Gender Differences in Vogt-Koyanagi-Harada Disease and Sympathetic Ophthalmia

Abstract

Vogt-Koyanagi-Harada disease (VKH) and sympathetic ophthalmia (SO) are types of T-cell mediated autoimmune granulomatous uveitis. Although the two diseases share common clinical features, they have certain differences in gender predilections. VKH classically has been reported as more prevalent in females than males, yet some studies in Japan and China have not found differences in gender prevalence. Male patients have a higher risk of chorioretinal degeneration, vitiligo, and worse prognosis. Conversely, the changing levels of estrogen/progesterone during pregnancy and the menstrual cycle as well as higher levels of TGF-β show a protective role in females. Potential causes of female predilection for VKH are associated with HLA-DR and HLA-DQ alleles. SO, a bilateral granulomatous uveitis, occurs in the context of one eye after a penetrating injury due to trauma or surgery. In contrast to the female dominance in VKH, males are more frequently affected by SO due to a higher incidence of ocular injury, especially during wartime. However, no gender predilection of SO has been reported in postsurgical cases. No clinically different manifestations are revealed between males and females in SO secondary to either ocular trauma or surgery. The potential causes of the gender difference may provide hints on future treatment and disease evaluation.

The Role of Sex in Uveitis and Ocular Inflammation

“…50 Long-term sequelae include choroidal neovascularization (CNV), sub-retinal fibrosis, and cataracts. 48, 51 Similar to other uveitic conditions with systemic involvement, gender affects the prognosis; 50 a male VKH patient is significantly more likely to have a poorer visual outcome than a female patient. An Indian group found that 37.5% of their male VKH patients had vision worse than 20/80, compared to only 3.3% of their female VKH cohort.…”

“…52 The reason for the poorer male visual outcomes is unclear, though female sex hormones and HLA-DR genes have been associated with the female predisposition to the disease. 50, 53-55 …”

“…Injury to the “exciting eye” results in an inflammatory response that develops later (90% of cases are within one year) in the uninjured “sympathizing eye”. 50 As men are more likely to suffer penetrating ocular trauma due to occupational and lifestyle factors, there seems an increased prevalence in men with 50-72.1% of SO patients being male. 50, 99, 100 In post-surgical cases, there have been no reported gender differences.…”

“…50 As men are more likely to suffer penetrating ocular trauma due to occupational and lifestyle factors, there seems an increased prevalence in men with 50-72.1% of SO patients being male. 50, 99, 100 In post-surgical cases, there have been no reported gender differences. 50, 99 SO classically presents as acute bilateral granulomatous inflammation with mutton-fat keratic precipitates, aqueous cells and flare, iridocyclitis, and posterior synechiae.…”

A case of Vogt-Koyanagi-Harada disease mimicking sympathetic ophthalmia

“…VKH is also common among females, while SO doesn't show any sexual predilection. SO is more common in young age due to trauma and in old age due to increased frequency of surgeries [7]. The inciting event is also different, usually, a penetrating ocular injury in SO.…”