| Abstract |
Corneal alkali injury is a clinical problem that endangers the anatomical integrity of the eye, since it leads to ulceration and melting of the cornea. This may result, according to the type of alkali and the severity of the injury, to corneal perforation and subsequent decrease or even total loss of vision. The oxygen free radicals are considered as one of the incriminating factors in the process of corneal melting following alkali burn. The purpose of the current work, is the study of the efficacy of desferrioxamine, zinc-desferrioxamine and gallium-desferrioxamine, compounds with proved free radical inhibitory properties, in protecting the cornea from melting following alkali injury. A corneal alkali burn model with caustic soda was used for this purpose, in two experiments hosting a total of fifty rabbits. Each experiment lasted 28 days. During the first experiment (20 rabbits), ten animals received topical application of zinc-desferrioxamine, while normal saline (vehicle) was applied to the other ten (control group). During the second experiment (30 rabbits), in three groups of ten animals each, one group received topical desferrioxamine, the second received topical gallium-desferrioxamine, and the third normal saline (control group). The topical use of treatment in both experiments was in the form of eye drops in the cornea, every two hours for twelve hours daily during the 28 days of the study. To evaluate the efficacy of the applied treatment, the rabbits were examined clinically in the slit-lamp twice a week, and the following parameters were studied: ulceration grade, ulceration area, area of epithelial defect, extent of neovascularization. Also, at the end of each experiment, the animals were sacrificed, and the corneas were excised for histopathological evaluation. In a third experiment hosting five rabbits, the toxicity of desferrioxamine was studied, using topical application of eye drops of the drug in healthy eyes every half-hour for twelve hours daily, during a period of one week. In the fellow eyes of those five rabbits normal saline was applied in the same manner (control group). To evaluate toxicity, the rabbits were examined clinically in the slit-lamp, before the institution and after the completion of the treatment, and toxicity signs were looked for, as: punctate keratitis, conjunctival irritation and cataract. Also for the evaluation of retinal toxicity, an electroretinogram was performed, before the institution and after the completion of the treatment. Lastly, at the end of the study, animals were sacrificed and the eyes were excised for histopathological evaluation.The results showed that desferrioxamine and zinc-desferrioxamine significantly reduced the corneal ulceration and melting in the alkali burn model, while gallium-desferrioxamine showed no statistically significant differences from the control group. None of the used drugs significantly reduced neovascularization or epithelial defect size, except desferrioxamine that showed some positive effect on epithelialization. The toxicity study showed that desferrioxamine had no toxic effect on the rabbits' eyes, according to the results of the clinical examination, the electroretinogram, as well as the histopathology report. From the above, it seems that the free radical scavenging effect of desferrioxamine and zinc-desferrioxamine protected the rabbits' alkali burned cornea, by reducing ulceration and melting. The non significant effect on other parameters such as neovascularization and epithelial healing, is attributed to the fact that the causes of alkali burn-induced inflammation are multifactorial, hence, controlling one factor alone, such as free radicals, seems to be insufficient to reverse the results of this inflammation. Therefore, these two drugs may play an adjuvant role in the management of corneal alkali burns.
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