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The seronegative spondyloarthropathies are a closely related group of inflammatory diseases that include ankylosing spondylitis, psoriatic arthritis, reactive arthritis, enteropathic arthritis, inflammatory bowel disease and undifferentiated spondyloarthritis. This review focuses on the spectrum of ocular manifestations associated with these diseases and the current approaches in treating these ocular manifestations. It also highlights the role ophthalmologists can play in identifying and appropriately treating human leukocyte antigen B27 (HLA-B27) associated uveitis and the associated spondyloarthropathies in order to limit ocular and systemic morbidity.Evolving treatment paradigms for the seronegative spondyloarthropathies should direct the choice in therapeutic agent for difficult to control associated uveitis. Biologic therapies, particularly tumor necrosis factor inhibitors, are playing an increasing role in the treatment.Acute anterior uveitis is the most common ocular manifestation in HLA-B27 positive seronegative spondyloarthropathies. Suspicion for HLA-B27 associated uveitis should prompt a careful clinical history and rheumatologic referral if symptoms of an inflammatory arthropathy are present. Therapy is tailored based on severity of ocular and systemic manifestations with interventions from topical corticosteroids to immunomodulating agents available in treating these diseases.