DefinePK

Abstract

Introduction


Chemical injuries are potentially devastating ocular surface injuries with possible permanent visual impairment.1-8 Because of their ability to penetrate the eye, alkalis can damage not only the corneal and conjunctival surface, but also the corneal stroma, endothelium and other anterior chamber structures.1,7-12 The ultimate outcome is related to the degree of injury to the limbal stem cells, which are vital for subsequent re-epithelialization.13-17 Complications include poor re-epithelialization, sterile ulcerations, bacterial keratitis, progressive corneal thinning with risk of perforation, elevated intraocular pressure (IOP), chemical iritis, cataract formation, goblet and mucin cell dysfunction resulting in tear film abnormalities and the development of severe corneal neovascularization. Corneal transplantation to replace scarred corneal tissue following alkali injury is complicated by a higher incidence of rejection because of the presence of corneal pannus.18 A large part of the post injury treatment plan is dedicated to decreasing inflammation and preventing the development of neovascularization using topical immunosuppressive and antiangiogenic agents.Thalidomide was developed in the 1950's as a sedative. It was nontoxic in rodent models. In 1961 McBride19 and Lenz20 described an association between Thalidomide use in pregnant women and limb defects in their offspring. It has been postulated that the limb defects occurred as a result of the direct inhibitory effect of Thalidomide on angiogenesis in the developing limb bud.21-24 It has been reintroduced into the US market for erythema nodosum leprosum and the skin manifestations of lupus erythematosus. In the past decade, there has been renewed interest in the antiangiogenic activity of this drug. This property is being investigated for activity against cancers of breast, ovary and prostate and multiple myeloma and preventing graft rejection.25-30 This inhibitory property of the drug has been clinically shown to be beneficial in various ailments of the eye.31 D'Amato et al showed that in a dose of 200 mg/ Kg/ Day Thalidomide produced significant inhibition of corneal angiogenesis in the basic fibroblast growth factor and induced corneal neovascularization model in rabbits.32 Later, Kruse et al showed the same effect when they induced corneal neovascularization with vascular endothelial growth factor.33 No data was reported on the effects of oral Thalidomide on alkali or chemical injury induced corneal neovascularization. We studied the efficacy of Thalidomide in preventing corneal angiogenesis in an alkali corneal injury model in rabbits.