Healing of a corneal epithelial defect occurs in phases and is completed when the regenerated epithelium forms adhesions to the underlying stroma.1,11
Common treatments available include tear supplementation5
and bandage contact lenses,12
and elimination of potentially epitheliotoxic preservatives and drugs.5,14
The newer treatments of treatment are amniotic membrane transplantation,15
allolimbal/autologous limbal cell transplant,4,16,17
acetylcholine and propolis extract,26
and a new biomaterial CxGelsix.27
Treatment by reconstruction with cultured corneal epithelial cells28
has also been tried.
Amniotic membrane transplantation has been shown to be effective in persistent epithelial defects resistant to conventional medical therapy.15,17
A possible mechanism of action is that it is a source of growth factors essential to the proliferation of the residual stem cell population.29
Likewise, autologous serum has been used in such circumstances to supply the ocular tissue with epidermal growth factor, vitamin A, transforming growth factor β, fibronectin, and other cytokines,7,30
and differentially modulates the proliferation of corneal and limbal cells.7,31
The recently recognised role of growth factors and the success of the amniotic membrane transplantation in the healing of persistent epithelial defect was the basis of our study. The cornea produces multiple growth factors such as epidermal growth factor (EGF) and fibroblast growth factor (FGF), neurotrophic growth factor which contribute to the maintenance of a healthy epithelial surface and its regeneration.23–24,32
Tsubota et al7
studied the in vitro cell migration in different concentrations of fetal calf serum and found them to be significantly higher than in serum free control media. The fact that fetal calf serum enhances cell migration and is very likely to be different from adult serum in terms of growth factors6,7
warranted an evaluation.
The reason why serum is of benefit to the ocular surface is not entirely clear but probably owes its efficacy to the presence of factors such as EGF, vitamin A, acidic and basic FGF, fibronectin, nerve growth factor, substance P, antiproteases like α2 macroglobulin, and enhanced mucin expression due to the serum.7,30
Umbilical cord serum presumably has these factors in a higher concentration although a formal comparison of the exact levels of these factors in both the sera does not find a mention in the literature. The support for this presumption comes from the fact that umbilical cord serum has been used extensively as a source of stem cells in treating haematopoietic malignancies and fetal calf serum is used commonly for cell and tissue cultures.6–8
A complete analysis of the growth factors in both cord blood serum and autologous serum would have eliminated all speculation but could not be accomplished for lack of facilities.
Our findings corroborated our hypothesis as we found a significantly higher rate of healing in the cord serum group when measuring the areas and perimeters on serial photographs in an automated manner using the software Image Pro Plus, thereby eliminating all measure of human error and accounting for irregular healing patterns.11
The mechanism of action of umbilical cord serum is likely to be the same as that of autologous serum, the difference being probably a higher concentration of the growth factors, which may in fact stimulate a faster growth of stem cells and hence lead to a faster re-epithelialisation. Another important observation was that the epithelial defects increased in size over the first 3 days as evident from Table 4 (the ranges becoming negative). This biphasic response was similar to that reported by Dua et al.11
Despite a faster rate of healing in the umbilical cord serum group the median time to closure of the epithelial defects was less in the autologous serum group probably because the epithelial defects treated with cord serum showed a considerably larger increase in size initially when compared to those in the autologous serum group.
In a report of 16 cases with persistent epithelial defect Tsubota et al7
reported a 43.8% healing within 2 weeks and a further 18.8% within a month on autologous serum drops. A similar case series by Poon et a.30
shows a healing in nine out of 15 cases with autologous serum drops in a mean period of 29 days with a recurrence in five eyes after cessation of serum therapy. To the best of our knowledge this is the first randomised controlled clinical trial evaluating the efficacy of umbilical cord serum. Our healing rate is comparable and a little faster, probably because of the washout given to the epithelial defects before commencement of the medication and non-administration of any epitheliotoxic drugs concurrently. Our aetiological groups and their distribution in the two treatment groups were heterogeneous; however, their distribution was not statistically different in the two groups of patients. As the basic cause of epithelial defect is different in various disease groups, it would be ideal to study each disease group separately.
Our study corroborates the fact that serum, either umbilical cord or autologous as a 20% solution, is a safe and non-toxic preparation that can be easily prepared and used.
The risk of allergies and possibilities of transmitting parenterally transmitted organisms must also be kept in mind when using umbilical cord serum apart from the legal and ethical issues. A routine testing of the mothers and a rapid test on the sera for viral contaminants is warranted. When the event to the time between the testing of the mother for HIV and the preparation of cord serum from the placental blood is more than 6 months, HIV testing should be undertaken again at the time of serum delivery to account for the window period of the infection.
The recurrence of epithelial defects in patients with diagnoses similar to ours is known.1,7,30
However it is noteworthy that none of the 21 patients who were on follow up for another month after complete re-epithelialisation showed a recurrence even at 3 months of follow up. Although the risk of a recurrence of epithelial defects in the patients lost to follow up cannot be denied, the trend in our group of patients does not entirely corroborate the theoretical risk. Also, it would have been worthwhile to evaluate the corneal sensitivity before and after therapy to find if there is a substantial difference or recovery with re-epithelialisation.
To conclude, we recommend that umbilical cord serum is an effective means of promoting epithelialisation and can be safely used.