Effect of a metalloproteinase inhibitor on established corneal ulcers after an alkali burn

Proteinase inhibitors have been shown to prevent corneal ulceration and perforation when used immediately after an experimental alkali burn injury. To evaluate the clinical efficacy of a synthetic metalloproteinase inhibitor, HSCH2CH[CH2CH(CH3)2]CO-Phe-Ala-NH2(SIMP), treatment with inhibitor was withheld until corneal ulceration ensued after a standard alkali injury to the rabbit eye. When topical therapy with a 1 mmol/l solution of SIMP was initiated after corneal ulceration had progressed to a mid-stromal level (clinical score of 2), there was no significant difference in the progression of corneal ulceration between the treated vs. control group after 6 d of therapy. In the second study in which treatment was initiated earlier at the onset of superficial ulceration (clinical score of 1), there was a significant difference in clinical scores between the two groups after 1 day of treatment until termination of the experiment at 21 d (P less than 0.005). In the inhibitor-treated group, 88.9% of the corneas showed a reversal or cessation of progression of the ulceration process. Eighty-seven-and-a-half percent of the control corneas progressed to descemetocele formation or perforation by day 14 of treatment. This study suggests that SIMP may be used for effective treatment of corneal ulcers resulting from an alkali burn injury in the human eye. It also shows that early and aggressive initiation of therapy is critical.