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Diabetic Macular Oedema


Evidence for Anti-vascular Endothelial Growth Factor Treatment of Diabetic Macular Oedema


Francesco Bandello,1 Maurizio Battaglia Parodi,1


Umberto De Benedetto,1 Maria Lucia Cascavilla1


Karl Anders Knutsson,1 and Pierluigi Iacono2


1. Department of Ophthalmology, Vita-Salute University, San Raffaele Scientific Institute, Milan; 2. GB Bietti Ophthalmology Foundation, Rome


Abstract


Diabetic macular oedema (DME) represents the most common cause of vision loss in patients affected by diabetes mellitus. Diabetic retinopathy has a significant impact on public health and the quality of life of many patients and thus requires serious consideration. The first line of treatment remains the management of systemic risk factors but this is often insufficient in controlling DME and currently, laser retinal photocoagulation is considered the standard of care. However, laser treatment reduces the risk of moderate visual loss by approximately 50% without guaranteeing remarkable effects on visual improvement. For these reasons, new approaches in the treatment of DME have been considered, in particular the employment of anti-vascular endothelial growth factor (VEGF) drugs. VEGF is a pluripotent growth factor that functions as a vasopermeability factor and an endothelial cell mitogen and thereby represents an appealing candidate as a therapeutic target for the treatment of DME. The goal of this article is to present the evidence behind the use of anti-VEGF drugs in the treatment of DME.


Keywords


Diabetic macular oedema, anti-vascular endothelial growth factor, ranibizumab, bevacizumab, pegaptanib, anti-vascular endothelial growth factor Trap-Eye, bevasiranib, rapamycin


Disclosure: Francesco Bandello is a consultant for Novartis, Allergan, Pfizer, Alcon, Bayer and Thea. The remaining authors have no conflicts of interest to declare. Received: 1 August 2011 Accepted: 13 September 2011 Citation: European Endocrinology, 2012;8(1):36–41 Correspondence: Francesco Bandello, Department of Ophthalmology, Vita-Salute University, San Raffaele Scientific Institute, Via Olgettina 60, 20132 Milan, Italy. E: bandello.francesco@hsr.it


Today, diabetic retinopathy is the leading cause of acquired blindness among young adults throughout developed countries.2


Population-based epidemiological studies have estimated


that, after 20 years, diabetic retinopathy can be identified at least to a certain extent and that, after 30 years, proliferative diabetic retinopathy is present in 70 % of patients with diabetes mellitus type 1.3


The World


Health Organization (WHO) estimates that about 171 million people are affected by diabetes with a likely doubling of the prevalence within 20 years.4


Diabetic macular oedema (DME) is the major cause of visual acuity (VA) impairment secondary to diabetic retinopathy.


DME is generally defined as retinal thickening or presence of hard exudates within one disk diameter from the centre of the macula.5 During past years, many therapeutic strategies have been proposed for the treatment of DME including focal/grid laser photocoagulation, ocular steroids, intravitreal anti-vascular endothelial growth factor (VEGF) drugs and vitreo-retinal surgery. VEGF is a pluripotent growth factor that acts as an endothelial cell-specific mitogen and vasopermeability factor, playing a critical role in promoting angiogenesis and vascular leakage.6–10


In diabetic retinopathy, the


alteration of the blood–retinal barrier and increased permeability are responsible for the development of DME. VEGF increases the extracellular accumulation of fluid from the intravascular compartment by disrupting the intercellular tight junctions between retinal


36


Diabetic retinopathy is considered the most frequent retinal vascular disorder and is detectable in about 40 % of diabetic patients 40 years of age and older.1


endothelial cells.8–11


The pathway between VEGF gene transcription and the activation of the VEGF receptor is the object of the new therapeutic approaches based on the use of VEGF antagonists. Pegaptanib, ranibizumab, bevacizumab and VEGF Trap are molecules able to directly bind the VEGF protein. A new and interesting therapeutic approach is the employment of bevasiranib. This molecule, interfering with messenger RNA (mRNA), interrupts the synthesis of the VEGF protein. Lastly, rapamycin, commonly employed as an immunosuppressive, anti-inflammatory, or antimycotic drug, reduces the activity of the VEGF molecule, interfering with the promoting signal and the active synthesis of VEGF and reducing the response of endothelial cells to VEGF. The aim of this article is to review the role of anti-VEGF drugs in the treatment of DME.


Ranibizumab


Ranibizumab is an antigen-binding fragment (Fab) derived from a humanised anti-VEGF antibody that inhibits all biologically active isoforms and active proteolytic fragments of VEGF-A. Many clinical investigations have shown its efficacy in the treatment of DME.


In the first pilot study, two dosing regimens of ranibizumab (0.3 and 0.5 mg) were used in 10 patients affected by clinically significant DME.12 At month three, 40 % of patients gained more than 15 letters, 50 % gained more than 10 letters, and 80 % obtained an improvement of at least one letter in best corrected visual acuity (BCVA) and a decrease in central retinal thickness (CRT) was detected in both groups.


© TOUCH BRIEFINGS 2012


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