Toxicity of indocyanine green in vitreoretinal surgery

Indocyanine green (ICG) selectively stains the internal limiting membrane (ILM) of the retina, and helps to visualize and remove the membrane from the retina. Toxicity and damage to the retina has been reported in in vitro and in vivo studies, and following macular surgery. Toxic effects can occur to retinal glial cells, to the nerve fiber layer, to retinal ganglion cells, and to the optic nerve. In case of subretinal application, the retinal pigment epithelium can be affected. The mechanisms of toxicity are unclear. Whether the dye itself or some preparations only are causing harm to the retina is subject of an ongoing debate. ICG changes the light absorption properties of the ILM and enhances the stiffness of the membrane, probably by crosslinking of collagen fibers. Beside better visualization, this effect is responsible for the ease of membrane removal compared to unaided ILM peeling. Whether a phototoxic effect, which has been demonstrated in vitro and in vivo, plays a clinically significant role in macular surgery has neither been proven nor ruled out yet. ICG at concentrations higher than 1.25% or application of the dye in air are very likely causing retinal damage. In addition, lower concentrations also carry the risk of iatrogenic damage, depending on the final concentration of potentially toxic substances at the vitreomacular interface and on other mechanisms. Due to its instability and the unpredictable effects of ICG at the macula, it cannot be recommended for clinical use before its safety has been proven. This chapter reviews the literature related to ICG toxicity, and summarizes dye-related untoward effects in postmortem eyes and ex vivo models, in in vitro and in vivo animal models, and in macular surgery.