Autoimmunity, Autoinflammation, and Infection in Uveitis

Funding/Support: No funding or grant support. Financial Disclosures: John V. Forrester has received an honorarium for lecturing from Janssen (London, UK). Lucia Kuffova has undertaken consultancy work for Abbvie (London, UK). Andrew D. Dick has undertaken consultancy work for Abbvie (London, UK), Roche (London, UK), and Genentech (London, UK) and has received honoraria from Janssen (London, UK) and Abbvie (London, UK). The authors attest that they meet the current ICMJE criteria for authorship.Peer reviewedPublisher PD

Quantitative Assessment of Experimental Ocular Inflammatory Disease

Ocular inflammation imposes a high medical burden on patients and substantial costs on the health-care systems that mange these often chronic and debilitating diseases. Many clinical phenotypes are recognized and classifying the severity of inflammation in an eye with uveitis is an ongoing challenge. With the widespread application of optical coherence tomography in the clinic has come the impetus for more robust methods to compare disease between different patients and different treatment centers. Models can recapitulate many of the features seen in the clinic, but until recently the quality of imaging available has lagged that applied in humans. In the model experimental autoimmune uveitis (EAU), we highlight three linked clinical states that produce retinal vulnerability to inflammation, all different from healthy tissue, but distinct from each other. Deploying longitudinal, multimodal imaging approaches can be coupled to analysis in the tissue of changes in architecture, cell content and function. This can enrich our understanding of pathology, increase the sensitivity with which the impacts of therapeutic interventions are assessed and address questions of tissue regeneration and repair. Modern image processing, including the application of artificial intelligence, in the context of such models of disease can lay a foundation for new approaches to monitoring tissue health

The Cellular Composition of the Uveal Immune Environment

The uveal tract consists of the iris, the ciliary body and the choroid; these three distinct tissues form a continuous layer within the eye. Uveitis refers to inflammation of any region of the uveal tract. Despite being grouped together anatomically, the iris, ciliary body and choroid are distinct functionally, and inflammatory diseases may affect only one part and not the others. Cellular structure of tissues direct their function, and understanding the cellular basis of the immune environment of a tissue in health, the "steady state" on which the perturbations of disease are superimposed, is vital to understanding the pathogenesis of those diseases. A contemporary understanding of the immune system accepts that haematopoietic and yolk sac derived leukocytes, though vital, are not the only players of importance. An array of stromal cells, connective tissue cells such as fibroblasts and endothelial cells, may also have a role in the inflammatory reaction seen in several immune-mediated diseases. In this review we summarise what is known about the cellular composition of the uveal tract and the roles these disparate cell types have to play in immune homeostasis. We also discuss some unanswered questions surrounding the constituents of the resident leukocyte population of the different uveal tissues, and we look ahead to the new understanding that modern investigative techniques such as single cell transcriptomics, multi-omic data integration and highly-multiplexed imaging techniques may bring to the study of the uvea and uveitis, as they already have to other immune mediated inflammatory diseases

Limited Utility of Keratic Precipitate Morphology as an Indicator of Underlying Diagnosis in Ocular Inflammation

Objectives: We aimed to establish the degree of consensus among clinicians on descriptors of KP morphology.// Methods: A web-based exercise in which respondents associated KP descriptors, as identified through a scoping review of the published literature, to images from different disorders. Inter-observer agreement was assessed using the Krippendorff kappa alpha metric.// Results: Of the 76 descriptive terms identified by the scoping review, the most used included “mutton-fat” (n = 93 articles, 36%), “fine/dust” (n = 76, 29%), “stellate” (n = 40, 15%), “large” (n = 33, 12%), and “medium” (n = 33, 12%). The survey of specialists (n = 26) identified inter-observer agreement for these descriptors to be poor (“stellate,” kappa: 0.15, 95% confidence interval 0.13–0.17), limited (“medium”: 0.27, 95% CI 0.25–0.29; “dust/fine”: 0.36, 95% CI 0.34–0.37), or moderate (“mutton fat”: 0.40, 95% CI 0.36–0.43; “large”: 0.43, 95% CI 0.39–0.46).// Conclusion: The clinical utility of KP morphology as an indicator of disease classification is limited by low inter-observer agreement./

Alemtuzumab-induced remission of multiple sclerosis-associated uveitis

Purpose The purpose of the study was to report a case of multiple sclerosis (MS)-associated uveitis refractory to conventional immunosuppressants, with subsequent remission following treatment with alemtuzumab. Methods Case report Patient was treated with intravenous alemtuzumab, a lymphocyte depleting anti-CD52 monoclonal antibody that has recently been approved for use in relapsing MS. Results A 17-year-old female presented with bilateral optic neuritis and subsequently bilateral intermediate uveitis and secondary macular oedema. She was diagnosed with active relapsing MS for which she received treatment with alemtuzumab. The intraocular inflammation previously refractory to conventional immunosuppressants responded to alemtuzumab, inducing remission. Conclusions To our knowledge, this is the first such report of alemtuzumab treatment in MS-associated ocular inflammatory disease and may demonstrate a potential utility for this drug in related conditions

Achieving Quiescence with Fluocinolone Implants

Persistent anterior uveitis causing cystoid macular oedema may necessitate either intraocular or systemic immunosuppression. This case report highlights how a newly licenced treatment, fluocinolone acetonide (Iluvien®, Alimera Sciences Ltd., England, UK) achieves quiescence in refractory and steroid-dependent disease and in the presence of an acute relapse

UNICORNS: Uveitis in childhood prospective national cohort study protocol

Background: Childhood uveitis is a rare inflammatory eye disease which is typically chronic, relapsing-remitting in nature, with an uncertain aetiology (idiopathic). Visual loss occurs due to structural damage caused by uncontrolled inflammation. Understanding of the determinants of long term outcome is lacking, including the predictors of therapeutic response or how to define disease control. Aims: To describe disease natural history and outcomes amongst a nationally representative group of children with non-infectious uveitis, describe the impact of disease course on quality of life for both child and family, and identify determinants of adverse visual, structural and developmental outcomes. Methods: UNICORNS is a prospective longitudinal multicentre cohort study of children newly diagnosed with uveitis about whom a core minimum clinical dataset will be collected systematically. Participants and their families will also complete patient-reported outcome measures annually from recruitment. The association of patient (childand treatment- dependent) characteristics with outcome will be investigated using logistic and ordinal regression models which incorporate adjustment for within-child correspondence between eyes for those with bilateral disease and repeated outcomes measurement. Discussion: Through this population based, prospective longitudinal study of childhood uveitis, we will describe the characteristics of childhood onset disease. Early (1-2 years following diagnosis) outcomes will be described in the first instance, and through the creation of a national inception cohort, longer term studies will be enabled of outcome for affected children and families

Applications of three-dimensional printing in ophthalmology

Three-dimensional (3D) printing is increasingly used to produce customised objects and is a promising alternative to traditional manufacturing methods in diverse fields, such as dentistry and orthopaedics. Already in use in other medical specialities, adoption in ophthalmology has been limited to date. This review aims to provide an overview of 3D printing technology with respect to current and potential applications in ophthalmic practice. Medline, Embase and internet search were performed with "3D printing", "ophthalmology", "dentistry", "orthopaedics" and their synonyms used as main search terms. In addition, search terms related to clinical applications such as "surgery" and "implant" were employed. 3D printing has multiple applications in ophthalmology, including in diagnosis, surgery, prosthetics, medications and medical education. Within the past decade, researchers have produced 3D printed models of objects such as implants, prostheses, anatomical models and surgical simulators. Further development is necessary to generate optimal biomaterials for various applications, and the quality and long-term performance of 3D models needs to be validated