Intraocular toxicity caused by MEROCTANE perfluorocarbon liquid

Abstract

Serious intraocular toxicity cases have been reported worldwide after the use of different perfluorocarbon liquids. The current study reports for the first-time the clinical pictures of cases of acute intraocular toxicity caused by MEROCTANE, a perfluoro-octane commercialized by a Turkish company and distributed in many countries. A series of 18 cases from Chile and Spain was retrospectively analysed. To evaluate the impurity profile, a suspicious MEROCTANE sample (lot OCT.01.2013) was analysed by gas chromatography mass spectrometry and compared with a non-suspicious sample of the same commercial perfluoro-octane (lot OCT 722011). Cytotoxicity was tested following a direct-contact method, taking into consideration the high volatility and hydrophobicity of perfluoro-octane and following the ISO 10993 guideline. Cytotoxicity test showed clear cytotoxic effects of the analysed batch (less than 9% of cell viability). Moreover, chemical analysis demonstrated the presence of many contaminants, some highly toxic (acids and alcohols). Perfluorocarbon liquids are useful tools for intraocular surgery but companies and Agencies of Medical Devices must implement measures that guarantee the safety of these products based on both chemical and cytotoxicity analysis for every batch. Medical staff should be encouraged to report any suspected case to their respective National Agencies.

Acute intraocular toxicity caused by perfluorocarbon liquids: safety control systems of medical devices

“…The very sensitive chemical analytical techniques detect most of the impurities present in a PFCL batch. Few of them have been reported in publications: - Nuclear magnetic resonance (NMR) [ 23 ] - Gas chromatography-mass spectrometry (GC–MS) [ 1 , 3 , 26 – 28 , 30 ] - Infrared spectroscopy (FT-IR) [ 1 , 28 ] - Fluoride-selective potentiometry [ 22 ] …”

“…It depends on their concentrations in the PFCL batch to produce low-to-high adverse biological responses in live cells; however, all of them should be eliminated from the final products. Table 3 shows few impurities that have been detected in different batches of the PFCL of AlaOcta®, BioOctane Plus®, Meroctane® [ 1 , 3 , 22 , 28 , 30 ]. Impurity profiles differ from one to another batch of the PFCL [ 1 , 3 , 22 , 28 , 30 ].…”

“…Table 3 shows few impurities that have been detected in different batches of the PFCL of AlaOcta®, BioOctane Plus®, Meroctane® [ 1 , 3 , 22 , 28 , 30 ]. Impurity profiles differ from one to another batch of the PFCL [ 1 , 3 , 22 , 28 , 30 ]. Batches’ impurity profiles may change during their shelf life due to reactions among the reactive underfluorinated compounds.…”

“…Nevertheless, what is the biological response of each profile of impurities is difficult to predict without performing an appropriate cytotoxicity test. PFCL toxicity is batch-dependent [ 3 , 5 , 22 , 26 , 30 ]. Considering all of these points, the biological response of each PFCL batch together with chemical analysis must be performed for releasing the final PFCL product to market.…”

Comparison of Perfluorocarbon Liquids Cytotoxicity Tests: Direct Contact Versus the Test on Liquid Extracts

“…Thus, the debate arose on the reliability of the cytotoxicity test on extracts versus the in vitro cytotoxicity test by direct contact, both described by ISO 10993-5. ,, The test on liquid extract does not take into full consideration the hydrophobic and volatile characteristics of the PFCLs and, therefore, may leave undetected the toxicity of some unextracted impurities. The direct contact test, coupled with accurate physical-chemical methods for testing the purity of the raw material (e.g., NMR analyses or gas chromatography techniques), could truly ascertain the complete absence of potentially hazardous impurities in the PFCLs medical devices. ,,,− …”