Optimal Concentration of hEGF for Epithelial Healing in Experimental Corneal Alkali Wounds

PURPOSE: An optimal concentration of hEGF to enhance epithelial healing was determined in the rabbit eyes after alkali wounds. METHODS: Alkali-injured corneas (=5.5 mm, 1N NaOH, 60s) were treated with 0 (control), 2, 5, 10, and 50microgram/ml hEGF 3 times per day. The measurement of epithelial healing rate, transmission electron microscopy and immunohistochemical observation were performed after 7 days treatment. RESULTS: No significant difference was observed in the rates of epithelial healing between control and each hEGF-treated group. Among the tested concentrations, 5microgram/ml hEGF induced the most active proliferation of basal cells and 50microgram/ml hEGF remarkably produced a vascular ingrowth to the central wound area. The number of epithelial layers was increased by hEGF in a concentration-dependent manner. CONCLUSIONS: A low concentration of hEGF may selectively enhance epithelial healing without inducing corneal neovascularization. The optimal concentration of hEGF for the stimulation of basal cell proliferation appears to be 5 microgram/ml in rabbit corneal alkali wounds.

Effects of Topically Applied Na-Hya luronan on Stromal and Endothelial Healing in Experimental Corneal Alkali Wounds

The effects of topical sodium-hyaluronan on the stromal and endothelial healing were examined in the repair process of experimental corneal alkali wounds. Corneal alkali wounds were produced in one eye of each rabbit by applying a 5.5 mm round filter paper soaked in 1N NaOH onto the central cornea for 60 seconds. Then the eyes were treated topically with either 1% Na-HA(the treatment group)or a phosphate buffered saline(PBS)(the con-trol group)4 times per day for 3 weeks. Endothelial wound morphometry was performed after alizarin red and trypan blue staining. The stromal healing was assessed by counting polymorphonuclear leukocytes(PMNs)and keratocytes in the central and marginal wounds areas. The stroma treated with Na-HA had less PMNs than that of the control group during the early healing period. The defect area of the endothelium was significantly smaller in the Na-HA treated group than in the control corneas. The present findings indicate that topically applied 1%Na-HA affects stromal and endothelial healing during the early repair process after corneal alkali wounds.

Effects of Topically Applied Na-Hyaluronan on Epithelial Healing and Aqueous Composition in Experimental Corneal Alkali Wounds

The effects of topical sodium-hyaluronan (Na-HA)on the epithelial healing and aqueous compositions were examined in the repair process of experimen-tal corneal alkali wounds.Corneal alkali wounds were produced in one eye of each rabbit by applying a 5.5 mmround filter paper soaked in 1N NaOH onto the central cornea for 60 seconds.Then the eyes were treated topically with either 1%Na-HA (the treatment group)or a phosphate buffered saline (PBS) (the control group)4 times per day.The epithelial healing was assessed using a quantitative method and the changes of the concentration of ascorbic acid and glucose in aqueous were evaluated.The initial epithelial healing rate was similar between 1%Na-HA treated and control groups and the later healing was enhanced in the treated group but statistically insignificant.The concentrations of ascorbic acid and glucose in aqueous humor are not statistically different in the early phase, but ascorbic acid concentration in later healing phase was higher in the treated group when compared with the control group.The present findings in dicate that topical-ly applied 1%Na-HA affects late epithelial healing and ascorbic acid concentration in aqueous humor during the repair process after corneal alkali wounds.

Effects of Topically Applied 0.1%Dexamethasone on Endothelial Healing and Aqueous Composition Following Experimental Corneal Alkali Wounds

The effects of topical dexamethasone on the endothelial healing and the change of aqueous composition were examined in the repair process of experimental corneal alkali wounds. Corneal alkali wounds were induced, then the eyes were treated topically with either 0.1%dexamethasone or abalanced salt solution[BSS]4 times per day for 8 weeks. Endothelial wound morphometry was performed after alizarin red and trypan blue staining. The concentrations of ascorbic acid, glucose, and the ions, Na, K , Ca2 and Mg2 , were measured in the aqueous humor. Endothelial healing in control corneas showed a biphasic pattern of healing:an initial short-term healing for the first week and then a late long-term healing following a secondary endothelial breakdown. Topical administration of 0.1%dexamethasone deterred endothelial healing during the early period and prevented secondary endothelial breakdown. Total repair process of endothelium was accelerated by the dexamethasone treatment. Among the various components of the aqueous humor examined, ascorbic acid seemed most sensitive to change caused by the alkali injury and dexametha-sone treatment. The present data indicate that dexamethasone may have a therapeutic potential in the management of endothelial healing after corneal alkali injury.

The Therapeutic Effect of Topically Applied 1% Sodium Hyaluronic Acid(Na-HA) on Corneal Alkali Burn

The effects of topically applied 1% Na-HA on corneal epithelial healing and visual outcomes were evaluated in 15 eyes of 12 corneal alkali-burned patients. 1 % Na-HA (Healon, Pharmacia, Sweden) together with antibiotics(Tarivid eye oint, Japan) in the treatment group and antibiotics ointment alone in the control group were given four times a day for the first one week and then antibiotics were used in both groups. For the assessment of the initial epitheilal healing, the eyes were examined at about 8 to 12 hours intervals during the first week. Individual epithelial healing rates were calculated by a linear regresion analysis from the epithelial defect areas. The best corrected visual acuity was compared between two groups. Initial epithelial healing rates were 0.81+/-0.53(mm2/hour) in the 1% Na-HA treated group and 0.40+/-0.21(mm2/hour) in the control group, respectively. A progressive improvement of visual acuity was observed in the 1% Na-HA treated group, while no change of vision was found in the control group. This clinical study suggests that topical application of 1 % Na-HA in combination with topical antibiotics could be considered for the management of corneal alkali wound.

Effects of 0.1% Dexamethasone on Experimental corneal Epithelial Healing Following Alkali Wounds

The effect of topical steroid on corneal alkali wound has been controversial due to a complexity of its mechanism and a risk of ulceration and perforation. In this study, the effect of topical 0,1% dexamethasone on corneal epithelial wound healing following alkali burn was evaluated quantitatively. 22 eyes wounded by alkali burn out of 22 white rabbits were divided into 3 groups ; A group treated with topical 0.1% dexamethasone for eight weeks, B grouptreated with topical 0.1% dexamethasone for the first one week followed by another seven weeks without treatment, C group with no treatment served as a control. The area of corneal epithelial defect was examined at 6, 18, 30, 42 hours following corneal alkali wound for initial wound healing and examined every other day from 4 days to 48 days following corneal alkali wound for late wound healing. In this study, it was found that topical 0.1% dexamethasone delayed corneal epithelial healing following corneal alkali burn in both stage of initial and late wound healing.

Effect of topically applied Na-hyaluronan on experimental corneal alkali wound healing

The effect of topically applied 1% sodium hyaluronate (Na-HA) on the healing of a standardized corneal alkali wound was studied. The healing of the epithelium, stroma, and endothelium was evaluated separately, using quantitative methods. Central corneal alkali wound was produced in one eye of the rabbits by applying a 5.5-mm round filter paper, soaked in 1 N NaOH, for 60 seconds. 1% Na-HA in the treatment group and phosphate buffered saline (PBS) in the control group were given topically 4 times per day for 2 days, 1- and 3-weeks. Epithelial and endothelial healing was assessed morphometrically from standardized photographs and micrographs, respectively. Stromal healing was determined by counting polymorphonuclear leukocytes (PMN) and keratocytes in the central and marginal wound areas. A positive healing influence was observed in the epithelium. In stromal healing, 1% Na-HA treated corneas showed less PMNs and more keratocytes than the control group, suggesting that topically applied 1% Na-HA may suppress the stromal PMN infiltration and enhance the keratocyte repopulation during corneal alkali wound healing. However, no significant difference was found in morphometric evaluation of endothelial healing between the two groups.