Comparing the mode of action of intraocular lutein-based dyes with synthetic dyes.PURPOSE:  To investigate and compare the mechanism by which lutein-based and synthetic intraocular dyes interact with their target membranes during ophthalmic surgeries. METHODS:  Surrogate membrane models were used in order to simulate the different intraocular membranes: internal limiting membrane (ILM), vitreous, anterior capsule (AC), and epiretinal membrane (ERM). Different lutein-based dyes, such as Phacodyne, Retidyne, Retidyne Plus, and Vitreodyne were tested, as well as Trypan Blue (TB), Indocyanine Green (ICG), Brilliant Blue (BB), and Triamcinolone Acetonide (TA). The interactions between the film components occurring at the air-water interface were investigated with surface pressure-area isotherms and polarization modulation infrared reflection-absorption spectroscopy (PM-IRRAS). RESULTS:  With the exception of TA and ICG, none of the tested dyes revealed toxicity to the analyzed membranes. The interaction of TA with the vitreous model affected deeply the biointerface structure of the model. A significant condensation of the monolayer is noted when ICG contacted with ILM by the isotherms or even a solubilization of part of the monolayer toward the aqueous subphase. Retidyne Plus may provide the fluidization of the membrane, but maintains intact the structure of proteins present in the model. CONCLUSIONS:  The present study demonstrates for the first time that lutein-based dyes interact through a physical mechanism of action with membrane models of structures present in human eye. On the other hand, the chemical interaction of synthetic dyes TA and ICG resulted in an alteration of the membrane models.