Search

Good syndrome (GS) is a rare primary immunodeficiency in adults consisting of hypogammaglobulinemia and thymoma that affects both cellular and humoral immunity. It usually appears in patients between the 4th and 6th decade of life and affects both genders equally. Ophthalmological clinical presentation is highly variable; associations with herpetic keratitis, toxoplasmosis, and cytomegalovirus retinitis (CMVR) have been described. GS associated with CMVR is uncommon. Ophthalmologists may be the first to diagnose systemic disease and change the outcome. Only18 cases of CMVR have been described, most of them unilateral with poor visual outcomes. We discuss the clinical features of CMVR in patients with reported GS, pathogenesis, and outline a work-up for diagnosis. CMVR in an apparently healthy patient should encourage the clinician to search for human immunodeficiency virus (HIV) and non-HIV-associated immunosuppression., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Umbilical cord blood (UCB) transplants (UCBTs) are becoming increasingly common in the treatment of a variety of hematologic and nonhematologic conditions. The T cells from UCB are naïve T cells, which have not yet been exposed to antigens and therefore do not contain T cells with specific immune functions against viruses. Cytomegalovirus (CMV) infections occur in more than 80% of patients after UCBT compared to other types of transplantation. Anti-CMV medications are currently restricted, with ganciclovir, foscarnet, and valganciclovir being the most common in China; however, with limited efficacy and considerable side effects, all these drugs are susceptible to viral resistance. In recent years, cytomegalovirus-specific T cells (CMVST) have advanced the treatment of viral infections in immunodeficient patients. CMVST usually uses the same donor as hematopoietic stem cell transplantation. CMVST should be administered to UCBT patients because of the absence of donors after UCBT. In China, there is no report on the use of CMVST to treat CMV infection after UCBT, and foreign reports are also limited. This paper reported a 20-year-old male patient with acute myeloid leukemia who developed cytomegalovirus retinitis (CMVR) after umbilical cord blood transplantation. After ineffective viral treatment, he was treated with a third-party donor CMVST and was successfully transformed into CMV nucleic acid negative., Competing Interests: The authors declare no competing interests., (Copyright © 2022 Na Li et al.)

Ganciclovir (GCV) is an antiviral drug approved for treatment of cytomegalovirus (CMV) retinitis. It can be delivered to the eye via systemic administrations. However, local delivery of GCV that targets the retina is considered as an alternative to increase efficacy of the treatment and lessen side effects. Thus, this study aimed to develop formulations of transferrin (Tf)-conjugated liposomes containing GCV (Tf-GCV-LPs) for intravitreal injection and topical instillation. Tf-GCV-LPs were prepared by the reverse-phase evaporation technique and then conjugated to Tf. Their physicochemical properties were evaluated. The optimized formulation was selected and subjected to the cytotoxicity test, cellular uptake study in the human retinal pigment epithelial cells (the ARPE-19 cells) and antiviral activity evaluation. The results showed that physicochemical properties of Tf-GCV-LPs were affected by formulation compositions. The optimized Tf-GCV-LPs had a particle size lower than 100 nm with a negative value of zeta potential. They were safe for the ARPE-19 cells. These Tf-GCV-LPs were taken up by these cells via Tf receptors-mediated endocytosis and showed inhibitory activity on CMV in the infected cells. Therefore, the optimized Tf-GCV-LPs could be accepted as a promising drug delivery system for targeted GCV delivery to the retina in the treatment of CMV retinitis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Aims: Cases of infectious uveitis in immunodeficient patients may present with atypical clinical features because the clinical course of disease is usually affected by the compromised immune system. Therefore, it is sometimes difficult to determine the correct diagnosis. The aim of this study was to evaluate a prevalence of immunodeficient HIV-negative individuals among patients with infectious uveitis and to assess diagnostic and therapeutic approaches. Methods: A retrospective study. Results: In years 2003-2017, we diagnosed 594 patients with infectious uveitis. In 35 of them, infectious uveitis occurred on the basis of immunodeficiency (malignancy, immunosuppressive therapy etc.). The most common infectious uveitis was cytomegalovirus retinitis, followed by acute retinal necrosis, herpetic anterior uveitis, endogenous fungal endophthalmitis, toxoplasmic retinochoroiditis, progressive outer retinal necrosis and syphilis. In indicated cases, intraocular fluid examination was a valuable diagnostic tool. After initiation of treatment, improvement of BCVA was observed in 13 eyes, stabilization in 13 eyes and deterioration in 11 eyes. In some patients who experienced adverse effects of medication, the recommended doses were decreased. Conclusion: Our experience shows that patients with diagnoses of acute retinal necrosis or progressive outer retinal necrosis have a poor visual prognosis. The occurrence of cytomegalovirus retinitis signifies a very unfavorable survival prognosis in patients who underwent hematopoietic stem cell transplantation; the patients in our study died within 1 year from cytomegalovirus retinitis diagnosis.

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]

Unlabelled: Human immunodeficiency virus (HIV) has the ability to affect any organ in the body. In 70% of HIV-infected patients ocular manifestations were observed, which in the vast majority reflect the systemic disease and may be the first sign of a disseminated infection., Aim: The purpose of this paper is to determine the prevalence and the clinical aspects of cytomegalovirus retinitis in HIV/AIDS (Acquired Immunodeficiency Syndrome) patients., Method: The study is retrospective, conducted in the Ophthalmology Office of "Matei Bals" Infectious Diseases Hospital in Bucharest during the period August 1, 2007 - August 1, 2013. Each patient was examined thoroughly at the slit lamp biomicroscope by using a lens of 90D and a 20D lens using the indirect microscope after administration of topical mydriatics., Results: 131 patients were followed for HIV / AIDS with posterior segment ocular involvement. 36.64% of the 131 patients having affected the posterior segment have been diagnosed with CMV retinitis., Conclusions: Doctors should be aware of the existence of ocular damage in HIV/AIDS and to emphasize the importance of regular ophthalmologic examination of patients with HIV/AIDS.

Background: Cytomegalovirus retinitis is a neglected disease in resource-poor settings, in part because of the perceived complexity of care and because ophthalmologists are rarely accessible. In this paper, we describe a pilot programme of CMV retinitis management by non-ophthalmologists. The programme consists of systematic screening of all high-risk patients (CD4 <100 cells/mm3) by AIDS clinicians using indirect ophthalmoscopy, and treatment of all patients with active retinitis by intravitreal injection of ganciclovir. Prior to this programme, CMV retinitis was not routinely examined for, or treated, in Myanmar., Methods: This is a retrospective descriptive study. Between November 2006 and July 2009, 17 primary care AIDS clinicians were trained in indirect ophthalmoscopy and diagnosis of CMV retinitis; eight were also trained in intravitreal injection. Evaluation of training by a variety of methods documented high clinical competence. Systematic screening of all high-risk patients (CD4 <100 cells/mm3) was carried out at five separate AIDS clinics throughout Myanmar., Results: A total of 891 new patients (1782 eyes) were screened in the primary area (Yangon); the majority of patients were male (64.3%), median age was 32 years, and median CD4 cell count was 38 cells/mm3. CMV retinitis was diagnosed in 24% (211/891) of these patients. Bilateral disease was present in 36% of patients. Patients with active retinitis were treated with weekly intravitreal injection of ganciclovir, with patients typically receiving five to seven injections per eye. A total of 1296 injections were administered., Conclusions: A strategy of management of CMV retinitis at the primary care level is feasible in resource-poor settings. With appropriate training and support, CMV retinitis can be diagnosed and treated by AIDS clinicians (non-ophthalmologists), just like other major opportunistic infections.

This paper provides an appreciation of the various forms and consequences of retinal inflammation caused by human herpesviruses. Herpes simplex virus types 1 and 2, varicella zoster virus, cytomegalovirus and Epstein-Barr virus are known to cause retinitis. The prognosis of herpetic retinitis remains poor because it is associated with a high incidence of complications, both during and after the acute disease phase. On diagnosis of retinal necrosis, antiviral treatment must be started promptly to limit disease progression; following this, prophylactic maintenance therapy may be required.

Cytomegalovirus (CMV) retinitis is a common ocular complication of immunosuppression. The management of CMV retinitis has been continuously evolving over the last decade. The mainstay of therapy remains ganciclovir and foscarnet. However, increasing resistance and ongoing toxicities to these agents remain a challenge. Additional frequently utilised agents include cidofovir and fomivirsen. The advent of highly active antiretroviral therapy (HAART) has allowed the restoration of immunocompetency to many patients previously challenged by CMV infection. In some circumstances, HAART has even eliminated the need for ongoing antiviral therapy. This paper reviews the current treatment modalities, including their toxicities and dosing recommendations.

This paper concerns the ophthalmic assessment of patients with acquired immunodeficiency syndrome (AIDS) for a number of eye conditions and in particular cytomegalovirus (CMV) retinitis. CMV has been the most common opportunistic infection associated with AIDS and the leading cause of blindness among AIDS patients. There have been early indications of a widespread fall in CMV prevalence internationally following the introduction of a new highly active antiretroviral triple (HAART) therapy. Our study sought to assess the position for Ireland. Our cohort was the entire population of stage IV AIDS patients attending the country's leading referral centre. The total number of patients examined was 167 and the period of examination was 1 May 1995 to 30 April 1997. HAART was introduced in March 1996, so the data permitted a 'before and after' comparison of various clinical findings. The incidence of new CMV cases was found to be 4 among the 102 patients examined in the first 12-month period and one among 107 patients examined in the second 12-month period. There were accompanying declines in HIV-related noninfectious retinal vasculopathy (HIVR), keratitis and other conditions. The findings are promising, but we argue that caution is needed in assessing long-term trends. In the paper we discuss a number of methodological issues in the collection and analysis of the clinical data and in the interpretation of results.

Background: Cytomegalovirus (CMV) retinitis is the most common ocular opportunistic infection in patients with AIDS. CMV retinitis is often asymptomatic and usually appears when the patient's CD4 lymphocyte levels fall below 50/mm3. The infection may present a variety of clinical appearances and must be carefully differentiated from cotton-wool spots in early infection., Purpose: This paper reviews the natural history of CMV infection in both the normal population and in patients with AIDS. CMV retinitis presenting in AIDS patients is then described in detail with clinical presentations of fundus features. Finally, the management of patients who may be at risk or have developed CMV retinitis is reviewed. Recent data on suggested management protocols are also provided., Conclusions: Cases of CMV retinitis will continue to increase as the AIDS epidemic progresses. The primary care practitioner will play an increasingly important role in the diagnosis and management of patients with this infection.

Cytomegalovirus (CMV) infection of the retina is the commonest potentially blinding ocular manifestation of AIDS. Recently the acyclic nucleoside dihydroxypropoxymethyl guanine (DHPG, ganciclovir) has become available to treat sight-threatening CMV retinopathy. This paper reports the clinical features and results of ganciclovir therapy in 48 patients seen over a four-year period. Seven patients were excluded from the study due to inadequate followup, leaving 41 patients as the study group. All patients responded clinically to this therapy. Patients were treated initially with high-dose ganciclovir (1 0 mglkglday) and then continued on lower dose treatment (5 mg/kg/day) indefinitely. Significant bone marrow toxicity developed in 12 patients (29.3%) requiring temporary cessation of therapy. Patients treated with ganciclovir retained vision and had increased survival times when compared to untreated patients. A poor visual outcome occurred when there was involvement of the macula or optic acquired nerve head at presentation or when there was an interruption of ganciclovir therapy. [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]

Introduction: The aim of this study was to evaluate the value of interleukin (IL)-8 in the development and management of cytomegalovirus retinitis (CMVR) in HIV-negative patients. Methods: A retrospective case series from January 2014 to May 2018 was conducted. Forty patients (40 eyes) received intravitreal injection of ganciclovir (IVG). The aqueous levels of the cytomegalovirus (CMV) DNA and IL-8 in each follow-up visit were tested. The initial and final best-corrected visual acuity (BCVA), the course of treatment, the recurrence rate, and the occurrence of complications were recorded and analyzed. Results: The aqueous value of IL-8 was significantly correlated with the aqueous level of the CMV DNA during treatment but was not associated with the BCVA or the number of IVG. No recurrence occurred in the condition in which a low aqueous IL-8 level was set as the endpoint of the treatment. Conclusion: In HIV-negative patients with CMVR, IL-8 was closely associated with CMV DNA concentration in the aqueous humor. The real-time aqueous level of IL-8 could be used as one of the evidences of disease recovery. [ABSTRACT FROM AUTHOR]

IRU is the most common form of immune reconstitution inflammatory syndrome in HIV-infected patients with cytomegalovirus retinitis who are receiving highly active antiretroviral therapy (HAART). Among patients with CMV in the HAART era, immune recovery may be associated with a greater number of inflammatory complications, including macular edema and epiretinal membrane formation. Given the range of ocular manifestations of HIV, routine ocular examinations and screening for visual loss are recommended in patients with CD4 counts <50 cells/μL. With the increasing longevity of these patients due to the use of HAART, treatment of IRU may become an issue in the future. The aim of this paper is to review the current literature concerning immune recovery uveitis. The definition, epidemiology, pathophysiology, clinical findings, complications, diagnosis, and treatment are presented. [ABSTRACT FROM AUTHOR]

Purpose: To determine the incidence of contralateral eye involvement and retinal detachment in HIV-infected patients with cytomegalovirus retinitis treated with repeated intravitreous ganciclovir. Methods: In a prospective cohort study in Northern Thailand, HIV-infected patients with cytomegalovirus retinitis were treated with antiretroviral therapy and intravitreous ganciclovir injections and followed for 3 months for contralateral cytomegalovirus retinitis and retinal detachment. Results: Of 49 participants with unilateral cytomegalovirus retinitis at enrollment, 7 developed contralateral eye involvement (4.8/100 person-months, 95% CI 1.9–9.8). Of 105 eyes without a retinal detachment at enrollment, 6 developed a retinal detachment (2.0/100 eye-months, 95% CI 0.7–4.3). Baseline clinical factors were not associated with the development of either outcome. Conclusion: Eyes treated with intravitreous ganciclovir experienced retinal detachment at a rate similar to other populations treated with systemic antivirals. The risk of contralateral eye involvement was relatively high during the first 3 months after initial diagnosis despite the institution of antiretroviral therapy. [ABSTRACT FROM AUTHOR]

Background: Cytomegalovirus (CMV) retinitis in patients with Non-Hodgkin's Lymphoma (NHL) can occur even in the presence of high CD 4 counts and can behave differently when compared to CMV retinitis in human immunodeficiency (HIV) patients. It, therefore, becomes important to understand its varied presentations and the challenges in management of these cases. The aim of this study was to analyse the various patterns of presentations and outcomes of CMV Retinitis in patients with NHL. Study design: A retrospective chart review of seven eyes of four patients of NHL presenting with CMV retinitis between June 2017 and May 2020 was done. Methods: Clinical patterns of CMV Retinitis, CD4 counts at the time of presentation and the duration of treatment along with recurrences and time for recurrence of retinitis were assessed. Results: Granular or indolent retinitis (6 out of 7 eyes) was the commonest form of CMV retinitis in patients of NHL. Three patients had a presenting CD4 count above 150 cells/mm3 and none of them were below 50 cells/mm3. Floaters were the commonest presenting complaint. All patients had vitritis and majority of the patients (3 out of 4) had anterior chamber (AC) inflammation. Two out of the 4 patients had a recurrence (mean time 33.8 days) after stopping the maintenance phase of ganciclovir and one patient had significant myelosuppression related to oral valganciclovir which required discontinuation of the drug. Conclusion: CMV retinitis in NHL patients is usually of an indolent or granular type and can occur even in the presence of high CD4 counts as compared to patients with HIV. These patients may require a long term maintenance in view of frequent recurrences after discontinuation of treatment. [ABSTRACT FROM AUTHOR]

Purpose: To analyze predisposing conditions in Turkish patients with CMV retinitis and to compare HIV-positive and HIV-negative patients. Methods: We reviewed medical charts and ocular images of 41 patients with CMV retinitis diagnosed between 1996 and 2019. Results: Eleven patients (27%) had HIV infection and 30 were immunocompromised from diverse causes. Initial visual acuity, type, zone, and extent of CMV retinitis, and response to anti-CMV treatment were not significantly different between the two groups. Vitreous haze and panretinal occlusive vasculopathy were the presenting features only in non-HIV patients, seen in 34% and 16% of eyes, respectively. Although not statistically significant, recurrent CMV retinitis was more common in non-HIV patients (17.4% vs. 4.3%/eye-year) and immune recovery uveitis was more common in HIV patients (43% vs. 26%/eye-year). Visual outcomes were similar. Final visual acuity of 1 logMAR or worse was significantly associated with the recurrence of CMV retinitis (odds ratio 9.67; p = 0.01) and also with the occurrence of immune recovery uveitis (odds ratio 4.31; p = 0.058). Conclusions: Diverse immunocompromising conditions are more commonly associated with CMV retinitis than HIV infection in Turkish patients. Intraocular inflammation was more commonly associated with active retinitis in non-HIV patients and immune recovery uveitis was more common in HIV patients. [ABSTRACT FROM AUTHOR]

Purpose: To explore the potential use of ultra-wide-field (UWF) imaging for screening of cytomegalovirus retinitis (CMVR) in AIDS patients. Methods: Ninety-four patients whose CD4 count was below 200 cells/μL were enrolled in a prospective study. Each patient underwent UWF imaging and indirect ophthalmoscopy. The main outcome measures were the concordance and detection rates of these 2 approaches and the sensitivity and specificity of UWF imaging. Results: Twenty-seven eyes in 18 patients were diagnosed with CMVR by the indirect ophthalmoscopy. UWF imaging missed the diagnosis in 1 eye because of a zone 3 CMVR lesion. The UWF image showed several CMVR patterns and locations: hemorrhagic necrotizing lesion, granular lesion, frosted branch angiitis, and optic neuropathy lesion. The concordance of the 2 approaches was excellent for the diagnosis of CMVR, classification of CMVR pattern, and location of CMVR. The detection rates of UWF imaging and indirect ophthalmoscopy were 14.0% (26/186; 95% CI 0.089–0.190) and 14.5% (27/186; 95% CI 0.094–0.196), respectively (p = 1.000). The sensitivity and specificity of UWF imaging were 96.3 and 100%, respectively. Conclusions: UWF imaging is capable of documentation of different CMVR lesions and AIDS-related CMVR screening when examination by an ophthalmologist is not available. [ABSTRACT FROM AUTHOR]

Introduction: The present study aimed to investigate the effect of anti-cytomegalovirus (anti-CMV) therapy at different stages on retinal detachment in patients with acquired immunodeficiency syndrome (AIDS) and cytomegalovirus retinitis (CMVR).Methods: Ninety-seven patients with AIDS and CMVR diagnosed and treated at the Ophthalmology and Infection Center of Beijing You'an Hospital, affiliated with Capital Medical University, from November 2017 to January 2020 were retrospectively analyzed. Of the 138 eyes included, 30 eyes with concomitant retinal detachment were enrolled as the study subjects. The eyes with retinal detachment were divided into a pre-induction group, an intra-induction group, and a post-induction group of anti-CMV therapy. The occurrence and characteristics of retinal detachment at different stages of anti-CMV therapy were observed.Results: Retinal detachment occurred in 30 of the 138 eyes of 97 patients, with an incidence of retinal detachment of 21.74%. Retinal detachment occurred in eight eyes in the pre-induction group, with an incidence of 26.67%, and in four eyes in the intra-induction group, with an incidence of 13.33%. The difference in incidence between the two groups was statistically significant (P = 0.000). Retinal detachment occurred in 18 eyes in the post-induction group, with an incidence of 60%. The difference in incidence between the intra-induction group and the post-induction group was statistically significant (P = 0.001).Conclusion: The incidence of retinal detachment at the intra-induction stages of anti-CMV therapy was lower than that at the pre-induction stage, and retinal detachment during the anti-CMV therapy predominantly occurred after the end of the induction stage. [ABSTRACT FROM AUTHOR]

Objective: Rare disease Background: Good syndrome (thymoma with immunodeficiency) is a frequently missed and forgotten entity. It is a rare cause of combined B and T cell immunodeficiency in adults. To date, fewer than 200 patients with Good syndrome have been reported in the literature. Case Report: We report a case of type AB Masaoka-Koga stage I thymoma which predated the evidence of immune dysregulation by 5 years, manifesting as bilateral cytomegalovirus retinitis, multiple bouts of pneumonia, and bronchiectasis in a HIV-seronegative 55-year-old man. Intravitreal ganciclovir was administered in addition to intravenous systemic ganciclovir, which resulted in severe neutropenic sepsis. A thorough immunodeficiency workup confirmed the presence of hypogammaglobulinemia with complete absence of B cells and reduced CD4/CD8 ratio. The patient responded well to monthly intravenous immunoglobulin replacement therapy, with no further episodes of infection since then. The immunoglobulin level doubled after 1 year of treatment. However, as the patient refused further intravitreal and CMV-targeted treatment, his vision did not recover. Conclusions: Clinicians should be aware that thymoma can precede the onset of immunodeficiency. Clinical suspicion should be heightened in at-risk patients who present with multiple bouts of infection, particularly in thymoma cases with adult-onset immune dysfunction. It is of paramount importance to follow up those patients with annual clinical reviews and immunodeficiency screening. [ABSTRACT FROM AUTHOR]

Purpose: To summarize the prognostic factors of cytomegalovirus (CMV) retinitis (CMVR) in HIV-negative patients treated with multiple intravitreal injections (IVs) of ganciclovir.Methods: A retrospective cohort study (70 eyes) was conducted. Clinical signs, initial and final best corrected visual acuity (BCVA), initial aqueous load of CMV DNA, course of treatment, and occurrence of complications were recorded and analyzed.Results: A positive correlation was found between the baseline and the final best corrected visual acuity (P < .001) and between the initial aqueous CMV DNA load and the number of IVs (P = .01). A lesion close to the posterior pole (P < .001) and a larger retinal lesion (P = .002) remarkably led to worse visual prognosis.Conclusions: Poor visual prognosis was significantly associated with poor initial visual acuity, proximity of lesion to the posterior pole, and an extensive CMV lesion. The treatment duration was positively correlated with the initial aqueous CMV DNA load. [ABSTRACT FROM AUTHOR]

Purpose: Cytomegalovirus retinitis (CMVR) is a serious and potentially sight-threatening infection in immunocompromised individuals. Strategies for the management of drug-resistant CMVR are described. Methods: A case of severe bilateral CMVR in a single lung transplant patient, with UL97 mutation conferring ganciclovir-resistance, is presented. Treatment with standard antiviral agent and adjuvant leflunomide, immunosuppression modifications (calcineurin inhibitors and corticosteroid), intravitreal antiviral therapy and novel use of CMV-immunoglobulin is described. A literature review to support drug-resistant CMVR management is presented. Results: Severe and progressive CMV retinitis was refractory to intravitreal foscarnet and systemic leflunomide. Drug-toxicity restricted systemic antiviral therapy options. The use of combined leflunomide and CMV-immunoglobulins, in the absence of viremia, has not been previously reported. Loss of ganciclovir-resistance was eventually observed permitting successful treatment with systemic and intravitreal ganciclovir. Conclusions: Drug-resistant CMVR is a complex clinical challenge. Multiple systemic and local treatment strategies may be necessary but toxicity, resistance, and co-morbidities may severely restrict available options. [ABSTRACT FROM AUTHOR]

Background: The incidence of ocular complications in HIV-infected patients varies from 42% to 75% and some of these complications may lead to blindness. Here we report a rare case of retroviral disease with cytomegalovirus (CMV) retinitis in one eye and papillitis secondary to cryptococcus meningitis in the other eye. Case Report: A 14 year old Malay girl who was diagnosed with AIDS since birth through vertical transmission presented with fever, headache, seizure and chronic poor vision in the right eye for about 8 months duration. She was on antiretroviral therapy (HAART). Visual acuity in the right eye was only perception to light and in the left eye was 6/9. Both anterior segments were unremarkable. Fundoscopy of the right eye showed generalised shallow retinal detachment and left swollen hyperaemic disc. Computed tomography (CT) scan of the brain was normal. Lumbar puncture opening pressure was normal as well. A diagnosis of retroviral disease with cryptococcal meningitis, right advanced CMV retinitis and left papillitis was made. Patient was treated with HAART regime, ganciclovir, amphotericin B, flucytosine and fluconazole. The papillitis responded well to treatment. However, the CMV retinitis persisted. Conclusion: In conclusion, AIDS patients are susceptible to multiple opportunistic infection that may co-exist with different severity in either eye. Prompt diagnosis and early medical intervention may preserve vision and improve life expectancy. [ABSTRACT FROM AUTHOR]

Purpose: To compare clinical features, complications, and outcomes of CMV retinitis in non-HIV immunocompromised patients with HIV infected patients.Methods: A retrospective study of patients diagnosed with CMV retinitis with or without HIV infection was performed. Results: Thirty-five eyes from 27 patients (median follow up 26 months) were included. Six patients had HIV infection, the others were immunocompromised from a range of causes. The baseline visual acuity (VA) was similar in the two groups. Prevalence of different types of retinitis (fulminant/indolent) was similar in the two groups. Presence of vitreous haze ≥1+ (p = .041), presence of arteritis, (p = .016) and widespread vascular occlusion (p = .003) were more common in the non-HIV group.Conclusion: CMV retinitis can present with different features depending on the cause of immunocompromise. Evidence of intraocular inflammation such as vitritis, retinal arteritis, and vascular occlusions was more common in HIV-negative subjects. [ABSTRACT FROM AUTHOR]

Purpose: To study the role of ultra-wide field (UWF) fundus autofluorescence (FAF) in the management of CMV (cytomegalovirus) retinitis.Material and methods: In this prospective, observational, non-randomized study, we followed up patients with active CMV retinitis on UWF fundus photograph (FP) and UWF-FAF.Results: A total of 16 patients (24 eyes) were studied. There were 13 males and mean age of patients was 37 (range 9-56) years. On UWF FP, out of 24 eyes, 13 (54.2%) had granular lesions, 3 (12.5%) had necrotizing pattern, 1 (4.1%) had a frosted branch angiitis (FBA), and 7 (29.2%) had a mixed pattern. UWF-FAF showed better delineation of borders of lesions in 7 eyes (29.1%), larger area of involvement in 8 eyes (33.3%), picked up 7 of 9 (77.77%) eyes of recurrence and helped differentiate cotton wool spots from retinitis lesion in one eye.Conclusion: UWF-FAF is useful in the management of CMV retinitis. [ABSTRACT FROM AUTHOR]

Purpose: To characterize the presenting features of cytomegalovirus (CMV) retinitis in HIV-positive patients in a developing country in the HAART era.Methods: Retrospective chart review of all patients with CMV retinitis seen at a tertiary-care referral center between January 2006 to June 2017. Demographic and clinical data were collected to study the presenting features and risk factors for blindness.Results: Fifty-five patients with treatment-naïve CMV retinitis were enrolled; 75% were males. CD4 counts were below 50 cells/µL in 51.1%. Bilateral presentation was seen in 61.5%. Half (50.6%) of the eyes were blind at first examination. Zone 1 involvement was present in 46% of the eyes. Retinal area involvement > 25% was the only factor associated significantly with higher incidence of blindness (p = 0.016).Conclusions: There was extensive and bilateral presentation of CMV retinitis due to delayed presentation. Screening for CMV retinitis, irrespective of CD4 counts, may help in developing nations. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the prevalence and characteristics of ocular manifestations of human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) in patients treated at a tertiary referral center in Taiwan during a time of highly active antiretroviral therapy (HAART) Materials and Methods: A retrospective cohort study in Taiwan was performed between January 2006 and July 2016. Ocular examination and systemic information were recorded from the HIV-infected patients. Results: 1242 patients with HIV/AIDS were identified. Ninety patients had ophthalmic records, and HIV-related ocular manifestations were reported in 57 patients. The most prevalent ocular manifestations were cytomegalovirus (CMV) retinitis, ocular syphilis, and HIV microvasculopathy. Mean CD4 count was significantly lower in patients with HIV-related ocular manifestations compared to those without. Conclusion: We found that lower CD4 count, especially <200 cells/μL, was a significant factor for detecting HIV-related ocular manifestations. Comprehensive ophthalmic screening in high-risk group is helpful for early diagnosis and prompt treatment of sight-threatening ocular complications. [ABSTRACT FROM AUTHOR]

Human cytomegalovirus (HCMV) generates a significant clinical burden worldwide, particularly among the immune compromised. In approximately 30% of untreated HIV/AIDS patients without access or sufficient response to antiretroviral therapies, for example, HCMV causes a sight-threatening retinitis. To study the mechanisms of AIDS-related HCMV retinitis, our lab has for many years used a mouse model in which a mixture of mouse retroviruses induces murine AIDS after approximately 10 weeks, rendering otherwise resistant mice susceptible to opportunistic pathogens. This immunodeficiency combined with subretinal inoculation of murine cytomegalovirus yields a reproducible model of the human disease, facilitating the discovery of many clinically relevant virologic and immunologic mechanisms of retinal destruction which we summarize in this review. [ABSTRACT FROM AUTHOR]

To report a case of cytomegalovirus retinitis (CMVR) with hypopyon and intense ocular inflammation. An 81-year-old female was referred to our hospital with a suspicion of postoperative endophthalmitis in the left eye. She had been treated with etoposide and prednisolone for non-Hodgkin's lymphoma. Examination revealed mutton-fat keratic precipitates and numerous infiltrating cells in the anterior chamber with hypopyon. The fundus was invisible due to intense vitreous opacity. Systemic and topical administration of antibiotics was started, and vitrectomy was performed. However, the ocular symptoms did not respond to treatment. Vitrectomy was repeated twice, but severe endophthalmitis findings recurred soon after surgery. Finally, a comprehensive viral PCR test using the intraocular fluid detected CMV with 3.34 × 109 copies/ml, leading to a diagnosis of CMV retinitis. If the causative agent is not identified in endophthalmitis that develops in immunosuppressive patients, CMV may also be considered as the possible cause. [ABSTRACT FROM AUTHOR]

Cytomegalovirus (CMV) retinitis is one of the rare but debilitating presentations of the CMV infection in children with leukemia. Herein, we report a 12-year-old boy with acute myeloid leukemia complicated by rapid progressive visual loss during relapse of leukemia. The definite diagnosis of CMV retinitis was made after vitreous aspiration. Despite prompt treatment and ophthalmologic intervention, he died because of AML relapse. Viral infections, especially cytomegalovirus infection, may present with vague clinical pictures during any time of chemotherapy, which may not be easily distinguishable from bacterial or fungal retinitis and also chemotherapy-induced retinopathies. Clinician should consider CMV retinitis in seropositive patients especially those without detectable viremia. [ABSTRACT FROM AUTHOR]

Purpose: To describe the incidence of and risk factors for visual acuity (VA) loss in patients with AIDS and cytomegalovirus (CMV) retinitis.Methods: A total of 132 patients were included. The main outcome measurements were the incidences of VA loss to ≤20/50 and ≤20/200.Results: The incidences of VA loss to ≤20/50 and ≤20/200 were 0.22/eye-year (EY) and 0.12/EY, respectively. Risk factors for the incidence of VA loss to ≤20/50 were low nadir CD4+ T-cell count (adjusted hazard ratio [aHR], 3.1), large area of retinitis (aHR, 3.7), and no immune recovery (IR) (aHR, 13.9). Risk factors for the incidence of VA loss to ≤20/200 were not receiving highly active antiretroviral therapy (HAART) (aHR, 4.4) and large retinitis area (aHR, 2.1).Conclusions: The incidence of VA loss in eyes affected by CMV retinitis was high. The use of HAART, particularly with subsequent immune recovery, substantially reduced the incidence of VA loss. [ABSTRACT FROM AUTHOR]

Purpose: To characterize the immunologic profile in aqueous humor (AqH) of HIV-infected individuals with cytomegalovirus retinitis (CMVr) or ocular syphilis and to assess if AqH and plasma represent independent cytokine compartments.Methods: Concentrations of 27 cytokines in AqH and plasma of HIV-infected individuals with CMVr (n = 23) or ocular syphilis (n = 16) were measured by multiplex assay. Cytokine profiles of both groups were compared.Results: Individuals with CMVr had higher plasma concentrations of interleukin (IL)-7, IL-8, IL-10, interferon (IFN)-γ, IFN-α2, G-CSF, IP-10 and IL-1α; as well as higher AqH concentrations of IL-1α, IP-10 and GM-CSF than those with ocular syphilis. AqH and plasma levels correlated only for IP-10 in both ocular infections.Conclusions: Individuals with CMVr had higher plasma cytokine levels than those with ocular syphilis. The immunologic profiles in AqH and plasma are independent. Therefore, AqH cytokine concentrations cannot be inferred from plasma cytokine concentrations in the population studied. [ABSTRACT FROM AUTHOR]

Purpose of Review: Ophthalmologic conditions were among the earliest described findings in patients with the acquired immunodeficiency syndrome (AIDS). The purpose of this review is to highlight recent changes in the pathophysiology and management of ophthalmologic conditions in patients infected with the human immunodeficiency virus (HIV). Recent Findings: The introduction of highly active antiretroviral therapy (HAART) in 1996 changed ophthalmologic findings from predominantly acute infectious diseases to chronic, slowly progressive, debilitating conditions. HIV-associated neuroretinal disorder infrequently leads to blindness, but it causes visual disability in a large percentage of patients. Cytomegalovirus retinitis is now seen less commonly in the USA, but it remains an important cause of blindness in HIV-infected patients from developing countries. Immune recovery uveitis has emerged as a major cause of visual disability in the USA. Summary: As HIV has become a chronic disease, visual disability due to chronic noninfectious diseases have become increasingly important. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the surgical outcomes, complications and postoperative progression in HIV patients undergoing cataract surgery in a teaching hospital.Methods: A retrospective cohort study of patients with HIV/AIDS who had cataract surgery from January 2000 until December 2011 at a tertiary referral multidisciplinary hospital in Singapore.Results: We identified 44 eyes from 29 patients. Preoperatively, 41.3% had no ophthalmic manifestations of HIV/AIDS, while 16 eyes had quiescent cytomegalovirus retinitis (CMVR). Postoperatively, 1 eye developed new CMVR, while 1 eye had reactivation of previous CMVR. Of eyes with new or previous CMVR, 1 eye developed rhegmatogenous retinal detachment (RD) postoperatively. Only 3 eyes had prolonged postoperative inflammation. There were no cases of endophthalmitis or cystoid macular edema. Postoperative improvement of at least two Snellen lines was achieved in 86.6% of eyes.Conclusions: Cataract surgery in HIV patients is generally safe, regardless of CD4 count, but their general and ocular health should be optimized preoperatively. [ABSTRACT FROM AUTHOR]

Purpose: To compare changes in the demographic profile and ocular manifestations in patients with HIV in the pre-HAART and HAART era in North India.Methods: In this single-center cross-sectional study, 100 HIV patients receiving HAART and 96 HIV patients in the pre-HAART era were enrolled. Prevalence of ocular manifestations of HIV was calculated for both cohorts.Results: The prevalence of ocular manifestations was not statistically different in the two eras (38%, SE: 4.85% in HAART era; 41.67%, SE: 5% in pre-HAART era) (p = 0.60). Mean CD4 counts were lower in the pre-HAART era compared with the HAART era (p < 0.001). In the HAART era, cytomegalovirus (CMV) retinitis and HIV retinopathy continued to remain the most common infectious and non-infectious cause of visual morbidity.Conclusions: While the introduction of HAART has resulted in a major impact on the overall health of patients with HIV, the spectrum of ocular disease remains largely unchanged in developing countries such as India. [ABSTRACT FROM AUTHOR]

Purpose: To describe leflunomide use in the treatment of drug resistant cytomegalovirus retinitis. Leflunomide has been shown to be effective in the treatment of systemic CMV viremia.Methods: Retrospective chart review of patients with CMV retinitis treated with leflunomide.Results: Two HIV-negative organ transplant recipients with UL 97 mutation resistant-genotype CMV were identified. Patient 1 developed CMV viremia post-kidney transplant and subsequently bilateral CMV retinitis. Retinitis progressed, despite intravitreal injection of ganciclovir and foscarnet, and IV foscarnet and oral valganciclovir. Retinitis control was achieved with the addition of oral leflunomide. Disease remained inactive for 22 months. Patient 2 developed CMV retinitis after lung transplant. Disease progressed despite intravitreal foscarnet injections and oral valganciclovir. Control of retinitis was achieved with addition of oral leflunomide, allowing cessation of intravitreal therapy. Disease remained inactive until his death.Conclusions: Leflunomide may be considered as a treatment option for resistant CMV retinitis. [ABSTRACT FROM AUTHOR]

Background: Cytomegalovirus (CMV) retinitis is one of the most important tissue-invasive CMV diseases in immunocompromised patients. Since 1980, non-invasive diagnostic methods, notably the CMV antigenemia assay, have been widely used as adjunct tests to diagnose tissue-invasive CMV diseases. However, there are limited data on the diagnostic value of the CMV antigenemia assay for diagnosing CMV retinitis. Materials and Methods: We performed a retrospective review of all cases of CMV retinitis at Asan Medical Center, Seoul, South Korea over a 9-year period. The diagnosis of CMV retinitis was made by experienced ophthalmologists according to medical history and an ophthalmoscopic appearance of typical retinopathy, together with absence of an alternative diagnosis. Results: We analyzed 44 patients with CMV retinitis (affecting 57 eyes) for whom the CMV antigenemia assay was performed. Of the 44 patients, 31 (70%) were HIV-uninfected and 13 (30%) were HIV-infected. The overall sensitivity of the CMV antigenemia assay was 66% (95% confidence interval [CI] 50-80%). The test's sensitivity showed a non-significant trend towards being higher in HIV-infected patients than in HIV-uninfected patients (sensitivity 85% vs 58%, respectively, P = 0.16). In a subgroup analysis of the 35 patients without other concurrent tissue-invasive CMV disease, the sensitivity of the CMV antigenemia assay was 57% (95% CI 40-74%). Conclusions: The CMV antigenemia assay has limited value as a non-invasive diagnostic adjunct test for CMV retinitis. Therefore, the results of the assay need to be interpreted in the context of underlying disease, clinical presentation, and ophthalmoscopic findings. [ABSTRACT FROM AUTHOR]

Background: The aim of this study is to analyse the clinical features of HIV patients with cytomegalovirus retinitis (CMVR) developing immune recovery uveitis (IRU) while on highly active antiretroviral therapy (HAART) and to identify the risk factors, visual outcomes and complications of IRU. Results: Majority ( n = 26, 86.7 %) of patients were male, with 76.7 % ( n = 23) of patients having bilateral disease. Twenty-seven eyes (50.9 %) had both anterior uveitis and vitritis. The median CD4 at IRU was 210 cells/μL (IQR 140-279), with 86.7 % having CD4 >100 cells/μL. The median duration from initiation of HAART to IRU was significantly different between those <50 years old (median 763 days, IQR 174-1872 days) and those ≥50 years old (median 161 days, IQR 84.5-278 days). Fourteen eyes (26.4 %) had loss of one or more Snellen lines visual acuity at 6 months while the rest maintained or improved vision. Complications developed in 21 eyes, with cataract (66.7 %), glaucoma and ocular hypertension (33.3 %) being the most common. The risk of complications was associated with the absolute difference in CD4 counts at IRU and at HAART commencement ( p = 0.041). Age was also negatively associated with the duration from HAART to IRU ( p = 0.005, Spearman's rho coefficient = −0.503). Conclusions: It is common to have both anterior uveitis and vitritis in IRU. There was a positive association between the increase in CD4 from HIV to IRU diagnoses and the risk of developing complications. Younger patients appeared to develop IRU later than older patients after HAART, suggesting that long-term follow-ups are essential for these patients. [ABSTRACT FROM AUTHOR]

Purpose: To calculate the incidence of, and to identify the risk factors for developing contralateral eye involvement among patients with AIDS and unilateral cytomegalovirus retinitis (CMV retinitis), who were treated, in the era of highly-active antiretroviral therapy (HAART), with repetitive intravitreal ganciclovir injections.Materials and Methods: The clinical records of 119 patients were included. The main outcome measurement was the occurrence of contralateral eye involvement.Results: Over a mean follow-up period of 1.6 years, the overall incidence rate of contralateral involvement was 0.17/person-year. The cumulative incidence of contralateral involvement at 6 months and 1 year was 23.8% and 28.4%, respectively. Receiving HAART at the visit before the event was associated with a decreased risk of developing contralateral retinitis (hazard ratio [HR] = 0.26, P = 0.002).Conclusions: The use of HAART, associated with subsequent immune recovery, significantly reduced the incidence of contralateral eye involvement by approximately 75% among patients in our setting. [ABSTRACT FROM AUTHOR]