Varicella Zoster Associated Vasculopathy and Retinitis with Natalizumab Use in Multiple Sclerosis.

Natalizumab (Tysabri®, NTZ) is a monoclonal autoantibody approved for treatment of relapsing-remitting multiple sclerosis. NTZ inhibits leukocyte migration across the blood-brain barrier, preventing autoreactive cells from inciting an inflammatory immune response. This immunosuppression is highly efficacious in attenuating the risk of relapse of disease, but has been associated with opportunistic central nervous system (CNS) infections, most notably progressive multifocal leukoencephalopathy. Varicella-zoster and herpes simplex viruses have also been associated with NTZ, inciting a spectrum of disease, including encephalitis, meningitis, and acute retinal necrosis. While rare, these infections can result in devastating outcomes even when promptly identified and treated.   We present a case of combined CNS varicella zoster vasculitis and acute retinal necrosis in a 57-year-old woman maintained on monthly Natalizumab therapy, who presented with headache and visual field deficits.

A case of recurrent viral retinitis treated with intravitreal antiviral agents in a silicone oil filled eye.

PURPOSE: To report a case of recurrent acute retinal necrosis (ARN) in an eye filled with silicone oil previously complicated by rhegmatogenous retinal detachment (RRD). OBSERVATIONS: A 68-year-old gentlemen with successfully treated herpes simplex virus type 1 (HSV1) ARN complicated by RRD requiring pars plana vitrectomy (PPV) with silicone oil tamponade, presented with a relapse of ARN with silicone oil in situ. Remission of recurrent retinitis was achieved using combined systemic oral and intravitreal antiviral therapy. CONCLUSIONS AND IMPORTANCE: RRD is a significant complication of ARN which may require surgery with silicone oil tamponade. Recurrence of ARN retinitis can be effectively treated with intravitreal Ganciclovir and Foscarnet injections in a silicone oil filled eye with concurrent oral antiviral therapy. Aqueous humour sampling proved useful in the monitoring of disease activity.

ACUTE RETINAL NECROSIS AFTER INTRAVITREAL DEXAMETHASONE IMPLANT. A CASE REPORT.

INTRODUCTION: Ozurdex® (Allergan Pharmaceuticals, Castlebar Road, Westport, Ireland) is an intravitreal implant containing 0.7 mg of dexamethasone. It is indicated in adult patients for the treatment of diabetic macular edema, cystoid macular edema due to central retinal vein occlusion, and in patients with non-infectious uveitis. Common complications after Ozurdex® administration include an increase in intraocular pressure, cataract progression or conjunctival suffusion. Acute retinal necrosis after Ozurdex® administration is a very rare and serious complication. According to our current research, this is the fourth published case. Extreme caution must be exercised when treating immunosuppressed patients with Ozurdex®. CASE REPORT: This is case report about an immunosuppressed 68-year-old patient with diabetic macular edema, who developed acute retinal necrosis 74 days after Ozurdex® implantation. He suffers from chronic myeloid leukemia and takes the cytostatic imatinib 400 mg once per day. Urgent pars plana vitrectomy (PPV) with silicone oil instillation was performed and antiherpetic drugs were initiated intravenously. Serological examination confirmed an active infection of cytomegalovirus etiology (CMV). CONCLUSION: Acute retinal necrosis is a rare necrotizing retinitis. Corticosteroids administered intravitreally reduce the local immune response, which may cause a primary infection or reactivation of a latent viral infection.

Surgical Outcomes of Acute Retinal Necrosis-Related Retinal Detachment in Polymerase Chain Reaction-Positive Patients: A Single-Center Experience.

PURPOSE: To evaluate the clinical features, operative techniques, and surgical outcomes of patients who underwent surgery for acute retinal necrosis (ARN)-related retinal detachment (RD). DESIGN: Retrospective, longitudinal, consecutive case series. PARTICIPANTS: Patients with polymerase chain reaction-positive ARN presenting from 2011 to 2021 who underwent vitreoretinal surgery for ARN-related RD at our institution. METHODS: Univariate, multivariate, and survival analyses were used to determine predictors of anatomic and functional outcomes. MAIN OUTCOME MEASURES: Single-surgery anatomic success rate, recurrent RD, and visual acuity (VA) at 1 year. RESULTS: Thirty-four eyes of 34 patients (32.4% women, mean age, 45.1 ± 20.4 years) were included for analysis with a median follow-up of 2.5 years (interquartile range [IQR], 0.8-5.5 years). Presenting VA was 1.1 ± 0.8 logarithm of the minimum angle of resolution (LogMAR) (Snellen ∼20/250). The median time from presentation to RD surgery was 1.7 months (IQR, 0.8-4.1 months), and the mean preoperative VA was 1.6 ± 0.8 LogMAR (Snellen ∼20/800). Small-gauge pars plana vitrectomy (PPV) with or without a scleral buckle (SB) was performed for all eyes with an overall single-surgery success rate of 63.6%, with no statistically significant differences in visual/anatomic outcomes between PPV and PPV/SB cases. Silicone oil was used for tamponade in 33 (97.1%) cases and was removed in 10 (30.3%) with good anatomic and final functional outcomes (Snellen âˆ¼20/80). Independent predictors of recurrent RD included the female sex (hazard ratio, 8.38; 95% confidence interval, 2.03-34.68; P < 0.01) and zone 1 retinitis involvement at presentation (hazard ratio, 10.95; 95% confidence interval, 2.12-56.48; P < 0.01). The mean VA at 1 year (VA1year) and at the final follow-up both had a Snellen equivalent of 20/640 (P > 0.05 for both compared with preoperative VA, respectively). Eyes that achieved single-surgery success had VA1year of 20/200 versus hand movements in those with single-surgery failure (P < 0.01). On multivariate linear regression, younger age (P = 0.04) and better presenting VA (P < 0.01) were both associated with better VA1year. CONCLUSIONS: Moderate single-surgery anatomic success can be achieved with modern vitreoretinal surgical techniques for ARN-related RD, although visual outcomes remain poor. Further studies investigating interventions for increasing single-surgery success rates, for the inflammatory complications of ARN, and for preventing ARN-related RD are needed.

EFFICIENCY OF LASER PHOTOCOAGULATION ON THE PREVENTION OF RETINAL DETACHMENT IN ACUTE RETINAL NECROSIS: A Systematic Review and Meta-Analysis.

BACKGROUND: Retinal detachment is a severe complication of acute retinal necrosis, threatening vision. The published articles on the effectiveness of laser in preventing retinal detachment in acute retinal necrosis are controversial. Therefore, we aim to evaluate whether prophylactic laser is effective for retinal detachment after acute retinal necrosis. METHODS: PubMed, Embase, and Cochrane databases were searched, and the retrieved records were screened. Each included study has well-defined laser-treated group and control group without laser treatment or with enough data for manual grouping. The quality of the included studies was assessed using ROBINS-I ("Risk Of Bias In Nonrandomized Studies-of Interventions"). Meta-analysis was conducted to calculate the pooled odds ratios and their 95% confidence interval. Sensitivity analysis was used to test the solidarity, and subgroup analysis was performed to determine the source of heterogeneity. RESULTS: Fourteen studies with a total of 532 eyes were eventually included. The quality of the included studies was moderate. The combined results showed that the pooled odds ratio was 0.61 (95% confidence interval [0.41∼0.90], P < 0.05, I 2 = 27%). Sensitivity analysis showed that the odds ratios were similar when excluding any study. Subgroup analysis showed moderate heterogeneity among three subgroups (I 2 = 48.0%, P = 0.15 for heterogeneity), and the odds ratio in antiviral therapy and steroid combined with prophylactic laser was 0.43 (95% confidence interval [0.25∼0.74], P < 0.05, I 2 = 0%). CONCLUSION: In patients with acute retinal necrosis, laser photocoagulation is an effective treatment to prevent retinal detachment, especially in the subgroup combined with antiviral therapy and steroid.

Risk Factors for Retinal Detachment in Acute Retinal Necrosis.

PURPOSE: Retinal detachment (RD) is associated with poor visual outcomes in patients with acute retinal necrosis (ARN). This research was undertaken to assess the risk factors for RD in ARN. DESIGN: Retrospective cohort study. SUBJECTS: Patients diagnosed with ARN at a tertiary referral center from 2010 to 2020. METHODS: A chart review was performed for all clinical and surgical encounters. Univariate and multivariate logistic analyses of demographic and clinical variables associated with RD were performed. Survival analyses with Kaplan-Meier estimates were performed to compare the time to RD in herpes simplex virus (HSV)- and varicella zoster virus (VZV)-associated ARN. MAIN OUTCOME MEASURES: Demographic information, clinical information (including visual acuity [VA]), intraocular pressure (IOP), intraocular inflammation level, the extent of retinitis, incidence and timing of retinal detachment, date of diagnosis, and treatments performed (including intravitreal injections of antiviral medications). RESULTS: Fifty-four eyes of 47 patients who were diagnosed with ARN were included, with equal proportions of eyes (n = 27; 50%) with VZV-ARN and HSV-ARN. Patients with VZV-ARN were, on average, older, more likely to be men, and more likely to be immunosuppressed compared with patients with HSV-ARN. The clinical characteristics, including the initial VA, initial IOP, anterior segment inflammation, clock hours, and posterior extent of retinitis, were similar between eyes with VZV- and HSV-ARN. In the univariate analysis of clinical and demographic variables associated with the development of RD, initial VA (P = 0.0083) and greater clock hours of retinitis (P = 0.009) were significantly associated with RD. These 2 variables remained significant in the multivariate logistic regression; worse VA at presentation had an odds ratio of 2.34 (95% confidence interval [CI], 1.01-5.44; P = 0.042), and greater clock hours of retinitis had an odds ratio of 1.23 (95% CI, 1.02-1.47; P = 0.025). A Kaplan-Meier survival analysis demonstrated no statistical difference in RD-free survival between HSV- and VZV-ARN. CONCLUSIONS: Patients with VZV-ARN were more likely to be older, male, and immunosuppressed compared with those with HSV-ARN, although no clear difference was observed in RD by viral etiology. Poor initial VA and clock hours of retinitis were significantly associated with RD development and may be relevant for patient counseling and prognosis.

Role of Prophylactic Vitrectomy in Acute Retinal Necrosis in Preventing Rhegmatogenous Retinal Detachment: Systematic Review and Meta-analysis.

PURPOSE: To evaluate the effects of prophylactic vitrectomy for rhegmatogenous retinal detachment (RRD) risk and visual outcome in acute retinal necrosis (ARN). METHODS: A systematic search of online databases was performed for articles published between 1994 June and 2020 March. The main outcomes that were assessed by a fixed effects model were RRD risk and visual outcome during a follow up period. RESULTS: A total of 7 trials involving 265 eyes (121 prophylactic vitrectomy eyes vs 144 routine antiviral treatment eyes) were analyzed in this study. RRD risk significantly decreased in the prophylactic vitrectomy group compared to the routine antiviral treatment group (P < .001, OR = 0.27, 95% CI: 0.16-0.46, I2 = 35.3%). Significantly deteriorated visual outcome was observed in the prophylactic vitrectomy group in comparison with the routine antiviral treatment group (P < .001, WMD = 0.47, 95%CI: 0.26-0.67, I2 = 32.2%). CONCLUSION: This meta-analysis of retrospective cohort studies revealed that prophylactic vitrectomy could reduce the risk of RRD. The silicone oil tamponade and long-term complications may result in deteriorated visual outcome.

Interferon Alpha-2a for the Treatment of Cystoid Macular Edema Secondary to Acute Retinal Necrosis.

PURPOSE: To report the results of interferon (IFN) α-2a treatment in patients with cystoid macular edema (CME) secondary to acute retinal necrosis (ARN). METHODS: We reviewed the records of seven patients (eight eyes) who received IFNα-2a for post-ARN CME. The initial dose of IFNα-2a was 3 MIU/day and it could be tapered down to 3 MIU twice a week. Efficacy was assessed by central macular thickness (CMT) on spectral-domain optical coherence tomography and visual acuity. RESULTS: Age range of seven patients (four men, three women) was 36-74 years. Mean CMT decreased from 477.9 ± 167.5 µm to 367.3 ± 120.5 µm at first week, and vision improved up to five lines in five eyes. CME relapsed after cessation of IFNα-2a in all and improved following reinstitution of treatment. Treatment was discontinued in one patient because of depression. Three patients electively discontinued treatment due to poor tolerability or lack of functional improvement. CONCLUSION: IFNα-2a is an effective therapeutic option for post-ARN CME, though side effects such as fatigue, elevated liver enzymes, neutropenia, and depression may limit tolerability. Lower initial doses may be a better tolerated.

Therapeutic prognostic factors associated with retinal detachment and visual outcomes in acute retinal necrosis.

BACKGROUND: Acute retinal necrosis (ARN) is a fulminant necrotizing vaso-occlusive retinitis associated with a high incidence of vision loss. Prognostic factors associated with the treatment of ARN have not been comprehensively identified. This study aimed to determine therapeutic prognostic factors associated with long-term clinical outcomes in eyes with ARN. METHODS: This retrospective cohort study included patients with ARN who were treated between 2005 and 2019 in two tertiary ophthalmology departments in Seoul, Korea. Multiple logistic regression analysis was performed to investigate prognostic factors associated with late-onset retinal detachment (RD) and vision loss (<20/200). RESULTS: Sixty-one eyes with ARN with an average follow-up of 63.5 months were included. Surgical intervention of vitrectomy (odds ratio [OR], 0.04; 95% confidence interval [CI], 0.004-0.47) and intraoperative prophylactic laser use (OR, 0.14; 95% CI, 0.02-0.81) were independently associated with a decreased risk of late RD. The factors independently associated with an increased risk of vision loss were worse initial visual acuity (OR, 3.28; 95% CI, 1.50-7.21), zone 1 involvement of necrotic retinitis (OR, 10.84; 95% CI, 1.62-72.41), and late-onset RD (OR, 5.38; 95% CI, 1.92-31.54). CONCLUSION: Vitrectomy and/or prophylactic intraoperative laser treatment may be effective treatment options in preventing delayed RD associated with an increased risk of vision loss in eyes with ARN.

Outcomes of 25-gauge pars plana vitrectomy with encircling scleral band for acute retinal necrosis-related rhegmatogenous retinal detachment.

Purpose: The aim of this study was to evaluate the anatomic and functional outcomes of 25-gauge pars plana vitrectomy (25G PPV) with encircling scleral band (ESB) in patients with acute retinal necrosis (ARN)-related rhegmatogenous retinal detachment (RRD). Methods: Single-center retrospective interventional case series of patients who underwent 25G PPV with ESB for ARN-related RRD. Complete anatomic success was defined as the complete attachment of retina after primary PPV. Functional success was measured by the final best-corrected visual acuity (BCVA) ≥20/400. Intraoperative and postoperative complications were also noted. Results: 14 eyes of 13 patients were included in the study. Six patients (46.1%) were immunocompromised. The mean follow-up was 23.64 ± 9.95 (range 6-42) months. Silicone oil was used as tamponade in 13 eyes and C3F8gas in one eye. After the primary PPV, complete anatomical success was seen in all eyes (100%), however, one eye developed phthisis bulbi after silicone oil removal (SOR). Statistically significant improvement of BCVA was seen, from LogMAR 2.03 ± 0.29 preoperatively to LogMAR 1.57 ± 0.63 postoperatively (p-value 0.014). Six eyes (42.9%) had functional success. Nine eyes (64.3%) had improvement in vision while 4 eyes (28.6%) maintained preoperative vision. 10 eyes (71.4%) underwent cataract surgery, nine eyes (64.3%) underwent SOR while 2 eyes (14.3%) had epiretinal membrane (ERM) under oil during follow-up. Conclusion: 25G PPV combines the advantages of minimally invasive vitrectomy surgery while offering improved anatomic outcomes in patients with ARN-related RRD. The functional outcome varies depending on the status of the optic disc and macula.

RETINAL DETACHMENT AFTER ACUTE RETINAL NECROSIS AND THE EFFICACIES OF DIFFERENT INTERVENTIONS: A Systematic Review and Metaanalysis.

PURPOSE: To estimate the rate of retinal detachment (RD) after acute retinal necrosis (ARN) and evaluate the efficacies of different interventions. METHODS: The databases Medline and EMBASE from inception to March 2020 were searched to identify the relevant studies. R software version 3.6.3 was used to perform the statistical analyses. Results in proportion with 95% confidence interval were calculated using generalized linear mixed models. RESULTS: Sixty-seven studies involving 1,811 patients were finally included. The pooling results suggested the general RD rate of ARN was 47%. The RD rate increased with the extent of retinitis and was slightly lower when involved Zone III. The RD rate was 37% for herpes simplex virus ARN and 46% for varicella-zoster virus ARN; 52% for immunocompetent patients and 39% for immunocompromised patients. Retinal detachment presented in 2% of eyes at the first visit. Systemic antiviral therapy could lower the RD rate significantly from 67% to 43%, and prophylactic vitrectomy could lower the RD rate significantly from 45% to 22%. Systemic antiviral therapy plus vitrectomy achieved the lowest RD rate to 18%. Although the efficacy of prophylactic laser or intravitreal antiviral therapy was still limited. Prophylactic vitrectomy might significantly increase the incidence of proliferative vitreoretinopathy from 7% to 32%. CONCLUSION: About half of the eyes might develop RD during the entire course of ARN. Systemic antiviral therapy and prophylactic vitrectomy are effective interventions to prevent RD, whereas the roles of prophylactic laser or adjunctive intravitreal antiviral therapy are still unclear. Varicella-zoster virus ARN and cases with extensive retinitis might need intensified interventions.

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 by herpes simplex virus type 1: an unusual presentation of a primary infection.

Herpes simplex virus (HSV) can affect the central nervous system causing meningitis, encephalitis and, rarely, acute retinal necrosis. We present a case of a 46-year-old man, previously healthy complaining of a 5-day persistent headache and sudden loss of vision of his left eye that progressed to the right. We started ceftriaxone, methylprednisolone and acyclovir for suspected encephalitis with vasculitis. HSV-1 was identified in vitreous and aqueous humour. Therapy with acyclovir was maintained and two intravitreous boluses of foscarnet were administered, without improvement. Usually being a benign infection, HSV can, in rare cases like this, have catastrophic effects in the optic tract.

Complications of herpes zoster in children.

BACKGROUND: Herpes zoster (HZ) may cause complications; however, information regarding complications of HZ in children is relatively sparse. We reviewed cases of HZ in children retrospectively and investigated the risk factors contributing to the development of complications. METHODS: A retrospective observational study was conducted at a tertiary care children's hospital in Japan. Children receiving a diagnosis of HZ between January 2010 and October 2016 were identified from electronic medical records. In this study, the following diseases were recognized as complications of HZ: bacterial skin infection, facial paralysis, meningitis, uveitis and keratitis, postherpetic neuralgia, acute retinal necrosis, pneumonia, and otitis interna. Details regarding clinical information of HZ patients with complications were described. RESULTS: We found 138 cases with HZ. Among these, 58 (42%) occurred in immunocompetent children and 80 cases (58%) occurred in immunocompromised children. Complications were observed in 10 cases of immunocompromised children and in eight cases of immunocompetent children. Although secondary bacterial skin infection was the most common complication (n = 6, 33.3%), severe complications such as facial paralysis (n = 3, 16.7%), meningitis (n = 2, 11.1%), uveitis and keratitis (n= 2, 11.1%), acute retinal necrosis (n = 1, 5.6%), pneumonia (n = 1, 5.6%), and otitis interna (n = 1, 5.6%) were observed. Patients with complications tended to have a rash on the head or neck, compared with those without complications (n = 9, 50% vs n = 18, 15%; P = 0.001). CONCLUSIONS: Severe HZ complications may occur in immunocompetent children. Development of a rash on the head or neck might be a risk factor for complications.

Neonatal bilateral acute retinal necrosis in a neonate with a history of severe intrauterine growth restriction.

We present the case of a baby girl born at term with severe intrauterine growth restriction (IUGR) to a gravida 1 mother who was previously healthy and HIV negative. The newborn was evaluated by an ophthalmologist because of her history of IUGR and was diagnosed with intraretinal hemorrhages associated with areas of peripheral retinal necrosis at the posterior pole of both eyes. A diagnosis of acute retinal necrosis of presumed viral origin due to cytomegalovirus virus was considered, and the infant was started on and responded well to valganciclovir.

Human encephalitis complicated with bilateral acute retinal necrosis associated with pseudorabies virus infection: A case report.

We report the case of a patient who presented with viral encephalitis and a pulmonary infection complicated with bilateral acute retinal necrosis after direct contact with diseased swine. Next-generation sequencing of the cerebrospinal fluid and vitreous humor detected pseudorabies virus (PRV) simultaneously. Intravenous acyclovir and dexamethasone treatment improved the symptoms of encephalitis, and vitrectomy surgery with silicone oil tamponade was used to treat the retinal detachment. This case implies that PRV can infect humans; thus, self-protection is imperative when there is contact with animals.