In vitro experiment to elucidate the mechanism of the ‘soft shell technique’ for preventing subretinal migration of perfluoro-octane

Chan, Yau Kei; Lu, Yongjie; Czanner, Gabriela; Wu, Jing; Cheng, Ho Ching; Hussain, Rumana; Sakamoto, Taiji; Shum, Ho Cheung; Wong, David

doi:10.1136/bjophthalmol-2016-309856

Cited by 7 publications

(8 citation statements)

References 21 publications

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“…The perfluorocarbon liquids (PFCLs) are considered to be a valuable tool as vitreous tamponade in the management of vitreoretinal diseases such as complex retinal detachments. 1 , 2 The rationale for using these compounds in vitreoretinal surgery lies in their highly specific gravity, optical clarity, and immiscibility with water. 3 , 4 One of the most largely used PFCLs is the fully fluorinated perfluoro-n-octane (PFO), whose safety profile has been extensively proved.…”

Section: Introductionmentioning

confidence: 99%

Toxicity Threshold of Perfluorocarbon Liquids for Intraocular Use: Dose–Response Assessment of In Vitro Cytotoxicity of Possible Contaminants

Romano

Gatto²,

Giurgola³

et al. 2021

Trans. Vis. Sci. Tech.

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Purpose This study assessed the cytotoxicity of the impurities detected in the perfluorooctane (PFO) batches for vitreoretinal surgery that were associated with serious adverse incidents of ocular toxicity, namely, the perfluorooctanoic acid (PFOA), 1H,1H,7H-dodecafluoro-1-heptanol (DFH), 1H-perfluorooctane (1H-PFO), ethylbenzene, anhydrous p-xylene, and perfluoro-2-butyltetrahydrofurane, and two additional substances 1H,1H,1H,2H,2H-perfluorooctane (5H-PFO) and hexafluoro-1,2,3,4-tetrachlorobutane. Methods Serial dilutions were tested by in vitro direct contact cytotoxicity test, validated in accordance with the ISO 10993-5:2009 standard using BALB3T3 and ARPE-19 cell lines, after sample application for 24 hours. Results Six of the eight tested substances were cytotoxic according to the above-mentioned ISO standard. Anhydrous p-xylene, ethylbenzene, and PFOA were the most cytotoxic impurities as traces 1.55 ppm, 1.06 ppm, and 28.4 ppm reached the cytotoxicity limit, respectively. Hexafluoro-1,2,3,4-tetrachlorobutane, DFH, and 1H-PFO were cytotoxic at 980, 22,500, and 123,000 ppm, respectively. Both 5H-PFO and perfluoro-2-butyltetrahydrofuran were non-cytotoxic at the highest available concentrations (≥970,000 ppm). The dose-response curves allowed to calculate the cytotoxic concentration (CC 30 ) for each tested substance that would reduce 30% of cell viability and corresponding to the cytotoxicity threshold according to ISO 10993-5. Conclusions Our study determined the in vitro cytotoxicity of several impurities in PFO associated with serious adverse incidents in retinal surgery patients. Translational Relevance Severe cytotoxicity of some impurities previously found in toxic perfluorocarbon liquids was confirmed. The cytotoxicity test validated according to the ISO 10993-5:2009 standard is a sensible and fast method for reliable detection of the cytotoxicity in perfluorocarbon liquids to guarantee maximal safety for the patients.

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Section: Introductionmentioning

confidence: 99%

Toxicity Threshold of Perfluorocarbon Liquids for Intraocular Use: Dose–Response Assessment of In Vitro Cytotoxicity of Possible Contaminants

Romano

Gatto²,

Giurgola³

et al. 2021

Trans. Vis. Sci. Tech.

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“…Physically PFCLs are characterized by specific gravity greater than water (ranging from 1.7–2.03 g/cm 3 );3 moderate interfacial tension (approximately 50 mN/m against water); and low viscosity, transparency, and immiscibility with water 4. Due to the aforementioned properties, PFCLs unfold and keep the detached retina flat, concurrently with the anterior displacement of the subretinal fluid, allowing to perform other surgical maneuvers, such as membrane removal or photocoagulation 5. Therefore, they are valid intraoperative tools for surgical treatment of complex retinal detachments (RDs), especially in the presence of severe proliferative vitreoretinopathy (PVR), giant retinal tears, funnel-shaped RDs, and proliferative diabetic retinopathy 5,6.…”

Section: Introductionmentioning

confidence: 99%

“…Due to the aforementioned properties, PFCLs unfold and keep the detached retina flat, concurrently with the anterior displacement of the subretinal fluid, allowing to perform other surgical maneuvers, such as membrane removal or photocoagulation 5. Therefore, they are valid intraoperative tools for surgical treatment of complex retinal detachments (RDs), especially in the presence of severe proliferative vitreoretinopathy (PVR), giant retinal tears, funnel-shaped RDs, and proliferative diabetic retinopathy 5,6. Moreover, PFCLs are used off-label for primary RDs, dropped lenses with or without RD, removal of foreign bodies, drainage of suprachoroidal hemorrhage, and management of submacular hemorrhage 6,7.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of Cytotoxicity of Perfluorocarbons for Intraocular Use by Cytotoxicity Test In Vitro in Cell Lines and Human Donor Retina Ex Vivo

Romano

Ferrara

Gatto³

et al. 2019

Trans. Vis. Sci. Tech.

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PurposeTo validate the cytotoxicity test of perfluorocarbon liquids (PFCLs) for intraocular use according to the ISO 10993-5 standard.MethodsBALB/3T3, ARPE-19 cell lines, and 3-mm human retina ex vivo samples were cultured in 96-well plates. Contact areas of 22%, 59%, and 83% and 2.5-, 12-, and 24-hour contact times were tested in cell lines. Cell viability was quantified by 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay in ARPE-19 and neutral red uptake (NRU) viability assay for BALB/3T3. Apoptosis was evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay in ARPE-19 cells. 1-H perfluorooctane (1H PFO) and purified perfluorooctane (PFO) were used as cytotoxic and not cytotoxic controls, respectively. Cell viability was assessed by MTT assay in retina ex vivo samples.ResultsQualitative evaluation showed that cytotoxic control induced apoptosis, severe reactivity zones, and cytotoxicity according to ISO 10993-5 in all tested conditions. Quantitative evaluation of 1H PFO showed no cytotoxicity according to ISO 10993-5 on 22% areas, whereas cytotoxicity was detected on 59%, and 83% contact areas. The PFO was confirmed not to be cytotoxic in all tested conditions. Quantitative evaluation in retina ex vivo samples confirmed no cytotoxicity with PFO and cytotoxicity with 1H PFO.ConclusionsThe direct contact cytotoxicity test according to ISO 10993-5 is a suitable method to detect the cytotoxicity of PFCLs and was validated using quantitative and qualitative approaches in ARPE-19 and BALB/3T3 cells covering 59% of the cell surface areas for 24 hours.Translational RelevanceDirect contact cytotoxicity test using specific conditions was validated, whereas different test conditions could not be validated.

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“…Further, despite successful application the ILM flap may be pushed out of the MH by the OVD. The effectiveness of sub-PFO injection of OVD depends on specific gravity of PFO, low viscosity property of PFO, and high interfacial tension between OVD and PFO [13]. The direction of OVD injection is just above the inverted ILM flap to cover it under PFO tamponade.…”

Section: Discussionmentioning

confidence: 99%

Sub-perfluoro-n-octane injection of ocular viscoelastic device assisted inverted internal limiting membrane flap for macular hole retinal detachment surgery: a novel technique

Lai

Chou

et al. 2020

BMC Ophthalmol

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Background: To evaluate the feasibility of a surgical technique using a sub-perfluoro-n-octane (PFO) injection of ocular viscoelastic device (OVD) to stabilize inverted internal limiting membrane (ILM) flap for the treatment of macular hole retinal detachment (MHRD). Methods: This study was a retrospective, consecutive, interventional case series. Patients who underwent MHRD surgery with sub-PFO injection of OVD to stabilize inverted ILM flap onto the macular hole (MH) were reviewed. The color fundus and optical coherence tomography (OCT) images were collected and evaluated. The bestcorrected visual acuity (BCVA) before and after surgery were compared as the functional outcome. Results: The study included 8 eyes of 8 consecutive patients (mean age: 61.8 ± 7.1 years; mean follow-up period: 9.0 ± 2.5 months). All eyes (100%) achieved successful MH closure; 7 eyes (87.5%) demonstrated complete retinal reattachment, and 1 eye (12.5%) had minimal residual subretinal fluid parafoveally. Of the 8 patients, 7 patients (87.5%) had achieved improvement in BCVA after the primary surgery, whereas 1 eye remained stable. The average BCVA before and after the surgery at the last visit improved from 20/843 (1.63 ± 0.48 logMAR) to 20/200 (1.00 ± 0.39 logMAR) (P = 0.016). Anatomically, near-normal foveal contour was noted in five (62.5%) eyes at the final follow-up. Conclusions: The use of sub-PFO injection of OVD in MHRD surgery could stabilize inverted ILM flaps, achieve good anatomical results and improve postoperative BCVA.

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In vitro experiment to elucidate the mechanism of the ‘soft shell technique’ for preventing subretinal migration of perfluoro-octane

Abstract: The interfacial tension between HA and PFO is higher than that between aqueous and PFO. This is a plausible physical explanation of how the 'soft shell' technique might work to prevent subretinal migration of PFCL.

Cited by 7 publications

References 21 publications

Toxicity Threshold of Perfluorocarbon Liquids for Intraocular Use: Dose–Response Assessment of In Vitro Cytotoxicity of Possible Contaminants

Toxicity Threshold of Perfluorocarbon Liquids for Intraocular Use: Dose–Response Assessment of In Vitro Cytotoxicity of Possible Contaminants

Evaluation of Cytotoxicity of Perfluorocarbons for Intraocular Use by Cytotoxicity Test In Vitro in Cell Lines and Human Donor Retina Ex Vivo

Sub-perfluoro-n-octane injection of ocular viscoelastic device assisted inverted internal limiting membrane flap for macular hole retinal detachment surgery: a novel technique

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