Acute retinal necrosis--a case report.

We present a case of acute retinal necrosis (ARN) which is a rare but devastating and rapidly progressive viral retinitis. It is caused mainly by Herpes simplex virus (HSV) or Varicella zoster virus (VZV) (2), but also Cytomegalovirus (CMV) and Epstein-Barr virus infections may be aethiological factors of ARN. A 17-year-old male patient was referred with history of painful sudden worsening of visual acuity in the left eye and the presence of floaters in the visual field of the right eye. Based on the ophthalmological examination the diagnosis of bilateral ARN was established. Aqueous humor aspirates were analyzed using polymerase chain reaction (PCR) for Herpes simplex virus (HSV), Varicella zoster virus (VZV), Cytomegalovirus (CMV) and Epstein-Baar virus (EBV). PCR confirmed the presence of Varicella zoster virus in aqueous humor samples. Prompt systemic antiviral therapy combined with steroids was initiated. Since a rapid and accurate diagnosis is crucial for prompt administration of antiviral therapy, PCR-based analysis of intraocular fluids orovides a valuable tool in the establishina an etiologic factor in patients with retinitis caused by herpesvirus.

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.

ACUTE RETINAL NECROSIS ASSOCIATED WITH HERPES ZOSTER VACCINATION.

PURPOSE: To report a case of Zostavax-associated acute retinal necrosis in a patient with chronic lymphocytic leukemia. METHODS: Case report. PATIENTS: A 76-year-old white man. RESULTS: Unilateral acute retinal necrosis with obliterative angiopathy developed in close proximity of a Zostavax vaccine. Treatment with valacyclovir hydrochloride (1 g orally three times a day) and intravitreal ganciclovir (4 mg/0.1 mL) was initiated on presentation. Because of continuous increase of the retinal necrosis, patient was switched to intravenous acyclovir (7.5 mg/kg body weight, adapted to reduced glomerular filtration rate) and given intravitreal foscarnet (2.4 mg/0.1 mL). Despite being on maximal antiviral therapy, the patient suffered a central retinal artery occlusion. DISCUSSION: Acute retinal necrosis is a severe complication and potentially blinding disease of herpes zoster, and can occur in association with herpes zoster immunization, in particular, in immune suppressed patients.