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We read the article ‘Acute retinal toxicity associated with a mixture of perfluorooctane and perfluorohexyloctane: Failure of another indirect cytotoxicity analysis ’ by Coco et al. with great interest. In this study, the authors reported on ocular toxicity due to perfluorooctane (PFO). They advised that the protocols used to determine the cytotoxicity of intraocular medical devices (which have been approved by the Organisation for the Standardisation of International Standards based on indirect methods) should be revised to ensure safety. We congratulate Coco et al.1 for their report because we believe that it has the potential to be a significant contribut or to the literature on this topic.
As is commonly known, PFO is saturated with PFO liquids, which have highly stable carbon-fluorine bonds that consequently make them inert. PFO has highly specific gravity, low viscosity, optical clarity immiscibility in water and interface tension towards water. It is regularly used in vitreoretinal surgery for complex retinal detachment repair because it displaces subretinal fluid and blood anteriorly, unfolds the retina in giant retinal tear cases and provides counter traction and retinal stabilisation during membrane peeling in eyes with proliferative vitreoretinopathy.[2,3] These properties make PFO useful for intraocular surgery. However, some limitations exist regarding PFO use as a long- term tamponade such as amaurosis, a lack of light perce...
As is commonly known, PFO is saturated with PFO liquids, which have highly stable carbon-fluorine bonds that consequently make them inert. PFO has highly specific gravity, low viscosity, optical clarity immiscibility in water and interface tension towards water. It is regularly used in vitreoretinal surgery for complex retinal detachment repair because it displaces subretinal fluid and blood anteriorly, unfolds the retina in giant retinal tear cases and provides counter traction and retinal stabilisation during membrane peeling in eyes with proliferative vitreoretinopathy.[2,3] These properties make PFO useful for intraocular surgery. However, some limitations exist regarding PFO use as a long- term tamponade such as amaurosis, a lack of light perception, optic nerve atrophy, acute retinal necrosis and retinal vascular occlusion (both arterial and/or venous) with disseminated haemorrhages.
Notably, there are controversial results regarding PFO toxicity in the literature. [3-9] The present study was one of the few reports to discuss ocular toxicity due to PFO in the last few years.
Using the current study by Coco et al.1 as a foundation, we would like to share our findings regarding the ocular toxicity of PFO. In our clinic, four patients underwent uneventful vitreoretinal surgery with PFO on the same day by two experienced surgeons (BB, SG). Each patient presented with vitritis, hypopyon and acute retinal toxicity, with no increases seen in either postoperative increased intraocular pressure or pain. Figure 1 (https://i.hizliresim.com/6NQWR0.jpg) shows macular atrophy due to PFO toxicity.
Ocular toxicity may be either mechanical or chemical due to inhibition of and/or changes to tissue functionality and/or rearrangement of tissue parts and inflammatory reactions and/or immune reactions that result in function loss. In the past, intraocular injections of aminoglycoside caused occlusive vascular changes, which were attributed to the pH of the antibiotic. The mechanism of PFO ocular toxicity may be similar. In addition, concentration and contact time may lead to toxicity. For instance, in 2013, some cases of acute blindness due to PFO were reported by Chile’s Health Authorities, while four cases were reported in Spain to the Agency of Medicines and Medical Devices. The problems were attributed to careless manipulation of the Turkish product ; variable concentrations of perfluorodecalin were found in the octane, after which the product was withdrawn.
Unfortunately, scientific reports have yet to clarify the causes of acute blindness. These results may help clinicians choose a short-term ocular tamponade when performing a vitrectomy. In addition, when faced with severe early postoperative intraocular inflammation, such as either vitritis or hypopyon, they should use PFO with care due to the possibility of toxicity and consider early systemic steroid treatment.
In conclusion, more chemical research is needed to clarify the acute ocular toxicity of PFO to ensure the safety of human patients. Additionally, immediate updates to both the European and Organisation for the Standardisation of International Standards guidelines for the biological evaluation of ophthalmic devices are needed.
1. Coco RM, Srivastava GK, Andrés-Iglesias C, et al. Acute retinal toxicity associated with a mixture of perfluorooctane and perfluorohexyloctane: Failure of another indirect cytotoxicity analysis British Journal of Ophthalmology Published Online First: 29 March 2018. doi: 10.1136/bjophthalmol-2017-311471.
2. Loewenstein A, Humayun MS, de Juan E Jr, et al. Perfluoroperhydrophenanthrene versus perfluoro-n-octane in vitreoretinal surgery. Ophthalmology. 2000;107:1078–1082.
3. Abboud EB, Al-Falah M. Nine Years of Retained Perfluoro-n-octane in the Anterior Chamber after Retinal Detachment Repair with No Signs of Ocular Toxicity. Middle East African Journal of Ophthalmology. 2014;21(3):279-282. doi:10.4103/0974-9233.134697.
4. Stefano Zenoni, Mario R Romano, Sonia Palmieri, Natalia Comi, Edoardo Fiorentini, Piero Fontana. Ocular tolerance and efficacy of short-term tamponade with double filling of polydimethyloxane and perfluoro-n-octane. Clinical Ophthalmology 2011:5 443–449.
5. Zeana D, Becker J, Kuckelkorn R, Kirchhof B. Perfluorohexyloctane as a long-term vitreous tamponade in the experimental animal. Experimental perfluorohexyloctane substitution. Int Ophthalmol. 1999;23(1):17-24.
6. Chang S, Sparrow JR, Iwamoto T, Gershbein A, Ross R, Ortiz R. Experimental studies of tolerance to intravitreal perfluoro-n-octane liquid. Retina. 1991;11(4):367-74. PMID: 1813951.
7. Alharbi SS, Asiri MS. Reversible Corneal Toxicity of Retained Intracameral Perfluoro-n-octane. Middle East African Journal of Ophthalmology. 2016;23(3):277-279. doi:10.4103/0974-9233.186160.
8. Pastor JC, Coco RM, Fernandez-Bueno I, Alonso-Alonso ML, Medina J, Sanz-Arranz A, Rull F, Gayoso MJ, Dueñas A, Garcia-Gutierrez MT, Gonzalez-Buendia L, Delgado-Tirado S, Abecia E, Ruiz-Miguel M, Serrano MA, Ruiz-Moreno JM, Srivastava GK. Acute retinal damage after using a toxic perfuoro-octane for vitreo-retinal surgery. Retina. 2017 Jun;37(6):1140-1151. doi: 10.1097/IAE.0000000000001680.
9. Pradeep S, Chhablani JK, Patel B, Rani P. Delayed inflammation associated with retained perfluorocarbon liquid. Indian J Ophthalmol. 2011 Sep-Oct;59(5):396-8. doi: 10.4103/0301-4738.83623. PMID: 21836352.
10. Waltz K, Margo CE. Intraocular gentamicin toxicity. Arch Ophthalmol 1991;109:911.
Figure 1: A 34-year-old man with a macula on a bullous retinal detachment of his right eye. His preoperative visual acuity was 16/20. He was operated on with a 23-G pars plana vitrectomy plus SF6 and a laser. One week after surgery, he complained of very low visual acuity, and he had vitritis, hypopyon and acute retinal toxicity. The patient treated with intravenous methylprednisolone ( 1 mg/kg) and topical prednisolone, moxifloxacin, nepafenac eyedrops four times a day during 4 weeks. One month after surgery, profound atrophy of all layers of the retina were seen on optical coherence tomography. His final visual acuity was counting fingers.