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Rapid Testing for Creutzfeldt-Jakob Disease in Donors of Cornea

Gregori, Luisa PhD; Serer, Arthur R. MS; McDowell, Kristy L. PhD; Cervenak, Juraj MD; Asher, David M. MD

doi: 10.1097/TP.0000000000001636
Original Basic Science—General

Background Creutzfeldt-Jakob disease (CJD) has been accidentally transmitted by contaminated corneal transplants. Eye donors are not ordinarily tested for CJD, in part because an easy test is not available. We propose a relatively simple postmortem procedure to collect brain samples without performing full autopsy and show that a test currently marketed for veterinary diagnosis would offer an effective screening test.

Methods We selected 6 brains from confirmed cases of human sporadic CJD and sampled each in triplicate (18 specimens), 28 control brains of individuals with non-CJD neurodegenerative diseases and 10 normal brains. We also applied a procedure involving retro-orbital puncture after enucleation and biopsied the frontal lobes and optic nerves of a macaque experimentally infected with variant CJD. All samples were tested with the IDEXX HerdChek BSE-Scrapie Ag Kit to detect the abnormal prion protein, PrPTSE.

Results The test discriminated between control and CJD-infected brains. All 18 infected brain samples diluted to 0.1%, except one, showed signals above cutoff, and a number of samples were reactive at even higher dilutions. These results suggest the test could detect the low concentrations of PrPTSE probably present in brains of donors at early stages of CJD. Our collection procedure obtained sufficient macaque brain and optic nerve tissues to detect PrPTSE.

Conclusions We showed that a commercial test combined with rapid sample collection might offer a practical solution to screen brains of cornea donors for evidence of CJD. Such a test might enhance safety of corneal transplants and some other tissue-derived products.

Eye donors are not ordinarily tested for Creutzfeldt-Jakob disease (CJD) because of difficulties of examination. The authors propose a simple postmortem collection of brain samples without performing full autopsy, which offers effective screening test for CJD. Supplemental digital content is available in the text.

1 Division of Emerging and Transfusion-Transmitted Diseases, Laboratory of Bacterial and Transmissible Spongiform Encephalopathy Agents, Center for Biologics Evaluation and Research, Office of Blood Research and Review, U.S. Food and Drug Administration, New Hampshire Avenue, Silver Spring, MD.

Received 20 October 2016. Revision received 9 December 2016.

Accepted 11 December 2016.

This work was funded by the U.S. Food and Drug Administration.

The authors declare no conflicts of interest.

L.G. designed the study, supervised the research, prepared and formatted figures and wrote the article. A.S. conducted the research, prepared figures and participated in the writing and reviewed the article. K.L.M. conducted early studies with IDEXX test that led to the work submitted; prepared figures and reviewed the article. J.C. conducted the macaque necropsy, removed tissues for testing and reviewed the article. D.M.A. designed the study, contributed to the writing, reviewed and edited the article.

Correspondence: Dr. Luisa Gregori, 10903 New Hampshire Avenue, FDA Building 52/72, Room 4336, Silver Spring, MD 20993. (

Supplemental digital content (SDC) is available for this article. Direct URL citations appear in the printed text, and links to the digital files are provided in the HTML text of this article on the journal’s Web site (

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