Is the new ISO 16672.2: 2019 the best prevention to avoid future cases of acute intraocular toxicity by perfluorocarbon liquids?

Abstract

Purpose : Since 2013, numerous cases of acute toxicity have been reported due to substances used in vitreo-retina surgery (VRS): internal limiting membrane dyes, heavy silicone oils and perfluoro-octane (PFO). All the products carried the CE mark, after having demonstrated that they complied with the UE directives and follow the harmonized ISO / DIS 16672 standard. Despite this, some have produced hundreds of blindness in many countries. Only in Spain 130 were officially reported. The purpose of this work was to determine the causes of acute toxicity, of PFO to analyse cytotoxic tests used and to check if new ISO 16672.2: 2019 standard (October 2019) has corrected previous weakness.

Methods : Batches of PFO distributed by different companies and provided by 5 different manufacturers were evaluated. Some of them showed clear acute toxicity in patients. Chemical analysis were performed by Raman and Fourier-transform infrared spectroscopy (FTIR) transmission and attenuated total reflectance (ATR). Cytotoxicity was evaluated by a direct cytotoxicity test (patented WO 2017/207845) and results were compared with other cytotoxicity procedures (extractive and indirect) used to get CE mark by the mentioned toxic batches, all complying with ISO 10993-5, 2009.

Results : Only the direct cytotoxicity method identify toxic lots since it takes into account two important PFO characteristics: immiscibility in water and volatile nature. In addition, some of the chemical analytical methods used by some companies did not identify some of the cytotoxic compounds present in toxic lots: perfluorooctanoic acid, dodecafluoro-1-heptanol, leachables (ethylbenzene and dimethylbenzene) and tributyltin bromide.
All this experience has turned into the new wording of the ISO (16672.2: 2019),made this time with the participation of a clinician expert in VRS,

Conclusions : The new drafting of ISO standards, carried out with the scientific support of experienced clinicians, has allowed the incorporation of some modifications to ISO 16672 standards. Only the combination of suitable chemical analyses, seeking maximum product purity, and performing a final direct cytotoxicity test can guarantee safer products and eliminate the risk of acute toxicity. ISO committees should always incorporate expert clinicians.

This is a 2020 ARVO Annual Meeting abstract.