Uveitis

This study is designed to evaluate the efficacy and safety of GenSci048 compared with placebo in subjects with active non-infectious uveitis.

The aim of this study is to apply a diagnostic test called 'metagenomic sequencing' to identify the involvement of potential infections in patients with ocular inflammation, where this hasn't been detected by currently available standard testing. For many people with ocular inflammation, no cause is ever found for their disease. In some cases, an infection or infectious trigger is suspected, but currently available tests are inadequate. Metagenomic sequencing can identify almost every globally known infection (bacteria, virus, fungi, parasites) in a sample. Therefore, it has the potential to identify an infection that has caused or triggered ocular inflammation, and as a consequence may help to identify specific treatments. It has the potential to improve our understanding of how to diagnose and treat people with this problem. This study will allow us to test the technique that has been previously optimised for brain infections, on ocular fluids. Participants will be 18 years of age or over and have active ocular inflammation which is suspected to be due to an infection, or an autoimmune process which has been triggered by an infection, but identification of this infection has not been possible using the investigations available as part of standard NHS care. Participants will be identified by the treating clinical team as requiring a sample of fluid from inside of the eye, and some of this fluid will be sent for metagenomic sequencing alongside standard testing. This study will be conducted at Moorfields Eye Hospital, London and will last for approximately a year. Participants will undergo additional non-invasive ocular imaging on the day of their clinic visit, but will not have to attend any additional research visits.

Uveitis and its complications are thought to account for 10 to 15% of preventable blindness in Western countries. The diagnosis of chronic non-infectious uveitis (CNUI) can be made after exclusion of pseudo uveitis or infectious uveitis, in the case of any persistent uveitis or uveitis with frequent relapses occurring less than 3 months after cessation of treatment. Adalimumab (ADA), an anti-TNFα monoclonal antibody, has marketing authorization and is widely used in the treatment of UCNI as a relay to corticosteroids. The use of ADA has been optimized, in particular through Therapeutic Drug Monitoring (TDM), based on the determination of serum ADA levels and anti-ADA antibodies. Recently, an article showed that a strategy of spacing ADA administrations in RA patients with concentrations \>8 μg/mL was not inferior to standard.

The goal of this observational study is to collect data regarding clinical features and current/past treatments in children under 18 with uveitis. The main questions it aims to answer are: * What are the frequency of uveitis subtypes in children? * What are clinical and demographic characteristics overall and within each type of uveitis? Participants will complete one enrollment visit with their doctor. Participants with uveitis onset \<6 months from enrollment date will also partake in a 12 month chart review.

Uveitis is an inflammatory disease of the uvea, one of the highly vascularized fundamental structures of the eye. It is a rare condition in children, with an incidence in the pediatric population ranging from 2% to 14% of all uveitis cases. The diagnosis and management of patients with uveitis rely on a multidisciplinary approach involving an ophthalmologist, a rheumatologist, and an infectious disease specialist to establish the correct diagnosis and assess the involvement of other organs. In Italy, there is no national or regional registry for non-infectious chronic uveitis as per the Prime Ministerial Decree (DPCM) of March 3, 2017 (Identification of surveillance systems and registries for mortality, tumors, and other diseases). However, many clinical centers adopt data recording systems to evaluate the quality of care and to study diseases and outcomes. The Universitary Hospital Meyer Institute Research Hospital (IRCCS) is a national referral center for managing these pediatric cases of non-infectious chronic uveitis, estimated to constitute 95% of all pediatric uveitis cases

In order to improve the investigators knowledge about uveitis and the underlying mechanism of disease, the investigators propose collecting blood from patients with uveitis, isolating DNA and sequencing the DNA to identify genetic mutations or associations in these patients.

A prospective, observational, case series investigating the feasibility of utilizing OCT scans of the anterior chamber of eyes with uveitis.

The main retinal diseases, whether or not associated with specific mutations genetic, cause progressive degeneration of vascular retinal structures and not vascular, resulting in decreased visual function. Often, such diseases affect the noblest part of the retina, called macula. Many retinal diseases can be complicated by choroidal neovascularization which causes frequent bleeding and fluid leakage that accumulates in the subretinal and intraretinal spaces. Although the investigators know many details of each disease affecting the retina, very often the correct diagnostic framework can be complicated, given the presence of morphological elements common to the different pathologies. Similarly, predicting the effect of treatment and the patient's outcome is a constant challenge for the ophthalmologists. Most of the current research has been focused on the assessment of vascular alterations localized in the macula. However, growing evidence highlight the importance of peripheral vascular changes on the outcome of retinal diseases. These changes can be detected only be wide field OCT devices. On the other hand, ocular inflammation and hyperemia represent major assessments in anterior segment disorders, such as dry eye disease. The current grading systems of ocular inflammation, redness and hyperemia are characterized by several limitations, thus making these evaluations still mainly confined to the subjective assessment performed by the ophthalmologist. However, the new generation OCT devices may include also an anterior segment module which can reconstruct anterior segment vessels, non-invasively, using the same technology described for retinal diseases. The main goal of the study is to evaluate the diagnostic contribution of a new generation wide field OCTA device in ocular diseases, which has recently received CE marking. In particular, the investigators will evaluate this new generation device both in retinal and anterior segments diseases, testing for common points and differences with the standard of care non-invasive diagnostic devices. Secondary outcomes include the assessment of the correlation between the patient's visual function (visual acuity) and morphological changes (standard of care imaging assessment) highlighted by the wide field OCT device, with particular attention to microstructural differences between major ocular diseases and the possible development of non-invasive biomarkers, useful for the diagnosis and follow-up of such pathologies.

The Use of Two YUTIQ versus Sham for Treatment of Chronic Non Infectious Intraocular Inflammation Affecting the Posterior Segment (TYNI Trial)

Autoinflammatory diseases (AID) are clinical entities characterized by recurrent inflammatory attacks in absence of infection, neoplasm or deregulation of the adaptive immune system. Among them, hereditary periodic syndromes, also known as monogenic AID, represent the prototype of this disease group, caused by mutations in genes involved in the regulation of innate immunity, inflammation and cell death. Based on recent experimental acquisitions in the field of monogenic AID, several immunologic disorders have been reclassified as polygenic/multifactorial AID, sharing pathogenetic and clinical features with hereditary periodic fevers. This has paved the way to new treatment targets for patients suffering from rare diseases of unknown origin, including Behçet's disease, Still disease, Schnitzler's disease, PFAPA (periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis) syndrome, chronic recurrent multifocal osteomyelitis (CRMO), non-infectious uveitis and scleritis. Gathering information on such rare conditions is made difficult by the small number of patients, along with the difficulty of obtaining an accurate diagnosis in non-specialized clinical settings. In this context, the AIDA project promotes international collaboration among clinical centres to develop a permanent registry aimed at collecting demographic, genetic, clinical and therapeutic data of patients affected by monogenic and polygenic AID, in order to expand the current knowledge of these rare conditions.

The LION Study is a prospective, single-center phase 1 clinical trial to evaluate the safety, tolerability, and distribution of Laquinimod administered as topical eye drops for two weeks in human participants.

Uveitis is an inflammation of the uvea, an ocular tunic comprising the iris, ciliary body and choroid. This inflammation can also involve other tissues such as the retina, the optic nerve and the aqueous humor. These diseases can result in significant vision loss and account for 10% of all blindness in developed countries, and up to 25% in developing countries. The main difficulty in this pathology is to make the etiological diagnosis, which then allows a specific treatment of the disease. The main etiologie are inflammatory or infectious (sarcoidosis, tuberculosis) but other cancerous etiologies are possible and are of more complicated diagnosis. Vitreoretinal lymphoma is a subtype of central nervous system lymphoma, which is generally associated with a poor prognosis. It is a diffuse non-Hodgkin's lymphoma, with large B cells. It can be primary ocular (Primary Intra-Ocular Lymphoma - LIOP), without brain involvement, but can also be secondary to central nervous system involvement, which explains the poor prognosis of the disease. Approximately 50-90% of LIOP develop brain involvement within 1-2 years of diagnosis, which encourages early diagnosis to avoid brain involvement as much as possible. The main obstacle to rapid diagnosis is the difficulty of identifying LIOP. Indeed, the clinical symptoms of this rare disease are often identical to classical uveitis, and the diagnostic means to detect it are invasive and require a trained ophthalmologist and hematologist team. LIOP diagnostic tests are often delay in the management of uveitis and lead to diagnostic erraticity that can last between 4 to 40 months. The INSERM U1183 unit is developing a diagnostic technology for lymphomas based on the analysis of blood NK cells and their phenotypes including those acquired by trogocytosis (WO/2016/005548). A rapid, simple, minimally invasive LIOP test using this technology could therefore be propose to all patients presenting with uveitis and whose clinical criteria could match those of LIOP. The research hypothesis is : Could the diagnostic wandering of patients with primary intraocular lymphoma be reduced by a rapid blood test for NK cell phenotype of patients with uveitis? Following a simple blood test, a rapid LIOP test, using this diagnostic technology, could therefore be proposed to all patients with uveitis and clinical criteria (age, intermediate and posterior location of the uveitis) corresponding to those of LIOP. The primary objective of this study is to compare the phenotype of circulating NK cells of patient with untreated intraocular lymphoma versus the phenotype of patient with non-cancerous uveitis.

The objective of this study is to compare and evaluate the efficacy of subcutaneous (40mg) adalimumab biweekly injections to intravitreal adalimumab (1.5 mg/ 0.03 mL) administration, given at zero, 2 weeks then every four weeks, in subjects with active non-infectious intermediate-, posterior-, or pan-uveitis.

This study intends to explore the epidemiology, pathogenesis, clinical manifestations, diagnosis and treatment of uveitis. This is a cohort study. The outcome of the study is the activity of inflammation and visual prognosis. The purpose of this study is to determine the optimal diagnosis and treatment scheme for uveitis patients based on real-world data.

This project is designed to evaluate the efficacy of YUTIQ® 0.18 mg intravitreal implant for the management of chronic non-infectious uveitis.

Autoimmune uveitis is one kind of non-infectious, sight-threatening, relapsing and severe ocular disease. Approximately 20%-25% autoimmune uveitis patients suffer from the dilemma of blindness for the chronic and persistent inflammatory state in the eyes, which results in continuous destroy in the structure of the eyes and gradually leads to irreversible damage on visual function. However, it shows limiting efficacy of current treatment including glucocorticoids, immunosuppressant and biologics for chronic autoimmune uveitis. Minocycline has been regarded to have anti-apoptosis and immunemodulatory function for decades and it has been illustrated to be beneficial in several neuro-degenerative and neuro-inflammatory diseases. This trial aims to investigate the efficacy and safety of minocycline for chronic autoimmune uveitis with retinal degenerative changes.

This study is a multi-center randomized non-inferiority study that aims to observe the short-term (3 months) efficacy and safety of adalimumab plus medium-dose glucocorticosteroid (30mg/d prednisone or equivalent) with slow tapering for recurrent Behçet's uveitis (BU) attack compared with adalimumab plus high-dose glucocorticosteroid (60mg/d prednisone or equivalent) with slow tapering.