Current and investigational pharmacotherapeutic approaches for modulating retinal angiogenesis

Abstract

Retinal vascular development is a carefully orchestrated developmental process during which retinal and choroidal vasculature form to provide a dual vascular supply to the neurosensory retina and retinal pigment epithelium. The most common causes of vision loss in children and adults involve at least in part perturbation of the normal vascular physiology or development. Vascular endothelial growth factor has emerged as a key molecular regulator of retinal vascular development as well as retinal and choroidal neovascularization, which underlie the pathophysiology of many retinal diseases. Over the past decade, the advent of injectable pharmacotherapeutic agents into the vitreous cavity of the eye has revolutionized our management of neovascular age-related macular degeneration and other retinal diseases and has, for the first time, offered an opportunity to improve vision rather than just slow the progression of disease processes. The transient duration of these agents, however, requires chronic treatment with repeated intraocular injections and significant treatment burden for patients and the healthcare system. Novel treatments modulating retinal angiogenesis offer the promise of improved efficacy, decreased treatment burden and improved cost–effectiveness.

Keywords::

• aflibercept
• age-related macular degeneration
• bevacizumab
• choroidal neovascularization
• diabetic retinopathy
• ranizbizumab
• retinal neovascularization

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Retinal angiogenesis is a carefully regulated developmental process at the cellular and molecular level.

• Neovascularization of the retina and choroid underlies the pathogenesis of many blinding retinal diseases including age-related macular degeneration and diabetic retinopathy.

• VEGF is currently the most important identified molecular factor regulating vascular development and neovascularization.

• Intravitreal agents in clinical use currently targeting VEGF include pegaptanib sodium, bevacizumab, ranibizumab and aflibercept.

• Despite attempts to optimize dosing regimens, most patients still require chronic and ongoing treatment with frequent intraocular anti-VEGF administration, which confers significant treatment burden on patients and the healthcare system.

• Novel pharmacotherapeutics offer the promise of improved efficacy and lowered treatment burden.

Notes