Influence of topical human epidermal growth factor on postkeratoplasty re-epithelialisation

Abstract

Aim-To test the eYcacy and safety of recombinant human epidermal growth factor (hEGF) on corneal reepithelialisation following penetrating keratoplasty. Methods-A prospective, randomised, placebo controlled study was carried out in which patients were matched for diagnosis and received either hEGF ophthalmic solution (30 µg/ml or 100 µg/ml) or placebo in a double masked fashion. Matched pairs of patients received donor corneas from the same donor and were operated by the same surgeon on the same day. At the end of surgery all donor epithelium was removed mechanically. Patients were examined twice daily and fluorescein stained photographs were taken until the epithelium had closed. The area of the defect was measured by planimetry of the fluorescein stained defect on the photographs. Results-There were no significant diVerences in re-epithelialisation of the donor cornea between the placebo group and the group treated with 30 µg/ml hEGF. Time until complete closure was slightly longer with 100 µg/ml hEGF compared with 30 µg/ml hEGF and with placebo. Mean healing rate of the epithelial defect with 100 µg/ml hEGF was significantly slower than in the other groups. Conclusion-No significant acceleration of corneal re-epithelialisation was demonstrated with the use of recombinant hEGF after penetrating keratoplasty in humans. (Br J Ophthalmol 1997;81:391-395)

Investigation of the potential of polymer therapeutics in corneal re-epithelialisation

“…The initial hope of EGF to progress to a licensed product for clinical use in the early 1990s14–16 did not come to fruition. The lack of significant effects from EGF, in humans, applied post penetrating keratoplasty17 did not match the previous findings from animal studies. The aforementioned clinical studies have involved the repeated administration of EGF because of the short half-life and the action of the tear film 18…”

Optimal concentration of human epidermal growth factor (hEGF) for epithelial healing in experimental corneal alkali wounds

“…5,6 Numerous investigations regarding the biological role of EGF on corneal wound healing have been performed experimentally and pre-clinically. [13][14][15][16][17][18][19][20][21][22][23][24] However, possible adverse effects such as developing neovascularization, inflammation, overgrowth of both epithelial and endothelial cells, benign and/or epithelial tumor in the ocular adnexa hindered the clinical administration of this agent to human eyes. 33 The major obstacle to the introduction of EGF into clinical use seems to be that the range of wound healing responses and the optimal concentration of EGF need to be determined precisely.…”

“…However, different therapeutic doses of hEGF were suggested in different wound models and even in the same wound model. [13][14][15][16][17][18][19][20][21][22][23][24] For example, the effect of EGF on corneal hEGF for epithelial healing in alkali wounds wound healing examined by measuring wound strength found that a different concentration of EGF was required in different wound types in order to increase the tensile strength. 12,25 Corneal alkali wounds have also been tested for the evaluation of the effect of hEGF on epithelial healing.…”

Comparative Study of the Effects of Recombinant Human Epidermal Growth Factor and Basic Fibroblast Growth Factor on Corneal Epithelial Wound Healing and Neovascularization in vivo and in vitro

“…the epidermal growth factor (EGF) family, the fibroblast growth factor family, insulin-like growth factor-I, the transforming growth factor-β family]. Past studies have implicated EGF and basic fibroblast growth factor (bFGF) as having the most outstanding potential for promoting corneal epithelium, stroma and endothelium repair [5,6,7,8,9]. …”