Immune Mediators in Birdshot Chorioretinopathy: A Systematic Review.

PURPOSE: Birdshot chorioretinopathy (BSCR) is a rare, chronic, bilateral posterior uveitis uniquely associated with HLA-A29. Despite this genetic linkage, the immune mechanisms driving BSCR remain poorly defined. We conducted a systematic review to synthesize evidence on immune mediators in BSCR and their potential as biomarkers or therapeutic targets.

METHODS

Canada a systematic search of OVID MEDLINE, PubMed and Embase databases was performed on August 1, 2024 following PRISMA guidelines. Eligible studies investigated cytokines, chemokines, and immune cell populations in BSCR. Non-English studies, animal models, and reviews were excluded. Data extraction and risk-of-bias assessments were independently completed by two reviewers.

RESULTS

Of the 130 screened studies, 14 met inclusion criteria. Samples from peripheral blood, aqueous humor, and vitreous humor were evaluated using enzyme-linked immunosorbent assay, flow cytometry, and RNA sequencing. Th17-associated signaling was implicated, with elevated intraocular IL-17 and systemic IL-21, IL-23, TGF-β that responded to treatment. Elevated intraocular IL-6, TNF, IP-10, MCP-1, and soluble adhesion molecules supported localized inflammation. Cellular studies showed consistent elevation of Th17 cells in the blood and CD8+ T-cells in the vitreous. Single-cell RNA sequencing revealed treatment-responsive expansion of pro-inflammatory natural killer (NK) cells. B-cells and T-regulatory cells showed minimal or inconsistent alterations.

CONCLUSION

BSCR pathogenesis involves a Th17-mediated inflammatory response, with CD8+ and NK cell involvement. While anti-TNF agents remain an established treatment for refractory BSCR, the clinical failure of IL-17A inhibitors suggests that broader inhibition, such as dual IL-17A/F blockade, may be needed. Future studies integrating single-cell techniques and tissue-specific insights are needed to understand disease mechanism and guide treatment.