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Ebola Virus Lives in Eye Long After Blood Clears

— 'Cured' in October, back in hospital in December

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A few months after he was declared Ebola-free, Ian Crozier, MD, developed uveitis in his left eye, and the cause was a reservoir of Zaire ebolavirus (EBOV) in that eye.

, of the Emory University School of Medicine, and colleagues, reported the finding in .

Crozier also shared his story with reporter Denise Grady. In the NYT article, he said the infection did not respond to prednisone but did resolve after he received an experimental antiviral drug combined with a prednisone injection.

Fluid extracted from the aqueous humor tested positive for EBOV RNA on quantitative reverse-transcriptase-polymerase-chain reaction (RT-PCR) assay with a threshold value of 18.7 -- a "high burden of viable EBOV," Varkey wrote.

When compared with blood samples taken when Crozier was hospitalized at Emory in September, the EBOV RNA had several mutations of "unknown" significance, they wrote in .

However, quantitative RT-PCR assays on specimens collected before and 24 hours after the aqueous humor sample was taken were negative for EBOV RNA. Similar tests performed on patient blood samples also tested negative.

Crozier began developing ophthalmic symptoms shortly after he was discharged from the hospital, including "ocular burning, foreign body sensation, and photophobia."

Doctors noted several chorioretinal scars and a small intraretinal hemorrhage consistent with posterior uveitis due to ebola virus disease (EVD). One month later, his symptoms had worsened, with "an acute onset of redness, blurred vision with halos, pain, and photophobia." Results of laboratory testing came back negative for Toxoplasma gondii, but his symptoms continued to worsen, even after 48 hours of treatment. Doctors then suspected the inflammation may be due to an infection.

They ascribed Crozier's symptoms to "active viral replication," similar to that of another infectious disease. "The acute onset of symptoms, unilateral location and extreme elevation of intraocular pressure that were seen in our patient are clinical findings similar to infectious uveitis syndromes caused by herpesvirus," they wrote.

The authors comment that they have observed ophthalmic symptoms in EVD patients before -- where EBOV RNA was detected on a RT-PCR assay of a 25-year-old patient who had recovered from the disease during a previous EVD outbreak.

"We believe that the severe, acute panuveitis was a direct cytopathic effect of active replication of EBOV persisting in an immune-privileged organ," they wrote. They suggest that further research is needed about the potential presence of EBOV in other immune-privileged sites, such as the central nervous system, gonads and articular cartilage.

But they also note that scant research has been done on post-EVD ocular complications. One retrospective study of 20 EVD survivors from the 1995 outbreak They also cite

"Further studies are needed to assess the persistence of EBOV during convalescence, to elucidate the mechanisms underlying this persistence in ocular and other immune-privileged tissue sites, and to develop strategies for the clinical management of EVD complications," the authors concluded.

Disclosures

The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the CDC.

Supported by a grant from the National Institutes of Health, an unrestricted grant from Research to Prevent Blindness, a grant from the National Eye Institute and a fellowship grant from the Australian Research Council.

Disclosure forms provided by the authors are available with the full text of this article at NEJM.org

Primary Source

The New England Journal of Medicine

Varkey JB, et al "Persistance of Ebola virus in ocular fluid during convalescence" N Engl J Med 2015; DOI: 10.1056/NEJMoa.1500306