Abstract
This review summarizes the latest findings in the literature of Angiopoietin-2 (Ang-2), Tyrosine-protein kinase receptor (Tie-2) complex, and faricimab along with their involvement for the treatment of retinal vascular diseases in various clinical trials. In ischemic diseases, such as diabetic retinopathy, Ang-2 is upregulated, deactivating Tie-2, resulting in vascular leakage, pericyte loss, and inflammation. Recombinant Angiopeotin-1 (Ang-1), Ang-2-blocking molecules, and inhibitors of vascular endothelial protein tyrosine phosphatase (VE-PTP) decrease inflammation-associated vascular leakage, showing therapeutic effects in diabetes, atherosclerosis, and ocular neovascular diseases. In addition, novel studies show that angiopoietin-like proteins may play an important role in cellular metabolism leading to retinal vascular diseases. Current therapeutic focus combines Ang-Tie targeted drugs with other anti-angiogenic or immune therapies. Clinical studies have identified faricimab, a novel bispecific antibody designed for intravitreal use, to simultaneously bind and neutralize Ang-2 and VEGF-A for treatment of diabetic eye disease. By targeting both Ang-2 and vascular endothelial growth factor-A (VEGF-A), faricimab displays an improved and sustained efficacy over longer treatment intervals, delivering superior vision outcomes for patients with diabetic macular edema and reducing the treatment burden for patients with neovascular age-related macular degeneration and diabetic macular edema. Phase 2 results have produced promising outcomes with regard to efficacy and durability. Faricimab is currently being evaluated in global Phase 3 studies.
Highlights
Retinal vascular disease (RVD) understanding and treatment has increased tremendously over the last decade; there is an increased focus on improving the current anti-angiogenesis mechanisms and agents
This review summarizes the latest findings in the literature of vascular endothelial growth factor (VEGF), angiopoietin and angiopoietinlike factors, and the Ang-2/Tie-2 complex
PubMed/MEDLINE to locate articles published on the topic, including literature reviews, case reports and series, clinical and observational studies, and meta-analyses with a specific aim in identifying articles pertaining to diabetic eye diseases
Summary
Retinal vascular disease (RVD) understanding and treatment has increased tremendously over the last decade; there is an increased focus on improving the current anti-angiogenesis mechanisms and agents. Different disease mechanisms exist perpetuating a variety of different diseases; commonly, these include diabetic macular edema (DME), “wet” age-related macular degeneration (nAMD), and central or branch retinal vein occlusion (CRVO/BRVO, respectively). Given the current therapeutic advancements, there is a strong need for reducing treatment burden and improving efficacy. Patients with diabetic macular edema receive monthly or bimonthly intravitreal (IVT) injections in a clinical setting. New molecules are designed to improve efficacy and durability compared to the current standard of care
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