Chemical compounds causing severe acute toxicity in heavy liquids used for intraocular surgery

Perfluorocarbon liquids (PFCLs) have been considered safe for intraocular manipulation of the retina, but since 2013 many cases of acute eye toxicity cousing blindness have been reported in various countries when using various commercial PFCLs. All these PFCLs were CE marked (Conformité Européenne), which meant they had been subjected to evaluation complying with the International Organization for Standardization (ISO) guidelines. These dramatic events raised questions about the safety of PFCLs and the validity of some cytotoxicity tests performed under ISO guidelines. Samples from toxic batches were analyzed by gas chromatography-mass spectrometry combined with Raman and infrared spectrometry. Perfluorooctanoic acid, dodecafluoro-1-heptanol, ethylbenzene and tributyltin bromide were identified and evaluated by a direct contact cytotoxicity test using ARPE-19 cell line, patented by our group (EP 3467118 A1). Perfluorooctanoic acid at a concentration of >0.06 mM and tributyltin bromide at a concentration of ≥0.016 mM were shown to be toxic, whereas the concentration found in the toxic samples reached 0.48 mM, and 0.111 mM, respectively. These finding emphasized the idea that determination of partially fluorinated compounds are not enough to guarantee the safety of these medical devices. [Display omitted] •Cases of total blindness immediately after intraocular surgery using various commercial PFCL with CE mark.•Current ISO guideline 16672 should take into account these findings to avoid future cases.•GC-MS and FTIR confirmed the presence of PFOA, DFH, ethylbenzene and TBT-Br in toxic batches.•Toxicity of heavy liquids for intraocular surgery was caused by specific chemical compounds.•Toxic impurities should be removed or reduced as low as possible and should remain under risk management.