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

OBJECTIVE: To investigate the risk factors and prognostic factors that affect the long-term clinical outcomes of acute retinal necrosis (ARN). METHODS: A retrospective study of patients with ARN who underwent treatment and completed follow-up in our ophthalmology department from 2011 to 2021 was conducted. The incidence and risk factors of retinal detachment (RD) and prognostic factors affecting long-term clinical outcomes, such as late-onset RD and final vision loss (< 20/200), were analyzed. RESULTS: Totally 59 ARN patients (65 eyes) with an average follow-up of 48.9 months were enrolled. During the follow-up period, RD occurred in 34 eyes (52.3%). The risk factors for RD included quadrants of involved retinal necrosis (odds ratio [OR], 4.181; 95% confidence interval [CI], 1.950-10.834) and initial intraocular viral load (OR, 1.721; 95% CI, 1.071-3.083). Early intravitreal antiviral treatment (OR, 1.204; 95% CI, 1.040-1.480) was independently associated with a decreased risk of late-onset RD. The factors independently associated with an increased risk of final vision loss were worse initial visual acuity (OR, 3.895; 95% CI, 1.551-13.662) and late-onset RD (OR, 8.043; 95% CI, 1.380-67.216). In addition, we utilized the fluctuating magnitude of viral load to quantify the extent of its reduction in comparison to its original value following the initial intravitreal antiviral injection (IAI). This ratio was strongly related to initial intraocular IL-8 concentration (Spearman correlation coefficient=-0.741, P = 0.000) and moderately related to the initial degree of aqueous flare (Spearman correlation coefficient=-0.508, P = 0.010). CONCLUSION: RD is a common and severe complication of ARN with multiple risk factors, such as initial retinitis involvement area and initial intraocular viral load. Active local antiviral therapy may reduce the risk of late-onset RD. The antiviral medication should be adjusted according to the inflammatory state. Therefore, timely detection of causative viruses and intensive systemic and local antiviral therapy is crucial for preserving visual function in ARN patients.

Ultrawidefield imaging aids in the early detection and management of acute retinal necrosis.

Acute retinal necrosis (ARN) is a rare and rapidly progressive disease characterised by the development of panuveitis and peripheral retinal lesions. These lesions can often be missed during a routine fundoscopic examination, making the early diagnosis of ARN a considerable challenge. This case report describes the utilisation of ultrawidefield (UWF) imaging in the early detection of peripheral lesions associated with ARN in a male patient in his late 60s, who presented with acute blurred vision and a documented history of herpes zoster ophthalmicus. During a comprehensive eye examination and UWF imaging, panuveitis and peripheral lesions were identified, eventually leading to a diagnosis of ARN. The early initiation of antiviral therapy led to a gradual clinical improvement over 3-4 months. The utilisation of serial UWF imaging played a critical role in the prompt diagnosis and effective monitoring of disease progression, thereby potentially improving the patient's outcome.

DYNAMIC VIRAL LOAD MONITORING AND METAGENOMIC SEQUENCING IN ACUTE RETINAL NECROSIS CAUSED BY VARICELLA-ZOSTER VIRUS.

PURPOSE: To analyze the trend of intraocular viral load after antiviral treatment in patients with varicella-zoster virus-induced acute retinal necrosis and to explore the effect of viral genotypes on clinical manifestations. METHODS: In this case series, viral load was detected using polymerase chain reaction from aqueous humor during treatment; viral load curves were fitted, and the time required to reach the inflection point between plateau phase and logarithmic reduction phase was estimated. Variations in viral genomes were detected by metagenomic sequencing. RESULTS: Twenty eyes of 20 patients were included. The median (interquartile range) initial viral load was 5.9 × 10 7 (1.1 × 10 7 -1.1 × 10 8 ) copies/mL. The average duration of retinitis was 5 ± 3 weeks. The average time required to reach the inflection point was 4.2 ± 1.6 days. Time required to reach the inflection point was correlated with the duration of retinitis ( P = 0.025). Patients with varicella-zoster virus carrying the p.S715* variation in ribonucleotide reductase ( RNR ) subunit 1 gene had lower initial viral loads (median 1.3 × 10 7 copies/mL) than those without (median 1.1 × 10 8 copies/mL; adjusted P = 0.030). CONCLUSIONS: The inflection of viral load curve is helpful to estimate the length of plateau phase and the duration of retinitis during antiviral treatment in patients with acute retinal necrosis. Loss-of-function variation in RNR gene might be correlated with lower virulence of varicella-zoster virus.

Factors at the initial visit associated with poor visual outcomes in patients with acute retinal necrosis.

BACKGROUND/OBJECTIVE: Acute retinal necrosis (ARN) is a vision-threatening disease caused by herpesvirus infection. This study aimed to investigate the visual prognostic factors that could be determined at the initial visit. SUBJECTS AND METHODS: This retrospective study included 34 patients with ARN. Logistic regression analysis was employed to evaluate the associations between poor final visual outcomes and various factors, including poor initial visual acuity, presence of retinal detachment at the initial visit, posterior extension of necrotizing retinitis, and circumferential extension of necrotizing retinitis. Posterior extension was evaluated with three zonings, from the periphery (zone 3), mid-periphery (zone 2), and macula (zone 1). Circumferential extension was evaluated according to the degree of necrotizing retinitis lesions using ultra-wide fundus imaging. RESULTS: The mean logarithm of the minimum angle of resolution was 0.63 ± 0.68 at the initial visit and 0.83 ± 0.65 at 12 months after the initial visit. Seven patients had a retinal detachment. The distribution of posterior extension at the initial visit was 5 in zone 1, 20 in zone 2, and 9 in zone 3. The average of necrotizing retinitis lesion angle was 249 ± 115°. The logistic regression analysis revealed that participants with wide angles of necrotizing retinitis were associated with final poor vision, with an odds ratio of 1.28 per 30° increase (95%CI: 1.00-1.65, p = 0.03). CONCLUSIONS: Assessment of the widespread circumferential extension of white necrotizing retinal lesions at the initial visit is a crucial risk factor for the visual prognosis in ARN.

Examining the etiological factors resulting in retinal detachment following prophylactic vitrectomy in the context of acute retinal necrosis syndrome.

OBJECTIVE: The aim of this study is to elucidate the factors contributing to the occurrence of retinal detachment (RD) following prophylactic vitrectomy in cases of acute retinal necrosis (ARN) syndrome. METHODS: A retrospective examination was undertaken, encompassing the medical records of patients diagnosed with ARN who underwent prophylactic vitreous intervention at the Ophthalmology Department of Wuhan University Renmin Hospital East Campus between October 2019 and September 2023. Subsequently, patients who manifested RD in the postoperative period were identified, and a comprehensive analysis was conducted to ascertain the factors underlying the occurrence of RD post-surgery. RESULTS: This study comprised 14 cases (involving 14 eyes) of patients diagnosed with ARN who underwent prophylactic vitreous intervention. The findings revealed that 4 patients experienced postoperative RD, resulting in an incidence rate of 28.57%. Notably, among these cases, 3 cases of RD manifested in the presence of silicone oil, while 1 case occurred subsequent to the removal of silicone oil. All 4 cases of RD exhibited varied degrees of proliferative vitreoretinopathy. Following the occurrence of RD, all patients underwent a secondary vitreous intervention coupled with silicone oil tamponade, leading to successful reattachment of the retina. However, despite these interventions, there was no significant enhancement observed in postoperative visual outcomes when compared to preoperative levels. CONCLUSION: RD following prophylactic vitrectomy in cases of ARN is not an infrequent occurrence and is primarily linked to the postoperative onset of proliferative vitreoretinopathy.

Case of acute retinal necrosis with rapid progression to proliferative vitreoretinopathy: A case report.

RATIONALE: Acute retinal necrosis (ARN) was first reported in 1971 by Urayama et al as an acute uveitis accompanied by retinal arteritis and white retinal lesions in the peripheral retina that can progress to a rhegmatogenous retinal detachment (RRD). We have experienced a case of ARN that, unlike the common developmental course to an RRD associated with ARN, progressed to proliferative vitreoretinopathy (PVR) involving the entire retina in 2 days. The purpose of this report is to present our findings in the case of ARN with an atypical rapid time course. PATIENT CONCERNS: The patient was a 56-year-old woman who was treated for uveitis of unknown origin by her primary care physician. She was referred to our hospital because of a worsening of the fundus findings. DIAGNOSIS: Fundus examination in our hospital revealed vitreous opacities in the right eye, yellowish-white lesions extending around the retina, and some retinal hemorrhages. Because the retinal changes suggested ARN, we performed a polymerase chain reaction of the anterior atrial fluid and detected varicella-zoster virus. Then, the diagnosis of ARN was confirmed, and treatment was begun. At 1 month and a half after beginning the treatment, focal retinal traction was observed in the right fundus. Two days later, a circumferential PVR and a total retinal detachment were detected. INTERVENTIONS: We then performed vitrectomy with an encircling buckle and a silicone oil tamponade. OUTCOMES: Our examination 6 months postoperatively showed that the retina was attached and the BCVA was 20/200. LESSONS: Our findings of a case of ARN showed that the progression from a local vitreous traction to a full circumferential PVR can develop in 2 days.

Acute retinal necrosis.

Acute retinal necrosis (ARN) is a rare, progressive viral uveitis, with the majority of cases caused by herpesviruses. The diagnosis of ARN is often delayed, and most patients will have some degree of permanent visual loss. We report a case of ARN in a previously healthy 32-year-old patient.

Diagnostic and therapeutic challenges in acute retinal necrosis; an update.

Acute retinal necrosis (ARN) is a rare but severe ophthalmic pathology defined by panuveitis, retinal necrosis, and high rates of retinal detachment. ARN may lead to poor visual outcomes even if promptly diagnosed and treated. ARN may present with a wide spectrum of clinical findings compatible with panuveitis including anterior uveitis, scleritis, vitritis, necrotizing retinitis, occlusive vasculitis, and optic disc edema. The American Uveitis Society introduced clinical criteria in 1994 for the diagnosis of ARN, while more recent criteria have been proposed by the Standardization of Uveitis Nomenclature (SUN) Working Group and the Japanese ARN Study Group. Multimodal imaging is a valuable tool in evaluating patients with ARN, particularly in unusual cases, while utilizing retinal imaging and applying AI algorithms in these areas of clinical research could be highly beneficial. Over the last few years, significant progress has been made in achieving timely diagnosis and treatment. The precise identification of the viral cause in suspected ARN cases has been greatly enhanced by the advancements in PCR techniques and flow cytometry used for intraocular fluids. systemic (intravenous or oral) antivirals with adjunctive intravitreal antiviral therapy are recommended as first-line therapy to reduce disease severity, the risk of vision loss, and retinal detachment incidence. Although aciclovir was the first existing antiviral agent, at present many clinicians prefer high-dose valaciclovir orally or intravenous aciclovir combined with intravitreal foscarnet. Despite significant progress in diagnosing and treating ARN, further research is needed to improve visual outcomes in this challenging clinical condition.

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.

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.

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.

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.