The ophthalmic implications of COVID-19: What we know so far

The respiratory symptoms caused by the severe acute respiratory coronavirus disease (COVID-19) that has been sweeping the world since late 2019 are well documented, given the regularity and consistency with which they occur. However, the role of the eyes and tears both as entry routes for the causative virus, SARS-CoV-2, and as sources of contagion are still the subject of debate, and relatively less is known about the ophthalmic implications of the disease.

It would appear from some recent studies that patients who experience the more severe forms of COVID-19 and present with pneumonia commonly display ocular symptoms. However, the authors of a recent Chinese study of 38 patients concluded that although a third of patients with the disease had ocular abnormalities, there was a low prevalence of the virus in tears1,2.

Nevertheless, it is possible that contact with infected eyes could be a route of transmission of SARS-CoV-2, especially given the knowledge that it can be spread via direct or indirect contact with other mucous membranes (the mouth and nose), so ophthalmologists should err on the side of caution and ensure rigorous prevention protocols are put in place.

Evidence of conjunctivitis

In a literature review recently published in Ophthalmology and Therapy, Prof. Jorge Alió and Dr Alejandra Amesty reported that when it occurred, conjunctivitis was the most common ophthalmologic sign related to coronavirus infection1. And there are clues from previous coronavirus outbreaks as to why this should be the case: inflammation of the conjunctiva was first associated with a human coronavirus back in 2004 when children started to fall prey to the symptoms during the severe acute respiratory syndrome (SARS) crisis.

Genetically speaking, SARS-CoV-2, the virus that caused SARS, is around 70% similar to SARS-CoV and uses the same receptor (ACE2) to insert itself into human cells. This is potentially quite significant when one considers that ACE2 receptors have been found in the aqueous humour3.

But could the fact that conjunctivitis is mainly being seen in the most poorly patients mean that the presence of the virus on the surface of the eye and subsequent ocular events are down to decreased immune function? The researchers do not think so: “Both viral diseases and immune problems can lead to ocular manifestations, such as conjunctivitis, uveitis, retinitis, among others. It is difficult to determine the pathology of the ophthalmic involvement. However, since the virus has been cultured from conjunctival secretions, COVID-19 ophthalmopathy is more likely to be related to the actual virus infestation rather than the secondary immune reaction that the infection may cause.”

Any sign of conjunctivitis in the clinical setting should be considered to be a “possible coronavirus conjunctivitis, especially when accompanied by other respiratory tract problems or fever”, the authors pointed out.

Thankfully, viral conjunctivitis usually amounts to no more than an uncomfortable nuisance, so treatment strategies are typically supportive in nature. That said, it is important to try to lessen the potential viral load on the ocular surface and some of the general ophthalmic recommendations for viral conjunctivitis could also apply to COVID-19 patients.

“These include hygienic measures (frequent hand washing, especially when eye drops need to be applied or contact lenses worn; avoiding touching or rubbing the eyes; changing pillowcases, sheets) … we should be meticulous when examining patients who have tested positive for COVID-19.”

Clinic guidelines

The close face-to-face proximity of ophthalmologists to their patients and frequent exposure to tears and ocular discharge, as well as regular handling of equipment such as slit lamps, tanometers and lasers, means they are perhaps at a higher risk of contracting COVID-19 than other types of healthcare professionals, the researchers said, referring to recent guidelines that have been published in an attempt to minimise the chances of infection spreading in ophthalmology clinics and hospital departments.4,5

In the guidance, ophthalmologists are advised to impose limits on the number of attending patients and to adhere to strict appointment timetables to prevent people from gathering in clinic waiting rooms. Online platforms, such as hospitals’ official websites, should be readily used, whilst simply making more telephone calls could reduce the need for patients to visit hospitals, for example, by helping them to distinguish between urgent and nonurgent ocular problems.

The guidelines go on to recommend triage systems to help to flag up patients with symptoms consistent with COVID-19 infection such as fever, and online ordering and delivery of prescribed medication, especially for chronic eye diseases such as glaucoma.

Recommendations for handling a patient’s visit include:

• Reducing the number of accessible entry points to the hospital/clinic;
• Screening patients for COVID-19 symptoms and contact history with confirmed or suspected within the past 14 days;
• Providing patients and staff with masks;
• Seeing patients with eye infections in separate clinics with their own waiting areas;
• Testing patients more than twice for evidence of SARS-CoV-2 RNA in the conjunctival sac and tears;
• Limiting numbers of people in examination rooms;
• Ensuring rooms are well ventilated and instruments used disinfected immediately after a patient’s visit; and
• Implementing infection control training.

In addition, slit lamps should be protected by shields and direct ophthalmoscope examination could be replaced by slit light lenses, optical coherence tomography or fundus photography.

For inpatients, the suggested adaptations include preoperative infection screening and use of local rather than general anaesthesia to avoid contamination. Negative-pressure operating rooms should be used for emergency operations on any COVID-19-positive patients.

Disinfectants

Human coronavirus is believed to be able to remain infectious on inanimate surfaces for as many as 9 days6, so disinfecting surfaces with water, detergent and commonly used disinfectants is extremely important, Prof. Alió and Dr Amesty explained. In addition, they suggested that some ocular spray disinfectants that contain hypochlorous acid (usually applied to treat blepharitis in order to reduce bacterial and viral load on the skin and eyelashes) could be used as “a measurement of prevention for the facial area where many other chemical agents cannot be applied”.

However, more studies are needed to establish a specific antiviral product that could be used to reduce the viral load on infected patients’ conjunctiva and lower the transmission rate via the eyes/tears. The authors conceded that this is no easy task when “so many doubts still remain regarding the ophthalmic implications” of the infection.

More research

Summarising, the authors have called for “well-designed trials” to be conducted “to rule out other ocular manifestations [besides conjunctivitis] that may result from COVID-19 infection and to better elucidate the mechanisms of transmission through the eyes.”

Until more light can be shed on the ophthalmic implications of COVID-19, ophthalmologists can only remain as up-to-date as possible on emerging disease findings, whilst maintaining a cautious approach when dealing with patients before, during and after appointments.

1. 1. Amesty MA, Alió del Barrio JL, Alió JL. COVID-19 disease and ophthalmology: An update. Ophthalmology and Therapy. 2020. https://doi.org/10.1007/s40123-020-00260-y
2. Wu P, Duan F, Luo C, et al. Characteristics of ocular findings of patients with coronavirus disease 2019 (COVID-19) in Hubei Province. China JAMA Ophthalmol. 2020. https://doi.org/10.1001/jamaophthalmol.2020.1291.
3. Holappa M, Vapaatalo H, Vaajanen A. Many faces of renin-angiotensin system—focus on eye. Open Ophthalmol J. 2017;11:122-142.
4. Lai THT, Tang EWH, Chau SKY, et al. Stepping up infection control measures in ophthalmology during the novel coronavirus outbreak: an experience from Hong Kong. Graefes Arch Clin Exp Ophthalmol. 2020. 258:1049-1055.
5. Yong Y, Ruixue T, Xu S, et al. A comprehensive Chinese experience against SARS-CoV-2 in ophthalmology. Eye Vis. 2020;7:19.
6. Kampf G, Todt D, Pfaender S, Steinmann E. Persistence of coronaviruses on inanimate surfaces and their inactivation with biocidal agents. J Hosp Infect. 2020;104:246-251.

Jorge Alió, MD

E: jlalio@vissum.com

Prof. Alió is professor and chairman of ophthalmology at the Miguel Hernandez University of Elche and scientific director at Vissum in Alicante, Spain. He has no financial interests in the subject matter.