The most common treatment to arrest blood seepage is antivascular endothelial growth factor A (anti-VEGF-A) medications that are delivered into the eye by intravitreal injection. These drugs have been a remarkable breakthrough, said Wykoff, changing the epidemiology of blindness and the prognosis of patients with diabetic macular edema and neovascular age-related macular degeneration. Despite the effectiveness of anti-VEGF-A medications, certain drawbacks made treatment adherence and widespread adoption a significant challenge. “Patients require an injection typically every four to 12 weeks, often indefinitely,” said Wykoff. “That is a substantial burden for patients, caregivers and eye care providers alike and a limitation of current therapeutics that has prevented us from fully realizing the potential of these drugs in the real world. Many of these patients face significant comorbidities and mobility issues related to advanced age or conditions associated with diabetes.” Unlike anti-VEGF-A medications that target a single biochemical signaling pathway, faricimab, an angiopoietin-2 and VEGF-A bispecific antibody, blocks two key signaling pathways that are implicated in the pathogenesis of diabetic macular edema and neovascular age-related macular degeneration. In particular, by inhibiting angiopoietin-2, native angiopoietin-1 can bind to the endothelial receptor tyrosine kinase transmembrane receptor Tie2, leading to increased intracellular signaling that improves vascular leakage and drives stabilization of the blood-retinal barrier, reductions in inflammation and improved cell survival. In preclinical studies and three phase 2 clinical trials concluded in 2019, the dual pathway inhibition demonstrated the potential for increased vascular stability and greater reductions in vascular leakage, neovascularization and inflammation over VEGF-A inhibition alone.