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Purpose: To evaluate the use of BAL for the diagnosis of sarcoidosic uveitis. Methods: Retrospective study of 109 consecutive patients with uveitis and minimum 2 signs of ocular sarcoidosis who had a BAL and chest imaging. BAL+ was defined as an alveolar (a) lymphocytosis (L) aL > 15% with aCD4/CD8 > 3.5. Serum angiotensin converting enzyme (sACE), tuberculin skin test and gallium scan were tested in 83, 95 and 24 patients. Results: BAL was + in 26.6% of patients (86.2% females, mean age 50.8y) with mean aL = 46.8% and mean aCD4/CD8 = 8.5 which significantly differed form BAL− patients: 62.5% females, p < 0.02, mean age 43.6y, p < 0.05, mean aL = 17.2%, p < 0.001 and mean aCD4/CD8 = 1.8, p < 0.001. BAL+ patients had 31% of bilateral hilar adenopathy (BHL+), and 59.1% of elevated sACE which significantly differed form BAL− patients: 8.8%, p = < 0.01 and 14.8% p < 0.001. Conclusion: Our findings suggest that BAL have a high diagnostic value and might be a useful additional test for the diagnosis of sarcoidosic uveitis, even with normal chest imaging. [ABSTRACT FROM AUTHOR]

ObjectiveTo determine whether some long-term diabetic patients with coexisting clinical osteoarthritis (OA) are less likely to develop diabetic retinopathy (DR) than other diabetic patients and whether there is a relation between the timing of the clinical OA onset and DR.Design, setting, and participantsRetrospective case-control study of 85 osteoarthritic patients with 20 years or more diabetes (A/DM) control group and of 85 non-osteoarthritic diabetic patients (NoA/DM) matched for age, race, duration, and type of diabetes. Digital fundus photographs were graded for retinopathy in masked manner.ResultsGlycosylated hemoglobin, hypertension, and smoking showed no significant difference. Twelve out of 85 patients (12.9%) in A/DM group developed proliferative diabetic retinopathy (PDR) whereas 79/85 (92.9%) NoA/DM patients developed PDR (P<0.001). The onset of OA symptoms was known in 80/85 of the A/D patients, including 47 patients with onset before or at the same year as DM and 33 patients with relative onset after the year of DM. All the 10 patients with PDR (10/33) developed OA subsequent to their initiation for diabetic treatment while 0/47 A/DM patients with the onset of osteoarthritic symptoms present before or the same year as their onset of diabetes developed PDR (P<0.001).ConclusionOur study suggests that in long-term DM, PDR was significantly associated with the absence of concomitant clinical OA. This observation was highly significant if the onset of the arthritis was the same year or before the onset of the diabetes. [ABSTRACT FROM AUTHOR]

To evaluate 18F-fluorodeoxyglucose Positron Emission Tomography/ultra low dose Computed Tomography (18F-FDG PET/ ULD CT) in the work-up of pediatric uveitis. Retrospective study of 12 children followed for uveitis who underwent whole body 18F-FDG PET/ULD CT between 2011 and 2019. The average age of the patients was 11 years. A total of 100% of patients presented with bilateral uveitis, 50% had panuveitis and 92% had various choroidal involvement. Relevant information for diagnosis was provided in four patients. 5/12 had an abnormal 18F-FDG uptake. Of these, three patients had pathognomonic images of active granulomatous diseases. Three patients underwent PET CT-guided biopsies of which two were positive for sarcoidosis. 18F-FDG PET/CT provided important information for final diagnosis in approximately 30% (4/12) of pediatric patients with bilateral uveitis. Whole body FDG PET/ULD CT can contribute to the final diagnosis thanks to pathognomonic image of active granulomatous disease and/or by indicating metabolically active site of biopsy that would not be visualized in thorax CT. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate neurosyphilis cerebrospinal fluid (CSF) findings and initial ophthalmic manifestations in patients with syphilitic uveitis.Methods: We retrospectively reviewed the records of CSF analysis of 14 patients with syphilitic uveitis with treponemal analysis - chemiluminescent immunoassay and TPHA- and non-treponemal analysis - Rapid Plasma Reagin test - RPR.Results: 86% were males and 43% HIV+. Ocular signs of syphilis lead to the diagnosis of syphilis in 78% of patients. Typical syphilitic uveitis presentations included: acute syphilitic posterior placoid chorioretinitis (50% of patients), retinitis (21% of patients) and punctate inner retinitis (7% of patients). 57% of patients had definite neurosyphilis by the CDC criteria, while 71% had CSF abnormalities suggestive of central nervous system involvement.Conclusion: Based on international guidelines, the frequent CSF abnormalities found in syphilitic uveitis patient supports the diagnosis of neurosyphilis in a majority of patients. [ABSTRACT FROM AUTHOR]

Adhesion molecules play a central role in leukocyte adhesion to the blood-retinal barrier (BRB) during uveitis. VCAM-1 expression on the BRB has been already described but although structurally similar, ICAM-1 has shown in various autoimmunity models to have distinct role and expression. Here, we induced uveitis in C57Bl/6 mice by adoptive transfer of semi-purified T cells from IRBP1-20-immunized mice. Using Flow cytometry analysis on transferred cells and immunofluorescence staining on retina we have studied the comparative ocular expression of both ICAM-1 and VCAM-1 and their ligands LFA-1 and VLA-4 at the surface of uveitogenic cells. Our results showed that LFA-1 and VLA-4 are expressed on both T and non T cells, VLA-4 sparsely and LFA-1 ubiquitously. Considering retinal expression, ICAM-1 is faintly present and VCAM-1 is absent in naive eyes. Only ICAM-1 is present on infiltrating cells in the retina and vitreous, while only VCAM-1 extends to perivascular glial cells and all along the internal limiting membrane. Finally, ICAM-1 is strongly expressed on the RPE, where VCAM-1 expression is much weaker. VCAM-1 seems most strongly expressed on the internal BRB while ICAM-1 predominates on the external BRB. Those major differences in the expression pattern could represent differential entry pathways for inflammatory cells to penetrate the eye. [ABSTRACT FROM AUTHOR]

Abstract: Leukocyte adhesion to the blood retinal barrier is a critical step in the pathogenesis of non-infectious uveitis and is mediated in part through the induction of adhesion molecules on retinal cells. Here, we have investigated the retinal expression of Vascular Cell Adhesion Molecule 1 (VCAM-1) in mouse experimental models of non-infectious uveitis. For each eyes, a histological score was given, and the expression of VCAM-1 analyzed by immunohistology. Co-labellings for GFAP, endoglin, aquaporin 4 and recoverin were also performed in order to determine which cell type expressed VCAM-1. In low grade uveitis, obtained after adoptive transfer of semi-purified autoreactive lymphocytes, VCAM-1 was only punctually expressed in the internal limiting membrane and epithelial cells of the ciliary body. Using the same adoptive transfer protocol, we found that, in correlation with disease severity, the staining extended to all internal limiting membranes, vasculitis lesions, Müller cell extensions, outer limiting membranes and RPE cells. VCAM-1 expression in the inner limiting membrane and Müller cell extensions co-stained with GFAP expression. In vasculitis lesions, VCAM-1 co-localized with either GFAP and endoglin expression. The labeling in the outer limiting membrane, did not exactly co-stained with AQ4 (Müller cells marker) or recoverin (photoreceptor marker) and the nature of this expression remained unexplained. Finally, VCAM-1 expression was also analyzed in classical experimental autoimmune uveitis eyes, and a similar pattern of expression was found. In conclusion VCAM-1 is expressed on all blood retinal barrier cells during experimental non-infectious uveitis and might thus play an important role in inflammatory cell recruitment during disease development. [Copyright &y& Elsevier]

Purpose To investigate the effect of dexamethasone intravitreal implant (Ozurdex; Allergan, Inc) in noninfectious uveitis. Methods Charts of patients with noninfectious uveitis treated by dexamethasone intravitreal implants were reviewed in a retrospective study. Uveitis etiologies, treatment indications, visual acuity, central retinal thickness measured by optical coherence tomography, intraocular pressure and number of injections were collected. Parameters were analyzed before injection (29 ± 6 days), after 5-6 weeks (49 ± 10 days) (short follow-up) and 4-5 months (134 ± 2 days) (long follow-up) post Ozurdex injection. Results We included 14 patients (20 eyes, 26 implants injections). Before injections, mean visual acuity was 0.5 ± 0.5 log MAR and improved to 0.3 ± 0.4 log MAR at short time follow-up and to 0.3 ± 0.5 log MAR at long time follow-up. Macular thickness has decreased by 101 ± 126 µm at short time follow-up and 83 ± 162 µm at long time follow-up. Mean intraocular pressure was 16 ± 5 mmHg before injections, 17 ± 6 mmHg at short time follow-up and 15 ± 3 mmHg at long time follow-up. Conclusions In noninfectious uveitis, dexamethasone implant can improve visual acuity and decrease macular thickness without significant increase of intraocular pressure. Although the effect seems limited in time. [ABSTRACT FROM AUTHOR]

Purpose Diagnosis and treatment of intraocular lymphoma remains a clinical challenge. Herein, we present a complicated case in which the diagnosis was made after the acute worsening of retinal lesions during oral steroid treatement. Methods A 49 year old woman complaning of progessive visual acuity decrease was referred with visual acuity of hand movements in the right eye accompanied by vitritis and two peripheral white retinal lesions with vasculitis. Futher examinations excluded the diagnosis of the main causes of infectious and non infectious uveitis and pathological examination of vitreous cells was not compatible with the diagnosis of lymphoma. Results Systemic steroid treatment were given with an initial improvement of the inflammatory conditions. However, a week later an acute worsening of the retinal lesions occured, taking the appearence of a very severe retinal necrosis. Another vitrectomy was thus performed to exclude again infectious causes but was negative for virus and toxo. Finally, the diagnosis of intraocular lymphoma was made on a 3rd diagnostic vitrectomy with retinal biopsy. The patient was treated with a series of intravitreous methotrexate injections followed by chemo‐ and radiotherapy. Conclusion Systemic administration of corticosteroids in patient with intraocular B lymphoma may lead to dramatic lesion extention preceeded by temporal clinical stabilisation or improvement. [ABSTRACT FROM AUTHOR]

Purpose Non infectious uveitis are characterized by the penetration of immune cells into the eye which depends on adhesion molecules expression on the blood retinal barrier (BRB). In this work, we have studied the expression of the adhesion molecules VCAM‐1 and ICAM‐1 in experimental autoimmune uveitis (EAU) by adoptive transfer and the expression of their ligands, VLA‐4 and LFA‐1, on autoreactive T‐lymphocyte (TL) Methods Autoreactive TL, obtained from the lymph node of C57BL6 mice immunized with IRBP 1‐20, were purified using CD4+ magnetic cell sorting. Those cells were studied by flow cytometry for their expression of VLA‐4 and LFA‐1. ELISAs and intracytoplasmic flow cytometry were performed to study the cytokine expression profile. Then, EAU were induced by adoptive transfer of those cells into naive mice. VCAM‐1 and ICAM‐1 histological and cellular expression was studied by immunofluorescence on eye cryosections Results Autoreactive TL were found to be from the Th1 and Th17 phenotypes. LFA‐1 was expressed on all T and non T cells and VLA‐4 mostly on non T cells. Only a minority of TL showed VLA‐4 expression. In the eye of naïve mice VCAM‐1 was absent and ICAM‐1 present only at very low level. VCAM‐1 and ICAM‐1 expression is correlated to the severity of the disease. Interestingly, VCAM‐1 was more expressed on the internal BRB and ICAM‐1 on the external BRB Conclusion This work shows that the adhesion molecules VCAM‐1 and ICAM 1 were expressed differently on the internal and external BRB and that their respective ligands VLA‐4 and LFA‐1 were also expressed differently on lymphocytes. This works complete the understanding of the major role of the adhesion molecules VCAM‐1 and ICAM‐1 in the induction uveitis in the adoptive transfer model [ABSTRACT FROM AUTHOR]

Purpose Aquaporin‐1 (AQP1) is involved in cell migration and proliferation. This study aims to investigate AQP1 expression in membranes from proliferative vitreoretinopathy (PVR) and epiretinal membranes (ERM) Methods 20 Membranes PVR and ERM were collected following eye surgery from 20 eyes from 20 patients. AQP1 mRNA and protein expression were determined by RT‐qPCR and immunofluorescence in both PVR and ERM Results AQP1 mRNA and protein were expressed in both PVR and ERM as shown by both RT‐qPCR and immunofluorescence. Moreover, AQP1 protein expression was heterogeneous among and between PVR and ERM, and was highly colocalized with alpha‐smooth muscle actin (SMA or Acta2) and slightly colocalized with glial fibrillary acidic protein (GFAP). Conclusion AQP1 mRNA and protein were expressed in membranes from PVR and in ERM. Due to the absence of SMA and GFAP colocalization, it is likely that AQP1 is expressed by at least two distinct cells types. AQP1 might play a role in cell migration and proliferation occurring during the formation of PVR and ERM, and could represent a new therapeutic target [ABSTRACT FROM AUTHOR]

Purpose To compare the clinical characteristics and visual prognosis of patients with anterior uveitis (AU) with intraocular fluid analysis positive for Rubella virus (RV), Herpes Simplex virus (HSV) or Varicella Zoster virus (VZV) in order to discriminate rubella virus AU from herpes virus AU. Methods Retrospective, observational study.Clinical records of 106 patients with anterior uveitis and positive Polymerase chain reaction and/ or Goldmann‐Witmer coefficients for RV (n=57), HSV (n=39) and VZV (n=10) were analyzed. Demographic constitution, ophthalmological characteristics and visual prognosis were compared. Results All three types of viral AU were characterized by unilateral involvement (80‐97%). RV‐AU was characterized by younger age at onset and chronic course, and was typically associated with cataract at presentation. Heterochromia was present in 23% of RV‐AU patients. AU associated with HSV or VZV infection occurred characteristically in older patients and frequently followed an acute course. Associated clinical features included conjunctival redness, corneal edema, history of keratitis and development of posterior synechiae. HSV‐AU had more often severe AU whereas the presence of vitritis was more common in RV‐AU and VZV‐AU. The prevalence of documented IOP above 30mm Hg (25‐50%, P=0.06) and development of glaucoma (18‐30%, P=0.687) were similar in all three groups. Retinal scarring was seen in 22% of RV‐AU eyes, 0% HSV‐AU eyes and in 11% of VZV‐AU eyes Visual prognosis was favorable for all three groups. Conclusion Our results point out clinical differences between RV‐AU, HSV‐AU and VZV‐AU and might be especially of value to ophthalmologists who lack the possibility of intraocular fluids analysis to discriminate rubella virus AU from herpes virus AU. [ABSTRACT FROM AUTHOR]

Purpose Retinal pigmented epithelium (RPE) cell activation by cytokines plays an important role in autoimmune uveitis development. The aim of this study was to investigate if Suppressors of Cytokine Signaling (SOCS1) overexpression in RPE cells can modulate this activation. Methods SOCS clone and control clone were isolated after stable transfection of APRE‐19 with plasmids containing or not the SOCS1 gene. qRT‐PCR was used to measure SOCS1 mRNA expression. Clones were stimulated by IFNγ or/and TNFα. Membrane expression of MHCII and CD54 was measured by flow cytometry, IL‐8 secretion by ELISA and (P‐)STAT‐1 and IκBα expression by Western Blot. Results We found a stable high expression of SOCS1 in the SOCS clone as compared to the control clone or native ARPE cells. This SOCS1 overexpression strongly decreased IFNγ‐mediated STAT‐1 phosphorylation, MHCII induction and CD54 upregulation. On the contrary, SOCS1 overexpression had no effect on TNFα‐mediated IκBα degradation, IL‐8 upregulation, but weakly inhibited CD54 upregulation. During simultaneous IFNγ and TNFα stimulation, SOCS1 overexpression canceled the inhibitory effect of IFNγ on TNFα‐induction of IL‐8 secretion. Conclusion SOCS1 overexpression can block IFNγ but have almost no effect on TNFα activation of retinal pigmented epithelium cells. Those data suggest that SOCS1 overexpression might only affect certain cytokine pathways important in autoimmune uveitis development. [ABSTRACT FROM AUTHOR]

Purpose To review the clinical outcome of our series of patients with uveitis and secondary glaucoma in which a trabeculectomy has been performed. Methods Each patient was classified according to clinical presentation, pre and postoperative IOP, visual acuity and number of antiglaucoma drops needed. The outcome of trabeculectomy was classified in 3 categories: absolute success defined as IOP controlled (< 21 mmHg) without other treatment, relative success defined as IOP controlled with hypotensive drops and failed when IOP was not controlled or required hypotensive drops and oral acetazolamide. Success ratio with and without perioperative mitomycin were compared. Results Mean visual acuity, IOP and number of drop used decreased at 3 month and at last follow‐up. The mean follow‐up was 19.3 months (2.9 – 67.1 months). At 3 month, we found 80% of overall success (53,33% of relative success and 26,67% of absolute success) and 20% of failure. At final follow‐up, we also found 80% of overall success(56,67% of relative success and 23,33% of absolute success) and 20% of failure. Patients in whom perioperative mitomycin were used where more likely to have a favorable outcome (last follow‐up: 83.33% vs 75%) but this difference between the two groups was not statistically significant. Conclusion Our data are in accordance with the rest of the literature which shows that trabeculectomy with antimetabolite agents allows IOP control in the majority of patients. However, many of them will still need topical hypotensive drugs. [ABSTRACT FROM AUTHOR]

Purpose Leukocyte adhesion to the blood retinal barrier is a critical step in the pathogenesis of autoimmune uveitis and is mediated through adhesion molecule expression. Here, we have investigated the retinal expression of VCAM1 in an adoptive transfer model of experimental autoimmune uveitis (EAU). Methods C57Bl6 mice were immunized with interphotoreceptor retinoid‐binding protein (IRBP) peptide 1–20. Activated IRBP‐specific T cells were prepared from their draining lymph nodes and spleens, cultured with IRBP peptide 1‐20 and adoptively transferred in C57BL/6 mice. The animals were sacrified after 3 weeks and the eyes processed for immunohistology. The severity of the disease was determined by histological grading. The expression of VCAM1 was analysed by immunofluorescence. Co‐labelling with GFAP (glial cells markers) and endoglin (endothelial cell marker) were also performed in order to determine which cell type expressed VCAM1. Results In eyes with low grade uveitis, VCAM1 was only expressed at certain location of the internal limiting membranes and epithelial cells of the ciliary body. In correlation with disease severity, the staining extend to all the limiting membranes, vasculitis lesions, Muller cells extension, the outer limiting membranes and RPE cells. VCAM1 expression on the inner limiting membrane and Müller cells extension co stained with GFAP. On vasculitis lesions, VCAM1 expression co localized with either GFAP or endogline. Conclusion VCAM1 is expressed on blood retinal cells during EAU. Moreover, the intensity and extension of its expression correlates with disease severity. Those data suggest that VCAM1 plays an important role in EAU development. [ABSTRACT FROM AUTHOR]

Purpose Activation of retinal cells by IFNγ is required for inflammatory cell recruitment during experimental autoimmune uveitis (EAU) development. IFNγ activates pro‐inflammatory genes transcription but also induces suppressor of cytokine signaling (SOCS) proteins, which negatively regulate IFNγ signaling. Methods To study the effects of retinal SOCS1 overexpression on EAU, adeno‐associated vectors AAV2‐SOCS1 or AAV2‐GFP were injected intravitreally in the right eye of C57Bl6 mice. Four weeks later, EAU was induced by s.c. immunisation with IRBP peptide 1‐20. Results A high inter‐animal variability of disease induction was observed, possibly masking the effect of SOCS1. In order to normalize for disease severity, the means of ratios of the clinical and histological scores of the AAV injected eyes over the contralateral non‐injected eyes (I/NI) were calculated and found to be significantly lower in the SOCS1 group, especially in the infected layers. Unexpectedly, the mean I/NI was significantly higher than 1 in the GFP group, suggesting that injection of AAV2‐GFP itself was pro‐inflammatory. MHCII was strongly expressed during EAU. None of the MHCII+ cells was GFP+, suggesting that SOCS1 effects were not mediated through a downregulation of MHCII in transduced cells. Nevertheless, the profile of MHC class II expression in the ciliary bodies was different in AAV2‐SOCS1 injected and contralateral eyes. Conclusion In conclusion, although AAV2‐mediated SOCS1 retinal expression did not globally protect against EAU development, it significantly reduced inflammation locally at the site of infection. [ABSTRACT FROM AUTHOR]

Purpose : To study the clinical characteristics of patients with uveitis seen in our center. Methods We have retrospectively analysed the charts of 567 patients with uveitis seen in the department of ophthalmology of the CHU St‐Pierre in Bruxelles, Belgium, between January 2004 and December 2008. Each patient was classified according to the clinical presentation, anatomic localization and results from the systemic work‐up. Results Anterior uveitis was most frequent (61.9%) followed by panuveitis (21.7%), posterior uveitis (11.3%) and intermediate uveitis (5.11%). Anterior uveitis were non granulomatous in 59,8%, granulomatous in 29,1% and associated with keratitis in 11,1% of the cases. HLA‐B27 with or without seronegative SPA uveitis were the most frequent forms of anterior uveitis followed by herpes (including one third demonstrated by PCR). Intermediate uveitis were most often idiopathic or due to Fuchs uveitis syndrome. Behcet disease, followed by toxoplasmosis was the most frequent cause of posterior uveitis. Toxoplasmosis and sarcoïdosis were the most frequent causes of panuveitis. Conclusion The distribution of the different forms of uveitis is relatively closed to other published studies for the referral tertiary center. Our high percentage of final diagnosis is in accordance with the more recent series. It might reflect a better definition of certain clinical entities and the development of new diagnostic tools. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 36-year-old man who suffered an acute bilateral pain and vision impairment. The old man was treated with moxifloxacin for otitis but the condition of the patient continued to get worse. It mentions that moxifloxacin can induce the development of a pseudouveitis characterised by an acute depigmentation of the iris.