Neurotrophic corneal defects are difficult to heal and all too often lead to scarring and vision loss. Medical management is often of limited success. We describe the results of nine patients (ages 37-84) with chronic nonhealing neurotrophic corneal epithelial defects who were treated with thymosin beta 4 (Tbeta4) sterile eye drops for 28 or 49 days with a follow-up period of 30 days. Those with geographic defects (six patients) showed dramatic healing without clinically significant neovascularization. Stromal thinning was observed in one patient. Three patients with punctate epithelial defects did not have a demonstrable change in their clinical findings. Reduced ocular irritation was reported by all patients soon after treatment initiation. Results from these compassionate use cases indicate that Tbeta4 may provide a novel, topical approach to wound healing in chronic nonhealing neurotrophic corneal ulcers.