Corticosteroid intravitreal implants.Diabetic macular edema Intravitreal implant corticosteroids remains an important worldwide cause of visual anavar weight loss stories. Corticosteroids have a role in the treatment of some patients with advanced or recurrent DME. The best studied steroids for this indication are triamcinolone acetonide, dexamethasone, and fluocinolone acetonide. All steroids are associated with risks of cataract and intraocular pressure elevation. In addition, intravitreal implant corticosteroids injection of any medication is associated with risks of infectious endophthalmitis, which has led to the investigation of various extended-release steroid implants.
Intravitreal Corticosteroids in the Management of Diabetic Macular Edema
Diabetic macular edema DME remains an important worldwide cause of visual loss. Corticosteroids have a role in the treatment of some patients with advanced or recurrent DME. The best studied steroids for this indication are triamcinolone acetonide, dexamethasone, and fluocinolone acetonide.
All steroids are associated with risks of cataract and intraocular pressure elevation. In addition, intravitreal injection of any medication is associated with risks of infectious endophthalmitis, which has led to the investigation of various extended-release steroid implants.
Diabetic retinopathy is thought to occur through a number of metabolic pathways, including the formation of reactive oxygen species, the formation of advanced glycation endproducts, the accumulation of polyol through the action of the enzyme aldose reductase, and activation of protein kinase C via expression of vascular endothelial growth factor VEGF. Tighter control of systemic factors, such as hypertension, hyperglycemia, and hyperlipidemia, is generally beneficial in reducing retinopathy in patients with both type 1 2 and type 2 3 diabetes mellitus.
The two most commonly used anti-VEGF agents are bevacizumab and ranibizumab. The mechanism of action of corticosteroids in the treatment of DME is thought to be multifactorial.
Three potent synthetic corticosteroids with similar chemical structures have been investigated as intravitreal treatments for DME: Intravitreal triamcinolone acetonide, a suspension, is typically effective for about 3 months in a non-vitrectomized eye, 22 so repeated injections may be necessary to maintain the treatment effect.
Intravitreal injections are associated with approximately a 0. In order to mitigate the cumulative risks associated with repeated intravitreal injections, extended-release steroid implants have been investigated for the treatment of DME. In addition, it has been suggested that extended delivery of lower doses of steroids may be more effective than intermittent bolus delivery of high doses.
At least four different preparations of triamcinolone acetonide have been used in various clinical trials: The DRCR reported that photocoagulation was associated with generally more favorable anatomic and visual outcomes at 2 years 32 and 3 years 33 follow-up. Nevertheless, triamcinolone remains effective for selected patients, especially those with poor presenting visual acuity and those with persistent or recurrent DME Figure 1. A year-old female with type 2 diabetes mellitus presented with bilateral recurrent diabetic macular edema DME following photocoagulation.
The patient was treated with intravitreal triamcinolone acetonide, 4 mg in 0. The DRCR reported that, compared with photocoagulation, ranibizumab plus photocoagulation prompt or deferred was associated with significantly improved visual outcomes at one year. Triamcinolone acetonide plus photocoagulation was associated with generally more favorable outcomes than was photocoagulation in pseudophakic eyes only.
In a pilot study of 12 patients followed for 3 months, a single injection of intravitreal dexamethasone 0. A bioerodable, extended-release dexamethasone implant Ozurdex, Allergan, Irvine, CA , which is injected in the clinic, has received US FDA approval for the treatment of macular edema associated with retinal vein occlusion 42 and noninfectious posterior segment uveitis.
In a monkey model, peak concentrations of dexamethasone were detected in the vitreous and retina for the first two months, followed by a gradual decrease to below the limits of quantitation by six months. A much smaller, non-bioerodable, extended-release fluocinolone acetonide injectable device Iluvien, Alimera, Alpharetta, GA , which is injected in a clinic setting, has been investigated for the treatment of DME.
The group reported sustained intraocular release of medication in both groups at one year. The primary end point was improvement in best-corrected visual acuity of at least 15 letters at 24 months. Increased IOP requiring incisional glaucoma surgery was reported in 3. Subsequently, the device has achieved approval in several European nations and the pharmaceutical company has reapplied for US FDA approval.
Nevertheless, steroids do have a role in the treatment of certain patients with persistent or recurrent disease, especially pseudophakes. The other extended-release devices Ozurdex and Retisert are FDA-approved for diagnoses other than DME, and are not frequently used in an off-label capacity because of their high costs.
Therefore, in the US, the various preparations of triamcinolone acetonide are used most frequently as off-label treatments for DME.
As data from RCTs continue to accumulate, a better understanding of the role of pharmacologic therapy for DME will be reached. Flynn, MD has performed consulting activities for Santen and has received lecture fees from Vindico.
Flynn, and Ingrid U. Scott declare that they have no conflict of interest. Human and Animal Rights and Informed Consent. This article does not contain any studies with human or animal subjects performed by any of the authors. National Center for Biotechnology Information , U. Author manuscript; available in PMC Sep 1. See other articles in PMC that cite the published article.
Abstract Diabetic macular edema DME remains an important worldwide cause of visual loss. Diabetic macular edema, triamcinolone acetonide, fluocinolone acetonide, dexamethasone, randomized clinical trial. Open in a separate window. Conflict of Interest Stephen G.
Human and Animal Rights and Informed Consent This article does not contain any studies with human or animal subjects performed by any of the authors. Contributor Information Stephen G. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus.
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