Corticosteroids in posterior segment disease: an update on new delivery systems and new indications.
OBJECTIVE
Corticosteroids are traditionally used for inflammatory disorders because of their ability to diminish neutrophil transmigration, limit access to sites of inflammation, and decrease cytokine production. More recently, however, investigators have focused on the angiostatic and antipermeability properties of corticosteroids for posterior segment diseases such as age-related macular degeneration (AMD), diabetic retinopathy, and macular edema. Both new angiostatic and traditional corticosteroids are currently undergoing evaluation as new delivery techniques such as intravitreal injection and intraocular sustained-release devices facilitate high local angiostatic and antipermeability concentrations while minimizing extraocular toxicity. The purpose of this review is to discuss recent work concerning both the mechanism and effectiveness of these newer treatments.


RESULTS
Steroids may exert a beneficial effect in AMD-related choroidal neovascular membranes (CNVM) through inhibition of CNVM-promoting macrophages and direct inhibition of angiogenic growth factors. They may also alter extracellular matrix turnover and inhibit matrix metalloproteinases involved in CNVM formation. Intravitreal steroid injections potently inhibit experimental CNVM in primates and rats and have shown promise in some early human pilot trials. In proliferative diabetic retinopathy, steroids may directly inhibit growth factors such as vascular endothelial derived growth factor and inhibit leukocytes that play an important role in early microvascular alterations. Intravitreal steroid injections inhibit experimental preretinal neovascularization in pigs and rats, and rubeosis in some early human studies. In addition, the effect of steroids on vascular permeability has led to their use for macular edema from many causes such as diabetes and venous occlusive disease.


CONCLUSIONS
The use of steroids to treat a number of retinal diseases is gaining wide spread acceptance. The apparent short-term success must be balanced by the fact that the long-term safety and efficacy have yet to be determined for any of these approaches. A number of large randomized prospective clinical trials of steroid compounds and new delivery systems are currently under way for AMD, diabetic retinopathy, uveitis, and other retinovascular diseases, and hopefully these studies will provide guidance about the use of these new modalities.
Ciulla
Thomas A
TA
Midwest Eye Institute, 201 Pennsylvania Parkway, Indianapolis, IN 46280, USA. thomasciulla@yahoo.com
Walker
Jonathan D
JD
Fong
Donald S
DS
Criswell
Mark H
MH
D015862:Choroid Diseases / Q000188:drug therapy*; D016503:Drug Delivery Systems; D005938:Glucocorticoids / Q000008:administration & dosage*; D006801:Humans; D012164:Retinal Diseases / Q000188:drug therapy*
D005938:Glucocorticoids