Corticosteroid retinal

Dinitrophenol Corticosteroids Retinal injury Carbon disulfide Quinine Vincristine... 

U. B. Kompella, N. Bandi, and S. P. Ayalasomayajula. Subconjunctival nano- and microparticles sustain retinal delivery of budesonide, a corticosteroid capable of inhibiting VEGF expression. Invest Ophthalmol Vis Sci 44 1192-1201 (2003)... 

Gass JD, Little H. Bilateral bullous exudative retinal detachment complicating idiopathic central serous chorioretinopathy during systemic corticosteroid therapy. Ophthalmology 1995 102(5) 737 I7. 

Several extended-release devices able to deliver a consistent level of corticosteroid to the retina have been devised. Two will be presented in this chapter, although other devices are under evaluation or in the development pipeline at the time of writing. The primary indications for these devices are persistent macular edema associated with several conditions, including diabetic retinopathy, retinal vascular occlusive disease, cataract surgery, and posterior uveitis. 

A 3-year follow-up of the patients in the ONTT demonstrated that treatment with intravenous methylprednisolone followed by oral corticosteroid regimens reduced the 2-year rate of MS development.The 10-year follow-up of the ONTT found that 92% of affected eyes had 20/40 or better vision. There was a 35% recurrence of optic neuritis, which was greatest in those patients who developed MS. Patients who were at the lowest risk category were those with a normal MRI, male gender, painless vision loss, profound disc edema, optic disc or retinal hemorrhages, and retinal exudates on presentation. 

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. 

The anti-inflammatory effects of corticosteroids reduce CME, vitreous inflammation, and retinal vasculitis. Use of corticosteroids is especially important if the macular area is threatened. Because they are immunosuppressive, they should never be used without concurrent antimicrobial agents. Oral prednisone 40 to 60 mg is given daily for 2 to 6 weeks depending on clinical response. Topical corticosteroids are used for the secondary anterior chamber reaction but have no impact on retinal inflammation, and periocular injections should be used cautiously, if at all, because of their intense anti-inflammatory activity. 

Posterior segment disease is unaffected by topical therapy and minimally requires periorbital administration of corticosteroids systemic therapy is needed if the condition is bilateral or sight threatening. Indications for posterior segment treatment include significant vision loss from macular edema or severe vitreitis, choroidal granulomas, optic nerve involvement, or retinal neovascularization. Conversely, if vision remains at 20/40 or better and there are no complicating factors, systemic... 

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). 

Corticosteroids have antiangiogenic, antifibrotic, and antipermeability properties. The principle effects of steroids are stabilization of the blood-retinal barrier, resorption of exudation, and downregulation of inflammatory stimuli. Antiangiogenesis is a secondary effect felt to be mediated primarily by upregulation of extracellular matrix protein plasminogen activator inhibitor-1 (PAI-1) in vascular endothelial cells (18). This inhibits activation of plasmin and alters extracellular matrix degradation. 

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. 

Dexamethasone alcohol and triamcinolone acetonide have been studied in PVR animal models (30-33). These agents are particularly suited for local delivery as they are both relatively lipophilic, and therefore, may be administered as a suspension. The crystalline drug then acts as a depot, providing relatively long-term intraocular levels of steroid that can be given at high doses without apparent retinal toxicity (33). While direct delivery of corticosteroids has been demonstrated to be both safe and effective in the treatment of PVR, few studies have been performed in humans (31,32). 

While corticosteroids, proven to reduce the incidence of retinal detachment in a rabbit PVR model, have some limited antiproliferative properties, they may play a more important role in stabilizing the blood-retinal barrier and preventing the access of inflammatory mediators (30,71,72). A combination of corticosteroid and 5-FU has the potential advantage of addressing both the inflammation and the proliferation associated with PVR formation. 

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). 

The previous section described treatment of retinal vein occlusion with one of the most recently proposed treatments, that of intravitreal corticosteroids. However, a variety of other treatments have either been proposed or are currently being used to treat patients with retinal vein occlusions. This section describes these treatments in greater detail. 

Hydroxychloroquine/chloroquine are often useful for patients with skin sarcoidosis (41). Their side-effect profile is much better than that of corticosteroids. However their maximum effect is often not achieved for several months. Therefore, they are often started simultaneously with corticosteroids, and the corticosteroids are tapered over several months while the antimalarials take effect. They cannot be used in patients with G6PD deficiency. Either drug, especially chloroquine, may cause retinal damage (41). Patients on antimalarial agents must therefore have regular ophthalmologic examinations. 

---