There is a growing body of evidence regarding links between COVID-19, eye health and ocular signs and symptoms. There has been conflicting, and sometimes contradictory advice on conjunctivitis as part of the suite of symptoms of COVID-19. Following is some of the most recent information, to assist you in making informed decisions about your patients. At the bottom are some important links.

General Advice

An Australian paper by Willcox et al. published in CXO, 13.05.2020 conducts a literature review on the ocular surface and its implications in COVID-19 infection.

Key points include;

  • “Coronavirus infection is rarely associated with conjunctivitis, with occasional cases reported in patients with confirmed COVID‐19, along with isolated cases of conjunctivitis as a presenting sign.“
  • “The evidence suggests coronaviruses are unlikely to bind to ocular surface cells to initiate infection.”
  • “The ocular manifestations such as conjunctivitis and presence of SARS‐CoV‐2 in tears have so far only been found rarely and primarily in people with confirmed, symptomatic COVID‐19.”

 However, it is very important to note;

  • “The potential, albeit rare, for (kerato)conjunctivitis to present as the first sign of COVID‐19. All eye‐care practitioners must bear this in mind when triaging patients and considering how best to review, and potentially examine, or refer, a patient in this situation.”

A recently review on the Implications of COVID-19 for Ophthalmologists showed;

  • “Ophthalmologists (and eye care professionals) will need to maintain vigilance given the increased risk of infection they face”
  • “Conjunctival swabs are positive in 2.5%… (however) viral transmission through ocular tissues has not been substantiated.”

Suggesting that whilst conjunctivitis is a possible presenting symptom of COVID-19, it is unlikely in otherwise asymptomatic patients. Also, that whilst the RNA can be present in eye fluids, the eye is an unlikely route of viral initiation. Consider all cases of keratoconjunctivitis to be potentially suspicious in areas of high community transmission and keep this in mind when triaging and deciding when to review patients.

An October case report published in JAMA looked ocular tissue samples of a patient who had suffered severe acute respiratory syndrome whilst suffering from COVID-19, and concurrently had an acute angle closure glaucoma attack during her recovery. During phacoemulsification and subsequent trabeculectomy surgery, tissue samples were conducted of the conjunctiva, trabecular and iris. The conjunctival cells had the COVID nucleocapsid protein antigen present, as did the iris and trabecular meshwork, however the post infection plasma testing suggested the patient was in recovery. This one case report suggests that unlike previous thinking the eye may be an infection pathway for the virus, and the virus was persistent in the ocular tissue despite the patient’s systemic blood results suggesting remission. The authors do caution however this requires further investigation, and at this stage changes no PPE or clinical recommendations.

 

Current Research

An Italian paper, published in April by Scalinci et al. “Conjunctivitis can be the only presenting sign and symptom of COVID-19” states that;

  • In the five patients in the case report; acute conjunctivitis was the presenting sign and symptom, but also remained the sole form of manifestation of COVID-19.”
  • The patients had signs and symptoms of acute conjunctivitis – conjunctival hyperemia, epiphora, discharge, and photophobia” that “did not seem to improve after several days.”
  • Patients were sent home to self-isolate, and followed up by phone in which none of them reported the development of fever, general malaise, or respiratory symptoms.”

A case report in JAMA Ophthalmol. published online on 27/08/2020 documented the progression of conjunctivitis in association with COVID-19 in two patients admitted to their mobile COVID-19 hospital in Wuhan China. In one patient the conjunctival “congestion” was noted on day 1 of symptoms, and in the second day 15. PCR detection confirmed presence of COVID-19 RNA up to 14 days post initiation of symptoms, with the symptoms persisting for up to 24 days. In this case study, the patients were given Ganciclovir eyedrops twice a day following positive swab results. The authors acknowledge that there is currently no evidence to the utilisation of Ganciclovir and this case provided no further insights to its effectiveness; however, the isolation of patients with conjunctivitis is suggested to reduce nosocomial transmission.

A novel study published in September 2020 in the Lancet looked at the effects of COVID-19 on the retinal vasculature. The authors note that like is common in other viral diseases such as cytomegalovirus and HIV retinopathy, COVID-19 is able to infect endothelial cells and can damage blood vessels in the retina. Mean Artery Diameter was statistically significantly larger only in patients whom had severe COVID-19. Mean venous diameter was statistically significantly larger in patients with both severe and non-severe COVID-19 infections. Similar finding had been observed in pulmonary vessels. Retinal haemorrhages and cotton wool spots were also discovered in the infected patients, and have been reported in other smaller case reports, however the authors caution that these are common findings and shouldn’t be attributed innapropriately to COVID-19 without further investigation.

A case report in JAMA Ophthalmol. published online on 27.08.2020 documented the progression of conjunctivitis in association with COVID-19 in two patients admitted to their mobile COVID-19 hospital in Wuhan China. In one patient the conjunctival “congestion” was noted on day 1 of symptoms, and in the second day 15. PCR detection confirmed presence of COVID-19 RNA up to 14 days post initiation of symptoms, with the symptoms persisting for up to 24 days. In this case study, the patients were given Ganciclovir eyedrops twice a day following positive swab results. The authors acknowledge that there is currently no evidence to the utilisation of Ganciclovir and this case provided no further insights to its effectiveness; however the isolation of patients with conjunctivitis is suggested to reduce nosocomial transmission.

A small scale review on patients in intensive care “Detection of coronavirus in tear samples of hospitalized patients with confirmed SARS-CoV-2 from oropharyngeal swabs” suggested that using tear sampling may yield higher results of Coronavirus presence. Rather than using a conjunctival swab, as has been standard over the past few months, using tear collection and assessment similar to the oropharyngeal swabs shows a much higher rate of 28% positive COVID-19 RNA in tears. Interestingly; none of these patients had frank conjunctivitis symptoms however all showed chemosis and conjunctival hyperemia.

On the 26th of August cross sectional study of 216 children hospitalised in Wuhan, China, with confirmed cases of COVID-19 were both clinically assessed and provided with self-reporting surveys on eye symptoms. 22.7% reported some ocular symptoms, the majority of whom were ten or under. 2.3% of the children had conjunctival discharge and 1.9% had conjunctival congestion as the first presenting symptom. This is low in comparison to the high rates of initial presentation being fever (37.5%) and cough (36.6%). Of interesting note, of the 43.1% of asymptomatically reported children 14% did indeed have ocular congestion on examination, but it still stands that children are far more likely to have conjunctivitis in association with other systemic symptoms. Discharge ranged from white mucoid to yellow-green purulent (see Figure 1 in the article). Eye rubbing, tearing, eyelid swelling and pain were all common, but eyelid swelling only in children 10 and over. On a positive conclusion, all children were discharged and recovered without ongoing complications.

Murdoch University released a Media Announcement on the 21st of August discussing how their recent research conducted in WA demonstrates that COVID-19 “is a multi-organ metabolic disease.” Samples were collected from 19 COVID-19 infected patients and were compared to uninfected control subjects of similar demographics and BMI. They found that there was much higher evidence of diabetes, liver disfunction, dyslipidaemia and heart disease risk factors in the COVID-19 group: similar to that of patients whom were infected with SARS. Whilst they acknowledge that the tests and outcomes for these patients have not yet been fully validated, they recommend careful investigations in recovered COVID-19 patients whom may now have higher risks and management implications for conditions such as diabetes. This highlights the important role of the optometrist in careful retinal investigation and assessment of vessels at the back of the eye.

A paper published in Graefe’s Archive for Clinical and Experimental Ophthalmology on the 6th June suggested there was a link between increased ESR, CRP and a higher fever and patients presenting with ocular symptoms. The study also found that 20.5% of patients have some form of ocular symptom.

In an article updated on the 2nd of April 2020, the American Academy of Ophthalmology acknowledged that “several reports suggest the virus can cause a mild follicular conjunctivitis otherwise indistinguishable from other viral causes, and possibly be transmitted by aerosol contact with conjunctiva”. We have learnt, from study of other coronavirus diseases, that conjunctivitis is within the realm of possible complications.

Patients who present to optometry or ophthalmology for conjunctivitis, who also have upper respiratory tract symptoms, fever, shortness of breath or whom have recently travelled could represent cases of COVID-19. It is suspected from some reports, that whilst conjunctivitis or red eye is unusual and not part of “classic” COVID-19, up to 1-3% of patients with COVID may have some form of red eye/conjunctivitis.  It is unlikely that a red eye will be the initial symptom of a COVID-19 patient, and it is not currently listed as a symptom by the Australian Department of Health. Patients are far more likely to present to GP or ED with respiratory symptoms being the main concern, but a high degree of suspicion of red eyes is required.

The Royal Australian and New Zealand College of Ophthalmologists (RANZCO) released the following statements on their page “Clinical Eye Care ” last updated 10th of July 2020

“COVID-19 is known to cause conjunctival congestion in approximately 0.8% of patients infected by SARS-CoV-2.1 To reduce the spread of COVID-19 infection General Practitioners (GPs) need to be aware of the necessary precautions when seeing patients presenting with red eyes .”

The Royal Australian and New Zealand College of Ophthalmologists (RANZCO) released the following statements on their page “Clinical Eye Care” last updated 10th of July 2020

“COVID-19 is known to cause conjunctival congestion in approximately 0.8% of patients infected by SARS-CoV-2.1 To reduce the spread of COVID-19 infection General Practitioners (GPs) need to be aware of the necessary precautions when seeing patients presenting with red eyes .”

Also on the 27th of March, the American Academy of Ophthalmology released the following statement:

“While it appears conjunctivitis is an uncommon event as it relates to COVID-19, other forms of conjunctivitis are common. Affected patients frequently present to eye clinics or emergency departments. That increases the likelihood ophthalmologists may be the first providers to evaluate patients possibly infected with COVID-19.

Therefore, protecting your mouth, nose (e.g., an N-95 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.”

This has since been replaced by “Important Coronavirus Updates for Ophthalmologists” last updated 11th of May 2020.

The American Academy of Ophthalmology page also discusses a report from CNN, in which a nurse at a residential home with an outbreak of COVID-19 reported “red eye was a common early sign in elderly patients who then became sick with COVID-19” which whilst an interesting observation by a clinician, has not been confirmed with studies or published reports.

Further research

A journal called “The Ocular Surface” published an article in their July 2020 issue (viewed 12th of May 2020) titled “The evidence of SARS-CoV-2 infection on the ocular surface” looking at 102 patients diagnosed with COVID-19 in Tongji hospital China. Two patients had conjunctivitis, and one of those patients had RNA fragments found in their ocular swabs. The authors suggest that when treating COVID-19 positive patients, all health care professionals should wear protective goggles.

A case report was published in the Annals of Internal Medicine on the 17th of April titled “SARS-CoV-2 Isolation from Ocular Secretions of a Patient with COVID-19 in Italy Prolonged Viral RNA Detection.” The 65 year old female had presented with bilateral conjunctivitis, non-productive cough and sore throat on day 1 of symptoms after travel from Wuhan, China. Fever was not present until day 4, which presented with nausea and vomiting. An ocular swab was collected on day 3, which revealed viral RNA. This continued to be detected until day 21. Samples continued to be collected daily and a reoccurrence of viral RNA was present on day 27. The authors suggest that this must be considered as a possible source of transmission, even after symptoms and 14 days have ceased.

On 31st March 2020 JAMA Ophthalmology published a case series of 38 patients with COVID-19. Reverse transcriptase–polymerase chain reaction results were positive for severe acute respiratory syndrome coronavirus 2 in 28 nasopharyngeal swabs and 2 conjunctival swabs, and more significant changes in blood test values appeared in patients with ocular abnormalities. In this study, one-third of patients with COVID-19 had ocular abnormalities such as epiphora, conjunctival congestion, or chemosis, which frequently occurred in patients with more severe COVID-19. Although there is a low prevalence of SARS-CoV-2 in tears, it is possible to transmit via the eyes.”

In February 2020, a small scale study was published in China; Evaluation of coronavirus in tears and conjunctival secretions of patients with SARS‐CoV‐2 infection. According to recent reports, a large number of ophthalmologists involved in the diagnosis and treatment of the disease on a daily basis accidentally acquired COVID-19. Thus, many doctors suspect that it is related to contact with tears or conjunctival secretions of patients. The present study assessed the tears and conjunctival secretions in SARS‐CoV‐2‐infected patients. The results showed that the virus existed in the patients’ tears and conjunctival secretions only in those with conjunctivitis. No viral RNA was detected in the tear fluid and conjunctival secretions of the patients with COVID-19 without conjunctivitis symptoms. The low abundance of the virus in tear and conjunctival secretions does not eliminate the risk of transmission through conjunctival tissue.

Another study published in February in The New England Journal of Medicine titled “Clinical Characteristics of Coronavirus Disease 2019 in China” on 1,099 confirmed COVID patients documented “conjunctival congestion in 0.8% of patients. No patients had eye swabs taken.

This has impacts on transmissibility from patients, and suggests clinicians working with confirmed cases, especially those with conjunctivitis, should be cautious and wear eye protection as part of COVID-19 PPE.

For more information:

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