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Diabetic Macular Oedema
An Overview of Intravitreal Aflibercept in Diabetic Macular Oedema
Jean-François Korobelnik 1–3 and Sebastian Wolf 4
1. Professor, Université de Bordeaux, Bordeaux, France; 2. INSERM (Institut National de la Santé et de la Recherche Médicale), ISPED (Institut de Santé
Publique d’Épidémiologie et de Développement), Centre INSERM U897-Epidemiologie-Biostatistique, Bordeaux, France; 3. Centre Hospitalier Universitaire
(CHU) de Bordeaux, Service d’Ophtalmologie, Bordeaux, France; 4. Director and Chief Physician, Department of Ophthalmology, Inselspital, University Hospital and
University Bern, Bern, Switzerland
Abstract Diabetic macular oedema (DMO) is responsible for much of the vision loss associated with diabetic retinopathy, which is the leading
cause of blindness in working-age adults. Approximately 21 million people worldwide have DMO. The standard of care for DMO has
been laser photocoagulation: this option has only a limited ability to reverse vision loss and is associated with a risk of scarring
and complications. Corticosteroids have also been used in DMO treatment, but are associated with side effects such as elevated
intraocular pressure and cataract. Knowledge of the role of vascular endothelial growth factor (VEGF) in the pathogenesis of DMO
has led to the widespread use of anti-VEGF agents. Intravitreal bevacizumab, which is not approved for any retinal disorders, is used
off-label for the treatment of DMO. Intravitreal ranibizumab (IVT-AFL) (once monthly) and intravitreal aflibercept (once every 2 months
after a loading dose) have been approved for the treatment of DMO. This review summarises the clinical evidence supporting the
role of IVT-AFL in the treatment of DMO. Analysis of efficacy and safety data suggests that aflibercept could be used as a first-line
treatment in DMO.
Keywords Diabetic macular oedema (DMO), diabetic retinopathy, intravitreal aflibercept, placental growth factor (PlGF) inhibitor, vascular endothelial
growth factor (VEGF) inhibitor
Disclosure: Jean-François Korobelnik is a consultant for Alcon, Alimera, Allergan, Bayer, Horus, Novartis, Roche, Thea and Zeiss. Sebastian Wolf is a consultant and/or
advisory board member for Alcon, Allergan, Bayer HealthCare, Heidelberg Engineering, Novartis, Roche and Zeiss.
Open Access: This article is published under the Creative Commons Attribution Noncommercial License, which permits any non-commercial use, distribution, adaptation
and reproduction provided the original author(s) and source are given appropriate credit.
Received: 26 March 2015 Accepted: 11 May 2015 Citation: European Ophthalmic Review, 2015;9(1):37–41
Correspondence: Jean-François Korobelnik, Service d’Ophtalmologie Hôpital Pellegrin, CHU de Bordeaux, Place Amélie Raba Léon, 33000 Bordeaux, France.
Support: Editorial support was provided by Michelle Olsher of PAREXEL, which was funded by Bayer Pharma AG. No publication fees were associated with the publication
of this article.
Diabetic macular oedema (DMO) is responsible for much of the vision
loss associated with diabetic retinopathy, the leading cause of blindness
in working-age adults. 1–3 DMO is characterised by thickening of the
central retina due to leakage of fluid from blood vessels, and can occur
at any stage of retinopathy. 4 Recent estimates suggest that around 21
million people worldwide have DMO. 5
Evaluation of DMO should be based on both functional (visual acuity)
and anatomical criteria. Optical coherence tomography (OCT) is
used to assess retinal morphology and thickness of the macula, and
additional methods for anatomical assessment include biomicroscopy,
fundus photography and fluorescein angiography. 6,7 Although focal
laser photocoagulation has been the standard of care for DMO, it
can only slow progression and its ability to reverse vision loss is
low; 8,9 in addition, it has been associated with a risk of scarring and
other thermal complications. 10,11 The corticosteroids (dexamethasone,
triamcinolone acetonide and fluocinolone acetonide) have also been
used for treatment of persistent or refractory DMO and provide
improvements in retinal thickness and visual acuity. However, steroid-
related side effects, such as elevated intraocular pressure and cataract,
must be considered. 12,13
Tou ch MEd ica l MEdia
Awareness of the role that vascular endothelial growth factor (VEGF)
plays in the pathogenesis of retinal diseases, including DMO, 14–16 has
led to the development and widespread use of VEGF inhibitors in this
area. Intravitreal ranibizumab (IVR) has been approved for the treatment
of DMO with once-monthly dosing, whereas intravitreal aflibercept
(IVT-AFL) has been approved with dose administration once every
2 months after a loading dose. IVT-AFL has recently been approved in
the EU and the US for the treatment of patients with visual impairment
due to DMO. 17,18 Further regulatory submissions for IVT-AFL in DMO have
been made in Japan, Asia-Pacific and Latin America. In addition to IVR
and IVT-AFL, intravitreal bevacizumab (IVB), which is not approved for
any retinal disorders, is often used off-label for the treatment of DMO.
This review summarises the evidence supporting the role of IVT-AFL in
the treatment of DMO.
How Does Intravitreal Aflibercept Work?
Aflibercept is composed of extracellular domains from human VEGF
receptors 1 and 2 fused to the Fc portion of human immunoglobulin-G1. 19
By contrast, bevacizumab is a recombinant, humanised monoclonal
antibody that binds all isoforms of VEGF-A, and ranibizumab is a
humanised anti-VEGF antibody fragment comprising the antigen-