Current and investigational drugs for the treatment of diabetic retinopathy

ABSTRACT

Introduction: Diabetic macular edema (DME) and proliferative diabetic retinopathy (PDR) are the two complications of diabetes that cause visual loss and blindness. Laser photo-coagulation in the past was used to prevent progression of disease to these advanced stages. Advances in pathophysiologic understanding of DME and PDR have ushered the development of effective targeted therapy that given intravitreally improves vision and prevents blindness. While effective, these therapies require frequent administration and are not universally effective.

Areas covered: This purpose of this paper is to review the current pathophysiologic understanding and treatments for DME and PDR as well as the novel treatments currently being developed. The treatments will be juxtaposed to the factor in the disease cascade being targeted. The potential role of these novel treatment in the clinical armamentarium are postulated.

Expert opinion: Mono-therapy, single category targeting is the current strategy being utilized clinically. However, diabetic retinopathy needs combination therapy. Therapies that will prove successful will address multiple factors involved in the pathogenesis of diabetic retinopathy.

KEYWORDS:

• Diabetes
• diabetic retinopathy
• VEGF
• macular edema
• retinal neovascularization
• integrins
• drug development

Article highlights

• Hyperglycemia produced advanced glycation end products stimulates vascular endothelial growth factor (VEGF) in normal retinas.

• VEGF is the only factor sufficient to produce all clinical findings of diabetic retinopathy in a dose dependent fashion.

• Inhibition of VEGF and inflammation only clinically validated targets for resolution of diabetic macular edema and non proliferative retinopathy

• VEGF inhibition main strategy to resolve retinal neovascularization in proliferative diabetic retinopathy

• Drug development for diabetic retinopathy is focused on better anti-VEGF, anti-inflammatory or anti-oxidative strategies.

• Novel strategies include modulation of TIE/Angiopoietin pathway, Integrin antagonism, and vitreolysis.

• Improving therapy will require targeting inflammation and VEGF either as a single agent or in combination

This box summarizes key points contained in the article.

Declaration of interest

This paper was supported by the Tolentino Eye Research Foundation. MJ Tolentino has received research grants from Regeneron, Bayer Healthcare, Allergan, Alimera Sciences, Allegro, Alcon, Novartis, Astellas, Ponoptica and Genentech Inc. The authors have no other 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 apart from those disclosed.

Additional information

Funding

This work was supported by the Tolentino Eye Research Foundation.