Michael W Stewart, MD
Intravitreal corticosteroids have been used as off-label treatments for many retinal disorders, including diabetic macular edema (DME). DME develops because of excessive vascular permeability in the retina induced by diabetes, which causes loosening of the tight junctions within capillaries and increases vascular permeability because of elevated vascular endothelial growth factor (VEGF) levels. It is thought that corticosteroids increase tight-junction function and reduce VEGF levels. Following an intravitreal injection of corticosteroid for DME, visual acuity typically improves after 3 days, and anatomic improvement (eg, reduced macular thickness) is typically noted after 1 week. Although triamcinolone, one of the most popular off-label corticosteroids has an 18-day half-life in vitreous fluid, measurable traces of the drug may persist for 1.5 years. Nevertheless, the effects of triamcinolone intravitreal injections wear off over time, necessitating reinjection.
High rates of cataract development or progression and elevated intraocular pressure (IOP) are associated with repeated intravitreal injections of triamcinolone (Gillies MC, Sutter FK, Simpson JM, et al. Intravitreal triamcinolone for refractory diabetic macular edema: two-year results of a double-masked, placebo-controlled, randomized clinical trial. Ophthalmology. 2006;113:1533-1538.) Furthermore, poorer response to treatment may be noted with repeat injection (Chan CK, Mohamed S, Shanmugam MP, et al. Decreasing efficacy of repeated intravitreal triamcinolone injections in diabetic macular oedema. Br J Ophthalmol. 2006;90:1137-1141.). A number of refinements in triamcinolone administration technique have been proposed for the sake of maintaining durability of benefit while minimizing cataract development or progression and IOP elevation.
A single intraoperative intravitreal injection of triamcinolone is associated with improved surgical outcomes and minimizes intraoperative hemorrhage. Single-dose intraoperative triamcinolone incurs a smaller risk of cataract development and IOP elevation than repeated intravitreal injection.
Sub-Tenon’s injection of triamcinolone prevents the development of DME as a complication of panretinal photocoagulation. Sub-Tenon’s injection also incurs a smaller risk of cataract development and IOP elevation than repeated intravitreal injection.
Corticosteroid implants are currently in clinical trials for the treatment of refractory DME. The posterior chamber implants permit time-release dosing of low levels of corticosteroids, which may avoid the problems associated with repeated intravitreal injections. Posurdex uses dexamethasone in a biodegradable implant and has been show to decrease macular thickness and reduce fluorescein leakage; Retisert and Medidur use fluocinolone. Retisert is surgically implanted and is not biodegradable; it appears to improve visual acuity. Medidur is injectable and biodegradable and is currently in Phase III clinical trials.
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