Safety parameters for indocyanine green in vitreoretinal surgery

Since the early nineties removal of the internal limiting membrane (ILM) has been shown to be an effective and safe treatment option for conditions that involve the vitreoretinal interface. Peeling of the barely visible ILM, however, represents a challenge and complete removal is difficult and not always obvious. Damage at the vitreoretinal interface or unsatisfactory peeling may therefore be the result of the genuine procedure. Introduction of indocyanine green (ICG) for ILM staining led to better visibility of the ILM and greatly facilitated this surgical maneuver making ILM peeling more controllable, easier and faster. Consequently, enthusiastic acceptance resulted in an uncritical use not supported by preclinical safety data. Soon thereafter some clinical reports raised concerns about potential cytotoxic effects related to the intravitreal use of ICG. The following chapter summarizes the results of in vitro, ex vivo, in vivo and clinical studies related to the use of ICG in vitreoretinal surgery. Critical appraisal of the methodical procedures and results leads to the nonnegligible fact that ICG has a cytotoxic effect enhanced by photoactivation. The results of several studies as well as our experimental workup, however, showed that ICG toxicity to the retinal pigment epithelium is dependent on the dye concentration, the osmolarity of the solvent solutions, as well as on the lengths of dye exposure time and of the vitrectomy endolight illumination time. With respect to the safety margins and profile, ICG is therefore a useful surgical tool that is still widely applied, but that may be replaced by more inert and as efficient vital dyes.