Cytomegalovirus Retinitis Research Articles

178 The Unexpected Guest: CMV Retinitis Without Viremia in a Kidney Transplant Recipient

178 The Unexpected Guest: CMV Retinitis Without Viremia in a Kidney Transplant Recipient

Определение активности очагов цитомегаловирусного ретинита без забора водянистой влаги

Cytomegalovirus retinitis is retinal necrosis, a disease that can lead to irreversible blindness, the most effective way to treat it is a series of intravitreal injections under the control of intraocular fluid polymerase chain reaction. This is possible only in conditions of close relationship with the laboratory. This paper proposes a technology for monitoring the state of foci of cytomegalovirus retinitis without laboratory analysis of aqueous humor.

Сравнение эффективности серии интравитреальных инъекций противовирусных препаратов в лечении цитомегаловирусного ретинита при помощи полимеразной цепной реакции водянистой влаги и при офтальмоскопическом контроле

Cytomegalovirus retinitis is a relapsing and progressive disease that can lead to the development of irreversible blindness. A method for its treatment has been developed, which consists in a series of intravitreal injections of an antiviral drug under the control of the polymerase chain reaction of the intraocular fluid. In this paper, this method is compared with the classical one, when decisions to stop or continue intravitreal injections are made based on the results of ophthalmoscopy. Analysis of the obtained results showed a significant decrease in the number of relapses and the number of retinal detachments in those patients in whom intravitreal injections of antiviral drugs were carried out under the control of polymerase chain reaction until complete elimination of cytomegalovirus copies.

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

PurposeTo review management, treatment, and outcomes of patients with necrotizing herpetic retinitis (NHR) to propose an algorithm for first-line management of NHR.MethodsRetrospective 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.ResultsForty-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.ConclusionsThe 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.

Predictors for Recurrence of Cytomegalovirus Retinitis in HIV-Negative Patients

ABSTRACT Purpose To investigate the incidence of and predictive factors for recurrent cytomegalovirus retinitis (CMVR) in human immunodeficiency virus (HIV)-negative patients. Methods A retrospective review of HIV-negative patients who were newly diagnosed with CMVR between January 2005 and February 2019. Results Of 28 patients (44 eyes), 35.9% of eyes had a recurrence of CMVR after discontinuation of anti-CMV therapy. The incidence of CMVR recurrence was 17 per 100 eye-years. The factors significantly associated with CMVR recurrence were eyes with retinitis area of more than 25% (P = .013), absence of vitreous haze (P = .003), neutropenia at presentation (P = .001), and absence of systemic immunosuppression therapy prior to presentation (P = .002). Conclusion Eyes with a large area of retinitis, absence of vitreous haze, and neutropenia at presentation are predictive of CMVR recurrence while receiving systemic immunosuppression prior to CMVR presentation has a lower risk of CMVR recurrence.

Cytomegalovirus Retinitis: An Overview

Alice Ditchfield Abstract Cytomegalovirus (CMV) retinitis primarily affects immunocompromised individuals. It causes full-thickness retinal necrosis and viral inclusion bodies are seen in infected cells. Patients present with painless vision loss or may be asymptomatic. It is diagnosed based on characteristic fundal appearances, often demonstrating white, wedge-shaped areas of necrosis with associated retinal haemorrhages. Treatment options […]

Surgery for Infectious Retinitis - When Medical Therapy Is Not Sufficient: The Moacyr E. Alvaro Pan-American Lecture 2023

ABSTRACT Background Viral retinitis composes a group of infectious ocular diseases with poor prognoses. With the advent of antivirals and HAART, the treatment of these diseases has evolved and ocular outcomes have improved. However, even with prompt medical treatment, a significant number of patients will experience complications that require surgical intervention. While there has been an abundance of research examining the medical treatment of CMV retinitis and acute retinal necrosis, the research examining surgical outcomes of complications such as retinitis-associated retinal detachment is comparatively limited. Methods Literature review. Results In this review, we discuss the current literature examining treatment of CMV retinitis and acute retinal necrosis, with a focus on surgical management of complications such as retinal detachment. Conclusions Despite significant improvements in the medical treatment of CMV retinitis and ARN over the last three decades, vision-threatening complications such as retinal detachment are relatively common and require surgical management via PPV, laser photocoagulation, and intraocular gas or silicone oil tamponade.

Risk Factors for Cytomegalovirus Retinitis in a National Survey in Sweden

ABSTRACT Purpose To investigate predisposing immunosuppressive conditions causing cytomegalovirus retinitis (CMVr) and risk factors for delayed diagnosis in patients diagnosed between 2008 and 2018 in the Swedish population of 10 million. Results Sixty-three consecutive patients (100 eyes) were diagnosed with CMVr. The most common immunosuppressive state predisposing for CMVr was hematopoietic stem cell transplant recipients (27%) and hematological malignancy (24%). Two patients (3.2%) had no other predisposing factor than diabetes mellitus (DM). Patients with delayed diagnosis (≤30 days) were older than those with earlier diagnosis, mean age 68.7 (±9.8) and 48.8 (±17.6), respectively, p = .001. Signs of intraocular inflammation (IOI) were seen in 42 (70%) of cases and more common in delayed than early diagnosis, 16 (89%) and 21 (60%) respectively (p = .03). Conclusion Delayed diagnosis was more common in older individuals with signs of IOI. DM may be a risk factor for CMVr, and clinical signs can be mistaken for diabetic retinopathy.

Umbilicated vesicles and multiple pustules on the genital area in a man

Umbilicated vesicles and multiple pustules on the genital area in a man

Application of iontophoresis in ophthalmic practice: an innovative strategy to deliver drugs into the eye

Delivery of drugs to special locations of ocular lesions, while minimizing systemic and local toxic effects, is recognized as a critical challenge in the ophthalmic practice. The special anatomy and physiology barriers within the eyeball entail effective drug delivery systems. Emerging attempts in drug delivery has led to developments in ocular iontophoresis, which acts as a noninvasive technology to enhance drug penetration using a small electric current. This technique offers greater flexibility to deliver desired drug dose in a controlled and tolerable manner. In previous studies, this technique has been testified to deliver antibiotics, corticoid, proteins and other gene drugs into the eye with the potency of treating or alleviating diverse ophthalmological diseases including uveitis, cataract, retinoblastoma, herpes simplex and cytomegalovirus retinitis (CMVR), etc. In this review, we will introduce the recent developments in iontophoresis device. We also summarize the latest progress in coulomb controlled iontophoresis (CCI), hydrogel ionic circuit (HIC) and EyeGate II delivery system (EGDS), as well as overview the potential toxicity of iontophoresis. We will discuss these factors that affect the efficacy of iontophoresis experiments, and focus on the latest progress in its clinical application in the treatment of eye diseases.

Cytomegalovirus Anterior Uveitis: Clinical Manifestations, Diagnosis, Treatment, and Immunological Mechanisms.

Little is known regarding anterior uveitis (AU), the most common ocular disease associated with cytomegalovirus (CMV) infection in immunocompetent populations. CMV AU is highly prevalent in Asia, with a higher incidence in men. Clinically, it manifests mainly as anterior chamber inflammation and elevated intraocular pressure (IOP). Acute CMV AU may resemble Posner-Schlossman syndrome with its recurrent hypertensive iritis, while chronic CMV AU may resemble Fuchs uveitis because of its elevated IOP. Without prompt treatment, it may progress to glaucoma; therefore, early diagnosis is critical to prognosis. Knowledge regarding clinical features and aqueous humor analyses can facilitate accurate diagnoses; so, we compared and summarized these aspects. Early antiviral treatment reduces the risk of a glaucoma surgery requirement, and therapeutic effects vary based on drug delivery. Both oral valganciclovir and topical ganciclovir can produce positive clinical outcomes, and higher concentration and frequency are beneficial in chronic CMV retinitis. An extended antiviral course could prevent relapses, but should be limited to 6 months to prevent drug resistance and side effects. In this review, we have systematically summarized the pathogenesis, clinical features, diagnostic and therapeutic aspects, and immunological mechanisms of CMV AU with the goal of providing a theoretical foundation for early clinical diagnosis and treatment.

Clinical Characteristics and Prognostic Factors Impacting Clinical Outcomes in Cytomegalovirus Retinitis with or without HIV Infection.

To explore the clinical features and outcomes of cytomegalovirus retinitis (CMVR) in HIV and non-HIV patients. This retrospective cohort study included all CMVR patients 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 equations (GEE) models were implemented to analyze the risk factors of poor visual prognosis. Kaplan-Meier survival analysis was performed to investigate recurrence and survival. 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 (VA), lesion area, or viral loads. Poor visual outcome was associated with poor initial VA, retinal detachment, and a higher plasma CMV 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). CMVR patients without HIV had higher mortality and recurrence rates than the HIV group. Risk factors of poor visual outcome included poor initial VA, retinal detachment, and a high plasma CMV titer.

An Unusual Case of Early Cytomegalovirus Retinitis with UTI, Invasive Pulmonary Aspergillosis, Klebsiella Pneumonia in a Renal Allograft Recipient

Cytomegalovirus (CMV) remains the most common opportunistic infection after a kidney transplant. CMV retinitis is a rare manifestation of CMV invasive disease and is potentially threatening to vision in immunocompromised individuals. Invasive aspergillosis (IA) is one of the major causes of invasive fungal infection in kidney transplant recipients. Posttransplant CMV significantly increases the risk of IA in solid organ transplants. However, simultaneous or superadded opportunistic infections are rare and often delay the diagnosis. We report a case of early CMV retinitis in a renal transplant recipient, who initially developed extended-spectrum beta-lactamase-positive Escherichia coli cystitis at 2 weeks posttransplant. At 4 weeks posttransplant, he developed CMV retinitis managed with intravenous and intravitreal ganciclovir. At around 6 weeks, he developed persistent low-grade fever and pancytopenia without any specific systemic symptoms with initial sterile cultures sterile and normal imaging except for high-resolution computed tomography chest, which was suggestive of fungal pneumonia. Bronchoscopy and bronchoalveolar lavage were done, which came positive for aspergillus colonies. The patient improved with Amphotericin B, which was later changed to oral voriconazole. A few days later, the patient again deteriorated with new-onset fever, cough, and expectoration, which were diagnosed with Klebsiella pneumonia by imaging supported by sputum culture, which was managed by appropriate antibiotics. CMV and IA are both uncommon opportunistic infections and simultaneous or superadded infection with bacterial pneumonia is very rare. In the presence of persistent symptoms, early suspicion of another infection is crucial for patient management and long-term prognosis.

CMV retinitis in a T-cell acute lymphoblastic leukaemia patient - a case report

The Sri Lankan Journal of Infectious Diseases (SLJID) is an open access, peer-reviewed, biannual journal published by the Sri Lankan Society for Microbiology (SSM). The Journal considers articles from all professional disciplines involved in the field of infectious diseases. The Journal has been in publication since 2011, is included in the DOAJ since 2018 and is a member of COPE since 2021. The SLJID practices a double-blind peer review policy. From 2022, the SLJID publishes accepted manuscripts online immediately after copy-editing, enabling rapid dissemination of scientific knowledge. The published articles are subsequently compiled into two issues in April and October. The SLJID does not charge any article processing or publication fee.

1453. Clinical Manifestation and Risk Factors Associated with Mortality of Cytomegalovirus Infection in Immunocompetent Patients in King Chulalongkorn Memorial Hospital, Bangkok, Thailand: a 3-year experience

Abstract Background Cytomegalovirus (CMV) infection usually occurs in organ transplant or HIV-infected patients. Recently, we found CMV infection was increased in non-transplant and non-HIV infected patients. Our study aimed to determine the epidemiology, clinical manifestation, clinical outcome, and risk factors associated mortality of CMV infection in this population. Methods The retrospective study was conducted in King Chulalongkorn Memorial Hospital. Patients aged above 18 years with diagnosis of CMV infection from January 2017 to September 2019 were collected and identified by ICD-10 code. Patients with HIV infection, solid organ transplant and hematopoietic stem cell transplant were excluded. Results A total of 51 patients, including 28 males (54.9%) were identified. The median age was 61 years (range 48-73 years). 46 patients (90.2%) had underlying disease which were 19 cases (37.3%) of autoimmune disease, 13 cases (25.5%) of hematologic disease (mostly hematologic malignancy), 4 cases (7.8%) of chronic kidney disease, and 10 cases (21.6%) of others. CMV viremia was found in 31.4%. Regarding CMV end-organ disease, there were 20 cases of gastrointestinal tract CMV infection, 10 cases were CMV retinitis, 5 cases were CMV pneumonitis and 1 case was CMV hepatitis and CMV transverse myelitis. The all-cause mortality was 25.5% and significantly in age over 70-year-old (p=0.037). The end-organ disease and CMV viral load were not different in survived and death group (p=0.445 and p=0.838, respectively). Factors associated with mortality of CMV infection Conclusion CMV infection was an emerging problem in non-transplant and non-HIV infected adult patients, especially in age over 70-year-old in our Institute. The study showed infections predominated in rheumatologic and hematologic malignant patients who were received chemotherapy or immunosuppressive agent. Viremia and gastrointestinal tract were organs that mainly involved. CMV infection will become an important complication in the era of treatment with immuno-chemotherapy. Clinician should be aware of this potentially life-threatening infection. Disclosures All Authors: No reported disclosures.

376. Testing for Cytomegalovirus Viremia in People with HIV/AIDS- An Opportunity for Diagnostic Stewardship

Abstract Background Guidelines recommend against testing for cytomegalovirus (CMV) viremia as a screening tool for CMV end-organ disease (EOD) in people with HIV/AIDS (PWHA) due to low positive predictive value. Additionally, a negative result does not exclude EOD. In this study, we aim to assess the clinical utility of plasma CMV quantitative PCR (qPCR) for the diagnosis of CMV EOD and to determine if positive results lead to further testing for EOD or earlier initiation of anti-CMV therapy. Methods We retrospectively identified PWHA who had a plasma CMV qPCR result or who were diagnosed with CMV EOD between 2014-2021. qPCR results that were undetectable or less than the minimum quantifiable value (300 IU/mL) were considered negative and results >300 IU/mL were considered positive. EOD was confirmed via tissue biopsy, ophthalmic exam, or cerebrospinal fluid analysis. We compared CMV qPCR results for participants with proven EOD and those without proven EOD. For participants diagnosed with CMV EOD, we evaluated if a positive qPCR prompted further workup for EOD diagnosis or triggered anti-CMV therapy. Results We identified 138 PWHA with a CMV qPCR result and 17 PWHA with CMV EOD. Participant characteristics are shown in Table 1. Among participants with a qPCR result, 27 (19.6%) were positive; 13 (9.42%) of those with a qPCR results had EOD. 4 participants with EOD did not have qPCR. Participants with a positive qPCR were 4.55 (95% CI 2.63-7.90) times more likely to have EOD than those with a negative result. Table 2 shows qPCR results among participants with and without EOD. Table 3 shows the performance of qPCR for the diagnosis of EOD. 9 (69.2%) of 13 participants with EOD had a positive qPCR. 7 of them were diagnosed with EOD and started on treatment before the qPCR resulted. In 1 case, the qPCR resulted as positive on the same day ophthalmology diagnosed CMV retinitis. In only 1 case did a positive qPCR result and initiation of therapy precede the diagnosis of EOD. Conclusion Contrary to guidelines, clinicians often order plasma CMV qPCR on PWHA. Although PWHA who have CMV EOD are more likely to a have a positive qPCR than those without EOD, our data confirm CMV qPCR should not be used as a screening tool for EOD. Instead, clinical assessment should guide diagnostic investigation. Disclosures All Authors: No reported disclosures.

CMV Retinitis with Panretinal Occlusive Vasculitis

ABSTRACT Purpose To report the clinical features of cytomegalovirus (CMV) retinitis with panretinal occlusive vasculitis. Methods Retrospective case series. Results Four eyes in 3 non-HIV patients (male: female = 3:0) were included. Previous medical history included diabetes mellitus (n = 2), age-related macular degeneration (n = 1), and Multiple myeloma under chemotherapy (n = 1). All patients were treated with oral valganciclovir and intravitreal ganciclovir. Slow resolution of retinitis related retinal opacification was noted in all 4 eyes. Two eyes had anti-viral agents discontinued despite the persistent retinitis related opacification and the lesions slowly resolved in the following months. The final decimal visual acuity was equal to or worse than 0.02 in 3 of the 4 eyes. Conclusion In eyes of CMV retinitis with panretinal occlusive vasculitis, rapid resolution of retinitis lesions is an unreliable sign evaluating the therapeutic efficacy of anti-viral agents. Besides, despite treatment of anti-viral agents, deteriorating vascular occlusion may further endanger macular function.

Relationship between opacity of cytomegalovirus retinitis lesion borders and aqueous viral load among patients after allogeneic hematopoietic stem cell transplantation

Objective: To evaluate the relationship between lesion features of cytomegalovirus (CMV) retinitis, including lesion size and degree of opacity of lesion borders, and aqueous CMV-DNA load in patients after allogeneic hematopoietic stem cell transplantation. Methods: It was a retrospective case series study. Data of patients diagnosed as CMV retinitis after allogeneic hematopoietic stem cell transplantation at the Department of Ophthalmology, Peking University Third Hospital from January 2018 to October 2020 were reviewed. Lesion size was detected by ultra-wide-field fundus image and measured by ImageJ, an image processing and analysis software. Opacity of lesion borders was evaluated by a masked reader. The CMV retinitis lesions were divided into 3 types according to the opacity degree of the border of the lesions: suspected active lesion mildly to moderately opacified lesion and severely opacified lesion. All eyes were diagnosed as active cytomegalovirus retinitis. CMV-DNA in aqueous humor was detected at the first visit and at the end of the induction period of antiviral drugs. CMV-DNA load was quantitatively detected by polymerase chain reaction after 100 μl of aqueous humor was extracted, and were converted to common logarithmic representations. Pearson correlation analysis was used to analyze the correlation between lesion area, opacity degree of lesion border and aqueous humor CMV-DNA load. Results: A total of 71 eyes from 46 patients were included and 26 was male and 20 was female. The age of the patients was 27(13, 33)years. The active lesion size of CMV retinitis was 40(12, 65) disc areas. Eight eyes (11.3%) had a suspected active lesion, 51 eyes (71.8%) had a mildly to moderately opacified lesion border, and 12 eyes (16.9%) had a severely opacified border. At the first visit, 67 eyes (94.4%) were CMV-positive, and the CMV-DNA load was 2.04×104 (6.24× 102, 1.48 ×105) copies/ml. After 2 weeks of induction therapy, the viral load was 2.47×102 (1.08× 10, 6.87 ×103) copies/ml. The correlation analysis showed that the CMV-DNA load in aqueous humor was significantly correlated with the lesion border opacity both at presentation and 2 weeks after intravitreal antiviral treatment (r=0.765, P<0.001; r=0.761, P<0.001), but was not related with the size of active fundus lesions (r=0.209, P=0.095; r=0.220, P=0.078). Conclusion: Degrees of lesion border opacity can reflect levels of aqueous viral load of CMV retinitis in patients after allogeneic hematopoietic stem cell transplantation and can become a useful measurement for investigation of CMV retinitis activity.

Efficacy of Ganciclovir in Cytomegalovirus Retinitis via Intravitreal Route in AIDS Patients.

A series of nine eyes of five patients at LRBT Tertiary Teaching Eye Hospital, from July 2020 to June 2021 is reported. Five patients with high clinical suspicion of CMV Retinitis were treated with weekly intravitreal injections of 2.0 mg ganciclovir for 3 weeks. Pre- and post-injection visual acuity and clinical findings were noted. After 3 injections, clinical signs of CMV retinitis started to resolve in all eyes (100%). Visual acuity improved in seven eyes (77.7%) and remained stable in two eyes (22.2%). Two of the seven eyes which initially showed improvement, later on developed retinal detachment. Patients were followed up for a minimum duration of 1 year. Intravitreal ganciclovir is effective for CMV retinitis but follow- up for a longer duration is needed as these patients are prone to develop peripheral retinal tractions and detachments. Key Words: Ganciclovir, CMV retinitis, AIDS.

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.