Pastor J Carlos, Coco Rosa M, Fernandez-Bueno Ivan, Alonso-Alonso Maria L, Medina Jesús, Sanz-Arranz Aurelio, Rull Fernando, Gayoso Manuel J, Dueñas Antonio, Garcia-Gutierrez Maria T, Gonzalez-Buendia Lucia, Delgado-Tirado Santiago, Abecia Emilio, Ruiz-Miguel Miguel, Serrano Miguel A, Ruiz-Moreno Jose M, Srivastava Girish K
*Institute of Applied Ophthalmobiology (IOBA), Eye Institute, University of Valladolid, Valladolid, Spain; †University Clinic Hospital of Valladolid, Valladolid, Spain; ‡Thematic Cooperative Health Network for Research in Ophthalmology (Oftared), Carlos III Health Institute, Madrid, Spain; §Crystallography and Mineralogy Department, University of Valladolid, Valladolid, Spain; ¶Cell Biology Department, University of Valladolid, Valladolid, Spain; **Toxicology Department, University of Valladolid, Valladolid, Spain; ††Vision I+D, Valladolid, Spain; ‡‡Miguel Servet Hospital, Zaragoza, Spain; §§Donostia Hospital, San Sebastian, Spain; ¶¶Canaries University Hospital, Canarias, Spain; ***Castille-La Mancha University, Albacete, Spain; and †††Regenerative Medicine Network and Cell Therapy Center, Valladolid, Spain.
Retina. 2017 Jun;37(6):1140-1151. doi: 10.1097/IAE.0000000000001680.
To describe a series of retinal acute toxicity cases with severe visual loss after intraocular use of a toxic perfluoro-octane (PFO). The clinical presentation is described, and the likely causes are analyzed. New biological methods for testing safety of intraocular medical devices are proposed.
Information regarding a series of eyes suffering acute severe events after intraocular use of a toxic PFO was analyzed. Four types of spectroscopy, nuclear magnetic resonance, and chromatography were used to identify the potential PFO contaminants. Cultures of human retinal pigment epithelial cells (ARPE-19) and porcine neuroretina were used to quantify the toxicity of the suspect PFO lots.
Of 117 cases of intraocular toxicity, 96 were considered clearly related to the use of PFO. Fifty-three cases had no light perception, and 97 had no measurable visual acuity. Retinal necrosis (n = 38) and vascular occlusion (n = 33) were the most characteristic findings. Two hydroxyl compounds, perfluorooctanoic acid and dodecafluoro-1-heptanol, and benzene derivatives were identified as the suspected toxic agents. While existing toxicity testing failed, we proposed new tests that demonstrated clear toxicity.
Protocols to determine cytotoxicity of intraocular medical devices should be revised to assure safety. Acute toxic events should be reported to health authorities and scientific media.
描述一系列眼内使用有毒全氟辛烷（PFO）后出现严重视力丧失的视网膜急性毒性病例。描述临床表现并分析可能的病因。提出用于测试眼内医疗器械安全性的新生物学方法。
分析一系列眼内使用有毒PFO后发生急性严重事件的眼部信息。使用四种光谱学、核磁共振和色谱法来识别潜在的PFO污染物。用人视网膜色素上皮细胞（ARPE-19）和猪神经视网膜培养物来量化可疑PFO批次的毒性。
在117例眼内毒性病例中，96例被认为与PFO的使用明显相关。53例无光感，97例视力无法测量。视网膜坏死（n = 38）和血管阻塞（n = 33）是最典型的表现。两种羟基化合物，全氟辛酸和十二氟-1-庚醇，以及苯衍生物被确定为可疑有毒物质。虽然现有的毒性测试失败了，但我们提出的新测试显示出明显的毒性。
应修订确定眼内医疗器械细胞毒性的方案以确保安全。急性毒性事件应报告给卫生当局和科学媒体。
