Search

Cytomegalovirus (CMV) retinitis is commonly associated with immunosuppression and can cause irreversible vision loss. Chimeric antigen receptor T-cell (CAR-T) therapy has emerged as an effective cancer treatment option but requires immunosuppression, thereby increasing the possibility of acquiring opportunistic infections such as CMV. We present the case of a 76-year-old female with a history of hypertension and type 2 diabetes mellitus who initially presented with shortness of breath and was diagnosed with the activated B-cell subset of diffuse large B-cell lymphoma (DLBCL). She received multiple cycles of chemotherapy and experienced relapses with cardiac involvement. The patient developed vision loss in the right eye and was diagnosed with bilateral posterior vitritis. She underwent various treatments, including radiotherapy, systemic chemotherapy, cataract extraction, and vitrectomy. After CAR-T therapy, she developed bilateral CMV retinitis, confirmed through polymerase chain reaction testing and managed by valganciclovir. Overall, this case report describes the first reported case of bilateral CMV retinitis following CAR-T therapy for DLBCL. It emphasizes the need for early recognition and treatment of CMV retinitis to prevent permanent vision loss. The report also underscores the importance of regular ocular screening and consideration of prophylactic measures in patients undergoing CAR-T therapy.

PurposeMethodsResultsConclusionTo explore the potential risk factors for the occurrence of human cytomegalovirus (HCMV) retinitis (CMVR) in allogeneic hematopoietic stem cell transplantation (allo-HSCT) patients.This is a retrospective, nested case-control study conducted in hematological patients with CMVR who underwent allo-HSCT. Patients diagnosed with CMVR after allo-HSCT were included as the case group, and those without CMVR were matched by a ratio of 1:2 and were recruited as controls. We selected 19 pre- and post-transplant indicators for univariate analysis between the cases and controls, and then Logistic regression analysis was used to calculate the odds ratio (OR) and 95% confidence intervals (CI) for exploration of risk factors of the CMVR occurrence.A total of 1308 allo-HSCT patients from January 1, 2020 to July 31, 2023 were analyzed, and 27 patients were diagnosed CMVR with a median onset time of 222 days after transplantation. In univariate analysis, donors of stem cells source, HLA-match types (including matched sibling donor, haploidentical donor, and unrelated donor), post-transplant Epstein-Barr virus (EBV) viremia, platelet implantation time, and serostatus of CMV-IgG were more easily to develop CMVR than controls (p < 0.001, p = 0.003, p < 0.001, p = 0.032, p = 0.038, respectively). Multivariate logistic regression analysis showed that stem cells source (OR 7.823, 95% CI 1.759-34.800), HLA-match types (OR 7.452, 95% CI 1.099-50.542), and post-transplant EBV infection (OR 7.510, 95% CI 1.903-29.640) were positively associated with the onset of CMVR.Stem cells derived from bone marrow and peripheral blood, HLA-match types, and post-transplant EBV viremia are important risk predictors of CMVR in allo-HSCT patients. These results suggest that clinicians should pay more attention to these indicators when formulating preventive measures pre- and post-transplant. [ABSTRACT FROM AUTHOR]

Cytomegalovirus (CMV) retinitis is a rare disease, and overlapping manifestations involving the anterior segment are extremely uncommon. We report a patient who initially presented with persistent corneal edema and was later diagnosed with CMV retinitis. A 72-year-old man with uncontrolled intraocular pressure (IOP) in his right eye visited a tertiary hospital. At initial presentation, the IOP was 36 mmHg and the fundus was not clear due to corneal edema. Spectral domain optical coherence tomography revealed paracentral acute middle maculopathy (PAMM). Panretinal obstructive vasculopathy was observed on ultra-widefield fluorescein angiography. Three weeks later, trabeculectomy was performed to resolve the persistently high IOP. Once corneal edema improved, a white patch-like peripheral lesion and silver wire-like retinal vasculature were observed. Polymerase chain reaction of the aqueous humor was positive for CMV. Oral valganciclovir and intravitreal ganciclovir were administered as antiviral therapies. Despite treatment for 4 months, the final visual acuity was no light perception, with persistent corneal edema and neovascularization of the iris. We describe a rare case of the simultaneous occurrence of hypertensive uveitis and CMV retinitis. The presence of PAMM could be an initial identifiable sign of CMV retinitis, even in the presence of media opacity.

Immune recovery uveitis (IRU) is an intraocular inflammation that typically occurs as part of immune reconstitution inflammatory syndrome (IRIS) in the eye. Typically, it affects human immunodeficiency virus (HIV)-infected patients with recognized or unrecognized cytomegalovirus (CMV) retinitis who are receiving highly active antiretroviral therapy (HAART). IRU is a common cause of new vision loss in these patients, and it manifests with a wide range of symptoms and an increased risk of inflammatory complications, such as macular edema. Recently, similar IRU-like responses have been observed in non-HIV individuals with immune reconstitution following immunosuppression of diverse etiologies, posing challenges in diagnosis and treatment. This review provides an updated overview of the current literature on the epidemiology, pathophysiology, biomarkers, clinical manifestations, diagnosis, differential diagnosis, and treatment strategies for IRU. [ABSTRACT FROM AUTHOR]

Background: Acquired human cytomegalovirus (CMV) is a noteworthy disease in infants. This case study will highlight the influence of early diagnosis of CMV retinitis (CMVR) on avoid visual impairment. Clinical Findings: We describe a preterm female infant with a birth weight of 2060 gr that was admitted for tracheostomy placement due to hypoxic-ischemic encephalopathy. There were no signs of CMV infection or sepsis in laboratory results upon admission such as serology (IgG, IgM antibodies), Toxoplasma gondii, Rubella virus, Herpes simplex virus, CMVR and urine polymerase chain reaction (PCR). Primary Diagnosis: Incidentally, upon screening for retinopathy of prematurity, diffuse occlusive vasculitis was detected in the retinal image on the 112th day of life. Intervention: Intravenous and intraocular ganciclovir were administered for 4 weeks. Outcomes: In the follow-up visit 6 weeks after discharge from the hospital, visual impairment was detected on both sides. Practice Recommendations: This is a report of a case of acquired CMVR, a silent finding, as an uncommon complication in preterm neonates during the hospital stay. This diagnosis should be taken into consideration in preterm infants, since early diagnosis and treatment are crucial to avoid visual impairment. [ABSTRACT FROM AUTHOR]

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. Literature review. 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. 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. [ABSTRACT FROM AUTHOR]

To investigate the incidence of and predictive factors for recurrent cytomegalovirus retinitis (CMVR) in human immunodeficiency virus (HIV)-negative patients. A retrospective review of HIV-negative patients who were newly diagnosed with CMVR between January 2005 and February 2019. 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). 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. [ABSTRACT FROM AUTHOR]

To report the clinical features of cytomegalovirus (CMV) retinitis with panretinal occlusive vasculitis. Retrospective case series. 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. 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. [ABSTRACT FROM AUTHOR]

Purpose: To report a case of unilateral, sectoral retinal metastasis of small cell lung cancer (SCLC) that mimicked cytomegalovirus retinitis. Method: Case report. Results: A 48-year-old woman presented with a 4-week history of a visual field loss in her right eye. She had a medical history of extensive-stage SCLC with brain metastasis, stable on maintenance atezolizumab for 2 years. On initial presentation, she was diagnosed with cytomegalovirus retinitis. No improvement was observed with 4 weeks of oral valganciclovir. Upon referral for a second opinion, her fundus examination appeared compatible with cytomegalovirus retinitis, and anterior chamber tap for polymerase chain reaction for viral etiologies was performed followed by intravitreal and IV ganciclovir without improvement. She was referred for a third opinion, where diagnostic vitrectomy with vitreous and retinal biopsies were consistent with SCLC metastatic to the retina. The patient underwent enucleation of the right eye for definitive pathologic analysis and subsequently was started on additional systemic chemotherapy. Conclusion: Retinal metastases are exceedingly rare, particularly retinal metastasis of SCLC. Retinal metastasis should be considered in patients initially diagnosed with viral retinitis who fail to improve despite antiviral therapy, particularly if they have a known history of malignancy. Furthermore, retinal metastasis of SCLC potentially could be misdiagnosed histopathologically as retinoblastoma if the patient's history is unknown and appropriate immunohistochemical stains are not performed. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to describe a case of a 64-year-old man presenting with cytomegalovirus and herpes simplex virus retinitis coinfection in the setting of Burkitt lymphoma. Methods: A case report including multimodal imaging and anterior chamber polymerase chain reaction results was used. Results: This case highlights the importance of the clinical examination and maintaining high diagnostic suspicion for viral retinitis in immunocompromised patients. Conclusion: Aqueous fluid PCR can be a useful adjunctive test to distinguish and confirm a diagnosis of viral retinitis. Given the limited sample volume of aqueous biopsy, it is important to prioritize the order of PCR testing based on clinical suspicion of the causative agent. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of the study was to analyze the occurrence of severe, typical cytomegalovirus (CMV) retinitis (CMVR) in human immunodeficiency virus (HIV) negative, partially immunosuppressed patients, emphasizing inconsistency in the clinical presentation of CMVR and to evaluate the role of combined anti-CMV therapy in the management of such patients. Materials and Methods: This study was a retrospective, observational, noncomparative case series. We examined and treated consecutive HIV-negative adult patients of CMVR. Blood-based polymerase chain reaction analysis of the CMV genome was done pre- and posttreatment. Details of underlying systemic conditions were collected. Patients were treated with simultaneous administration of intravitreal and intravenous (IV) anti-CMV therapy. Follow-up was for 1 year. All outcomes were determined retrospectively. Results: A total of 6 eyes of 4 consecutive patients were diagnosed with CMVR in HIV-negative patients. Patients were only partially immunosuppressed but revealed typical severe fulminant CMVR. Patients received a total of 2 intravitreal ganciclovir injections, and IV ganciclovir/oral valganciclovir was given. All patients achieved complete healing within the treatment period. Conclusion: As opposed to the general perception, typical, fulminant, severe CMVR may occur in patients with limited immune dysfunction. Our report underlines this inconsistency in the clinical presentation of CMVR in partially immunosuppressed patients. The immune status of the patients seems a significant factor in determining the clinical phenotypes of CMVR. Combined intravitreal and IV ganciclovir/oral valganciclovir therapy was successful in treating this group of CMVR patients.

Abstract Purpose To report the use of Fluocinolone intravitreal implant (Iluvien) for the treatment of persistent cystoid macular edema (CME) due to immune recovery uveitis syndrome in a patient with previous cytomegalovirus retinitis and acute myeloid leukemia. Design Case report. Methods The clinical history of a patient who received an Iluvien implant in one eye for the treatment of cystoid macular edema due to immune recovery uveitis syndrome, previously treated with peribulbar Triamcinolone and intravitreal Dexamethasone injections, was reviewed. Results A 48-year-old woman presented with cystoid macular edema due to immune recovery uveitis syndrome. The patient had a history of cytomegalovirus retinitis 3.5 years prior, secondary to immunosuppressive treatment for an acute myeloid leukemia. Three periocular triamcinolone injections and two dexamethasone intravitreal implants were performed, but the edema recurred, so fluocinolone intravitreal implant was used, achieving a sustained control of the condition at one year of follow-up. Conclusion The Fluocinolone intravitreal implant may be an effective treatment for persistent CME in patients with immune recovery uveitis syndrome.

Purpose: To report the use of Fluocinolone intravitreal implant (Iluvien) for the treatment of persistent cystoid macular edema (CME) due to immune recovery uveitis syndrome in a patient with previous cytomegalovirus retinitis and acute myeloid leukemia. Design: Case report. Methods: The clinical history of a patient who received an Iluvien implant in one eye for the treatment of cystoid macular edema due to immune recovery uveitis syndrome, previously treated with peribulbar Triamcinolone and intravitreal Dexamethasone injections, was reviewed. Results: A 48-year-old woman presented with cystoid macular edema due to immune recovery uveitis syndrome. The patient had a history of cytomegalovirus retinitis 3.5 years prior, secondary to immunosuppressive treatment for an acute myeloid leukemia. Three periocular triamcinolone injections and two dexamethasone intravitreal implants were performed, but the edema recurred, so fluocinolone intravitreal implant was used, achieving a sustained control of the condition at one year of follow-up. Conclusion: The Fluocinolone intravitreal implant may be an effective treatment for persistent CME in patients with immune recovery uveitis syndrome. [ABSTRACT FROM AUTHOR]

Lowe syndrome (oculocerebrorenal syndrome of Lowe -- LS) is an ultra-rare, recessive X-linked, multisystem disorder that primarily occurs in males and affects the eyes, nervous system, and kidneys. It is a consequence of mutation of the OCRL gene on chromosome Xq25-26, which encodes phosphatidylinositol 4,5-bisphosphate 5 phosphatase, a protein present in the Golgi complex, lysosomes, and endosomes. The most common symptoms of LS involve congenital cataracts, neurological retardation, and incomplete Fanconi syndrome, ultimately leading to end-stage renal disease between the second and fourth decade of life. The authors present a boy with the intoxication of vitamin D3 and suspicion of congenital cytomegaly eventually diagnosed with LS at the age of 16 months. [ABSTRACT FROM AUTHOR]

Since the introduction of combination antiretroviral therapy (cART) in Japan in 2008, the spectrum of ocular manifestations in patients with human immunodeficiency virus (HIV) has changed. This study, conducted at Tokyo Medical and Dental University Hospital between January 2012 and August 2023, aimed to understand the epidemiology and clinical features of ocular manifestations in patients with HIV during the cART era. Of the 218 patients diagnosed with HIV, 23 (10.55%) exhibited ocular manifestations; all were male, aged 32–73. The most prevalent ocular complication was uveitis (60.67%). Notably, the prevalence of uveitis in this cART era has surged compared to earlier Japanese studies. Our data also suggest a potential direct link between uveitis and HIV, particularly in patients who have not yet undergone cART. However, cytomegalovirus retinitis, another prevalent ocular disease in our study, appeared more strongly associated with patients who commenced cART. Neither ocular condition was significantly correlated with CD4+ T-cell count. Importantly, our observed ocular manifestation prevalence (10.55%) was lower than that in previous studies, emphasizing the potential influence of cART and national healthcare support. These findings provide unique insights into the evolution of ocular manifestations in patients with HIV in Japan amidst cART availability. [ABSTRACT FROM AUTHOR]

Background: Ophthalmological screening for cytomegalovirus retinitis (CMVR) for HIV/AIDS patients is important to prevent lifelong blindness. Previous studies have shown good properties of automated CMVR screening using digital fundus images. However, the application of a deep learning (DL) system to CMVR with ultra-wide-field (UWF) fundus images has not been studied, and the feasibility and efficiency of this method are uncertain. Methods: In this study, we developed, internally validated, externally validated, and prospectively validated a DL system to detect AIDS-related from UWF fundus images from different clinical datasets. We independently used the InceptionResnetV2 network to develop and internally validate a DL system for identifying active CMVR, inactive CMVR, and non-CMVR in 6960 UWF fundus images from 862 AIDS patients and validated the system in a prospective and an external validation data set using the area under the curve (AUC), accuracy, sensitivity, and specificity. A heat map identified the most important area (lesions) used by the DL system for differentiating CMVR. Results: The DL system showed AUCs of 0.945 (95 % confidence interval [CI]: 0.929, 0.962), 0.964 (95 % CI: 0.870, 0.999) and 0.968 (95 % CI: 0.860, 1.000) for detecting active CMVR from non-CMVR and 0.923 (95 % CI: 0.908, 0.938), 0.902 (0.857, 0.948) and 0.884 (0.851, 0.917) for detecting active CMVR from non-CMVR in the internal cross-validation, external validation, and prospective validation, respectively. Deep learning performed promisingly in screening CMVR. It also showed the ability to differentiate active CMVR from non-CMVR and inactive CMVR as well as to identify active CMVR and inactive CMVR from non-CMVR (all AUCs in the three independent data sets >0.900). The heat maps successfully highlighted lesion locations. Conclusions: Our UWF fundus image-based DL system showed reliable performance for screening AIDS-related CMVR showing its potential for screening CMVR in HIV/AIDS patients, especially in the absence of ophthalmic resources.

Effective treatment of HIV-infected patients has changed the previous view of the clinical picture of cytomegalovirus uveitis (CMV uveitis).Purpose: to determine the prevalence and structure of clinical forms of CMV uveitis in HIV-infected patients.Material and methods. 66 patients (97 eyes), aged 39.6 ± 3.91, were diagnosed with stage 4c HIV infection. In 35 patients (53%), the duration of infection exceeded 5 years, in 13 patients (19.7%), it exceeded 10 years, and another 13 patients (19.7%) had the condition for over 15 years. The ophthalmological follow-up of patients diagnosed with CMV uveitis ranged from 6 months to 13 years (the median of 45.5 months).Results. By the time CMV uveitis was detected, the median CD4 cell count was 34 cells/μL (the norm being 570–1100 cells/μL). The content of whole blood CMV DNA was 2.43 lg copies/105 cells. The main form of the disease was chorioretinitis, diffuse and generalized forms of the disease were diagnosed in 68.0% of cases. In predicting visual acuity, the leading regression criterion was the clinical form of the disease.Conclusion. Diffuse and generalized forms of the disease prevailed in clinical practice. The prevalence of chorioretinal lesion determined visual acuity, which in 39.2% of the eyes met the criteria for blindness according to the WHO classification (1977)

PurposeTo describe ocular outcomes in eyes with cytomegalovirus (CMV) retinitis treated with adoptive immunotherapy using systemic administration of CMV-specific cytotoxic Tlymphocytes (CMV-specific CTLs).DesignRetrospective cohort study.ParticipantsPatients with active CMV retinitis evaluated at a tertiary care academic center.MethodsTreatment of CMV retinitis with standard-of-care therapy (systemic or intravitreal antivirals) or CMV-specific CTLs (with or without concurrent standard-of-care therapies).Main outcome measuresThe electronic medical record was reviewed to determine baseline characteristics, treatment course, and ocular outcomes, including best-corrected visual acuity (BCVA), treatments administered (CMV-specific CTLs, systemic antivirals, intravitreal antivirals), resolution of CMV retinitis, any occurrence of immune recovery uveitis, cystoid macular edema, retinal detachment, or a combination thereof.ResultsSeven patients (3 of whom had bilateral disease [n = 10 eyes]) were treated with CMV-specific CTLs, whereas 20 patients (6 of whom had bilateral disease [n = 26 eyes]) received standard-of-care treatment. Indications for CMV-specific CTL therapy included persistent or progressive CMV retinitis (71.4% of patients); CMV UL54 or UL97 antiviral resistance mutations (42.9%); side effects or toxicity from antiviral agents (57.1%); patient intolerance to longstanding, frequent antiviral therapy for persistent retinitis (28.6%); or a combination thereof. Two patients (28.6%; 4 eyes [40%]) received CMV-specific CTL therapy without concurrent systemic or intravitreal antiviral therapy for active CMV retinitis, whereas 5 patients (71.4%; 6 eyes [60%]) continued to receive concurrent antiviral therapies. Resolution of CMV retinitis was achieved in 9 eyes (90%) treated with CMV-specific CTLs, with BCVA stabilizing (4 eyes [40%]) or improving (4 eyes [40%]) in 80% of eyes over an average follow-up of 33.4 months. Rates of immune recovery uveitis, new-onset cystoid macular edema, and retinal detachment were 0%, 10% (1 eye), and 20% (2 eyes), respectively. These outcomes compared favorably with a nonrandomized cohort of eyes treated with standard-of-care therapy alone, despite potentially worse baseline characteristics.ConclusionsCMV-specific CTL therapy may represent a novel monotherapy or adjunctive therapy, or both, for CMV retinitis, especially in eyes that are resistant, refractory, or intolerant of standard-of-care antiviral therapies. More generally, adoptive cell transfer and adoptive immunotherapy may have a role in refractory CMV retinitis. Larger prospective, randomized trials are necessary.

Abstract Purpose To compare the efficacy and injection frequency of intravitreal low-dose vs. intermediate-dose ganciclovir therapy in acquired immune deficiency syndrome (AIDS) patients exhibiting cytomegalovirus retinitis (CMVR). Methods A prospective, single-centre, double-blinded, randomized controlled interventional study was conducted. Fifty patients with a total of 67 included eyes were randomly divided into low-dose (0.4 mg ganciclovir per week) and intermediate-dose (1.0 mg ganciclovir per week) groups. The primary clinical outcomes were the changes in best corrected visual acuity (BCVA) from baseline to the end of treatment and the 12-month follow-up visit as well as the number of intravitreal injections. Results In both groups, the median BCVA, expressed as the logarithm of the minimum angle of resolution (logMAR), improved significantly from baseline to the end of treatment (both p 0.05). Regarding the location of CMVR, we found that Zone I lesions led to a worse visual outcome, more injections and a higher occurrence rate of complications than lesions in other zones (p

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. [ABSTRACT FROM AUTHOR]

Purpose: To compare the efficacy and injection frequency of intravitreal low-dose vs. intermediate-dose ganciclovir therapy in acquired immune deficiency syndrome (AIDS) patients exhibiting cytomegalovirus retinitis (CMVR). Methods: A prospective, single-centre, double-blinded, randomized controlled interventional study was conducted. Fifty patients with a total of 67 included eyes were randomly divided into low-dose (0.4 mg ganciclovir per week) and intermediate-dose (1.0 mg ganciclovir per week) groups. The primary clinical outcomes were the changes in best corrected visual acuity (BCVA) from baseline to the end of treatment and the 12-month follow-up visit as well as the number of intravitreal injections. Results: In both groups, the median BCVA, expressed as the logarithm of the minimum angle of resolution (logMAR), improved significantly from baseline to the end of treatment (both p < 0.001), while vision loss from CMVR continued to occur at the 12-month visit. The mean number of injections was 5.8 in the low-dose group and 5.4 in the intermediate-dose group. No significant differences were detected between the two groups (p > 0.05). Regarding the location of CMVR, we found that Zone I lesions led to a worse visual outcome, more injections and a higher occurrence rate of complications than lesions in other zones (p < 0.05). Conclusions: The efficacy and frequency of injections to treat CMVR in AIDS patients were not significantly different between low and intermediate doses. Zone I lesions were associated with a worse visual outcome, more injections and a higher occurrence rate of CMVR-related complications than lesions in other zones. [ABSTRACT FROM AUTHOR]

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. Afew 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. [ABSTRACT FROM AUTHOR]

Background: Cytomegalovirus retinitis (CMVR) is the most common and sightthreatening 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/mL. 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/mL. 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. [ABSTRACT FROM AUTHOR]

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.

AIM: To demonstrate the clinical features, the risk factors, the visual prognosis and the recurrence of cytomegalovirus (CMV) retinitis (CMVR) in HIV-negative patients. METHODS: HIV-negative patients with CMVR were involved in this study. Best corrected visual acuity (BCVA), intraocular pressure (IOP), CMV-DNA load in aqueous and/or serum samples, treatment, follow-up time, recurrence and complications were recorded. Ocular characteristics were evaluated by fundus photographs. Association between ocular factors and visual prognosis were analyzed by regression analysis. RESULTS: Twenty-five eyes of 16 patients were included. All 25 eyes underwent intravitreal injections of anti-viral agents. The mean logMAR BCVA improved from 0.94±0.98 (0.98-0.78) initially to 0.77±0.73 (0.82-0.68) at last visit, but not significantly. After antiviral treatment, the aqueous CMV DNA load significantly reduced to (3.42±1.47)×102 copies/mL (P=0.001), compared with (2.51±3.11)×105 copies/mL at baseline. Macular involvement (R2=0.475, P=0.049) and initial visual acuity (R2=0.475, P=0.017) were significantly associated with the poor visual prognosis (BCVA

Objective: To determine tenofovir (TFV) penetration into intraocular tissues using ultra high-performance liquid chromatography/tandem mass spectrometry (UHPLC-MS/MS). Methods: Nineteen participants taking tenofovir in combination antiretroviral therapy (cART) regimen who underwent pars plana vitrectomy (PPV) surgery were enrolled in the observational retrospective study between January 2019 and August 2021. The participants were divided into mild, moderate, and severe groups according to retinal manifestations. Basic information was recorded during PPV surgery. Paired blood plasma and vitreous humor samples (n = 19) were collected for UHPLC-MS/MS. Results: The median plasma and vitreous tenofovir concentrations were 106.00 ng/mL (interquartile range[IQR], 54.6–142.5) and 41.40 ng/mL (IQR 9.4–91.6), respectively. The median vitreous/plasma concentration ratio from the paired samples was 0.42 (IQR 0.16–0.84). The plasma and vitreous tenofovir concentrations were significantly correlated (r = 0.483, P = 0.036). The median vitreous tenofovir concentration was the lowest in the mild group (4.58 ng/mL). Six vitreous samples were below 50% inhibitory concentration (IC50) (11.5 ng/mL), and 2 of them were undetectable. Significant differences were noted in vitreous/plasma and vitreous tenofovir concentrations (P = 0.035 and P = 0.045, respectively) among the 3 groups but not in plasma tenofovir concentration (P = 0.577). No correlation was noted between vitreous HIV-1 RNA and vitreous tenofovir concentrations (r = 0.049, P = 0.845). Conclusion: Vitreous tenofovir did not reliably or consistently achieve concentrations sufficient to inhibit viral replication in intraocular tissues due to poor penetration of the blood–retinal barrier (BRB). The higher vitreous tenofovir concentrations were associated with moderate or severe disease compared with mild disease, indicating an association with the severity of BRB disruption. [ABSTRACT FROM AUTHOR]

Objective: To analyze and summarize the clinical and imaging characteristics of patients with cytomegalovirus retinitis (CMVR) relapse after hematopoietic stem cell transplantation (HSCT). Methods: This retrospective case series study recruited patients with CMVR after HSCT. The study compared the patients with stable lesions and CMV-negative aqueous humor after treatment with those with relapse lesions and a CMV DNA load in aqueous humor which had increased again after treatment. The observation indexes were basic clinical information, best-corrected visual acuity, wide-angle fundus photography, optical coherence tomography (OCT), blood CD4+ T lymphocyte count, and aqueous humor CMV load of the patients. We summarized the data and statistically analyzed the differences between the relapse and non-relapse groups, as well as the correlations of the observed indicators. Results: The study recruited 52 patients with CMVR (82 eyes) after HSCT, of whom 11 patients (15 eyes) had recurrence after treatment (21.2%). The recurrence interval was 6.4 ± 4.9 months. The final best-corrected visual acuity of recurrent patients was 0.3 ± 0.3. The number of CD4+ T lymphocytes in recurrence patients at the time of onset was 126.7 ± 80.2/mm3. The median CMV DNA load detected in aqueous humor at the time of recurrence was 8.63 × 103 copies/mL. There was a significant difference in the CD4+ T lymphocyte count between the recurrence and the non-recurrence groups at onset. The onset of visual acuity in recurrence patients was significantly correlated with final visual acuity and recurrence lesion area. The fundus of recurred CMVR showed increased marginal activity of the original stable lesion. Concurrently, yellow-white new lesions appeared around the stable, atrophic, and necrotic lesions. OCT showed new diffuse hyperreflexic lesions in the retinal neuroepithelial layer near the old lesions. Inflammatory punctate hyperreflexes were observed in the vitreous, with vitreous liquefaction and contraction. Conclusion: This study suggests that the clinical features, fundus manifestations, and imaging features of CMVR recurrence after HSCT are different from those at the initial onset. Patients should be closely followed up after their condition is stable to be alert for CMVR recurrence. [ABSTRACT FROM AUTHOR]

Since the introduction of combination antiretroviral therapy (cART) in Japan in 2008, the spectrum of ocular manifestations in patients with human immunodeficiency virus (HIV) has changed. This study, conducted at Tokyo Medical and Dental University Hospital between January 2012 and August 2023, aimed to understand the epidemiology and clinical features of ocular manifestations in patients with HIV during the cART era. Of the 218 patients diagnosed with HIV, 23 (10.55%) exhibited ocular manifestations; all were male, aged 32–73. The most prevalent ocular complication was uveitis (60.67%). Notably, the prevalence of uveitis in this cART era has surged compared to earlier Japanese studies. Our data also suggest a potential direct link between uveitis and HIV, particularly in patients who have not yet undergone cART. However, cytomegalovirus retinitis, another prevalent ocular disease in our study, appeared more strongly associated with patients who commenced cART. Neither ocular condition was significantly correlated with CD4+ T-cell count. Importantly, our observed ocular manifestation prevalence (10.55%) was lower than that in previous studies, emphasizing the potential influence of cART and national healthcare support. These findings provide unique insights into the evolution of ocular manifestations in patients with HIV in Japan amidst cART availability.

Patients with AIDS-related cytomegalovirus (CMV) retinitis receiving combined antiretroviral therapy (cART), but not specific anti-CMV therapy, consistently showed active retinitis for several months. Delayed diagnosis and treatment of CMV retinitis may have severe consequences. Patients first entering care with advanced HIV infection and vulnerability to reactivation of latent CMV infection should be screened immediately for CMV retinitis by dilated indirect ophthalmoscopy and treated with specific anti-CMV therapy without delay, in addition to cART.

Frosted branch angiitis (FBA) is an uncommon form of severe retinal perivasculitis associated with systemic inflammatory/infectious diseases. In this report, we describe a case of FBA and macular edema as a result of immune recovery response in a patient newly diagnosed with HIV infection and cytomegalovirus viremia. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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.

Background: The human immunodeficiency virus infection and acquired immunodeficiency syndrome (HIV/AIDS) is a multi-systemic disease with known manifestations involving all ocular structures from the orbit and ocular adnexa, anterior segment to the retina and vitreous. Some of these manifestations including cytomegalovirus (CMV) retinitis and HIV retinopathy are HIV/AIDS-defining illnesses. The aim of this study is to determine the vitreoretinal manifestations in patients with HIV/AIDS attending an antiretroviral therapy clinic in Nigeria. Methods: This was a prospective, cross-sectional study of consenting, confirmed HIV/AIDS patients attending an antiretroviral therapy clinic in Nigeria. All willing, consecutive patients who gave an informed consent were recruited. Sociodemographic data and clinical information were collected with the use of a structured interviewer–administered questionnaire. Best-corrected visual acuity was recorded. Anterior segment and ocular adnexa examination was performed with a pen torch. Detailed anterior and posterior segment examination was performed with slit lamp biomicroscopy with Volks +78 diopter lens and binocular indirect ophthalmoscopy. The data were analyzed with SPSS (statistical package for social sciences) version 16. Ethical approval was obtained from the institutional ethics committee. Results: Three hundred and eighteen patients were studied of which 85 (26.7%) had disorders affecting the retina and vitreous. The female-to-male ratio was 2:1. More than a third of patients (38.7%) were in the 40–49 years of age group and the mean age was 47.2 years. The most common vitreoretinal lesion was presumed ocular toxoplasmosis present in 9.7% of all respondents. This was closely followed by HIV retinopathy in 3.5%, ocular tuberculosis in 1.8%, and CMV retinitis in 1.6% respondents. Two hundred and seventy-seven (87.1%) respondents were on highly active antiretroviral therapy and 41 (12.9%) were not on treatment. Conclusion: A high prevalence of ocular conditions especially those affecting the retina and vitreous exists in patients with HIV/AIDS attending the antiretroviral therapy clinic in a tertiary hospital in Nigeria. Regular eye examinations are recommended for these patients to prevent potentially visual debilitating disorders.