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Simunovic, Matthew P. MBBChir, PhD, FRANZCO*,†,‡; Maberley, David A. L. MSc, MD, FRCSC§

doi: 10.1097/IAE.0000000000000723

Purpose: To systematically review and perform meta-analysis on the available randomized controlled trial data for anti-vascular endothelial growth factor (anti-VEGF) agents in the management of proliferative diabetic retinopathy and its complications.

Methods: The authors identified randomized controlled trials using anti-VEGF agents, either as stand-alone therapy or combined with other interventions, in the management of proliferative diabetic retinopathy. The primary outcome measures were change in best-corrected visual acuity and (in the context of vitrectomy) duration of surgery and postoperative vitreous hemorrhage. Secondary outcomes were change in central retinal thickness and (in the context of vitrectomy) intraoperative variables suggestive of complex surgery (retinal breaks, intraoperative bleeding, and endodiathermy applications). The quality of evidence for all outcomes was appraised using the GRADE criteria.

Results: Twenty-two studies involving 1,397 subjects met the criteria for inclusion in this study. One study compared intravitreal ranibizumab with saline, one compared intravitreal pegaptanib to pan-retinal photocoagulation (PRP), one compared intravitreal bevacizumab to PRP, 3 compared combined intravitreal ranibizumab/PRP to PRP, 5 compared combined intravitreal bevacizumab/PRP to PRP alone, and 11 compared combined intravitreal bevacizumab/PPV to PPV alone. When used in conjunction with PRP, there is a high-quality evidence to suggest that intravitreal ranibizumab is associated with superior visual acuity and central retinal thickness outcomes at 3 months to 4 months. In the context of PPV, there is moderate quality evidence to suggest that preoperative intravitreal bevacizumab results in a significant reduction in the duration of surgery, fewer retinal breaks, less intraoperative bleeding, and fewer endodiathermy applications. Although there is evidence to suggest occurrence of early postoperative vitreous hemorrhage is reduced, the quality of evidence in support of this finding is low.

Conclusion: The use of anti-VEGF agents before PRP results in superior functional and structural outcomes at 3 months to 4 months. The use of anti-VEGF agents before PPV results in decreased duration of surgery, fewer breaks, and less intra-operative bleeding. Although there is evidence for a decreased incidence of early postoperative vitreous hemorrhage, the quality of evidence is low. The available data therefore support the use of anti-VEGF agents as adjuncts to PRP and PPV in patients with complicated proliferative diabetic retinopathy primarily as a means of facilitating, and potentially minimizing the iatrogenic damage resulting from, these procedures.

This systematic review and meta-analysis summarizes and critically appraises the key points from a total of 22 randomized control trials (involving 1,397 subjects) investigating anti-vascular endothelial growth factor therapy in the management of proliferative diabetic retinopathy.

*Nuffield Laboratory of Ophthalmology, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom;

Oxford Eye Hospital, Oxford University Hospitals NHS Trust, Oxford, United Kingdom;

Moorfields Eye Hospital, London, United Kingdom; and

§Department of Ophthalmology and Visual Science, University of British Columbia, Eye Care Centre, Vancouver General Hospital, Vancouver, BC, Canada.

Reprint requests: Matthew P. Simunovic, MBBChir, PhD, FRANZCO, Nuffield Laboratory of Ophthalmology, Level 6, John Radcliffe Hospital, Oxford OX3 9DU, United Kingdom; e-mail:

None of the authors have any financial/conflicting interests to disclose.

© 2015 by Ophthalmic Communications Society, Inc.