Sep 21, 2017 | Updated: 09:54 AM EDT

Can Ebola Stay Hidden in the Orbits of the Eye?

May 16, 2015 06:54 PM EDT

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Dr. Ian Crozier fought Ebola for his life for an extended period of time at Emory University Hospital until, in October, the lengthy, bloody battle seemed to have ended with him the victor. But not even two months later searing pressure and pain in his left eye and failing sight landed him back in the hospital. His terrifying discovery? The Ebola virus was thriving inside his eye.

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Naturally, his medical team realized there could be a connection to his recent bout with Ebola, but these results were yet surprising. Crozier's blood was free of the virus when he left the hospital. Experts know that the virus may remain in semen for some months after it disappears from the blood, but previous to this case they had no information about the ability of the Ebola virus to live on inside the eyeball.

Thankfully, the surface of Crozier's eye and his tears were free of the virus; casual contact with him posed no threat to others.

"I want to emphasize that as far as we know, the Ebola virus is not transmitted by casual contact," the American Academy of Ophthalmology said in a statement. "The current study does not suggest that infection can be transmitted through contact with tears or the ocular surface of patients who have recovered from their initial infection."

Dr. Crozier fell sick while working as a volunteer for the World Health Organization (WHO) in a Sierra Leone Ebola treatment ward during the period when the virus seemed to be engulfing West Africa. A year after the crisis began, the medical community is still searching for answers to questions about longterm effects of exposure to the virus in survivors, and the progression of the disease. In the past doctors had far less Information about the virus and its after effects-ironically because outbreaks had been better controlled with fewer people infected and even fewer survivors due to high death rates. Now the scientific community has thousands of survivors to work with, and medical professionals are detecting new patterns.

Dr. Crozier's eye problems were caused by uveitis, a serious inflammation inside the eye. This is a problem which has been found in other survivors, and because it threatens sight it has been a priority for doctors. Dr. Daniel Bausch, a Tulane University infectious-disease specialist who consults for WHO, notes the new efforts on the organization's behalf to investigate eye trouble caused by Ebola.

"It's a major thing we need to study and provide support for," Bausch says. Extra support is badly needed, because only ophthalmologists, rare in West Africa, can diagnose conditions inside the eye like uveitis.

Dr. John Fankhauser works with survivors in Liberia and explains that eye trouble along with headaches and eye trouble are among the most common aftereffects seen among Ebola survivors. About 40 percent of survivors have blind spots in their visual fields, blurred vision, eye pain, and inflammation, including uveitis. Most will need care for months or years.

"We're seeing symptoms in patients who've been out of the treatment unit for up to nine months," Fankhauser says. "They're still very severe and impacting their life every day."

Dr. Fankhauser hopes that more members of the medical community will temporarily get involved in their care, in particular ophthalmologists, rheumatologists, and specialists in rehabilitation medicine.

"If they see enough patients, they can help us with the trends of what they are seeing, and that may help direct some of our therapy in the future, even after the team's gone."

When Dr. Crozier first started to experience problems with his eye, he and his team assumed that another virus may have opportunistically invaded the eye after his immune system was weakened. Wanting to treat him for the viral infection, his ophthalmologist, Dr. Steven Yeh, drew a few drops of his ocular fluid for analysis. The results were shocking to the team, and to Crozier.

Dr. Yeh wore protective gear when taking the sample, but as an extra measure of safety he avoided touching his infant son and slept in his home's guest room for three weeks, the time the virus needs to incubate and manifest symptoms. And once the results came back, a team from Emory hurried to disinfect every surface in the examination room.

The delicate interior of the eye is protected well from the immune system; this is important to preventing inflammation-a common autoimmune response-that can damage vision. This immune privilege is formed by minute blood vessels filled with tightly packed cells that exclude certain molecules and cells that inhibit the immune response. But this same set of protections can sometimes allow viruses to replicate unhampered in the inner eye. Similarly, the virus can persist in semen for months because the testes are immune-privileged.

The medical team was concerned about being able to save Dr. Crozier's sight. Spreading to the other eye was a risk. And the team had no proven antiviral treatment against Ebola, not to mention an utter lack of precedent for use of this kind of agent inside the eye. There was the additional problem of parsing out the actual cause of damage in Crozier's eye: was it the inflammation, the virus, or both together?

Doctors typically treat inflammation with steroids, but these kinds of drugs can worsen infections. Still, as Dr. Crozier's vision failed, the team had to make the best guesses they could.

"What if it unleashed the virus?" Crozier says. "We were on a tightrope."

The team tried high dose prednisone, a steroid, to reduce the inflammation, without success. The eye lost its pressure and seemed to be turning to mush. His once perfect vision deteriorated to 20/400. And only days later, Dr. Crozier was shocked to see that his formerly blue left eye had turned bright green.

Fearing that he was running out of time, Dr. Crozier tried an experimental antiviral drug. It was orally administered, and doctors were unsure it would hit its mark. Crozier also received more steroids, this time in injection form just above the eyeball. Finally, about one week later, Crozier started to regain his sight. Over the course of several months his eye regained its old color and his sight returned.

Dr. Jay Varkey, an infectious-disease specialist on Dr. Crozier's case, believes that the treatments lessened Crozier's symptoms just enough to enable his immune system to fight the virus. "I think the cure was Ian's own immune system," Varkey says.

Dr. Crozier hopes and believes that his case may help prevent blindness in the many West African Ebola survivors. On April 9 Crozier, Dr. Yeh, and a team from Emory traveled to Liberia to examine the eyes of Ebola survivors.

"Maybe we can change the natural history of the disease for survivors," Crozier says. "I want to start that conversation."

The Emory team emphasizes the importance of the findings for a public health approach to Ebola outbreaks-and survivors.

"This case highlights an important complication of Ebola virus disease with major implications for both individual and public health that are immediately relevant to the ongoing West African outbreak," Varkey says.

Since the outbreak in late 2013, the West African outbreak infected more than 26,000 and killed more than 11,000 of them. Researchers are still working to fully understand the disease and its impact. One study has indicated that Ebola may even become airborne in some circumstances.

"There was almost a rush to ensure the public that we knew a lot more than we did," said Michael T. Osterholm, author of the work on Ebola possibly becoming airborne, and a University of Minnesota epidemiologist. "But we're saying you can't rule out respiratory transmission."

The report on the incident surrounding Crozier's eye, "Persistence of Ebola Virus in Ocular Fluid During Convalescence," was published this week in The New England Journal of Medicine.

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