Dr Kusy Suleiman¹*, Dr Omar Mostafa²*, Dr Yusuf Abdallah³, Mr Simon N Madge⁴

¹ Academic Foundation Year 2 Doctor, Ophthalmology Department, Sandwell and West Birmingham NHS Trust ^{Contact author}

² Foundation Year 1 Doctor, Acute Medical Unit, Walsall Manor Hospital ^{Contact author}

³ Ophthalmology ST1 Doctor, Heartlands Hospital, University Hospital Birmingham. ^{Contact author}

⁴ Consultant Ophthalmologist, Wye Valley NHS Trust, Stonebow Rd, Hereford, HR1 2ER.

*Joint first author

Key points

• A thorough systems review is crucial for any new consult.
• COVID-19 has been linked to conjunctivitis amongst other eye complaints.
• Eye protection is crucial for clinicians especially those working in close contact with patients.
• There are currently no sight threatening manifestations of COVID-19 reported however larger studies and longer follow up are necessary to conclude this with confidence
• Patients with COVID-19 can present solely with ocular manifestations and these may predict more severe disease.

Abstract

In December 2019, Dr. Li Wenliang, a 34-year-old ophthalmologist, became the first doctor to notify the public of the emergence of the SARS-CoV-2 (COVID-19) outbreak.  Unfortunately, he died due to COVID-19 shortly after. COVID-19 is caused by a novel virus affecting the respiratory system primarily but with multi-systemic manifestations. In previous SARS-CoV outbreaks, a study demonstrated the presence of the virus in the patients’ ocular secretions. In addition to offering a possible route of transmission, the eyes can be implicated in the initial presentation of COVID-19.  Throughout the pandemic, a minority of cases have presented with ocular symptoms such as sore eyes, itching, foreign body sensation, floaters, and red eye. At times, ocular complaints have also been found to precede respiratory complaints or be the only presenting complaint of COVID-19. Ocular complaints also appear to be possibly linked with more severe disease processes clinically and biochemically. Consequently, it is important to consider COVID-19 in patients with new conjunctivitis or ocular complaints.

Introduction

In December of 2019, coronavirus disease 2019 (COVID-19) developed into a global pandemic. COVID-19 is caused by an infectious novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has spread geographically at an unprecedented rate [1]. Previous studies demonstrate Coronaviruses rarely cause ocular manifestations in humans and those that occur are rare and mild [2]. The American Academy of Ophthalmology also reported conjunctivitis is rare in cases of COVID-19 and that it only affects 1-3% of patients [3]. However, emerging evidence suggests that a wider scope exists for ocular symptoms with COVID-19 than previously thought [4]. This may also have implications on the perceived route of transmission. Indeed, one of the first whistleblowers in the pandemic was the late Li Wenliang who contracted COVID-19 while working as an ophthalmologist, leading to his death [5].

Background

SARS-CoV-2 is a novel RNA coronavirus. The origin of the pandemic is speculative but world health organization (WHO) officials in China were first alerted to a pneumonia of unknown cause on December 31, 2019 when a local eruption occurred in Wuhan, Hubei, China [6]. Although transmission of COVID-19 is thought to be primarily airborne, emerging data also suggests evidence of transmission of SARS-CoV-2 via the ocular surface [4,7]. Eyecare providers may be at increased risk of infection due to the proximity and nature of ophthalmic examination [8].  Globally, as of 13^th of July 2020, there have been 12,768,307 confirmed cases of COVID-19 including 566,654 deaths reported to the WHO [9]. The pathophysiology of COVID-19 is reviewed by Yuki et Al who note that the lack of targeted therapies continues to be problematic in the treatment of COVID-19 [10].

Clinical presentation

COVID-19 research is mostly focused on the respiratory system and for good reason: most cases presented with nonspecific and/or upper respiratory symptoms (dry cough, pyrexia, fatigue, myalgia, headache) with or without mild pneumonia. Cases with pneumonia may also exhibit shortness of breath in addition to pleuritic chest pain. Critical disease causes outright respiratory failure with or without multiple organ failure due to sepsis. Clearly the respiratory system is the prime target of SARS-CoV-2, however multisystemic manifestations should not be ignored as they can form a possible route of transmission as well as present before the respiratory symptoms as illustrated by emerging evidence [1,11,12].

Review of case studies/series

An Italian case series details five patients between the ages of 37-65 (four male, one female) who all presented with signs and symptoms of acute conjunctivitis such as conjunctival hyperemia, epiphora, discharge and photophobia [12]. They were seen in the eye clinic as referred by their general practitioners. Acute conjunctivitis was diagnosed in each case. Patients were covered with moxifloxacin eye drops four times a day for five days. With the pandemic in mind, clinicians successfully established travel history to Lombardy in all five patients which had, around the time, reported a high incidence of COVID-19 cases. The diagnosis of COVID-19 was confirmed with nasopharyngeal swab using polymerase chain reaction (PCR) which were positive in all five cases. Interestingly, none of the patients reported fever or respiratory symptoms highlighting the importance of a high clinical suspicion of COVID-19 in the current pandemic and the multi-systemic nature of disease.

Another case series in Singapore isolated SARS-2-CoV from PCR performed on tear samples. Consequently, it is hypothesized that the ocular surface can provide a previously unheralded route of transmission [13]. A retrospective case series also reported that a minority of patients recall appearance of ocular symptoms one to seven days before the onset of fever or respiratory symptoms [2].  Another case study demonstrates the case of a twenty-seven-year-old patient who presented with ocular symptoms and within a few hours had become systemically unwell with severe dyspnea, fever, headache, and dry cough [14]. This resonates with a Chinese study of the characteristics of ocular findings of patients with COVID-19 which found that patients with ocular manifestations were more likely to be systemically more unwell [15]. A study concerning the paediatric population the ocular manifestations drew similar conclusions, with regards to the ocular presentations, to their adult counterparts except for generally milder disease processes in children [16]. Ocular manifestations (mostly conjunctivitis) are treated symptomatically in addition to the advice regarding self-isolation if PCR results confirm SARS-CoV-2 infection. In terms of chronic sequalae of SARS-CoV-2, it is uncertain whether chronic ocular complaints can occur.

Impact on Ophthalmologists

Amid the pandemic, healthcare professionals such as otolaryngologists, dental practitioners, and ophthalmologists, who rely heavily on close examination find themselves in a precarious situation. A cough or sneeze can be propelled for up to 6 meters. Furthermore, the anecdotal evidence discussed above suggests the possibility of a compromised ocular surface (e.g. dry eye) leading to infection and a route to the respiratory system. Strategies including full PPE, including strict eye protection, good hand hygiene, decontamination and sterilization protocols of clinical areas and equipment are recommended. Furthermore, the risks of viral transmission must be weighed against the surgical benefits of any elective procedure which may be better performed later. For emergency operations, full PPE will likely reduce transmission [9].

Conclusion

COVID-19 has been anecdotally shown to affect the ocular surface. It is speculated that this is via a compromised ocular surface that allows viral colonization of the surface with consequent hematogenous spread to the respiratory system. Anecdotal case reports speculate that COVID-19 can present in many other systems other than the respiratory system such as gastrointestinal distress and ocular surface symptoms. These symptoms can be either part of the disease process, preceding it or be the only symptoms in the disease process. It has also been shown that SARS-CoV-2 has been isolated from tears and conjunctival secretions of patients with no ocular complaints. This illustrates the necessity of a high clinical suspicion in the context of a pandemic to successfully diagnose and treat these atypical cases as well as to terminate the transmission chain. Further studies are needed to establish the long-term sequalae of COVID-19 in terms of ocular manifestations.

References

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