Adalimumab for prevention of uveitic flare in patients with inactive non-infectious uveitis controlled by corticosteroids (VISUAL II):a multicentre, double-masked, randomised, placebo-controlled phase 3 trial

Background Non-infectious uveitis is a potentially sight-threatening ocular disorder caused by chronic inflammation and its complications. Therapeutic success is limited by systemic adverse effects associated with long-term corticosteroid and immunomodulator use if topical medication is not sufficient to control the inflammation. We aimed to assess the efficacy and safety of adalimumab in patients with inactive, non-infectious uveitis controlled by systemic corticosteroids. Methods We did this multicentre, double-masked, randomised, placebo-controlled phase 3 trial at 62 study sites in 21 countries in the USA, Canada, Europe, Israel, Australia, and Latin America. Patients (aged >= 18 years) with inactive, non-infectious intermediate, posterior, or panuveitic uveitis controlled by 10-35 mg/day of prednisone were randomly assigned (1: 1), via an interactive voice and web response system with a block size of four, to receive either subcutaneous adalimumab (loading dose 80 mg; biweekly dose 40 mg) or placebo, with a mandatory prednisone taper from week 2. Randomisation was stratified by baseline immunosuppressant treatment. Sponsor personnel with direct oversight of the conduct and management of the study, investigators, study site personnel, and patients were masked to treatment allocation. The primary efficacy endpoint was time to treatment failure, a multicomponent endpoint encompassing new active inflammatory chorioretinal or inflammatory retinal vascular lesions, anterior chamber cell grade, vitreous haze grade, and visual acuity. Analysis was done in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT01124838. Findings Between Aug 10, 2010, and May 14, 2015, we randomly assigned 229 patients to receive placebo (n=114) or adalimumab (n=115); 226 patients comprised the intention-to-treat population. Median follow-up time was 155 days (IQR 77-357) in the placebo group and 245 days (119-564) in the adalimumab group. Treatment failure occurred in 61 (55%) of 111 patients in the placebo group compared with 45 (39%) of 115 patients in the adalimumab group. Time to treatment failure was significantly improved in the adalimumab group compared with the placebo group (median not estimated [>18 months] vs 8.3 months; hazard ratio 0.57, 95% CI 0.39-0.84; p=0.004). The 40th percentile for time to treatment failure was 4.8 months in the placebo group and 10.2 months in the adalimumab group. No patients in either group had opportunistic infections (excluding oral candidiasis and tuberculosis). No malignancies were reported in the placebo group whereas one (1%) patient in the adalimumab group reported non-serious squamous cell carcinoma. The most common adverse events were arthralgia (12 [11%] patients in the placebo group and 27 [23%] patients in the adalimumab group), nasopharyngitis (16 [17%] and eight [16%] patients, respectively), and headache (17 [15%] patients in each group). Interpretation Adalimumab significantly lowered the risk of uveitic flare or loss of visual acuity upon corticosteroid withdrawal in patients with inactive, non-infectious intermediate, posterior, or panuveitic uveitis controlled by systemic corticosteroids. No new safety signals were observed and the rate of adverse events was similar between groups. These findings suggest that adalimumab is well tolerated and could be an effective treatment option in this patient population. An open-label extension study (NCT01148225) is ongoing to provide long-term safety data for adalimumab in patients with non-infectious uveitis

Fundus topographical distribution patterns of ocular toxoplasmosis

BACKGROUND: To establish topographic maps and determine fundus distribution patterns of ocular toxoplasmosis (OT) lesions. METHODS: In this retrospective study, patients who presented with OT to ophthalmology clinics from four countries (Argentina, Turkey, UK, USA) were included. Size, shape and location of primary (1°)/recurrent (2°) and active/inactive lesions were converted into a two-dimensional retinal chart by a retinal drawing software. A final contour map of the merged image charts was then created using a custom Matlab programme. Descriptive analyses were performed. RESULTS: 984 lesions in 514 eyes of 464 subjects (53% women) were included. Mean area of all 1° and 2° lesions was 5.96±12.26 and 5.21±12.77 mm2, respectively. For the subset group lesions (eyes with both 1° and 2° lesions), 1° lesions were significantly larger than 2° lesions (5.52±6.04 mm2 vs 4.09±8.90 mm2, p=0.038). Mean distances from foveola to 1° and 2° lesion centres were 6336±4267 and 5763±3491 µm, respectively. The majority of lesions were found in temporal quadrant (p<0.001). Maximum overlap of all lesions was at 278 µm inferotemporal to foveola. CONCLUSION: The 1° lesions were larger than 2° lesions. The 2° lesions were not significantly closer to fovea than 1° lesions. Temporal quadrant and macular region were found to be densely affected underlining the vision threatening nature of the disease

Spectral optical coherence tomography findings in an elderly patient with syphilitic bilateral chronic panuveitis

Purpose: To report the spectral domain optical coherence tomography (SD-OCT) features of a focal retinitis in an elderly male patient with bilateral syphilitic panuveitis. Observations: In the left eye (LE), spectral domain SD-OCT images during the active period revealed hyperreflectivity extending through the full thickness of the retina with no individualization of the layers, except for the retinal pigment epithelium. Once the lesion healed, SD-OCT imaging revealed an inner retinal atrophy and a mild disruption of the retinal pigment epithelium. Conclusions and importance: In our patient, treponemal infection seemed to produce full-thickness retinal damage with partial involvement of the retinal pigment epithelium. The severe retinal damage, in this case, led to a poorer visual outcome than in other forms of syphilitic retinal involvement

Acute syphilitic posterior placoid chorioretinopathy: An infectious or autoimmune disease?

Purpose: To report a case of acute syphilitic posterior placoid chorioretinopathy (ASPPC) that demonstrated partial resolution with immunosuppressive therapy secondary to a misdiagnosis as Behçet's disease followed by a relapse which was successfully treated with the appropriate treatment. Observations: A 34-year-old female patient presented to our service with complaints of decreased vision in the left eye (OS). She initially developed similar symptoms seven months prior to presentation and was diagnosed as Behçet's disease based on the clinical picture of papillitis, vasculitis and placoid chorioretinitis in the posterior pole of OS. She was started on daily oral prednisone 60 mg and weekly methotrexate 10mg by her rheumatologist. The patient's ocular symptoms improved one month prior to presentation with resolution of the placoid lesion but persistence of vasculitis and papillitis. At that time, the dose of the prednisone was decreased to 30 mg which resulted in a relapse of the placoid chorioretinal lesions and worsened visual acuity at the time of presentation to us. Extensive laboratory workup demonstrated positive serology for syphilis. A diagnosis of syphilitic placoid chorioretinitis was made and the patient was treated with intravenous penicillin G for 2 weeks. The vitritis, papillitis, and placoid chorioretinitis resolved along with improvement in vision following the treatment. Conclusions and importance: Ocular findings in syphilis are heterogeneous and may mimic variety of ocular diseases. ASPPC is a rare ocular manifestation of syphilis and its natural course and underlying pathophysiology is not well understood. However, irrespective of the underlying mechanism of the disease, all patients with ASPPC should receive treatment to prevent recurrence and long-term functional damage. Keywords: Uveitis, Syphilis, Acute syphilitic posterior placoid chorioretinopathy, Immunosuppressio

The Occam's Razor - The Simplest Explanation is Usually the Correct One

Leptomeningeal carcinomatosis (LCM) is an uncommon site of metastasis in solid tumors. In gastric cáncer (GC) it is associated with a devastating prognosis. We report a case of LMC secondary to GC, initially presenting as papilledema and then, the definitive diagnosis was reached

Ocular Syphilis with Retinal and Disc Neovascularization Treated with Bevacizumab: A Case Report

We report the findings observed in a young woman with ocular syphilis complicated with retinal and disc neovascularization successfully treated with intravitreal bevacizumab. Fluorescein angiography revealed in both eyes intense hyperfluorescence at the level of the disc, multifocal venous wall staining, multifocal paravenous leakage, multiple peripheral saccular venular dilations, diffuse retinal and macular edema, and retinal and disc neovascularization. There was no evidence of retinal ischemia in both eyes. After antibiotic and corticosteroid treatment, the neovascularization persisted in both eyes. Three consecutive doses of intravitreal bevacizumab were administered, with total regression of the retinal and disc neovascularization. Disc and retinal neovascularization along with nonocclusive retinal vasculitis may be a form of presentation of ocular syphilis. Combination of specific treatment, oral corticosteroids, and intravitreal bevacizumab may be useful for treating this clinical manifestation

Ocular Cicatricial Pemphigoid: Clinical Manifestations, Diagnosis and Current Management

El penfigoide ocular cicatricial es una enfermedad crónica, bilateral, y progresiva, de etiología autoinmune, en la que se observan depósitos de autoanticuerpos en el epitelio de la membrana basal de las mucosas. Se considera un subtipo del penfigoide de las membranas mucosas (PMM), una dermatosis bullosa, caracterizada por ampollas en diferentes tejidos mucosos como nariz, boca, tracto respiratorio, y genitales. El compromiso ocular en estos casos se encuentra en un 70% de los pacientes con PMM. En contrapartida, el compromiso ocular sin manifestación sistémica se observa hasta en un tercio de los pacientes. Las manifestaciones oftalmológicas inician de forma asimétrica con una conjuntivitis que progresa hacia la fibrosis, provocando insuficiencia de la superficie ocular, y complicaciones inflamatorias e infecciosas, así como una pérdida visual potencialmente devastadora. El diagnóstico oportuno, con un abordaje interdisciplinario y un tratamiento sistémico adecuado, son sumamente importantes y requieren un alto nivel de experiencia, ya que esta condición puede ser extremadamente difícil de identificar y tratar.Ocular cicatricial pemphigoid is a progressive, bilateral, chronic disease, of autoimmune etiology, in which autoantibody deposits are observed in mucosal basement membranes. It is regarded as a mucous membrane pemphigoid subtype, a bullous dermatitis, characterized by blistering in mucosal tissues of nose, mouth, respiratory tract, and genitalia. As a counterpart, ocular involvement without systemic manifestations is observed up to one third of the patients. Ophthalmological presentation is asymmetric, with a conjunctival inflammation which evolves to fibrosis, leading to an ocular surface insufficiency, and infectious and inflammatory complications, as well as a potentially devastating visual loss. A timely diagnosis, with an interdisciplinary approach and a suitable systemic treatment, are pivotal and they require a high level of experience, since this condition may be extremely difficult in identifying and treating.Fil: Schlaen, Bernardo Ariel. Universidad Austral. Hospital Universitario Austral; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Montoya, Juliana. Universidad Austral. Hospital Universitario Austral; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Heredia, Milagros. Universidad Austral. Hospital Universitario Austral; ArgentinaFil: Ficoseco, Carla. Universidad Austral. Hospital Universitario Austral; Argentina. Hospital Alemán; ArgentinaFil: Dominguez, Lucia. Universidad Austral. Hospital Universitario Austral; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentin

Ocular Cicatricial Pemphigoid: Clinical Manifestations, Diagnosis and Current Management

El penfigoide ocular cicatricial es una enfermedad crónica, bilateral, y progresiva, de etiología autoinmune, en la que se observan depósitos de autoanticuerpos en el epitelio de la membrana basal de las mucosas. Se considera un subtipo del penfigoide de las membranas mucosas (PMM), una dermatosis bullosa, caracterizada por ampollas en diferentes tejidos mucosos como nariz, boca, tracto respiratorio, y genitales. El compromiso ocular en estos casos se encuentra en un 70% de los pacientes con PMM. En contrapartida, el compromiso ocular sin manifestación sistémica se observa hasta en un tercio de los pacientes. Las manifestaciones oftalmológicas inician de forma asimétrica con una conjuntivitis que progresa hacia la fibrosis, provocando insuficiencia de la superficie ocular, y complicaciones inflamatorias e infecciosas, así como una pérdida visual potencialmente devastadora. El diagnóstico oportuno, con un abordaje interdisciplinario y un tratamiento sistémico adecuado, son sumamente importantes y requieren un alto nivel de experiencia, ya que esta condición puede ser extremadamente difícil de identificar y tratar.Ocular cicatricial pemphigoid is a progressive, bilateral, chronic disease, of autoimmune etiology, in which autoantibody deposits are observed in mucosal basement membranes. It is regarded as a mucous membrane pemphigoid subtype, a bullous dermatitis, characterized by blistering in mucosal tissues of nose, mouth, respiratory tract, and genitalia. As a counterpart, ocular involvement without systemic manifestations is observed up to one third of the patients. Ophthalmological presentation is asymmetric, with a conjunctival inflammation which evolves to fibrosis, leading to an ocular surface insufficiency, and infectious and inflammatory complications, as well as a potentially devastating visual loss. A timely diagnosis, with an interdisciplinary approach and a suitable systemic treatment, are pivotal and they require a high level of experience, since this condition may be extremely difficult in identifying and treating.Fil: Schlaen, Bernardo Ariel. Universidad Austral. Hospital Universitario Austral; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Montoya, Juliana. Universidad Austral. Hospital Universitario Austral; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Heredia, Milagros. Universidad Austral. Hospital Universitario Austral; ArgentinaFil: Ficoseco, Carla. Universidad Austral. Hospital Universitario Austral; Argentina. Hospital Alemán; ArgentinaFil: Dominguez, Lucia. Universidad Austral. Hospital Universitario Austral; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentin