Necrosis retinal aguda. Dos casos clínicos / Acute retinal necrosis. A report of two clinical cases

La necrosis retinal aguda es una afección grave que amenaza la visión. Es frecuente en adultos, tanto inmunocompetentes como inmunocomprometidos. Se presentan dos pacientes, uno de 38 años, con antecedentes de salud anterior que acude a consulta con síntomas y signos de necrosis retinal aguda en el ojo izquierdo, la que fue diagnosticada luego; y otro de 48 años de edad con antecedentes de infección por herpes zóster, tres meses antes de los síntomas oculares, que concluyó con igual diagnóstico. No existió evolución satisfactoria, a pesar del tratamiento adecuado, lo que demostró que independientemente de datos estadísticos y estudios realizados que demuestran lo infrecuente de esta enfermedad, se diagnosticaron dos casos en el periodo de un año, dato que nos exhorta al estudio y práctica de alternativas diagnósticas y terapéuticas para minimizar las consecuencias devastadoras de esta afección.

Acute retinal necrosis is a serious vision-threatening condition. It is common in both immunocompetent and immunocompromised adults. We present two male patients; one aged 38 years, with a previous health history who comes to consultation with symptoms and signs of acute retinal necrosis in his left eye, which was later diagnosed; and another one aged 48 years with a history of herpes zoster infection three months before the ocular symptoms, which concluded with the same diagnosis. Regardless of the statistical data and research carried out on this rare disease, there was no satisfactory evolution despite adequate treatment. Two cases were diagnosed in a period of one year, data that urges us to study and practice diagnostic and therapeutic alternatives to minimize the devastating consequences of this condition.

Changes of viral DNA load in the early stages of antiviral treatment in varicella zoster virus-induced acute retinal necrosis / 中华眼底病杂志

Objective:To observe the changes of varicella zoster virus (VZV)-DNA load in aqueous humour samples in VZV-induced acute retinal necrosis (ARN) in the early stages of antiviral treatment.Methods:A retrospective observational clinical study. From April 2016 to April 2018, 24 patients with 24 eyes of VZV-induced ARN who were diagnosed by Department of Ophthalmology, Eye and ENT Hospital of Fudan University and received complete aqueous humor sampling were included in the study. Among them, there were 13 males with 13 eyes, 11 females with 11 eyes; 12 left eyes and 12 right eyes; the age was 52.0±9.5 years old (39-71 years old). The time from the onset of ocular symptoms to the diagnosis of ARN was 16.6±6.1 days (7-30 days). Best-corrected visual acuity (BCVA) and ultra-wide-field fundus imaging were performed in all affected eyes. The BCVA examination was carried out using the Snellen visual acuity chart, which was converted into the logarithm of the minimum angle of resolution (logMAR) visual acuity. All patients were given intravitreal injection of 40 mg/ml ganciclovir 0.1 ml (including 4 mg of ganciclovir), 2 times a week, until the active necrotizing retinal lesions subsided, at most after the diagnosis 4 weeks, with a maximum of 9 injections. The follow-up period was 12.8±5.6 months. The aqueous humor samples were collected at presentation and 4, 7, 14, 21, 28 days after the initiation of antiviral therapy, and the VZV-DNA load was detected by real-time quantitative polymerase chain reaction. A plateau phase and a logarithmic reduction phase of the DNA load changes were observed after antiviral treatment began. Wilcoxon rank sum test was used to compare and analyze the differences in BCVA between the eyes at baseline and last follow-up.Results:The mean viral load at presentation was 8.6×10 7±1.3×10 8 copies/ml. The initial plateau phase last for an average of 7.4±2.4 days. In the following logarithmic reduction phase, the mean slope of the decline in viral load was -0.13±0.04 log/day, and the expected time for half reduction of the initial viral load was 2.5±0.7 days. After 28 days antiviral treatment, the viral load decreased to 1.7×10 5±1.8×10 5 copies/ml. In the course of the disease, rhegmatogenous retinal detachment occurred in 16 eyes. Before treatment and at the last follow-up, the logMAR BCVA of the affected eye was 1.1±0.6 and 0.8±0.7, respectively. The results of correlation analysis showed that the logMAR BCVA at the last follow-up was correlated with the initial VZV-DNA load ( r=0.467, P=0.033). Conclusion:The VZV-DNA load in the aqueous humor of eyes with VZV-induced ARN is significantly decreased after antiviral treatment, which is closely related to the clinical process of ARN.

Necrosis retiniana aguda por virus varicela zoster en un paciente inmunocompetente con seguimiento de la respuesta terapéutica mediante reacción de polimerasa en cadena / Acute retinal necrosis by varicella zoster virus in an immunocompetent patient with therapeutic follow up by PCR

Resumen Presentamos el caso de un varón de 63 años, inmunocompetente, con una necrosis retinal aguda (NRA) unilateral. Consultó por visión borrosa, dolor ocular, fotofobia y cefalea. Se confirmó una papilitis y coriorretinitis periférica asociada a vasculitis e isquemia retinal periférica. El estudio molecular por RPC de humor acuoso detectó la presencia de virus varicela zoster. El paciente fue tratado con terapia combinada con corticoesteroides orales, aciclovir oral/intravenoso, ganciclovir intravítreo semanal y luego valaciclovir oral por tres meses. Se demostró una disminución progresiva de la carga viral en el humor acuoso durante el tratamiento. El seguimiento mostró una mejoría del cuadro inflamatorio y una leve recuperación de la agudeza visual, sin embargo, finalmente presentó un desprendimiento de retina con pérdida casi total de la visión unilateral. La NRA es una complicación infrecuente provocada por algunos virus herpes con mal pronóstico visual, desenlace que puede ser mejorado con un diagnóstico y tratamiento precoz con antivirales. El tratamiento prolongado permite evitar la recaída y el compromiso contralateral.

Abstract We present the case of a 63-year-old immunocompetent man with unilateral acute retinal necrosis (ARN). He consulted for blurred vision, eye pain, photophobia, and headache. Papillitis and peripheal chorioretinitis associated with vasculitis and peripheral retinal ischemia was confirmed. PCR from aqueous humor sample detected varicella zoster virus. The patient was treated with a combined therapy of oral corticosteroids, oral / intravenous acyclovir along with weekly intravitreous ganciclovir doses followed by oral valaciclovir for three months. A progressive decrease in viral load in aqueous humor was demonstrated during treatment. Follow-up showed improvement in the inflammatory condition and a slight recovery of visual acuity, however, finally he presented a retinal detachment with total loss of one-sided vision. ARN is an uncommon complication caused by some herpesviruses with a poor visual prognosis, an outcome that can be improved with early diagnosis and treatment using appropriate antivirals. Prolonged treatment reduces relapse frequency and fellow eye compromise.

Toxoplasmose sistêmica associada à forma ocular bilateral atípica mimetizando necrose retiniana aguda / Systemic toxoplasmosis associated to the atypical bilateral ocular involvement mimicking acute retinal necrosis

RESUMO A toxoplasmose ocular pode se manifestar de forma atípica, rara, bilateral e associada à necrose retiniana aguda. É apresentada em pacientes imunossuprimidos, resultando em grave perda visual, se não for solucionada rapidamente. Relata-se um caso atípico de toxoplasmose ocular em paciente diabético, que, em sua internação prévia, já evidenciava aspecto sistêmico, o qual foi elucidado pelo exame clínico oftalmológico e pela anamnese. Além disso, a rotina do setor de uveítes, ao solicitar as sorologias de forma direcionada e criteriosa, foi imprescindível para o diagnóstico da toxoplasmose sistêmica associado à lesão ocular atípica bilateral, mimetizando necrose retiniana aguda com desfecho favorável.

Abstract Ocular toxoplasmosis can present with an atypical, rare, bilateral involvement, and associated with acute retinal necrosis. It occurs in immunosuppressed patients, resulting in severe visual loss, if not quickly solved. We report an atypical case of ocular toxoplasmosis in a diabetic patient, who already showed a systemic aspect in a previous hospitalization, which was elucidated by the ophthalmologic examination and history. In addition, the routine of the uveitis sector requesting serology in a directed and careful way was essential for the diagnosis of systemic toxoplasmosis associated with atypical bilateral ocular lesion, mimicking acute retinal necrosis with good outcome.

Retinal Toxicity Following the Injection Ganciclovir into Silicone Oil-filled Eye to Treat Acute Retinal Necrosis

PURPOSE: To report a case of retinal toxicity after an intravitreal ganciclovir injection to treat acute retinal necrosis in an eye filled with silicone oil.CASE SUMMARY: A 56-year-old male presented with ocular pain and visual loss in his right eye. His best-corrected visual acuity was 20/25, inflammatory cells in the anterior chamber, multiple retinitis lesions and retinal vessel occlusions in the peripheral retina and vitreous opacity were showed. Acute retinal necrosis was suspected, anterior chamber polymerase chain reaction (PCR) test was done. Aciclovir 2,400 mg/day intravenously and ganciclovir 2.0 mg were administered by intravitreal injection. After 4 days, retinitis was worsened and PCR test was positive for varicella zoster virus. Ganciclovir intravitreal injections were increased twice a week. After 16 days, retinal detachment occurred, so scleral encircling, vitrectomy, laser photocoagulation, and silicone oil tamponade were conducted. Ganciclovir 1.0 mg was injected at the end of surgery. The patient's visual acuity decreased to hand motion, and multiple crystal deposits with multiple retinal hemorrhages were observed in the right eye the next day. Visual acuity did not recover and optical coherent tomography showed that the macula was thinned.CONCLUSIONS: Visual loss seemed to be related with the retinal toxicity of ganciclovir. The increased local concentration due to the silicone oil tamponade is thought to have caused the toxicity.

Bilateral Acute Retinal Necrosis and Encephalomalacia Due to Herpes Simplex Virus Infection in a Premature Infant

Herpes simplex virus (HSV) is a common pathogen, that causes a broad spectrum of diseases, ranging from minor skin infections to severe encephalitis and widespread infections. Acute retinal necrosis (ARN), one of the most serious manifestations of HSV infection, is defined as a rapidly progressing necrotizing retinopathy that presents discrete areas of circumferential retinal necrosis, along with signs of uveitis, vitreitis, and retinal vasculitis. We encountered a case of a female infant, born at 33 weeks of gestation with a body weight at birth of 2,080 g, who had ARN and encephalomalacia due to HSV infection. ARN associated with HSV infection should be suspected when nonspecific retinal exudates are observed in neonates, especially preterm infants.

Advancement in diagnosis and treatment of acute retinal necrosis syndrome / 国际眼科杂志(Guoji Yanke Zazhi)

Acute retinal necrosis syndrome (ARNS) is a group of eye syndrome.Acute uveitis, retinal artery occlusive vasculitis, fused necrotic retinitis and late stage of retinal detachment is the main clinical manifestation.A part of patients may be associated with increased intraocular pressure.The etiology and pathogenesis is still not clear completely and most people think that may be related to the virus infection, which mainly to reflected to be herpes simplex virus (HSV), varicella zoster virus (VZV), EB virus and giant cell virus (CMV) infection.Its diagnosis mainly depends on clinical manifestation, examination and etiological examination.Acute retinal necrosis syndrome is urgent and develops quickly, and it is lack of specific clinical symptoms in early times.By the way, it enjoys high misdiagnosis rate and poor prognosis.It is hard to cure, therefore, it is an important reason for the blindness.Once diagnosed, treatment should be adopted by carrying local and systemic antiviral, preventive laser photocoagulation in time.At the same time, it is essential that vitreous body resection combine with silicone oil tamponade treatment when necessary.The study shows that the effective measures of early treatment will be able to prevent disease progression and improve visual acuity.Therefore, early diagnosis and treatment of acute retinal necrosis syndrome is very important.In this paper, combination of the literature on the diagnosis and treatment of acute retinal necrosis syndrome were reviewed.

Comparison of two different drug therapies for acute retinal necrosis syndrome / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate clinical efficacy of two drug therapies ( acyclovir with prednisone acetate tablets, ganciclovir with prednisone acetate tablets and aspirin) for acute retinal necrosis syndrome. METHODS: Thirty patients (40 eyes) with acute retinal necrosis syndrome in our hospital were randomly divided into group A and B. Group A was treated with acyclovir with prednisone acetate tablets, and group B was given ganciclovir with prednisone acetate tablets and aspirin. Clinical effects in the two groups were observed and compared. RESULTS: After treatment, the overall response rate in group B (90%) was obviously higher than that in group A (70%), both of two regimens were effective, without significant difference (P>0. 05). There was no significant difference on the pre - treatment visual acuity between the two groups (P>0. 05). After different treatments, the visual acuity in group B was ≥0. 5 in 12 eyes, 0. 1≤andCONCLUSION: Two drug therapies ( acyclovir with prednisone acetate tablets, ganciclovir with prednisone acetate tablets and aspirin ) both have positive therapeutic effect, but the latter can better restore visual acuity and decrease the complications.

Acute retinal necrosis following intravitreal dexamethasone (Ozurdex®) implant / Necrose aguda de retina após implante de dexametasona intravítrea (Ozurdex®)

A 52-year-old woman undergoing azathioprine treatment for rheumatoid arthritis developed acute retinal necrosis a month after intravitreal dexamethasone (Ozurdex ®) implantation for posterior uveitis in the left eye. Varicella zoster virus (VZV) DNA was detected in the anterior chamber and vitreous samples on polymerase chain reaction (PCR) analysis. Retinal detachment occurred despite systemic and intravitreal antiviral therapy. Favorable structural and functional outcomes were achieved after retinal surgery with silicone oil. To the authors’ knowledge, this is the first reported case of acute retinal necrosis following placement of an Ozurdex® implant. Physicians practicing Ozurdex® implantations should be aware of this unusual but devastating complication. Extra caution and frequent follow-up are required in all immunocompromised patients receiving Ozurdex® implantation.

Uma mulher de idade de 52 anos em tratamento azatioprina para a artrite reumatóide desenvolveu necrose aguda de retina um mês após implantação Ozurdex® para uveíte posterior do olho esquerdo. DNA de varicela zoster (VZV) foi detectado em amostras de câmara anterior e vítreo por análise de PCR. Apesar da terapia antiviral sistêmica e intravítrea, o paciente apresentou descolamento de retina. Desfecho favorável estrutural e funcional foi obtida após a cirurgia retiniana com óleo de silicone. Pelo conhecimento dos autores, este é o primeiro caso relatado de necrose aguda de retina após a colocação de um implante Ozurdex®. Os médicos que implantam Ozurdex® devem estar cientes desta complicação incomum, mas devastadora. É necessário cuidado extra e acompanhamento frequente dos pacientes que recebam o implante Ozurdex® e apresentem qualquer condição imunocomprometedora.

Necrose retiniana aguda por presumível etiologia viral por herpes simples resultando em endoftalmite: relato de caso / Acute retinal necrosis due to herpes simplex resulting in endofthalmitis: case report

A necrose retiniana aguda é uma rara e devastadora retinite necrotizante, que pode ser causada pelo vírus herpes simples tipo 1 ou 2. Afeta tipicamente pacientes saudáveis de todas as idades. Este estudo é um relato de caso de um paciente de 18 anos, previamente hígido, que apresentou necrose aguda de retina por presumível etiologia viral por herpes simples, e descreve sua apresentação clínica e ultrassonográfica. Por não ter sido diagnosticado e tratado precocemente, a necrose retiniana aguda cumpriu sua história natural e evoluiu para um quadro compatível com endoftalmite.

The acute retinal necrosis is a rare and devastating necrotizing retinitis, which can be caused by the herpes simplex virus type 1 or 2. It typically affects healthy patients of all ages. This study report a case of 18 year-old healthy male patient, with the the diagnosis of the acute retinal necrosis due to herpes simplex, and presents its clinical and ultrassonographic features. The acute retinal necrosis results in endofthalmitis because of lack of early diagnosis and therapy.

Acyclovir-induced Acute Renal Failure in a Patient With Suspected Acute Retinal Necrosis Syndrome

PURPOSE: To report a case of acyclovir-induced acute renal failure (ARF) suspected as acute retinal necrosis syndrome. CASE SUMMARY: The authors report a 55-year-old male patient who presented with left eye visual disturbance due to suspected acute retinal necrosis syndrome. Non-oliguric ARF developed after the infusion of intravenous acyclovir (850 mg every 8 hours). The patient did not show any uremic symptoms or signs. The crystal was not discovered in the urine. After stopping the acyclovir infusion and hydration, acyclovir-induced ARF was reversed. CONCLUSIONS: Although possessing critical nephrotoxicity, acyclovir is a useful antiviral drug. Therefore, when using acyclovir, the importance of hydration and preventing acyclovir-induced ARF should be considered.

Therapeutic effects of ganciclovir with different injection methods on experimental retinal necrosis / 中华眼底病杂志

Objective To observe the therapeutic effects of ganciclovir(GCV)with differentInjection methods on experimental acute retinal necrosis(ARN).Methods The right eyes of 41pigmented rabbits were infected by herpes simplex virus(HSV-1)(COS strain)to establish ARN animalmodel.After 24 and 72 hours,GCV was given by intravitreal injection(10 eyes),intravenous injection(11 eyes)and the intravitreal+intravenous injection(10 eyes);intravitreal injection of GCV anddexamethasone(6 eyes)was also included.Four eyes were not treated as the control.The dosage of GCVin intravitreal and intravenous injection was 800 μg and 5 mg/kg weight,respectively.Retina necrosis wasobserved and the grade was recorded 1-21 days after injection according to the grade standard ofretinopathy.The maximum grades of retinal necrosis in different groups were compared.Results Thegrade of retinal necosis was 3.8 in the control group,and 0.2,0.4,0.8,and 2.2 in intravitreal iniection,intravitrcal+intravenous injection,intravitreal injection with GCV and dexamethasone,and intravenousrejection,respectively,24 hours after the model was set up.The effects of the first 3 groups wereobviously better than the Iast group(P=0.003,0.011,0.045);while the difference among the first 3groups were not significant(P=0.881,0.054,0.107).Seventy-two hours after the mode J was set up,thegrades of retinal necrosis were above 1.4 in 4 groups,and the differences among the 4 groups were notapparent(P=0.214).Conclusions In the animal model of ARN,intravitreal injection with GCV caneffectively decrease the grade of retinal necrosis.The difference among intravitrealinjection,intravitreal+intravenous injection,intravitreal injection with GCV and dexamethasone,and intravenous injection is notsignificant.

The effect of vitrectomy,endolaser photocoagulation and silicone oil injection for acute retinal necrosis syndrome / 医学研究生学报

Objective:Acute retinal necrosis syndrome(ARNS) is a rare disease with high blinding rate.The surgery of vitrectomy,endolaser photocoagulation and silicone oil injection is considered an effective treatment of ARNS.The study investigated the effect of vitrectomy,endolaser photocoagulation and silicone oil injection treating ARNS.Methods:A consecutive 16 eyes of 16 patients with ARNS were treated with vitrectomy,endolaser photocoagulation and silicone oil injection.The 5 eyes without retinal detachment were photocoagulated from the posterior border of necrosis to the ora serrata.The 11 eyes with retinal detachment were treated with subtotal retinal photocoagulation,air/fluid exchange and silicone oil injection.The follow-up time were 6 months at least,16 months in average.Results:The final best-correcting visual acuity was counting fingers in 3 eyes(18.8%),0.02-0.3 in 7 eyes(43.8%),0.4-0.6 in 5 eyes(31.3%),0.7 in 1 eye(6.3%).The silicone oil was uneventfully removed in 14 patients(87.5%) from 3 to 12 months.No one had a recurrent retinal detachment.Conclusion:There is a favorable effect in ARNS with the treatment of vitrectomy,endolaser photocoagulation and silicone oil injection.

Characteristics of fundus angiography in acute retinal necrosis syndrome / 中华眼底病杂志

Objective To observe the characteristics of images of fundus fluorescein angiography (FFA) and indocyanine green angiography (ICGA) in patients with acute retinal necrosis syndrome (ARNS), and investigate the applied value of FFA and ICGA in clinical diagnosis. Method The data of the ocular fundus, FFA and ICGA of 20 patients (28 eyes) with ARNS were retrospectively analyzed. Results The images of FFA indicated hyperfluorescence of optic disc in 24 eyes (85.71%) at the late phase; widespread retinal vascular occlusion at the peripheral focus in 23 eyes (82.14%) with some occlusive vascular shadow and the fluorescein in some white-line-like blood vessels; fluorescent leakage at the junction of normal and abnormal retina in 22 eyes (78.57%); retinal detachment in 20 eyes (71 42%), including 9 with retinal hole (45% of the patients retinal detachment); and macular cystoid edema in 8 eyes (28 57%). The images of ICGA showed hyperfluorescence of optic disc in 8 eyes (28 57%) including 5 with dotted staining at the optic disc at the late phase; unclear choroidal vasculature in the peripheral focus in 20 eyes (71.42%); and choriodal scattered hypofluorescent patch at the focus area in 19 eyes (67.85%). At the late phase of ICGA, some intravascular emboli and segments of retinal vascular occlusion were clearly demonstrated. Conclusion The main manifestations of patients with ARNS in the images of FFA were hyperfluorescence of optic disc and retinal vascular occlusion; and unclear choroidal vessels and scattered hypofluorescent patch at the focus area.Combination of FFA and ICGA is helpful to understand the extent of the lesions and the relations between choroids and retina, which has great significance in diagnosing ARNS.

Vitreous Surgery for Retinal Detachment associated with Acute Retinal Necrosis Syndrome

The acute retinal necrosis syndrome(ARN) is characterized by acute peripheral necrotizing retinitis, occlusive arteritis, and panuveitis. ARN is often complicated by late retinal detachment and a poor visual outcome. We describe herein a series of 4 consecutive patients(5 eyes) with ARN, complicated by retinal detachment. A patient with bilateral ARN(case 1) underwent prophylactic vitrectomy, 360 degrees scleral buckling, and intravitreal injection of acyclovir on the right eye while the retina was attached. Subsequently, the retina became detached. The retina was successfully reattached by performing fluid-gas exchange and laser photocoagulation. Argon laser photocoagulation was performed as a prophylaxis to prevent retinal detachment in two eyes. However, the two retinas subsequently detached. The two eyes were treated with vitrectomy, 360 degrees scleral buckling, fluid-gas exchange, and endolaser photocoagulation. Remaining two eyes required vitrectomy, silicone oil injection, and endolaser photocoagulation with(case 3) or without(case 4) 360 degrees scleral buckling. The retinas remined attached in all five eyes with no additional treatment. Four eyes achieved a visual acutiy of 0.1 or better. One had a final visual acuity of FC/40cm because of macular pucker and optic nerve atrophy.

Establishment of rabbit model for acute retinal necrosis and experimental study of infectious pathway in opposite eye / 眼科

Objective To establish the rabbit model for acute retinal necrosis(ARN) and investigate the possible route of the virus migrates from one eye to the other. Design Experimental study. Participants 41 chinchilla rabbits. Methods HSV-1 COS strain was inoculated into subretina in 41 rabbits to establish ARN animal model. Ganciclovir was used to treat by intraocular and/or intravenous injection 1 day or 3 days after virus inoculation. PCR test of blood samples was performed for HSV detection. Histopathological examinations were also conducted in some eyeballs, optic nerves and brains of the rabbits. Main Outcome Measures Results of blood PCR and histopathology. Results 10 rabbits appeared bilateral retina necrosis (10 to 18 days after virus inoculation) and 15 rabbits appeared central nervous system damages. PCR samples of 5 rabbits obtained before and after the contralateral retina damages appeared (9 to 19 days after virus inoculation) had all negative results. Histopathological damages were found in bilateral eyeballs, optic nerves and brains. Conclusion The ARN model can be established by injection of HSV-1 into subretina of rabbits. Blood samples PCR don't support the hypothesis of virus transmission through circulation system in bilateral ARN cases. Trans-optic chiasm transmission may be a possible route.

Electron Microscopic Findings of the Acute Retinal Necrosis Syndrome

One case of unilaterally developed acute retinal necrosis syndrome was studied with retina and vitreous from biopsy during operation through electronmicroscope pathologically and virolo gically. In photoreceptor cells, generalized necrosis was found: loss of outer segments, fragmentation of inner segments, and decrease of mitochondria in ellipsoids. Bipolar cells and axons were well preserved. Internal limiting membrane was intact, and covered by an unidentified cell. Degenerated retinal proper had various sized vacuoles. Around the intraretinal vessels, neutrophils and lymphocytes were infiltrated considering vasculitis. In ganglion cells, swelling of mitochondrias were seen, and their cell organelles were decreased, No virus particle was detected in all layers of the retina with electronmicroscope.