Diabetic retinopathy is one of the major complications of diabetes mellitus and a leading cause of visual loss. Diabetic macular edema (DME) is an ocular manifestation of the disease causing visual deterioration. The prevalence of visual impairment due to DME is estimated to be 5.4% in Europe. Vascular endothelial growth factor (VEGF) is overexpressed in diabetic eyes and plays a key role in the development of DME. VEGF levels were proven to be elevated in the vitreous and retina in patients with diabetic retinopathy. VEGF causes a breakdown of the blood-retinal barrier by influencing the tight junctions of retinal endothelial cells and leading to accumulation of fluid in the macula. Therefore, intravitreal VEGF inhibitors are ideal candidates to treat DME by counteracting VEGF overexpression. This review summarizes the results of the most recent prospective, controlled studies on DME with promising novel VEGF inhibitors. It focuses on the efficacy and safety aspects of anti-VEGF treatment of DME.

Keywords:
Bevacizumab, Diabetic macular edema, Pegaptanib, Ranibizumab, Aflibercept, Anti-VEGF
1.
Lang GE, Lang SJ: Clinical treatment of diabetic macular edema. Klin Monatsbl Augenheilkd 2011;228:R1–R11.
2.
Lang GE: Pharmacological treatment of diabetic retinopathy. Ophthalmologica 2007;221:112–117.
3.
Caldwell RB, Bartoli M, Behzadian MA, El-Remessy AEB, Al-Shabrawey M, Platt DH, Caldwell RW: Vascular endothelial growth factor and diabetic retinopathy: pathophysiological mechanisms and treatment perspectives. Diabetes Metab Res Rev 2003;19:442–445.
4.
Deissler HL, Lang GE: In vitro studies on the mechanism of action of VEGF and its inhibitors. Klin Monatsbl Augenheilkd 2008;225:623–628.
5.
Deissler H, Deissler H, Lang S, Lang GE: VEGF-induced effects on proliferation, migration and tight junctions are restored by ranibizumab (Lucentis) in microvascular retinal endothelial cells. Br J Ophthalmol 2008;92:839–843.
6.
Massin P, Bandello F, Garweg JG, et al: Safety and efficacy of ranibzumab in diabetic macular edema (RESOLVE Study): a 12- month randomized, controlled, double-masked, multicenter phase II study. Diabetes Care 2010;33:2399–2405.
7.
Mitchell P, Bandello F, Schmidt-Erfurth U, Lang GE, Massin P, Schlingemann RO, Sutter F, Simader C, Burian G, Gerstner O, Weichselberger A, RESTORE study group: The RESTORE study: ranibizumab monotherapy or combined with laser versus laser monotherapy for diabetic macular edema. Ophthalmology 2011;118:615–625.
8.
Bandello F, Cunha-Vaz J, Chong NV, Lang GE, Massin P, Mitchell P, Porta M, Prünte C, Schlingemann R, Schmidt-Erfurth U: New approaches for the treatment of diabetic macular oedema: recommendations by an expert panel. Eye (Lond) 2012, DOI: 10.1038/eye.2011.337, E-pub ahead of print.
9.
Bandello F, De Benedetto U, Knutsson KA, Parodi MB, Cascavilla ML, Iacono P: Ranibizumab in the treatment of patients with visual impairment due to diabetic macular edema. Clin Ophthalmol 2011;5:1303–1308.
10.
Nguyen QD, Shah SM, Khwaja AA, er al: Two-year outcomes of the ranibizumab for edema of the macula in diabetes (READ-2) study. Ophthalmology 2010;117:2146–2151.
11.
Diabetic Retinopathy Clinical Research Network, Scott IU, Edwards AR, Beck RW, Bressler NM, Chan CK, Elman MJ, Friedman SM, Greven CM, Maturi RK, Pieramici DJ, Shami M, Singerman LJ, Stockdale CR: A phase 2 randomized clinical trial of intravitreal bevacizumab for diabetic macular edema. Ophthalmology 2007;114:1860–1867.
12.
Diabetic Retinopathy Clinical Research Network, Elman MJ, Aiello LP, Beck RW, Bressler NM, Bressler SB, Edwards AR, Ferris FL 3rd, Friedman SM, Glassman AR, Miller KM, Scott IU, Stockdale CR, Sun JK: Randomized trial evaluating ranibizumab plus prompt or deferred laser or triamcinolone plus prompt laser for diabetic macular edema. Ophthalmology 2010;117:1064–1077.
13.
Elman MJ, Bressler NM, Qin H, Beck RW, Ferris FL 3rd, Friedman SM, Glassman AR, Scott IU, Stockdale CR, Sun JK, Diabetic Retinopathy Clinical Research Network: Expanded 2-year follow-up of ranibizumab plus prompt or deferred laser or triamcinolone plus prompt laser for diabetic macular edema. Ophthalmology 2011;118:609–614.
14.
Michaelides M, Kaines A, Hamilton RD, et al: A prospective randomized trial of intravitreal bevacizumab or laser therapy in the management of diabetic macular edema (BOLT study) 12-month data: report 2. Ophthalmology 2010;117:1078–1086.
15.
Sultan MB, Zhou D, Loftus J, Dombi T, Ice KS, Macugen 1013 Study Group: A phase 2/3, multicenter, randomized, double-masked, 2-year trial of pegaptanib sodium for the treatment of diabetic macular edema. Ophthalmology 2011;118:1107–1118.
16.
Stewart MW: Aflibercept (VEGF-TRAP): the next anti-VEGF drug. Inflamm Allergy Drug Targets 2011;10:497–508.
17.
Do DV, Schmidt-Erfurth U, Gonzalez VH, Vitti R, Rückert R, Sandbrink R, Stein D, Yang K, Beckmann K, Heier: The DA VINCI Study: phase 2 primary results of VEGF Trap-Eye in patients with diabetic macular edema. Ophthalmology 2011;118:1819–1826.
18.
Kakkassery V, Winterhalter S, Joussen AM: Anti-VEGF inhibitors and their role in the treatment of diabetic macular oedema. Klin Monatsbl Augenheilkd 2010;227:701–711.
© 2012 S. Karger AG, Basel
2012
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.