Efficacy and safety of intravitreal anti-VEGF therapy in diabetic retinopathy: what we have learned and what should we learn further?

ABSTRACT

Introduction

Diabetic retinopathy (DR) is one of the most frequent microvascular complications of diabetes that can lead to blindness. Laser treatment has been the gold standard treatment for diabetic macular edema (DME) and proliferative diabetic retinopathy (PDR) for many years. Recently, the role of vascular endothelial growth factor (VEGF) has been established in the pathogenesis of DR, and the use of intravitreal anti-VEGF therapy has gained popularity for the management of DR.

Areas covered

This review includes a brief overview of the efficacy and safety of currently available (bevacizumab, ranibizumab, and aflibercept) and potential future (brolucizumab, faricimab, and KSI-301) anti-VEGF agents in patients with DR based mainly on publicly available data from phase 1, 2 and 3 clinical trials.

Expert opinion

Clinical trials investigating the efficacy of intravitreal bevacizumab, ranibizumab, and aflibercept injections demonstrated favorable functional and anatomical outcomes in patients with DME. Moreover, the use of these anti-VEGF agents showed a significant improvement in the severity of DR. Recent clinical research for future anti-VEGF molecules aims to provide higher target-protein binding affinity and prolonged therapeutic effect. Brolucizumab, faricimab, and KSI-301 are three novel anti-VEGF agents that demonstrate promising data for the management of DME and potentially DR.

KEYWORDS:

• Aflibercept
• bevacizumab
• diabetic macular edema
• diabetic retinopathy
• ranibizumab
• vascular endothelial growth factor
• anti-vascular endothelial growth factor

Article highlights

• Vascular endothelial growth factor (VEGF), particularly VEGF-A, is known to be a key mediator in the pathophysiology of diabetic retinopathy.

• Intravitreal anti-VEGF therapy is the first-line treatment for center-involved diabetic macular edema.

• Currently available intravitreal anti-VEGF agents, bevacizumab, ranibizumab, and aflibercept, have shown significant superiority in visual acuity (VA) and anatomical improvement compared to laser treatment for center-involved diabetic macular edema in the key clinical trials.

• Intravitreal anti-VEGF agents have demonstrated additional benefits in improving severity of diabetic retinopathy in patients with both non-proliferative and proliferative diabetic retinopathy.

• Brolucizumab, faricimab, and KSI 301 are three novel anti-VEGF pharmacologic agents that have demonstrated promising results on efficacy and durability in patients with diabetic macular edema as well as other retinal vascular diseases.

• Recent safety data from the HAWK and HARRIER studies as well as the KITE and KESTREL studies, and other case reports and case series, have shown an increased risk of intraocular inflammation and occlusive retinal vasculitis following intravitreal brolucizumab administration, more among eyes with neovascular age-related macular degeneration than eyes with diabetic macular edema.

Declaration of interests

QD Nguyen serves on the scientific advisory boards for Bausch and Lomb, Bayer, Genentech/Roche, Regeneron, Novartis and Santen. QD Nguyen has also chaired the steering committee for the RISE and RIDE studies and was on the steering committee for the VISTA Study, as well as other studies sponsored by Genentech and Regeneron. DV Do serves on the scientific advisory boards for Allergan, Kodiak, Genentech and Regeneron. 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.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.