PURPOSE: To investigate the effects of a single prolonged exposure to recombinant epidermal growth factor on the healing of anterior keratotomy wounds in New Zealand white rabbits. METHODS: After wounding, eyes were perfused for 1, 2, 4, and 8 hours with either epidermal growth factor solution at a concentration of 50 micrograms/ml or balanced saline solution using a Morgan therapeutic lens (Mortan Inc, Missoula MT) and a syringe pump. Furthermore, concentration response was evaluated by perfusing with epidermal growth factor solutions at concentrations of 5, 50, 100 and 500 micrograms/ml for 4 hours. Wound healing rates were determined by quantitative morphometry of the wound area. The ratio of healing rates of eyes perfused with epidermal growth factor and control eyes provided a measure of the effect of epidermal growth factor on wound healing, and was defined as the epidermal growth factor enhancement factor. RESULTS: The enhancement factor was found to be 1.04 +/- 0.08, 1.17 +/- 0.07, 1.43 +/- 0.09, and 1.59 +/- 0.07 for perfusion times of 1, 2, 4, and 8 hours, respectively. The concentration response enhancement factors were 0.99 +/- 0.08, 1.43 +/- 0.09, 1.21 +/- 0.09, and 0.95 +/- 0.07 for the 5, 50, 100, and 500 micrograms/ml 4-hour perfusions, respectively. CONCLUSION: The results indicated that continuous epidermal growth factor exposures of as few as 2 hours produced a significant increase in healing rates (P < 0.05); increasing the time of exposure further increases the rate of wound healing. Results from the concentration response experiments showed that the optimum epidermal growth factor concentration for enhancing epithelial wound healing is approximately 50 micrograms/ml.
