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Stephen C Foster - One of the best experts on this subject based on the ideXlab platform.
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mc5r and a2ar deficiencies during experimental autoimmune Uveitis identifies distinct t cell polarization programs and a biphasic regulatory response
Scientific Reports, 2016Co-Authors: Darren J Lee, Stephen C Foster, Janine M Preble, Stacey Lee, Andrew W TaylorAbstract:Autoantigen-specific regulatory immunity emerges in the spleen of mice recovering from experimental autoimmune Uveitis (EAU), a murine model for human autoimmune uveoretinitis. This regulatory immunity provides induced tolerance to ocular autoantigen, and requires melanocortin 5 receptor (MC5r) expression on antigen presenting cells with adenosine 2 A receptor (A2Ar) expression on T cells. During EAU it is not well understood what roles MC5r and A2Ar have on promoting regulatory immunity. Cytokine profile analysis during EAU revealed MC5r and A2Ar each mediate distinct T cell responses, and are responsible for a functional regulatory immune response in the spleen. A2Ar stimulation at EAU onset did not augment this regulatory response, nor bypass the MC5r requirement to induce regulatory immunity. The importance of this pathway in human autoimmune Uveitis was assayed. PBMC from Uveitis patients were assayed for MC5r expression on monocytes and A2Ar on T cells, and comparison between Uveitis patients and healthy controls had no significant difference. The importance for MC5r and A2Ar expression in EAU to promote the induction of protective regulatory immunity, and the expression of MC5r and A2Ar on human immune cells, suggests that it may be possible to utilize the melanocortin-adenosinergic pathways to induce protective immunity in uveitic patients.
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anterior chamber intraocular lens implantation in patients with a history of chronic Uveitis five year follow up
Journal of Cataract and Refractive Surgery, 2014Co-Authors: Ana M Suelves, Sana S Siddique, Brian Schurko, Stephen C FosterAbstract:Purpose To compare the incidence of long-term complications after cataract surgery with primary anterior chamber intraocular lens (AC IOL) implantation in uveitic patients and patients without a history of intraocular inflammation (control group). Setting Single-center private practice. Design Retrospective clinical study. Methods The study comprised patients who between November 2005 and August 2010 had cataract extraction followed by AC IOL implantation because conventional placement was not possible. Outcome measures were the incidence of intraoperative and postoperative complications, preoperative corrected distance visual acuity (CDVA), and CDVA after 1 year. Results Of the 39 patients identified through electronic medical records, 17 (17 eyes) had a history of chronic Uveitis and 22 (23 eyes) had no intraocular inflammatory disease. There were no significant differences in the incidence of intraoperative and postoperative complications between the 2 groups during follow-up (range 12 to 68 months) (P=.702). Although uveitic eyes had a greater risk for epiretinal membrane formation, the incidence of Uveitis flareups attributed to the IOL and deposits on IOL surfaces was comparable to that in the control group (P Conclusion In uveitic eyes with inadequate capsule support, AC IOL implantation restored visual function without a significant increase in long-term postoperative complications compared with eyes that had no history of Uveitis. Financial Disclosure No author has a financial or proprietary interest in any material or method mentioned.
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risk of choroidal neovascularization among the uveitides
American Journal of Ophthalmology, 2013Co-Authors: Sally L Baxter, Douglas A Jabs, Jennifer E Thorne, Stephen C Foster, Maxwell Pistilli, Siddharth S Pujari, Teresa L Liesegang, Eric B SuhlerAbstract:Purpose To evaluate the risk, risk factors, and visual impact of choroidal neovascularization (CNV) in Uveitis cases. Design Retrospective cohort study. Methods Standardized medical record review at 5 tertiary centers. Results Among 15 137 uveitic eyes (8868 patients), CNV was rare in the cases of anterior or intermediate Uveitis. Among the 4041 eyes (2307 patients) with posterior Uveitis or panUveitis, 81 (2.0%) had CNV at presentation. Risk factors included posterior Uveitis in general and specific Uveitis syndromes affecting the outer retina–retinal pigment epithelium–choroid interface. Among the 2364 eyes (1357 patients) with posterior Uveitis or panUveitis and free of CNV at the time of cohort entry, the cumulative 2-year incidence of CNV was 2.7% (95% confidence interval [CI], 1.8% to 3.5%). Risk factors for incident CNV included currently active inflammation (adjusted hazard ratio [aHR], 2.13; 95% CI, 1.26 to 3.60), preretinal neovascularization (aHR, 3.19; 95% CI, 1.30 to 7.80), and prior diagnosis of CNV in the contralateral eye (aHR, 5.79; 95% CI, 2.77 to 12.09). Among specific syndromes, the incidence was greater in Vogt-Koyanagi-Harada syndrome (aHR, 3.37; 95% CI, 1.52 to 7.46) and punctate inner choroiditis (aHR, 8.67; 95% CI, 2.83 to 26.54). Incident CNV was associated with a 2-line loss of visual acuity (+0.19 logarithm of the minimal angle of resolution units; 95% CI, 0.079 to 0.29) from the preceding visit. Conclusions CNV is an uncommon complication of Uveitis associated with visual impairment that occurs more commonly in forms affecting the outer retina–retinal pigment epithelium–choroid interface, during periods of inflammatory activity, in association with preretinal neovascularization, and in second eyes of patients with unilateral CNV. Because CNV is treatable, a systematic approach to early detection in high-risk patients may be appropriate.
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glaucoma and Uveitis
Survey of Ophthalmology, 2013Co-Authors: Sana S Siddique, Ana M Suelves, Ujwala Baheti, Stephen C FosterAbstract:Despite its relative rarity, Uveitis is the third leading cause of preventable blindness worldwide. Glaucoma associated with Uveitis is one of the most serious complications of intraocular inflammation. We review in detail the epidemiology and pathogenesis of uveitic glaucoma and the safety and efficacy of the current medical and surgical treatment modalities.
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flare up rates with bimatoprost therapy in uveitic glaucoma
American Journal of Ophthalmology, 2008Co-Authors: Egidio Fortuna, Rene A Castanedacervantes, Pooja Bhat, Priyanka P Doctor, Stephen C FosterAbstract:Purpose To evaluate the rate of flares in patients with uveitic glaucoma treated with topical bimatoprost and to assess its effect on intraocular pressure (IOP) in this subset of patients. Design Retrospective case series. Methods All patients seen at one subspecialty Uveitis practice with history of uveitic glaucoma treated with topical bimatoprost were identified and the data collected, which included onset, type, duration of Uveitis, onset of secondary glaucoma, and previous therapies for glaucoma. The time of onset of bimatoprost therapy, the IOP, and flare-up rate before and after initiation of treatment with bimatoprost were recorded at one week and one, three, and six months of follow-up. Results Of the 42 patients (59 eyes) identified, 12 patients had used other topical lipid agents, which were replaced by bimatoprost. Twenty-three patients had not used any lipid agents and bimatoprost was added to their existing antiglaucoma regimen. Seven patients were newly diagnosed with uveitic glaucoma and were commenced with topical bimatoprost. The rate of Uveitis flares while on other antiglaucoma therapy was 52 per 100 person-years follow-up, while on bimatoprost therapy it was 32.4 per 100 person-years follow-up ( P = .206). The mean IOP prior to bimatoprost therapy was 27 ± 13.2 mm Hg and after initiation of topical bimatoprost was 15 ± 5.5 mm Hg at the end of six months ( P = .0008). Conclusion These data suggest that bimatoprost is an effective IOP-lowering agent in patients with uveitic glaucoma in whom the Uveitis is controlled on immunomodulatory therapy, and it does not increase the rate of flares of Uveitis in these patients.
Douglas A Jabs - One of the best experts on this subject based on the ideXlab platform.
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assessing the precision of icd 10 codes for Uveitis in 2 electronic health record systems
JAMA Ophthalmology, 2018Co-Authors: Alan G Palestine, Douglas A Jabs, Jennifer E Thorne, Pauline T Merrill, Sophia M SaleemAbstract:Importance Electronic health record (EHR) systems based onInternational Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) coding of disease entities are increasingly being used to generate large data sets for analysis. However, the reproducibility ofICD-10coding in Uveitis has not been assessed across EHR platforms, and imprecision in coding may lead to improper conclusions in big-data analyses. Objective To compareICD-10coding of Uveitis using 2 EHR systems. Design, Setting, and Participants This study comparesICD-10codes for 27 uveitic diseases generated by the Epic and MDIntelleSys EHR systems to theICD-10descriptions associated with the codes. No patient data were assessed in this study. Main Outcomes and Measures The number of diseases for whichICD-10coding differed between the 2 systems. Results Thirteen of 27 uveitic diseases were coded differently by the 2 EHR systems. Coding imprecision was notable in that the Epic system returned 16ICD-10codes and the MDIntelleSys returned 12ICD-10codes to describe 13 diseases; 4 diseases had multiple codes returned, and 6 codes were used to describe more than 1 disease. For example, MDIntelleSys usesICD-10code H30.13 for both birdshot choroiditis and acute retinal necrosis, while Epic uses H30.9 for both birdshot choroiditis and multiple evanescent white dot syndrome; MDIntelleSys uses this code for multifocal choroiditis. Furthermore, theICD-10descriptions for certain codes lack specificity, allowing variable interpretation by the coder. Conclusions and Relevance This study suggests there is substantial disparity in theICD-10codes that are generated for specific uveitides by the 2 EHR systems studied. This result implies that analysis of large databases generated from the pooling of EHR data could produce results with substantial bias because of misclassification resulting from conflicting and imprecise coding of uveitides. Therefore, research into outcomes, costs, health care utilization, and epidemiology in Uveitis might be improved if a more uniform coding system to describe ocular inflammatory disease is implemented.
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interobserver agreement among Uveitis experts on uveitic diagnoses the standardization of Uveitis nomenclature experience
American Journal of Ophthalmology, 2018Co-Authors: Douglas A Jabs, Amod Gupta, Susan Lightman, Alan G Palestine, Andrew D Dick, John T Doucette, Peter Mccluskey, Annabelle A Okada, James T RosenbaumAbstract:Purpose To evaluate the interobserver agreement among Uveitis experts on the diagnosis of the specific uveitic disease. Design Interobserver agreement analysis. Methods Five committees, each comprised of 9 individuals and working in parallel, reviewed cases from a preliminary database of 25 uveitic diseases, collected by disease, and voted independently online whether the case was the disease in question or not. The agreement statistic, κ, was calculated for the 36 pairwise comparisons for each disease, and a mean κ was calculated for each disease. After the independent online voting, committee consensus conference calls, using nominal group techniques, reviewed all cases not achieving supermajority agreement (>75%) on the diagnosis in the online voting to attempt to arrive at a supermajority agreement. Results A total of 5766 cases for the 25 diseases were evaluated. The overall mean κ for the entire project was 0.39, with disease-specific variation ranging from 0.23 to 0.79. After the formalized consensus conference calls to address cases that did not achieve supermajority agreement in the online voting, supermajority agreement overall was reached on approximately 99% of cases, with disease-specific variation ranging from 96% to 100%. Conclusions Agreement among Uveitis experts on diagnosis is moderate at best but can be improved by discussion among them. These data suggest the need for validated and widely used classification criteria in the field of Uveitis.
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association between long lasting intravitreous fluocinolone acetonide implant vs systemic anti inflammatory therapy and visual acuity at 7 years among patients with intermediate posterior or panUveitis
JAMA, 2017Co-Authors: John H Kempen, Michael M Altaweel, Janet T Holbrook, Elizabeth A Sugar, Jennifer E Thorne, Douglas A JabsAbstract:Importance A randomized clinical trial comparing fluocinolone acetonide implant vs systemic corticosteroids and immunosuppression for treatment of severe noninfectious intermediate, posterior, and panuveitides did not result in a significant difference in visual acuity at 2 and 4.5 years; longer-term outcomes are not known. Objective To compare the association between intravitreous fluocinolone acetonide implant vs systemic therapy and long-term visual and other outcomes in patients with Uveitis. Design, Setting, and Participants Nonprespecified 7-year observational follow-up of the Multicenter Uveitis Steroid Treatment (MUST) randomized clinical trial comparing the alternative treatments. Follow-up was conducted in tertiary Uveitis subspecialty practices in the United States (21), the United Kingdom (1), and Australia (1). Of 255 patients 13 years or older with intermediate, posterior, or panUveitis (active within ≤60 days) enrolled in the MUST trial between December 6, 2005, and December 9, 2008, 215 consented to ongoing follow-up through at least 7 years postrandomization (last visit, February 10, 2016). Interventions Participants had been randomized to receive a surgically placed intravitreous fluocinolone acetonide implant or systemic corticosteroids supplemented by immunosuppression. When both eyes required treatment, both eyes were treated. Main Outcomes and Measures Primary outcome was change from baseline in best-corrected visual acuity in uveitic eyes (5 letters = 1 visual acuity chart line; potential range of change in letters read, −121 to +101; minimal clinically important difference, 7 letters), analyzed by treatment assignment accounting for nonindependence of eyes when patients had 2 uveitic eyes. Secondary outcomes included potential systemic toxicities of corticosteroid and immunosuppressive therapy and death. Results Seven-year data were obtained for 161 uveitic eyes (70% of 90 patients assigned to implant) and 167 uveitic eyes (71% of 90 patients assigned to systemic therapy) (77% female; median age at enrollment, 48 [interquartile range, 36-56] years). Change in mean visual acuity from baseline (implant, 61.7; systemic therapy, 65.0) through 7 years (implant, 55.8; systemic therapy, 66.2) favored systemic therapy by 7.2 (95% CI, 2.1-12) letters. Among protocol-specified, prospectively collected systemic adverse outcomes, the cumulative 7-year incidence in the implant and systemic therapy groups, respectively, was less than 10%, with the exceptions of hyperlipidemia (6.1% vs 11.2%), hypertension (9.8% vs 18.4%), osteopenia (41.5% vs 43.1%), fractures (11.3% vs 18.6%), hospitalization (47.6% vs 42.3%), and antibiotic-treated infection (57.4% vs 72.3%). Conclusions and Relevance In 7-year extended follow-up of a randomized trial of patients with severe intermediate, posterior, or panUveitis, those randomized to receive systemic therapy had better visual acuity than those randomized to receive intravitreous fluocinolone acetonide implants. Study interpretation is limited by loss to follow-up. Trial Registration clinicaltrials.gov Identifier:NCT00132691
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risk of choroidal neovascularization among the uveitides
American Journal of Ophthalmology, 2013Co-Authors: Sally L Baxter, Douglas A Jabs, Jennifer E Thorne, Stephen C Foster, Maxwell Pistilli, Siddharth S Pujari, Teresa L Liesegang, Eric B SuhlerAbstract:Purpose To evaluate the risk, risk factors, and visual impact of choroidal neovascularization (CNV) in Uveitis cases. Design Retrospective cohort study. Methods Standardized medical record review at 5 tertiary centers. Results Among 15 137 uveitic eyes (8868 patients), CNV was rare in the cases of anterior or intermediate Uveitis. Among the 4041 eyes (2307 patients) with posterior Uveitis or panUveitis, 81 (2.0%) had CNV at presentation. Risk factors included posterior Uveitis in general and specific Uveitis syndromes affecting the outer retina–retinal pigment epithelium–choroid interface. Among the 2364 eyes (1357 patients) with posterior Uveitis or panUveitis and free of CNV at the time of cohort entry, the cumulative 2-year incidence of CNV was 2.7% (95% confidence interval [CI], 1.8% to 3.5%). Risk factors for incident CNV included currently active inflammation (adjusted hazard ratio [aHR], 2.13; 95% CI, 1.26 to 3.60), preretinal neovascularization (aHR, 3.19; 95% CI, 1.30 to 7.80), and prior diagnosis of CNV in the contralateral eye (aHR, 5.79; 95% CI, 2.77 to 12.09). Among specific syndromes, the incidence was greater in Vogt-Koyanagi-Harada syndrome (aHR, 3.37; 95% CI, 1.52 to 7.46) and punctate inner choroiditis (aHR, 8.67; 95% CI, 2.83 to 26.54). Incident CNV was associated with a 2-line loss of visual acuity (+0.19 logarithm of the minimal angle of resolution units; 95% CI, 0.079 to 0.29) from the preceding visit. Conclusions CNV is an uncommon complication of Uveitis associated with visual impairment that occurs more commonly in forms affecting the outer retina–retinal pigment epithelium–choroid interface, during periods of inflammatory activity, in association with preretinal neovascularization, and in second eyes of patients with unilateral CNV. Because CNV is treatable, a systematic approach to early detection in high-risk patients may be appropriate.
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the standardization of Uveitis nomenclature sun project development of a clinical evidence base utilizing informatics tools and techniques
Methods of Information in Medicine, 2013Co-Authors: Brett Trusko, Douglas A Jabs, Jennifer E Thorne, Andrew D Dick, Rubens Belfort, Sapna Gangaputra, R B Nussenblatt, A Okada, J T RosenbaumAbstract:Background: Given the recent increased focus on evidence-based medicine, it is critical that diseases and syndromes have accurate and complete descriptions, including standardized and widely accepted terminologies. Standardizing these descriptions and terminologies is necessary to develop tools such as computerized data entry forms and classification criteria. This need is especially true for diseases that are relatively uncommon, such as Uveitis. Objectives: To develop a standardized and internationally accepted terminology for the field of Uveitis. Methods: The Standardization of Uveitis Nomenclature (SUN) Working Group (WG) is an international group of 79 Uveitis experts from 18 countries and 62 clinical centers. Initial terminology was developed utilizing a “modified” green field approach, which was enhanced through web-based surveys and teleconferences via a “modified” Delphi technique. Terms were mapped provisionally into ontologic dimensions for each syndrome. The Working Group then met and utilized nominal group techniques as a formalized method of finalizing the mappings. Results: Mapping of terms into dimensions to describe 28 major uveitic diseases was confirmed using nominal group techniques (achieving super-majority consensus) for each of the diseases at a meeting of the entire WG. Conclusions: The SUN WG utilized an informatics-based approach to develop a standardized and internationally accepted terminology for the uveitides.
Sofie Struyf - One of the best experts on this subject based on the ideXlab platform.
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soluble cytokine receptor levels in aqueous humour of patients with specific autoimmune uveitic entities scd30 is a biomarker of granulomatous Uveitis
Eye, 2019Co-Authors: Ahmed Abu M Elasrar, Nele Berghmans, Saleh A Alobeidan, Priscilla W Gikandi, Jo Van Damme, Sofie StruyfAbstract:Soluble cytokine receptors are potential biomarkers for immune activation and have a promising potential as immunotherapeutic agents. We investigated the levels of soluble cytokine receptors in aqueous humour (AH) samples from patients with specific autoimmune uveitic entities. Patients with active Uveitis associated with Behcet’s disease (BD) (n = 13), sarcoidosis (n = 8), HLA-B27-related inflammation (n = 12), Vogt–Koyanagi–Harada (VKH) disease (n = 12) and control subjects (n = 9) were included. AH samples were analyzed with the use of multiplex assays for the proinflammatory cytokine tumour necrosis factor (TNF)-α and the soluble cytokine receptors sCD30, sCD163, sgp130, sIL-6 receptor-α (sIL-6R), sTNFRI and sTNFRII. TNF-α and soluble cytokine receptor AH levels were significantly higher in Uveitis patients (n = 45) compared with controls (n = 9). When nongranulomatous Uveitis (BD and HLA-B27-associated Uveitis) was compared with granulomatous Uveitis (sarcoidosis and VKH disease), the levels of sCD30 and sTNFRI/TNF-α and sTNFRII/TNF-α ratios were significantly enhanced in granulomatous Uveitis. Finally, when comparing the profile in the specific Uveitis entities, sCD30 levels were highest in patients with VKH disease. sgp130, sCD163, sIL-6R, sTNFRI and sTNFRII did not differ significantly between the four different clinical uveitic subgroups. Soluble cytokine receptors are significantly upregulated in autoimmune Uveitis. CD30+ T cells might contribute to the inflammatory process in granulomatous Uveitis, particularly in VKH disease. Granulomatous Uveitis is also characterized by significantly higher sTNFRs/TNF-α ratios than nongranulomatous Uveitis.
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the cc chemokines ccl8 ccl13 and ccl20 are local inflammatory biomarkers of hla b27 associated Uveitis
Acta Ophthalmologica, 2019Co-Authors: Ahmed Abu M Elasrar, Nele Berghmans, Saleh A Alobeidan, Priscilla W Gikandi, Ghislain Opdenakker, Jo Van Damme, Sofie StruyfAbstract:Purpose To determine the concentrations of the CC chemokines CCL2, CCL7, CCL8, CCL11, CCL13, CCL20, CCL24 and CCL26 in aqueous humour (AH) samples from patients with specific uveitic entities. Methods Aqueous humour samples from patients with active Uveitis associated with Behcet's disease (BD) (n = 13), sarcoidosis (n = 8), HLA-B27-related inflammation (n = 12), Vogt-Koyanagi-Harada (VKH) disease (n = 12) and control patients (n = 9) were assayed with the use of a multiplex assay. Results When considering all Uveitis patients as one group, all chemokine levels except CCL2 were significantly increased compared to controls. CCL8, CCL13 and CCL20 were the most strongly upregulated, 48-fold, 118-fold and 173-fold, respectively, above control AH levels. CCL8 and CCL13 levels were significantly higher in HLA-B27-associated Uveitis than in sarcoidosis and VKH disease. CCL20 levels were significantly higher in HLA-B27-associated Uveitis than in BD, sarcoidosis and VKH disease. In addition, CCL20 levels were significantly higher in BD than in VKH disease. In HLA-B27-associated Uveitis, CCL8, CCL13 and CCL20 were upregulated 111-fold, 255-fold and 465-fold, respectively, compared with controls. CCL8, CCL13 and CCL20 levels were significantly higher in nongranulomatous Uveitis (BD and HLA-B27-associated Uveitis) than in granulomatous Uveitis (sarcoidosis and VKH disease). Conclusion Immune responses mediated by CCL8, CCL13 and CCL20 appear to be more potent in nongranulomatous Uveitis, particularly in HLA-B27-associated Uveitis.
Ahmed Abu M Elasrar - One of the best experts on this subject based on the ideXlab platform.
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soluble cytokine receptor levels in aqueous humour of patients with specific autoimmune uveitic entities scd30 is a biomarker of granulomatous Uveitis
Eye, 2019Co-Authors: Ahmed Abu M Elasrar, Nele Berghmans, Saleh A Alobeidan, Priscilla W Gikandi, Jo Van Damme, Sofie StruyfAbstract:Soluble cytokine receptors are potential biomarkers for immune activation and have a promising potential as immunotherapeutic agents. We investigated the levels of soluble cytokine receptors in aqueous humour (AH) samples from patients with specific autoimmune uveitic entities. Patients with active Uveitis associated with Behcet’s disease (BD) (n = 13), sarcoidosis (n = 8), HLA-B27-related inflammation (n = 12), Vogt–Koyanagi–Harada (VKH) disease (n = 12) and control subjects (n = 9) were included. AH samples were analyzed with the use of multiplex assays for the proinflammatory cytokine tumour necrosis factor (TNF)-α and the soluble cytokine receptors sCD30, sCD163, sgp130, sIL-6 receptor-α (sIL-6R), sTNFRI and sTNFRII. TNF-α and soluble cytokine receptor AH levels were significantly higher in Uveitis patients (n = 45) compared with controls (n = 9). When nongranulomatous Uveitis (BD and HLA-B27-associated Uveitis) was compared with granulomatous Uveitis (sarcoidosis and VKH disease), the levels of sCD30 and sTNFRI/TNF-α and sTNFRII/TNF-α ratios were significantly enhanced in granulomatous Uveitis. Finally, when comparing the profile in the specific Uveitis entities, sCD30 levels were highest in patients with VKH disease. sgp130, sCD163, sIL-6R, sTNFRI and sTNFRII did not differ significantly between the four different clinical uveitic subgroups. Soluble cytokine receptors are significantly upregulated in autoimmune Uveitis. CD30+ T cells might contribute to the inflammatory process in granulomatous Uveitis, particularly in VKH disease. Granulomatous Uveitis is also characterized by significantly higher sTNFRs/TNF-α ratios than nongranulomatous Uveitis.
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the cc chemokines ccl8 ccl13 and ccl20 are local inflammatory biomarkers of hla b27 associated Uveitis
Acta Ophthalmologica, 2019Co-Authors: Ahmed Abu M Elasrar, Nele Berghmans, Saleh A Alobeidan, Priscilla W Gikandi, Ghislain Opdenakker, Jo Van Damme, Sofie StruyfAbstract:Purpose To determine the concentrations of the CC chemokines CCL2, CCL7, CCL8, CCL11, CCL13, CCL20, CCL24 and CCL26 in aqueous humour (AH) samples from patients with specific uveitic entities. Methods Aqueous humour samples from patients with active Uveitis associated with Behcet's disease (BD) (n = 13), sarcoidosis (n = 8), HLA-B27-related inflammation (n = 12), Vogt-Koyanagi-Harada (VKH) disease (n = 12) and control patients (n = 9) were assayed with the use of a multiplex assay. Results When considering all Uveitis patients as one group, all chemokine levels except CCL2 were significantly increased compared to controls. CCL8, CCL13 and CCL20 were the most strongly upregulated, 48-fold, 118-fold and 173-fold, respectively, above control AH levels. CCL8 and CCL13 levels were significantly higher in HLA-B27-associated Uveitis than in sarcoidosis and VKH disease. CCL20 levels were significantly higher in HLA-B27-associated Uveitis than in BD, sarcoidosis and VKH disease. In addition, CCL20 levels were significantly higher in BD than in VKH disease. In HLA-B27-associated Uveitis, CCL8, CCL13 and CCL20 were upregulated 111-fold, 255-fold and 465-fold, respectively, compared with controls. CCL8, CCL13 and CCL20 levels were significantly higher in nongranulomatous Uveitis (BD and HLA-B27-associated Uveitis) than in granulomatous Uveitis (sarcoidosis and VKH disease). Conclusion Immune responses mediated by CCL8, CCL13 and CCL20 appear to be more potent in nongranulomatous Uveitis, particularly in HLA-B27-associated Uveitis.
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the cytokine interleukin 6 and the chemokines ccl20 and cxcl13 are novel biomarkers of specific endogenous uveitic entities
Investigative Ophthalmology & Visual Science, 2016Co-Authors: Ahmed Abu M Elasrar, Nele Berghmans, Saleh A Alobeidan, Ahmed Mousa, Ghislain Opdenakker, Jo Van DammeAbstract:PURPOSE The purpose of this study was to determine levels of the cytokines IL-1β, IL-6, IL-21, IL-22, and IL-23 and the chemokines CXCL13, CCL19, CCL20, and CCL21 in aqueous humor (AH) samples from patients with specific uveitic entities. METHODS Paired serum samples (n = 13) and AH samples (n = 111) from patients with active idiopathic granulomatous Uveitis (IGU) or with Uveitis associated with HLA-B27-related inflammation, Behcet's disease (BD), Vogt-Koyanagi-Harada (VKH) disease, or sarcoidosis and control patients were analyzed in two different multiplex assays. RESULTS Cytokines IL-1β, IL-21, IL-22, and IL-23 were not detected in any AH sample. Chemokine CCL21 concentrations in serum were significantly higher than those in AH. CCL19 levels in AH and serum were not significantly different. Levels of CCL20 and CXCL13 in AH were significantly higher than those in serum. IL-6 was not detected in serum samples. IL-6 AH levels were significantly higher in patients with HLA-B27-associated Uveitis and in BD patients than in patients with VKH disease, sarcoidosis, and IGU (P < 0.0001). CCL20 AH levels were significantly higher in HLA-B27-associated Uveitis than in BD, VKH, sarcoidosis, and IGU (P = 0.001), whereas CXCL13 AH levels were significantly higher in VKH disease and IGU than in HLA-B27-associated Uveitis, BD, and sarcoidosis (P = 0.007). CONCLUSIONS IL-6-driven immune responses are more potent in HLA-B27-associated Uveitis and BD than in VKH disease, sarcoidosis, and IGU. CCL20 appears to be a specific biomarker of HLA-B27-associated Uveitis, whereas CXCL13 appears to be a biomarker of VKH disease and IGU. Our findings suggest that IL-6, CCL20, and CXCL13 could serve as drug targets for treatment of specific clinical entities of endogenous Uveitis.
Jennifer E Thorne - One of the best experts on this subject based on the ideXlab platform.
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assessing the precision of icd 10 codes for Uveitis in 2 electronic health record systems
JAMA Ophthalmology, 2018Co-Authors: Alan G Palestine, Douglas A Jabs, Jennifer E Thorne, Pauline T Merrill, Sophia M SaleemAbstract:Importance Electronic health record (EHR) systems based onInternational Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) coding of disease entities are increasingly being used to generate large data sets for analysis. However, the reproducibility ofICD-10coding in Uveitis has not been assessed across EHR platforms, and imprecision in coding may lead to improper conclusions in big-data analyses. Objective To compareICD-10coding of Uveitis using 2 EHR systems. Design, Setting, and Participants This study comparesICD-10codes for 27 uveitic diseases generated by the Epic and MDIntelleSys EHR systems to theICD-10descriptions associated with the codes. No patient data were assessed in this study. Main Outcomes and Measures The number of diseases for whichICD-10coding differed between the 2 systems. Results Thirteen of 27 uveitic diseases were coded differently by the 2 EHR systems. Coding imprecision was notable in that the Epic system returned 16ICD-10codes and the MDIntelleSys returned 12ICD-10codes to describe 13 diseases; 4 diseases had multiple codes returned, and 6 codes were used to describe more than 1 disease. For example, MDIntelleSys usesICD-10code H30.13 for both birdshot choroiditis and acute retinal necrosis, while Epic uses H30.9 for both birdshot choroiditis and multiple evanescent white dot syndrome; MDIntelleSys uses this code for multifocal choroiditis. Furthermore, theICD-10descriptions for certain codes lack specificity, allowing variable interpretation by the coder. Conclusions and Relevance This study suggests there is substantial disparity in theICD-10codes that are generated for specific uveitides by the 2 EHR systems studied. This result implies that analysis of large databases generated from the pooling of EHR data could produce results with substantial bias because of misclassification resulting from conflicting and imprecise coding of uveitides. Therefore, research into outcomes, costs, health care utilization, and epidemiology in Uveitis might be improved if a more uniform coding system to describe ocular inflammatory disease is implemented.
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association between long lasting intravitreous fluocinolone acetonide implant vs systemic anti inflammatory therapy and visual acuity at 7 years among patients with intermediate posterior or panUveitis
JAMA, 2017Co-Authors: John H Kempen, Michael M Altaweel, Janet T Holbrook, Elizabeth A Sugar, Jennifer E Thorne, Douglas A JabsAbstract:Importance A randomized clinical trial comparing fluocinolone acetonide implant vs systemic corticosteroids and immunosuppression for treatment of severe noninfectious intermediate, posterior, and panuveitides did not result in a significant difference in visual acuity at 2 and 4.5 years; longer-term outcomes are not known. Objective To compare the association between intravitreous fluocinolone acetonide implant vs systemic therapy and long-term visual and other outcomes in patients with Uveitis. Design, Setting, and Participants Nonprespecified 7-year observational follow-up of the Multicenter Uveitis Steroid Treatment (MUST) randomized clinical trial comparing the alternative treatments. Follow-up was conducted in tertiary Uveitis subspecialty practices in the United States (21), the United Kingdom (1), and Australia (1). Of 255 patients 13 years or older with intermediate, posterior, or panUveitis (active within ≤60 days) enrolled in the MUST trial between December 6, 2005, and December 9, 2008, 215 consented to ongoing follow-up through at least 7 years postrandomization (last visit, February 10, 2016). Interventions Participants had been randomized to receive a surgically placed intravitreous fluocinolone acetonide implant or systemic corticosteroids supplemented by immunosuppression. When both eyes required treatment, both eyes were treated. Main Outcomes and Measures Primary outcome was change from baseline in best-corrected visual acuity in uveitic eyes (5 letters = 1 visual acuity chart line; potential range of change in letters read, −121 to +101; minimal clinically important difference, 7 letters), analyzed by treatment assignment accounting for nonindependence of eyes when patients had 2 uveitic eyes. Secondary outcomes included potential systemic toxicities of corticosteroid and immunosuppressive therapy and death. Results Seven-year data were obtained for 161 uveitic eyes (70% of 90 patients assigned to implant) and 167 uveitic eyes (71% of 90 patients assigned to systemic therapy) (77% female; median age at enrollment, 48 [interquartile range, 36-56] years). Change in mean visual acuity from baseline (implant, 61.7; systemic therapy, 65.0) through 7 years (implant, 55.8; systemic therapy, 66.2) favored systemic therapy by 7.2 (95% CI, 2.1-12) letters. Among protocol-specified, prospectively collected systemic adverse outcomes, the cumulative 7-year incidence in the implant and systemic therapy groups, respectively, was less than 10%, with the exceptions of hyperlipidemia (6.1% vs 11.2%), hypertension (9.8% vs 18.4%), osteopenia (41.5% vs 43.1%), fractures (11.3% vs 18.6%), hospitalization (47.6% vs 42.3%), and antibiotic-treated infection (57.4% vs 72.3%). Conclusions and Relevance In 7-year extended follow-up of a randomized trial of patients with severe intermediate, posterior, or panUveitis, those randomized to receive systemic therapy had better visual acuity than those randomized to receive intravitreous fluocinolone acetonide implants. Study interpretation is limited by loss to follow-up. Trial Registration clinicaltrials.gov Identifier:NCT00132691
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risk of choroidal neovascularization among the uveitides
American Journal of Ophthalmology, 2013Co-Authors: Sally L Baxter, Douglas A Jabs, Jennifer E Thorne, Stephen C Foster, Maxwell Pistilli, Siddharth S Pujari, Teresa L Liesegang, Eric B SuhlerAbstract:Purpose To evaluate the risk, risk factors, and visual impact of choroidal neovascularization (CNV) in Uveitis cases. Design Retrospective cohort study. Methods Standardized medical record review at 5 tertiary centers. Results Among 15 137 uveitic eyes (8868 patients), CNV was rare in the cases of anterior or intermediate Uveitis. Among the 4041 eyes (2307 patients) with posterior Uveitis or panUveitis, 81 (2.0%) had CNV at presentation. Risk factors included posterior Uveitis in general and specific Uveitis syndromes affecting the outer retina–retinal pigment epithelium–choroid interface. Among the 2364 eyes (1357 patients) with posterior Uveitis or panUveitis and free of CNV at the time of cohort entry, the cumulative 2-year incidence of CNV was 2.7% (95% confidence interval [CI], 1.8% to 3.5%). Risk factors for incident CNV included currently active inflammation (adjusted hazard ratio [aHR], 2.13; 95% CI, 1.26 to 3.60), preretinal neovascularization (aHR, 3.19; 95% CI, 1.30 to 7.80), and prior diagnosis of CNV in the contralateral eye (aHR, 5.79; 95% CI, 2.77 to 12.09). Among specific syndromes, the incidence was greater in Vogt-Koyanagi-Harada syndrome (aHR, 3.37; 95% CI, 1.52 to 7.46) and punctate inner choroiditis (aHR, 8.67; 95% CI, 2.83 to 26.54). Incident CNV was associated with a 2-line loss of visual acuity (+0.19 logarithm of the minimal angle of resolution units; 95% CI, 0.079 to 0.29) from the preceding visit. Conclusions CNV is an uncommon complication of Uveitis associated with visual impairment that occurs more commonly in forms affecting the outer retina–retinal pigment epithelium–choroid interface, during periods of inflammatory activity, in association with preretinal neovascularization, and in second eyes of patients with unilateral CNV. Because CNV is treatable, a systematic approach to early detection in high-risk patients may be appropriate.
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the standardization of Uveitis nomenclature sun project development of a clinical evidence base utilizing informatics tools and techniques
Methods of Information in Medicine, 2013Co-Authors: Brett Trusko, Douglas A Jabs, Jennifer E Thorne, Andrew D Dick, Rubens Belfort, Sapna Gangaputra, R B Nussenblatt, A Okada, J T RosenbaumAbstract:Background: Given the recent increased focus on evidence-based medicine, it is critical that diseases and syndromes have accurate and complete descriptions, including standardized and widely accepted terminologies. Standardizing these descriptions and terminologies is necessary to develop tools such as computerized data entry forms and classification criteria. This need is especially true for diseases that are relatively uncommon, such as Uveitis. Objectives: To develop a standardized and internationally accepted terminology for the field of Uveitis. Methods: The Standardization of Uveitis Nomenclature (SUN) Working Group (WG) is an international group of 79 Uveitis experts from 18 countries and 62 clinical centers. Initial terminology was developed utilizing a “modified” green field approach, which was enhanced through web-based surveys and teleconferences via a “modified” Delphi technique. Terms were mapped provisionally into ontologic dimensions for each syndrome. The Working Group then met and utilized nominal group techniques as a formalized method of finalizing the mappings. Results: Mapping of terms into dimensions to describe 28 major uveitic diseases was confirmed using nominal group techniques (achieving super-majority consensus) for each of the diseases at a meeting of the entire WG. Conclusions: The SUN WG utilized an informatics-based approach to develop a standardized and internationally accepted terminology for the uveitides.
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incidence of cystoid macular edema after cataract surgery in patients with and without Uveitis using optical coherence tomography
American Journal of Ophthalmology, 2009Co-Authors: Marie Lyne Belair, Douglas A Jabs, Jennifer E Thorne, Stephen J Kim, James P Dunn, Sanjay Kedhar, Diane M BrownAbstract:Purpose To determine the incidence of cystoid macular edema (CME) after cataract surgery among eyes with and without Uveitis using optical coherence tomography (OCT) and to determine risk factors for postoperative CME among eyes with Uveitis. Design Prospective, comparative cohort study. Methods Single-center, academic practice. Forty-one eyes with Uveitis and 52 eyes without Uveitis underwent clinical examination and OCT testing within 4 weeks before cataract surgery and at 1-month and 3-month postoperative visits. The main outcome measure was incidence of CME at 1 and 3 months after surgery. Results Both uveitic and control eyes gained approximately 3 lines of vision ( P = .6). Incidence of CME at 1 month was 12% (5 eyes) for Uveitis and 4% (2 eyes) for controls ( P = .2). Incidence of CME at 3 months was 8% (3 eyes) for Uveitis and 0% for eyes without Uveitis ( P = .08). Eyes with Uveitis treated with perioperative oral corticosteroids had a 7-fold reduction in postoperative CME (relative risk [RR], 0.14; P = .05). In uveitic eyes, active inflammation within 3 months before surgery increased the risk of CME when compared with eyes without inflammation (RR, 6.19; P = .04). CME was significantly associated with poorer vision ( P = .01). Conclusions Eyes with well-controlled Uveitis may obtain similar outcomes to control eyes after cataract surgery (up to 3 months). Use of perioperative oral corticosteroids and control of Uveitis for more than 3 months before surgery seemed to decrease the risk of postoperative CME among uveitic eyes in this study.
