Intravitreal injection of triamcinolone acetonide

Jonas JB, Kreissig 1, Degearing R. Intraocular pressure after intravitreal injection of triamcinolone acetonide. Br J Ophthalmol 2003 87 24-27. 

Spaide RF, Sorenson J, Maranan L, et al. Photodynamic therapy with verteporfin combined with intravitreal injection of triamcinolone acetonide for choroidal neovascularization. Ophthalmology 2005 112 301. 

Tano Y, Chandler D, Machemer R. Treatment of intraocular proliferation with intravitreal injection of triamcinolone acetonide. Am J Ophthalmol 1980 90(6) 810 816. 

Recently, macular edema associated with uveitis (29), diabetic retinopathy (30), and central retinal vein occlusion (31,32) has been treated with intravitreal injection of triamcinolone acetonide. Macular edema decreased after treatment but recurred three to six months after injection. A sustained-release steroid delivery system may be more attractive than a simple injection of triamcinolone as it could reduce or eliminate the need for multiple intravitreal injections. 

Degenring RF, Jonas JB. Intravitreal injection of triamcinolone acetonide as treatment for chronic uveitis. Br J Ophthalmol 2003 87 361. 

Currently, there are three main pharmacologic approaches to the treatment of DME in practice or under study steroids (the intravitreal injection of triamcinolone acetonide, fluocinolone acetonide sustained drug delivery implant, dexamethasone biodegradable implant), PKC inhibitors, and VEGF inhibitors. 

Detry-Morel M, Escarmelle A, Hermans I. Refractory ocular hypertension secondary to intravitreal injection of triamcinolone acetonide. Bull Soc Beige Ophthalmol 2004 292 45-51. 

Recently, intravitreal triamcinolone acetonide has been used clinically to treat retinal vascular disease (Fig. 4). A case report by Jonas and Sofker (32) described a patient with nonproliferative diabetic retinopathy and a six-month history of persistent, diffuse macular edema despite grid photocoagulation. Following one intravitreal injection of triamcinolone acetonide, the visual acuity of this patient improved from 20/200 to 20/50 over a five-month follow-up period. It was also noted that there was marked regression of macular edema on clinical examination. Martidis et al. (33,34) reported on the use of intravitreal triamcinolone for refractory diabetic macular edema. Sixteen eyes with a macular thickness of at least 300 pm despite prior photocoagulation were treated with 4 mg injections of triamcinolone. At three-month follow-up the mean decrease in central retinal thickness was 57.5%, with a visual acuity increase of 2.4 Snellen lines. Those with six-month follow-up demonstrated some recurrence of edema and visual acuity improvement was reduced to 1.3 lines. 

Cardillo JA, Melo LA, Costa RA, et al. Comparison of intravitreal versus posterior sub-Tenon s capsule injection of triamcinolone acetonide for diffuse diabetic macular edema. Ophthalmology 2005 112 1557-1563. 

The largest randomized trial to date was performed by Gillies et al. (49). This study was a randomized, double-masked, placebo-controlled trial of triamcinolone acetonide intravitreal injection in patients with classic CNV associated with AMD. Patients were randomized to receive a single injection of triamcinolone acetonide, 4mg (n = 75) or to receive a sham injection (n = 76). At 12 months the risk of severe visual loss (30 letters) was 35% for both the treated group and the placebo group. Although the visual acuity did not differ between the treated and control groups, at three months, the choroidal neovascular complex appeared to be smaller in the... 

One of the most common adverse events associated with the type of treatment is ocular hypertension. In one study intravitreal injections of 25 mg triamcinolone acetonide resulted in ocular hypertension in approximately 50% of treated eyes, commencing 1 to 2 months after the injection. lOP was responsive to topical therapy and normalized after approximately 6 months after the injection. Other studies reported that patients who feiled medical therapy required surgical intervention to reduce iatrogenic pressure elevations. 

Deeper or more severe forms of uveitis may not respond to topical therapy hence, injectable and/or oral routes of administration may be required. Periocular corticosteroids may be used occasionally for anterior uveitis however, this therapy is more often used in cases of intermediate uveitis or, less commonly, unilateral posterior uveitis.A small amount of depot corticosteroid (e.g., 1 ml of 40 mg/ml triamcinolone acetonide injected superiorly or inferiorly in the orbit) is considered acceptable and appropriate treatment in such situations. In cases of chronic posterior uveitis or uveitis associated with CME, intravitreal triamcinolone has also been used with some success. A retrospective study in 2005 demonstrated that intravitreal injection of 4 mg/0.1 ml triamcinolone acetonide can effectively reduce CME and improve visual acuity and, in some eyes, allow for the reduction of immimosuppressive therapy. 

Beer PM, Bakri SJ, Singh RJ, et al. Intraocular concentration and pharmacokinetics of triamcinolone acetonide after a single intravitreal injection. Ophthalmology 2003 110 681-688. 

Efficacy. Corticosteroids have an inhibitory effect on the growth of fibroblasts (47,48). Triamcinolone acetonide inhibits experimental intraocular proliferation in rabbits (36). Intravitreal injection of 1 mg of triamcinolone significantly reduced both retinal neovascularization and retinal detachment in an experimentally induced rabbit model (36). A 4-mg intravitreal triamcinolone injection inhibited preretinal and optic nerve head neovascularization in a pig model of iatrogenic branch vein occlusion all untreated eyes developed neovascularization by six weeks (49). Intravitreal triamcinolone is also a potent inhibitor of laser-induced CNV in a rat model however, this animal model may not be ideal since laser-induced CNV may be caused by a traumatic repair process or inflammatory response and may be more susceptible to steroids than neovascularization in human disease states (50). In addition, the intravitreal triamcinolone acetonide was administered at the time of laser treatment thus, the treatment may only inhibit new vessel formation and not existing neovascularization. 

In contrast 4 mg of triamcinolone acetonide, a minimally water-soluble steroid, injected intravitreally has a mean elimination half-life of 18 days in nonvitrectomized... 

Jonas JB. Intraocular availability of triamcinolone acetonide after intravitreal injection. Am J Ophthalmol 2004 137 560-562. 

The FDA approved intraocular injections include miotics, triamcinolone acetonide, pegaptanib sodium, ranibizumab, formivirsen sodium, viscoelastics and viscoadherents, and an antiviral agent for intravitreal injection. There are many small and large molecules currently in clinical trials that are delivered via intravitreal injection for the treatment of a variety of retinal diseases with a large area of focus on the treatment of AMD and macular edema. 

The use of intravitreal corticosteroids was first popularized by Machemer in 1979 (33) in an effort to halt cellular proliferation after retinal detachment surgery, and Graham (34), McCuen (35), Tano (36), and others have studied its use in both animal models and humans. In contrast to other corticosteroids with short half-lives following intravitreal injection, triamcinolone acetonide is an effective and well-tolerated (35,37) agent for intravitreal injection in conditions such as uveitis (38,39), macular edema secondary to ocular trauma or retinal vascular disease (40), proliferative diabetic retinopathy (41), intraocular proliferation such as proliferative vitreoretinopathy (42), and choroidal neovascularization from AMD (43,44). 

Penfold et al. (46) published in 1995 a pilot study of neovascular AMD treatment with intravitreal triamcinolone acetonide. Their preliminary data evaluating 30 eyes treated with intravitreal triamcinolone injection demonstrated decreased leakage by fluorescein angiography and increased visual acuity. In an 18-month follow-up to this trial, of the 20 eyes with initial visual acuity of 20/200 or better, the vision was maintained ( 1 Bailey-Lovie lines) in 11 eyes (55%), while six eyes (30%) suffered severe visual loss (six or more lines). The visual acuity improved by five to six lines in three of 10 eyes with initial vision of 3/60 or worse. 

As discussed previously, corticosteroids downregulate VEGF production in experimental models and possibly reduce breakdown of the blood retinal barrier (15,16). Similarly, corticosteroids have antiangiogenic properties possibly due to attenuation of the effects of VEGF (20,21). These properties of steroids are commonly used. Clinically, triamcinolone acetonide is used locally as a periocular injection to treat cystoid macular edema secondary to uveitis or as a result of intraocular surgery (22,23). In animal studies, intravitreal triamcinolone acetonide has been used to prevent proliferative vitreoretinopathy and retinal neovascularization (24—27). Intravitreal triamcinolone acetonide has been used clinically to treat proliferative vitreoretinopathy and choroidal neovascularization (28-31). 

FIGURE 51.7 Intravitreal injection distribution of triamcinolone on the lens surfaces and a large part of the vitreous. (Reprinted from Vet. J., 176(3), Molleda, J.M., Tardon, R.H., Gallardo, J.M., and Martm-Suarez, E.M., The ocular effects of intravitreal triamcinolone acetonide in dogs, 326-332. Copyright 2008, with permission from Elsevier.)... 

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