The Value of Anti-VEGF Therapy vs PRP for Proliferative Diabetic Retinopathy

William C. Ou; Charles C. Wykoff, MD, PhD


September 06, 2018

In This Article

Diabetic retinopathy (DR) is a leading cause of vision loss and blindness among the adult population.[1] Clinical manifestations of DR include microaneurysms, exudates, intraretinal hemorrhages, and diabetic macular edema (DME), the latter of which is a major cause of visual impairment and blindness.

As the underlying retinal ischemia progresses in DR, eyes can develop proliferative diabetic retinopathy (PDR), which affects approximately 7% of people with diabetes.[2] PDR is characterized by abnormal blood vessel growth potentially associated with a fibrotic component. This aberrant neovascular tissue can lead to vitreous hemorrhage and retinal detachment if not adequately treated.

Studies That Led the Way

The Diabetic Retinopathy Study and the Early Treatment Diabetic Retinopathy Study, conducted in the 1970s to 1980s, demonstrated that panretinal photocoagulation (PRP) significantly reduces the risk for severe vision loss in eyes with PDR.[3,4] The mechanisms driving the efficacy of PRP are believed to involve improved oxygenation of the inner retina and decreased production of vascular endothelial growth factor-A (VEGF) and other cytokines that drive proliferative changes.[5] Because VEGF plays a key role in the pathogenesis of PDR, it naturally follows that intravitreal VEGF antagonists could be of therapeutic benefit in PDR.

The Diabetic Retinopathy Clinical Research Network ( Protocol S trial, conducted from 2012 to 2015, was the first major head-to-head clinical trial comparing anti-VEGF treatment with PRP in this disease population.[6] Protocol S randomized 394 eyes to either PRP at baseline or ranibizumab (3-5 monthly injections followed by retreatment as needed based on progression or regression of neovascularization). Eyes in either cohort with DME could receive ranibizumab injections or macular photocoagulation as needed.

Outcomes at 2 years demonstrated that ranibizumab treatment was noninferior to PRP, with visual acuity gains of +2.8 and +0.2 letters in the ranibizumab and PRP groups, respectively. Additionally, eyes in the PRP group experienced greater peripheral visual field losses, an increased incidence of DME development, and an increased frequency of vitrectomy compared with the ranibizumab group.[6]

It could be reasonably concluded from this and other trials[7,8] that anti-VEGF therapy is a viable, or perhaps even superior, alternative to PRP for the management of PDR. However, data comparing long-term outcomes between these two treatment modalities was lacking. Such comparative data is critical to this discussion, given potential differences in treatment durability and burden, cost, and safety. Fortunately, recently published 5-year outcomes data for Protocol S may begin to provide answers on this front.[9]


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