Angiopoietins as Potential Targets in Management of Retinal Disease

Abstract

The Ang/Tie2 pathway complements VEGF-mediated activity in retinal vascular diseases such as DME, AMD, and RVO by decreasing vascular integrity, increasing neovascularization, and increasing inflammatory signaling. Faricimab is a bispecific antibody that has been developed as an inhibitor of both VEGF and Ang2 that has shown positive results in phase I, II and III trials. Recent Year 1 data from phase III clinical trials YOSEMITE, RHINE, TENAYA, and LUCERNE have confirmed the efficacy, safety, durability, and superiority of faricimab in patients with DME and nAMD. Faricimab, if approved, may significantly decrease treatment burden in patients with retinal vascular diseases to a greater extent than would current standard of care anti-VEGF injections.

Association between Retinal Thickness Variability and Visual Acuity Outcome during Maintenance Therapy Using Intravitreal Anti-Vascular Endothelial Growth Factor Agents for Neovascular Age-Related Macular Degeneration

“…This may be achieved by adopting a more objective individualized treat-and-extend treatment approach using OCT and visual acuity findings to increase the chance of maintaining a dry macula. A form of automated modified treat-and-extend protocol is being evaluated in the faricimab personalized treatment interval arm in the LUCERNE and TENAYA studies for nAMD [ 24 , 25 ]. Another potential option for minimizing the variation in retinal thickness is to utilize newer therapeutic agents which have stronger ability to resolve macular fluids or have increased treatment durability [ 24 , 25 , 26 ].…”

“…A form of automated modified treat-and-extend protocol is being evaluated in the faricimab personalized treatment interval arm in the LUCERNE and TENAYA studies for nAMD [ 24 , 25 ]. Another potential option for minimizing the variation in retinal thickness is to utilize newer therapeutic agents which have stronger ability to resolve macular fluids or have increased treatment durability [ 24 , 25 , 26 ]. For example, brolucizumab has been shown to result in a significantly greater proportion of eyes with fluid resolution compared with aflibercept; thus, it might be useful in achieving less fluid fluctuation over the course of anti-VEGF therapy [ 27 ].…”

Faricimab in the Treatment Landscape for Retinal Diseases: A Review

“…25 Tie-2 is a tyrosine kinase receptor found on vascular endothelial cells, and its two major physiological ligands are angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2), which have opposing effects. 26 Ang-1, normally expressed in pericytes, is an agonist that causes the phosphorylation of Tie-2 and activates downstream signalling that promotes vessel stabilization, anti-inflammation, pericyte health and vascular homeostasis. 17 One such downstream pathway that reduces vascular permeability is by migration of the phosphorylated Tie-2 receptor to the cell junction, where it helps strengthen and stabilize the adherens protein vascular endothelial cadherin (VE-cadherin) that serves as a protective barrier against inflammatory stress and vascular permeability.…”

Faricimab for treatment of diabetic macular oedema

“…In this direction, the role of the Ang/Tie pathway has been investigated with promising results for the treatment of DME. 4,9,17,18 In adulthood, the Ang/Tie pathway is responsible for regulating vascular homeostasis, modulating vascular permeability, neoangiogenesis, and inflammation.…”

“…Some can be treated with cortico‐steroid implants; however, these have a higher side effects profile such as development of cataract and glaucoma. In this direction, the role of the Ang/Tie pathway has been investigated with promising results for the treatment of DME 4,9,17,18 . In adulthood, the Ang/Tie pathway is responsible for regulating vascular homeostasis, modulating vascular permeability, neoangiogenesis, and inflammation.…”