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

Insurance Coverage During Transitions: Evidence From Medicaid Automatic Enrollment for Children Receiving Supplemental Security Income

OBJECTIVES: To analyze relationships between Medicaid automatic enrollment for child Supplemental Security Income (SSI) recipients and health insurance coverage during transitions. DATA SOURCES AND STUDY SETTING: Medical Expenditure Panel Study, 2000-2020 and National Survey for Children with Special Health Care Needs, 2001-2010. STUDY DESIGN: Leveraging variation in SSI-Medicaid automatic enrollment status across regions and over time, we estimate a regression model to quantify associations between automatic enrollment and insurance coverage. We validate our findings in the NS-CSHCN. DATA COLLECTION: Our sample includes children receiving SSI for a disability. We also analyze a subsample of children newly enrolled in SSI. PRINCIPAL FINDINGS: Automatic enrollment is associated with a statistically significant increase in insurance coverage. Expanding automatic enrollment to all states is associated with increases in Medicaid enrollment of 3% (CI 0.9%-6.7%) among all SSI children and 7% (CI 1.1%-13.9%) among children newly enrolled in SSI. We find similar decreases in uninsurance. Analysis in the NS-CSHCN replicates these findings. CONCLUSIONS: Medicaid automatic enrollment policies are associated with increased insurance coverage for SSI children, particularly those transitioning into the program. Medicaid policy defaults could play an important role in reducing administrative burdens to improve children\u27s coverage and access to care

Establishing the Normative Data Set Necessary for Imaging-Based Childhood Uveitis Surveillance: A Cross-Sectional Study

PURPOSE. Anterior segment optical coherence tomography (AS-OCT) is an emerging diagnostic and monitoring tool for anterior uveitis. We investigated AS-OCT findings in the eyes of a large, diverse population of children free of uveitis to establish its potential to “rule out” accurately those without disease. METHODS. In this cross-sectional observational study, image acquisition was performed with swept source AS-OCT (Heidelberg Anterion), using a protocol of 13 B-scans per volume, from 217 children (434 eyes) aged 5 to 15 years, with analysis of acquired images (identification of apparent inflammatory cells, or “cell events”) by multiple graders. Outcomes of interest were median and maximum cell event count (MEDCC, MAXCC) per B-scan from each eye and the total cell event count (TCC) per volume scan. RESULTS. At least one cell event was detected in volume scans of 76% of eyes (329/434) and 87% of children (189/217). The maximum number (MAXCC) per scan ranged from 0 to 6 (median, 2). There was a strong positive association between increasing age (years) and the number of cell events detected within a volume scan following adjustment for gender and iris color (adjusted regression coefficient for TCC 0.5; P < 0.0001; 95% confidence interval, 0.4–0.7). CONCLUSIONS. Our findings demonstrate that apparent inflammatory cells are detectable on AS-OCT in the apparently healthy eyes of children and furthermore suggest early life developmental changes in blood–iris barrier stability that merit further exploration. We provide the foundation for the normative data set necessary for establishing the clinical utility of AS-OCT for surveillance of children with inflammatory eye diseases

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./

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

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