This paper describes the current literature on the molecular pathophysiology of interleukin-6 (IL-6) in the genesis of macular edema and on the outcomes with IL-6 inhibitors in the treatment of non-infectious macular edema. The role of IL-6 in the development of macular edema has been well elucidated. IL-6 is produced by multiple cells of the innate immune system and leads to a higher likelihood of developing autoimmune inflammatory diseases, such as non-infectious uveitis, through a variety of mechanisms. These include increasing the helper T-cell population over the regulatory T-cell population and leading to the increased expression of inflammatory cytokines, such as tumor necrosis factor-alpha. In addition to being key in the generation of uveitis and subsequent macular edema through these inflammatory pathways, IL-6 also can lead to the development of macular edema through other pathways. IL-6 induces the production of vascular endothelial growth factor (VEGF) and facilitates vascular leakage by downregulating tight junction proteins in retinal endothelial cells. Clinically, the use of IL-6 inhibitors has been found to be efficacious primarily in the context of treatment-resistant non-infectious uveitis and secondary macular edema. IL-6 is a key cytokine in retinal inflammation and macular edema. It is thus not surprising that the use of IL-6 inhibitors in treatment-resistant macular edema in the setting of non-infectious uveitis has been well documented as an effective treatment option. The use of IL-6 inhibitors in macular edema secondary to non-uveitic processes has only begun to be explored.
Keywords: interleukin-6 inhibitors; macular edema; non-infectious uveitis; sarilumab; tocilizumab.