Topical therapeutic corneal and scleral tissue cross-linking solutions: in vitro formaldehyde release studies using cosmetic preservatives

Our recent tissue cross-linking studies using formaldehyde releasers (FARs) suggest that corneal and scleral tissue strengthening may be possible without using ultraviolet irradiation or epithelial removal, two requirements for the photochemical method in widespread clinical use. Thus, the present study was carried out in order to better understand these potential therapeutic solutions by studying the effects of concentration, pH, buffer, time, and tissue reactivity on formaldehyde release of these FARs. Three FARs, sodium hydroxymethyl glycinate (SMG), DMDM, and diazolidinyl urea (DAU) were studied using a chromotropic acid colorimetric FA assay. The effects of concentration, pH, and buffer were studied as well as the addition of corneal and scleral tissues. The main determinant of release was found to be dilution factor (concentration) in which maximal release was noted at the lowest concentrations studied (submillimolar). In time dependent studies, after 60 min, FA levels decreased by 38% for SMG, 30% for DMDM, and 19% for DAU with corneal tissue added; and by 40% for SMG, 40% for DMDM, and 15% for DAU with scleral tissue added. We conclude that concentration (dilution factor) was found to be the most important parameter governing the percent of FA released.