COVID Through the Eye? Time Will Tell

Current information shows eye as an uncommon site of pathology.

CHERYL GUTTMAN KRADER REPORTS

Although SARS-CoV-2 RNA has been detected in tear and conjunctival samples from patients with COVID-19, ocular findings in patients with the virus are uncommon, showing it unlikely the eye is a portal for the infection, current research indicates.

“We do not see a lot of eye disease in patients with COVID-19. However, ophthalmologists do not see many patients at the time of acute illness,” noted Uri S Soiberman MD.

“It is very possible that COVID-19 could cause conjunctivitis, and eye disease is more prevalent in severely ill patients. Perhaps SARS-CoV-2 also causes secondary inflammation in the eye or very late-onset disease. These are unanswered questions. Only time will tell.”

The lack of relevant studies with large numbers of patients has hampered a better understanding of the potential for SARS-CoV-2 to cause eye disease. An early paper from China reported 12 of 38 patients hospitalised for COVID-19 had conjunctivitis.

“Most likely, however, the patients had chemosis only, which is something expected in severely ill patients,” Dr Soiberman said.

One paper reviewing 500 patients admitted to the hospital for COVID-19 pneumonia found that fewer than 10% had ocular surface signs or symptoms. Based on findings from a literature review of 28 papers, conjunctivitis appears to be the most common COVID-19-related eye disease, but its prevalence is likely below 5%, Dr Soiberman said.

The eye as an entry point

Discussing literature addressing whether the eye is a portal for SARS-CoV-2 infection, Dr Soiberman noted some conflicting information from studies investigating the presence of viral RNA in ocular surface cells.

An early case report from the Wilmer Eye Institute (Johns Hopkins University, Baltimore, Maryland, US) showed SARSCo-V-2 detected by real-time polymerase chain reaction (RTPCR) in ocular surface swabs from a patient with COVID-19, while a large study from another institution found ocular surface specimens from patients who died of COVID-19 tested positive for the virus. The latter group also showed SARSCoV-2 could infect cultured human embryonal stem cell-derived ocular epithelium, suggesting the ocular surface could be a portal for viral entry.

However, another group reported negative RT-PCR virus testing in a series of postmortem eyes of patients who died from COVID-19, and researchers using RT-PCR to test tear and conjunctival secretions in patients with confirmed COVID-19 pneumonia reported a positive result in only about 3% of cases.

An early study conducted in China, Dr Soiberman said, showed a lower proportion of inpatients with confirmed COVID-19 wore eyeglasses daily for more than eight hours compared to the general population, suggesting the eye could be a portal of viral entry. In addition, studies show ocular surface cells express the surface receptors necessary for SARSCoV-2 binding and internalisation.

Stronger evidence for SARS-CoV-2 possibly infecting human conjunctiva comes from a study where researchers transduced fresh conjunctival tissue from healthy patients with the virus in an ex vivo model. After 48 hours, the fixed specimens stained positive for the SARS-CoV-2 nucleoprotein.

“Although this finding suggests the eye is a portal, the staining was mainly in the deeper layer of the conjunctiva versus in the superficial layer, as we might expect. In addition, the increase in COVID-19 transcript 48 hours after transfection was not that dramatic,” said Dr Soiberman.

“Furthermore, some animal studies suggest the conjunctiva is not the site of penetration into the body. Instead, the entry occurs through autoinoculation from the conjunctiva to the respiratory mucosa.”

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