A Review of Anti-VEGF Agents for Proliferative Diabetic Retinopathy

P Osaadon; XJ Fagan; T Lifshitz; J Levy


Eye. 2014;28(5):510-520. 

In This Article

Abstract and Introduction


Previous research has implicated vascular endothelial growth factor (VEGF) in the pathogenesis of diabetic retinopathy (DR). Although many studies reviewed the use of anti-VEGF for diabetic macular oedema, little has been written about the use of anti-VEGF for proliferative diabetic retinopathy (PDR). This study is a review of relevant publications dealing with the use of anti-VEGF for the treatment of PDR. The articles were identified through systematic searches of PUBMED and the Cochrane Central Register of Controlled Trials. At the end of each section, we summarized the level of evidence of the scientific literature. Off-label use of anti-VEGF agents was found to be beneficial in PDR, especially in cases with neovascular glaucoma, persistent vitreous haemorrhage, and before vitrectomy. The disadvantages of the use of anti-VEGF are its short-effect duration, causing tractional retinal detachment in cases with pre-existing pre-retinal fibrosis and endophthalmitis in rare cases. There is no conclusive evidence from large randomized trials regarding the efficacy of anti-VEGF treatment in PDR. However, numerous case series, sound biochemical mechanism of action, and increasing experience with using anti-VEGF drugs can be used to support the ongoing use of this treatment modality in selected patients.


Proliferative diabetic retinopathy (PDR) is a major cause of blindness. Approximately, 1.5% of adults with diabetes have PDR.[1] The Diabetic Retinopathy Study showed that about half of all eyes with PDR that are left untreated will have severe vision loss (ie, visual acuity of <20/800 for at least 4 months).[2]

PDR is characterized by retinal neovascularization, serum leakage, haemorrhage, and fibrovascular proliferation in the vitreous retinal interface, which further results in vitreous haemorrhage and traction retinal detachment.[3]

The pro-angiogenic cytokine vascular endothelial growth factor (VEGF) is considered the primary factor involved in neovascularization in PDR.[4] In the base of PDR pathophysiology stands angiogenesis.[5] A key player in this process is VEGF.[6,7] Increased levels of VEGF have been reported in the vitreous humour and in fibrovascular tissues from eyes with PDR.[8–13] VEGF activates two tyrosine kinase receptors, VEGFR-1 and VEGFR-2. These receptors regulate physiological and pathological angiogenesis. VEGFR-2 is expressed mostly on vascular endothelial cells.[14] Activation of VEGFR-2 stimulates endothelial cell proliferation, migration, and survival, as well as angiogenesis and microvascular permeability as in PDR.[14]

Until recent years, panretinal photocoagulation (PRP) was the first and only choice for treating PDR. For PDR with high-risk characteristics, the Diabetic Retinopathy Study (DRS) showed a >50% decrease in the rate of severe vision loss when PRP was executed.[15] When new vessels respond to PRP by regressing within the first 3 months after treatment, the visual outcome tends to be excellent.[16] Although proven beneficial, PRP had its own complications, such as pain during treatment, loss of peripheral vision, nyctalopia, uveal effusions, worsening of macular oedema, vitreous haemorrhage and difficulty in treating eyes with vitreous haemorrhage, and advanced cataract.[16–19] These complications brought the need for new modalities in treating PDR, such as anti-VEGF. This review will summarize the literature on anti-VEGF in treating PDR.