• CDC, WHO
    Comprehensive Ophthalmology

    For complete coverage of the COVID-19 pandemic, visit the Academy's resource page Coronavirus and Eye Care.

    The Academy is sharing important ophthalmology-specific information related to the novel coronavirus, referred to as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The highly contagious virus can cause a severe respiratory disease known as COVID-19. 

    This page is principally authored by James Chodosh, MD, MPH, with assistance from Gary N. Holland, MD, and Steven Yeh, MD.

    What you need to know

    • Published reports suggest that SARS-CoV-2 can cause a mild follicular conjunctivitis otherwise indistinguishable from other viral causes, and possibly be transmitted by aerosol contact with conjunctiva. However, at this point in the COVID-19 pandemic, practically any patient seen by an ophthalmologist could be infected with SARS-CoV-2, regardless of presenting diagnosis, risk factors, indication for visit or geographic location.
    • SARS-CoV-2 is 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 same disinfection practices already used to prevent office-based spread of other viral pathogens are recommended before and after every patient encounter.
    • The Academy and federal officials strongly recommend protection for the mouth, nose and eyes when caring for patients potentially infected with SARS-CoV-2.

    Background

    SARS-CoV-2 is an enveloped, single-stranded RNA virus that causes COVID-19. It is highly transmissible and has a significant fatality rate, especially in the elderly and those with comorbidities such as immune suppression, respiratory disease and diabetes mellitus. A significant number of global fatalities have occurred, and the impact is being felt worldwide.

    Symptoms of COVID-19 typically appear within 2 to 14 days after exposure to the virus. As recently reported by the CDC, these may include cough and shortness of breath (or difficulty breathing), or at least 2 of the following: fever, chills, repeated shaking chills, muscle pain, headache, sore throat and new-onset loss of taste or smell. Elderly patients may show only lethargy and confusion. Anecdotes suggest that diarrhea is common early in infection; conjunctivitis and severe eye pain have also been reported. Complications in severe cases include pneumonia, renal failure, cardiomyopathy, stroke and encephalopathy. A March 10 study in the Annals of Internal Medicine found that the mean incubation period for SARS-CoV-2 was 5 to 7 days, and patients were typically infectious for several days prior to symptom onset. More than 97% of those who developed symptoms did so within 11.5 days of exposure, findings that further support current 14-day quarantine recommendations. Recently, SARS-CoV-2 infection in children was associated with a severe multi-system inflammatory syndromewith features that overlap with Kawasaki disease and toxic shock syndrome.

    Transmission

    Current understanding about how COVID-19 spreads is based largely on what is known about other similar coronaviruses. The virus is believed to spread primarily via person-to-person through respiratory droplets produced when an infected person coughs or sneezes. It also could be spread if people touch an object or surface with virus present from an infected person, and then touch their mouth, nose or eyes. Viral RNA has also been found in stool samples from infected patients, raising the possibility of transmission through the fecal/oral route.

    Existing evidence suggests that SARS-CoV-2 is commonly spread by asymptomatic and presymptomatic transmission. A Feb. 21 report in JAMA details a case of an asymptomatic carrier who possibly infected 5 family members despite having normal chest computed tomography (CT) findings. In an outbreak at a long-term care skilled nursing facility in King County, Washington, 30% of residents tested positive for SARS-CoV-2; half of these were asymptomatic on the day of testing. In another study from China, the transmission rate from those with “undocumented” infections (asymptomatic or symptomatic but not meeting testing criteria) was lower but still significant, with an estimated transmission rate about half that of those with classical symptoms. Because undocumented infections are more common than current testing levels can account for, they may serve as a greater source of transmission than those of symptomatic carriers who have tested positive. The median duration of viral shedding in a study of 191 COVID-19 positive inpatients by RT-PCR was 20 days; the longest duration observed was 37 days. Li Wenliang, MD, the whistleblower ophthalmologist who sounded the initial alarms on the coronavirus, and later died from the disease, believed he was infected by an asymptomatic glaucoma patient. The sum of these reports points to asymptomatic and presymptomatic transmission as a significant source of spread.

    Environmental contamination by SARS-CoV-2 is another cause for concern. In a study published in the New England Journal of Medicine, scientists were able to detect viable SAR-CoV-2 in aerosols up to 3 hours post-aerosolization, although in an experimental setup lacking any ventilation, and not necessarily reflecting how the virus behaves in real-life conditions. The study also found infectious virus could survive up to 24 hours on cardboard, up to 4 hours on copper, and up to 2 to 3 days on plastic and stainless steel. In another study by the CDC of the cruise ship outbreaks of COVID-19, SARS-CoV-2 RNA (not necessarily indicating infectious virus) was identified on various surfaces within cabins of passengers who tested positive, for up to 17 days after they disembarked the ship.

    In a report from the University of Nebraska, the authors used RT-PCR to test room air, personal articles and environmental surfaces for SARS-CoV-2 in the hospital rooms of COVID-19 patients. They found evidence of viral RNA throughout the rooms—even on windowsills and in ambient air. However, infectious virus could not be cultured from air samplers. These data emphasize the need to use personal protective equipment (PPE) meticulously, per local guidelines, and to remain vigilant in handwashing and disinfecting surfaces and materials possibly contaminated by respiratory secretions from infected patients.

    Personal protective equipment (PPE) for ophthalmic use

    There is heightened controversy regarding what constitutes appropriate PPE for ophthalmologists performing ophthalmic examinations, particularly around the use of masks and goggles. Reports of ophthalmologist and otolaryngologist deaths in China and Italy, new data about environmental virus contamination and increased awareness of asymptomatic and presymptomatic spread of new infections all favor mouth, nose, and eye protection. However, global shortages of PPE and concerns about mask effectiveness with extended wear and reuse have thus far impacted widespread adoption. Consequently, U.S. hospital guidance varied initially from forbidding physicians from wearing masks except in high-risk interactions, presumably for fear of shortages, to mandating all hospital staff and patients wear surgical masks to reduce asymptomatic transmission. In hotspots, some hospitals require all caregivers to wear N-95 masks. The Academy relies on expert guidance from the CDC with regards to indications for extended mask wear and reuse, but recommends that patients wear masks or face coverings and that physicians wear surgical masks and eye protection during routine ophthalmic examinations. 

    Treatment and vaccine

    Currently, there are multiple ongoing clinical trials of agents for prophylaxis or therapy for SARS-CoV-2 infection. In a randomized, placebo-controlled treatment trial recently reported, treatment with remdesivir led to a more rapid recovery than treatment with placebo. On May 1, 2020, the FDA issued an emergency use authorization for remdesivir for the treatment of suspected or laboratory-confirmed COVID-19 in adults and children hospitalized with severe disease. In another study published May 8, 2020, adults with COVID-19 with a median duration of symptoms 5 days prior to treatment became PCR negative more quickly when treated with a combination of lopinavir, ritonavir, ribavirin, and interferon beta-1b, than when treated with lopinavir and ritonavir (control group). Both these studies suggest the potential for antiviral therapy, if given early enough in infection, to alter the course of disease.

    Monoclonal antibody IL-6 receptor antagonists are being studied to address the “cytokine storm” seen in some patients with severe COVID-19. There are also efforts to use convalescent sera from COVID-19 survivors as therapy, and anticoagulant therapy to reduce the risk of thromboembolic events associated with COVID-19. More information about developments in the treatment of COVID-19 by these agents is available from the CDC.

    At this time there is no vaccine to prevent infection, but numerous efforts to develop a vaccine are in progress, including an mRNA coronavirus vaccine trial that began enrollment in early March.

    Use of chloroquine and hydroxychloroquine

    Chloroquine and hydroxychloroquine, oral agents approved for malaria and autoimmune disorders, respectively, are also under study but concerns about potential cardiotoxicity have limited their use. The American Academy of Ophthalmology has no opinion on the use of chloroquine or hydroxychloroquine in COVID-19 patients. However, in a review of published guidelines for the use of these 2 drugs as treatment for COVID-19, a working group* from the Asia-Pacific Vitreo-Retina Society found that proposed doses in many of the ongoing studies worldwide exceeded the maximum daily dose considered safe for long-term therapy (generally <5mg/kg of real weight for hydroxychloroquine) for rheumatic and other chronic diseases (WF Mieler, MD, personal communication, March 25, 2020).

    The risk of irreversible maculopathy at these higher doses for short periods of time is unknown. Patients should be informed of the potential for macular toxicity before starting therapy. Furthermore, the need for baseline fundus examination and/or imaging is also unknown in cases with high doses over a relatively short duration. Additional diagnostic testing, such as an ERG, prior to placing a patient on hydroxychloroquine for treatment of COVID-19 is likely unnecessary due to the short treatment duration. Additionally, performing an ERG in this setting carries an unnecessary risk of virus transmission. Until more is learned about the toxicity associated with current regimens, decisions should be made on an individual basis, taking into consideration any pre-existing retinal disease. As in all cases, the Academy urges ophthalmologists to make decisions guided by available scientific evidence.
    * Ruamviboonsuk P, Lai T, Chang A, Lai C, Mieler W, Lam D

    Ophthalmology ties

    There are now numerous published reports of patients with COVID-19 who either presented with conjunctivitis as a first or only sign of illness or developed conjunctivitis during hospitalization for severe COVID-19 disease. In many of these reports, SARS-CoV-2 mRNA was identified by RT-PCR on conjunctival swabs. In one study, infectious virus was cultured from an eye swab. ACE2 is the cellular receptor for SARS-CoV-2. Two studies (Zou et al. and Sungnak et al.) have shown mRNA expression for ACE2 in human conjunctival epithelial cells. The expression of ACE2 protein has been shown in conjunctiva by immunohistochemistry in one study, but its presence in conjunctival epithelium remains controversial. One study purported to show that SARS-CoV-2 could infect human conjunctival explants. It is possible that SARS-CoV-2 is transmitted to the conjunctiva by aerosol or through hand to eye contact.

    • In a Journal of Medical Virology study of 30 patients hospitalized for COVID-19 in China, 1 had conjunctivitis. That patient—and not the other 29—had SARS-CoV-2 RNA in ocular secretions. This suggests that SARS-CoV-2 can cause conjunctivitis, and that infectious viral particles might be present in tears of COVID-19 patients with conjunctivitis. This observation was confirmed in a recent case report from China and another from Italy of patients with conjunctivitis in the setting of COVID-19.
    • In a larger study published in the New England Journal of Medicine, researchers documented "conjunctival congestion" in 9 of 1,099 patients (0.8%) hospitalized with laboratory-confirmed COVID-19 from 30 hospitals across China. None of the patients were documented to have seen ophthalmologists, and tears were not sampled.
    • In a retrospective case series published March 31 in JAMA Ophthalmology, 12 of 38 “clinically confirmed” hospitalized cases of COVID-19 in Hubei Province, China, had ocular "abnormalities," characterized most commonly as chemosis and/or secretions. Two patients had a positive conjunctival swab for SARS-CoV-2 RNA, one with signs of conjunctival hyperemia and the other with chemosis and epiphora. This paper was discussed in the New England Journal of Medicine Journal Watch, which stated that “a third [of patients in the JAMA Ophthalmology paper] had conjunctivitis.” We disagree with the latter characterization; chemosis in a critically ill patient most likely represents third-spacing or fluid overload, not conjunctivitis.
    • Two preprint studies posted on MedRxiv also suggest a relatively low likelihood of infectious virus in tears of COVID-19 patients. In a study by Zhang et al. of 72 confirmed COVID-19 patients at Tongji Medical College, 2 patients had conjunctivitis. One of the 2 with conjunctivitis and none of the other 70 patients had SARS-CoV-2 RNA in their tears. In a paper by Zhou et al. of 63 confirmed COVID-19 patients in Wuhan, only 1 had conjunctivitis; that patient had a negative conjunctival swab for SARS-CoV-2 RNA. One other patient’s conjunctival swab was positive and 2 were “probable."
    • In a case report published in the Annals of Internal Medicine, the first patient in Italy to be diagnosed with COVID-19 also had conjunctivitis in addition to fever and respiratory and gastrointestinal signs. RT-PCR on conjunctival swabs showed SARS-CoV-2 RNA from day 3 of hospitalization until day 21 (1 day after the conjunctivitis resolved), and again at day 27, at which point nasal swabs were negative. Infectious virus was isolated by cell culture from a sample taken on day 3.
    • In a story from CNN, a registered nurse in a nursing home in Washington state with a large COVID-19 outbreak reported that red eye was a common early sign in elderly patients who then became sick with COVID-19.

    Unless or until the CNN report is confirmed, existing data suggest that conjunctivitis is an uncommon event as it relates to COVID-19. However, because conjunctivitis is a common condition overall, and patients with conjunctivitis frequently present to eye clinics or emergency departments, ophthalmologists are commonly the first providers to evaluate patients possibly infected with COVID-19. Almost all reports of SARS-CoV-2 associated conjunctivitis described to date are of bilateral, mild, follicular conjunctivitis without corneal involvement. However, a patient with unilateral conjunctivitis and a coarse epithelial keratitis was recently found to be RT-PCR positive on a conjunctival swab. Another patient who developed COVID-19 while on a cruise ship developed a bilateral pseudomembranous conjunctivitis. A third patient hospitalized for COVID-19 in France developed a bilateral hemorrhagic, pseudomembranous conjunctivitis. Based on these studies, it is possible that the ocular secretions of a patient with COVID-19 associated conjunctivitis could contain infectious virus.

    Therefore, protecting your mouth, nose (e.g., an N95 mask) and eyes (e.g., goggles or shield) is recommended when caring for patients potentially infected with COVID-19. In addition, slit-lamp breath shields (e.g., here ) are helpful for protecting both health care workers and patients from respiratory illness. Free slit-lamp breath shields are being offered by some manufacturers, including Topcon and Zeiss.

    Resources

    WHO

    CDC

    Relevant articles

    EyeNet magazine

     Journal studies and scientific articles


    James Chodosh, MD, MPH, is the Edith Ives Cogan Professor of Ophthalmology at Harvard Medical School’s Department of Ophthalmology, a member of Harvard’s PhD program in virology and an expert in cornea and external disease working at the Massachusetts Eye and Ear.

    Gary N. Holland, MD, is the Jack H. Skirball Professor of Ocular Inflammatory Diseases, director of the Ocular Inflammatory Disease Center, and a member of the cornea/external disease and uveitis divisions at the Jules Stein Eye Institute, David Geffen School of Medicine at UCLA. 

    Steven Yeh, MD, is the M. Louise Simpson Associate Professor of Ophthalmology, a member of the uveitis and vitreoretinal surgery divisions at the Emory Eye Center, and a faculty fellow of the Emory Global Health Institute.