Diagnostic Approach to Ocular Toxoplasmosis

Toxoplasmic retinochoroiditis is deemed a local event, which may fail to evoke a detectable systemic immune response. A correct diagnosis of the disease is a necessary basis for estimating its clinical burden. This is not so difficult in a typical clinical picture. In atypical cases, further diagnostic efforts are to be installed. Although the aqueous humor may be analyzed for specific antibodies or the presence of parasitic DNA, the DNA burden therein is low, and in rare instances a confirmation would necessitate vitreous sampling. A laboratory confirmation of the diagnosis is frustrated by individual differences in the time elapsing between clinical symptoms and activation of specific antibody production, which may result in false negatives. In congenital ocular toxoplasmosis, a delay in the onset of specific local antibody production could reflect immune tolerance. Herein, the authors attempt to provide a simple and practicable algorithm for a clinically tailored diagnostic approach in atypical instances

Rubella virus-associated uveitis in a nonvaccinated child

PURPOSE: To report presumed Fuchs heterochromic uveitis (FHU) associated with Rubella virus (RV)-specific intraocular antibody production in a child who was not vaccinated against rubella. DESIGN: Observational case report. METHODS: We examined a 13-year-old boy with chronic anterior uveitis complicated by mature cataract. Two aqueous humor (AH) samples taken with an interval of four weeks were analyzed for intraocular antibody production against RV by calculation of the Goldmann-Witmer coefficient. RESULTS: The patient showed all the clinical signs for FHU: iris atrophy, stellate keratic precipitates, and cataract. Analysis of the AH demonstrated intraocular antibody production against RV in two sequential samples. CONCLUSIONS: The data show that RV-associated uveitis can already present during childhood. Moreover, this finding suggests that nonvaccinated children may be at risk to develop uveitis after RV infectio

No Value for Routine Serologic Screening for Borrelia burgdorferi in Patients with Uveitis in the Netherlands

Purpose To determine whether routine serologic screening for Borrelia burgdorferi and subsequent aqueous or vitreous humor analysis is useful in patients with uveitis. Design Cross-sectional study. Methods All patients referred to our tertiary uveitis referral clinic in the period of from January 1, 2004 to October 31, 2014, in whom routine serologic screening for Borrelia burgdorferi (IgG as determined by enzyme-linked immunosorbent assay and confirmed by immunoblot) was performed were retrospectively reviewed. In patients with an unclassified uveitis, aqueous and vitreous humor and cerebrospinal fluid were also analyzed. Local antibody production was determined by Goldmann-Witmer coefficient calculation or polymerase chain reaction for B burgdorferi. The seroprevalence of B burgdorferi among patients with uveitis was compared to the general population. Results Borrelia burgdorferi screening was performed in 1126 uveitis patients (44.3% male, mean age 45.9 ± 19.6 years). The seroprevalence of B burgdorferi among uveitis patients was 3.7% (95% confidence interval 2.6%-4.8%) (n = 42) as compared to 5%-10% in the general Dutch population. Of these 42 patients, 14 (1.2% of all uveitis patients) had an unclassified uveitis, 7 of whom underwent aqueous humor (n = 5) or vitreous humor (n = 2) analysis and cerebrospinal fluid analysis (n = 2). None of the patients had local antibody production in either ocular or cerebrospinal fluid. Conclusion The prevalence of immunoblot-confirmed B burgdorferi IgG seropositivity in our uveitis patients is only slightly lower as compared to the general Dutch population. Intraocular antibody production and DNA was absent in all tested patients. These findings do not support routine serologic examination for Borrelia in uveitis patients

Challenges of Diagnosing Viral Anterior Uveitis

The viral causes of anterior uveitis (AU) emerged with the use of novel molecular diagnostic tests and serologic tests adapted for small volumes (Goldmann-Witmer Coefficient). The viral causes of AU may be underestimated, and some of the presumed idiopathic AU cases will probably be proven to be of viral origin in the coming years. So far, a viral origin of AU was suspected in patients who presented with unilateral hypertensive AU. It is not clear which clinical presentations should raise a suspicion of viral etiology. There is an overlap in the clinical manifestations of AU caused by viruses and other non-viral forms of AU. A viral cause of AU should be suspected in patients with unilateral AU, exhibiting small or medium sized KPs, some form of iris atrophy, high IOP and early development of a cataract and the definitive diagnosis can be proven by aqueous humor analysis

No Value for Routine Serologic Screening for Borrelia burgdorferi in Patients with Uveitis in the Netherlands

Purpose To determine whether routine serologic screening for Borrelia burgdorferi and subsequent aqueous or vitreous humor analysis is useful in patients with uveitis. Design Cross-sectional study. Methods All patients referred to our tertiary uveitis referral clinic in the period of from January 1, 2004 to October 31, 2014, in whom routine serologic screening for Borrelia burgdorferi (IgG as determined by enzyme-linked immunosorbent assay and confirmed by immunoblot) was performed were retrospectively reviewed. In patients with an unclassified uveitis, aqueous and vitreous humor and cerebrospinal fluid were also analyzed. Local antibody production was determined by Goldmann-Witmer coefficient calculation or polymerase chain reaction for B burgdorferi. The seroprevalence of B burgdorferi among patients with uveitis was compared to the general population. Results Borrelia burgdorferi screening was performed in 1126 uveitis patients (44.3% male, mean age 45.9 ± 19.6 years). The seroprevalence of B burgdorferi among uveitis patients was 3.7% (95% confidence interval 2.6%-4.8%) (n = 42) as compared to 5%-10% in the general Dutch population. Of these 42 patients, 14 (1.2% of all uveitis patients) had an unclassified uveitis, 7 of whom underwent aqueous humor (n = 5) or vitreous humor (n = 2) analysis and cerebrospinal fluid analysis (n = 2). None of the patients had local antibody production in either ocular or cerebrospinal fluid. Conclusion The prevalence of immunoblot-confirmed B burgdorferi IgG seropositivity in our uveitis patients is only slightly lower as compared to the general Dutch population. Intraocular antibody production and DNA was absent in all tested patients. These findings do not support routine serologic examination for Borrelia in uveitis patients

Cytokines and Chemokines Involved in Acute Retinal Necrosis

Purpose: To investigate which cytokines and chemokines are involved in the immunopathogenesis of acute retinal necrosis (ARN), and whether cytokine profiles are associated with clinical manifestations, such as visual outcome. Methods: Serum and aqueous humor (AH) samples of 19 patients with ARN were analyzed by multiplex immunoassay. Infectious controls consisted of 18 patients with rubella virus-associated Fuchs' uveitis and 20 patients with ocular toxoplasmosis all confirmed by intraocular fluid analyses. The control group consisted of seven paired AH and serum samples from seven noninflammatory control patients with age-related cataract. In each sample, 4 anti-inflammatory, 12 proinflammatory, 2 vascular, and 4 other immune mediators were measured. In addition, various clinical characteristics were assessed. Results: In ARN, 10 of the 22 mediators, including most proinflammatory and vascular mediators such as IL-6, IL-8, IL-18, MIF, MCP-1, Eotaxin, IP-10, IL-15, sICAM-1, and sVCAM-1, were significantly elevated when compared to all controls. In addition, one anti-inflammatory mediator (IL-10) was significantly elevated in ARN as compared to the controls. No association was found between the time of sampling and the extent and levels of immune mediator expression. Conclusions: The pathogenesis of ARN is characterized by the presence of predominantly proinflammatory cytokines and chemokines with high expression levels as compared to other infectious causes of uveitis. There are no indications for an obvious Th-1 or Th-17 pathway. The combined data suggest that immune mediator expression is related to severity of disease, which is more fulminant in ARN, rather than to a specific uveitis entity

Immunology and Microbiology Cytokines and Chemokines Involved in Acute Retinal Necrosis

PURPOSE. To investigate which cytokines and chemokines are involved in the immunopathogenesis of acute retinal necrosis (ARN), and whether cytokine profiles are associated with clinical manifestations, such as visual outcome. METHODS. Serum and aqueous humor (AH) samples of 19 patients with ARN were analyzed by multiplex immunoassay. Infectious controls consisted of 18 patients with rubella virusassociated Fuchs' uveitis and 20 patients with ocular toxoplasmosis all confirmed by intraocular fluid analyses. The control group consisted of seven paired AH and serum samples from seven noninflammatory control patients with age-related cataract. In each sample, 4 antiinflammatory, 12 proinflammatory, 2 vascular, and 4 other immune mediators were measured. In addition, various clinical characteristics were assessed. RESULTS. In ARN, 10 of the 22 mediators, including most proinflammatory and vascular mediators such as IL-6, IL-8, IL-18, MIF, MCP-1, Eotaxin, IP-10, IL-15, sICAM-1, and sVCAM-1, were significantly elevated when compared to all controls. In addition, one anti-inflammatory mediator (IL-10) was significantly elevated in ARN as compared to the controls. No association was found between the time of sampling and the extent and levels of immune mediator expression. CONCLUSIONS. The pathogenesis of ARN is characterized by the presence of predominantly proinflammatory cytokines and chemokines with high expression levels as compared to other infectious causes of uveitis. There are no indications for an obvious Th-1 or Th-17 pathway. The combined data suggest that immune mediator expression is related to severity of disease, which is more fulminant in ARN, rather than to a specific uveitis entity. Keywords: acute retinal necrosis, cytokine, aqueous humor A cute retinal necrosis (ARN) represents an intraocular herpetic infection characterized by severe inflammatory symptoms, including progressive retinitis and choroiditis with occlusive vasculitis and papillitis. Acute retinal necrosis has a poor visual prognosis, due to extensive retinal inflammation with necrosis, occlusive vasculitis, frequent development of retinal detachment, and optic disc atrophy. 1,2 Varicella zoster virus (VZV) is the most frequent cause of ARN in adults, 3 but it may also be caused by other members of the herpes virus family, including herpes simplex virus (HSV) types 1 and 2, and rarely, cytomegalovirus. The aim of this study was to investigate which cytokines and chemokines are involved in the immunopathogenesis of ARN, caused by HSV or VZV, and whether specific cytokine profiles are associated with clinical manifestations. To this end, cytokine and chemokine expression patterns in the AH and serum were determined by multiplex immunoassay (Luminex, Austin, Texas, USA) technology, highly suited for high-throughput analysis in microvolumes, including ocular fluids

Betacoronavirus Adaptation to Humans Involved Progressive Loss of Hemagglutinin-Esterase Lectin Activity

Human beta1-coronavirus (β1CoV) OC43 emerged relatively recently through a single zoonotic introduction. Like related animal β1CoVs, OC43 uses 9-O-acetylated sialic acid as receptor determinant. β1CoV receptor binding is typically controlled by attachment/fusion spike protein S and receptor-binding/receptor-destroying hemagglutinin-esterase protein HE. We show that following OC43's introduction into humans, HE-mediated receptor binding was selected against and ultimately lost through progressive accumulation of mutations in the HE lectin domain. Consequently, virion-associated receptor-destroying activity toward multivalent glycoconjugates was reduced and altered such that some clustered receptor populations are no longer cleaved. Loss of HE lectin function was also observed for another respiratory human coronavirus, HKU1. This thus appears to be an adaptation to the sialoglycome of the human respiratory tract and for replication in human airways. The findings suggest that the dynamics of virion-glycan interactions contribute to host tropism. Our observations are relevant also to other human respiratory viruses of zoonotic origin, particularly influenza A virus