Uveitis is a heterogeneous collection of diseases. We tested the hypothesis that despite the diversity of uveitides, there could be common mechanisms shared by multiple subtypes, and that evidence of these common mechanisms may be detected as gene expression profiles in whole blood. Cohort study. Ninety subjects with uveitis including axial spondyloarthritis (n = 17), sarcoidosis (n = 13), inflammatory bowel disease (n = 12), tubulointerstitial nephritis with uveitis (n = 10), or idiopathic uveitis (n = 38) as well as 18 healthy controls were enrolled, predominantly at Oregon Health & Science University. RNA-Seq data generated from peripheral, whole blood identified 19,859 unique transcripts. We analyzed gene expression pathways via Kyoto Encyclopedia of Genes and Genomes and Gene Ontology (GO). We validated our list of upregulated genes by comparison to a previously published study on peripheral blood gene expression among 50 subjects with diverse forms of uveitis. Both the Kyoto Encyclopedia of Genes and Genomes and GO analysis identified multiple shared pathways or GO terms with a P value of <.0001. Almost all pathways related to the immune response and/or response to an infection. A total of 119 individual transcripts were upregulated by at least 1.5-fold and false discovery rate <.05, and 61 were downregulated by similar criteria. Comparing mRNA from our study with a false discovery rate <.05 and the prior report, we identified 10 common gene transcripts: ICAM1, IL15RA, IL15, IRF1, IL10RB, GSK3A, TYK2, MEF2A, MEF2B, and MEF2D. Many forms of uveitis share overlapping mechanisms. These data support the concept that a single therapeutic approach could benefit diverse forms of this disease.

To describe eight patients with toxoplasma retinochoroiditis following exposure to wild game.Retrospective, multicenter case seriesEight men, aged 29 to 71 (mean, 56 years), developed toxoplasmic r...

Importance: Randomized clinical trials have shown the safety and efficacy of faricimab as a novel vascular endothelial growth factor and angiopoietin-2 inhibitor in the treatment of neovascular age-related macular degeneration (nAMD) and macular edema of various etiologies. However, more rare adverse events may not be considered in clinical trials.Objective: To describe 3 eyes that developed irreversible vision loss following initial mild intraocular inflammation (IOI) to faricimab.Design, Setting, and Participants: This retrospective case series from a single academic tertiary referral center (University of Nebraska Medical Center) from October 2023 to August 2024 included 3 patients who developed occlusive retinal vasculitis (ORV) following an initial sensitization with intravitreal faricimab. Two eyes were being treated with faricimab for nAMD, and the other 2 eyes were treated for diabetic macular edema.Intervention: Patients exposed to faricimab after the prior development of mild IOI.Main Outcomes and Measures: Clinical symptoms, signs, and clinical course of patients who were diagnosed with ORV following rechallenge with faricimab.Results: Mild IOI developed in 4 eyes following faricimab, and ORV developed in 3 eyes with repeated challenge. This resulted in profound, irreversible vision loss, despite treatment with topical and systemic steroids. In the eye that did not develop ORV following rechallenge, there have been no repeated adverse events despite restarting intravitreal faricimab injections.Conclusions and Relevance: Given these observations with repeated challenge, caution is advisable when using the same biologic after the development of even mild IOI with prior injection. It appears an immunological memory response is elicited with these repeated exposures, resulting in the development of ORV.

Purpose: Acute retinal necrosis (ARN) is a herpesvirus infection of the retina with blinding complications. In this study, we sought to create a reproducible mouse model of ARN that mimics human disease to better understand innate immunity within the retina during virus infection. Methods: C57Bl/6J wild type (WT) and type I interferon receptor–deficient (IFNAR^−/−) mice were infected with varying amounts of herpes simplex virus type 1 (HSV-1) via subretinal injection. Viral titers, optical coherence tomography (OCT) and fundus photography, the development of encephalitis, and ocular histopathology were scored and compared between groups of WT and IFNAR^−/− mice. Results: The retina of WT mice could be readily infected with HSV-1 via subretinal injection resulting in retinal whitening and full-thickness necrosis as determined by in vivo imaging and histopathology. In IFNAR^−/− mice, HSV-1-induced retinal pathology was significantly worse when compared with WT mice, and viral titers were significantly elevated within two days after infection and persisted to day 5 after infection within the retina. These results were also observed in the brain where there were significantly higher viral titers and frequency of encephalitis in IFNAR^−/− when compared to WT mice. Conclusions: Collectively, these findings show that our new mouse model of ARN mimics human disease and can be used to study innate immunity within the retina. We conclude that type I interferons are critical in containing HSV-1 locally within retinal tissues and prohibiting spread into the brain.

Ocular infectious diseases are an important cause of potentially preventable vision loss and blindness. In the following manuscript, we will review ocular immunology and the pathogenesis of herpesviruses and Pseudomonas aeruginosa infections of the cornea and posterior segment. We will highlight areas of future research and what is currently known to promote bench-to-bedside discoveries to improve clinical outcomes of these debilitating ocular diseases.