Intraocular Corticosteroids

Sustained intraocular corticosteroid delivery can overcome systemic side effects associated with oral topical and periocular therapy while at the same time provide effective suppression of intraocular inflammation (5-9). However, sustained intraocular therapeutic corticosteroid levels are required to adequately treat uveitis that typically has a chronic and recurrent course. Some corticosteroids such as dexa-methasone phosphate are less suitable for treatment of chronic intraocular inflammation as they have half-lives of < 4 hours when administered intravitreally and are rapidly removed from the eye (5,9). 

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... 

If mast cell stabilizers or multiple-action agents are not successful, a trial of a topical NSAID is appropriate. Ketorolac is the only approved topical agent for ocular itching. NSAIDs do not mask ocular infections, affect wound healing, increase intraocular pressure, or contribute to cataract formation like the topical corticosteroids. However, for allergic conjunctivitis, topical ketorolac is not as effective as olopatadine or emedas-tine in trials.15 Full efficacy of ketorolac takes up to 2 weeks.17... 

Iritis, which affects up to 25% of patients undergoing fomivirsen therapy, can be managed with topical corticosteroids. Vitreitis and increased intraocular pressure may also result from fomivirsen administration. Fomivirsen is contraindicated in patients who have been treated with cidofovtr within the previous 2 to 4 weeks because cidofovir increases the risk of ocular inflammation. 

The most commonly observed side effects associated with vidarabine are lacrimation, burning, irritation, pain, and photophobia. Vidarabine has oncogenic and mutagenic potential however, the risk of systemic effects is low because of its limited absorption. It should not be used in conjunction with ophthalmic corticosteroids, since these drugs increase the spread of HSV infection and may produce side effects such as increased intraocular pressure, glaucoma, and cataracts. 

Opatowsky I, Feldman RM, Gross R, Feldman ST. Intraocular pressure elevation associated with inhalation and nasal corticosteroids. Ophthalmology 1995 102(2) 177-9. 

Ozturk F, Yuceturk AV, Kurt E, Unlu HH, Ilker SS. Evaluation of intraocular pressure and cataract formation following the long-term use of nasal corticosteroids. Ear Nose Throat J 1998 77(10) 846-51. 

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. 

In recent years intraocular delivery of medication, including anti-vascular endothelial growth fector, corticosteroids and related compounds, and antiviral agents, has either been approved or is under study for treatment of macular degeneration, uveitis, cytomegalovirus, or diabetic macular edema (Table 2-5).This area of research and development is growing rapidly. 

Figure 12-3 Weekly intraocular pressure responses of eyes treated with medrysone 1%, fluorometholone 0.1%, and dexamethasone phosphate 0.1%. Each point represents a mean value (mm Hg) of 12 eyes. (Reprinted with permission from Mindel JS, Tovitian HO, Smith H, et al. Comparative ocular pressure elevations of topical corticosteroids. Arch Ophthalmol 1980 98 1578. Copyright 1980, American Medical Association.)...

Figure 12-4 Mean intraocular pressure response in known corticosteroid responders to loteprednol etabonate LE) 0.5% or prednisolone acetate (EM) 1.0%. (Reprinted with permission from Bardett JD, Horowitz B, Laibovitz R, et al. Intraocular pressure response to loteprednol etabonate in known steroid responders. J Ocul Pharmacol 1993 9 l6l.)...

Use of systemic, periocular, or topical corticosteroids reduces intraocular inflammation, particularly vitreous opacification, but does not affect the severity of retinal necrosis. The usual dosage is 60 to 80 mg of oral prednisone for at least 1 week, followed by tapering over 2 to 6 weeks. Topical corticosteroids should be used to treat anterior segment inflammation. 

Increases in intraocular pressure and development of posterior subcapsular cataracts are femiliar sequelae to corticosteroid therapy. Increased intraocular pressure after IVTA is considerably more common than endophthalmitis and has been established in different studies. Results are not readily comparable, because different amounts of triamcinolone were administered. However, it should be noted that approximately 30% or more of patients had an increase in intraocular pressure, regardless of the dose given, which is consistent with the finding that a significant number of patients are steroid... 

The ocular side effects of corticosteroids are many and are related to the route of administration. The most common concerns are increased intraocular pressure (lOP) and cataracts, but delayed epithelial woimd healing and increased risk of infection due to immime modulation and decreased tear lysozyme levels are issues for the cornea. Changes to other ocular tissues have been noted (subconjunctival hemorrhages, blue sclera, eyelid hyperemia and edema, retinal emboUc events, central serous choroidopathy) and neurologic compUcations reported (diplopia, nerve palsies, intracranial hypertension) (see Appendix 35-1). 

Tano Y, Sugita G, Abrams C, Machemer R. Inhibition of intraocular proliferation with intravitreal corticosteroids. Am J Ophthalmol 1980 89 131-136. 

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. 

Hida T, Chandler D, Arena JE, Machemer R. Experimental and clinical observations of the intraocular toxicity of commercial corticosteroid preparations. Am J Ophthalmol 1986 101(2) 190 195. 

All intraocular disorders that require systemic administration or frequent local administration of the drug may be appropriate for these biodegradable systems. Uveitis is a chronic disorder that requires long-term medical therapy. Topical drug treatment is not effective in the treatment of posterior uveitis because of limited intraocular penetration. Systemic administration of corticosteroid or immunosuppressive agents may be effective but are associated with systemic side effects. Sustained drug delivery systems may be effective in the treatment of uveitis. In... 

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