Intraocular corticosteroids, injection

Low-dose regimens frequently result in very low corticosteroid concentrations in body fluids (e.g., low pg/mL range in plasma). PK analysis that is often necessary to manage these therapies is hindered by the inadequate sensitivity by most established analytical methods. In addition, certain drug delivery strategies, such as inhalation or intraocular injection, result in systemic levels too low to be detected by current methods. Furthermore, administration of some corticosteroid prodrugs, such as these in the forms of acetates/propionate, often results in sustained, low concentrations in plasma. Therefore, a highly sensitive and selective analytical approach is necessary for cases in which sustained low concentration of corticosteroids may be present systemically or in tissues. 

Injection of corticosteroids into the eye at the time of endophthalmitis therapy simultaneously with the injection of antimicrobials has been advocated. Corticosteroids administered by other routes have been demonstrated in numerous studies to improve the outcome of antimicrobial treatment of intraocular infection. Each patient in the EVS received prednisone 30 mg twice a day (1). Animal models consistently demonstrated improved inflammatory scores without interfering with the ability of the antimicrobial to sterilize the vitreous cavity. However, in an animal model negative as well as positive effects have been noted in studies of intraocular injection (48,51,53). 

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). 

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. 

Intravitreal injections to deliver corticosteroids minimize systemic side effects however, they may be associated with complications such as retinal detachment, retinal tears, vitreous hemorrhage, endophthalmitis, increased intraocular pressure (IOP), cataract formation, and, with repeated use (required for successful treatment), fibrosis and ptosis. The most common side effect is increased IOP, which has been found on rare occasion to increase drastically (up to 50mmHg in one case report by Detry-Morel et al.) (16,34,35). Close IOP monitoring is crucial following intravitreal injection. 

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). 

Several human studies have attempted to analyze the outcome of intraocular dexamethasone injection along with intraocular antimicrobials. In a small randomized study by Das et al. (54), an early beneficial effect on inflammatory scores was noted when patients were treated with vitrectomy and intraocular antibiotics and intraocular corticosteroids. No significant influence could be demonstrated on visual outcome 12 weeks after therapy (54). Others have attempted to analyze the effect of intraocular corticosteroids on the outcome in retrospective reviews. While... 

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