The Role of Sex in Uveitis and Ocular Inflammation

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


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

In This Article


The burden of blindness worldwide is unequal with regards to sex, with women accounting for 64.5% of blindness.[1] While some of this discrepancy can be explained by factors such as poorer access to care, it is not sufficient to explain the entirety of the problem.[2] The uveitides are a collection of diseases that result in inflammation of the uveal tract that may also involve the retina and vitreous. The causes of uveitis can be either noninfectious (most are considered forms of autoimmune uveitis) or infectious. If left untreated, uveitis can lead to poor visual outcomes, including blindness. Interestingly, these diseases affect the sexes differently, with some being more common in women and others more common in men.[3] Along with the finding that the prevalence of autoimmunity in women is higher than in men, uveitides with autoimmune etiologies, such as those resulting from systemic lupus erythematosus (SLE) and sarcoidosis tend to be reported more frequently in women than in men.[4] Although the cause for this is unclear, recent evidence has pointed towards how sex hormones affect the autoimmune response; estrogen increases the response, whereas androgens suppress it. However, other evidence suggests that estrogen's effect on autoimmunity may be dose dependent with lower levels being immune-stimulatory and higher levels immune-inhibitory.[5] Furthermore, women respond to injury or infection with a dominant Th2 immune response (leading to increased antibody production), whereas men respond with a stronger Th1 response. This may play a role in the increased prevalence of Th2-mediated autoimmune disorders in women.[4] Moreover, estrogen has recently been shown to play a significant role in the development and function of Th17 cells, as well as the production of interleukin (IL)-17.[6,7] It has also been noted that men and women may present with the same underlying cause of uveitis but with differing severity or ophthalmic manifestations.[8] In addition, infectious uveitides do show sex differences in prevalence, primarily because of behavioral and/or cultural sources.[9] All these reports point to sex differences in clinical manifestations and pathogenesis of uveitis that may be important for disease prevention and treatment.