New dyes for ocular surgery : synthesis and preclinical testing
- In cases of vitreoretinal interface diseases, such as macular hole or macular pucker, the inner limiting membrane (ILM) or epiretinal membranes (ERM) need to be surgically removed. The challenging step in the surgery is the transparency of ILM and ERM that makes the membranes difficult to identify and to peel without risk of damaging the retina. Only a few vital dyes have been proposed to stain the ILM and ERM and no perfect dye is available that would stain the tissue of interest sufficiently, while being non-toxic and stable in aqueous solution. During cataract surgery a dye to stain outer part of a capsule of the lens is used when the red reflex from the fundus is absent. Dyes used for capsulorhexis need to be safe for corneal endothelial cells. Phototoxicity needs to be tested for dyes intended to be used in vitreoretinal surgery. A very strong source of light is present during the surgery, that can cause the dyes to become toxic while illuminated. A set-up for testing phototoxicity on a 96-well plate has been developed. New models for staining ability of dyes for ILM and ERM are suggested, as porcine eye was proved not reliable for those studies. Instead, a model for ILM and ERM was developed with good correlation to staining of human ILM and human ERM. Pig eyes can, however, serve as a useful model for capsule staining when cataract is induced in them.
A new dye for capsulorhexis is presented. No safe, green dye that would stain the capsule had been suggested before. The new dye is an alternative to the currently used Trypan Blue and provides as strong staining while being slightly less toxic to corneal endothelial cells.
Fourteen new dyes, that belong to the cyanine family, were synthesized and investigated for staining ability, toxicity, and stability in aqueous solution. Two of the new substances were found to stain the model for ILM in green, while being safe to retinal epithelial cells. Their stability in aqueous solution can be achieved with additives.