Local and Systemic Inflammatory Biomarkers of Diabetic Retinopathy: An Integrative Approach

PURPOSE. To review the usefulness of local and systemic inflammatory biomarkers of diabetic retinopathy (DR) to implement a more personalized treatment. METHODS. An integrated research (from ophthalmologist and diabetologist point of view) of most significant literature on serum, vitreous, and aqueous humor (AH) biochemical biomarkers related to inflammation at early and advanced stages of DR (including diabetic macular edema [ DME] and proliferative DR) was performed. Moreover, novel imaging retinal biomarkers of local "inflammatory condition'' were described. RESULTS. Multiple inflammatory cytokines and chemokines are increased in DR in both serum as well as in the eye (vitreous and AH). Nevertheless, local rather than systemic production of proinflammatory cytokines seems more relevant in the pathogenesis of both DR and DME. In the eye, retinal glia cells (macroglia and microglia) together with RPE are major sources of proinflammatory and angiogenic modulators. Retinal imaging allows for noninvasive clinical evaluation of retinal inflammatory response induced by diabetes mellitus. CONCLUSIONS. Proinflammatory cytokines/chemokines play an essential role in the pathogenesis of DR. Therefore, circulating biomarkers and retinal imaging aimed at assessing inflammation have emerged as useful tools for monitoring the onset and progression of DR. In addition, "liquid biopsy'' of AH seems a good option in patients with advanced stages of DR requiring intravitreous injections. This strategy may permit us to implement a more personalized with better visual function outcome. Further evaluation and validation of circulating and local biomarkers, as well as multimodal imaging is needed to gain new insights into this issue.