The role of ranibizumab in the management of diabetic retinopathy

Abstract

Diabetic retinopathy (DR) comprises a major challenge to the public health and economy, being the leading cause of vision loss in working-aged adults in developed countries. If left untreated, DR will eventually progress leading to devastating blinding consequences including diabetic macular edema (DME), vitreous hemorrhage and tractional retinal detachment. Ranibizumab is a humanized monoclonal antibody fragment that targets the vascular endothelial growth factor (VEGF). It has been approved by the US FDA for the treatment of DME and DR in patients with DME. Given its proven efficacy and favorable safety profile, it has been widely used as one of the preferred therapeutic option for DME in modern clinical practice. This review provides a comprehensive overview on the safety and efficacy of ranibizumab in the management of DR and its associated sight-threatening microvascular complications.

Keywords:

• intravitreal injection
• laser photocoagulation
• macular edema
• monoclonal antibodies
• neovascularization
• Ranibizumab
• retinopathy severity
• vascular endothelial growth factor
• vitreous hemorrhage

Financial & competing interests disclosure

Q Nguyen serves on the scientific advisory boards for Genentech, Inc. and Regeneron, Inc. D Do serves on the scientific advisory boards for Genentech, Inc. and Regeneron, 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.

Key issues

• Diabetic retinopathy (DR) is the leading cause of vision loss in working-age adults, comprising a major challenge to the public health and economy.

• DR presents in two main subtypes: non-proliferative and proliferative diabetic retinopathy. If left untreated, DR will eventually progress leading to serious blinding consequences including diabetic macular edema (DME), which is the most frequent cause of vision loss in DR patients, retinal ischemia and neovascularization, vitreous hemorrhage and ultimately traction retinal detachment and irreversible vision loss.

• Hyperglycemia-induced microvascular damage and the resultant retinal ischemia lead to up-regulation of the vascular endothelial growth factor, a key mediator in the pathogenesis of DR and DME and a major target for current therapies.

• Ranibizumab, a humanized monoclonal antibody fragment, is an US FDA-approved therapy that acts through neutralizing vascular endothelial growth factor. It is widely used for the treatment of DME with established efficacy and favorable safety profile.

• Ranibizumab has been thoroughly evaluated in many multicenter randomized clinical trials and demonstrated rapid and sustained gain in visual acuity and reduction in excess macular thickness in diabetic patients.

• In addition to visual acuity gain and resolution of DME, clinical studies also showed that treatment with ranibizumab improved the severity of DR, halted progression to proliferative diabetic retinopathy and expedited resolution of vitreous hemorrhage, allowing better visualization of the fundus and proper application of laser photocoagulation. The FDA has approved ranibizumab for the treatment of DR in patients with DME.

• Ranibizumab monotherapy is more effective than laser monotherapy, whereas, combination of laser and ranibizumab seems to be equally effective (and dose not bring significant advantages) as ranibizumab monotherapy in the treatment of DME.

• As shown in the protocol T of the DRCR.net study, there are no significant differences in safety or efficacy among ranibizumab, aflibercept and bevacizumab for patients with DME who present with a visual acuity of 20/40 or better. However, in the same study, improvement in visual acuity was shown to be greatest with aflibercept for patients who present with a visual acuity of 20/50 or worse, whereas the visual acuity gain reportedly is similar with either ranibizumab or bevacizumab in this patient population.

• The significant burden placed on patients, physicians and the health care system from frequent dosing, multiple visits and the potential of injection-related complications urge the need to look for alternative targets in the pathogenic pathway of DR and develop new therapeutic approaches.