Diagnostic pars plana vitrectomy and aqueous analyses in patients with uveitis of unknown cause.

PURPOSE: To compare the yield of diagnostic pars plana vitrectomy (PPV) with the yield of aqueous analyses in patients with uveitis of unknown cause. METHODS: Seventy-five consecutive patients (84 eyes) with uveitis involving posterior eye segment who undergo a diagnostic PPV from 2005 through 2009 were retrospectively reviewed. Vitreous specimens were simultaneously analyzed by microbiological culture, flow cytometry, and cytology as well as by polymerase chain reaction and for intraocular antibody production by Goldmann-Witmer coefficient. In 53 eyes, both aqueous and vitreous samples were assessed. The primary outcome measure was the comparison between vitreous and aqueous analyses. RESULTS: Vitreous analysis was positive in 18 of 84 eyes (21%). Positive results indicated infectious uveitis in 12 of 18 cases (67%) and lymphoma in 6 of 18 (33%) cases. Of the 53 eyes with both aqueous and vitreous samples available, aqueous analysis revealed the diagnosis in 6 of 53 eyes and vitreous in 9 of 53 eyes. Unilateral uveitis (P = 0.022), panuveitis and uveitis posterior (P ≤ 0.001), preoperative immunosuppressive therapy (P = 0.004), and increasing age (P = 0.018) were associated with an increased diagnostic yield of PPV. Overall, 1 year after PPV, median visual acuity improved from 20/200 to 20/80 (Snellen, P ≤ 0.001). Of 18 patients who were on immunosuppressive treatment before PPV, 8 (44%) were able to stop immunosuppressive therapy during 1-year follow-up. The complications of PPV consisted predominantly of cataract development (33/65, 51%). CONCLUSION: Diagnostic PPV with the analysis of vitreous fluid by multiple laboratories for infectious and malignant disorders was useful in diagnosing uveitis of unknown cause. Previous aqueous analysis was especially valuable for the diagnosis of intraocular infections and may therefore decrease the number of patients who would otherwise undergo an invasive diagnostic PPV. Furthermore, PPV was associated with improved visual acuity and decreased use of immunosuppressive therapy.

High concordance of intraocular antibody synthesis against the rubella virus and Fuchs heterochromic uveitis syndrome in Slovenia.

PURPOSE: To prospectively study the relationship between Fuchs heterochromic uveitis syndrome (FHUS) and intraocular production of specific antibodies against the rubella virus (RV) in Slovenia. METHODS: Using the Goldmann-Witmer coefficient technique, intraocular synthesis of specific antibodies against RV, herpes simplex virus, varicella-zoster virus, cytomegalovirus (CMV) and Toxoplasma gondii-specific immunoglobulin G antibodies was performed in 12 consecutive patients with clinically diagnosed FHUS and 12 patients with idiopathic recurrent unilateral anterior uveitis (AU) without clinical features of FHUS. RESULTS: Specific intraocular antibody synthesis against RV with a positive Goldmann-Witmer coefficient was proven in 11 of 12 (92%) FHUS patients, and in none of the non-FHUS AU patients (Fisher's exact test <0.0001). In one patient with FHUS, specific antibodies against RV and varicella-zoster virus were concurrently detected. Specific antibodies against cytomegalovirus were detected in one patient with unilateral recurrent AU. CONCLUSIONS: Intraocular production of specific immunoglobulin G against RV was proven in the majority of tested cohort of FHUS patients from Slovenia as compared to the group of patients with idiopathic AU, which suggests that RV is involved in the pathogenesis of FHUS in this geographic area.

Intraocular and serum cytokine profiles in patients with intermediate uveitis.

PURPOSE: To study the intraocular and serum cytokine and chemokine profile in patients with intermediate uveitis (IU) at various stages of inflammatory activity. METHODS: Institutional, prospective association study. Paired aqueous humor (AqH) and serum samples were collected from 36 consecutive IU patients and 10 controls. The concentrations of interleukin (IL)-1ß, IL-6, IL-8, IL-10, IL-12p70, tumor necrosis factor (TNF)-α, CC--chemokine ligand 5/regulated upon activation normal T-cell expressed, and secreted (CCL5/RANTES), CC--chemokine ligand 3/macrophage inflammatory protein 1alpha (CCL3/MIP-1α), CCL4/MIP-1ß, and CC--chemokine ligand 2/monocyte chemotactic protein--1 (CCL2/MCP-1) were measured in both AqH and serum by multiplex immunoassay. Main outcome measures were serum and intraocular levels of the analyzed cyto- and chemokines. RESULTS: Patients with IU had higher serum levels of TNF-α than non-uveitic controls (p<0.0001), whereas their AqH TNF-α levels did not show a difference (p=0.323). IU patients had higher intraocular levels of IL-1ß, IL-6, IL-8, IL-10, IL-12p70 and CCL2/MCP-1 than the controls (p=0.020, 0.001, <0.0001, 0.005, 0.003, and 0.003, respectively). Active stages of IU were characterized by higher levels of IL-6, IL-8, CCL5/RANTES and CCL2/MCP-1 (p=0.003, <0.0001, 0.033, and 0.033, respectively). Higher levels of IL-6 and IL-8 were found in IU patients with cystoid macular edema (CME) compared to non-CME IU patients (p=0.026 and 0.012, respectively). Significant positive correlations between various observed mediators were present in the AqH of IU patients only. CONCLUSIONS: Significantly elevated concentrations of multiple intraocular cytokines were found in IU patients, especially IL-6 and IL-8 in those with CME and active disease. In serum elevated TNF-α levels were observed in IU patients. Our findings improve the understanding of the pathogenesis of IU and contribute to the identification of factors which may contribute to the activity of IU.

Comparison of rubella virus- and herpes virus-associated anterior uveitis: clinical manifestations and visual prognosis.

PURPOSE: To compare the clinical characteristics and visual prognosis of patients with anterior uveitis (AU) and intraocular fluid analysis positive for rubella virus (RV), herpes simplex virus (HSV), or varicella zoster virus (VZV). DESIGN: Retrospective, observational study. PARTICIPANTS: The study included 106 patients with AU and positive polymerase chain reaction (PCR) results, Goldmann-Witmer coefficients (GWCs), or both, for RV (n = 57), HSV (n = 39), or VZV (n = 10). METHODS: Clinical records of the included patients were analyzed retrospectively; demographic constitution, ophthalmologic characteristics, and visual prognosis were compared. MAIN OUTCOME MEASURES: Age, gender, and diverse clinical and laboratory characteristics, including course and laterality of AU; prevalence of positive results for PCR, GWC, or both; conjunctival redness; corneal edema; history of keratitis; presence of keratic precipitates; synechiae; heterochromia; and grade of inflammation. In addition, complications and visual acuity at 1 and 3 years of follow-up were recorded. RESULTS: All 3 types of viral AU were characterized by unilateral involvement (80%-97%). Rubella virus AU was characterized by younger age at onset and chronic course and typically was associated with cataract at presentation. Heterochromia was present in 23% of RV AU patients. Anterior uveitis associated with HSV or VZV occurred characteristically in older patients and frequently followed an acute course. Clinical features associated with herpetic AU included conjunctival redness, corneal edema, history of keratitis, and development of posterior synechiae. Herpes simplex virus AU often had severe anterior chamber inflammation, whereas the presence of vitritis was more common in RV AU and VZV AU. The prevalence of documented intraocular pressure (IOP) of more than 30 mmHg (25%-50%; P = 0.06) and development of glaucoma (18%-30%; P = 0.686) were similar in all 3 groups. Focal chorioretinal scars were seen in 22% of RV AU eyes, in 0% of HSV AU eyes, and in 11% of VZV AU eyes (P = 0.003). Visual prognosis was favorable for all 3 groups. CONCLUSIONS: These observations identify clinical differences between RV AU, HSV AU, and VZV AU and may be of particular value to ophthalmologists who are unable to carry out intraocular fluid analysis to discriminate between these types of viral AU. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Immunoblot and Polymerase Chain Reaction to Diagnose Ocular Syphilis and Neurosyphilis in HIV-positive and HIV-negative Patients.

Purpose: To evaluate immunoblot (IB) and polymerase chain reaction (PCR) to diagnose ocular- and neurosyphilis. Methods: Prospective cross-sectional study. Aqueous humor (AH) and cerebrospinal fluid (CSF) samples were tested for treponemal DNA or antibodies to treponemal antigens. Results: Thirteen of 106 cases had positive syphilis serology of which 69.2% were HIV+ (median CD4+ = 181 cells/µL). Four cases met CDC criteria for neurosyphilis (3 confirmed, 1 probable) and 2 additional cases required neurosyphilis treatment according to UpToDate algorithms. All AH and CSF samples tested PCR negative. Five cases were CSF IB+ and 3 cases AH IB+. Using our classification, eight patients had confirmed neurosyphilis, one had probable neurosyphilis, three had confirmed ocular syphilis and nine had probable ocular syphilis. Conclusion: Our findings suggest that IB of AH and CSF provides additional evidence to diagnose ocular and neurosyphilis and allows us to classify them as probable or confirmed.

Polymerase Chain Reaction and Goldmann-Witmer Coefficient to Examine the Role of Epstein-Barr Virus in Uveitis.

PURPOSE: To use polymerase chain reaction (PCR) and Goldmann-Witmer Coefficient (GWC) calculation to search for evidence that Epstein-Barr virus (EBV) causes uveitis. METHODS: A prospective cross-sectional study where participants with positive multiplex EBV PCR results were further investigated by: 1) real-time PCR for EBV viral loads (VL) and 2) EBV GWC. RESULTS: Eleven of 106 consecutive uveitis patients (10.4%) had positive multiplex PCR for EBV on aqueous humor sampling and 7/11 (63.6%) were HIV-positive. Only 4/10 (40%) cases had detectable intraocular EBV VLs which were always lower than the blood or plasma VL. EBV GWC was negative in all 10 cases tested. In 9/11 (81.8%) of these cases an alternative, more plausible cause of uveitis was identified. CONCLUSION: We found no evidence of active intraocular replication or antibody production to prove that EBV caused uveitis in these cases. In most cases an alternative treatable cause of uveitis was identified.

Polymerase Chain Reaction and Goldmann-Witmer Coefficient Testing in the Diagnosis of Infectious Uveitis in HIV-Positive and HIV-Negative Patients in South Africa.

PURPOSE: To use polymerase chain reaction (PCR) and Goldmann-Witmer coefficient (GWC) calculation to diagnose infectious uveitis. METHODS: Prospective cross-sectional study. RESULTS: Twenty-seven of 106 patients had positive PCR and/or GWC results on aqueous humor (AH) sampling and 15 of 27 (55.6%) were HIV-positive. Patients with non-anterior uveitis (NAU) were more likely to be HIV+ (p = 0.005). More than 1 possible pathogen was identified in 9 of 27 patients of whom 7 were HIV+. The final clinical diagnosis was discordant with AH findings in 9 of 27 cases. A positive EBV PCR result was associated with a discordant diagnosis (p = 0.001). All cases of herpetic anterior uveitis (42.9% HIV+) tested PCR-/GWC+ while all cases of herpetic NAU tested PCR+/GWC- (83.3% HIV+). All rubella virus cases were PCR+/GWC+. CONCLUSION: PCR is useful to diagnose herpetic NAU in HIV+ patients while GWC is useful to diagnose herpetic anterior uveitis.

The Etiology of Intraocular Inflammation in HIV Positive and HIV Negative Adults at a Tertiary Hospital in Cape Town, South Africa.

PURPOSE: To describe the patterns of uveitis in South Africa. METHODS: Prospective cross-sectional study. RESULTS: One hundred and six patients were enrolled and 37.7% had human immune-deficiency virus (HIV) infection. Anterior and panuveitis occurred most frequently. Infectious, non-infectious and idiopathic uveitis were diagnosed in 66.0%, 17.0% and 17.0% of all cases, respectively. Eighty percent of HIV+ cases had infectious uveitis. Overall, intraocular tuberculosis (IOTB), herpetic and syphilitic uveitis were the commonest infectious causes. Sarcoidosis and HLA-B27-associated uveitis were the commonest non-infectious causes. In anterior uveitis, HIV+ cases most frequently had probable IOTB, syphilitic or idiopathic uveitis while HIV- cases had possible IOTB, idiopathic or HLA-B27-associated uveitis. In panuveitis, HIV+ cases mostly had syphilis, probable IOTB, toxoplasma and varicella-zoster virus whereas HIV- cases mostly had possible IOTB, sarcoidosis and idiopathic uveitis. CONCLUSION: Infectious uveitis is common in South Africa, especially amongst HIV+ patients. Causes of anterior and panuveitis differ between HIV+ and HIV- patients.

Human immunodeficiency virus-induced uveitis: intraocular and plasma human immunodeficiency virus-1 RNA loads.

OBJECTIVE: To report on a human immunodeficiency virus (HIV)-infected patient with uveitis and an intraocular HIV1 RNA load largely exceeding that of plasma and no evidence of other intraocular infectious agents causing uveitis than HIV itself. DESIGN: Interventional case report. PARTICIPANT: A 37-year-old male HIV-infected patient with uveitis and no retinal manifestations. METHODS: Clinical and laboratory examinations including extensive intraocular fluid analyses for various pathogens and HIV-1 RNA loads in the aqueous and plasma. MAIN OUTCOME MEASURES: Results of aqueous analysis and ophthalmologic features. Correlations between the results of aqueous testing and clinical characteristics. RESULTS: A 37-year-old patient presented with progressive uveitis. He was positive for HIV-1, and his HIV-1 RNA plasma load was 44,600 copies/mL. His intraocular HIV-1 RNA load was >1,900,000 copies/mL, which largely exceeded his concurrent plasma load. No evidence of infectious agents other than HIV itself was found, and the uveitis reacted promptly to solely the antiretroviral treatment. CONCLUSIONS: Our findings suggest that HIV can locally replicate within the eye and cause an intraocular inflammatory reaction.

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.

Diagnosis of ocular toxocariasis by establishing intraocular antibody production.

PURPOSE: To investigate the role of Toxocara canis in posterior uveitis of undetermined origin. DESIGN: Retrospective case-study. METHODS: Paired ocular fluid (47 aqueous humor [AH] and two vitreous fluids) and serum samples of 37 adults and 12 children with undetermined posterior uveitis were retrospectively analyzed for intraocular IgG antibody production against Toxocara canis by enzyme-linked immunosorbent assay and Goldmann-Witmer coefficient (GWC) determination. Previous diagnostic investigation by polymerase chain reaction and GWC for Herpes simplex virus, Varicella zoster virus, and Toxoplasma gondii had not provided a cause of the posterior uveitis. RESULTS: Three of 12 (25%) children showed intraocular IgG production against Toxocara canis. One child had vitritis, one presented with a low-grade uveitis and a peripheral retinal lesion, and the third had posterior uveitis and a chorioretinal scar. All three children had AH IgG titers exceeding those of the corresponding serum. In fact, two children had low Toxocara serum IgG titers (<1:32) and would have been considered seronegative upon routine serology screening. Intraocular antibody production against Toxocara canis was absent in all 37 adults, including five seropositive patients. CONCLUSIONS: Our results indicate that ocular toxocariasis is mainly a pediatric disease. Serological screening is not informative for the diagnosis of intraocular Toxocara infection. Toxocara GWC analysis, however, can be of value when diagnosing patients with posterior focal lesions or vitritis of unknown etiology.

Immunopathology of Virus-Induced Anterior Uveitis.

Herpes simplex virus, varicella zoster virus, human cytomegalovirus, and rubella virus are the most common causes of virus-induced anterior uveitis. They can present in a variety of entities not only with typical but also overlapping clinical characteristics. These viral infections are commonly associated with ocular infiltration of T cells and B/plasma cells, and expression of cytokines and chemokines typical of a proinflammatory immune response. The infections differ in that the herpes viruses cause an acute lytic infection and inflammation, whereas rubella virus is a chronic low-grade infection with slowly progressing immunopathological responses. The outcome of an intraocular viral infection may largely be guided by the characteristics of the virus, which subsequently dictates the severity and type of the immune response, and the host immune status.

Diagnosis of Cytomegalovirus Anterior Uveitis in Two European Referral Centers.

PURPOSE: To evaluate diagnostic methods and clinical signs of CMV anterior uveitis (AU), a rarely described entity in Europe. METHODS: We included patients with clinical characteristics of CMV AU and positive PCR and/or Goldmann-Witmer coefficient (GWc) for CMV. RESULTS: We report 21 patients with unilateral uveitis (100%) and signs of Posner-Schlossman syndrome (PSS) (n = 20, 95.2%), Fuchs uveitis syndrome (FUS) (n = 1, 4.7%), and endotheliitis (n = 4, 19,04%). PCR was positive in 15/21 (71.4%) and GWc in 8/9 patients (88.9%) in aqueous for CMV. GWc was the only positive test in 6/9 patients (66,6%). When PCR alone was performed (without GWc) in the first tap, repeated aqueous taps were needed, twice in five cases and thrice in one case. CONCLUSION: Combining PCR and GWc were very helpful to confirm the clinical diagnosis of CMV AU. In case of very high clinical suspicion and negative results, repeated tap seems to be recommended.

Potential Diagnosis of Vitreoretinal Lymphoma by Detection of MYD88 Mutation in Aqueous Humor With Ultrasensitive Droplet Digital Polymerase Chain Reaction.

Importance: The diagnostic workup of patients suspected of having vitreoretinal lymphoma (VRL) is primarily based on vitreous fluid analysis, including the recently emerging myeloid differentiation primary response gene 88 (MYD88) mutation analysis. Aqueous humor paracentesis is a relatively less invasive and safer procedure than taking vitreous fluid specimens, and aqueous humor-based MYD88 mutation analysis would provide an additional liquid biopsy tool to diagnose and monitor patients with VRL. Objective: To investigate whether the detection of MYD88 L265P by highly sensitive droplet digital polymerase chain reaction (ddPCR) is feasible in the vitreous fluid and aqueous humor of patients with VRL. Design, Setting, and Participants: This cohort study includes aqueous humor and vitreous fluid samples from patients with VRL who were treated at the University Medical Center Utrecht, in Utrecht, the Netherlands, from August 2005 to August 2017. Ocular fluids were randomized and masked before MYD88 L265P analysis, which was performed using an in-house validated ddPCR platform. Patients with uveitis were included as a comparison group. Main Outcomes and Measures: The presence of MYD88 L265P mutation detected by ddPCR in AH and VF. Results: The study included 96 samples from 63 individuals, including 23 patients with VRL (of whom 10 were female and 13 male, with a mean [SD] age of 72 [7.3] years) and 40 individuals with uveitis (of whom 23 were female and 17 male, with a mean [SD] age of 58 [20.9] years). In 17 of 23 patients with VRL (74%), MYD88 L265P was detected; it was not detected in any of the patients with uveitis. It was detectable in both vitreous fluid and aqueous humor samples. In the paired samples, the mutation was detected in 8 of 9 aqueous humor samples (89%) of the MYD88 L265P-positive vitreous fluid samples. In vitreous fluid, the MYD88 ddPCR test showed a sensitivity of 75% (95% CI, 50%-92%) and a positive predictive value of 100%; in aqueous humor, sensitivity was 67% (95% CI, 42%-92%), and positive predictive value was 100%. Specificity was 100% in both fluids. After treatment, the mutation was no longer detectable in any ocular fluids. Conclusions and Relevance: The high concordance between aqueous humor and vitreous fluid samples suggests that use of the easily accessible aqueous humor is nearly as informative as vitreous fluid in the identification of key somatic mutations in patients with VRL. This approach may provide an additional minimally invasive tool for accurate diagnosis, detection of recurrence, and monitoring of treatment.

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 infection.

Infectious uveitis in immunocompromised patients and the diagnostic value of polymerase chain reaction and Goldmann-Witmer coefficient in aqueous analysis.

PURPOSE: To establish the causes of uveitis in immunocompromised patients and to determine the contribution of polymerase chain reaction (PCR) and Goldmann-Witmer coefficient (GWC) analysis of aqueous humor in patients with an infectious etiology. DESIGN: Retrospective case series of 56 consecutive immunocompromised patients with uveitis. METHODS: All patients underwent full ophthalmologic examination and laboratory blood analysis for uveitis. Aqueous humor analyses were performed using PCR and GWC for cytomegalovirus (CMV), herpes simplex virus (HSV), varicella zoster virus (VZV), and Toxoplasma gondii. RESULTS: Of 56 immunocompromised patients, 43 (77%), all posterior and panuveitis, had intraocular infections. Twenty-one (49%) had CMV, three (7%) had VZV, 11 (26%) had T. gondii, six (14%) had Treponema pallidum, and one (2%) each had Aspergillus and Candida. In AIDS patients, CMV was the most common cause. A strong correlation between AIDS and ocular syphilis was also observed (P = .007). In nonAIDS immunocompromised patients, T. gondii was most frequently detected. Twenty-seven patients were examined by both PCR and GWC; five (18.5%) were positive by both assays, 15 (55.5%) were positive by PCR alone and seven (26%) by GWC alone. Viral infections were detected by PCR in 16 of 17 (94%) cases; T. gondii in four of 10 (40%) patients. Using GWC, a viral infection was diagnosed in three of 17 (18%) and T. gondii in nine of 10 (90%) cases. CONCLUSIONS: In immunocompromised patients, PCR is superior in diagnosing viral infections. Analysis of intraocular antibody production played a decisive role in the diagnosis of ocular toxoplasmosis.

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.

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.