IL-23 drives uveitis by acting on a population of tissue-resident entheseal T cells.

Recurrent acute anterior uveitis is a frequent extra-articular manifestation of the axial spondyloarthropathies (AxSpA); chronic inflammatory diseases affecting the spine, enthesis, peripheral joints, skin, and gastrointestinal tract. Pathology in AxSpA has been associated with local tissue-resident populations of interleukin (IL)-23 responsive lymphoid cells. Here we characterize a population of ocular T cell defined by CD3+CD4-CD8-CD69+gdTCR+IL-23R+ that reside within the anterior uvea as an ocular entheseal analogue of the mouse eye.

Evidence and Consensus-Based Imaging Guidelines in Acute Posterior Multifocal Placoid Pigment Epitheliopathy (APMPPE) - Multimodal imaging in Uveitis (MUV) Taskforce Report 7.

Purpose: To develop consensus-based guidelines on use and interpretation of multimodal imaging in acute posterior multifocal placoid pigment epitheliopathy (APMPPE).

Design: Consensus agreement led by literature, and an expert committee using a nominal group technique (NGT).

Methods: The expert committee for APMPPE performed a thorough review of representative cases of APMPPE.

Uveitis in Adults: A Review.

Importance: Uveitis is characterized by inflammation of the uvea-the middle portion of the eye composed of the iris, ciliary body, and choroid-causing eye redness, pain, photophobia, floaters, and blurred vision. Untreated uveitis may cause cataracts, glaucoma, macular edema, retinal detachment, optic nerve damage, and vision loss.

Observations: Uveitis predominantly affects individuals aged 20 to 50 years.

Bayesian trial of adalimumab versus secukinumab for children with juvenile idiopathic arthritis associated uveitis or chronic anterior uveitis.

Background: Juvenile idiopathic arthritis (JIA)-associated uveitis and chronic anterior uveitis in children may result in permanent sight loss. Currently, the only licensed and approved treatment for JIA-uveitis is adalimumab. However, even in patients where adalimumab may be initially effective, therapeutic response may subside for example, due to neutralising drug antibodies.

Age-Associated Decline in Autophagy Pathways in the Retinal Pigment Epithelium and Protective Effects of Topical Trehalose in Light-Induced Outer Retinal Degeneration in Mice.

Age is a primary risk factor for chronic conditions, including age-related macular degeneration (AMD). Impairments in autophagy processes are implicated in AMD progression, but the extent of autophagy's contribution and its therapeutic potential remain ambiguous. This study investigated age-associated transcriptomic changes in autophagy pathways in the retinal pigment epithelium (RPE) and evaluated the protective effects of topical trehalose, an autophagy-enhancing small molecule, against light-induced outer retinal degeneration in mice.

Gene Therapy-Associated Uveitis (GTAU): Understanding and mitigating the adverse immune response in retinal gene therapy.

Retinal gene therapy using adeno-associated viral (AAV) vectors has been a groundbreaking step-change in the treatment of inherited retinal diseases (IRDs) and could also be used to treat more common retinal diseases such as age-related macular degeneration and diabetic retinopathy. The delivery and expression of therapeutic transgenes in the eye is limited by innate and adaptive immune responses against components of the vector product, which has been termed gene therapy-associated uveitis (GTAU). This is clinically important as intraocular inflammation could lead to irreversible loss of retinal cells, deterioration of visual function and reduced durability of treatment effect associated with a costly one-off treatment.

Characterization of the ocular inflammatory response to AAV reveals divergence by sex and age.

Progress for ocular adeno-associated virus (AAV) gene therapy has been hindered by AAV-induced inflammation, limiting dose escalation and long-term efficacy. Broadly, the extent of inflammatory responses alters with age and sex, yet these factors are poorly represented in pre-clinical development of ocular AAV gene therapies. Here, we combined clinical imaging, flow cytometry, and bulk sequencing of sorted microglia to interrogate the longitudinal inflammatory response following intravitreal delivery of AAV2 in young (3-month-old), middle aged (9-month-old), and old (18-month-old) Cx3cr1-creER:R26tdTomato mice of both sexes.

Stage 1 Extensive Macular Atrophy with Pseudodrusen-Like Appearance Complicated by Multiple Evanescent White Dot Syndrome-Like Reaction.

Purpose: To describe a case of early-stage Extensive Macular Atrophy with Pseudodrusen-like appearance (EMAP) presenting with acute monocular loss and atypical retinal lesions suggestive of posterior uveitis.

Methods: Case report with longitudinal follow-up including visual field testing and multimodal imaging.

Results: A 53-year-old woman presented with sudden vision loss in her right eye (RE).

Imaging-Based Detection of Anterior Chamber Inflammation: A Comparative Diagnostic Accuracy Study.

Purpose: We investigated the impact of operator parameters on the diagnostic performance of anterior-segment optical coherence tomography (AS-OCT) in anterior uveitis.

Design: Prospective comparative diagnostic analysis.

Methods: Setting: Single site.

Integration of Genetic and Clinical Risk Factors for Risk Classification of Uveitis in Patients With Juvenile Idiopathic Arthritis.

Objective: Juvenile idiopathic arthritis (JIA)-associated uveitis (JIAU) is a serious JIA comorbidity that can result in vision impairment. This study aimed to identify genetic risk factors within the major histocompatibility complex for JIAU and evaluate their contribution for improving risk classification when combined with clinical risk factors.

Methods: Data on single nucleotide polymorphisms, amino acids, and classical HLA alleles were available for 2,497 patients with JIA without uveitis and 579 patients with JIAU (female 2,060, male 1,015).

UNICORNS: Uveitis in childhood prospective national cohort study protocol.

: 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.

Long-Term Visual Outcome of Patients with Blau Syndrome.

Purpose: To document the long-term visual outcomes in patients with Blau syndrome.

Methods: A retrospective institutional cohort study was conducted, and 13 patients with genetically confirmed Blau syndrome were included. Demographic and clinical data were collected from standardised medical charts.

Quality assessment of anterior segment OCT images: Development and validation of quality criteria.

Background: The utility of medical imaging is dependant on image quality. We aimed to develop and validate quality criteria for ocular anterior segment optical coherence tomography (AS-OCT) images.

Methods: We undertook a cross-sectional study using AS-OCT images from patients aged 6-16.

Replenishing Age-Related Decline of IRAK-M Expression in Retinal Pigment Epithelium Attenuates Outer Retinal Degeneration.

Unchecked, chronic inflammation is a constitutive component of age-related diseases, including age-related macular degeneration (AMD). Here we identified interleukin-1 receptor-associated kinase (IRAK)-M as a key immunoregulator in retinal pigment epithelium (RPE) that declines with age. Rare genetic variants of IRAK-M increased the likelihood of AMD.

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.

Elastin Layer in Bruch's Membrane as a Target for Immunization or Tolerization to Modulate Pathology in the Mouse Model of Smoke-Induced Ocular Injury.

Age-related macular degeneration (AMD) is associated with an overactive complement system and an increase in circulating antibodies. Our search for potential neoantigens that can trigger complement activation in disease has led us to investigate elastin. A loss of the elastin layer (EL) of Bruch's membrane (BrM) has been reported in aging and AMD together with an increase of serum elastin-derived peptides and α-elastin antibodies.

The Infectious Uveitis Treatment Algorithm Network (TITAN) Report 2-global current practice patterns for the management of Cytomegalovirus anterior uveitis.

Aims: To present current practice patterns in the diagnosis and management of Cytomegalovirus anterior uveitis (CMV AU) by uveitis experts worldwide.

Methods: A two-round modified Delphi survey with masking of the study team was performed. Based on experience and expertise, 100 international uveitis specialists from 21 countries were invited to participate in the survey.

CAR-Treg cell therapies and their future potential in treating ocular autoimmune conditions.

Ophthalmic autoimmune and autoinflammatory conditions cause significant visual morbidity and require complex medical treatment complicated by significant side effects and lack of specificity. Regulatory T cells (Tregs) have key roles in immune homeostasis and in the resolution of immune responses. Polyclonal Treg therapy has shown efficacy in treating autoimmune disease.