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Diabetic Macular Oedema, Retina/Vitreous
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Long-term Therapies for Diabetic Macular Edema

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Published Online: Aug 5th 2012 European Ophthalmic Review, 2012;6(4):236-241 DOI: http://doi.org/10.17925/EOR.2012.06.04.236
Authors: Andrew J Lotery
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Abstract
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Article Information
Abstract:
Overview

Diabetic macular edema (DME) is one of the main causes of visual loss in diabetic patients. Although photocoagulation and intensive control of systemic metabolic factors have achieved improved outcomes, improvement is slow and some patients with DME continue to lose vision despite treatment. Pharmacological treatment options for DME include vascular endothelial growth factor (VEGF) antagonists such as ranibizumab, bevacizumab and pegaptanib and corticosteroids, whose multiple mechanisms of action include reduction of VEGF expression. Intravitreal delivery of these agents has shown efficacy in the treatment of DME but is associated with adverse effects including cataract progression and sustained rises in intraocular pressure. The physical characteristics and potent anti-inflammatory properties of fluocinolone acetonide (FAc) have led to its use in intravitreal implants. A number of intravitreal implants have been evaluated, of which the most effective at providing sustained drug release with an acceptable safety profile is the ILUVIEN® implant. This FAc intravitreal implant provides significant, long-lasting improvements in visual acuity for patients with chronic DME and has a manageable safety profile.

Keywords

Corticosteroids, diabetic macular edema, fluocinolone acetonide, ILUVIEN®, intravitreal implant

Article:

Diabetic retinopathy is the leading cause of blindness among patients 20 to 70 years old in developed countries. Diabetic macular edema (DME) can develop at any stage of diabetic retinopathy and is a major cause of preventable vision loss. It is also a public health concern, given the increasing prevalence of diabetes.1–3 A recent pooled individual participant meta-analysis estimated that there are 21 million people with DME worldwide with an overall prevalence of 6.81 % among individuals with diabetes.4 The prevalence is higher in those with type 1 than with type 2 diabetes.

The pathogenesis of DME involves overlapping and inter-related pathways initiated by hyperglycaemia. These are responsible not only for vascular events, but also in continued tissue insult that result in chronic DME. Angiogenesis, inflammation and oxidative stress lead to hyperpermeability, disruption of vascular endothelial cell junctions and leukostasis.5 Diabetes generally becomes more inflammatory ith duration, and there is growing evidence that the levels of inflammatory cytokines increases with duration of DME. Retinal hypoxia has been implicated in DME pathogenesis and stimulates vascular endothelial growth factor (VEGF) transcription.5–11 VEGF increases retinal vascular permeability, causes breakdown of the blood–retina barrier and results in retinal edema.12 It is up-regulated in diabetic retinopathy, making it an important therapeutic target in DME. However the products of other hypoxia-inducible genes, such as placental growth factor13 and hepatocyte growth factor,12–14 also induces the influx of leukocytes into the retina which can cause vascular leakage, hypoxia or ischaemia.

Laser photocoagulation, which is the current standard of care, results in slow improvement in a minority of patients. Furthermore, some patients suffer permanent visual loss even after intensive treatment.15,16 Visions worsen in approximately 20 % of laser-treated patients after two years,17 following ranibizumab combined with laser treatment, 30 % show a halving of their visual angle.18 The control of systemic metabolic factors can minimise visual loss. In patients unresponsive to standard laser techniques, pharmacological treatment may be beneficial in addition to improving control of blood pressure and blood sugar. The aim of this article is to review the current pharmacological treatment options for DME, particularly the use of intravitreal implants.

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Article Information:
Disclosure

The author was an investigator on the FAME study.

Correspondence

Andrew Lotery, University of Southampton, Southampton General Hospital, LD 70 MP 806, Tremona Road, Southampton, SO16 6YD. E: j.lotery@soton.ac.uk

Support

The publication of this article was funded by Alimera. The views and opinions expressed are those of the author and not necessarily those of Alimera.

Received

2012-07-25T00:00:00

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