A COVID-19 perspective of multiple evanescent white dot syndrome (MEWDS).

Multiple evanescent white dot syndrome (MEWDS) is a rare form of posterior uveitis characterized by involvement in the posterior pole and mid-periphery. A viral etiology that provokes an immune-mediated response has been hypothesized to be the inciting factor of the pathology. Recently, there has been an increase in the literature regarding new-onset uveitis and reactivation of previously diagnosed cases of uveitis following COVID-19 vaccinations. The COVID-19 vaccination has been speculated to trigger an immunomodulatory shift in recipients, resulting in an autoimmune event. MEWDS following COVID-19 vaccination was reported in 31 patients. It was most commonly observed following the first dose, affecting 15 patients, and least commonly after the booster dose, in only one patient. MEWDS-like disease following anti-SARS-CoV-2 vaccinations was reported the most in 16 cases after the Pfizer-BioNTech vaccination (BNT162b2 mRNA). Most of these cases had Primary MEWDS without any previous history of a similar event in the past.

Un caso de retinitis herpética no necrosante / A case of non-necrotising herpetic retinitis

En países en vías de desarrollo la principal etiología de uveítis posterior es de origen infeccioso, siendo el herpes virus el agente viral más común, con un amplio espectro de manifestaciones oculares que puede depender del estado inmunológico del paciente: desde una forma leve focal de retinitis herpética no necrosante (RHNN) hasta una forma severa de necrosis retiniana aguda. Presentamos un caso de RHNN por VHS 2 y los diferentes diagnósticos diferenciales planteados previos a su diagnóstico: toxoplasmosis ocular atípica, tuberculosis ocular y necrosis retiniana aguda. Durante su evolución presentó una caída súbita de la agudeza visual a pesar del tratamiento antiviral y con corticoides sistémicos y de la mejoría clínica de la lesión. Este evento conllevó a replantear las entidades sospechadas, estableciendo la RHNN como diagnóstico definitivo por exclusión, lo cual constituyó un reto diagnóstico. (AU)

In developed countries, the main origin of posterior uveitis is an infection. Herpes is the most common viral agent, as it has a wide spectrum of ocular manifestations. These manifestations may depend on the immunological state of the patient, and range from a mild focal form of non - necrotising herpetic retinitis (NNHR) to a severe form of acute retinal necrosis (ARN). A case of NNHR due to Herpes simplex virus type 2 (HSV-2) is reported, along with the different differential diagnostics prior to its diagnosis: atypical ocular toxoplasmosis, ocular tuberculosis, and ARN. During its course, despite the antiviral treatment, systemic corticoids and the clinical improvement of the injury, there was a drastic drop in the visual acuity. This event led to the re-evaluation of the suspected entities, establishing the NNHR as a definitive diagnostic by exclusion, which was a diagnostic challenge (AU)

RETINAL FINDINGS IN PRESUMED INFECTIOUS POSTERIOR UVEITIS AND CORRELATION WITH POLYMERASE CHAIN REACTION RESULTS.

PURPOSE: To correlate demographics, retinal lesion characteristics, and host immune status with the pathogen found on polymerase chain reaction analysis of aqueous fluid in patients with suspected infectious posterior uveitis. METHODS: Medical records of patients who underwent anterior chamber paracentesis for suspected infectious posterior uveitis and had retinal photographs between 2014 and 2016 at a single institution were reviewed. Data collection included demographics, clinical appearance of the lesions, and polymerase chain reaction results. Fundus photographs were evaluated by two masked observers for the clinical features of the retinitis. RESULTS: Twenty-eight patients were included in the study. There was substantial to almost perfect agreement on retinitis location (κ = 0.67) and number (κ = 0.76) between the masked photograph graders. Polymerase chain reaction results were positive for herpes simplex virus or varicella zoster virus in 43%, cytomegalovirus in 11%, and toxoplasmosis in 3%; 43% had negative polymerase chain reaction results. Detection of herpes simplex virus or varicella zoster virus on polymerase chain reaction of the aqueous was associated with paucifocal lesions (82%, P = 0.021) and lesions involving the peripheral retina (91%, P = 0.023), consistent with the diagnosis of acute retinal necrosis. CONCLUSION: These data suggest that the diagnosis of acute retinal necrosis can be reasonably inferred on clinical examination, providing a guide for initial empiric therapy.

ZIKA virus infection causes persistent chorioretinal lesions.

Zika-infected patients can have eye involvement ranging from mild conjunctivitis to severe chorioretinal lesions, however the possible long-term sequelae of infection and timeline to recovery remain unknown. Here we describe the partial recovery of chorioretinal lesions in an immunocompetent patient diagnosed with bilateral posterior uveitis associated with Zika infection and show that some lesions resolved with focal atrophy evident as pigmentary changes on funduscopy. To better understand the progression of the lesions and correlate the changes in fundus imaging with local viral load, immune responses, and retinal damage, we developed a symptomatic mouse model of ocular Zika virus infection. Imaging of the fundus revealed multiple hypopigmentary patches indicative of chorioretinal degeneration as well as thinning of the retina that mirror the lesions in patients. Microscopically, the virus primarily infected the optic nerve, retinal ganglion cells, and inner nuclear layer cells, showing thinning of the outer plexiform layer. During acute infection, the eyes showed retinal layer disorganization, retinitis, vitritis, and focal choroiditis, with mild cellular infiltration and increased expression of tumor necrosis factor, interferon-γ, granzyme B, and perforin. Focal areas of gliosis and retinal degeneration persisted 60 dpi. The model recapitulates features of ZIKA infections in patients and should help elucidate the mechanisms underlying the damage to the eyes and aid in the development of effective therapeutics.

Varicella zoster virus-associated Chorioretinitis: a case report.

BACKGROUND: Chorioretinitis is an unusual form of varicella zoster virus (VZV)-associated uveitis, and no report has described VZV-associated chorioretinitis using serial optical coherence tomography (OCT) images obtained during the course of resolution. CASE PRESENTATION: A 61-year-old woman presented with acute, unilateral vision loss in her right eye. Her visual acuity was count fingers in the right eye and 16/20 in the left eye, and she exhibited skin vesicles on her right forehead. Slit lamp biomicroscopy, funduscopy, OCT, and intraocular fluid analysis were performed. The right eye exhibited multiple inflammatory lesions at the posterior pole, macular edema, and disc swelling on the fundus examination. OCT revealed predominant involvement of the choroid and the retinal pigment epithelium (RPE). Intraocular fluid analysis showed positivity for VZV. The patient was admitted and treated with intravenous acyclovir. Additional oral prednisolone was used to reduce the inflammatory reaction. After 2 weeks of treatment with acyclovir, the lesion resolved, with undulation of the RPE. Her final visual acuity was 20/20. CONCLUSIONS: VZV-associated posterior uveitis may present as multifocal chorioretinitis. Intraocular fluid analysis is important to detect an infectious origin.

Viral Retinopathy in Experimental Models of Zika Infection.

Purpose: Emerging evidence has shown that both congenital and adult Zika virus (ZIKV) infection can cause eye diseases. The goals of the current study were to explore mechanisms and pathophysiology of ZIKV-induced eye defects. Methods: Wild-type or A129 interferon type I receptor-deficient mice were infected by either FSS13025 or Mex1-7 strain of ZIKV. Retinal histopathology was measured at different time points after infection. The presence of viral RNA and protein in the retina was determined by in situ hybridization and immunofluorescence staining, respectively. Growth curves of ZIKV in permissive retinal cells were assessed in cultured retinal pigment epithelial (RPE) and Müller glial cells. Results: ZIKV-infected mice developed a spectrum of ocular pathologies that affected multiple layers of the retina. A primary target of ZIKV in the eye was Müller glial cells, which displayed decreased neurotrophic function and increased expression of proinflammatory cytokines after infection. ZIKV also infected RPE; and both the RPE and Müller cells expressed viral entry receptors TYRO3 and AXL. Retinitis, focal retinal degeneration, and ganglion cell loss were observed after the clearance of viral particles. Conclusions: Our data suggest that ZIKV can infect infant eyes with immature blood-retinal barrier and cause structural damages to the retina. The ocular findings in microcephalic infants may not be solely caused by ZIKV-induced impairment of neurodevelopment.

Viral posterior uveitis.

The causes of posterior uveitis can be divided into infectious, autoimmune, or masquerade syndromes. Viral infections, a significant cause of sight-threatening ocular diseases in the posterior segment, include human herpesviruses, measles, rubella, and arboviruses such as dengue, West Nile, and chikungunya virus. Viral posterior uveitis may occur as an isolated ocular disease in congenital or acquired infections or as part of a systemic viral illness. Many viruses remain latent in the infected host with a risk of reactivation that depends on various factors, including virulence and host immunity, age, and comorbidities. Although some viral illnesses are self-limiting and have a good visual prognosis, others, such as cytomegalovirus retinitis or acute retinal necrosis, may result in serious complications and profound vision loss. Since some of these infections may respond well to antiviral therapy, it is important to work up all cases of posterior uveitis to rule out an infectious etiology. We review the clinical features, diagnostic tools, treatment regimens, and long-term outcomes for each of these viral posterior uveitides.

Chronic herpes simplex virus type 2 encephalitis associated with posterior uveitis.

We report on a patient with chronic herpes simplex virus-2 encephalitis who was characteristic for concomitantly having chronic or recurrent posterior uveitis. A 66-year-old immunocompetent man suffering from a 6-month refractory posterior uveitis developed a 1-month history of impaired short-term memory and orientation. Brain MRI demonstrated hyperintense lesions in the right parietal lobe in diffusion and fluid attenuated inversion recovery (FLAIR) sequences. Cerebrospinal fluid (CSF) examination showed mild pleocytosis and increased protein concentration. Quantitative PCR for HSV-2 DNA was positive in CSF. Treated with acyclovir, his cognitive functions gradually improved and the posterior uveitis was cured. Clinicians must be aware that HSV-2 should be considered in the aetiological investigation of chronic encephalitis in an immunocompetent patient. HSV-2 is well known for its ability to cause unilateral chronic or recurrent posterior uveitis. Therefore, posterior uveitis should be considered as an associated feature of HSV-2 encephalitis.

Clinical manifestations of cytomegalovirus-associated posterior uveitis and panuveitis in patients without human immunodeficiency virus infection.

IMPORTANCE: Little attention has been paid to clinical features of cytomegalovirus (CMV) infections in individuals without human immunodeficiency virus (HIV). OBJECTIVE: To describe the clinical manifestations and comorbidities of patients without HIV infection who have CMV-associated posterior uveitis or panuveitis. DESIGN AND SETTING: Retrospective observational case series in an academic research setting. PARTICIPANTS: The medical records were reviewed of 18 patients (22 affected eyes) diagnosed as having posterior uveitis or panuveitis who had aqueous positive for CMV by polymerase chain reaction techniques. MAIN OUTCOME MEASURES: Demographic data, clinical manifestations, and associated systemic diseases were recorded. RESULTS: Ocular features included focal hemorrhagic retinitis (n = 13) and peripheral retinal necrosis (n = 7). Two eyes had no focal retinal lesions but manifested vasculitis and vitritis. All patients exhibited vitreous inflammation. Inflammatory reactions in anterior segments developed in 14 of 22 eyes (64%). Retinal vasculitis was observed in 16 of 22 eyes (73%) and included mostly arteries (in 13 of 16 eyes [81%]). Eleven of 18 patients were taking immunosuppressive medications (5 for hematologic malignant diseases, 4 for systemic autoimmune diseases, and 2 following organ transplants). One additional patient was diagnosed as having non-Hodgkin lymphoma 3 months after the onset of CMV-associated panuveitis, and another patient had primary immunodeficiency disorder. Of the remaining 5 patients, 2 had diabetes mellitus, and 3 had no associated systemic diseases and exhibited no evidence of immune deficiency. CONCLUSIONS AND RELEVANCE: Cytomegalovirus-associated infections of posterior eye segments can develop in patients without HIV infection who have compromised immune function of variable severity but may occur also in individuals who have no evidence of immune insufficiency. Cytomegalovirus infections located in posterior eye segments in patients without HIV infection caused intraocular inflammatory reaction in all cases and demonstrated more variable clinical presentation than classic CMV retinitis observed in patients with HIV infection.

Infectious causes of posterior uveitis.

The differential diagnosis of posterior infectious uveitis is broad. There are, however, a few common infectious causes of posterior uveitis that should always be considered. The more common infectious causes of posterior uveitis include syphilis, toxoplasmosis, tuberculosis, endogenous endophthalmitis, and viral causes (including herpes simplex virus, herpes zoster virus, and cytomegalovirus). The clinical features, diagnostic tools, and treatment options for each of these are reviewed in this article.

New infectious etiologies for posterior uveitis.

Emergent and resurgent arthropod vector-borne diseases are major causes of systemic morbidity and death and expanding worldwide. Among them, viral and bacterial agents including West Nile virus, Dengue fever, Chikungunya, Rift Valley fever, and rickettsioses have been recently associated with an array of ocular manifestations. These include anterior uveitis, retinitis, chorioretinitis, retinal vasculitis and optic nerve involvement. Proper clinical diagnosis of any of these infectious diseases is based on epidemiological data, history, systemic symptoms and signs, and the pattern of ocular involvement. The diagnosis is usually confirmed by the detection of a specific antibody in serum. Ocular involvement associated with emergent infections usually has a self-limited course, but it can result in persistent visual impairment. There is currently no proven specific treatment for arboviral diseases, and therapy is mostly supportive. Vaccination for humans against these viruses is still in the research phase. Doxycycline is the treatment of choice for rickettsial diseases. Prevention, including public measures to reduce the number of mosquitoes and personal protection, remains the mainstay for arthropod vector disease control. Influenza A (H1N1) virus was responsible for a pandemic human influenza in 2009, and was recently associated with various posterior segment changes.

Infectious causes of posterior uveitis and panuveitis in Thailand.

PURPOSE: To determine the infectious causes of posterior uveitis (PU) and panuveitis (panU) in Thailand. METHODS: We investigated the infectious causes of uveitis involving the posterior segment of the eye by using real-time polymerase chain reaction (PCR) for cytomegalovirus (CMV), herpes simplex virus (HSV-1, HSV-2), varicella zoster virus and Toxoplasma gondii (T. gondii) DNA in intraocular samples of 80 human immunodeficiency virus (HIV)-negative patients. Additionally, in 61 patients, we performed Goldmann-Witmer coefficient (GWC) analysis for T. gondii. RESULTS: Twenty-four (30 %) patients with PU and/or panU had a positive PCR result. Overall, CMV was the most frequently identified organism. While CMV was the most common cause of uveitis in the patients on immunosuppressive medications for nonocular disorders, HSV was the most common cause of posterior and panuveitis in the patients not receiving such medication. In 38 PU patients, CMV was the most common detected pathogen. In 42 panU patients, CMV and HSV-2 were the most frequently identified pathogens. Out of 61 paired samples analyzed for T. gondii by GWC analysis, only 1 revealed a positive result. There was no difference in PCR results between aqueous humor and vitreous samples. CONCLUSIONS: CMV was the most frequently identified infectious organism in posterior and panuveitis of HIV-1-negative Thai patients. Aqueous humor and vitreous samples showed similar diagnostic values in PCR analysis.

Real-time polymerase chain reaction and intraocular antibody production for the diagnosis of viral versus toxoplasmic infectious posterior uveitis.

PURPOSE: The aim of this work was to determine the diagnostic performance of real-time polymerase chain reaction (RT-PCR) and to assess intraocular specific antibody secretion (Goldmann-Witmer coefficient) on samples from patients with signs of posterior uveitis presumably of infectious origin and to target the use of these two biologic tests in the diagnostic of Toxoplasma/viral Herpesviridae posterior uveitis by the consideration of clinical behavior and delay of intraocular sampling. METHODS: Aqueous humour and/or vitreous fluid were collected from patients suspected of having posterior uveitis of infectious origin at presentation (140 samples). The diagnosis was confirmed by quantification of antibodies with the Goldmann-Witmer coefficient (GWC) and for detection of Herpesviridae and Toxoplasma gondii genomes with RT-PCR. Forty-one patients had final diagnosis of uveitis of non-Toxoplasma/non-viral origin and 35 among them constituted the control group. The main outcome measures were sensitivity, specificity, and positive and negative predictive values (PPV and NPV). RESULTS: When pre-intraocular testing indication was compared with final diagnosis, GWC was a more sensitive and specific method than RT-PCR, and was successful in detecting T. gondii, especially if the patient is immunocompetent and the testing is carried out later in the disease course, up to 15 months. For viral Herpesviridae uveitis, the sensitivity and PPV of PCR evaluation was higher than detected with GWC with respectively 46% compared with 20% for sensitivity and 85% versus 60% for PPV. In either viral retinitis or toxoplasmosis infection, RT-PCR results were positive from 24 h, although GWC was not significant until 1 week after the onset of signs. In toxoplasmosis patients, positive RT-PCR results were statistically correlated with the chorioretinitis area (more than three disc areas; p = 0.002), with the age older than 50 (p = 0.0034) and with a clinical anterior inflammation (Tyndall ≥1/2+) and panuveitis; (p = 0.0001). CONCLUSIONS: For the diagnosis of viral or toxoplasmosis-associated intraocular inflammation, the usefulness of laboratory diagnosis tools (RT-PCR and GWC) depends on parameters other than the sensitivity of the tests. Certain patient characteristics such as the age of the patients, immune status, duration since the onset of symptoms, retinitis area, predominant site and extent of inflammation within the eye should orientate the rational for the choice of laboratory testing in analysis of intraocular fluids.

Necrotizing and nonnecrotizing variants of herpetic uveitis with posterior segment involvement.

OBJECTIVE: To describe the clinical characteristics and prognosis of diverse variants of herpetic uveitis with posterior segment involvement. METHODS/DESIGN: Retrospective observational study of clinical, imaging, and laboratory data. RESULTS: Twenty-five patients were classified as having typical acute retinal necrosis (ARN) and 13 patients as not having ARN (non-ARN). Age at symptom onset, sex, bilateral involvement, and prevalence of viral species were not significantly different between patients in the ARN and non-ARN groups. All patients in the ARN group had necrotic retinal lesions that progressed quickly, whereas only 4 of 13 patients (31%) in the non-ARN group (P < .001) had necrotic retinal lesions that progressed slowly. Necrotizing variants were noted in 29 of 38 patients (76%), including 4 patients with slowly progressing lesions. Nine remaining patients in the non-ARN group had non-necrotizing posterior uveitis without retinal lesions; their cases were characterized by vitritis, vasculitis, and/or papillitis, or as panuveitis without any distinct features (5 patients [38.5%]). At 6 months' follow-up, visual acuity of less than 0.1 developed in 13 of 25 patients (52%) in the ARN group and in 4 of 13 patients (31%) in the non-ARN group (P = .30). CONCLUSIONS: Herpes simplex and varicella zoster viruses can cause a wide spectrum of clinical manifestations ranging from severe ARN to slow-progressing necrotizing and non-necrotizing types of inflammation. The non-ARN variants are currently underdiagnosed. Patients with these variants could potentially benefit from earlier recognition and treatment.

Polymerase chain reaction analysis of aqueous and vitreous specimens in the diagnosis of posterior segment infectious uveitis.

PURPOSE: To assess polymerase chain reaction (PCR) analysis of intraocular fluid as a test for infectious uveitis of the posterior segment in a representative patient population. DESIGN: Retrospective, interventional case series. METHODS: One hundred and thirty-three patients with possible infectious chorioretinitis underwent PCR testing of aqueous or vitreous in a university setting. Baseline characteristics predictive of test positivity were identified. Positive and negative predictive values were calculated. RESULTS: Four hundred and thirty-three PCR tests of 105 aqueous and 38 vitreous specimens (mean, 3.3 tests per patient) identified 77 of the 95 patients with a final clinical diagnosis of infectious uveitis (81%). Herpes simplex virus, varicella zoster virus, and cytomegalovirus PCR analysis were performed in almost all cases, with fewer tests for toxoplasmosis or Epstein-Barr virus. Clinical features associated with positive PCR results were retinal vascular inflammation (P < .001), optic nerve involvement (P = .008), immunocompromised state (P = .039), and extensive retinitis (P = .002). Cases sampled within one week of presentation were more likely to have positive PCR results than those sampled later (P = .071). The predictive value of positive and negative tests was 98.7% and 67.9%, respectively, in this patient group. Alteration in treatment based on PCR and syphilis serologic results led to resolution in 25 of 26 patients after treatment was changed. CONCLUSIONS: PCR testing is a useful adjunct in the diagnosis of infectious causes of posterior uveitis. Cases with vascular or optic nerve inflammation, extensive retinitis, or immunocompromise are more likely to have positive PCR results and may benefit from PCR testing of aqueous humor.

Posterior segment manifestations of human immunodeficiency virus/acquired immune deficiency syndrome.

Ocular manifestations can occur in up to 50% of human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) patients and posterior segment involvement is the most common presentation. The posterior segment manifestations of AIDS can be divided into four categories: retinal vasculopathy, opportunistic infections, unusual malignancies and neuro-ophthalmologic abnormalities. Retinal microvasculopathy and cytomegalovirus (CMV) retinitis are the most common manifestations, even in the era of highly active anti-retroviral therapy (HAART). Highly active anti-retroviral therapy has been shown to cause regression of CMV retinitis, reduce the incidence of CMV-related retinal detachments, and prolong patient survival. Immune recovery uveitis is a new cause of vision loss in patients on HAART. Diagnosis and treatment are guided by the particular conditions and immune status of the patient.

Usefulness of aqueous humor analysis for the diagnosis of posterior uveitis.

PURPOSE: To assess the clinical usefulness of aqueous fluid analysis for the diagnosis and treatment of patients suspected of having infectious posterior uveitis (PU). DESIGN: Case-control study. PARTICIPANTS: From 2002 through 2005, 152 eyes from 152 patients with active PU (16 of whom were immunosuppressed) underwent diagnostic aqueous testing. As controls, 20 patients with Fuchs' heterochromic uveitis and 20 patients with age-related cataract were included. METHODS: Aqueous samples were examined by real-time polymerase chain reaction (PCR) and by pathogen-specific analysis of intraocular antibody production (Goldmann-Witmer coefficient [GWC]) for herpes simplex virus (HSV), varicella zoster virus (VZV), cytomegalovirus (CMV), and the parasite Toxoplasma gondii. MAIN OUTCOME MEASURES: Results of aqueous analysis and any adverse effects of aqueous sampling. Correlations between the results of aqueous testing and clinical characteristics as well as the treatment of patients. RESULTS: Of 152 patients, 44 (29%) had positive results for at least one diagnostic assay (37/136 [28%] immunocompetent and 7/16 [44%] immunocompromised patients). None of the controls had positive results using PCR or GWC. A positive result was obtained predominantly in patients with focal chorioretinitis (37/87 [40%]) and in extensive retinitis (7/9 [78%]), whereas in multifocal chorioretinitis, neuroretinitis, and retinal vasculitis only a few samples demonstrated positive results (2/19, 1/29, and 0/10, respectively). Of 37 immunocompetent PU patients with positive results, 28 (76%) cases were caused by T. gondii, whereas viral infections were most common in immunocompromised patients (5/7 [71%]). In immunocompetent and toxoplasmosis PU patients, GWC was the most informative assay (34/37 [92%] and 28/30 [93%], respectively), in contrast to immunosuppressed patients (PCR positive in 5/7 and GWC positive in 4/7). Independent of the immune status of patients, positive PCR results were observed more frequently in viral infections than in toxoplasmosis (P<0.001). As a consequence of aqueous analysis, change of treatment was necessary in 36 patients (24%). None of the patients experienced complications during or after aqueous sampling. CONCLUSIONS: Despite the posterior location of inflammation, aqueous analyses with PCR and GWC for HSV, VZV, CMV, and T. gondii revealed an infectious cause in 29% of patients with PU.