Treatment of Refractory Acute Retinal Necrosis with Intravenous Foscarnet or Cidofovir

Purpose: To report use of intravenous foscarnet or cidofovir for the treatment of refractory acute retinal necrosis (ARN).

Methods: Retrospective chart review.

Results: Four immunocompetent men aged 45–90 years presented with ARN from 2008–2014. One patient with two prior episodes of herpes simplex virus (HSV) ARN developed ARN after 6 years of antiviral prophylaxis. His condition worsened on acyclovir followed by intravenous foscarnet but responded to intravenous cidofovir (final VA in involved eye 20/20). Another patient with HSV ARN had received prolonged acyclovir prophylaxis for HSV keratitis; ARN improved after switching from acyclovir to intravenous foscarnet (final VA 20/125). Two patients with varicella zoster virus (VZV) ARN initially responded to acyclovir but developed fellow eye involvement 2–8 weeks later that worsened on acyclovir but responded to intravenous foscarnet (fellow eye final VA 20/20, 20/40).

Conclusions: Cases of HSV or VZV ARN that worsen despite intravenous acyclovir treatment may respond to intravenous foscarnet or cidofovir.     

Correlation of Clinical Outcomes with Quantitative Polymerase Chain Reaction DNA Copy Number in Patients with Acute Retinal Necrosis

Purpose: To correlate visual acuity outcomes and clinical features with quantitative PCR DNA copy number in patients with acute retinal necrosis (ARN).

Methods: Retrospective, consecutive case series.

Results: In total, 14 eyes of 13 patients were diagnosed with ARN, based on the American Uveitis Society criteria, and were followed for a mean of 324.5 days (median 250.5 days, SD ± 214 days). Anterior chamber fluid analyzed by quantitative PCR identified viral DNA in 11 of 14 eyes (78.5%). Varicella zoster virus (VZV) was identified in seven eyes (50%) and herpes simplex virus (HSV) in four eyes (28.5%). Mean DNA copy number was 7.9 × 10⁶/mL (median 2.10 × 10⁶/mL, range: 0–5.60 × 10⁷/mL). Eyes with quantitative PCR DNA copy number of ≥5.0 × 10⁶/mL (n = 6 eyes) had worse baseline visual acuity (logMAR 1.48 ± 0.71 vs 0.94 ± 0.76, p = 0.196) and final visual acuity (logMAR 2.10 ± 0.60 vs 0.82 ± 0.81, p = 0.007) compared with patients with a DNA copy number <5.0 × 10⁶/mL (n = 8 eyes). Patients with a DNA copy number of ≥5.0 × 10⁶/mL were more likely to have at least 5 clock hours of retinitis on funduscopic exam (p = 0.03) and developed retinal detachment more frequently (p = 0.08).

Conclusions: Quantitative DNA copy number of ≥5.0 × 10⁶/mL is associated with more extensive retinitis, worse visual acuity, and development of retinal detachment in patients with acute retinal necrosis.     

Acute Retinal Necrosis

Acute retinal necrosis represents a distinct, recently recognized clinical syndrome. Four patients who presented with rapid visual loss associated with uveitis and coalescent areas of retinal necrosis, followed by development of retinal detachments were examined. This paper emphasizes the following: (1) unilateral involvement does occur, (2) the distribution of lesions can be peripheral or central, and (3) early lesions are not associated with retinal vascular abnormalities either clinically or angiographically. Signs and symptoms are suggestive of an infectious process, possibly viral.     

Development of Acute Retinal Necrosis in a Patient with Ocular Sarcoidosis: A Case Report

Purpose: To report a case of acute retinal necrosis (ARN) caused by varicella-zoster virus (VZV) in an elderly patient with ocular sarcoidosis after oral corticosteroid indication.

Methods: Retrospective case report.

Results: A 75-year-old male with a past history of ocular sarcoidosis came with blurred left vision. Ocular findings in the left eye were consistent with ocular sarcoidosis, while no inflammation in the right eye. On day 14, intraocular inflammation in the left eye resolved by topical corticosteroid, but inflammatory cells were found in the right eye. Suspecting recurrence of ocular sarcoidosis, systemic corticosteroid was initiated. On day 21, inflammation worsened, and the presence of extended yellowish white peripheral retinal lesion in the right eye suggested ARN. Polymerase chain reaction (PCR) testing using ocular fluid detected 3.0 × 107 copies/ml of VZV DNA.

Conclusions: In the case of poor response to immunosuppressive therapy in elderly uveitis, infection including ARN should be considered. Immediate PCR testing for pathogen screening is required.     

Overview and Diagnosis of Acute Retinal Necrosis Syndrome

Acute retinal necrosis (ARN) syndrome, also known as Kirisawa's uveitis, is one of the most serious ocular diseases, and is characterized by a combination of peripheral, confluent, necrotizing retinitis, retinal arteritis, and intraocular inflammation. ARN syndrome is caused by the herpesvirus family, including herpes simplex virus (HSV) and varicella-zoster virus (VZV). The diagnosis of ARN syndrome is fundamentally based on clinical appearance and the demonstration of viral infection. Recently, polymerase chain reaction techniques permit detection of very small amounts of viral DNA in intraocular specimens. This knowledge can help in both the diagnosis and design of therapeutic strategy for ARN syndrome. Here we review the clinical presentation and the current advances in the diagnosis of ARN syndrome.     

An Unusual Case of Central Serous Chorioretinopathy in a Patient with Acute Retinal Necrosis

Purpose: In acute retinal necrosis, which is caused by herpes virus, urgent treatment is essential. Design and Methods: Here we present a 47years old male patient, who developed an acute retinal necrosis in his left eye. Therapy was initiated with systemic aciclovir and corticosteroids. Results: During the course of disease our patient achieved improvement of acute retinal necrosis but he developed central serous chorioretinopathy. Conclusions: The development of central serous chorioretinopathy in our patient was most probably due to the systemic corticosteroids he received. Especially in patients with an intraocular inflammation this diagnosis may lead to severe differential diagnostic problems.     

The Acute Retinal Necrosis Syndrome: Part 2: Histopathology and Etiology

The acute retinal necrosis syndrome is manifested by diffuse uveitis, vitritis, retinal vasculitis, and acute necrotizing retinitis (see Part 1). We studied the histopathology and electron microscopic findings of an eye enucleated from a 67-year-old man with typical acute retinal necrosis. Histology showed profound acute necrosis of the retina, retinal arteritis, and eosinophilic intranuclear inclusions in retinal cells. Electron microscopy demonstrated a herpes group virus in all layers of affected retina. The implications of these findings for antiviral and other treatments are discussed.     

Analysis of Retinal Findings of Acute Retinal Necrosis Using Optical Coherence Tomography

Purpose: To analyze the retinal findings in patients with ARN, optical coherence tomography (OCT) was performed. Methods: Seven patients (7 eyes) with ARN were studied using OCT. Results: OCT images depicted highly reflective areas in the inner layers of the retina in all seven cases, corresponding with the yellowish-white lesions of the retina in the acute phase. Disorganization of the retinal structure was also observed in these retinal lesions, especially in cases with severe inflammation. Subretinal changes including retinal exudate and/or fluid were observed in only one case. After regression of the yellowish-white lesions in the retina, a significant reduction in retinal thickness was observed on OCT. Conclusions: OCT permits the detection of full-thickness retinal necrosis in the acute phase and complete absence of retinal structure in the resolution phase, corresponding with the yellowish-white lesions seen in patients with ARN.     

Bilateral Acute Retinal Necrosis: Clinical Features and Outcomes in a Multicenter Study

Purpose: To describe clinical features and outcome in bilateral acute retinal necrosis (BARN).

Methods: Observational retrospective longitudinal review of ocular findings.

Results: Thirty eyes of 15 patients (age 44.1 ± 15.8). Delay of involvement between eyes was 57.2 ± 105.2 months (median 3, range 0.5–360). Herpes simplex virus (HSV)-1 was the most frequent (20 eyes, 66.6%), followed by HSV-2 (five eyes, 16.7%) and varicella zoster virus (VZV, four eyes, 13.3%). Visual acuity worsened in 7 (23%) eyes, improved in 4 (13%), and remained stable in 19 (63%). Major complications included retinal detachment (11 eyes, 36%), optic atrophy (11 eyes, 33%), proliferative vitreoretinopathy (four eyes, 13.3%), neovascular glaucoma (four eyes, 13.3%), phthisis bulbi (three eyes, 10%). Symptoms-to-referral average time was 2.7 ± 1.0 weeks (range 1–4).

Conclusions: In our study BARN was associated with severe visual outcome and high rate of ocular complications. Although BARN is a rare disease, the course is aggressive, regardless prompt referral in tertiary-care uveitis centers.     

急性视网膜坏死18例临床分析

目的 探讨急性视网膜坏死(acute retinal necrosis,ARN)的早期诊断和治疗方法.方法 回顾性研究18例21只眼急性视网膜坏死患者的临床表现和治疗方法.结果 17只眼玻璃体切除联合眼内硅油填充术,术后视网膜复位14只眼(82.35%),早期大剂量抗病毒药物治疗后单眼发病者未发现对侧眼发病.结论 尽早诊断和应用足量的抗病毒药物,结合预防性视网膜激光光凝和玻璃体切除术可提高急性视网膜坏死的治疗效果,同时减少对侧眼的发病率.     

Rate of Retinal Detachment after Early Prophylactic Vitrectomy for Acute Retinal Necrosis

Purpose: To compare the rate of retinal detachment after acute retinal necrosis in eyes that underwent early vitrectomy versus no early vitrectomy.

Methods: Charts of patients (61 eyes) who presented to Texas Retina Associates between January 1, 2006 and December 30, 2014 for acute retinal necrosis were reviewed. Charts with incomplete documentation or follow­up less than 6 months were excluded. Twenty-nine remaining eyes were divided into two groups: early vitrectomy and no early vitrectomy. Primary outcome measure was rate of retinal detachment.

Results: Out of 29 eyes, 12 underwent early vitrectomy within 30 days of diagnosis and 17 either underwent vitrectomy after 30 days or did not undergo prophylactic vitrectomy at all. Three out of 12 eyes (25%) developed retinal detachment in the early vitrectomy group versus 10 out of 17 eyes (59%) in the no early vitrectomy group (p = 0.076).

Conclusions: Early vitrectomy within 30 days may prevent retinal detachment after acute retinal necrosis.     

Acute retinal necrosis results in low vision in a young patient with a history of herpes simplex virus encephalitis

Acute retinal necrosis (ARN), secondary to herpes simplex encephalitis, is a rare syndrome that can present in healthy individuals, as well as immuno‐compromised patients. Most cases are caused by a secondary infection from the herpes virus family, with varicella zoster virus being the leading cause of this syndrome. Potential symptoms include blurry vision, floaters, ocular pain and photophobia. Ocular findings may consist of severe uveitis, retinal vasculitis, retinal necrosis, papillitis and retinal detachment. Clinical manifestations of this disease may include increased intraocular pressure, optic disc oedema, optic neuropathy and sheathed retinal arterioles. A complete work up is essential to rule out cytomegalovirus retinitis, herpes simplex encephalitis, herpes virus, syphilis, posterior uveitis and other conditions. Depending on the severity of the disease, the treatment options consist of anticoagulation therapy, cycloplegia, intravenous acyclovir, systemic steroids, prophylactic laser photocoagulation and pars plana vitrectomy with silicon oil for retinal detachment. An extensive history and clinical examination is crucial in making the correct diagnosis. Also, it is very important to be aware of low vision needs and refer the patients, if expressing any sort of functional issues with completing daily living skills, especially reading. In this article, we report one case of unilateral ARN 20 years after herpetic encephalitis.     

Intraocular Detection of Herpes viruses by xTAG Liquid Chip Technology in Patients with Acute Retinal Necrosis

Purpose: To evaluate the performance of the xTAG liquid chip technology (xTAG-LCT) for etiological diagnosis of acute retinal necrosis (ARN).

Methods: Fifteen vitreous and 3 aqueous samples from 18 ARN patients were analyzed by xTAG-LCT and multiplex PCR (mPCR)/quantitative PCR (qPCR).

Results: xTAG-LCT revealed positive results in 17 of the 18 samples: 10 for Varicella Zoster Virus (VZV) alone; 5 for VZV and Epstein-Barr virus (EBV); 1 for herpes simplex viruses type 1 (HSV-1) and EBV; 1 for VZV, HSV-1 and EBV. While mPCR revealed the same results as xTAG-LCT for VZV and HSV-1 in all samples, only 2 of the 7 samples positive for EBV on xTAG-LCT were confirmed by qPCR. None of the 28 control vitreous samples from 8 non-ARN patients and 10 pair of cadaveric eyes was positive for any of the tested viruses.

Conclusions: xTAG-LCT could be a useful alternative for etiological diagnosis of ARN.     

Vitrectomy with Silicone Oil Tamponade in Rhegmatogenous Retinal Detachment following Acute Retinal Necrosis: Clinical Outcomes and Prognostic Factors

Purpose: The purpose of the study is to report the prognostic factors and outcomes of vitrectomy (PPV) with silicone oil tamponade in rhegmatogenous retinal detachment (RRD) secondary to acute retinal necrosis (ARN).

Methods: This retrospective, non-randomized, interventional comparative study included 38 eyes of 38 patients. All cases underwent PPV with silicone oil tamponade. The main outcome measure was improvement of final visual acuity relative to the presenting visual acuity and factors affecting the same Group A included eyes with favorable vision of 20/400 or better and Group B included the others.

Results: Group A included 16 eyes (42.10%), group B included 22 eyes (57.89%). In Group A 2 eyes out of 16 (12.5%) and in Group B 12 eyes out of 22 (54.54%) had RRD at presentation (p = 0.02, 95% CI for the difference 7.88–65.78%). The time interval between first presentation and development of RRD in Group A was 30.94 ± 38.8 days (median 30 days) whereas that in Group B was 10.81 ± 11.73 days (median 8 days) (p = 0.02). The odds of visual improvement post-vitrectomy when RRD occurred later was 8.4 (p = 0.01, 95% CI 1.53–46.1). The usage of systemic steroids (odds 5.2, p = 0.03, 95% CI 1.14–23.54) and oral valacyclovir (odds 4.33, p = 0.04, 95% CI 1.05–17.84) were associated with odds favoring a good visual outcome. Recurrent RRD was noted in 3/16 eyes (18.75%) in Group A and 13/22 eyes (59.09%) in Group B (p = 0.03).

Conclusion: Delayed occurrence of RRD after ARN is a good prognostic factor. Usage of systemic steroids and oral valacylocvir are associated with a favorable visual outcome when started before the onset of RRD.     

Bilateral Acute Retinal Necrosis (BARN): Identification of the Presumed Infectious Agent

We describe histopathologic features of an enucleated eye of a patient suffering bilateral acute retinal necrosis (BARN). Retinal tissue was found focally degenerated, and the choroid massively enlarged by lymphoidlike agranular cells. An association of the disease with a viral infection could be demonstrated by (a) the presence of virus particles of the herpesvirus type in retinal tissue, (b) the transmission of the infected principle to human embryo fibroblast cultures, and (c) the visualization of CMV-antigens by immunofluorescence microscopy in such infected cultures. Slow growth of the virus in vitro and the presence of CMV-antigens after infection indicate that the herpesvirus involved in BARN was of the type CMV. On the basis of these findings we propose a guideline for therapy.     

Acute Retinal Necrosis: Diagnostic and Treatment Strategies in Germany

Purpose: To analyze the preferred practice respective diagnosis, treatment, and complications in patients with acute retinal necrosis in Germany.

Methods: The uveitis-section of the German Ophthalmologic Society developed a questionnaire with 12 questions concerning patients with acute retinal necrosis seen in the 5 years up to August 2009.

Results: In total, 35 eye hospitals answered the questionnaire and reported 213 patients with acute retinal necrosis. Diagnosis was made clinically in 86%. Anterior chamber tap, vitreous biopsy, diagnostic vitrectomy, and serology were performed for confirmation. Therapy was started with acyclovir in all institutions, and continued with ganciclovir, foscarnet and brivudine in some cases. Intravitreal injections were performed in 46%. Additional oral steroids were given in 80%. A following oral antiviral treatment was performed in 94%.

Conclusions: Relevant variations were seen in diagnosis and treatment practices. The survey outlines the need for a unique diagnostic and therapeutic guideline.     

Acute Retinal Necrosis: Is The Current Valacyclovir Regimen Adequate?

ABSTRACT

Acute Retinal Necrosis (ARN) is a potentially devastating form of Uveitis. Antivirals are the mainstay treatment for this syndrome. In this letter, we question the current oral Valacyclovir dosage, based on the experience we had with a recent unresponsive ARN case.     

急性视网膜坏死综合征的误诊分析

目的 分析急性视网膜坏死综合征(Acute retinal necrosis syndrome,ARN)临床诊断中存在的问题.方法 收集1998年1月至2006年10月中山眼科中心确诊住院治疗、以往资料完整的114例ARN病人的临床资料,重点分析初诊时误诊、漏诊原因,发病至确诊时间、确诊前诊断、治疗等情况.结果 114例(141眼)ARN病人的盲目率(42/141)为29.79%;初诊时,Ⅰ、Ⅱ、Ⅲ-Ⅳ期误诊率分别为61/70(87.14%)、23/25(93.0%)、13/19(73.68%),发病至确诊时间最短为3 d,最长为420 d,平均为46.16 d.结论 ARN综合征漏诊、误诊率较高,急需提高ARN的早期确诊率使病人保存部分有用视力.     

Ocular toxoplasmosis associated with scleritis

We report an atypical presentation of Toxoplasma retinochoroiditis with associated scleritis in a young and immunocompetent patient. The diagnosis was done on the basis of Polymerase chain reaction of vitreous sample, and the clinical response to specific treatment. This case highlights the unusual presentation of ocular toxoplasmosis as scleritis.