Vogt-Koyanagi-Harada disease: Novel insights into pathophysiology, diagnosis and treatment

Vogt-Koyanagi-Harada (VKH) disease is one of the major vision-threatening diseases in certain populations, such as Asians, native Americans, Hispanics and Middle Easterners. It is characterized by bilateral uveitis that is frequently associated with neurological (meningeal), auditory, and integumentary manifestations. Although the etiology and pathogenesis of VKH disease need to be further elucidated, it is widely accepted that the clinical manifestations are caused by an autoimmune response directed against melanin associated antigens in the target organs, i.e. the eye, inner ear, meninges and skin. In the past decades, accumulating evidence has shown that genetic factors, including VKH disease specific risk factors (HLA-DR4) and general risk factors for immune mediated diseases (IL-23R), dysfunction of immune responses, including the innate and adaptive immune system and environmental triggering factors are all involved in the development of VKH disease. Clinically, the criteria of diagnosis for VKH disease have been further improved by the employment of novel imaging techniques for the eye. For the treatment, early and adequate corticosteroids are still the mainstream regime for the disease. However, immunosuppressive and biological agents have shown benefit for the treatment of VKH disease, especially for those patients not responding to corticosteroids. This review is focused on our current knowledge of VKH disease, especially for the diagnosis, pathogenesis (genetic factors and immune mechanisms), ancillary tests and treatment. A better understanding of the role of microbiome composition, genetic basis and ongoing immune processes along with the development of novel biomarkers and objective quantitative assays to monitor intraocular inflammation are needed to improve current management of VKH patients.