The gut microbiome and HLA-B27-associated anterior uveitis: a case-control study.

BACKGROUND: The human gut microbiome (GM) is involved in inflammation and immune response regulation. Dysbiosis, an imbalance in this ecosystem, facilitates pathogenic invasion, disrupts immune equilibrium, and potentially triggers diseases including various human leucocyte antigen (HLA)-B27-associated autoinflammatory and autoimmune diseases such as inflammatory bowel disease (IBD) and spondyloarthropathy (SpA). This study assesses compositional and functional alterations of the GM in patients with HLA-B27-associated non-infectious anterior uveitis (AU) compared to healthy controls. METHODS: The gut metagenomes of 20 patients with HLA-B27-associated non-infectious AU, 21 age- and sex-matched HLA-B27-negative controls, and 6 HLA-B27-positive healthy controls without a history of AU were sequenced using the Illumina NovaSeq 6000 platform for whole metagenome shotgun sequencing. To identify taxonomic and functional features with significantly different relative abundances between groups and to identify associations with clinical metadata, the multivariate association by linear models (MaAsLin) R package was applied. RESULTS: Significantly higher levels of the Eubacterium ramulus species were found in HLA-B27-negative controls (p = 0.0085, Mann-Whitney U-test). No significant differences in microbial composition were observed at all other taxonomic levels. Functionally, the lipid IVA biosynthesis pathway was upregulated in patients (p < 0.0001, Mann-Whitney U-test). A subgroup analysis comparing patients with an active non-infectious AU to their age- and sex-matched HLA-B27-negative controls, showed an increase of the species Phocaeicola vulgatus in active AU (p = 0.0530, Mann-Whitney U-test). An additional analysis comparing AU patients to age- and sex-matched HLA-B27-positive controls, showed an increase of the species Bacteroides caccae in controls (p = 0.0022, Mann-Whitney U-test). CONCLUSION: In our cohort, non-infectious AU development is associated with compositional and functional alterations of the GM. Further research is needed to assess the causality of these associations, offering potentially novel therapeutic strategies.

Clonal cutaneous and neurosyphilis: A pitfall in pseudolymphoma diagnosis.

Syphilis is a sexually transmitted infectious disease caused by the bacterium Treponema pallidum and can cause a wide variety of cutaneous manifestations, most commonly, a papulosquamous eruption of the trunk and extremities. Treatment with penicillin is curative. We report a case of a 69-year-old man who presented with recent onset of blurry vision and a nonpainful, nonpruritic eruption of pink-to-violaceous dermal nodules on his upper trunk and upper extremities. Biopsies of two separate locations revealed a dense superficial and deep perivascular atypical lymphocytic infiltrate with admixed plasma cells, histiocytes, and eosinophils. Some scattered cells expressed CD30, PD1, BCL-6, and ICOS. T-cell receptor (TCR)-rearrangement showed an identical TCR-gamma clone between both biopsy specimens. The patient was subsequently seen by ophthalmology and diagnosed with acute anterior uveitis. Rapid plasma reagin was reactive and cerebrospinal fluid studies showed findings consistent with a diagnosis of neurosyphilis. A T. pallidum immunostain of the skin biopsies was performed upon re-review, and was diffusely positive for spirochetes at the dermal-epidermal junction and within injured vessels. The patient was treated with penicillin G with near-resolution of his skin lesions. This case highlights the unusual ability of syphilis to mimic a T-cell lymphoma with matching clones across two different biopsy sites.

Collaborative Ocular Tuberculosis Study Consensus Guidelines on the Management of Tubercular Uveitis-Report 2: Guidelines for Initiating Antitubercular Therapy in Anterior Uveitis, Intermediate Uveitis, Panuveitis, and Retinal Vasculitis.

TOPIC: The Collaborative Ocular Tuberculosis Study (COTS), supported by the International Ocular Inflammation Society, International Uveitis Study Group, and Foster Ocular Immunological Society, set up an international, expert-led consensus project to develop evidence- and experience-based guidelines for the management of tubercular uveitis (TBU). CLINICAL RELEVANCE: The absence of international agreement on the use of antitubercular therapy (ATT) in patients with TBU contributes to a significant heterogeneity in the approach to the management of this condition. METHODS: Consensus statements for the initiation of ATT in TBU were generated using a 2-step modified Delphi technique. In Delphi step 1, a smart web-based survey based on background evidence from published literature was prepared to collect the opinion of 81 international experts on the use of ATT in different clinical scenarios. The survey included 324 questions related to tubercular anterior uveitis (TAU), tubercular intermediate uveitis (TIU), tubercular panuveitis (TPU), and tubercular retinal vasculitis (TRV) administered by the experts, after which the COTS group met in November 2019 for a systematic and critical discussion of the statements in accordance with the second round of the modified Delphi process. RESULTS: Forty-four consensus statements on the initiation of ATT in TAU, TIU, TPU, and TRV were obtained, based on ocular phenotypes suggestive of TBU and corroborative evidence of tuberculosis, provided by several combinations of immunologic and radiologic test results. Experts agreed on initiating ATT in recurrent TAU, TIU, TPU, and active TRV depending on the TB endemicity. In the presence of positive results for any 1 of the immunologic tests along with radiologic features suggestive of past evidence of tuberculosis infection. In patients with a first episode of TAU, consensus to initiate ATT was reached only if both immunologic and radiologic test results were positive. DISCUSSION: The COTS consensus guidelines were generated based on the evidence from published literature, specialists' opinions, and logic construction to address the initiation of ATT in TBU. The guidelines also should inform public policy by adding specific types of TBU to the list of conditions that should be treated as tuberculosis.

Ophthalmologic findings associated with Rhodococcus equi bronchopneumonia in foals.

OBJECTIVE: To describe ocular findings associated with Rhodococcus equi bronchopneumonia in foals, and to determine whether severity of the ocular lesions is related with outcome. ANIMALS STUDIED: Foals diagnosed with R equi infection at the VTH-UAB from January 2002 to December 2017. PROCEDURE: Rhodococcus equi infection was diagnosed by means of clinical signs, radiographic/ultrasonographic findings, and/or positive culture. In all the foals, a complete ophthalmic examination by a boarded ophthalmologist was performed and ocular signs were recorded and graded (0-4). RESULTS: Thirty-nine foals were included in the study, from which 12 showed signs of bilateral anterior uveitis (30.8%). Among these, three foals were classified as mildly uveitis-affected (MUA:7.7%) and nine as severely uveitis-affected (SUA:23.1%). Five SUA foals showed green aqueous flare (5/9;55.5%). Despite the systemic treatment, 9/39 sick foals died (23.1%), the fatality rate being different between groups: SUA (4/9;44.4%), MUA (0/3; 0%) and nonuveitis-affected foals (5/27;18.5%). Among SUA foals, only one with green aqueous flare died (1/5;20%). CONCLUSION: Bilateral anterior uveitis is highly prevalent in foals with R equi pneumonia (30.8%). The severity of anterior uveitis might be considered a nonsurvival prognostic factor and, until proven otherwise, green aqueous flare could be taken as a strongly suggestive ocular sign of the disease. Findings of this study remark the clinical relevance of performing a complete ophthalmic examination in sick foals, in order to help in the diagnosis and prognosis of uveal diseases, as well as to guaranteeing visual soundness.

Nongranulomatous Uveitis as the First Manifestation of Syphilis.

PURPOSE: The incidence of syphilis appears to be increasing in recent years. Although any structure of the eye can be involved in syphilis, isolated unilateral anterior uveitis as an initial sign of the disease is rare. We report a case of ocular syphilis presenting as a mild unilateral, nongranulomatous, anterior uveitis in an otherwise asymptomatic patient. CASE REPORT: A 64-year-old white male patient presented with a 3-day history of mildly reduced vision, photophobia, and pain in his left eye. The patient denied prior occurrences, and no contributing ocular or medical history was elicited. Entering corrected distance acuities were 20/25+ in the right eye and 20/20- in the left eye. Slit lamp examination of the left eye revealed a moderate circumlimbal flush, numerous fine keratic precipitates, and mild-to-moderate white blood cells in the anterior chamber. The patient was diagnosed as having acute, idiopathic, nongranulomatous, anterior uveitis, and topical steroid/cycloplegic treatment was initiated. Despite an initially positive, although somewhat sluggish response to treatment, the patient's uveitis suddenly worsened on day 44, exhibiting increased anterior chamber cells, several mutton-fat keratic precipitates, and elevated intraocular pressure. Systemic diagnostic workup led to the diagnosis of neurosyphilis, and the patient subsequently admitted to high-risk sexual behaviors. Treatment with intravenous aqueous penicillin-G 24 million units per day for 14 days led to complete resolution of uveitis. The case was reported to the local health department within 24 h of syphilis diagnosis. CONCLUSIONS: Syphilis, although an uncommon cause of ocular inflammation, is a highly contagious, but curable disease. Given its potentially devastating neurologic consequences, syphilis should be considered in all patients presenting with uveitis. A high index of clinical suspicion and a detailed sexual history are crucial for the accurate and timely diagnosis of ocular syphilis.

Granulomatous uveitis and reactive arthritis as manifestations of post-streptococcal syndrome.

To report a case of bilateral granulomatous post-streptococcal syndrome uveitis in association with reactive arthritis as manifestation of post-streptococcal syndrome. To our knowledge, this could represent the first reported case in the literature. A 9-year-old girl, with no past ocular history, presented with a 5-day history of bilateral blurred vision, red eyes, photophobia and walking difficulties because of a right ankle pain. Ophthalmic examination disclosed a visual acuity limited to hand motion, mutton-fat keratic precipitates, anterior chamber cells and posterior synechiae in both eyes. Ocular pressure was normal. Physical examination showed a fever (38 °C), inflammatory ankle arthritis and scarlet fever (streptococcal lesion). Anti-streptococcal lysine O titer was 419 µ/ml. The patient was treated with topical steroids, cycloplegics, high-dose oral steroids and preventive course of penicillin with total improvement and no recurrence. Post-streptococcal syndrome should be considered in the etiology of acute bilateral granulomatous uveitis in children, and anti-streptococcal lysine O titer should be considered in serodiagnostic testing.

[Endogenous endophthalmitis as a complication in erysipelas]. / Endophtalmie endogène compliquant un érysipèle.

BACKGROUND: Endogenous endophthalmitis is a devastating infection of the eye that leads to blindness in about two-thirds of patients. It results from the haematogenous spread of a microorganism from a focus of sepsis, mainly gastro-intestinal, genitourinary or cardiac. PATIENTS AND METHODS: We describe the case of a diabetic subject presenting endogenous endophthalmitis following erysipelas of the leg due to Streptococcus agalactiae. The outcome was favourable thanks to prompt initiation of appropriate antibiotic treatment. DISCUSSION: Endogenous endophthalmitis as a complication of a skin infection is a rare entity, with only about 30 reported cases in the literature. Awareness of this condition among dermatologists would allow prompt intervention, which is essential for sparing of the patient's eyesight.

[Bilateral anterior uveiopapillitis, suspicious of Lyme disease--case report]. / Uveopapilita anterioara bilaterala--suspiciune boala lyme--prezentare de caz.

We present the case of a patient which associated bilateral anterior uveitis manifestations with those of bilateral anterior inflammatory optic neuropathy. We followed the evolution of the case under treatment and we discussed the differential diagnosis and the association of the two ocular pathologies.

Direct detection of Ehrlichia canis by PCR in the conjunctiva of a dog with bilateral anterior uveitis.

The following report describes the direct detection of Ehrlichia canis by real-time PCR in the conjunctiva of a 1-year-old female Maltese dog. After being imported from Brazil, the dog was presented because of anorexia, dehydration, fever, and palpable mandibular lymph nodes. A few days later, the dog developed bilateral blepharospasm, photophobia and anterior uveitis. Monocytic ehrlichia was diagnosed by a positive PCR result and the detection of IgM and IgG antibodies. Because of the massive uveitis a conjunctival sample was taken with a cytobrush, which also tested positive for Ehrlichia canis DNA by real-time PCR. Only one week after starting treatment with systemic doxycycline and local anti-inflammatory and cyclopalgic therapy the dog recovered from systemic and eye diseases. After therapy the follow-up examination revealed a full remission of clinical and hematological parameters and negative PCR result.

Bilateral anterior uveitis in a patient with bacterial meningitis.

We report a case of bilateral iridocyclitis accompanied by bacterial meningitis in an immunocompetent patient. Case report. A 48 year-old healthy female visited our hospital with strong headache, fever, bilateral hyperemia, and blurred vision in both eyes. A slit-lamp examination revealed moderate cells and flare in the anterior chamber of both eyes, with fine keratoprecipitates. There were no obvious inflammatory changes in the vitreous, retina, and optic disc of both eyes. Elevation of peripheral blood white blood cells, C-reactive protein, and an elevated number of cerebrospinal fluid (CSF) cells suggested bacterial meningitis. The patient was admitted to our hospital and received intravenous antibiotics. Finally, a CSF culture revealed infection with gram-positive rods, suspected Listeria monocytogenes, confirming bacterial meningitis. For iridocyclitis, we prescribed betamethasone eyedrops and 0.5 % tropicamide eyedrops with intravenous adminstration of systemic antibiotics. 3 days later, her headache and bilateral hyperemia disappeared. This case is better described as sterile reactive uveitis rather than endogenous bacterial endophthalmitis, because bilateral anterior uveitis was resolved without chronic uveitis, iris atrophy, and vitreous opacity. When clinicians see patients with meningitis and bilateral anterior uveitis, sterile reactive uveitis should be considered in the differential diagnosis of uveitis.

[Hypopyon]. / Hipopionul.

The hypopyon represents an anterior chamber exudative syndrome which has important clinical and prognostic implications. It is very important to be able to differentiate between the sterile and infectiouos hypopyon and also to separate it by pseudohypopyon. A clear view over the etiology is strongly correlated with the therapeutical approach and the patient evolution.

Chronic Unilateral Uveitis as a Manifestation of Leprosy: A Case Report and Literature Review.

Purpose: To describe a case of leprosy presenting chronic anterior uveitis associated with other systemic lesions.Methods: Case report and systematic literature review.Results: We describe the case of a 65-year-old patient presenting clinical features of chronic uveitis and poor response to topical and intravitreal steroid treatment. Upon ocular examination, diffuse iris atrophy and macular edema were observed and laboratory tests for autoimmune and infectious diseases were within normal range. Physical examination revealed the presence of skin lesions on trunk and extremities, which were biopsied and identified as positive for leprosy.Conclusion: The case reported herein presented atypical characteristics of uveitis due to the involvement of the posterior segment of the eye. Leprosy diagnosis could be a challenge, a systematic approach is mandatory to achieve adequate treatment.

Recent Developments in HLA B27 Anterior Uveitis.

There has been steady progress in understanding the pathogenesis, clinical features, and effective treatment of acute anterior uveitis (AU) over the past 5 years. Large gene wide association studies have confirmed that AU is a polygenic disease, with overlaps with the seronegative arthropathies and inflammatory bowel diseases, associations that have been repeatedly confirmed in clinical studies. The role of the microbiome in AU has received increased research attention, with recent evidence indicating that human leukocyte antigen B27 (HLA B27) may influence the composition of the gut microbiome in experimental animals. Extensive clinical investigations have confirmed the typical features of acute AU (AAU) and its response to topical, regional and systemic immunosuppressive treatment. Increased understanding of the role of cytokines has resulted in studies confirming the value of anti-cytokine therapy [anti-tumor necrosis factor (anti-TNF) and interleukin 6 (IL-6) therapy] in severe and recurrent cases of AAU, particularly in subjects with an associated spondyloarthopathy (SpA) and in juvenile idiopathic arthritis (JIA)-associated AAU.

Earlier use of systemic immunosuppression is associated with fewer ophthalmic surgeries in paediatric non-infectious uveitis.

BACKGROUND/AIMS: There is a paucity of large trials investigating the effect of management strategies for paediatric non-infectious uveitis on complications requiring surgery. The purpose of our study is to investigate whether earlier initiation of systemic immunosuppression in paediatric non-infectious uveitis is associated with fewer ophthalmic surgeries. METHODS: A retrospective review was conducted on 48 children with non-infectious uveitis assessed in 1998-2013. Patients were divided into uveitis diagnosed before December 2008 (group 1) and after January 2009 (group 2). Duration from uveitis onset to methotrexate initiation (U-MTX) and biological addition (U-Biologic) were reviewed. Follow-up visits with topical corticosteroids >3 times daily and active uveitis (≥1+ cells) during 3.5 years were documented. The main outcome measure was the need for ≥1 ophthalmic surgery at 3.5 years. RESULTS: In group 1, 69.5% of patients required ≥1 ophthalmic surgery at 3.5 years versus 26.9% in group 2 (p=0.005). U-MTX was 28.9±11.8 weeks and 14.2±10.0 weeks for groups 1 and 2 (p=0.028). U-Biologic was 134.6±46.0 weeks and 82.3±43.3 weeks for groups 1 and 2 (p=0.0016). Corticosteroid use >3 times daily was 85.9±52.7 weeks and 14.6±11.1 weeks for groups 1 and 2. Multivariate regression showed methotrexate initiation within 6 months of uveitis onset lowered the likelihood of needing ophthalmic surgery at 3.5 years (OR=6.2, 95% CI 1.2 to 33.4; p=0.033). Univariate regression demonstrated biological addition within 18 months of uveitis onset reduced the likelihood of requiring ophthalmic surgery (OR 12.57, 95% CI 1.28 to 123.48; p=0.030). CONCLUSION: Earlier control of uveitis by addition of immunosuppressive therapy reduced the need for ophthalmic surgery.

Case Report: Bilateral Granulomatous Anterior Uveitis in HIV-patient with Disseminated Talaromycosis (penicilliosis) Marneffei Infection.

We report on a 22-years-old Thai male patient with congenital HIV infection. Due to his non-adherence to antiretroviral treatment he developed disseminated Talaromyces marneffei infection and was treated with intravenous amphotericin B. Despite this treatment, he presented with bilateral granulomatous anterior uveitis. Uveitis improved only after intracameral injection of amphotericin B.

Acute conjunctivitis with episcleritis and anterior uveitis linked to adiaspiromycosis and freshwater sponges, Amazon region, Brazil, 2005.

We conducted an epidemiologic investigation of an outbreak of ocular disease among children to determine whether the disease was linked to Emmonsia sp., a rarely-reported fungus and an agent of adiaspiromycosis. Using an unmatched case-control study design, we compared case-patients with asymptomatic controls randomly selected from the population. Scleral biopsies were analyzed microscopically. Of 5,084 children examined, 99 case-patients were identified; mean age (+1 SD) was 11.0 +/- 4.4 years. Symptoms included photophobia (57%), ocular pain (42%), and blurred vision (40%). In the multivariate analysis, risk factors included diving in the Araguaia River (odds ratio 5.2; 95% confidence interval 2.4-12.0). Microscopy identified foreign bodies consistent with adiaconidia. This outbreak probably resulted from foreign-body-type reactions to adiaspiromycosis conidia after initial irritation caused by conjunctival contact with spicules of sponges in the river. Symptomatic children responded to corticosteroid treatment. Adiaspiromycosis is a preventable cause of ocular disease in the Amazon region.

Supposed endogenous endophthalmitis caused by Serratia marcescens in a cat.

An 8-year-old male neutered domestic shorthair cat was presented for evaluation of acute respiratory distress. Respiratory auscultation revealed a diffuse and symmetric increase in bronchovesicular sounds. Thoracic radiographs showed a diffuse unstructured interstitial pulmonary pattern with multifocal alveolar foci. Despite an aggressive treatment with supportive care, including oxygenotherapy and systemic antibiotics, progressive respiratory distress increased. Three days after the presentation, acute anterior uveitis was noticed on left eye. Ophthalmic examination and ocular ultrasonography revealed unilateral panuveitis with ocular hypertension. The right eye examination was unremarkable. Cytological examination of aqueous humor revealed a suppurative inflammation. Serratia marcescens was identified from aqueous humor culture. Primary pulmonary infection was suspected but was not confirmed as owners declined bronchoalveolar lavage. Active uveitis resolved and cat's pulmonary status improved after appropriate systemic antibacterial therapy. Vision loss was permanent due to secondary mature cataract. To the best of authors' knowledge, this is the first report of endogenous bacterial endophthalmitis secondary to S. marcescens infection in a cat.

Iris root abscess and necrotizing sclerokeratitis caused by Mycobacterium abscessus and presenting as hemorrhagic anterior uveitis.

PURPOSE: To report a case of an iris abscess and necrotizing sclerokeratitis caused by Mycobacterium abscessus and presenting as hemorrhagic uveitis. METHODS: An 86-year-old white woman was diagnosed with hemorrhagic anterior uveitis and treated with high-frequency topical steroids. The inflammation progressed to involve the cornea and the sclera, and the treatment was changed to intensive antibiotics. There was no improvement. Direct microscopy of a biopsy specimen of the lesion wrongly identified Nocardia as the cause, but antibiotic sensitivity suggested clarithromycin as a suitable therapeutic agent. Therapy was changed but there was continued deterioration. The eye could not be saved and the causative organism was subsequently discovered to be M. abscessus. RESULTS: The eye was enucleated 6 months after initial presentation. CONCLUSIONS: Ocular infection with M. abscessus is an extremely rare cause of necrotizing sclerokeratitis and may present as a hemorrhagic uveitis. There is a high risk of misdiagnosis and late detection, which may have severe consequences.

Unilateral granulomatous post-streptococcal uveitis with elevated tension.

PURPOSE: We document a presumptive case of unilateral post-streptococcal uveitis. The affected eye manifested a granulomatous anterior uveitis with elevated intra-ocular pressure (IOP) compared with the contra-lateral eye. This presentation was preceded by a recent streptococcal pharyngitis. CASE REPORT: An asymptomatic, otherwise healthy 13-year-old black female presented with anterior chamber cells, mutton fat resembling keratic precipitates, and elevated IOP in the left eye relative to the right eye. The patient had been diagnosed with streptococcal pharyngitis approximately 1 week before her eye examination. A blood chemistry analysis, rheumatoid profile panel and antistreptolysin antibody titer were requested. The patient was prescribed predinisolone acetate 1% ophthalmic suspension in the left eye. RESULTS: Anti-streptolysin antibody titers were significantly elevated (291 IU/ml). The patient responded favorably to topical ophthalmic steroid treatment with a reduction of IOP and inflammation. CONCLUSIONS: Unilateral, granulomatous anterior uveitis may be a variant manifestation of post-streptococcal uveitis. The IOP elevation in these cases may result secondary to concurrent trabeculitis.

The microbiome and HLA-B27-associated acute anterior uveitis.

Acute anterior uveitis (AAU) and the spondyloarthritis (SpA) subtypes ankylosing spondylitis, reactive arthritis and psoriatic arthritis are among the inflammatory diseases affected by the biology of the intestinal microbiome. In this Review, the relationship between AAU, SpA and the microbiome is discussed, with a focus on the major SpA risk gene HLA-B*27 and how it is associated with both intestinal tolerance and the loss of ocular immune privilege that can accompany AAU. We provide four potential mechanisms to account for how dysbiosis, barrier function and immune response contribute to the development of ocular inflammation and the pathogenesis of AAU. Finally, potential therapeutic avenues to target the microbiota for the clinical management of AAU and SpA are outlined.