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

Anna Takaoka,Kerry Cao,Eric M Oste,Takayuki Nagasaki,David C Paik

doi:10.1042/bsr20182392

Abstract

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.

Highlights

Ultraviolet-A riboflavin photochemical corneal cross-linking has created a new option in the field of corneal therapeutics
We recently reported on the in vitro testing of a group of potential cross-linking compounds in widespread use as chemical preservatives in cosmetics and other personal care products (PCPs) known as formaldehyde releasing agents [14]
Formaldehyde solution (36.8–38%), Diazolidinyl urea (N-hydroxymethyl-N-(1,3-di(hydroxymethyl)-2,5-dioxoimidazolidin-4-y [diazolidinyl urea (DAU)]), chromotropic acid disodium salt dehydrate, sulfuric acid (99.99%), 1N hydrochloric acid, and sodium bicarbonate were purchased from Sigma–Aldrich Corp

Summary

Introduction

Ultraviolet-A riboflavin photochemical corneal cross-linking (known as ‘CXL’) has created a new option in the field of corneal therapeutics. The indications are ever-expanding to include investigations into treating bullous keratopathy, corneal infections and melts, pellucid marginal degeneration, and in combination with refractive surgery (either pre- or postprocedure) [10,11,12,13]. As good as it is, CXL has limitations and developing a topically delivered adjunct (or alternative) method of inducing corneal tissue cross-linking could improve patient care. Potential benefits include the following: (1) eliminate the need for ultraviolet irradiation, (2) self-administration, (3) more homogeneous cross-linking throughout the extent of the corneal stroma, and (4) the possibility of modulation of degree of cross-linking effect

Methods

Results

Conclusion