Describing the Clinical and Laboratory Features and HLA-B Pattern of Adult-Onset Idiopathic Autoimmune Uveitis at a Tertiary Hospital in South India: A Cross-Sectional Study.

INTRODUCTION: There is a scarcity of information available on clinical and laboratory features of adult-onset idiopathic autoimmune uveitis. Therefore, we conducted a single centre descriptive cross-sectional study. Patients and Methods. A chart review of all patients with idiopathic autoimmune uveitis with onset after 18 years of age who were referred to the rheumatology department between January 2017 and December 2018 was performed. Their clinical features, demographic features, and HLA-B genotypes were documented and described. RESULTS: Out of 210 patients referred to rheumatology, 66 were found to have uveitis, and 16 of these had an adult-onset idiopathic autoimmune uveitis. Apart from a slight female preponderance (62.5%), our patients were characterized by a high proportion of panuveitis (4 out of 16, i.e., 25%). There was an increased frequency of occurrence of synechiae (5 out of 16, i.e., 31.3%), retinal vasculitis (4 out of 16, i.e., 25%), optic disc edema (3 out of 16, i.e., 18.8%), and cystoid macular edema (seen in 2 patients, i.e., 12.5%). These features correlated with the anatomical subtypes. Retinal vasculitis and optic disc edema present in three fourth of all panuveitis cases were the most prominent features. The odds of finding HLA-B∗35 in retinal vasculitis were 33 times higher than odds of finding it in idiopathic autoimmune uveitis patients not having retinal vasculitis (OR 33; 95% CI 1.6-698). CONCLUSION: Idiopathic autoimmune uveitis in our patients is characterized by a high frequency of panuveitis and retinal vasculitis, and complications with a probable association between HLA-B∗35 and retinal vasculitis.

Study of ocular manifestations in tuberculosis and its association with HIV AIDS in a tertiary care hospital.

OBJECTIVE: To assess and understand the prevalence and clinical presentation of ocular morbidity in patients suffering from tuberculosis and compare it with ocular involvement in patients coinfected with tuberculosis and HIV AIDS. MATERIALS AND METHODS: This was a non-comparative, observational, cross sectional study done on 580 patients, who were diagnosed cases of tuberculosis, pulmonary or extrapulmonary, on or off treatment, visiting the Ophthalmology OPD, Tuberculosis OPD and ART Centre of the institute in the period from March 2015 to March 2018, screened for ocular morbidity. RESULTS: Out of 580, 408 patients had only tuberculosis and 172 had tuberculosis with HIV AIDS. 108 patients were found to have ocular involvement (18.6%) out of which 63 were males and 45 were females. The prevalence of ocular morbidity in patients with only tuberculosis was found to be 16.4% and in those having both tuberculosis and HIV AIDS was found to be 23.8%. CONCLUSION: Our study concludes that posterior uveitis, pan uveitis, periphlebitis and vitritis are the most common ocular manifestations in tuberculosis. In patients with both tuberculosis and HIV most common ocular findings included vitritis and herpes zoster ophthalmicus. Our study also concludes that lower CD4 counts (less than 200) in HIV AIDS patient is significantly associated with ocular involvement.

Comparison of conventional immunosuppressive drugs versus anti-TNF-α agents in non-infectious non-anterior uveitis.

OBJECTIVE: To compare the efficacy and safety of Disease-modifying antirheumatic drugs (DMARDs) and anti-TNF-α agents in patients with non-infectious non-anterior uveitis. METHODS: Single center retrospective study including adult patients with non-infectious intermediate, posterior or pan-uveitis. Outcomes were compared between patients treated with DMARDs or anti-TNF-α agents. The primary outcome was treatment failure or occurrence of serious adverse events. Treatment failure was determined by ophthalmologic criteria. RESULTS: Seventy-three patients were included, mostly female (52%). Among them, 39 were treated with DMARDs and 34 with anti-TNF-α agents. The main uveitis causes were idiopathic (30%), birdshot chorio-retinopathy (25%), sarcoidosis (16%) and Behçet's disease (14%). The primary outcome was observed in 56% of patients treated with anti-TNF-α agents versus 59% of patients treated with DMARDs (p = 0.82). Median time to observe the primary outcome was 16 months (anti-TNF-α group) versus 21 months (p = 0.52). There was no significant difference between the two groups in terms of treatment failure, corticosteroid sparing effect, visual acuity improvement or adverse events. Earlier control of ocular inflammation was achieved with anti-TNF-α agents than with DMARDs (p = 0.006). In relapsing patients, anti-TNF-α agents allowed better corticosteroid sparing (p = 0.06). CONCLUSION: DMARDs could still be used as first-line therapy for non-infectious non-anterior uveitis after corticosteroid therapy. However, anti-TNF-α agents could be proposed as an alternative in cases of severe inflammation or initial high level of steroid dependency.

Intravitreal thalidomide ameliorates inflammation in a model of experimental uveitis induced by BCG.

Uveitis encompasses a heterogeneous and complex group of conditions characterized by intraocular inflammation, frequently affecting young individuals and representing an important cause of irreversible blindness worldwide. Animal models have been critical to understand etiology and pathogenesis of uveitis, being also employed to assess new therapeutic strategies, preceding human studies. However, there is still a need of developing and studying different models, due to the difficulties in recapitulating all forms of human uveitis effectively. Although corticosteroids are usually the first-line therapy for non-infectious uveitis, their long-term use is limited by potentially serious side effects in all possible delivery routes. Thus, thalidomide, a drug with anti-inflammatory and antiangiogenic properties, was investigated in a novel experimental model of uveitis, induced by Mycobacterium bovis Calmette-Guérin Bacillus (BCG), in rabbits. The experimental protocol consisted of two subcutaneous injections of BCG, followed by two intravitreal injections of the same antigen, inducing panuveitis. Animals were treated with a single intravitreal injection of thalidomide suspension or PBS. Clinical manifestations of uveitis improved after intravitreal thalidomide, involving both anterior and posterior segments. Protein content, N-acetyl-b-glucosaminidase (NAG) and myeloperoxidase (MPO) activities were elevated in ocular tissues after disease induction, further decreasing post-treatment with intravitreal thalidomide. This therapeutic response was also confirmed on ocular electrophysiology, as well as histopathology. This experimental model induced panuveitis in rabbits using a low-cost mycobacterial antigen, with intraocular inflammation subsequently improving after treatment. Intravitreal thalidomide may be a potential alternative to treat intraocular inflammation in corticosteroid-sparing therapies.

Features of ectopic lymphoid-like structures in human uveitis.

Persistent non-infectious uveitis has a significant morbidity, but the extent to which this is accompanied by inflammation driven remodelling of the tissue is unclear. To address this question, we studied a series of samples selected from two ocular tissue repositories and identified 15 samples with focal infiltration. Eleven of fifteen contained lymphocytes, both B cells (CD20 positive) and T cells (CD3 positive). In 20% of the samples there was evidence of ectopic lymphoid like structures with focal aggregations of B cells and T cells, segregated into anatomically different adjacent zones. To investigate inflammation in the tissue, an analysis of 520 immune relevant transcripts was carried out and 24 genes were differentially upregulated, compared with control tissue. Two of these (CD14 and fibronectin) were increased in ocular inflammation compared to control immune tissue (tonsil). We demonstrate that in a significant minority of patients, chronic persistent uveitis leads to dysregulation of ocular immune surveillance, characterized by the development of areas of local ectopic lymphoid like structures, which may be a target for therapeutic intervention directed at antibody producing cells.

Successful multi-modality approach in management of human leukocyte antigen-B27 associated fulminant panuveitis - rare presentation.

Objective: To report a multimodality approach in the management of human leukocyte antigen B27 (HLA-B27) associated fulminant posterior uveitis, an uncommon presentation, with good visual and anatomical recovery. Methods: A 33-year-old young male presented with HLA-B27 associated severe posterior uveitis, which is a relatively uncommon presentation. The patient had severe vitritis with papillitis, which was sequentially and stepwise managed with oral steroids, pars plana vitrectomy, immunosuppressive agents and sustained release intravitreal steroid implant. Results: The patient had a good recovery of vision with complete resolution of inflammation and without any long-term complication. Conclusion: HLAB27 positivity can be associated with an uncommon presentation of fulminant posterior uveitis that requires a judicious and stepwise multimodality approach in its management, and can have a good visual and anatomical outcome as demonstrated in our case.

Unusual panuveitis in a child: toxocariasis associated with ocular myiasis.

Most panuveitis in children are caused by infectious agents. A detailed clinical history and clinical examination are helpful in the diagnosis, but specific techniques are sometimes required to identify the causing specimen. We report the first published case of panuveitis in a child caused by simultaneous ocular infection by Toxocara canis and a fly larva and the innovative use of immunodiffusion technique in the vitreous for the diagnosis.

Clinical manifestations of cytomegalovirus-associated posterior uveitis and panuveitis in patients without human immunodeficiency virus infection.

IMPORTANCE: Little attention has been paid to clinical features of cytomegalovirus (CMV) infections in individuals without human immunodeficiency virus (HIV). OBJECTIVE: To describe the clinical manifestations and comorbidities of patients without HIV infection who have CMV-associated posterior uveitis or panuveitis. DESIGN AND SETTING: Retrospective observational case series in an academic research setting. PARTICIPANTS: The medical records were reviewed of 18 patients (22 affected eyes) diagnosed as having posterior uveitis or panuveitis who had aqueous positive for CMV by polymerase chain reaction techniques. MAIN OUTCOME MEASURES: Demographic data, clinical manifestations, and associated systemic diseases were recorded. RESULTS: Ocular features included focal hemorrhagic retinitis (n = 13) and peripheral retinal necrosis (n = 7). Two eyes had no focal retinal lesions but manifested vasculitis and vitritis. All patients exhibited vitreous inflammation. Inflammatory reactions in anterior segments developed in 14 of 22 eyes (64%). Retinal vasculitis was observed in 16 of 22 eyes (73%) and included mostly arteries (in 13 of 16 eyes [81%]). Eleven of 18 patients were taking immunosuppressive medications (5 for hematologic malignant diseases, 4 for systemic autoimmune diseases, and 2 following organ transplants). One additional patient was diagnosed as having non-Hodgkin lymphoma 3 months after the onset of CMV-associated panuveitis, and another patient had primary immunodeficiency disorder. Of the remaining 5 patients, 2 had diabetes mellitus, and 3 had no associated systemic diseases and exhibited no evidence of immune deficiency. CONCLUSIONS AND RELEVANCE: Cytomegalovirus-associated infections of posterior eye segments can develop in patients without HIV infection who have compromised immune function of variable severity but may occur also in individuals who have no evidence of immune insufficiency. Cytomegalovirus infections located in posterior eye segments in patients without HIV infection caused intraocular inflammatory reaction in all cases and demonstrated more variable clinical presentation than classic CMV retinitis observed in patients with HIV infection.

Poststreptococcal syndrome uveitis in South African children.

OBJECTIVE: To describe the demographics, clinical features and management of the largest case series to date on poststreptococcal syndrome uveitis (PSU), a newly recognised immune-mediated response to group A ß-haemolytic streptococcus infection. METHODS: Case notes of all patients presenting to the Red Cross War Memorial Children's Hospital, Cape Town, with serologically confirmed PSU between 2004 and 2010, were retrospectively reviewed. RESULTS: A total of 22 cases were identified. Ages ranged from 4 to 12 years. 64% were black children and 64% were boys. Presenting visual acuities ranged from 6/6 to hand movements (median 6/24). 68% had bilateral disease. All had anterior uveitis (27% with posterior synechiae and 27% with hypopyon). 36% had vitritis and 23% had panuveitis. None had systemic illness or features of other poststreptococcal syndromes such as rheumatic fever, glomerulonephritis or polyarthritis. Anti-streptococcal titres (anti-streptolysin O and/or anti-deoxyribonuclease B) were significantly raised in all cases. Treatment comprised topical steroids and cycloplegic agents. Those with severe posterior segment involvement (41%) were treated with systemic corticosteroids. 55% received a course of oral penicillin. 82% had a single episode of uveitis. Four children had recurrences. Final visual acuities ranged from 6/6 to 6/36 (median 6/6). CONCLUSION: This case series significantly increases the evidence for PSU currently available in the world literature. The condition can manifest with the full spectrum of ocular inflammation, and most cases respond well to standard uveitis regimens. The role of antibiotic therapy remains unclear and requires further investigation.

Bilateral panuveitis following intravesical BCG immunotherapy for bladder carcinoma.

PURPOSE: To report a case of bilateral panuveitis following local treatment with Bacille Calmette-Guérin (BCG) immunotherapy for superficial bladder carcinoma. DESIGN: Case report and literature review. METHODS: A 70-year-old female presented with severe bilateral anterior chamber inflammation 5 days after intravesical BCG instillation. Despite topical steroids and mydriatics, inflammation worsened and bilateral optic nerve swelling developed. RESULTS: Oral corticosteroids settled the ocular inflammation, and optic nerve function recovered. A trial of steroid cessation caused rebound uveitis, so she remains on maintenance doses of oral corticosteroid. CONCLUSIONS: Ocular inflammations following BCG therapy for bladder cancer are rare, and little is known about the management of such cases. This is the first report of bilateral panuveitis with optic nerve edema following such treatment.

Uveitis in DiGeorge syndrome: a case of autoimmune ocular inflammation in a patient with deletion 22q11.2.

PURPOSE: Del22q11.2, also known as DiGeorge syndrome, has a spectrum of ocular, facial and systemic features. Despite features of T cell dysfunction, infection and autoimmunity (including juvenile idiopathic arthritis), uveitis has not been described in patients with DiGeorge syndrome. METHODS: We describe a case of a 25-year-old male with bilateral granulomatous panuveitis who after initial investigation and treatment for an infectious cause was determined to have autoimmune-related uveitis with evidence on clinical, laboratory and imaging assessments suggestive of ocular sarcoidosis. RESULTS: The patient was found to have a normal T cell count and T cell proliferative response that was compared to a control patient, and phenotypes determined by flow cytometry were normal. However, the CD4/CD8 ratio in this patient was slightly lower than normal and the number of CD28 negative T cells, in both CD4 and CD8 populations, were significantly higher than a control. CONCLUSIONS: The significance of these T cell abnormalities is unknown in the context of this patient's uveitis but is suggestive of a role in autoimmunity, which is a known phenomenon in del22q11.2 syndrome, although autoimmune-related uveitis is not a previously described feature.

Elevated serum IL-23 correlates with intraocular inflammation after cataract surgery in patients with Vogt-Koyanagi-Harada disease.

PURPOSE: Patients with Vogt-Koyanagi-Harada (VKH) disease are known to have severe inflammation after cataract surgery. This study was designed to investigate the role of IL-17-producing T helper (Th17) cell-related pro-inflammatory cytokines on postoperative inflammation in VKH patients. METHODS: Serum from nine VKH patients and nine controls with age-related or congenital cataract was collected before and 1, 7, 30 and 90 days after surgery, and aqueous humor (AqH) at the commencement of surgery. Protein levels of IL-23, IL-27, IL-17 and IFN-gamma in serum and AqH were measured by ELISA. A laser flare-cell photometer was used to quantify intraocular inflammation. RESULTS: Serum IL-23 levels were significantly increased in VKH compared with control patients and peaked at 1 day postoperative, decreased rapidly in the first week, then attenuated gradually. In VKH patients, serum levels of IFN-gamma were elevated in the first week after surgery and IL-27 was upregulated in the first month. Importantly, serum IL-23 levels were strongly correlated with aqueous flare value (r=0.689; p=0.007) and cell counts (r=0.671; p=0.01) in VKH compared with control patients. CONCLUSIONS: The data indicate that serum IL-23 levels are significantly elevated in VKH compared with control patients and are strongly associated with postoperative intraocular inflammation.

[Ophthalmologic disease in sarcoid-like granulomatosis and true sarcoidosis in immunodeficiency. Four case reports]. / Atteintes ophtalmologiques de la sarcoïdose et des "sarcoid-like reaction" dans les déficits immunitaires. A propos de 4 cas.

Granulomatosis lesions occurring after diagnosis of primary or secondary immunodeficiency are not accidental and have been described in a small number of patients suffering from various diseases: common variable immunodeficiency (CVID), malignancy (lymphoma and solid tumors), and acquired immunodeficiency syndrome (AIDS). Two types of granulomatosis can appear: true sarcoidosis and sarcoid-like reaction. We report four patients, two with CVID and two with malignancy, in whom clinical granulomatosis appeared a few months to a few years after diagnosis of immunodeficiency. They developed noncaseating granulomas of the lung, spleen and liver associated with conjunctival granulomas and bilateral panuveitis. The granulomatous disorder was diagnosed after immunodeficiency on histopathological studies revealing noncaseating granulomas. Causation agents such as infectious organisms and environmental compounds were excluded. The relationship between sarcoid-like reaction, true sarcoidosis and immunodeficiency is discussed. The underlying pathophysiology responsible for the association between granuloma formation and immunodeficiency in the same patient remains obscure. It may be quite difficult to distinguish true sarcoidosis and sarcoid-like reaction. It is possible that these two entities are the clinical extremes of a common pathological process.

Inter- and intramolecular epitope spreading in equine recurrent uveitis.

PURPOSE: To test the hypothesis that inter- and intramolecular spreading to S-antigen (S-Ag) and interphotoreceptor retinoid binding protein (IRBP)-derived epitopes occurs in a spontaneous model of recurrent uveitis in the horse. METHODS: The immune response of eight horses with equine recurrent uveitis (ERU) was compared with that of five control horses with healthy eyes. Lymphocytes derived from peripheral blood (PBLs) were tested every 8 weeks for their reactivity against S-Ag and various S-Ag and IRBP-derived peptides for 12 to 39 months (median, 22 months). During uveitic episodes, additional blood samples were analyzed. RESULTS: Intermolecular epitope spreading was detectable in all ERU cases during the study. Intramolecular spreading occurred in seven (of eight) horses with ERU. Fourteen relapses were analyzed during the observation period. Ten uveitic episodes were accompanied by neoreactivity to S-Ag or IRBP-derived peptides during the relapse. Shifts in the immune response profile were also detectable without any clinical signs of inflammation. Eye-healthy control horses were negative at all time points in the in vitro proliferation assays. CONCLUSIONS: Inter- and intramolecular spreading was detectable in a spontaneous model of recurrent uveitis. The shifts in immunoreactivity could account for the remitting-relapsing character of the disease.

Intracellular T lymphocyte cytokine profiles in the aqueous humour of patients with uveitis and correlation with clinical phenotype.

This study aimed to investigate whether T cells in aqueous humour are different in different types of uveitis and correlate with clinical phenotype. Patients with clinically different types of uveitis, but all displaying active anterior uveitis, were phenotyped and samples of aqueous humour (AH) and peripheral blood (PB) collected. Cells from AH and PB were separated by centrifugation and by density gradient centrifugation (to obtain mononuclear cells PBMC), respectively. Cells were activated with PMA and ionomycin in the presence of Brefeldin A, stained for surface markers and intracellular cytokines, and analysed by flow cytometry. The cytokine profile was correlated with the clinical phenotype. Increased percentages of interleukin (IL)-10+-, but not interferon (IFN)-gamma+ T lymphocytes were found in AH compared with PB in patients with acute anterior uveitis (AAU), FHC or chronic panuveitis (PU). There was a trend towards elevated levels of IL-10+ T cells in AH from patients with FHC compared with AH from acute uveitis and panuveitis patients. Increased levels of IL-10+ T cells in AH compared with PB were also found in samples from patients with isolated uveitis, but not those with associated systemic disease. Levels of cytokine-positive T cells were not associated with the use of topical steroids or to the severity of the anterior uveitis. While type I cytokine-producing T lymphocytes are present in AH during AU, the presence of increased proportions of IL-10+ T lymphocytes in AH from patients with uveitis may be indicative of an anti-inflammatory mechanism that may influence the type and course of ocular inflammation in these patients.