The role of aflibercept in the management of diabetic macular edema

Chang, Andrew A; Hong, Thomas; Ewe, Shaun Y P; Bahrami, Bobak; Broadhead, Geoffrey K

doi:10.2147/DDDT.S62778

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The role of aflibercept in the management of diabetic macular edema

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Author(s): Andrew A Chang ¹ ^, ² ^, ³ , Thomas Hong ¹ ^, ² , Shaun Y Ewe ¹ ^, ² , Bobak Bahrami ¹ ^, ² , Geoffrey K Broadhead ¹ ^, ² ^, ³

Publication date (Electronic): 06 August 2015

Journal: Drug Design, Development and Therapy

Publisher: Dove Medical Press

Keywords: diabetic macular edema, aflibercept

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Abstract

Diabetic macular edema (DME) represents one of the leading causes of visual impairment in working-age adults. Although there are several proven treatments available for this condition, pharmacotherapy through the use of intravitreal antivascular endothelial growth factor agents has revolutionized the management of DME over the past decade with superior outcomes compared to laser therapy. This review summarizes the pathophysiology and available treatment options for the management of DME, with an emphasis on the efficacy and safety profile of a single particular intravitreal antivascular endothelial growth factor agent, aflibercept.

Most cited references 57

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Randomized trial evaluating ranibizumab plus prompt or deferred laser or triamcinolone plus prompt laser for diabetic macular edema.

Michael Elman, Lloyd Paul Aiello, Roy Beck … (2010)

Evaluate intravitreal 0.5 mg ranibizumab or 4 mg triamcinolone combined with focal/grid laser compared with focal/grid laser alone for treatment of diabetic macular edema (DME). Multicenter, randomized clinical trial. A total of 854 study eyes of 691 participants with visual acuity (approximate Snellen equivalent) of 20/32 to 20/320 and DME involving the fovea. Eyes were randomized to sham injection + prompt laser (n=293), 0.5 mg ranibizumab + prompt laser (n=187), 0.5 mg ranibizumab + deferred (> or =24 weeks) laser (n=188), or 4 mg triamcinolone + prompt laser (n=186). Retreatment followed an algorithm facilitated by a web-based, real-time data-entry system. Best-corrected visual acuity and safety at 1 year. The 1-year mean change (+/-standard deviation) in the visual acuity letter score from baseline was significantly greater in the ranibizumab + prompt laser group (+9+/-11, P<0.001) and ranibizumab + deferred laser group (+9+/-12, P<0.001) but not in the triamcinolone + prompt laser group (+4+/-13, P=0.31) compared with the sham + prompt laser group (+3+/-13). Reduction in mean central subfield thickness in the triamcinolone + prompt laser group was similar to both ranibizumab groups and greater than in the sham + prompt laser group. In the subset of pseudophakic eyes at baseline (n=273), visual acuity improvement in the triamcinolone + prompt laser group appeared comparable to that in the ranibizumab groups. No systemic events attributable to study treatment were apparent. Three eyes (0.8%) had injection-related endophthalmitis in the ranibizumab groups, whereas elevated intraocular pressure and cataract surgery were more frequent in the triamcinolone + prompt laser group. Two-year visual acuity outcomes were similar to 1-year outcomes. Intravitreal ranibizumab with prompt or deferred laser is more effective through at least 1 year compared with prompt laser alone for the treatment of DME involving the central macula. Ranibizumab as applied in this study, although uncommonly associated with endophthalmitis, should be considered for patients with DME and characteristics similar to those in this clinical trial. In pseudophakic eyes, intravitreal triamcinolone + prompt laser seems more effective than laser alone but frequently increases the risk of intraocular pressure elevation. Copyright 2010 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

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Photocoagulation for diabetic macular edema. Early Treatment Diabetic Retinopathy Study report number 1. Early Treatment Diabetic Retinopathy Study research group.

(1985)

Data from the Early Treatment Diabetic Retinopathy Study (ETDRS) show that focal photocoagulation of "clinically significant" diabetic macular edema substantially reduces the risk of visual loss. Focal treatment also increases the chance of visual improvement, decreases the frequency of persistent macular edema, and causes only minor visual field losses. In this randomized clinical trial, which was supported by the National Eye Institute, 754 eyes that had macular edema and mild to moderate diabetic retinopathy were randomly assigned to focal argon laser photocoagulation, while 1,490 such eyes were randomly assigned to deferral of photocoagulation. The beneficial effects of treatment demonstrated in this trial suggest that all eyes with clinically significant diabetic macular edema should be considered for focal photocoagulation. Clinically significant macular edema is defined as retinal thickening that involves or threatens the center of the macula (even if visual acuity is not yet reduced) and is assessed by stereo contact lens biomicroscopy or stereo photography. Follow-up of all ETDRS patients continues without other modifications in the study protocol.

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Role of the Flt-1 receptor tyrosine kinase in regulating the assembly of vascular endothelium.

G H Fong, J Rossant, M Gertsenstein … (1995)

The vascular endothelial growth factor (VEGF) and its high-affinity binding receptors, the tyrosine kinases Flt-1 and Flk-1, are thought to be important for the development of embryonic vasculature. Here we report that Flt-1 is essential for the organization of embryonic vasculature, but is not essential for endothelial cell differentiation. Mouse embryos homozygous for a targeted mutation in the flt-1 locus, flt-1lcz, formed endothelial cells in both embryonic and extra-embryonic regions, but assembled these cells into abnormal vascular channels and died in utero at mid-somite stages. At earlier stages, the blood islands of flt-1lcz homozygotes were abnormal, with angioblasts in the interior as well as on the periphery. We suggest that the Flt-1 signalling pathway may regulate normal endothelial cell-cell or cell-matrix interactions during vascular development.

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Author and article information

Journal

Journal ID (nlm-ta): Drug Des Devel Ther

Journal ID (iso-abbrev): Drug Des Devel Ther

Journal ID (publisher-id): Drug Design, Development and Therapy

Title: Drug Design, Development and Therapy

Publisher: Dove Medical Press

ISSN (Electronic): 1177-8881

Publication date Collection: 2015

Publication date (Electronic): 06 August 2015

Volume: 9

Pages: 4389-4396

Affiliations

[1 ]Sydney Institute of Vision Science, University of Sydney, Sydney, NSW, Australia

[2 ]Sydney Retina Clinic and Day Surgery, University of Sydney, Sydney, NSW, Australia

[3 ]Save Sight Institute, University of Sydney, Sydney, NSW, Australia

Author notes

Correspondence: Andrew Chang, Sydney Retina Clinic and Day Surgery, Level 13, Park House, 187 Macquarie Street, Sydney, NSW 2000, Australia, Tel +61 2 9221 3755, Fax +61 2 9221 1637, Email achang@ 123456sydneyretina.com.au

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Publisher ID: dddt-9-4389

DOI: 10.2147/DDDT.S62778

PMC ID: 4532215

SO-VID: 3c238b83-23a8-45f0-bded-6e70065ec1e4

License:

The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

Drug Design, Development and Therapy (submit here)

The role of aflibercept in the management of diabetic macular edema

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Abstract

Most cited references 57

Randomized trial evaluating ranibizumab plus prompt or deferred laser or triamcinolone plus prompt laser for diabetic macular edema.

Photocoagulation for diabetic macular edema. Early Treatment Diabetic Retinopathy Study report number 1. Early Treatment Diabetic Retinopathy Study research group.

Role of the Flt-1 receptor tyrosine kinase in regulating the assembly of vascular endothelium.

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