Human U90926 orthologous long non-coding RNA as a novel biomarker for visual prognosis in herpes simplex virus type-1 induced acute retinal necrosis.

Acute retinal necrosis (ARN) is a form of infectious uveitis caused by alpha herpesviruses, including herpes simplex virus type 1 (HSV-1). We previously found that the long non-coding RNA (lncRNA) U90926 is upregulated in murine retinal photoreceptor cells following HSV-1 infection, leading to host cell death. However, to date, an orthologous transcript has not been identified in humans. We investigated U90926 orthologous transcript in humans and examined its utility as a prognostic marker for visual acuity in patients with ARN. We identified two human orthologous transcripts (1955 and 592 bases) of lncRNA U90926. The amount of the longer human U90926 transcript was approximately 30- and 40-fold higher in the vitreous fluid of patients with ARN than in those with sarcoidosis and intraocular lymphoma, respectively. Furthermore, the expression of the longer human U90926 transcript in the vitreous fluid was highly correlated with the final best-corrected logarithm of the minimum angle of resolution visual acuity in patients with ARN (r = 0.7671, p = 0.0079). This suggests higher expression of the longer human U90926 transcript in the vitreous fluid results in worse visual prognosis; therefore, expression of the longer human U90926 transcript is a potential negative prognostic marker for visual acuity in patients with ARN.

Association of retinal detachment with age 50 years or younger at onset in patients with acute retinal necrosis.

BACKGROUND: Due to the guarded prognosis of acute retinal necrosis (ARN), it is relevant to develop a strategy to early categorize those patients in a higher risk of worse outcomes. The purpose of this study is to describe clinical features and predictive factors for retinal detachment (RD) in patients with ARN. METHODS: Retrospective observational case series of 34 adult patients (38 eyes) with ARN examined between January 2005 and July 2015 in the National Eye Institute (Bethesda, USA), the Department of Ophthalmology, University of Chile (Santiago, Chile), and APEC (CDMX, Mexico). RESULTS: A total of 16 males and 18 females with a mean age at presentation of 44.5 ± 16.8 years were included. Twenty-seven patients (79.4%) received intravenous acyclovir as first-line treatment, and 7 patients received either oral antiviral (4 patients) or oral plus intravitreal antiviral (3 patients). All subjects were treated with prednisone, with a mean initial dose of 57.7 ± 16.3 mg per day. Seventeen patients (50.0%) developed retinal detachment. An association of retinal detachment with age at onset was observed (p = 0.04), with patients younger than 50 years presenting a higher risk (OR = 14.86, p = 0.0009). Additionally, patients in this higher risk group had more inflammation in both anterior chamber and vitreous (p = 0.04 and 0.03, respectively). No other predictive factor for retinal detachment was found in the present study. CONCLUSIONS: RD represents an important complication in patients with ARN. Younger patients may be at higher risk of this complication, possibly secondary to the presence of a higher level of inflammation.

Concomitant herpetic keratitis and acute retinal necrosis: clinical features and outcomes.

BACKGROUND/OBJECTIVES: The aim of this study was to identify risk factors, prognosis, and management in patients with concomitant herpetic keratitis and acute retinal necrosis (ARN). SUBJECTS/METHODS: In this retrospective observational series, ARN patients in the Greater Vancouver area from 2004 to 2018 were identified through key words, billing codes, and dispensing data from medical records of affiliate researchers and the pharmacy at Vancouver General Hospital. RESULTS: Twenty-eight patients were diagnosed with ARN during this period. Five of those were also diagnosed with herpetic keratitis. Thus, the incidence of combined keratitis and ARN was 18% of patients with ARN. The two diseases occurred concomitantly in four out of five patients. Mean age at diagnosis was 55 ± 17 years. Of the five patients with both corneal and retinal involvement, three patients were immunocompromised and three had a history of herpetic diseases. Three developed disciform keratitis and two developed stromal immune keratitis. Clinical management and outcomes of these patients did not differ from patients with ARN alone, except for a lower rate of retinal detachment (p = 0.006) and a higher proportion with visual acuity ≥ 20/200 (p = 0.01). CONCLUSIONS: Keratitis may complicate the clinical picture of one out of five to six patients with ARN. Comprehensive ophthalmic examination, including careful anterior segment exams in patients with ARN and sequential dilated fundus exams in patients with herpetic keratitis, should always be conducted to identify cases of concomitant disease.

Analysis of inflammatory mediators in the vitreous humor of eyes with pan-uveitis according to aetiological classification.

Treatment of uveitis is complicated because of its multiple aetiologies and elevation of various inflammatory mediators. To determine the mediators that are elevated in the vitreous humor according to the aetiology of the uveitis, we examined the concentrations of 21 inflammatory cytokines, 7 chemokines, and 5 colony-stimulating/growth factors in vitreous samples from 57 eyes with uveitis associated with intraocular lymphoma (IOL, n = 13), sarcoidosis (n = 15), acute retinal necrosis (ARN, n = 13), or bacterial endophthalmitis (BE, n = 16). Samples from eyes with idiopathic epiretinal membrane (n = 15), which is not associated with uveitis, were examined as controls. Heat map analysis demonstrated that the patterns of inflammatory mediators in the vitreous humor in eyes with uveitis were disease-specific. Pairwise comparisons between the 5 diseases showed specific elevation of interferon-α2 in ARN and interleukin (IL)-6, IL-17A, and granulocyte-colony stimulating factor in BE. Pairwise comparisons between IOL, ARN, and BE revealed that levels of IL-10 in IOL, RANTES (regulated on activation, normal T cell expressed and secreted) in ARN, and IL-22 in BE were significantly higher than those in the other 2 types of uveitis. These mediators are likely to be involved in the immunopathology of specific types of uveitis and may be useful biomarkers.

Acute retinal necrosis following herpes simplex encephalitis: a nationwide survey in Japan.

PURPOSE: Acute retinal necrosis (ARN) is a severe necrotizing retinitis caused by varicella-zoster virus or herpes simplex virus (HSV) that often results in blindness. Occasionally, HSV-caused ARN develops after herpes simplex encephalitis (HSE). It remains unknown, however, when and how often ARN develops after HSE. To investigate the actual conditions of patients with ARN following HSE and the interval period between the prior HSE and the onset of ARN, a retrospective nationwide survey of the Japanese population was performed. STUDY DESIGN: Retrospective. METHODS: Questionnaires were sent out to the neurology and ophthalmology departments of teaching hospitals in Japan. They inquired about HSE patients in neurology departments and ARN patients diagnosed with HSV in ophthalmology departments. The proportion of the HSV-ARN patients with a history of HSE and their interval periods were obtained from the questionnaires returned by the ophthalmology departments. RESULTS: Neurology departments of 324 hospitals responded to the questionnaires (response proportion: 40.9%), and 53 HSE cases were reported. Ophthalmology departments of 535 hospitals responded the questionnaires (response proportion: 54.3%), and 67 HSV-ARN cases were reported. Among the 67 HSV-ARN cases, 16 (23.9%) had histories of prior HSE. Although the interval periods from the prior HSE to the onset of HSV-ARN varied among cases, nearly half developed HSV-ARN within 2 years. CONCLUSIONS: This nationwide survey of the Japanese population showed that HSV-ARN develops after HSE in higher frequency within 2 years. Neurologists and ophthalmologists should be aware that HSE survivors have a risk of contracting HSV-ARN.

Pattern of Acute Retinal Necrosis in a Referral Center in Tunisia, North Africa.

PURPOSE: To describe the pattern of acute retinal necrosis (ARN) syndrome in a referral center in Tunisia. METHODS: Retrospective review of the charts of 12 patients (12 eyes). RESULTS: Necrotizing retinitis involved >50% of the retina in 33.3% of eyes. Polymerase chain reaction on aqueous humor sample identified herpes simplex virus-1 in 4 eyes (33.3%) and varicella zoster virus in 3 eyes (25%), and was negative in 5 eyes (41.7%). All patients received intravenous acyclovir, followed by oral antivirals. Follow-up ranged from 6 to 16 months. Retinal detachment (RD) occurred in 3 eyes (25%), but no patient developed bilateral ARN. Final visual acuity was 20/200 or worse in 7 eyes (58.3%). Delay in diagnosis (p = 0.015), macular involvement (p = 0.045), development of RD (p = 0.018), and 25-50% of retinal involvement (p = 0.045) were associated with a worse visual outcome. CONCLUSION: ARN carries poor visual prognosis in Tunisia.

Necrosis retinal aguda vs. necrosis retinal externa progresiva: reporte de caso y revisión de la literatura / Acute retinal necrosis vs. progressive outer retinal necrosis: case report and literature review

Se describen las características principales de la necrosis retinal aguda, la relación fisiopatológica con su principal diagnóstico diferencial, la necrosis retinal externa progresiva. Exponemos las diferencias clínicas y paraclínicas de ambas enfermedades, con base en las cuales construimos un sistema de clasificación que las contempla como un espectro continuo de enfermedad dependiente del estado inmunológico.

The main characteristics of acute retinal necrosis, the pathophysiological connection with the main differential diagnosis and progressive outer retinal necrosis are described. We analize the clinical and paraclinical differences of both diseases, based on which we built a classifi cation system that take them into a continuous spectrum dependent of the immune state.

Acute retinal necrosis in the United Kingdom: results of a prospective surveillance study.

BACKGROUND: To determine the incidence of acute retinal necrosis (ARN) in the United Kingdom and to describe the demographics, management, and visual outcome in these patients. METHODS: This was a prospective study carried out by the British Ophthalmological Surveillance Unit (BOSU) between September 2007 and October 2008. Initial and 6-month questionnaires were sent to UK ophthalmologists who reported cases of ARN via the monthly BOSU report card system. RESULTS: In all, 45 confirmed cases (52 eyes) of ARN were reported in the 14-month study period, giving a minimum incidence of 0.63 cases per million population per year. There were 20 females and 25 males. Age ranged from 10 to 94 years. Eight patients had a history of herpetic CNS disease. Aqueous sampling was carried out in 13 patients, vitreous in 27, and cerebrospinal fluid (CSF) in 4. Varicella-zoster virus followed by herpes simplex were the most common causative agents. Treatment in 76% of the cases was with intravenous antivirals; however, 24% received only oral antivirals. In all, 47% of patients had intravitreal antiviral therapy. Visual outcome at 6 months was <6/60 in 48% of the affected eyes. CONCLUSION: The minimum incidence of ARN in the UK is 0.63 cases per million. Patients with a history of herpetic CNS disease should be warned to immediately report any visual symptoms. There is increased use of oral and intravitreal antivirals in initial treatment.

Viral retinitis after intravitreal triamcinolone injection in patients with predisposing medical comorbidities.

PURPOSE: To review the cases of viral retinitis after intravitreal steroid administration at a single center, to estimate the incidence, and to propose risk factors for its occurrence. DESIGN: Retrospective, observational case series. METHODS: Seven hundred thirty-six intravitreal triamcinolone (IVTA) injections were administered in the clinic and operating room by 3 retina specialists at a single academic medical center between September 2002 and November 2008. Inclusion criteria were simply a history of 1 or more IVTA injections during the period. The overall incidence of viral retinitis after IVTA injection was calculated. Subsequently, a chart audit was performed to estimate the number of patients with immune-altering conditions who had received IVTA during the period, and the incidence within this subgroup was calculated. RESULTS: Viral retinitis developed after IVTA injection in 3 patients, yielding an overall incidence of 3 in 736 or 0.41%. An estimated 334 injections were administered to patients with an immune-altering condition, including diabetes. All 3 of the patients in whom viral retinitis developed after IVTA injection possessed abnormal immune systems, yielding an incidence rate of 3 in 334 or 0.90% within this subgroup. CONCLUSIONS: Our high reported incidence for this potentially devastating complication can be attributed to multiple factors, including coexisting medical immunocompromising comorbidities, a higher dose with a longer duration of local immunosuppression in the vitreous, multiple injections, as well as previous viral retinitis. Caution with a high index of clinical suspicion and frequent follow-up is advised in patients receiving IVTA injection with potentially immune-altering conditions, even after apparent immune recovery.

[Research situation of acute retinal necrosis].

Acute retinal necrosis is an uncommon but devastating, potentially blinding ophthalmopathy characterized by acute uveitis, vitreitis, retinal arteritis and full-thickness retinal necrosis, frequently complicated by secondary retinal detachment and proliferative vitreoretinopathy in late stages. However, it usually cannot be diagnosed and treated promptly, with unfavorable prognosis for the lesions tend to a rapid circumferential progression in few days. This review summarizes the epidemiology, pathogenesis, clinical features, diagnosis, differential diagnosis and recent situation in the study of treatment of acute retinal necrosis.

Acute retinal necrosis: a national population-based study to assess the incidence, methods of diagnosis, treatment strategies and outcomes in the UK.

AIM: To determine the incidence, methods of diagnosis, treatment strategies and outcomes for acute retinal necrosis (ARN) in the UK. METHODS: A 12-month active case ascertainment study was carried out between March 2001 and March 2002 to record cases of ARN presenting to ophthalmologists via the British Ophthalmological Surveillance Unit (BOSU) reporting system. Questionnaires were sent to the reporting consultants, requesting data on patient characteristics, presentation, clinical findings, investigations and treatment. Diagnosis was made using the American Uveitis Society diagnostic criteria. Further questionnaires were sent at 2 weeks and 6 months to assess outcome and therapies. RESULTS: 74 cases of ARN were reported by 58 consultants between March 2001 and March 2002. Questionnaires were returned for 49 cases (66.2%), of which 18 (36.7%) were excluded. Of the 31 cases included, 22 (71.0%) were male and 9 (29.0%) were female. The age range was 13 to 85 years (mean 54.3 years). 28 cases (90.3%) were unilateral, with 3 patients (9.7%) presenting with bilateral ARN. An aqueous or vitreous biopsy was performed in only 18 patients, with one patient having both. Herpes viral DNA analysis was performed on all 19 biopsies, with identification of the viral DNA in 16; results from 3 biopsies were not documented. Varicella zoster virus (VZV) was the commonest cause identified in 10 patients (56%). Of the 31 subjects, 27 (87.1%) were treated for ARN with systemic antiviral treatment: with intravenous antiviral in 23 cases (85.2%) and oral antiviral in 4 cases (14.8%). 21 of these patients went on to receive oral antiviral maintenance therapy. In addition to antiviral treatment, systemic steroids were given to 16 subjects (51.6%). Surgical intervention for retinal detachment was performed on 5 patients. CONCLUSIONS: During the 12-month study period, 31 cases of ARN met the diagnostic criteria set by the American Uveitis Society. The incidence in the UK based on this study is approximately 1 case per 1.6 to 2.0 million population per year. We have ascertained that the management of ARN throughout the UK is variable, suggesting that national guidelines would be of benefit.

Ocular findings in Japanese patients with varicella-zoster virus infection.

PURPOSE: To examine ocular findings in Japanese patients with varicella, herpes zoster ophthalmicus, and acute retinal necrosis. METHODS: A retrospective study was conducted. Information on the ocular, cutaneous, systemic, and virologic findings on pediatric and adult patients was obtained from medical records. RESULTS: A total of 77 (45 male and 32 female) patients were enrolled in the study: 4 children had varicella, 68 adults had herpes zoster ophthalmicus, and 5 adults had acute retinal necrosis. Children with varicella had eruptions on the eyelid. Patients with herpes zoster ophthalmicus had eruptions, conjunctivitis, keratitis, iridocyclitis, and other findings. Patients with acute retinal necrosis had intracameral cells and retinal lesions. Some patients with herpes zoster ophthalmicus had malignancy, type 2 diabetes mellitus, or other disease. One pregnant woman developed acute retinal necrosis shortly after varicella infection. A total of 48% of patients with negative Hutchinson sign had ocular lesions, while all patients with positive sign showed ocular lesions. Patients with varicella and herpes zoster ophthalmicus had good visual acuity at the last visit. Some patients with acute retinal necrosis had poor visual acuity at the last visit. CONCLUSIONS: Patients with varicella, herpes zoster ophthalmicus, and acute retinal necrosis had several ocular complications. Some patients with acute retinal necrosis had poor visual outcomes. Ophthalmologists should be aware that acute retinal necrosis may develop shortly after varicella infection.

Role of viral serology in the diagnosis of acute retinal necrosis syndrome.

Due to the devastating nature of acute retinal necrosis syndrome (ARNS), early diagnosis is essential. 5 cases of clinically diagnosed ARNA were investigated for CMC, herpes simplex and varicella zoster virus (VZV) infections. Of the three VZV IgM positive cases, two were positive in acute blood samples and one in vitreous fluid. Thus VZU can be incriminated as the causative agent of ARNS cases in North India.

Herpes simplex virus epidemiology and ocular importance.

PURPOSE: To review the changing epidemiology of herpes simplex disease and correlate it with the epidemiology of ocular herpes simplex disease. METHOD: A review of pertinent reports in the world literature about the epidemiology of herpes simplex and specifically about ocular herpes simplex. RESULTS: In developed countries, many individuals are reaching adolescence and adulthood without prior herpesvirus infection. Herpes simplex genital infection is increasing at a rapid rate in sexually active adolescents and adults, with about one in six adults now infected in the United States. Similar statistics are confirmatory worldwide in developed countries. Active herpes simplex infection is a risk factor for acquisition of human immunodeficiency virus. The Herpetic Eye Disease Study, as well as prior studies from Moorfields Eye Hospital and the Mayo Clinic in Rochester, Minnesota, provides us with the epidemiology of ocular herpes simplex. Recent studies suggest an older age of onset and perhaps overall more severe ocular disease as compared with the older literature. CONCLUSIONS: Herpes simplex is a significant health concern at present with genital infections increasing in epidemic proportions. This is also reflected in a rise in the incidence of neonatal herpes. Herpes simplex virus type 1 (HSV-1) infection is being acquired for the first time in an older age group. A significant and increasing proportion of genital herpes is caused by HSV-1. Serologic studies are no longer as useful in distinguishing orofacial herpes from genital herpes. More acute retinal necrosis syndrome cases are associated with HSV-2. Speculation about the future of ocular herpes is made based on this changing epidemiology.

High prevalence of herpes simplex virus type 2 in acute retinal necrosis syndrome associated with herpes simplex virus in Japan.

PURPOSE: To determine the type of herpes simplex virus in acute retinal necrosis syndrome associated with herpes simplex virus. METHODS: Herpes simplex virus type 1, herpes simplex virus type 2, varicella-zoster virus, Epstein-Barr virus, and cytomegalovirus were examined by polymerase chain reaction in intraocular specimens from 16 patients with acute retinal necrosis syndrome. Anti-herpes simplex virus type 1 and anti-herpes simplex virus type 2 type-specific antibodies in serum from the patients were detected by enzyme immunoassay. RESULTS: Of 16 patients with acute retinal necrosis syndrome, seven were polymerase chain reaction positive for herpes simplex virus type 2 and nine were positive for varicella-zoster virus. Anti-herpes simplex virus type 2 antibody was positive and anti-herpes simplex virus type 1 antibody was negative in the sera of the seven patients with herpes simplex virus type 2 DNA-positive acute retinal necrosis syndrome. In contrast, anti-herpes simplex virus type 2 antibody was absent in all nine varicella-zoster virus DNA-positive acute retinal necrosis syndrome patients. CONCLUSION: Herpes simplex virus type 2 has been demonstrated to be the major causative agent in acute retinal necrosis syndrome associated with herpes simplex virus by molecular biological and serological methods. Negative preexisting anti-herpes simplex virus type 1 antibody may play an important role in acute retinal necrosis syndrome associated with herpes simplex virus type 2.