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.

Atypical acute retinal necrosis accompanied by Terson's syndrome: a case report.

BACKGROUND: Acute retinal necrosis (ARN) has characterized by panuveitis, vitritis, severe vaso-occlusive vasculitis, and diffuse necrotizing retinitis. There are no case reports on atypical ARN combined with Terson's syndrome. Herein, we report a case of ARN with atypical clinical features combined with Terson's syndrome that we successfully treated by intravitreal ganciclovir injection. CASE PRESENTATION: A 64-year-old man visited our eye clinic with a complaint of decreased visual acuity in his right eye. At the initial visit, his best corrected visual acuity was 20/125 in the right eye. Slit-lamp examination demonstrated mild hyperemia, keratic precipitates, and anterior chamber inflammatory reaction. Fundus examination revealed multiple diffuse white-yellowish infiltrations in the peripheral retina combined with dot hemorrhages. Ultra-wide-field fluorescence angiography showed obstructive arteritis with peripheral non-perfusion and leakage from the retinal vessels. As a result of the PCR analysis, varicella zoster virus DNA was identified in the aqueous humor. Under the diagnosis with VZV-mediated ARN, we started with intravenous acyclovir and oral prednisolone. After 3 days of the above treatment, the anterior chamber inflammation and vitreous opacity were increased. On fundus examination, multiple whitish infiltrations were increased. In addition, newly developed vitreous and peripapillary hemorrhages were detected. On the T2 brain magnetic resonance imaging (MRI) demonstrated a sub-acute or old hemorrhagic infarction in the right occipital lobe, and contrast-enhancing lesions in the right basal ganglia. The spinal tapping was performed in the department of neurology in our hospital at the time when the patient complained of headache, and intracranial pressure was 31 mmHg. Under the diagnosis of ARN with Terson's syndrome, we started intravitreal ganciclovir (2 mg/0.5 ml) injections. After 5 intravitreal ganciclovir injections over a period of 8 months, the diffuse whitish infiltrating retinal lesions combined with dot hemorrhage were decreased. The vitreous and peripapillary hemorrhage was significantly reduced. There was no recurrence in the patient's right eye, in which his visual acuity had improved to 20/60. CONCLUSIONS: In the event of a poor response to traditional treatment such as intravenous acyclovir, intravitreal ganciclovir may have a role as an adjunctive therapy in patients of VZV associated ARN combined with Terson's syndrome.

Acyclovir resistant acute herpes simplex encephalitis associated with acute retinal necrosis: A case report and review of the literature.

A 55-year-old man was admitted to our hospital for investigation of high fever, decreased consciousness and bilateral visual impairment. His cerebrospinal fluid analysis revealed pleocytosis of mononuclear cells and an increased protein concentration. FLAIR images revealed multiple high-intensity lesions in the frontal lobe, part of which was enhanced with gadolinium. Despite initiating treatment with acyclovir and corticosteroids, his consciousness and visual acuity deteriorated. Immunopathological examination of brain biopsies showed numerous herpes simplex virus type 2-positive neurons and macrophages, leading to a diagnosis of herpes simplex encephalitis (HSE). Fundoscopic examination revealed multiple foci of retinitis with vasculopathies, and inflammation in the anterior chamber and vitreous, indicating acute retinal necrosis (ARN). Foscarnet treatment was initiated in place of acyclovir and his consciousness improved, with a slight improvement in visual acuity. ARN is typically caused by a herpes virus infection limited to the eyeball, and rarely in combination with HSE. In such cases, there is a latency of approximately 2-4 weeks between ARN and the onset of encephalitis. Our case is unique in that HSE and ARN developed simultaneously, and it highlights that there may not always be a latency between the onsets of the two disorders. Finally, foscarnet should be considered in cases of HSE and ARN with acyclovir resistance.

[Role of oral antiviral therapy in the treatment of acute retinal necrosis]. / Intérêt de la thérapie antivirale par voie orale dans le traitement des nécroses rétiniennes aigues.

Acute retinal necrosis syndrome (ARNS) is a rare but devastating uveitic syndrome with devastating visual outcome (visual prognosis ++). It should be diagnosed as early as possible because of its severity and its risk of bilateralization. This is a rare entity caused by the group of herpes viruses. In immunocompromised patients the complications of RNA syndrome often lead to loss of visual acuity. After the discovery of this disease using polymerase chain reaction (PCR) and immune load coefficient (ILC) usually by puncturing the cornea to evacuate the aqueous humour, the confirmation of this diagnosis allows for faster optimization of disease management decreasing the time required to confirm the diagnosis. ARN syndrome is associated with a very poor prognosis. Recent studies have shown that oral antiviral (valaciclovir, famciclovir and valganciclovir) and intravitreal therapies without initial intravenous treatment are an effective treatment for RNA. OBSERVATION: We report the clinical features of a 39-year-old young patient admitted to our emergency department with visual loss. Ophthalmologic examination objectified unilateral acute retinal necrosis. The patient was treated with oral antiviral therapy (valacyclovir) associated with corticosteroids and evolution was very favorable. CONCLUSION: the prognosis of acute retinal necrosis syndrome or RNA is usually severe. The patient should be treated as early as possible in order to limit bilateralization and the occurrence of complications. This study confirms that oral antiviral (valacyclovir, famciclovir and valganciclovir) and intravitreal therapies without initial intravenous treatment are an effective treatment for RNA.

Inhibition of calpain on oxygen glucose deprivation-induced RGC-5 necroptosis.

The purpose of this study was to investigate the effect of inhibition of calpain on retinal ganglion cell-5 (RGC-5) necroptosis following oxygen glucose deprivation (OGD). RGC-5 cells were cultured in Dulbecco's-modified essential medium and necroptosis was induced by 8-h OGD. PI staining and flow cytometry were performed to detect RGC-5 necrosis. The calpain expression was detected by Western blotting and immunofluorescence staining. The calpain activity was tested by activity detection kit. Flow cytometry was used to detect the effect of calpain on RGC-5 necroptosis following OGD with or without N-acetyl-leucyl-leucyl-norleucinal (ALLN) pre-treatment. Western blot was used to detect the protein level of truncated apoptosis inducing factor (tAIF) in RGC-5 cells following OGD. The results showed that there was an up-regulation of the calpain expression and activity following OGD. Upon adding ALLN, the calpain activity was inhibited and tAIF was reduced following OGD along with the decreased number of RGC-5 necroptosis. In conclusion, calpain was involved in OGD-induced RGC-5 necroptosis with the increased expression of its downstream molecule tAIF.

[The clinical features of 10 cases of acute retinal necrosis complicated by viral encephalitis].

OBJECTIVE: To investigate the clinical features of acute retinal necrosis (ARN) complicated by viral encephalitis. METHODS: Ten cases of ARN complicated by viral encephalitis were treated in the Department of Ophthalmology, Beijing Tongren Hospital from November 2013 to August 2014. Clinical manifestation, especially the fundus characteristics, was summarized. RESULTS: In the10 patients (19 eyes; 6 men and 4 women) with an age of (40.1 +/- 13.44) years, 1 patients had unilateral ARN, and 9 patients had bilateral ARN. The visual acuity was no light perception in 9 eyes, light perception to hand motion in 7 eyes, 0.05 in 1 eye, 0.2 in 1 eye, and 0.3 in 1 eye. Seven cases suffered ARN during the onset of viral encephalitis, and other cases suffered ARN at 2 to 3 months after the recovery of viral encephalitis. Seventeen eyes had mild to moderate vitreous opacity, and 2 eye shad severe vitreous opacity. Sixteen eyes had focal (1 or 2 quadrants) retinal necrosis, and 2 eyes had massive ( > 2 quadrants) retinal necrosis. Occlusive vasculitis obviously occurred in 18 eyes. Sixteen eyeshad retinal detachment. All affected eyes had early optic nerve atrophy. CONCLUSION: ARN can occur during the onset of viral encephalitis or after the recovery of viral encephalitis. The clinical features of ARN complicated by viral encephalitis may be generally mild to moderate vitreous opacity,small range retinal necrosis foci, early and severe optic atrophy, and occlusive retinal vasculitis.

Subretinal fluid in eyes with active ocular toxoplasmosis observed using spectral domain optical coherence tomography.

PURPOSE: To describe the clinical finding of subretinal fluid (SRF) in the posterior pole by spectral domain optical coherence tomography (SD-OCT) in eyes with active ocular toxoplasmosis (OT). DESIGN: Retrospective case series. PARTICIPANTS: Thirty-nine eyes from 38 patients with active OT [corrected].. METHODS: Eyes with active OT which underwent SD-OCT were reviewed. SRFs in the posterior pole were further analyzed. MAIN OUTCOME MEASURES: Presence of SRF; its accompanying features, e.g. retinal necrosis, cystoid macular edema (CME), choroidal neovascularization (CNV); and longitudinal changes of SRF, including maximum height and total volume before and after treatment. RESULTS: SRF presented in 45.5% (or 15/33) of eyes with typical active OT and in 51.3% (or 20/39) of eyes with active OT. The mean maximum height and total volume of SRF were 161.0 (range: 23-478) µm and 0.47 (range: 0.005-4.12) mm3, respectively. For 12 eyes with SRF related to active retinal necrosis, SRF was observed with complete absorption after conventional anti-toxoplasmosis treatment. The mean duration for observation of SRF clearance was 33.8 (range: 7-84) days. The mean rate of SRF clearance was 0.0128 (range: 0.0002-0.0665) mm3/day. CONCLUSIONS: SRF (i.e., serous retinal detachment) is a common feature in patients with active OT when SD-OCT is performed. The majority of SRF was associated with retinal necrosis and reacted well to conventional therapy, regardless of total fluid volume. However, SRF accompanying with CME or CNV responded less favorably or remained refractory to conventional or combined intravitreal treatment, even when the SRF was small in size.

[Atypical case of acute retinal necrosis secondary to the primary herpes simplex infection]. / Nietypowy przypadek ostrej martwicy siatkówki w przebiegu pierwotnego zakazenia wirusem herpes simplex.

Acute retinal necrosis is a rare manifestation of viral chorioretinitis, accompanied by occlusive vasculitis, which is associated with poor visual prognosis. The main causal factors include varicella-zoster virus in older patients and herpes simplex in younger ones. The disease typically manifests as a reactivation of latent infections. We present a case of a 57-year-old female with atypical clinical manifestation of acute retinal necrosis secondary to the primary viral infection with herpes simplex. The serology panel of vitreous tap and blood sample confirmed viral aetiology (H. simplex). The initial clinical signs included optic disc edema with retinitis presenting as self-limiting, slowly progressing, peripheral lesions, later followed by uveitis. The antiviral therapy resolved the symptoms of uveitis and enabled healing of retinal lesions, however the natural course of disease was later complicated with retinal detachment. It was successfully treated with vitreoretinal surgery. Despite aggressive treatment, the final visual outcome was unfavourable, due to optic nerve atrophy.

Clinical manifestation of self-limiting acute retinal necrosis.

BACKGROUND: The purpose of this paper was to present a case series of self-limiting, peripheral acute retinal necrosis and to demonstrate efficacy of treatment with valacyclovir in patients resistant to acyclovir. The diagnosis was made on ophthalmoscopic examination and positive serum tests for herpes viruses. MATERIAL AND METHODS: Ten patients (6F and 4M) aged 19-55 years were diagnosed and treated for self-limiting acute retinal necrosis (ARN). The following endpoints were reported: visual outcomes, clinical features, disease progression, treatment, and complications. Patients received only symptomatic treatment because they did not consent to vitreous puncture. RESULTS: Peripheral, mild retinitis was diagnosed in all eyes at baseline. Initially, all patients were treated with systemic acyclovir (800 mg, 5 times a day), prednisone (typically 40-60 mg/day), and aspirin in an outpatient setting. In 6 patients, treatment was discontinued at 6 months due to complete resolution of the inflammatory process. Four patients with immune deficiency showed signs and symptoms of chronic inflammation. Two patients did not respond to acyclovir (2 non-responders); however, those patients were successfully treated with valacyclovir. Complete resolution of inflammatory lesions was observed in 8 patients. In 2 patients, the disease progressed despite treatment - 1 female patient after kidney transplant who stopped the prescribed medications, and 1 male patient with SLE and antiphospholipid syndrome who experienced breakthrough symptoms on-treatment. He died due to cerebral venous sinus thrombosis. Neurological complications (encephalitis and meningitis) were observed in 2 female patients. Prophylactic laser photocoagulation was performed in 1 subject. CONCLUSIONS: A series of cases of self-limiting acute retinal necrosis (ARN) is presented. This clinical form of ARN can resemble toxoplasmic retinitis in some cases. Oral antiviral medications provide an effective alternative to intravenous formulations in patients with self-limiting ARN. Retinitis is associated with the risk of encephalitis.

Acute retinal necrosis associated with Epstein-Barr virus: immunohistopathologic confirmation.

IMPORTANCE: Acute retinal necrosis (ARN) is an infectious retinitis primarily caused by the herpesviruses. Although the Epstein-Barr virus (EBV) has been implicated as a cause of ARN, to our knowledge, there has been no histopathologic documentation. We report the clinical history and histopathologic confirmation that EBV can cause ARN. OBSERVATIONS: Clinical course and histopathology of a patient diagnosed with ARN caused by infection with EBV confirmed by molecular pathology. CONCLUSIONS AND RELEVANCE: Epstein-Barr virus is a recognized cause of intraocular inflammation and has been implicated as a possible cause of ARN. However, to our knowledge, tissue demonstration of EBV in a patient with ARN has not previously been reported. We identified the organism in the necrotic retina of a patient receiving immunosuppression because of idiopathic pulmonary fibrosis.

Neonatal herpes simplex virus type-1 central nervous system disease with acute retinal necrosis.

We report a case of neonatal herpes simplex virus (HSV)-1 central nervous system disease with bilateral acute retinal necrosis (ARN). An infant was presented at 17 days of age with focal seizures. Cerebrospinal fluid polymerase chain reaction was positive for HSV-1 and brain magnetic resonance imaging showed cerebritis. While receiving intravenous acyclovir therapy, the infant developed ARN with vitreous fluid polymerase chain reaction positive for HSV-1 necessitating intravitreal foscarnet therapy. This is the first reported neonatal ARN secondary to HSV-1 and the first ARN case presenting without external ocular or cutaneous signs. Our report highlights that infants with neonatal HSV central nervous system disease should undergo a thorough ophthalmological evaluation to facilitate prompt diagnosis and immediate treatment of this rapidly progressive sight-threatening disease.

Serpiginous choroiditis and acute retinal necrosis occurring in the same patient.

We describe a rare association of serpiginous choroiditis with necrotizing retinitis having clinical features of acute retinal necrosis (ARN). A 23-year-old male developed ARN in the fellow eye while he was on tapering doses of immunosuppressive medications for unilateral serpiginous choroiditis. The association may represent a common viral etiology of the two diseases or may be due to the development of ARN due to general state of iatrogenic immunosuppression. This report also highlights the importance of a detailed evaluation of both the eyes on regular follow-up visits in the patients receiving iatrogenic immunosuppression.

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.

Bilateral acute retinal necrosis associated with neuroinfection in patient after renal transplantation.

BACKGROUND: Acute retinal necrosis (ARN) is characterized by the triad of acute vitritis, peripheral necrotizing retinitis and vasculitis. CASE REPORT: We report a case of 54-year-old woman with bilateral acute retinal necrosis associated with neuroinfection. Her past medical history included renal transplantation, hypertension and aortic stenosis. Observational case report: Diagnostic investigations included biochemical tests, lumbar puncture, eye ultrasonography and MRI of the brain. Anti-HSV IgG antibody titers were elevated in the blood and cerebrospinal fluid. In MRI T2-mode, inflammatory changes were found in the white matter of the right hemisphere. The patient was treated with systemic acyclovir, itraconazole, metronidazole and ciprofloxacin for 3 weeks. Retinal detachment was observed in both eyes. CONCLUSIONS: Acute retinal necrosis can be the single manifestation of herpes virus reactivation in patients after organ transplantation.

Indocyanine green angiography findings in acute retinal necrosis syndrome.

BACKGROUND: Acute retinal necrosis syndrome is clinically defined by the presence of peripheral necrotizing retinitis associated with severe occlusive vasculitis caused primarily by herpes simplex virus and varicella zoster virus. Previously considered as an exclusively retinal pathology, choroidal involvement, as demonstrated by indocyanine green angiography, has not been extensively studied. HISTORY AND SIGNS: Indocyanine green angiography was performed in 4 patients with ARN. Observed angiographic patterns included: 1. a characteristic triangular area of hypo-perfusion, 2. hypofluorescent lobular patches and areas of fuzzy choroidal vascular hyperfluorescence, and 3. isolated hypofluorescent lobular patches of the contralateral eye. THERAPY AND OUTCOME: Marked choroidal hypo-perfusion on indocyanine green angiography was associated with extensive retinal ischemia. Treatment included a combination of antiviral agents and corticosteroids complemented by prophylactic acetylsalicylate. CONCLUSION: Indocyanine green angiography may provide important information regarding choroidal vascular involvement in ARN. It may also permit the timely identification of sub-clinical contralateral eye involvement.

A patient with acute visual loss and transient neurologic symptoms. Diagnosis: an acute central retinal artery occlusion (CRAO) in the left eye with severe retinal ischemia.

A 73-year-old man presented with acute visual loss in his left eye associated with transient left upper extremity numbness. Diagnosis was made in the emergency room, where treatment strategies were discussed.

[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.

Clinical features, management and outcomes of progressive outer retinal necrosis (PORN) in southern Thailand.

OBJECTIVE: To study the demographics, clinical features, treatment, and visual outcomes of progressive outer retinal necrosis (PORN) in a group of Thai patients. MATERIAL AND METHOD: All cases of AIDS with a clinical diagnosis of PORN in a major tertiary referral hospital in southern Thailand between January 2003 and June 2007 were retrospectively reviewed. Demographic data, clinical features, treatment regimens, and visual outcomes were analyzed. RESULTS: Seven patients (11 eyes) were studied. The mean age was 44.7 years. The median CD4 count was 12 cells/mm3. A known history of cutaneous zoster was documented in 57% of cases. The median follow-up period was 17 weeks. Fifty-seven percent of the patients had bilateral disease. A majority of eyes (45.4%) had initial visual acuity of less than 20/50 to equal to or better than 20/200. About two-thirds of the eyes had anterior chamber cells. Vitritis and retinal lesions scattered throughout both posterior pole and peripheral retina were found in 72.7%. Either intravenous acyclovir in combination with intravitreal ganciclovir injections or intravenous aclyclovir alone was used for initial treatment. Retinal detachment occurred in 54.5%. Final visual acuity worsened (loss of 3 lines on the ETDRS chart or more) in 60%. Visual acuity was no light perception in 45.5% at the final recorded follow-up. CONCLUSION: Demographics, clinical features and treatment outcomes of PORN in this group of Thai patients were comparable with studies from other countries. Visual prognosis is still poor with current treatment regimens.

Herpetic encephalitis is a risk factor for acute retinal necrosis.

BACKGROUND: Acute retinal necrosis (ARN) has been observed in several cases after herpetic encephalitis (HE). ARN is a devastating ocular disease with a very disappointing visual outcome. Therefore, early recognition and diagnosis are crucial. OBJECTIVE: To study the association between ARN and preceding neurologic illness, especially the co-occurrence of HE in patients with ARN; to compare the causal agent in ARN and HE; and to determine the visual outcome of ARN with HE vs ARN without HE. METHODS: A retrospective study including ophthalmologic and neurologic follow-up together with virologic data of patients with ARN. PARTICIPANTS: Seven patients with ARN diagnosed with a history of HE (13.5%) out of a source population of 52 patients with ARN admitted to a major academic ophthalmologic referral center between 1983 and 2008. RESULTS: In five out of seven patients unilateral ARN occurred after HE under immunocompetent conditions, and both ARN and HE were caused by the herpes simplex virus (HSV), whereas the other two patients were immunocompromised, had bilateral ARN, and both ARN and HE were caused by the varicella zoster virus (VZV). The latency period between the HE and the ARN was shorter when VZV was involved than with HSV (5 weeks vs 20.6 months). The visual outcome in patients with ARN with HE, as defined by legally blind eyes after a follow-up of 1 year, did not differ significantly from patients with ARN without HE. CONCLUSION: Herpetic encephalitis seems to be a risk factor for acute retinal necrosis syndrome. Since treatment may improve the outcome at least for the second eye, it is relevant for clinicians to be aware of this association.