The Complexities of COVID-19 in Ophthalmology

With Michelle YT Yip, Ji Peng Olivia Li, Jessica Shantha, Steven Yeh, James Chodosh, Adrian T Fung, Haotian Lin, Jod Mehta

We are currently living in the COVID-19 pandemic; a formal declaration by the World Health Organization (WHO) on March 11, 2020, and a public health emergency of international concern. Although the origin of this outbreak is still speculative, authorities in the WHO Country Office in China were first alerted to a “pneumonia of unknown etiology” on December 31, 2019, when a cluster of cases were detected in Wuhan, Hubei, China.

The virus isolated from these patients has not been previously isolated from humans, suggesting a novel pathogen. Since then, it has spread to over 150 countries and territories in the last few months. The rapid expansion and severity of the virus has alarmed citizens, heads of state, and WHO leaders across the globe. We explore the COVID-19 outbreak in relation to the role of the eye, risks to ophthalmologists, and measures to reduce transmission.

Global prevalence and virology

As of April 16, there have been more than 2 million cases worldwide, claiming almost 150,000 lives (1). 

COVID-19 is a disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), belonging to the Coronaviridae family. This family is characterized as an enveloped, positive-sense, single-stranded ribonucleic acid (RNA) virus which, when visualized on electron microscopy, have unique characteristic surface projections resembling a corona, “crown” in Latin. SARS-CoV-2 is similar to the severe acute respiratory syndrome coronavirus (SARS-CoV) that plagued the East in 2003. Based on phylogeny, taxonomy and established practice, it has been determined to be the same species. Other viruses in this family include the Middle East respiratory syndrome coronavirus (MERS-CoV), the causative virus for the MERS outbreak that started in 2012 and was first isolated in Saudi Arabia. The COVID-19 pandemic is the third cross-species spillover of animal coronavirus to humans in the last two decades to result in outbreaks. Although these three coronaviruses have been at the center of attention in recent years, there are other human coronaviruses responsible for causing mild upper respiratory symptoms commonly reported as a cold.

The physicians affected 

Li Wenliang, a 34-year-old ophthalmologist at the Central Hospital of Wuhan, gained worldwide publicity for his role as a whistle-blower, sparking outrage within China and globally, after reports of the Chinese government’s dealings with him surfaced. He contracted the virus and subsequently passed away on February 7, 2020. Based on what has been reported thus far, two other ophthalmologists from the Central Hospital of Wuhan, Mei Zhongming and Zhu Heping, have also passed away from this virus.  

Although the exact number of physician deaths from the virus is unclear, it is apparent that ophthalmologists have been particularly affected (4, 5). The reasons why ophthalmologists might be more at risk include the proximity to patients during examination, predisposing them to droplet transmission, and the unavoidable physical contact they have with patients’ eyes, resulting in susceptibility through direct contact.

Wenliang speculated that he had contracted the virus from a glaucoma patient who was initially asymptomatic and only began to develop a fever the day after the clinic visit, possibly suggesting transmission via his ocular surface (6, 7).  

Clinical features and ocular manifestations

Common symptoms in patients that have tested positive for COVID-19 include fever, cough, sputum production, fatigue, shortness of breath and gastrointestinal symptoms. However, a study published in the New England Journal of Medicine demonstrated that a small minority of patients (nine out of 1,099 patients) had clinical features of conjunctival congestion (8). In addition, a study in the Journal of Medical Virology reported PCR results from 30 patients hospitalized for COVID-19, one of whom had conjunctivitis (9), thus, it is important to consider COVID-19 in patients presenting with conjunctivitis, especially if they have risk factors such as respiratory symptoms, or contact or travel history. Although SARS and MERS also commonly presented with fever and cough as the predominant symptoms, no studies to our knowledge reported ocular manifestation in SARS or MERS patients.  

Role of the eye in the spread of the disease

Although COVID-19, SARS and MERS are largely thought to be respiratory diseases due to the symptoms and resulting pneumonia, the involvement of the eye is often overlooked. Xia et al demonstrated polymerase chain reaction (PCR) detection of SARS-CoV2 from tears of a patient with COVID-19 that had conjunctivitis and conversely, the lack of detection in 29 COVID-19 patients without ocular symptoms (10). During the SARS outbreak in 2003, one study also demonstrated the presence of the virus through PCR in the tears of three SARS patients (11). On the other hand, other studies were not able to reproduce this detection of SARS-CoV from tears, suggesting further work may be necessary to confirm the role of the eye as an entry and exit point for transmission. However, with the nasolacrimal duct providing direct entry of tears into the nasopharynx, continuous with the respiratory tract, WHO’s precautionary measures to avoid contact with the eye to reduce transmission are reasonable.

Protective measures

Whether in the community or in the healthcare environment, performance of regular hand hygiene, avoidance of touching the eyes, nose and mouth, and maintenance of social distancing of at least one meter, forms the basis of preventive measures. When taking care of patients, healthcare workers may require additional personal protective equipment (PPE); in the case of a suspected or confirmed COVID-19 patient, or a patient with respiratory symptoms, WHO advisory guidelines suggest the use of a medical mask, gown, gloves and eye protection (goggles or face shield).  

Unfortunately, when caring for patients with no respiratory symptoms, the guidelines become less clear, simply stating to put on PPE “according to risk assessment.” As an ophthalmological examination may often involve contact with the patient’s eyes, frequent hand hygiene in between patients and avoidance of contact with mucous membranes are necessary. Alternatively, lifting of the eyelid could be performed using orange sticks or long cotton buds to avoid direct contact with the hand and ocular surface. With ophthalmologists’ close proximity to patients during physical examination, the decision to wear a mask is dependent on the rigor of screening for respiratory symptoms before consultation, patients’ transparent disclosure of symptoms, patients’ compliance to mask-wearing if symptomatic, and availability of slit-lamp breath shields, whilst also recognizing that asymptomatic spread occurs. Thus, consideration has to be made on an institutional and case-by-case basis, with the understanding of resource stewardship. In a randomized control trial, the effectiveness of N95 respirators was found to be comparable with medical masks in preventing laboratory-confirmed influenza in an outpatient setting (10). To minimize transmission to patients, the American Academy of Ophthalmology has advised that ophthalmologists postpone non-urgent outpatient visits and procedures, encouraging patients at-risk of COVID-19 to avoid entering the outpatient setting and to seek appropriate help in a hospital-based facility. This advice is consistent with that from the Royal College of Ophthalmologists, which also highlights the need to minimize the duration of examinations, as well as prolonged treatments such as pan-retinal photocoagulation.

Looking to the future

Despite the fear perpetuated by the increasing number of cases and deaths, this period of adversity has also demonstrated our humanity. With countries providing reciprocal aid, with research groups collaborating to develop treatment and vaccines, this outbreak will naturally follow a course of peak and decline, as evidenced by the decrease in the number of new cases in China in March. Minimizing deaths will depend on individual precautionary measures, national-driven policies to identify, isolate, and reduce the spread within community and at-risk groups, and ultimately, the healthcare sectors’ resources and resilience.