January 2009




CJD found in four corneal transplant cases

by Vanessa Caceres EyeWorld Contributing Editor



Study does not identify graft as CJD cause

Scanning electron micrograph of a Teflon block used several times for punching donor corneas; disposable instruments and careful sterilization are highly recommended to avoid contamination Source: William Trattler, M.D.

A set of disposable instruments for donor eye retrieval Source: William Trattler, M.D.

Even with strict screening measures in place at donor banks, sporadic Creutzfeldt-Jakob disease (CJD) is likely to occur in corneal transplant patients once every 1.5 years, a new study reports. Still, that doesn’t necessarily mean that the donor cornea is the cause of CJD.

The study was led by Ryan A. Maddox, M.P.H., Centers for Disease Control and Prevention, Atlanta, and published in the August 2008 issue of Cornea.

Investigators analyzed eye bank documents and genetic and neuropathologic tests of CJD cases. They also did a statistical analysis to calculate the expected number of coincidental CJD cases in U.S. corneal transplant patients. As it is now, one case of CJD occurs annually in the United States per million people. Between 1990 and 2006, 34,145 corneal transplants were performed each year in the United States, the investigators reported. Only six cases of corneal transplant-associated CJD have been reported in the past, including one with a definite link and one with a probable link, the investigators wrote.

Sizing up cases

The investigators’ analysis identified four additional cases of sporadic CJD in corneal transplant patients and described the patients’ conditions.

All four cases involved patients over the age of 55, with an age range of 56 to 67 years. (CJD usually occurs in older patients, the investigators wrote.) CJD manifested in these patients nearly three years to 18 months after corneal transplantation. All but one case occurred in the United States.

One case involved a 67-year-old man who traveled frequently to Europe. He had declining neurological symptoms, cognitive impairment, and forgetfulness, and he eventually became mute and could not walk. An abnormal electroencephalogram (EEG) was consistent with encephalopathy, or CJD. A prion protein gene sequencing showed his disease as consistent with sporadic CJD type VV2. There were no signs of a genetic form of CJD. The man died after a five-month bout with his declining symptoms.

When possible, investigators took a close look at the medical history of all cornea donors.

In this case, the patient had received two corneas from two separate donors for his macula edema and glaucoma nine and 11 years before the onset of CJD. The first cornea donor was a 44-year-old man who died of myocardial infarction and respiratory failure; there was no evidence of prion disease in his eye bank records. The second donor was a 16-year-old boy who had died in a car accident. He did not have any evidence of neurologic disease or dysfunction.

Another sample case from the four studied by the investigators is that of a 56-year-old man who became forgetful and depressed. He quit his job because he could not remember details, and he was diagnosed with a transient ischemic attack and monocular vision loss. Within a year’s time, his gait became slower, and he had significant language problems. The patient eventually had hallucinations and delusions. An MRI and EEG showed results suggestive of a CJD diagnosis. The patient died after a three-year bout with his illness. Analysis of autopsy brain tissue later confirmed sporadic CJD type MV2 and discounted the possibility of any family history of CJD.

The patient had received a corneal transplant in his right eye 18 years before the onset of his symptoms. The donor was a 17-year-old boy who had committed suicide.

The other two cases involved a 59-year-old woman from Japan and a 66-year-old man. No neurologic disease or family history of CJD was found in their cornea donors, although one of the donors had traveled to France, Ireland, and Germany.

“Although the four patients in this report had a diagnosis of CJD, three of which were confirmed by autopsy, it is unlikely that their CJD deaths were related to corneal transplantations,” the investigators wrote.


The Eye Bank Association of America has guidelines in place to screen out potential donors with CJD. Their guidelines specify that tissue from patients with CJD, variant CJD, or even those who have family members with CJD should not be used for corneal transplantation. Any tissue from donors with CJD requires special handling at the eye bank, the guidelines state.

Still, even with the eye bank guidelines and hospitals’ screening measures to avoid a CJD threat, some cases will likely occur in corneal transplant patients, the study concluded. Considering that the study only identified four cases but their statistical analysis shows a probability of 11 CJD cases associated with corneal transplants in the United States right now, “There are probably additional unidentified CJD cases among corneal transplant recipients that have occurred in the United States,” investigators wrote.

“We found that a coincidental case of CJD would be expected in the U.S. corneal transplant recipient population approximately once every 1.5 years,” Mr. Maddox said.

Some recent reports related to CJD raise interesting questions about the disease’s onset, said study co-investigator Michael D. Geschwind, M.D., Ph.D., assistant professor, Department of Neurology, University of California, San Francisco Medical Center, San Francisco. For example, he cited a report within the past year in Lancet that showed that CJD can have an incubation period of more than 50 years. “There may be many more cases of CJD in whom it just has not been documented in the records that they had a corneal transplant in the past. This article highlights the need to continue to look for possible causes of sporadic CJD,” Dr. Geschwind said. “It also highlights the need to question CJD patients about all potential risks—all surgeries, exposures, travel histories, etc.”

The threat of CJD may raise future questions if it is shown that the variant form, mad cow disease, can have a second presentation with a long incubation period in humans, said Randall J. Olson, M.D., professor and chairman, John A. Moran Eye Center, University of Utah School of Medicine, Salt Lake City. Investigators should also continue to analyze the spread of a form of CJD associated with elk and deer wasting disease and whether it is transmissible to humans, as well as the impact of instrument contamination when operating on a CJD patient, Dr. Olson added.

Editors’ note: Drs. Maddox, Gerschwind, and Olson have no financial interests related to their comments.

Contact information

Gerschwind: 415-476-6880, mgerschwind@memory.ucsf.edu
Maddox: 404-639-1170, rmaddox@cdc.gov
Olson: 801-581-2352, randall.olson@hsc.utah.edu

CJD found in four corneal transplant cases CJD found in four corneal transplant cases
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