Multitask Deep Learning for Joint Detection of Necrotizing Viral and Noninfectious Retinitis From Common Blood and Serology Test Data.

Purpose: Necrotizing viral retinitis is a serious eye infection that requires immediate treatment to prevent permanent vision loss. Uncertain clinical suspicion can result in delayed diagnosis, inappropriate administration of corticosteroids, or repeated intraocular sampling. To quickly and accurately distinguish between viral and noninfectious retinitis, we aimed to develop deep learning (DL) models solely using noninvasive blood test data. Methods: This cross-sectional study trained DL models using common blood and serology test data from 3080 patients (noninfectious uveitis of the posterior segment [NIU-PS] = 2858, acute retinal necrosis [ARN] = 66, cytomegalovirus [CMV], retinitis = 156). Following the development of separate base DL models for ARN and CMV retinitis, multitask learning (MTL) was employed to enable simultaneous discrimination. Advanced MTL models incorporating adversarial training were used to enhance DL feature extraction from the small, imbalanced data. We evaluated model performance, disease-specific important features, and the causal relationship between DL features and detection results. Results: The presented models all achieved excellent detection performances, with the adversarial MTL model achieving the highest receiver operating characteristic curves (0.932 for ARN and 0.982 for CMV retinitis). Significant features for ARN detection included varicella-zoster virus (VZV) immunoglobulin M (IgM), herpes simplex virus immunoglobulin G, and neutrophil count, while for CMV retinitis, they encompassed VZV IgM, CMV IgM, and lymphocyte count. The adversarial MTL model exhibited substantial changes in detection outcomes when the key features were contaminated, indicating stronger causality between DL features and detection results. Conclusions: The adversarial MTL model, using blood test data, may serve as a reliable adjunct for the expedited diagnosis of ARN, CMV retinitis, and NIU-PS simultaneously in real clinical settings.

Acute retinal necrosis in a patient with cervical malignant tumor treated with sintilimab: a case report and literature review.

Acute retinal necrosis (ARN) is an inflammatory disease that is primarily caused by herpesvirus infection, most commonly varicella-zoster virus (VZV), followed by herpes simplex virus (HSV) and occasionally cytomegalovirus (CMV). Sintilimab is an immune checkpoint inhibitor (ICI) that can enhance the body's anti-tumor immune response. However, treatment with ICIs may lead to reactivation of the VZV. Here, we present a case of ARN caused by VZV infection in a patient receiving sintilimab for cervical cancer. A 64-year-old female patient developed vision loss and floaters with left eye redness for one week after 22 cycles of sintilimab for cervical cancer. Based on clinical manifestations, ophthalmological examination, and vitreous humor biopsy, the patient was diagnosed with acute retinal necrosis syndrome secondary to VZV. After receiving systemic antiviral and anti-inflammatory therapy, retinal necrosis lesions and visual function improved. In conclusion, clinicians should be aware of the risk of ARN when using sintilimab and should actively monitor patients for prompt diagnosis and optimal management of this rare adverse drug reaction.

Unilateral Acute Retinal Necrosis with Contralateral Non-necrotizing Herpetic Uveitis.

PURPOSE: The objective of this study is to report a case of unilateral acute retinal necrosis (ARN) with contralateral eye presenting as non-necrotizing herpetic uveitis. CASE REPORTS: Case 1: A 48-year-old female presented at our clinic with blurred vision in the right eye for 7 days. She was diagnosed with ARN in the left eye 2 weeks ago. Ophthalmic examination revealed reduced visual acuity in the right eye (20/33) with the presence of optic disc swelling and macular exudation without peripheral necrotic lesions. With systemic antiviral therapy, optic disc swelling of the right eye vanished gradually, and the visual acuity improved to 20/20. Loss of retinal nerve fiber layer (RNFL) and decreased retinal thickness in the corresponding area occurred during follow-up. CONCLUSION: Non-necrotizing herpetic uveitis may occur in the contralateral eye of unilateral ARN under rare conditions. Structure abnormities, including loss of RNFL and focal decreased retinal thickness, are irretrievable.

Treatment outcomes of PCR-positive acute retinal necrosis.

BACKGROUND: Acute retinal necrosis (ARN) is a progressive necrotizing retinitis caused by viral infection. Optimal management strategies have not been established for this detrimental disease. Previous literature published suggests that Varicella-zoster virus (VZV) and Herpes simplex virus-1 (HSV1) are the most common promoters of acute retinal necrosis (ARN). AIMS: The purpose of our study was to investigate the viral distribution, demographic, and treatment outcomes of ARN. METHODS: A retrospective chart review evaluated data from PCR-positive ARN patients diagnosed between 2009 and 2018. RESULTS: Analysis of fourteen eyes from 12 patients found CMV and VZV as the commonest causes of ARN. Patients on 1 g of valacyclovir three times a day (V1T) had worse vision between first and final visits (mean difference of 1.25 ± 0.65, n = 2) compared with patients treated with 2 g of valacyclovir three times a day (V2T), or 900 mg twice a day of valganciclovir (V9B) (mean difference of - 0.067 ± 0.13, n = 6, and 0.067 ± 0.067, n = 6, respectively). Both V1T patients developed retinal detachments (RD). Both CMV patients treated with intravitreal triamcinolone developed ARN, elevated IOP, and one developed multiple RD. CONCLUSIONS: Our review found increased incidence of CMV-positive ARN. Patients with zone 1 disease had worse initial visual acuity. Moreover, patients had more favorable outcomes with V2T and V9B compared to V1T. CMV-positive patients clinically worsened after intravitreal steroid injections, further underscoring the value of a PCR diagnosis to tailor the patients' treatment plan accordingly.

Clinical characteristics and management outcomes of acute retinal necrosis.

This study investigates patient's clinical characteristics and management outcomes of PCR-positive Acute Retinal Necrosis (ARN). The patient's clinical characteristics of the disease, and therapeutic approaches were assessed. Data from the medical records of 40 eyes of 40 patients were analyzed. The mean ± standard deviation (SD) of the age of the patients was 47.8 ± 14.1 years (16-84 years old). The median follow-up time was 160 days, with a range of 120-370 days. The mean ± SD of patients' primary and final BCVA was 1.24 ± 0.78 and 1.08 ± 0.86 LogMAR, respectively. The final BCVA increased significantly after the treatment in the last follow-up period in patients who did not undergo PPV (p = 0.029). Although, vision changes were not statistically significant in patients who underwent PPV (p = 0.549). 75% of our patients had a positive aqueous PCR for VZV, and the second most common causative agents were CMV and HSV (10% for each). Besides, rhegmatogenous retinal detachment (RRD) occurred in 25% of our patients. Our analysis showed that the presenting visual acuity and RRD occurrence are the significant prognostic factors for final blindness in ARN.

Pigmentary retinopathy and nodular granuloma associated with acute retinal necrosis from varicella zoster virus and human herpes virus type 6: Case report.

RATIONALE: Acute retinal necrosis (ARN) caused by human herpes virus type 6 (HHV-6) is uncommon. We described a case of consecutive bilateral ARN, which was found to be a coinfection of varicella zoster virus (VZV) and HHV-6 in a 50-year-old woman, not well responded with systemic acyclovir. We showed the atypical findings with corresponding fundus and optical coherence tomography imaging. PATIENT CONCERNS: She presented with anterior segment inflammation with peripheral retinitis and vasculitis in the left eye with disease progression despite of initial antiviral treatment, end up with retinal detachment. The right eye, subsequently, developed focal retinitis. DIAGNOSIS: ARN was diagnosed by clinical fundus picture, confirmed by polymerase chain reaction (PCR). INTERVENTIONS: Initially, she was treated with intravenous acyclovir and intravitreal ganciclovir for left eye. Retinal necrosis progressed, followed by retinal detachment. Pars plana vitrectomy with silicone oil was performed. The right eye, subsequently, developed focal retinitis. Medication was switched to intravenous ganciclovir and then oral valganciclovir. OUTCOMES: Retinitis was resolved, generalized hyperpigmentation appeared as a salt-and-pepper appearance in the right eye. The left eye presented preretinal deposits on silicone-retina interphase along retinal vessels. Spectral-domain optical coherence tomography (SD-OCT) showed multiple hyperreflective nodules on retinal surface. LESSONS: ARN from coinfection of VZV and HHV-6 is rare. Preretinal granulomas and generalized hyperpigmentation could be one of the HHV-6 features. HHV-6 should be in the differential diagnosis for ARN. It responds well to systemic ganciclovir.

Posterior Herpetic Uveitis: A Comprehensive Review.

PURPOSE: To report and illustrate the main clinical presentations of posterior herpetic uveitis. METHODS: Narrative review. RESULTS: The ocular manifestations of posterior herpetic uveitis include different clinical presentations. Herpes simplex and varicella zoster can cause acute retinal necrosis, progressive outer retinal necrosis, and non-necrotizing herpetic retinopathies. Cytomegalovirus has been associated with fulminant retinitis with confluent areas of retinal necrosis and retinal hemorrhages, indolent/granular retinitis, and frosted branch angiitis. These diverse clinical presentations are often associated with specific risk factors and different immunological profiles of the host. CONCLUSIONS: Herpetic viruses can cause posterior uveitis, presenting various clinical findings. Specific ocular manifestations and the immunological status of the host can help to differentiate the various herpetic entities before laboratory tests confirm the diagnosis.

First-line management of necrotizing herpetic retinitis by prioritizing the investigation of immune status and prognostic factors for poor visual outcomes.

PURPOSE: To review management, treatment, and outcomes of patients with necrotizing herpetic retinitis (NHR) to propose an algorithm for first-line management of NHR. METHODS: Retrospective evaluation of a series of patients with NHR at our tertiary center between 2012 and 2021 using demographic, clinical, ophthalmologic, virological, therapeutic, and prognostic characteristics was performed. Patients were classified by NHR type: acute retinal necrosis (ARN), progressive outer retinal necrosis (PORN), cytomegalovirus (CMV) retinitis. RESULTS: Forty-one patients with NHR were included: 59% with ARN, 7% with PORN, and 34% with CMV retinitis. All patients with CMV retinitis and PORN were immunocompromised versus 21% of patients with ARN. CMV infection was found in 14 (34%) patients, varicella zoster virus infection in 14 (34%) patients, herpes simplex virus type 2 infection in 8 (20%) and type 1 infection in 5 (12%) patients. Intravenous antiviral therapy was received by 98% of patients and intravitreal antiviral injections by 90% of patients. The overall complication rate during follow-up was 83% of eyes. Most frequent complications were retinal detachment (33% eyes) and retinal break (29% eyes). Prognostic factors for poor visual outcomes were pre-existing monocular vision loss in contralateral eye among 17% of patients, bilateral NHR in 17% of patients, posterior pole involvement in 46% of eyes, and involvement > 2 retinal quadrants in 46% of eyes. CONCLUSIONS: The visual prognosis of patients with NHR remains poor. Prompt investigation of immune status and presence of factors justifying intravitreal antiviral injections must be prioritized to initiate and adapt management while awaiting causative virus confirmation.

Acute Retinal Necrosis: A Covid-19 Perspective.

Acute retinal necrosis (ARN) is a relatively uncommon yet devastating cause of vision-threatening uveitis. This manuscript analyzed the cases of ARN that have been reported following SARS-CoV-2 infections and anti- SARS-CoV-2 vaccinations. A total of nine cases of ARN were reported in the literature. Among them, four patients with ARN were attributed to SARS-CoV-2 infections, and a history of recent Covid vaccination was present in five patients when a diagnosis of ARN was made. ARN has been described following SARS-CoV-2 infections or vaccinations against the virus, and many of these cases may be based on a cause-to-effect hypothesis.

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.

A Case of Acute Retinal Necrosis Associated with Reactivation of Varicella Zoster Virus after COVID-19 Vaccination.

PURPOSE: To report a case of acute retinal necrosis (ARN) after receiving COVID-19 vaccination. METHODS: A case report. RESULTS: A 78-year-old man complained of blurred vision and floaters in the right eye 2 days after receiving BNT162b2 mRNA-based COVID-19 vaccine and was referred to our hospital with worsening visual acuity after 7 days. He had no systemic symptoms and no history of systemic diseases. Ophthalmic examination revealed white-yellowish placoid lesions spreading to the entire circumference of the retina, and temporal and upper lesions extending to the posterior pole, although anterior inflammation and vitreous opacity were mild. Diagnostic and therapeutic vitrectomy was performed, and VZV-DNA was detected by comprehensive PCR using a vitreous fluid sample. The ocular inflammation subsided by systemic administration of antivirals and corticosteroids. However, total retinal detachment requiring repeat vitrectomy using silicone oil occurred after the second vaccination. CONCLUSION: ARN associated with VZV reactivation may develop after SARS-CoV-2 mRNA vaccination.

Choroidal Involvement in a Case of Acute Retinal Necrosis.

PURPOSE: To report choroidal involvement in a case of ARN. CASE REPORT: A 26-year-old immunocompetent female presented with a history of decreased vision in the right eye for 4 days. The best corrected visual acuity in the right eye was 3/60. Anterior segment examination showed circumciliary congestion, endothelial pigments, and 1+ cells in the anterior chamber. Fundus examination revealed mild vitritis, disc edema, multifocal patchy retinitis lesions involving the fovea and mid periphery, and arteriolitis. OCT revealed an RPE bump at the macula corroborating with hypocyanacent lesions on indocyanine angiography, which persisted till the late phase, indicating choroidal involvement. The patient was started on oral valacyclovir and oral steroids. Additionally, intravitreal ganciclovir injection was added, leading to a favorable outcome. The final visual acuity post silicone oil removal was 6/60. CONCLUSION: This is a unique case of ARN having choroidal involvement along with the previously described classical features.

Tocilizumab and Aflibercept as a Treatment Option for Refractory Macular Edema after Acute Retinal Necrosis.

Introduction: The inflammatory milieu after acute retinal necrosis (ARN) may lead to a breakdown of the inner and outer blood-retinal barrier and consequently to a cystoid macular edema (CME) with accumulation of intra- and subretinal fluid. Up to now, there is no established therapeutic approach for CME in ARN patients.Case report: We report a case of an immunocompetent 14-year-old female with chronic ARN-related CME, which was unresponsive to valacyclovir, prednisone and intravitreal ranibizumab injections. A combination treatment of tocilizumab, an interleukin-6 receptor inhibitor, and intravitreal aflibercept was successful to control the CME.Conclusion: In selected patients with treatment-refractory CME following ARN a therapy with tocilizumab and intravitreal aflibercept might be considered.

Varicella Zoster Reactivation Causing Acute Retinal Necrosis following mRNA COVID-19 Vaccination in a Young Immunocompetent Man.

BACKGROUND: Varicella zoster reactivation is an increasingly recognised event following mRNA COVID-19 vaccination. In addition, various ocular inflammatory and infectious adverse events following COVID-19 vaccination have been described in the literature. This case report describes acute retinal necrosis (ARN) secondary to varicella zoster virus (VZV) reactivation following COVID-19 mRNA vaccination. CASE DESCRIPTION: A 42-year-old immunocompetent man developed left ARN 12 days following first dose of Pfizer BioNTech mRNA COVID-19 vaccination. Aqueous and vitreous tap polymerase chain reaction testing was positive for VZV. Good visual outcome was achieved with combination therapy, including intravitreal foscarnet, oral valaciclovir and prednisolone, topical dexamethasone and atropine, and barrier retinal laser. Second dose of the vaccine is planned under cover of high-dose oral valaciclovir therapy. CONCLUSION: This case illustrates the possible association between COVID-19 vaccination and potentially blinding VZV reactivation. Therefore, prompt ophthalmic assessment is recommended in patients with visual disturbance following COVID-19 vaccination.

Reactivation of varicella zoster infection presenting as acute retinal necrosis post COVID 19 vaccination in an Asian Indian male.

PURPOSE: To present the clinical features of a rare case of varicella zoster infection following one dose of Coronavirus Disease 2019 (COVID-19) vaccination in an elderly Asian Indian male. METHODS: Retrospective observational case report. RESULTS: A 71-year-old gentleman presented to us with complaints of reduced vision associated with redness and pain in his right eye for 1 week. On examination he revealed a right eye pan uveitis picture with circumcorneal congestion, multiple fine keratic precipitates, anterior chamber cells and flare, vitritis and widespread areas of acute retinal necrosis. His left eye was within normal limits. Ten days prior to the presentation he had received the first dose of COVID-19 vaccine following which he had developed fever for 2 days that preceded the red eye. The patient's aqueous sample tested positive for varicella zoster virus (VZV) by nested polymerase chain reaction (PCR) method. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in reverse transcriptase polymerase chain reaction (RT-PCR) assay from the aqueous and also from the nasopharyngeal swab was negative. CONCLUSION AND SIGNIFICANCE: To the best of our knowledge this is the earliest description of a case that has a viral reactivation following COVID-19 vaccination. Elderly people with pre-existing comorbidities, may be at a risk of both primary coronavirus infection and unconceivable risk of aberrant immune reactions leading to a different virus infection or reactivation need to be kept in mind. We present a possible link between SARS-CoV-2 virus vaccination and varicella zoster reactivation in this patient.