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Diabetic Macular Oedema


Triamcinolone Acetonide for the Treatment of Diabetic Macular Oedema Valentina Sarao, Daniele Veritti and Paolo Lanzetta Department of Ophthalmology, University of Udine


Abstract


Diabetic macular oedema is a major cause of severe visual loss whose pathogenesis appears to be complex and multifactorial. For many years laser photocoagulation has been the standard of care for the treatment of this condition. Emerging pharmacologic approaches are being evaluated through randomised controlled trials. Triamcinolone acetonide has been proposed as a promising option, due to its well-known anti-inflammatory, anti-permeability and anti-angiogenic properties. Intravitreal delivery allows bypassing of the blood–retinal barrier to achieve a more concentrated dose of steroid in the vitreal cavity for a prolonged time. Intravitreal triamcinolone acetonide is effective in reducing central macular thickness and improving visual acuity, even if the duration of action is often provisional and requires repeated injections. Drug-related and injection-related side effects have been reported; the most common are induced cataract and increased intraocular pressure. To extend the duration of steroid effects and to minimise the risk of complications, alternative routes of administration and extend-release implants are being investigated.


Keywords Diabetic macula oedema, diabetic retinopathy, laser photocoagulation, intraocular pressure, triamcinolone acetonide


Disclosure: Valentina Sarao and Daniele Veritti have no conflicts of interest to declare. Paolo Lanzetta is consultant to Novartis Pharma AG, Allergan and Bayer AG. Received: 17 October 2011 Accepted: 18 November 2011 Citation: European Endocrinology, 2012;8(1):42–7 Correspondence: Paolo Lanzetta, Department of Ophthalmology, University of Udine, Piazzale S. Maria della Misericordia, 33100 Udine, Italy. E: paolo.lanzetta@uniud.it


Triamcinolone acetonide (TA) is a synthetic steroid of the glucocorticoid family with a fluorine in the ninth position.1


It is commercially available


as an ester and represents one of the most commonly used steroid agents for the treatment of several retinal conditions.2


TA has an anti-inflammatory potency five times higher than hydrocortisone with a 10th of the sodium-retaining potency. It appears as a white- to cream-colored crystalline powder and it is practically insoluble in water and very soluble in alcohol.3


and induces the expression of anti-inflammatory factors such as pigment epithelium-derived factor (PEDF).9–11


Some studies show that


TA, at therapeutic concentrations, significantly inhibits the expression of TNF-α, interleukin 1-beta (IL-1β), thromboxane B2 (TxB2) and leukotriene B4 (LTB4), in a dose-dependent manner.12 Additionally, TA seems to reduce the expression of matrix metalloproteinases (MMPs) and to downregulate intercellular adhesion molecule 1 (ICAM-1) on choroidal endothelial cells.13


The decreased water


solubility accounts for its prolonged duration of action. It has been observed that adequate concentrations of TA could provide therapeutic effects for approximately three months after 4 mg intravitreal TA injection.4 been suggested.5,6


A maximum effect duration of 140 days has Mechanism


TA has been shown to inhibit the inflammatory response, thereby reducing oedema formation, leukocyte migration, capillary dilatation and fibroblast proliferation. Steroids are thought to act by the induction of proteins called lipocortins, in particular phospholipase A2. These proteins reduce leukocyte chemotaxis, control biosynthesis and inhibit the release of arachidonic acid from the phospholipid membrane, which is one of the most important common precursors of potent inflammatory cell mediators such as prostaglandins and leukotrienes.8


The anti-inflammatory, angiostatic


and anti-permeability proprieties of corticosteroids seem also to be related to the regulation of gene expression components. This regulation influences the expression of vascular endothelial growth factor (VEGF), inhibits pro-inflammatory genes such as tumour necrosis factor-alpha (TNF-α) and other inflammatory chemokines,


42


Efficacy of Intravitreal Triamcinolone Acetonide Based on several studies, intravitreal administration of TA has provided promising results for the treatment of disorders associated with an abnormal endothelial cell proliferation and conditions complicated by intra-retinal and subretinal fluid accumulation. The anti-inflammatory, angiostatic and anti-permeability properties of TA have gained interest in chronic retinal diseases, such as diabetic macular oedema (DMO).14–18


DMO is the leading cause of vision loss in


the working-age population and it occurs as an increased accumulation of fluid within the intra-retinal layers of the macula as a result of retinal microvascular changes and disruption of the blood–retinal barrier. The rationale for using a steroidal drug for the treatment of oedematous and proliferative diseases is that abnormal proliferation of cells is often associated with and trigged by inflammation and intra-retinal accumulation of fluid is usually accompanied by a blood–retinal barrier dysfunction that can be restored with steroid therapy.19


Intravitreal TA has been widely studied


in many randomised clinical trials on DMO demonstrating significant improvements both in morphological and functional outcomes.20–23 Focal and grid laser photocoagulation has been considered the standard of care for the treatment of DMO for many years.24,25


© TOUCH BRIEFINGS 2012


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