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Ophthalmic Manifestations Of Coronavirus


Ophthalmic Manifestations Of Coronavirus

Article Author:
Katherine Hu
Article Author:
Jay Patel
Article Editor:
Bhupendra Patel
Updated:
8/8/2020 8:19:43 PM
For CME on this topic:
Ophthalmic Manifestations Of Coronavirus CME
PubMed Link:
Ophthalmic Manifestations Of Coronavirus

Introduction

Since December 2019, coronavirus disease 2019 (COVID-19) has become a global pandemic caused by the highly transmissible severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).[1] There have been several reports of eye redness and irritation in COVID-19 patients, both anecdotal and published, suggesting that conjunctivitis may be an ocular manifestation of SARS-CoV-2 infection. 

A study conducted during the 2003 Severe Acute Respiratory Syndrome (SARS) outbreak detected SARS-CoV in tear samples in SARS patients in Singapore.[2] Lack of eye protection was a primary risk factor of SARS-CoV transmission from SARS patients to healthcare workers in Toronto, prompting a concern that respiratory illness could be transmitted through ocular secretions.[3][4] Similar concerns have been raised with SARS-CoV-2, especially among eye care providers and those on the front lines triaging what could be initial symptoms of COVID-19.

As conjunctivitis is a common eye condition, ophthalmologists may be the first medical professionals to evaluate a patient with COVID-19. Indeed, one of the first providers to voice concerns regarding the spread of Coronavirus in Chinese patients was Li Wenliang, MD, an ophthalmologist. He later died from COVID-19 and was believed to have contracted the virus from an asymptomatic glaucoma patient in his clinic.

The authors of this article have attempted to collect the most up-to-date information on ophthalmic manifestations of COVID-19 as a resource for identifying symptoms, providing diagnostic pearls, and mitigating transmission.

Etiology

SARS-CoV-2 is a novel enveloped, positive single-stranded RNA beta coronavirus that causes COVID-19, originally linked to an outbreak in Wuhan of China's Hubei province.[1] Direct contact with mucous membranes, including the eye, is a suspected route of transmission.

Coronaviruses can cause severe ocular disease in animals, including anterior uveitis, retinitis, vasculitis, and optic neuritis in feline and murine species. However, ocular manifestations in humans are mild and rare.[5] There are no described ocular manifestations of Middle East Respiratory Syndrome (MERS) or SARS, though, as previously stated, SARS-CoV was isolated in ocular secretions.[2] Other coronaviruses have been found to cause viral conjunctivitis in humans.[6]

Epidemiology

At the time of writing this article on April 4, 2020, there have been 1,272,953 confirmed cases and 69,428 deaths due to COVID-19 worldwide according to the World Health Organization (WHO), with 79,332 new cases confirmed in the last 24 hours. The Center for Disease Control and Prevention (CDC) has reported 337,278 cases and 9,637 deaths in the United States to date.

Ocular manifestations of COVID-19 are overall rare in the published literature. Only 9 (0.8%) out of 1,099 patients from 552 hospitals across 30 provinces in China were reported to have "conjunctival congestion."[7]

A recent case series reported ocular symptoms in 12 (31.6%) of 38 hospitalized patients with COVID-19 in Hubei province, China.[8] These 12 of 38 patients had conjunctival hyperemia (3 patients), chemosis (7 patients), epiphora (7 patients), or increased secretions (7 patients). Of note is that one patient who had epiphora presented with epiphora as the first symptom of COVID-19. Of those with ocular manifestations, 2 (16.7%) patients had positive results of SARS-CoV-2 on reverse-transcriptase polymerase chain reaction (RT-PCR) by a conjunctival swab as well as by nasopharyngeal swabs. Only one patient in this study presented with conjunctivitis as the first symptom.[8] The authors noted that patients with ocular symptoms had higher white blood cell and neutrophil counts, C-reactive protein, and higher levels of procalcitonin and lactate dehydrogenase compared to patients without ocular abnormalities. 

Out of 30 hospitalized patients with COVID-19 tested by Xia et al., one patient had conjunctivitis and was also the sole patient in the study to test positive for SARS-CoV-2 in ocular secretions by a conjunctival swab. This patient did not have a severe fever or respiratory symptoms at the time of testing.[9]

Pathophysiology

The potential of infection through ocular secretions is currently unknown, and it remains unclear how SARS-CoV-2 accumulates in ocular secretions. Possible theories include direct inoculation of the ocular tissues from respiratory droplets or aerosolized viral particles, migration from the nasopharynx via the nasolacrimal duct, or even hematogenous spread through the lacrimal gland.[5]

History and Physical

Patients infected with SARS-CoV-2 can present with symptoms of conjunctivitis, including eye redness, ocular irritation, foreign body sensation, tearing, and chemosis. These symptoms have more commonly affected patients with severe systemic symptoms of COVID-19, though they can rarely present as an initial manifestation of the disease.[8]

Examination findings include those consistent with mild follicular conjunctivitis, including unilateral or bilateral bulbar conjunctiva injection, follicular reaction of the palpebral conjunctiva, watery discharge, and mild eyelid edema. Bilateral chemosis alone may represent third-spacing in a critically ill patient rather than a true ocular manifestation of the virus.

There have been no reports of COVID-19 patients experiencing blurred vision, subconjunctival hemorrhage, eyelid ecchymoses, conjunctival scarring, keratitis, or pseudomembrane formation.

Evaluation

A thorough history should be conducted regarding the onset, duration, and characteristics of symptoms. A presumptive diagnosis can be made based on detailed history taking alone, provided that the patient denies more concerning symptoms such as significant eye pain, decreased vision, or light sensitivity. Anterior segment examination at the slit lamp or bedside can confirm findings of conjunctivitis. Measurement of visual acuity, intraocular pressure, and dilated fundus examination may be warranted to rule out more harmful ocular diseases.

SARS-CoV-2 can be detected in RT-PCR by sweeping the lower eyelid fornices to collect tears and conjunctival secretions with a virus sampling swab.[9]

All patients should be questioned about recent fever, respiratory symptoms, exposure, and travel history to assess the need for further evaluation of COVID-19.

Treatment / Management

As with other viral infections, ocular manifestations of COVID-19 are presumed to be self-limited and can be managed with symptomatic care.

As of March 18, 2020, the American Academy of Ophthalmology has urged all ophthalmologists to provide only urgent or emergent care to reduce the risk of SARS-CoV-2 transmission and to conserve disposable medical supplies. In the absence of significant eye pain, decreased vision, or light sensitivity, many patients can be managed remotely with a trial of frequent preservative-free artificial tears, cold compresses, and lubricating ophthalmic ointment. A short course of topical antibiotics can be added to prevent or treat bacterial superinfection based on the patient's symptoms and risk factors (e.g., contact lens wear).[10] Specific criteria are presented below. 

Although preliminary studies suggest that the risk of viral transmission through ocular secretions is low, large-scale research has not yet been done, and new data is emerging daily. Healthcare providers are, therefore, still urged to wear proper protection of the eyes, nose, and mouth when examining patients (see below). It has been suggested that ocular transmission of the COVID-19 virus may occur.[4]

Eye care providers and technicians may be more susceptible to infection due to the nature and proximity of the ophthalmic examination.[11] Eye care providers are encouraged to use slit lamp breath shields and should counsel patients to speak as little as possible when sitting at the slit lamp to reduce the risk of virus transmission. Disinfection and sterilization practices should be employed for shared clinic equipment such as tonometers, trial frames, pinhole occluders, B-scan probes, and contact lenses for laser procedures.[2][11] Disposable barrier protection of clinic tools should be used where possible.

Stratification of Ophthalmic Patients for Clinic Visits

In the presence of life-threatening infections such as this, ophthalmologists have to achieve a balance between providing ophthalmic care and infection control. Most ophthalmic conditions are not life-threatening. Furthermore, many can be managed with some delay in treatment as they progress relatively slowly (cataracts, glaucoma, ptosis, etc.). However, some conditions like retinal detachments, acute infections (cellulitis, orbital cellulitis), severe inflammation (uveitis), and trauma require more urgent attention. To that end, the following is suggested for the management of ophthalmic patients:

1. All routine ophthalmic patients are delayed until the severity of disease spread reduces as determined by the WHO and the local Chief Medical Officer. These include chronic conditions and routine clinic annual and other follow-ups as well as new patients with chronic conditions like cataracts, ptosis, etc. 

2. New patient referrals are reviewed by the consultant surgeon to determine urgency. If necessary, telephone interviews with the referring doctor and/or the patient are held. 

3. All patients considered for a clinic visit are reviewed for three things: 

  • presence of a fever, cough or shortness of breath
  • any foreign travel or travel to an area with a high infection rate within the prior 14 days
  • any contact with patients who have been diagnosed as having COVID-19

The presence of any of these would be a reason to consider the necessity of seeing and examining the patient more closely. If a patient has two of the three are referred for medical assessment. If a patient with COVID-19 or one with a fever, cough, or shortness of breath needs to be examined, the patient is seen in a separate isolation room. Ideally, only one person (physician, technician, etc.) should be present in the room (as ophthalmic rooms tend to be small) and should wear the full personal protective equipment (PPE): gown, N95 mask, face shield, and gloves. Hands are washed before and after examination for a minimum of 20 seconds with soap and water. Once the ophthalmic examination is completed, the patient is referred for further assessment by the medical team. 

Protection of Medical Workers:

Although the 2003 SARS-CoV crisis did not create quite so severe a spread of infection in the United States, it was noted that health care workers (HCW) accounted for about 20% of all patients with infections.[12] Most recent figures show that HCWs make up 9% of Italy's COVID-19 cases, and more than 100 health care workers have died from COVID-19 infections, including, at the last count, more than 60 doctors (in Italy). Figures in other countries will continue to increase. 

It is, therefore, vital that front-line medical workers wear proper protection. Secondly, it is important to monitor these health care workers for disease and implement appropriate containment measures. 

As has become increasingly evident, there is a severe shortage of appropriate personal protective equipment for healthcare providers. To that end, it behooves us to choose the level of protective gear based upon the risk of infection. The following is suggested:

  • For all patients who have none of the three criteria mentioned above, the medical workers will wear a surgical mask, a face shield, and gloves. Hands are washed before and after every encounter.
  • If a patient is positive for any of the three criteria, the full PPE of gown, face shield, gloves, and the N95 mask are worn. 
  • It has been noted that droplets from sneezes can travel up to 6 m.[13] To that end, inventive ophthalmic technicians at the Moran Eye Center have developed a slit-lamp shield made by passing two plastic sheets through a laminator without a paper in between and cutting openings for the eye-pieces (Fig 1). Others have used old x-ray films in a similar way since commercially available shields are in short supply. 
  • Conversations are kept to a minimum during the consultation. Ophthalmologists are, by nature, a gregarious lot. Such temptations are to be resisted. 
  • As a shortage of surgical masks has become a reality, some institutions are storing used masks at the end of each day in a container with a view to re-sterilization if necessary. 
  • As many as a quarter of patients being injected under sedation may develop a severe involuntary sneeze.[14][15] This is more common with eyelid injections than with retrobulbar injections. Ophthalmic surgeons should be acutely aware of this to take appropriate precautions during the administration of the local anesthetic. 

Surveillance of Medical Workers:

  • In Singapore, health workers report their temperatures twice a day via an online system: this is eminently sensible as the "walk-by" temperature-testing that is currently practiced may not be as accurate or complete with staff arriving early, leaving late, etc.[16]
  • All travel outside the state or country should be declared to the medical administration for review. 
  • All health workers should self-report any symptoms, so appropriate testing may be performed: isolation and contact-tracing would then be undertaken as deemed necessary. 

Sterilization of Equipment

  • The slit-lamp shields are disinfected with 70% ethyl alcohol after each patient. 70% ethyl alcohol has been shown to reduce coronavirus infectivity.[13]
  • Slitlamps, B-scan probes, and any other tools are similarly cleaned with 70% ethyl alcohol.
  • Goldman tonometers are sterilized with a 10% diluted sodium hypochlorite solution, which inactivates coronaviruses.[17]

 

Differential Diagnosis

Ocular manifestations of COVID-19 have so far been uncommon, with most patients experiencing mild conjunctivitis otherwise indistinguishable from other viral etiologies. Differential diagnosis includes a broad range of common ocular manifestations of eye redness and increased tearing:

  • Other viral conjunctivitis (e.g., Adenovirus)
  • Bacterial conjunctivitis
  • Allergic conjunctivitis
  • Herpes simplex virus keratitis
  • Anterior uveitis
  • Corneal abrasion
  • Foreign body
  • Dry eye syndrome
  • Exposure keratopathy in an intubated patient
  • Chemosis in a critically ill patient

 

Prognosis

Ocular manifestations of COVID-19 are currently thought to be self-limited. There are currently no reports of sight-threatening manifestations of COVID-19.

Complications

There have been no complications of ocular manifestations of COVID-19 reported, though larger studies and long-term follow up of these patients have not yet been conducted.

Deterrence and Patient Education

Prevention strategies are vital to limiting the spread of disease. In addition to physical distancing and practicing good hand-washing hygiene, patients should employ behavioral changes that reduce the direct touching of the eyes and face.

  • Refraining from wearing contact lenses during the outbreak
  • Refraining from applying cosmetics
  • Wearing glasses and sunglasses

Pearls and Other Issues

  • Ocular shedding of SARS-CoV-2 via tears is a distinct possibility of which ophthalmologists should be aware.
  • Conjunctivitis or tearing can be the first presentation in a patient with the COVID-19 infection.
  • Patients may present with chemosis in advanced cases (Fig 2), or follicular conjunctivitis (Fig 3).
  • The ocular examination should be performed while wearing gloves and the use of extension instruments (cotton swabs, etc.) to avoid direct contact with secretions.
  • As many patients who visit the ophthalmic clinic are elderly, many with comorbidities, it is important to screen the need for the visit ahead of time and only see patients who need urgent care.
  • Social distancing, as advocated in many countries, means being 6 ft away from others: this is clearly impossible in the clinical world and certainly in the small confines of ophthalmic examination lanes. One way to practice it is to have only one person in the room with the patient.
  • Anecdotally, it has been observed that physicians most at risk of becoming infected include ophthalmologists, otolaryngologists, and anesthesiologists because of the proximity of the examiners to mucosal surfaces.
  • When performing surgery under general anesthesia, it has been recommended that surgeons and other staff do not enter the room for 15 minutes after intubation or extubation. In our institution, this is applied to all general anesthesia cases, whether the patient is COVID-19 positive or negative.

Enhancing Healthcare Team Outcomes

Within the outpatient, inpatient, and surgical settings, an interprofessional approach is necessary to manage COVID-19 patients and mitigate the spread of disease successfully.

There should be clear communication between hospital administration, provider teams, and clinic support staff regarding expectations for screening patients, wearing personal protective equipment, and utilizing new technologies for telemedicine consultations. [Level 5 evidence]



(Click Image to Enlarge)
This illustration, created at the Centers for Disease Control and Prevention (CDC), reveals ultrastructural morphology exhibited by coronaviruses. Note the spikes that adorn the outer surface of the virus, which impart the look of a corona surrounding the virion, when viewed electron microscopically. In this view, the protein particles E, S, and M, also located on the outer surface of the particle, have all been labeled as well. A novel coronavirus, named Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2), was identified as the cause of an outbreak of respiratory illness first detected in Wuhan, China in 2019. The illness caused by this virus has been named coronavirus disease 2019 (COVID-19).
This illustration, created at the Centers for Disease Control and Prevention (CDC), reveals ultrastructural morphology exhibited by coronaviruses. Note the spikes that adorn the outer surface of the virus, which impart the look of a corona surrounding the virion, when viewed electron microscopically. In this view, the protein particles E, S, and M, also located on the outer surface of the particle, have all been labeled as well. A novel coronavirus, named Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2), was identified as the cause of an outbreak of respiratory illness first detected in Wuhan, China in 2019. The illness caused by this virus has been named coronavirus disease 2019 (COVID-19).
Contributed from the CDC, Alissa Eckert, MS; Dan Higgins, MAM (Public Domain)

(Click Image to Enlarge)
A slit-lamp shield to protect the examiner as designed by Moran Technicians Stein Erickson, Emily Petersen and Anna Reed together with help from others: made by passing two lamination sheets together through a laminator without anything inbetween. Results in a rigid shield which can be cleaned with alcohol and reused. Other materials that may be used include used X-Ray films but these do not have the clarity needed.
A slit-lamp shield to protect the examiner as designed by Moran Technicians Stein Erickson, Emily Petersen and Anna Reed together with help from others: made by passing two lamination sheets together through a laminator without anything inbetween. Results in a rigid shield which can be cleaned with alcohol and reused. Other materials that may be used include used X-Ray films but these do not have the clarity needed.
Contributed on behalf of the Moran Eye Center by Dr. Katherine Hu MD and Prof. BCK Patel MD, FRCS

(Click Image to Enlarge)
Chemosis: conjunctival edema and inflammation. Can be seen with viral and bacterial infections, after eyelid surgery, trauma, thyroid disease and orbital tumors
Chemosis: conjunctival edema and inflammation. Can be seen with viral and bacterial infections, after eyelid surgery, trauma, thyroid disease and orbital tumors
Contributed by Prof. BCK Patel MD, FRCS

(Click Image to Enlarge)
Follicular conjunctivitis may be seen with viral infections like herpes zoster, Epstein-Barr virus infection, infectious mononucleosis), chlamydial infections, and in reaction of topical medications and molluscum contagiosum. Follicular conjunctivitis has been described in patients with the COVID-19 infection (coronavirus infection). The inferior and superior tarsal conjunctiva and the fornices show gray-white elevated swellings which are about 0.5 - 1 mm in diameter and have a velvety appearance
Follicular conjunctivitis may be seen with viral infections like herpes zoster, Epstein-Barr virus infection, infectious mononucleosis), chlamydial infections, and in reaction of topical medications and molluscum contagiosum. Follicular conjunctivitis has been described in patients with the COVID-19 infection (coronavirus infection). The inferior and superior tarsal conjunctiva and the fornices show gray-white elevated swellings which are about 0.5 - 1 mm in diameter and have a velvety appearance
Contributed by Prof. Bhupendra C. K. Patel MD, FRCS

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