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.

Ocular syphilis masquerading as CMV retinitis in a transplanted patient.

BACKGROUND: Syphilis has historically been referred to as "the great imitator", for the extent of disease manifestations secondary to infection. Ocular manifestations include a wide range of intra-ocular inflammation. METHODS: In this study, we report the case of a 52 years-old male patient with syphilitic hemorrhagic necrotizing retinitis. RESULTS: The patient presented to the emergency room for rapid and progressive vision loss and ocular redness lasting three weeks and was under immunosuppressive treatment. The diagnosis was syphilitic hemorrhagic necrotizing retinitis mimicking the typical clinical picture of retinitis caused by Cytomegalovirus infection in immunocompromised patients. CONCLUSIONS: The presented case highlights the need to consider ocular syphilis as a great masquerader even in the presence of atypical presentations such as hemorrhagic retinitis. Syphilis should be tested for treponemal and non-treponemal tests, and it should be ruled out as an etiological agent in every case of new-onset intra-ocular inflammation.

GOOD SYNDROME: CYTOMEGALOVIRUS RETINITIS CASE CHALLENGE.

PURPOSE: To describe cytomegalovirus retinitis in a patient with Good syndrome (hypogammaglobulinemia and thymoma), ocular progression despite treatment and fatal outcome. METHODS: A 71-year-old woman with unilateral panuveitis of unknown cause and a history of thymoma resection was referred to the clinic. Visual acuity was 20/100 in her right eye and light perception in her left eye. In slit-lamp examination, the right eye had inferior, fine, pigmented keratic precipitates, 2+ anterior chamber cells, cataract, and 2+ vitreous cells, with no fundus detail and normal ocular ultrasound results. Left eye presented a white cataract, chronic hypotony, and increased choroidal thickness with calcifications. Laboratory evaluations showed normal or negative results for common causes of infection and inflammation. Prednisolone acetate eye drops were started, with improvement of AC inflammation. Cataract surgery was performed, reaching visual acuity of 20/30. Two years later, visual acuity had decreased and 2+ vitritis and retinitis were found. On clinical suspicion of masquerade syndrome, a vitrectomy biopsy was performed; pathologic assessments reported no data on ocular lymphoma. Leukopenia and lymphopenia were found: immunoglobulin levels, CD4 count, and viral load revealed systemic immunosuppression. The aqueous tap was positive for cytomegalovirus. Oral valganciclovir and intravitreal ganciclovir were initiated. RESULTS: In a patient with previous resection of thymoma and hypogammaglobulinemia, final diagnosis was Good syndrome, with cytomegalovirus retinitis being secondary to immunosuppression. Despite treatment, cytomegalovirus retinitis progressed and systemic deterioration resulted in mortal outcome. CONCLUSION: Good syndrome is an extremely rare disease, and association with cytomegalovirus retinitis is uncommon. To the authors' knowledge, only 14 cases exist in the literature.

Diffuse retinal dysfunction following immune reconstitution uveitis in patients with prior cytomegalovirus retinitis: a novel observation.

PURPOSE: To report continuing diffuse retinal dysfunction following resolution of immune reconstitution uveitis (IRU) in patients with cytomegalovirus retinitis (CMVR). METHODS: Retrospective case series describing two patients with IRU following CMVR who underwent serial fundus photography and macular optical coherence tomography. One patient had serial electrophysiology. RESULTS: Both patients had CMVR successfully treated with antiviral medication. The affected eyes later developed IRU that resolved with steroids. However, following resolution, chronic retinal damage was evidenced by ellipsoid line loss in one case and gradual optic disc cupping in the other. Electrophysiology in both cases revealed generalized retinal dysfunction worse in the eye with more severe IRU and demonstrated objectively the efficacy of treatment intervention in the patient with serial recordings. CONCLUSIONS: Patients with IRU following CMV retinitis may have continuing diffuse retinal dysfunction despite apparent recovery and normal visual acuity. An aggressive approach to inflammation control may be warranted in such patients.

Clinical features of Cytomegalovirus retinitis in patients with acquired immunodeficiency syndrome and efficacy of the current therapy.

Background: Cytomegalovirus retinitis (CMVR) is the most common and sight-threatening opportunistic retinal infection in patients with acquired immunodeficiency syndrome (AIDS) and several controversies remain to be settled. We aimed to summarize the current evidence and clarify the clinical features and prognosis of CMVR in AIDS patients. Methods: The databases PubMed, EMBASE, and Ovid from inception to April 2022 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 (CI) were calculated using the Freeman-Tukey variant of arcsine square transformation. Results: We finally included 236 studies comprising 20,214 patients. CMVR in AIDS was male-dominated (88%, 95%CI 86%-89%), with 57% (95%CI 55%-60%) aged <41 years and 44% (95%CI 41%-47%) being bilaterally involved. CMVR was preponderant in AIDS patients with the following characteristics: white and non-Hispanic, homosexual, HIV RNA load ≥ 400 copies/mL, and CD4+ T-cells <50 cells/µL. The positivity of CMV-DNA in blood, aqueous humor, and vitreous humor was 66% (95%CI 52%-79%), 87% (95%CI 76%-96%), and 95% (95%CI 85%-100%), respectively. The most common symptoms were blurred vision (55%, 95%CI 46%-65%), followed by asymptomatic, visual field defect, and floaters. CMVR was first diagnosed and regarded as the clue to AIDS diagnosis in 9% (95%CI 6%-13%) of CMVR patients. Approximately 85% (95%CI 76%-93%) of the CMVR patients have received cART. CMVR remission was observed in 72%-92% of patients depending on the specific category of anti-CMV therapy. The general incidence of CMVR-related RD in the entire course was 24% (95%CI 18%-29%), of which most patients received PPV with SO or gas tamponade and the rate of anatomic success was 89% (95%CI 85%-93%). Conclusion: CMVR is a common opportunistic infection with diverse clinical features in AIDS patients, preponderant in those who are male, homosexual, or with CD4+ T-cells <50 cells/µL. Current therapies for CMVR and CMVR-related RD were shown to be effective. Early detection and routine ophthalmic screening should be promoted in AIDS patients. Systematic review registration: PROSPERO, identifier CRD42022363105.

Human immunodeficiency virus retinopathy with presumed cytomegalovirus retinitis with macular oedema in a diabetic.

A man in his early 50s on regular follow-up for a stable non-proliferative diabetic retinopathy (NPDR) presented with decreased vision, worsening of retinal pathology and macular oedema in both eyes. His corrected distance visual acuity (CDVA) was 6/9 in the right eye and 6/15 in the left eye and fundus examination showed multiple intraretinal haemorrhages in all quadrants. His systemic workup revealed a severe thrombocytopaenia, which prompted a further detailed systemic evaluation revealing him to be positive for HIV with retinopathy complicating the pre-existing NPDR. Given the significant inflammation and macular oedema, a cocktail of intravitreal bevacizumab, ganciclovir and dexamethasone was administered. The retinopathy and macular oedema resolved and the CDVA improved to 6/6 in both eyes over a 6-month follow-up period. Any sudden worsening of fundus findings in a patient with diabetes necessitates immediate and detailed ocular and systemic evaluation, especially when the immune status is unknown.

Cytomegalovirus immunoglobulin therapy for CMV retinitis post hematopoietic stem cell transplantation.

PURPOSE: To report a case of cytomegalovirus (CMV) retinitis complicated with ganciclovir-related myelosuppression, which was successfully managed with intravenous (IV) ganciclovir and CMV immunoglobulin (CMVIG) therapy. METHODS: Observational case report. RESULTS: A 51-year-old male with follicular type non-Hodgkin lymphoma post hematopoietic stem cell transplantation (HSCT) developed vision-threatening retinitis. polymerase chain reaction (PCR) of the aqueous humour showed positive for CMV. Despite myelosuppression occurred during IV ganciclovir therapy, the retinitis resolved and intraocular CMV viral load significantly improved after CMVIG therapy. CONCLUSION: Combined IV ganciclovir treatment and CMVIG therapy can significantly improve visual outcome and reduce intraocular CMV viral load in vision-threatening CMV retinitis.

A Case of Good Visual Outcome following Retinal Ganciclovir Toxicity.

We present a case of CMV retinitis with retinal toxicity secondary to inadvertent overdose of intravitreal ganciclovir. To our knowledge, this is the first case published with good visual outcome from timely intervention.

Bilateral cytomegalovirus retinitis as the presenting feature of Dyskeratosis Congenita.

PURPOSE: To describe a young male with bilateral sequential Cytomegalovirus retinitis (CMVR) as the presenting feature of Dyskeratosis Congenita. CASE REPORT: A 25-year-old human immunodeficiency virus (HIV) negative male developed CMVR in his left eye, while on a three week course of oral valganciclovir therapy for CMV retinitis in his right eye. Systemic examination revealed reticular hypopigmentation of the forearms, dystrophic nails, oral leukoplakia and complete blood counts showed pancytopenia. A diagnosis of Dyskeratosis Congenita was confirmed with genetic testing. CONCLUSION: CMVR in non-HIV individuals should be considered as a harbinger of systemic immunosuppressive conditions. Ophthalmologists may be the first ones to suspect and diagnose congenital immunosuppressive disorders like Dyskeratosis Congenita in these patients.

CMV Retinitis in Wiskott Aldrich Syndrome.

PURPOSE: Wiskott-Aldrich syndrome (WAS) is an X-linked recessive disease whose optimal curative treatment is hematopoietic stem cell transplantation (HSCT). Patients with WAS may suffer from cytomegalovirus retinitis (CMVR) which can cause vision loss. This study is to report the progression and prognosis of patients with WAS and CMVR. METHODS: A retrospective case series of ten patients with WAS and CMVR before and after HSCT who were referred to the Ophthalmology Department of Xinhua Hospital from June 2018 to February 2021. Progression and prognosis were recorded. RESULTS: Five patients were diagnosed with CMVR before receiving HSCT at a median age of 10.5 months (range: 4-23 months). Eight patients developed CMVR post-transplantation with a median interval from HSCT of 3.5 months (range: 1-9 months). CONCLUSION: Regular fundus examinations and prompt treatments in patients with WAS are therefore crucial before they receiving HSCT or approximately 3.5 months after HSCT until complete reconstitution of immune function.

Efficacy of ganciclovir versus foscarnet in ganciclovir-resistant cytomegalovirus retinitis: A case report.

PURPOSE: To report a case of cytomegalovirus (CMV) retinitis improved by treatment with ganciclovir in a patient with ganciclovir-resistant CMV infection associated with Good syndrome. STUDY DESIGN: Case report. RESULT: A 52-year-old gentleman with Good syndrome presented with visual disturbance in his right eye. He had a history of receiving intravitreal ganciclovir treatment with CMV retinitis a year ago. During treatment for CMV colitis three months ago, in systemic blood, UL97 mutation was identified and improved after changing treatment from ganciclovir to foscarnet. CMV retinitis recurred, and intravitreal ganciclovir injection was performed but there was no improvement. Therefore, the treatment was changed to foscarnet, but retinal infiltration progressed. Accordingly, it was changed to ganciclovir again and as a result, the progression of retinitis could be stopped. CONCLUSIONS: Even in the case of CMV retinitis, which has been genetically confirmed to be ganciclovir resistance in systemic blood, ganciclovir treatment can be considered if other anti-CMV agents are not effective.

CLINICAL CHARACTERISTICS AND PROGNOSTIC FACTORS AFFECTING CLINICAL OUTCOMES IN CYTOMEGALOVIRUS RETINITIS WITH OR WITHOUT HIV INFECTION.

PURPOSE: To explore the clinical features and outcomes of cytomegalovirus retinitis (CMVR) in patients with HIV and non-HIV. METHODS: This retrospective cohort study included all patients with CMVR in National Taiwan University Hospital from 2013 to 2018. Demographic data, clinical characteristics, CMVR recurrence, and overall survival were compared between the HIV and non-HIV groups. Generalized estimating equation models were implemented to analyze the risk factors of poor visual prognosis. The Kaplan-Meier survival analysis was performed to investigate recurrence and survival. RESULTS: A total of 66 patients (95 eyes) with CMVR were enrolled, with no significant differences between the HIV (41 patients; 61 eyes) and non-HIV (25 patients; 34 eyes) groups in initial/final visual acuity, lesion area, or viral loads. Poor visual outcome was associated with poor initial visual acuity, retinal detachment, and a higher plasma cytomegalovirus titer. The HIV group had significantly longer survival rate ( P = 0.033) and lower recurrence rate ( P = 0.01) than the non-HIV group, and it also presented with better prognosis in recurrence-free survival analysis ( P = 0.01). CONCLUSION: Patients with CMVR without HIV had higher mortality and recurrence rates than the HIV group. Risk factors of poor visual outcome included poor initial visual acuity, retinal detachment, and a high plasma cytomegalovirus titer.

Successful treatment of cytomegalovirus retinitis with oral/intravitreal antivirals in HIV-negative patients with lymphoma.

OBJECTIVES: To report patients with systemic lymphoma and cytomegalovirus (CMV) retinitis, treated with a combination of oral and intravitreal antiviral agents on an outpatient basis. METHODS: Retrospective cases series. Information was gathered from the database of the Uveitis clinics at Moorfields Eye Hospital, United Kingdom from December 2014 to December 2018. The inclusion criteria comprised the diagnosis of systemic lymphoma, associated with a diagnosis of CMV retinitis. Exclusion criteria were alternative ocular diagnosis, human immunodeficiency virus (HIV), primary intraocular lymphoma, or other causes of immunosuppression. RESULTS: All seven subjects had been under oncologist care for systemic lymphoma. CMV retinitis presented with a median of 61 months after the systemic lymphoma diagnosis. Five patients underwent a vitreous biopsy, and four of them returned PCR positive for CMV and the fifth patient had PCR positive in a blood sample. All patients were treated with oral Valganciclovir, with an induction dose of 900 mg every 12 h for up to 3 weeks until disease resolution and a maintenance dose thereafter. All but one received additional intravitreal Foscarnet injections, with a dose of 2.4 mg /0.1 ml. CONCLUSIONS: The management of patients with systemic lymphoma and CMV retinitis with oral and intravitreal antiviral agents, resulted in effective disease control.

Cytomegalovirus retinitis in hospitalized people living with HIV in the late antiretroviral therapy era in São Paulo, Brazil.

BACKGROUND: There is scarce information on AIDS-related cytomegalovirus (CMV) retinitis in middle-income countries. The objectives of this study were to identify the prevalence of active CMV retinitis in severely immunosuppressed people living with HIV (PLWHIV) and to describe its main features. METHODS: This retrospective cohort study was carried out at a tertiary center in São Paulo, Brazil. We included hospitalized adults PLWHIV with CD4 count ≤100 cells/µL, ≥ one quantitation of CMV DNA in plasma, and indirect ophthalmoscopy evaluation. RESULTS: Thirty-eight (21.6%) of 176 participants had at least an ophthalmoscopy diagnosis and only 3 (1.7%) individuals presented active CMV retinitis. All these participants were male, and retinitis was asymptomatic in 2 cases. Two participants had extraocular end-organ CMV disease and detectable CMV DNA in plasma. CONCLUSIONS: These results show a low prevalence of active CMV retinitis in the evaluated population. However, 2 of 3 participants had asymptomatic active CMV retinitis and a fifth of participants had at least one ophthalmoscopy diagnosis, suggesting the need for routine ophthalmologic evaluation in hospitalized severely immunosuppressed PLWHIV. The profile of participants with active CMV retinitis was similar to that described in the pre-ART era and quantitation of CMV DNA in plasma was variable.

Changes and Treatment Prognosis of Aqueous Humor Cytokine Concentrations of Patients with Acquired Immune Deficiency Syndrome Complicated by Cytomegalovirus Retinitis.

Purpose: The purposes of this study were to investigate cytokine changes in the aqueous humor after treatment of acquired immune deficiency syndrome (AIDS) complicated with cytomegalovirus retinitis (CMVR) and to determine whether these changes are useful prognostic indicators. Methods: This study included 12 patients (15 eyes) undergoing treatment for AIDS and CMVR. The patients received intravitreal injections and systemic intravenous treatment with ganciclovir and foscarnet sodium. The aqueous humor of each eye was sampled before treatment and before the third and fifth injections. The samples were tested to determine the concentrations of each of 27 cytokines using the Luminex 200™ liquid phase chip. Results: The concentrations of cytokines interleukin (IL)-1rα (P = 0.002), IL-1b (P = 0.001), IL-8 (P = 0.001), basic fibroblast growth factor (bFGF) (P < 0.001), interferon γ-induced protein 10 (IP-10) (P = 0.001), and tumor necrosis factor (TNF)-α (P = 0.004) in the aqueous humor before the third and fifth injections were significantly lower after than before treatment. The reductions in TNF-α (P = 0.028) and IL-1b (P = 0.028) concentrations after treatment were statistically significant compared with the postoperative visual acuity improvement (≥3 lines and <3 lines). The difference in TNF-α (P = 0.018) level before and after treatment (the difference between before treatment and before the fifth intravitreal injection) was also statistically significant compared with the number of injections (≥6 times and <6 times). Conclusion: The cytokines IL-1rα, IL-1b, IL-8, bFGF, IP-10, and TNF-α may offer new avenues for evaluation of therapeutic effect, and TNF-α and IL-1b may be important cytokines for prognostic evaluation (based on visual acuity and the number of injections) in patients suffering from AIDS and CMVR. Clinical Trial Registration: Number: ChiCTR2200056955.

Clinical characteristics in the misdiagnosis of cytomegalovirus retinitis: A retrospective analysis of eight patients.

Purpose: To highlight characteristics in the misdiagnosis of cytomegalovirus retinitis (CMVR). Methods: Misdiagnosed cases related to CMVR were analyzed retrospectively at the Department of Ophthalmology, Beijing Youan Hospital, from July 2017 to October 2019. The medical records were reviewed by two independent senior ophthalmologists and the patients' clinical characteristics were analyzed. Results: Eight patients (16 eyes) were identified with misdiagnoses related to CMVR. Six of the patients with CMVR were previously unaware of their human immunodeficiency virus (HIV) infection; one patient with CMVR concealed their history of HIV infection. The cases were initially misdiagnosed as diabetic retinopathy (1/7, 14.3%), branch retinal vein occlusion (1/7, 14.3%), ischemic optic neuropathy (1/7, 14.3%), Behçet's disease (1/7, 14.3%), iridocyclitis (2/7, 28.6%), and progressive outer retinal necrosis (1/7, 14.3%). One patient with binocular renal retinopathy and chronic renal insufficiency was misdiagnosed with CMVR. Four eyes (4/16, 25%) presented with pan-retinal involvement. Fourteen eyes (14/16, 87.5%) had optic disc or macular area involvement. At the final diagnosis, one patient was blind, and two patients had low vision. Seven AIDS patients showed an extremely low level of CD4+ T lymphocytes (median of 5 cells/µl; range 1-9 cells/µl). Conclusion: CMVR may be misdiagnosed in the absence of known immune suppression. CMVR and HIV screening cannot be overlooked if a young male patient presents with yellowish-white retinal lesions. These misdiagnosed patients had severe retinitis associated with poor vision.