Not only clinical symptoms of respiratory disorders, but Coronavirus 2019 (COVID-19) also causes ophthalmological clinical manifestations. One of the clinical manifestations of ophthalmology that has been reported is conjunctivitis. Conjunctivitis is inflammation of the eye's conjunctiva, characterized by redness of the eye, eye irritation, epiphora, and gritty eyes.

Eye Clinical Manifestations of COVID-19
Viral Conjunctivitis


Actually, the eye clinical manifestations of COVID-19 are rare. However, considering the severe acute respiratory syndrome coronavirus (SARS-CoV) during the SARS pandemic in 2003 was present in patients' tears, so this is thought can also happen in COVID-19 cases. Doctors need to understand the ophthalmological clinical manifestations of COVID-19 patients to identify this disease and prepare for optimal self-protection.



Identifying the Ophthalmological Clinical Manifestations of COVID-19

The doctor needs to ask about a history of:
  • fever, 
  • acute respiratory infections, 
  • travel to a COVID-19 transmission area, 
  • contact with a COVID-19 patient. 
Also, find out about the onset, duration, and characteristics of symptoms.

The doctor also needs to ask about symptoms that could lead to more serious eye conditions, such as eye pain, decreased vision, or increased sensitivity to light. COVID-19 generally does not cause eye pain and decreased vision.



Eye clinical manifestations of COVID-19 Patients


a. Anterior Eye Segments 

Six case series reported conjunctivitis in <5% of all COVID-19 patients. Most of the eye symptoms are bilateral and mild. These eye clinical manifestations onset has been reported to vary between studies, from day 5 to day 25, since the onset of respiratory symptoms.

A meta-analysis by Tong L et al., which collected 20 case series (2228 COVID-19 patients), reported that 95 patients (4.3%) experienced ophthalmological manifestations at one time during illness and 21 patients (0.9%) who came to health facilities with eye complaints as complaints main.
Of the 412 patients who underwent conjunctival swabs, 12 (2.9%) tested positive for COVID-19 in a reverse transcription-polymerase chain reaction (RT-PCR). Of the 12 positive patients, three patients had no eye complaints.

Several studies also reported other symptoms in a smaller percentage, such as: 
  • conjunctival chemosis, 
  • gritty eyes, 
  • epiphora, 
  • and dry eye. 

However, there were no reports that COVID-19 patients experience:
  • decreased visual, 
  • subconjunctival bleeding, 
  • keratitis, 
  • the pseudomembranous formation, 
  • or conjunctival scarring.

Data from Unpublished Studies
A meta-analysis and systematic review by Sarma et al., which is currently in publication, reported that 3.17% (95% CI, 1.16 - 6.13) of patients with COVID-19 developed conjunctivitis.
Additionally, a cross-sectional study, which is also in the publication process, studied 534 cases of COVID-19 and reported that 4.68% of patients had the conjunctival injection.
However, the data from these two studies have not been peer-reviewed.


b. Posterior Eye Segments

Data regarding the manifestation of COVID-19 in the posterior segment of the human eye is still minimal. However, animal studies have identified retinitis and optic neuritis as an impact of COVID-19 on the eye's posterior segment. A case series reported 4 cases of COVID-19 with signs of retinal microangiopathy of the human eye on optical coherence tomography (OCT).



The potential for thromboembolism in the eyes due to COVID-19

Currently, COVID-19 is becoming recognized as a disease with high thromboembolic potential because there is a strong association between increased D-dimer and the severity of COVID-19. Patients with COVID-19 have been reported to experience pulmonary embolism, stroke, disseminated intravascular coagulation (DIC), and infarction of the extremities. Microvascular involvement in COVID-19 is thought to be related to eye manifestations because the retinal circulation is an end arterial system.



Eye Transmission of COVID-19

Currently, the potential for transmission of COVID-19 through ocular secretions is still not known with certainty. There is a theory that SARS-CoV-2 may accumulate in the ocular secretions in 3 ways:
  • direct injection of the droplets into the eye mucosa,
  • migration of the virus from the nasopharynx through the nasolacrimal duct,
  • or hematogenous spread to the tear glands.
Several studies tried to explore the presence of SARS-CoV-2 genetic material on the eye's surface by various attempts. They used conjunctival swabs or Schirmer paper to collect tears and then performing RT-PCR or virus isolation with Vero-6 cell inoculation.

From these studies, SARS-CoV-2 was reported to be detectable by RT-PCR from the viral sampling of the lower eyelid fornix. However, some studies unable to find the virus in tears.  In general, by viewed these existing journals, the percentage of SARS-CoV-2 particles in tears is 0–7.14% of the sample.

These controversial results mean that researchers have not concluded with certainty about the potential of tears as a transmission source. This conclusion's difficulty is also caused by variations in the sampling time from symptom onset, variations in the patient's condition (with/without ocular symptoms), and the small number of samples. To date, SARS-CoV-2 from eye secretions cannot be cultured.

Conjunctiva as a portal of entry Infection

A study reported two cases of positive paramedic SARS-CoV-2 via nasopharyngeal and conjunctival swabs. 

The first case was an anesthesiologist who intubated a COVID-19 patient. He wore personal protective equipment (PPE) without eye protection. Three days later, he experienced red eyes, conjunctival discharge, and respiratory symptoms until later diagnosed with COVID-19. The second case involved a nurse with a similar PPE condition with conjunctival congestion and respiratory symptoms. 

Both cases mentioned supporting the theory of the conjunctival mucosa as the portal of entry of SARS-CoV-2.


Summary
The most common eye clinical manifestations of COVID-19 is the anterior eye segment disorders, such as conjunctivitis characterized by redness, epiphora, and chemosis. Data regarding clinical manifestations in the posterior eye segment are still very limited, but some case reports stated that retinal microangiopathy is found in some COVID-19 patients.

SARS-CoV-2 can be transmitted through the conjunctival mucosa. However, currently, there is no conclusive data regarding the potential of tears as a transmission source. Some studies have found SARS-CoV-2 in tear samples, but others have not. Until now, the virus from eye secretions cannot be cultured.

The eye's physical examinations should be performed wearing gloves and an extension device such as a cotton swab to avoid direct contact with the patient's eye secretions. This is especially important because the eye examinations carried out have involved very close contact with the patient.


References
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2. Emparan JPO, Sardi-Correa C, López-Ulloa JA, et al. COVID-19 and the eye: how much do we really know? A best evidence review. Arq Bras Oftalmol. 2020 Jun;83(3):250–61.
3. Ho D, Low R, Tong L, et al. COVID-19 and the Ocular Surface: A Review of Transmission and Manifestations. Ocul Immunol Inflamm. 2020;28(5):726-734. doi: 10.1080/09273948.2020.1772313.
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8. Novel coronavirus disease with conjunctivitis and conjunctivitis as first symptom: Two cases report. Chinese Journal of Experimental Ophthalmology. 2020. https://cjeo-journal.org/novel-coronavirus-disease-with-conjunctivitis-and-conjunctivitis-as-first-symptom-two-cases-report/
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