One of the most frequent retinal vascular occlusions, retinal vein occlusion (RVO) is a multifactorial disease that involves a complicated interplay between several vascular and inflammatory factors, note the authors of a review published in Frontiers in Pharmacology. There are reports of implicated cytokines, chemokines, growth factors, and cell adhesion molecules. RVO treatments address underlying risk factors and vision-threatening consequences, such as macula edema (ME) and neovascularization. Intravitreal anti-VEGF drugs are presently the first-line treatment for ME secondary to RVO (RVO-ME), yet anti-VEGF agents fail to work in many patients. Because RVO-ME is resistant to anti-VEGF drugs reacted to corticosteroids and have a negative relationship with disease duration, predicting therapy response at baseline in RVO-ME could enhance cost-effectiveness and visual prognosis. In addition, several bioactive compounds detected in the aqueous humor have been linked to the RVO disease state. In providing a comprehensive overview of intraocular biomolecules reported in RVO–such as VEGF, IL-6, IL-8, MCP-1, sICAM-1, IL-12, IL-13, sVEGFR-1, sVEGFR-2, PDGF-AA, and others–and highlighting their associations with disease severity and phenotype, as well as their potential roles in prognostic prediction and treatment selection, the authors note that in the future, some of these compounds could be used as biomarkers in aqueous humor-based companion diagnostics for the treatment of RVO.