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Pastor, J. Carlos MD, PhD*,†,‡; Coco, Rosa M. MD, PhD*,‡; Fernandez-Bueno, Ivan BVSc, PhD*,‡; Alonso-Alonso, Maria L. BVSc, MSc*; Medina, Jesús PhD§; Sanz-Arranz, Aurelio MSCheE§; Rull, Fernando PhD§; Gayoso, Manuel J. MD, PhD; Dueñas, Antonio MD, PhD*,**; Garcia-Gutierrez, Maria T. CLT*,††; Gonzalez-Buendia, Lucia MD, MSc*; Delgado-Tirado, Santiago MD, MSc*,†; Abecia, Emilio MD, PhD‡,‡‡; Ruiz-Miguel, Miguel MD‡,§§; Serrano, Miguel A. MD, PhD¶¶; Ruiz-Moreno, Jose M. MD, PhD‡,***; Srivastava, Girish K. PhD*,†††

doi: 10.1097/IAE.0000000000001680
Original Study

Purpose: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Inadequate cytotoxicity testing accepted by European Union (EU) and International Organization for Standardization (ISO) standards for perfluoro-octane used in intraocular surgery resulted in 117 cases of acute intraocular toxicity and severe loss of visual function. Clinical findings and an alternative method to determine cytotoxicity are described.

*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.

Reprint requests: J. Carlos Pastor, MD, PhD, Institute of Applied Ophthalmobiology (IOBA), Eye Institute, University of Valladolid, 47011, Valladolid, Spain; e-mail:

Several authors G. K. Srivastava, M. L. Alonso-Alonso, I. Fernandez-Bueno, M. T. Garcia-Gutierrez, R. M. Coco, J. Carlos Pastor are included in the patent derived from this study. The remaining authors has no financial/conflicting interests to disclose.

© 2017 by Ophthalmic Communications Society, Inc.