Ebola Virus Persists in Eyes Months After Clearing Blood

Diana Swift

May 07, 2015

Viable Ebola virus was present in the aqueous humor of a survivor 14 weeks after onset of Ebola virus disease (EVD) and 10 weeks after the clearance of viremia, researchers reported today in a plenary session at the 2015 Association for Research in Vision and Ophthalmology meeting in Denver, Colorado.

The case report was based on the experience of Ebola survivor Ian Crozier, MD, an American infectious disease specialist mentoring in HIV management at the Infectious Diseases Institute, Mulago Hospital Complex, Kampala, Uganda, and four physicians who subsequently treated him for severe unilateral uveitis at Emory University Eye Hospital in Atlanta, Georgia.

The case also was published online May 7 as a Brief Report in the New England Journal of Medicine.

As far back as the 1995 Ebola outbreak in Kikwit, Democratic Republic of the Congo, African clinicians reported ocular manifestations in survivors who had been asymptomatic for a month. These included pain, photophobia, hyperlacrimation, and loss of visual acuity.

Ocular Symptoms Appeared After Discharge

Three weeks after joining the international effort against Ebola in Sierra Leone in August 2014, Dr Crozier, 43, contracted EVD, and in September he was evacuated to Emory University Hospital in critical condition with multiple organ failure.

Shortly after discharge from hospital, Dr Crozier developed ocular symptoms — bilateral burning, foreign body sensation, and photophobia — and had to have his reading glasses changed. He also had lower back pain and distal lower-limb paresthesias.

Although several eye tests were normal, examination of the dilated posterior eye revealed multiple peripheral chorioretinal scars with hyperpigmented halos in both eyes and a small intraretinal hemorrhage near a scar in his left eye. The diagnosis was posterior uveitis (chorioretinitis), a likely sequela of EVD. Ten weeks after symptom onset, his blood and urine were negative for Ebola virus by quantitative reverse transcriptase-polymerase chain reaction in serial tests, and he was discharged from the hospital.

A month later, 14 weeks after his EVD diagnosis, Dr Crozier presented with acute-onset redness and blurred vision, with halos, pain, and photophobia in the left eye, with a highly elevated intraocular pressure of 44 mm Hg (normal = 1 - 21 mm Hg). He had conjunctival injection, mild corneal edema, rare nongranulomatous keratic precipitates, and grade 1+ leucocytes plus protein flare in the anterior chamber.

Although treated with prednisone eye drops and ocular hypotensive agents, the inflammation escalated, and therapy was upregulated. As the inflammation continued to progress, physicians performed paracentesis of the anterior chamber, and the aqueous humor extracted tested positive for Ebola virus (EBOV) RNA. Encouragingly, both a preprocedure conjunctival swab and a peripheral blood specimen tested negative for EBOV RNA.

When uveitis continued to progress 5 days after symptom onset and visual acuity decreased to 20/60 with evidence of scleritis and intermediate uveitis on the posterior segment, oral prednisone was added to the ocular regimen. During the next 72 hours, the scleritis resolved and the anterior uveitis decreased. Three months after uveitis onset, Dr Crozier's left eye visual acuity had recovered to 20/15. He continues to undergo ophthalmic evaluation.

"Although the pathogenesis of EVD-associated uveitis is unknown, we believe that the severe, acute panuveitis that developed in our patient was a direct cytopathic effect of active EBOV persisting in an immune-privileged organ," write investigators led by Jay B. Varkey, MD, from Emory's Division of Infectious Disease. The authors note that the cluster of symptoms (acute onset, unilateral location, and extreme elevation of intraocular pressure) resembles that of uveitis caused by the herpes virus, in which the pathogenesis is a direct consequence of viral replication.

Uveitis Incidence in Survivors Unknown

After the 1995 outbreak in the Democratic Republic of the Congo, 20 survivors were enrolled in a retrospective study that found evidence of uveitis 42 to 72 days after onset of EVD. Data on ocular complications in the recent West African outbreak remain limited. In one survey of survivors, 40% of 85 respondents reported eye problems; however, the actual incidence of uveitis in this cohort is unknown.

Eye problems can be common after infections, "since the eye is a site that is not as aware of what's happening in the rest of the body," William F. Mieler, MD, a professor of ophthalmology at the University of Illinois at Chicago, told Medscape Medical News. Similar to other immune-privileged sites such as the testicles and placenta, the eyes can tolerate the introduction of antigens without the eliciting of an immune response.

"Right now there's really no prophylactic treatment for eye disease related to Ebola other than being aware that this scenario is a potential consequence and monitoring carefully, especially for eye pressure," continued Dr Mieler, ARVO's outgoing president. "This is the first report of definitive eye problems after Ebola, and with the disease having such a high mortality rate, so far the focus has been on keeping patients supported and alive."

This case highlights an important complication of EVD, with major implications for individual and public health that are immediately relevant to the ongoing West African outbreak, the authors note. They stress the need for further studies to determine persistence and pathogenic mechanisms and develop strategies for managing EVD complications.

According to coauthor Steven Yeh, MD, an ophthalmologist at Emory Eye Center, the presence of viable virus in Dr Crozier's eye could mean that other Ebola survivors may also be at risk for uveitis. "The thousands of Ebola survivors in West Africa and health care workers in their home countries will need to be monitored for eye disease in the post-Ebola period," he said in an ARVO media release.

This report was supported by grants from the National Center for Advancing Translational Sciences, Research to Prevent Blindness, the National Eye Institute, and the Australian Research Council. Dr Yeh reported receiving personal fees from industry unrelated to the current report. The other authors have disclosed no relevant financial relationships.

N Engl J Med. Published online May 7, 2015. Full text


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