The Role of Sex in Uveitis and Ocular Inflammation

Ian Y. L. Yeung, MD; Nicholas A. Popp, BS; Chi-Chao Chan, MD

Disclosures

Int Ophthalmol Clin. 2015;55(3):111-131. 

In This Article

Male Predominant Uveitides With Systemic Involvement

Spondyloarthropathies are a group of inflammatory arthritides. Uveitis occurs in up to 37% of spondyloarthopathy patients.[50,112] These diseases tend to be more prevalent in males.[51] For example, up to 80% of ankylosing spondylitis patients are male.[113] Up to 90% of ankylosing spondylitis patients, 40% to 80% of reactive arthritis patients, and 40% to 50% of psoriatic arthritic patients are positive for HLA-B27.[50,51,112] HLA-B27 anterior uveitis is more prevalent in males with 66.5% to 75% of patients being male.[52,63] This is important because HLA-B27 anterior uveitis is one of the most common types of uveitis in western countries, accounting for 50% to 80% of anterior uveitis patients.[50–55] Recently, a genome-wide association study showed that a single allele of HLA-B27 conferred an odds ratio of 66.8 for developing acute anterior uveitis and homozygosity conferred an odds ratio of 130.6 when compared with HLA-B27-negative controls.[114] In general, an HLA-B27-associated uveitis has a poorer prognosis than a HLA-B27-negative uveitis.[56,115] Male sex is also a risk factor for an associated occlusive retinal vasculitis, a younger age of onset, and single-visit vision loss of 20/50 or worse.[51,57,64,116,117] However, there is no sex difference in the risk of hypopyon, vitritis, cystoid macular edema, secondary glaucoma, or final visual acuity.[51]

Behçet disease (BD) is a rare immune-mediated systemic vasculitis of unknown etiology. In BD, 54% to 85% of patients are male.[18,35,59,60] It predominantly affects patients with ancestry from the Silk Road (especially from Turkey). Uveitis occurs in 50% to 90% of BD patients.[61,62] BD frequently presents as a bilateral pan-uveitis, particularly with a retinal vasculitis.[59,118] Other features include oral and genital ulcers, vascular complications, arthritis, skin lesions, and central nervous system lesions.[8] There is a strong association with HLA-B51.[119,120] BD tends to be more severe in males, patients with a younger age of onset, and in HLA-B51-positive patients.[61,121] Men also are more likely to have a poorer response to therapy for ocular BD.[122,123] This is thought to be due to the higher incidence of retinal vasculitis and posterior-segment involvement in men than in women.[5]

The systemic vasculitides are a group of conditions associated with uveitis, which were classified according to the size of the involved blood vessels. The 2012 International Chapel Hill Consensus Conference updated the nomenclature. The new term "antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV)" now encompasses: granulomatosis with polyangiitis (GPA instead of Wegener granulomatosis), eosinophilic granulomatosis with polyangiitis (EGPA instead of Churg-Strauss Syndrome), and microscopic polyangiitis.[5,124] No obvious sex difference for AAV has been reported.[44] In 1 study, 53.8% of AAV patients were male.[125] Interestingly, mildly increased male prevalence was pronounced in patients over 50 years of age.[45] The most common ophthalmic manifestations of ANCA-associated vasculitides are conjunctivitis, episcleritis, and scleritis. Uveitis tends to occur in <10% of patients and is thought to be spillover of inflammation from adjacent scleritis or keratitis.[126–129] Occlusion of retinal veins and arteries is uncommon but can occur in GPA and EGPA.[130–133]

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