Precision management of autoimmune ocular complications: Th17 mechanisms and therapeutic innovations

Precision management of ocular complications in systemic autoimmune diseases, such as Sjögren's syndrome (SS), systemic lupus erythematosus (SLE), Behçet's disease, and thyroid-associated ophthalmopathy (TAO), requires integration of immune mechanisms with clinical translation. These disorders manifest as dry eye, uveitis, retinal vasculitis, optic neuritis, and orbital fibroinflammatory disease, posing a substantial risk of irreversible visual loss. Recent studies highlight the T-helper 17 (Th17)/interleukin-17 (IL-17) axis, tumor necrosis factor-alpha (TNF-α), complement component 5a (C5a), and TAO-related immunostromal remodeling as pivotal inflammatory drivers. Specifically, TAO is increasingly recognized as an immunostromal disorder in which fibroblast-immune crosstalk connects thyrotropin receptor antibody/insulin-like growth factor-1 receptor signaling with orbital edema, adipogenesis, and fibrosis. Disease-specific pathways, including anti-Sjögren's-syndrome-related antigen A (anti-SSA)-mediated lacrimal damage and the human leukocyte antigen B27 (HLA-B27) gut-eye axis, further enrich etiological insights. Diagnostically, aqueous IL-17, C-X-C motif chemokine ligand 10 (CXCL10), tear biomarkers, and optical coherence tomography angiography (OCTA) enable more precise phenotyping, whereas invasive ocular-fluid testing requires careful risk-benefit evaluation. Therapeutically, anti-TNF-α monoclonal antibodies, teprotumumab, and avacopan target critical pathways and improve refractory cases, while Janus kinase inhibitors, B-cell-directed combinations, and engineered regulatory T-cell therapies show promise but require rigorous safety and translational validation. This review discusses major advances in immunopathogenesis, diagnostics, and therapeutics, comparing disease commonalities and distinctions to propose a framework for precision management. It envisions multi-omics phenotyping, artificial intelligence-assisted diagnostics, and pathway-directed immunomodulation to reduce blindness and enhance quality of life, bridging rheumatology and ophthalmology.