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Coronaviruses have been known to affect systems other than the respiratory tract, including gastrointestinal tract and ocular tissues. However, most of the research is focused on the respiratory tract due its life threatening nature. The fact that Coronaviruses can be present in other systems cannot be ignored since they can represent alternate modes of transmission.

In a review article by Ivan Seah and Rupesh Aggarwal, in Ocular Immunology and Inflammation, an attempt was made to identify ocular inflammations caused by coronaviruses in animals and humans. During the SARS-CoV outbreak in 2003, it was reported that a severe outbreak of SARS-CoV occurring at a housing estate in Hong Kong was likely transmitted through the sewage system. It has already been established that the SARS-CoV-2 can be shed through the oral/fecal route.

There have been reports from the previous Coronavirus epidemics about the ocular involvement. In 2004, towards the end of the SARS-CoV epidemic, a new Human Coronavirus was identified which was called HCoV-NL63. This was isolated from a seven month old child and later identified in seven other patients. The seven month old child had bronchiolitis and conjunctivitis. A case series was published in 2004, which highlighted the presence of SARS-CoV RNA in tears. In this series, out of a total of 36 suspected cases of SARS-CoV patients, the viral RNA was found in the tear samples of three patients by the RT-PCR method.

It is still unclear how SARS-CoV can end up in tears. Proposed theories about the mode of infection of the eyes are, direct inoculation of the conjunctiva with the virus from respiratory droplets, the migration of the upper respiratory tract infection through the nasolacrimal duct or even hematogenous infection of the lacrimal gland.

The other Coronaviruses have been known to cause ocular manifestations in cat and mice. The Feline Coronavirus (FCoV) is an alphacoronavirus that effects both domestic and wild cats. Five percent of the cats effected by FCoV develop Feline Infectious Peritonitis (FIP). The ocular manifestations of the FIP are likely due to underlying vasculitis resulting in inflammation of various ocular segments. Ninety percent of them had FCoV antigen in the conjunctiva. Viral isolates from conjunctival swabs also contained live FCoV, which suggest ocular tissues and secretions were potentially infectious as well. Apart from conjunctivitis, other ocular manifestations in cats include pyogranulomatous anterior uveitis, choroiditis with retinal detachment and retinal vasculitis.

In the present pandemic, there have been anecdotal reports of ocular infection by SARS-CoV-2. In January 2020 Guangfa Wang, a member of the National expert on Pneumonia, had developed conjunctivitis during an inspection of Wuhan, the epicenter of the outbreak. He subsequently tested positive for SARS-CoV-2. It has been reported that SARS-CoV-2 has a similar receptor binding motif as SARS-CoV which allows it to infect host cells via the Angiotensin-Converting-Enzyme-2 (ACE 2). The human eye has its own Renin Angiotensin System (RAS). This finding is of interest to people developing anti-glaucoma drugs. ACE 2 has been found in Aqueous Humor. However, the expression of ACE 2 in more anterior tissues such as Conjunctiva or Cornea has yet to be established.

In a study by Ping Wu et al, published in JAMA Ophthalmology, it was shown that out of 38 confirmed cases of COVID-19, admitted in a hospital in China, 12 (31.6%) had ocular manifestations. The manifestations consisted of conjunctival hyperemia, chemosis, epiphora, and increased secretions. None of them experienced blurred vision. It was also found that patients with ocular symptoms were more likely to have higher WBC and neutrophil counts and higher levels of procalcitonin, C-reactive protein and LDH than patients without ocular symptoms. 11 out of 12 patients with ocular symptoms had positive results for SARS-CoV-2 on RT-PCR from nasopharyngeal swabs. Of these, two (16.7%) had positive results for SARS-CoV-2 on RT-PCR from both conjunctival and nasopharyngeal swabs. Unprotected eyes were associated with increased risk of transmission of SARS-CoV-1. The above results could suggest that SARS-CoV-2 may be transmitted through the eyes.

But another prospective study, done at Singapore, on tear samples collected from patients with confirmed COVID-19, showed that risk of transmission of Coronavirus through tears was low. This study was published in Ophthalmology.

A recent study of thirty hospitals across China, published in New England Journal of Medicine, found conjunctival congestion in 9 of the 1099 patients (0.8%) with a confirmed diagnosis of COVID-19. Another study in the Journal of Medical Virology, of 30 hospitalized patients of COVID-19 had only one patient diagnosed with conjunctivitis. This patient had SARS-CoV-2 in there ocular secretions. So the incidence of conjunctivitis in COVID-19 patients is very low, as seen by these studies.

Recommendations of American Academy of Ophthalmology (AAO)

Recommendation regarding Contact Lens Use

The AAO recommends the use of glasses in place of contact lenses as a way to reduce the risk of contracting the SARS-CoV-2 virus through respiratory droplets. Contact Lens users tend to touch their eyes more often than those wearing glasses, which could enhance their risk of getting infected.

Recommended Protocols when Scheduling Patients

Reschedule appointments for patients with non-urgent ophthalmic problems, who have respiratory illness, fever or have returned from high risk areas of COVID-19 in past two weeks. For those who are scheduled for examination, inform the patients that both the patient and the doctor should avoid speaking during the slit lamp examination.

Recommended Protocols for Patients who have come to the Clinic

All such patients should be asked about respiratory symptoms (cough, runny nose), fever and sick contacts. If the answer to any of these questions is in the affirmative, then send the patient home and advise them to consult their primary care physician.

Recommendations for patients with Urgent Eye Conditions

Patients with urgent eye conditions like sudden loss of vision, recent onset of flashes of light or halos around lights and patients with physical or chemical injuries need to be examined even if they are suspected to be COVID-19 positive. Adequate Personal Protective Equipment (PPE) should be used by healthcare staff during examination. The patient should wear a facemask and should be isolated in the examination room with the doors closed. Rooms should be thoroughly disinfected afterwards. The PPE to be used by the staff includes gloves, gowns, respiratory protection (N95 mask if possible) and eye protection. Preferably, COVID-19 suspects or COVID-19 patients, with urgent ophthalmic problems, should be sent to the ER or other hospital based facility equipped to evaluate for, and manage, COVID-19. That hospital should have an Ophthalmic set up where the eye problem can be addressed.

Recommendations for disinfection

The SARS-Cov-2 is very likely susceptible to the same alcohol and bleach based disinfectants that ophthalmologists commonly use to disinfect ophthalmic instruments and office furniture. To prevent SARS-CoV-2 transmission, the disinfection practices already in use to prevent office based spread for other viral pathogens, are recommended before and after every patient encounter. The use of commercially available slit-lamp barriers or breath shields is recommended.

The tonometer tips cleaned with 70% alcohol solutions and allowed to dry, are adequate for protection against SARS-CoV-2, but not against adenoviruses (the more common viruses in ophthalmic practices). Ideally single use, disposable tonometer tips should be used, if possible. Tips cleaned with diluted bleach remain a safe and acceptable practice.

Slit lamps, including controls and accompanying breath shields, should be disinfected, particularly wherever patients put their hands and face. The current CDC recommendations for disinfectants specific to COVID 19 include:

1. Diluted Household bleach (5 tablespoons bleach per gallon of water).
2. Alcohol solutions with at least 70% alcohol
3. Common EPA (Environmental Protection Agency) registered household disinfectants. Currently recommended for use against SARS-CoV-2 include Clorox, Lysol and Purell brand products.

In conclusion, eyes need to be protected during examination of confirmed COVID-19 patients and PUI (Persons under investigation) because eyes could be a portal of entry for the virus into the body. Conjunctivitis is not a very common manifestation of COVID-19 patients. There is still debate regarding spread of virus via the ocular secretions. As with every other aspect of the Novel Coronavirus disease, more research needs to be done which shall reveal more information in the times to come.

References:

1. Ping Wu, Fang Duan, Chunhua Leo, et al, Characterstics of Ocular findings of Patients with Coronavirus 2019 (COVID-19) in Hubei Provice, China. JAMA Ophthalmol. Published March 31, 2020
2. Ivan Seah, Rupesh Aggarwal. Can the Coronavirus (COVID-19) effect the eyes? A Review of Coronaviruses and Ocular implications in Humans and Animals. Ocular Immunology and Inflammation 2020. Published online 2020 March 16.
3. Jianhua Xia, Jianping Tong, Mengyun Liu, Ye Shen, Dongyu Guo. Evaluation of Coronavirus in Tears and Conjunctival Secretions of Patient with SARS-CoV-2 Infection. Journal of Medical Virology. Published 26th February 2020.
4. Loon S-C, Teoh SCB, Oon LLE, et al. The severe acute respiratory syndrome coronavirus in tears. British J Ophthalmol. 2004;88(7):861–863. doi:10.1136/bjo.2003.035931.
5. Yeo C, Kaushal S, Yeo D. Enteric involvement of coronaviruses: is faecal & oral transmission of SARS-CoV-2 possible? Lancet Gastroenterol Hepatol. 2020. epub ahead of print. doi:10.1016/S2468-1253(20)30048-0.
6. Hung LS. The SARS epidemic in Hong Kong: what lessons have we learned? J R Soc Med. 2003;96(8):374–378. doi:10.1177/014107680309600803
7. Van der Hoek L, Pyrc K, Jebbink MF, et al. Identification of a new human coronavirus. Nat Med. 2004;10(4):368–373. doi:10.1038/nm1024
8. Pedersen NC, Boyle JF, Floyd K, Fudge A, Barker J. An enteric coronavirus infection of cats and its relationship to feline infectious peritonitis. Am J Vet Res. 1981;42:368–377.
9. Chang HW, Egberink HF, Rottier PJ. Sequence analysis of feline coronaviruses and the circulating virulent/avirulent theory. Emerg Infect Dis. 2011;17(4):744–746. doi:10.3201/eid1704.102027
10. Doherty MJ. Ocular manifestations of feline infectious peritonitis. J Am Vet Med Assoc. 1971;159:417–424.