Prevalence of Positive QuantiFERON-TB Gold In-Tube Test in Uveitis and its Clinical Implications in a Country Nonendemic for Tuberculosis.

PURPOSE: To report on the prevalence and clinical implications of positive QuantiFERON-Gold (QFT-G) test results in the diagnostic evaluation of a large cohort of consecutive patients with uveitis in the Netherlands. DESIGN: Retrospective cross-sectional study. METHODS: This study included 710 consecutive patients who all underwent evaluation for uveitis including QFT-G testing. The ocular features, comorbidity, and abnormalities in diagnostic imaging and laboratory tests were registered for QFT-G-positive patients with uveitis. RESULTS: Of all patients, 13% (92/710) were positive for QFT-G. Previously treated tuberculosis (TB) was documented in 2 patients. Of all 92 QFT-G-positive patients, culture-proven active TB was observed in 1 case. The proportion of patients with uveitis of unknown etiology was higher in QFT-G-positive than in the QFT-G-negative patients (54/92, 59% vs 238/618, 39%; P = .0004). The uveitis features of QFT-G-positive patients were mainly nonspecific. Of all QFT-G-positive patients with uveitis, 17 patients had chest imaging changes suggesting either TB or sarcoidosis. Twenty-nine QFT-G-positive patients with otherwise unexplained uveitis completed antituberculous therapy (29/710; 4% of all included patients) with beneficial effect in most cases. CONCLUSION: The QFT-G tested positive in 13% of patients with uveitis in the Netherlands, whereas only sporadic patients had a documented previous or active TB infection. The proportion of patients with unexplained uveitis was higher in QFT-G-positive patients. Though the association between uveitis and a positive QFT-G test might be coincidental, the majority of treated QFT-G-positive patients with otherwise unexplained severe uveitis cause had a beneficial response to antituberculous therapy.

Clinical Manifestations, Prognosis, and Vaccination Status of Patients With Rubella Virus-Associated Uveitis.

PURPOSE: To assess the clinical and laboratory manifestations and vaccination status of uveitis patients positive for rubella virus (RV) in aqueous humor and investigate its relationship to Fuchs uveitis syndrome (FUS). METHODS: Retrospective study of all uveitis patients, positive for RV in aqueous humor analysis (polymerase chain reaction [PCR] and/or Goldmann-Witmer coefficient [GWC]) between January 2010 and October 2016 at the ophthalmology departments in the Erasmus Medical Center (Rotterdam) and University Medical Center Utrecht. Outcomes of aqueous analyses of FUS patients during this period were assessed. RESULTS: We included 127 patients (144 eyes) positive for RV in aqueous fluid: 23 (20%) by PCR, 120 (97%) by GWC, and 16 (13%) by both. The average age at first presentation was 37 years. Patients typically complained of blurred vision and exhibited a combination of unilateral anterior uveitis, keratic precipitates, vitritis, and absence of posterior synechiae, but the classical FUS was observed in a minority. The main cause of untreatable visual loss was glaucoma. Cystoid macular edema (CME) before intraocular surgery was not encountered. None of the unilateral cases developed involvement of the other eye. None of the patients was vaccinated against RV. All FUS patients, except 2 (5%), were positive for RV. CONCLUSION: RV-associated uveitis and FUS are not exchangeable. Chronic anterior uveitis, vitritis, early development of cataract, and the absence of posterior synechiae and CME characterize RV-associated uveitis. Almost all FUS cases had documented intraocular RV infection, but only some of the patients with RV-associated uveitis presented with FUS.

Relevance of erythrocyte sedimentation rate and C-reactive protein in patients with active uveitis.

PURPOSE: To relate erythrocyte sedimentation rates (ESR) and C-reactive protein (CRP) values to different uveitis entisties. METHODS: A retrospective study of patients with a first episode of active uveitis visiting the Erasmus University Medical Center, uveitis clinic, Rotterdam, the Netherlands, was performed. Levels of ESR and CRP were determined within 2 weeks and 1 week after onset of uveitis, respectively. Uveitis had to be of unknown origin at that moment. The specific etiologic groups were related to ESR and CRP values. RESULTS: The majority of patients with uveitis had ESR and/or CRP values within the normal limits and no association of ESR and/or CRP with the specific cause of uveitis was observed. However, elevation of ESR ≥ 60 mm/h and/or CRP ≥ 60 mg/L was mostly seen in patients with systemic immune-mediated diseases (8/59, 14% of all with immune-mediated diseases) or systemic infectious causes (7/38, 18% of all infectious uveitis). Patients with ocular toxoplasmosis typically exhibited normal ESR and CRP (9/11, 82%) while patients with endogenous endophthalmitis had elevated ESR and/or CRP in 6/7, 86%. Sarcoidosis-associated uveitis showed predominantly elevated ESR (13/24, 54%; range 20-59 mm/h in 11/13, 85%). Human immunodeficiency virus-positive patients had more often elevated ESR values when compared to the remainder of patients (9/11, 82% vs. 64/163, 39%, 18%, P = 0.009). The cause of uveitis was established in 19/20 (95%) of patients with ESR ≥ 60 mm/h and/or CRP ≥ 60 mg/L. CONCLUSIONS: The majority of patients with first attack of uveitis had ESR and CRP within the normal limits. Elevated levels of ESR and CRP reflected systemic involvement and high levels of both values were associated with established uveitis cause.

Lymphopaenia as a predictor of sarcoidosis in patients with a first episode of uveitis.

BACKGROUND/AIMS: The diagnostic properties of conventional diagnostic tests (ACE and chest radiography) for sarcoidosis-associated uveitis are not ideal. The diagnostic value of lymphopaenia for sarcoidosis-associated uveitis is investigated. METHODS: A retrospective study of 191 consecutive patients with a first uveitis episode visiting the ophthalmology department (Erasmus Medical Center, Rotterdam, The Netherlands). Receiver operating characteristics (ROC) analysis was performed and compared with known ROC values from literature of conventional diagnostic tests for sarcoidosis-associated uveitis. An ideal cut-off was determined for lymphopaenia by calculation of the highest Youden index. RESULTS: Out of all patients with first uveitis attack, 32/191 or 17% were subsequently diagnosed with biopsy-proven or radiological diagnosis of sarcoidosis. Lymphopaenia (<1.5×109/L) was significantly more often observed in patients with sarcoidosis-associated uveitis compared with patients with non-sarcoidosis-associated uveitis (p<0.05). The sensitivity and specificity of lymphopaenia was 75 % and 77 %, respectively. The optimal cut-off for lymphopaenia for diagnosing sarcoidosis-associated uveitis was 1.47 ×109/L. Lymphopaenia resulted in a 12.0 (95% CI 4.7 to 30.5 fold risk for having sarcoidosis, corrected for sex, race and age at onset of uveitis in patients with a first uveitis attack. CONCLUSION: Lymphopaenia is a non-invasive and useful marker for diagnosing sarcoidosis-associated uveitis.

Diagnostic Value of Serum-Soluble Interleukin 2 Receptor Levels vs Angiotensin-Converting Enzyme in Patients With Sarcoidosis-Associated Uveitis.

Importance: New and improved diagnostic tests for sarcoidosis-associated uveitis are needed because the currently available laboratory diagnostic biomarkers (eg, lysozyme and angiotensin-converting enzyme [ACE]) are lacking in high sensitivity and specificity. Objective: To compare the value of soluble interleukin 2 receptor (sIL-2R) with ACE as diagnostic biomarkers of sarcoidosis in patients with uveitis. Design, Setting, and Participants: A cross-sectional retrospective study was conducted using data collected from 249 consecutive patients with uveitis at the Erasmus University Medical Center uveitis outpatient clinic, Rotterdam, the Netherlands, from April 3, 2013, through November 25, 2015. Measurements of sIL-2R and ACE in serum samples and data extraction from patient files were conducted from December 2016 through February 2017, and analysis from April to May 2017. Main Outcomes and Measures: Serum levels of sIL-2R and ACE and chest radiographic findings were assessed. Receiver operating characteristics analysis was used to determine the probability that individual tests correctly identified patients with sarcoidosis. The Youden Index was used to determine the optimal cutoff points for serum sIL-2R and ACE levels to define sarcoidosis in patients with uveitis. Results: Data were analyzed from 249 patients with uveitis who had their serum sIL-2R and ACE levels determined and underwent chest radiography. Mean (SD) age at the time of sampling was 51 (16) years, 161 patients (64.7%) were women, and 191 (76.7%) were white. Although patients with sarcoidosis-associated uveitis had the highest mean (SD) serum sIL-2R (6047 [2533] pg/mL) and ACE (61 [38] U/L) levels, elevated serum sIL-2R levels were also found in patients with HLA-B27­associated (4460 [2465] pg/mL) and varicella-zoster virus­associated (5386 [1778] pg/mL) uveitis. Serum sIL-2R and ACE levels were significantly correlated (Pearson correlation coefficient, 0.205; P = .001, 2-sided), but no association was found between uveitis activity and sIL-2R (Spearman rank correlation coefficient [ρ], 0.070, P = .27) nor uveitis activity and ACE (ρ, −0.071; P = .27). The highest Youden index for sIL-2R alone was 0.45, corresponding to an optimal cutoff of 4000 pg/mL and providing 81% (95% CI, 74%-89%) sensitivity and 64% (95% CI, 56%-72%) specificity alone but combined with chest radiography yielded 92% sensitivity and 58% specificity. Chest radiography combined with sIL-2R at a cutoff of 6000 pg/mL resulted in 77% sensitivity and 73% specificity. Combined chest radiography and serum ACE levels at the standard cutoff of 68 U/L resulted in 70% sensitivity and 79% specificity. Conclusions and Relevance: This cross-sectional study demonstrates that sIL-2R is a useful marker for diagnosing sarcoidosis in patients with uveitis and has slightly better diagnostic value than ACE.

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.