Uveitis comprises a group of potentially blinding diseases of mainly the young and working aged population. Some cases are caused by an infection, in others it is part of a systemic disease but in many patients we never find a cause. When vision is threatened systemic treatment in the form of corticosteroids, immunosuppressants and biological agents are required.
The eye is an immunologically privileged site. Recent developments are beginning to suggest specific molecular mechanisms for this process. Nevertheless, uveitis is a clear challenge to this tolerant paradigm. Research is aimed at trying to answer why the mechanisms of immune privilege in the eye are circumvented or overwhelmed leading to inflammation inside the eye (uveitis). What factors are then driving the inflammatory response? If these mechanisms can be elucidated then specific targeted novel treatments can be developed.
Our large cohort of uveitis patients, including having a National Centre for Behçet’s Disease, allows for translational-based studies. The ability to take blood and aqueous humour samples, and to compare them with healthy individuals, has led us to have a greater understanding of the cells and cytokines inside the inflamed eye.
Our work has been supported by grant funding from the Medical Research Council, The Wellcome Trust, the National Institute for Health Research and Fight for Sight.
We are studying the use of a new way of examining peripheral blood mononuclear cells using flow cytometry known as Supercell technology. Supercell randomly allocates multiple single cells into a “supercell” and calculates a single score for all parameters that is used to compare between different uveitis patient groups. Then applying novel machine learning algorithms we are able to accurately predict patients with different types of uveitis on the basis of different cell surface markers.
Our future work aims to investigate the relationship between immune responses, host genotype and gut microbiome profile that may contribute to the clinical manifestations and disease course in patients with Behçet’s disease.
We are also using metabolomics in aiding the diagnosis and prognosis of different types of uveitis.
In the past our studies of uveitis addressed the roles of a number of potentially harmful immune cell subsets (T cells). This has also enabled us to identify specific patterns of cytokines inside the inflamed eye. We also shown that the microenvironment in the eye suppresses the function of a key population of immune cells (dendritic cells) involved in the initiation of immune responses, and that the microenvironment continues to suppress the function of dendritic cells despite the on-going active inflammation in individuals with uveitis.
We are also examining the genetic basis of ocular disease in particular the concept that condition such as Behçet’s Disease and idiopathic intermediate uveitis are autoinflammatory rather than autoimmune in nature. Analysis of new polymorphisms in the IL-10 gene has shown that those associated with Behçet’s or inflammation at the back of the eye, are not linked to disease solely at the front of the eye suggesting a different mechanism.
We are actively involved in undertaking Pharmaceutical clinical trials for new therapies for uveitis. At present this involves looking at a long acting steroid pellet that is injected into the eye and we are about to start a clinical trial funded by the Medical Research Council and National Institute for Health Research comparing two biological drugs for the treatment of Behçet’s Disease.
We are looking at novel imaging techniques using Optical Coherence Tomography as a validated methodology to accurately quantify inflammation inside the eye that could be used in the clinic and in drug trials.
Our work has recently expanded in to more qualitative research as we are exploring the quality of life issues that uveitis patients who have poor central vision related to their inflammation (cystoid macular oedema) experience. This would lead to the development of a Core Outcome Set of Patient Report Outcomes that could be added to the outcomes already measured in clinical trials of new drugs.
We recently published a large retrospective study of the outcome of cataract surgery in patients with uveitis. Although cataract surgery is highly successful in the elderly, in patients with uveitis the outcome is not as good. We are investigating the results of our cataract surgery in uveitis and are finding that with the appropriate pre-and post-operative management uveitis patients see very well.