Abstract
Purpose :
Myopia is recognised as a significant public health issue hence strategies to reduce the prevalence of myopia and the progression are needed. Studies have shown the inhibition of myopia in children and juveniles by low-dose atropine eye drops; however, they provide little information on the manufacturing process and the exact composition of the atropine dilutions. The aim of this study was to assess if the presence of benzalkonium chloride (BAK) can affect the penetration of low dose (0.01%) atropine through the corneal epithelium and the impact of diluting commercial preparations on preservative effect
Methods :
Corneal cells were cultured from immortalized human corneal (HCE-2) cell line. The cytotoxicity of atropine and BAK solutions (in Hanks’ Balanced Salt Solution) separately and in combination on cultured cells was assessed. The 60 minute permeability study was performed on cells grown on transwell inserts for 4 weeks using 0.01% atropine, 0.01% atropine+0.005% BAK (BAK concentration in marketed eyedrops), 0.01% atropine+0.0001% BAK (if diluted from commercial 0.05% eyedrops), 0.01% atropine+ 0.00005%BAK (if diluted from commercial 1% eyedrops), 0.5 % atropine, 0.5% atropine+ 0.005% BAK, 1% atropine, 1% atropine+ 0.005% BAK and samples were analysed using HPLC to determine amount of drug permeated through the corneal epithelium
Results :
The pH of all solutions was 7-7.4, within an acceptable range tolerated by the eye. Over 90% of cells were viable in cytotoxicity assay for up to 1% atropine and 75% for up to 0.004% BAK; as expected due to the solubilising effect of BAK. After three consecutive days of exposure, more cells survived (≥60%) in solutions containing 0.01% atropine and up to 0.004% BAK. The BAK preserved solutions had significantly higher permeability of 0.01% atropine than unpreserved solutions. The preservative effect of BAK used in the study was also evaluated against both gram positive and gram-negative bacteria and observed that at the lowest concentration of 0.00005%, BAK had no potential preservative effect. Thus, multidose 0.01% atropine eyedrops should not be prepared by dilution of a commercial 1% solution
Conclusions :
Corneal epithelial penetration of low dose atropine significantly varied depending on BAK concentration without causing significant cytotoxicity. This fact should be considered when atropine is prescribed in children
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.