Acute retinal toxicity associated with a mixture of perfluorooctane and perfluorohexyloctane: failure of another indirect cytotoxicity analysis

Abstract

ABSTRACT: AIMS To report new information related to acute retinal toxicity of Bio Octane Plus®, a mixture of 90% perfluorooctane (PFO) and 10% perfluorohexyloctane. METHODS This retrospective, descriptive case series reports the occurrence of acute retinal toxicity after vitreoretinal surgery in which Bio Octane Plus® (batch 1605148) was used as an endotamponade. Cytotoxicity biocompatibility tests and chemical analyses by Fourier-transformed infrared spectroscopy (FTIR) and gas chromatography-mass spectrometry (GC-MS) of the presumed toxic product were performed. RESULTS Four patients presented with acute severe visual loss after uneventful ocular surgery assisted by Bio Octane Plus® (batch 1605148) as endotamponade. Patients experienced extensive retinal vascular occlusion leading to retinal and optic nerve atrophy. The viability of ARPE-19 cells directly exposed to the suspect batch for 30 minutes was 0%. The agarose overlay method used by the manufacturer according to EU regulations and ISO International Standards failed to detect toxicity. FTIR spectroscopy showed small differences between the nontoxic and toxic batches. GC-MS analysis showed the presence of bromotributyl stannane (whose toxicity was demonstrated in the dose response curve) only in the toxic batch of Bio Octane Plus®. CONCLUSION This is the third report of retino-toxicity due to PFO in 4 years. The clinical profiles may be missed, as they resemble other post-surgical complications; therefore, more cases worldwide could have gone unreported. Protocols to determine cytotoxicity of intraocular medical devices and approved by the ISO International Standards based on indirect methods have failed and should be revised to ensure safety.