Effect of epidermal growth factor ointment on persistent epithelial defects of the cornea

Abstract

Background: Healthy corneal epithelium acts as a barrier against damage to the deeper structures in the eye. Failure in the mechanisms of corneal epithelization can lead to persistent epithelial defects of the cornea (PEDs) and can compromise its function. Epidermal growth factor (EGF) promotes the proliferation, migration, and differentiation of epithelial cells, endothelial cells, and fibroblasts during wound healing and may be beneficial in treating patients with PEDs. We, therefore, investigated the effect of EGF ointment on patients with PEDs. Methods: Fifteen patients with PEDs refractory to conventional treatment were treated twice a day with EGF ointment. Patient demographics and comorbidities were noted. The epithelial healing time was determined along with the primary outcome measures in the areas of the epithelial defects, visual acuity, visual analog scale (VAS) scores, and esthesiometer scores 1 month and 2 months after treatment.Results: Five eyes of herpetic keratitis (33.3%), 3 eyes of dry eye disease (20.0%), 3 eyes of bacterial keratitis (20.0%), 2 eyes of limbal stem cell deficiency (13.3%), 1 eye of diabetic neurotrophic keratitis (6.7%), and 1 eye of filamentary keratitis (6.7%) were associated with PEDs, respectively. Two months following treatment with EGF ointment, there was a reduction in the area of the epithelial defects (5.7 ± 3.9 to 0.1 ± 0.3 mm 2 ) as well as a significant improvement in best-corrected visual acuity (0.9 ± 0.8 to 0.6 ± 0.5 LogMAR) and VAS scores (4.5 ± 1.2 to 2.5 ± 0.7) in 12 eyes (80%). Among these cases, the mean epithelial healing time was 5.5 ± 1.8 weeks. Amniotic membrane transplantation was performed on the remaining 3 (20.0%) patients that did not respond to EGF treatment.Conclusions: EGF ointment could reduce symptoms and promotes corneal epithelialization of refractory PEDs. It may, therefore, be well-tolerated and a potentially beneficial addition in the management of refractory PEDs.

Topical insulin for refractory persistent corneal epithelial defects

“…However, 20% of patients showed no response to rEGF treatment, including no improvement in visual acuity and no decrease in the area of the corneal epithelial defect. 12 Results from these studies compare favorably to the data obtained in the current study. Furthermore, the developing field of corneal neurotization has also achieved promising results, with improvement in corneal sensation as measured by Cochet-Bonnet aesthesiometry.…”

“…23 Recombinant human EGF ointment (Easyef, Daewoong Pharmaceutical Co., Ltd., Seoul, Korea), applied to the lower conjunctival fornix twice a day, has been described in a series of patients with refractory PED. 12 Corneal epithelial defects were completely healed in 11 eyes (73.3%) with a mean duration to healing of 5.5 ± 1.8 weeks. However, 20% of patients showed no response to rEGF treatment, including no improvement in visual acuity and no decrease in the area of the corneal epithelial defect.…”

“…2,4,9,10 Recently, new non-invasive medical treatments have shown utility for the treatment of PEDs, including recombinant nerve growth factor (rNGF) or epidermal growth factor (rEGF). 11,12 Furthermore, a new surgical procedure, corneal neurotization, has been shown to improve epithelial healing, corneal sensation, and reinnervation in patients with neurotrophic PED. 13 When the epithelium loses its integrity, it heals through activation of stem cells residing in the corneoscleral junction that are stimulated by growth factors, cytokines, and extracellular matrix signals.…”

Comparison of the efficacy of topical insulin with autologous serum eye drops in persistent epithelial defects of the cornea

“…Recently, new non‐invasive medical treatments have shown utility for the treatment of PED, including recombinant nerve growth factor (NGF), epidermal growth factor (EGF) and topical insulin (Moon et al. 2020; Pflugfelder et al. 2020).…”

Treatment of persistent epithelial defects with single-dose autologous serum eye drops

“…Tears provide lubrication for the cornea and contain epidermal growth factor (EGF), fibroblast growth factor (FGF), transforming growth factor beta (TGF-β), nerve growth factor (NGF), insulin like growth factor (IGF), fibronectin, lysozyme, Ig A, and serum anti-proteases, which are thought to maintain epithelial health. 5,8 –10 EGF, FGF, and fibronectin have been shown to accelerate the healing of epithelial defects 10 –13 ; vitamin A reduces squamous metaplasia in patients with dry eye 14,15 and inhibits corneal collagenases of antiproteases such as α2 macroglobulin, providing benefits in alkaline burns 16 ; and lysozyme and Ig G have antibacterial properties. 14,16 On the other hand, TGF-β slows epithelial healing and causes scarring and fibrosis.…”