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 Table of Contents  
Year : 2021  |  Volume : 33  |  Issue : 1  |  Page : 22-28

Ocular manifestations of COVID-19 infection: A review of available information

Division of Ophthalmology, College of Medicine, King Faisal University, Hofuf, Saudi Arabia

Date of Submission22-Sep-2020
Date of Decision07-Dec-2020
Date of Acceptance09-Dec-2020
Date of Web Publication19-Apr-2021

Correspondence Address:
Dr. Kaberi Biswas Feroze
PRA 14, CC 33 987 A, Pattathu Road, Chalikkavattom, Vennala PO, Kerala
Saudi Arabia
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/kjo.kjo_147_20

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Ocular signs and symptoms have been reported in COVID-19 patients, and there is increasing recognition of conjunctivitis as a prodromal symptom of this disease. There is also a surge of information about corneal, uveal, retinal, and neuroophthalmological involvement in COVID-19 infection. This review attempts to determine from various researches published during the time of the pandemic, the various ocular presentations of COVID-19 infection, its significance, correlation to the severity of systemic disease, and its importance as a mode of transmission of the disease. An extensive search strategy was employed to retrieve articles of ocular manifestations of COVID-19 published from January 2020 to date. Conjunctivitis was found to be the most common ocular manifestation, and viral RNA was noted in conjunctiva and tears, posing a risk for ophthalmologists. Other less commonly seen findings in COVID-19 infections include keratoconjunctivitis, blepharitis, retinal changes, and ophthalmoparesis. However, recent studies show increasing reports of retinal and neuroophthalmological manifestations of the COVID-19 infection.

Keywords: Conjunctivitis, COVID-19, novel coronavirus, ocular, ophthalmic, severe acute respiratory syndrome coronavirus 2

How to cite this article:
Feroze KB. Ocular manifestations of COVID-19 infection: A review of available information. Kerala J Ophthalmol 2021;33:22-8

How to cite this URL:
Feroze KB. Ocular manifestations of COVID-19 infection: A review of available information. Kerala J Ophthalmol [serial online] 2021 [cited 2021 Jul 26];33:22-8. Available from: http://www.kjophthal.com/text.asp?2021/33/1/22/314088

  Introduction Top

One of the most significant medical events in current times is the emergence of the novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV2), causing coronavirus disease 2019 (COVID-19).[1] The first cases, which presented as pneumonia of unknown origin, were identified in Wuhan, the capital city of Hubei province in China.[2] This condition is now recognized as a pandemic, and there are almost 65,870,030 confirmed cases of COVID-19, including 1,523,583 deaths, reported to the WHO.[3] The clinical features of COVID-19 are ubiquitous, ranging from being completely asymptomatic to acute respiratory distress and multiorgan dysfunction. The presenting symptoms range from fever, cough, dyspnea, to headaches, fatigue, myalgia, and even conjunctivitis.[4] Ocular signs and symptoms have also been reported in COVID-19 patients, and there is increasing recognition of conjunctivitis as a prodromal symptom of this disease.[5] As this is an ongoing pandemic, there is a lot of information being accrued on a daily basis, with newer researches contributing to better understanding of the disease process. Over the past couple of months, more and more studies are emerging of the virus affecting not only the conjunctiva, but also other structures such as the cornea, uvea, retina, and the optic nerve. This review attempts to determine from various researches published during the time of the pandemic, the different ocular presentations of COVID-19 infection, its significance, correlation to the severity of systemic disease, and its importance as a mode of transmission of the disease.

  Methods Top

The aim of this study was to review the available data on the ocular signs and symptoms of COVID-19 infection, demographics, correlation to the severity of systemic disease if any, and its importance from a public health point of view.

Search strategy

An extensive search was employed to retrieve articles of COVID-19 published from january 2020 to date. The search strategy included the following keywords, novel coronavirus or COVID-19 or SARS-CoV2, or eye or ophthalmology or ocular, either singly or variably combined. Databases searched included PubMed, Scopus, and Embase.

The following were the inclusion and exclusion criteria

Inclusion criteria

  1. Patients with COVID-19 infection having ocular symptoms
  2. Cross-sectional studies, case series, and case reports of the same

Exclusion criteria

  1. Studies of other designs
  2. Studies not in English language or in which an English translation could not be obtained
  3. Studies not demonstrating ocular signs and symptoms of COVID-19 infection.

  Results Top

After fulfilling the inclusion and exclusion criteria, 31 articles were obtained. Of these, 13 were cross-sectional studies [Table 1],[6],[7],[8],[9],[10],[11],[12],[13],[14],[15],[16],[17],[18] 2 were case series [Table 2],[19],[20] and the remaining were case reports [Table 3].[21],[22],[23],[24],[25],[26],[27],[28],[29],[30],[31],[32],[33],[34],[35],[36] Studies conducted purely at the molecular level were excluded.
Table 1: Cross sectional studies of coronavirus disease 19 patients with ocular manifestations

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Table 2: Case series of COVID-19 patients with ocular manifestations

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Table 3: Case reports of COVID-19 patients with ocular manifestations

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These studies involved 2804 patients of COVID-19. Of the 13 cross-sectional studies on COVID-19 patients, 11 of them noted that the most common ocular manifestation was a self-limited conjunctivitis.[6],[7],[8],[9],[10],[11],[12],[15],[16],[17],[18] Four of these studies were from China, two from Italy, and one each from Iran, Israel, Spain, Germany, and Turkey. Two of the cross-sectional studies were focused on the retinal signs of COVID-19, which included a reduction in the radial peripapillary capillary plexus (RPCP) density and an increase in retinal arterial and venous caliber.[13],[14] In a case series reported from Sao Paulo by Marinho et al., retinal and OCT changes were noted in 12 patients (age group: 25–69 years), 11–33 days after developing symptoms of COVID-19.[19] Another case series of five patients from Italy in the age group of 37–65 years showed that all patients presenting with conjunctival congestion were otherwise asymptomatic.[20] There were eight case reports of conjunctivitis, usually of the follicular type, and which resolved spontaneously without sequelae.[21],[22],[23],[24],[25],[26],[27],[28] However, there were two case reports of conjunctivitis due to the SARS-CoV2 virus, which subsequently developed into a keratoconjunctivitis[29],[30] Benito-Pascual et al. also described a case of COVID-19 conjunctivitis, which was followed by the development of ocular pain and defective vision, and on examination, revealed panuveitis.[31] There were three reports of patients developing retinopathy following COVID infection.[32],[33],[34] Ophthalmoparesis was noted in two case reports with patients presenting with diplopia following COVID-19 infection.[35],[36]

  Discussion Top

This review investigated the various ocular manifestations of COVID-19 infection. Conjunctivitis was found to be the most common ophthalmological manifestation. The incidence of conjunctivitis among COVID patients was found to range from 0.8% to almost 65% in different study populations. Wong et al. described a prevalence of 0.8%–31.6%.[37] Conjunctivitis was considered a rare COVID manifestation by other authors.[38],[39] Amesty et al. described it as a rare manifestation of nonsevere coronavirus infection.[40] The type of conjunctivitis noted most commonly seen was the follicular type and was associated in some cases with chemosis, pseudomembranes, and preauricular lymphadenopathy.[6],[7],[8],[9],[10],[11],[12],[15],[16],[17],[18],[20] The most common ocular sign noted was conjunctival hyperemia and the most common symptoms were tearing and burning sensation. Chen et al., Guan et al., Abrishami et al., Bostanci Ceran et al., Wu et al. and Zhou et al. noted that conjunctivitis was seen more often in patients with more severe form of the disease.[6],[7],[9],[10],[12],[16] Similar findings were also reported by Amesty et al.[40] In a study from Israel, conjunctivitis was associated with loss of sense of taste and smell and a more serious clinical course.[18] Conjunctival congestion could thus provide a clue to the severity of the COVID infection. Regarding the timing of onset of conjunctivitis, there were varying reports, some starting before onset of systemic symptoms, some even up to 13 days after disease onset. However, most studies in this review seem to suggest that conjunctivitis tends to occur more in the middle phase of the disease process. There are also descriptions of COVID-positive patients with conjunctivitis, who did not develop any systemic manifestations.[20] Therefore, a high index of suspicion for COVID-19 should be kept in mind in any patient presenting with signs of conjunctivitis during the present conditions. Taking a conjunctival swab would thus seem to be judicious in these circumstances. Paradoxically, many of the studies and case reports state that conjunctival swab was negative despite having a positive nasopharyngeal swab report.[10],[17],[28] It is also extremely important to ask a history of fever and respiratory complaints and travel history in any patient coming with viral conjunctivitis. The importance of personal protection of doctors should be of prime concern. Telemedicine consults could prove very useful in the diagnosis and reducing the risk to doctors and health-care workers. In most of the cases, conjunctivitis was found to be self-limited and subsided with the reduction of systemic manifestations.[8],[20] Conjunctivitis was reported to be seen more often in COVID patients with a history of hand–eye contact.[6] Thus, hand hygiene and frequent handwashing could represent one method to reduce the occurrence of COVID-related conjunctivitis.

Other manifestations of COVID-19 infection include blepharitis in a child with COVID-19,[16] keratoconjunctivitis,[29],[30] panuveitis,[31] retinal changes,[13],[14],[32],[33],[34] and ophthalmoparesis.[35],[36] Guo et al. described a case of bilateral keratoconjunctivitis, which responded to steroids.[29] The authors postulated that keratoconjunctivitis could reflect the cytokine surge which occurs as a part of the disease process. Cheema et al. presented a case report of a 29-year-old Canadian woman, who presented with a 1-day history of redness, watering, and photophobia in one eye.[30] Ocular examination showed conjunctival congestion and follicles, a pseudodendrite, and subepithelial infiltrates. Benito-Pascual et al. described a case of panuveitis following follicular conjunctivitis and although the uveitis resolved, there was residual disc pallor.[31] S-protein and ACE2 receptors are key pathways for the viral entry into cells.[41] The choroid, neural, and vascular endothelium are rich in ACE2 receptors, which could represent a site for virus adhesion and replication.

With the passage of time in the COVID pandemic, there are increasing reports of retinal involvement in COVID-19 patients. Two cross-sectional studies showed that there were alterations in retinal vasculature, one showing an increase in retinal venous caliber, and this correlates with the peak inflammatory response in the disease process and the severity of the disease process as well.[14] There was also a reduction in RPCP density, and this correlated with the severity of the disease.[13] Both these studies highlight the susceptibility of the retinal vasculature to the virus; it could also represent the virus affinity for the ACE2 receptors in the vascular endothelium. There were two reports of COVID-positive patients presenting with scotomas. Examination in one of them showed the presence of retinal hemorrhages, Roth's spots and a clinical picture resembling acute macular neuroretinopathy and paracentral acute middle maculopathy (PAMM).[32] The other patient showed a picture resembling an impending CRVO.[33] Both cases point to the prothrombotic nature of the disease as reported systemically as well.[42] There was also a case presenting with multifocal choroiditis (with choroidal hypoperfusion on imaging) and an Adie's pupil, which represent the affinity of the virus for the vascular endothelial ACE2 receptors and the neural tissue as well.[34]

There were two cases of ophthalmoparesis. Belghmaidi et al. reported a case of a 24-year-old confirmed COVID-19 patient who presented with sudden onset of diplopia and strabismus and was diagnosed as acute, partial third nerve palsy. She was treated with chloroquine and azithromycin and improved in 6 days. The authors suggest that this represents the neurotropism of the virus.[35] Dinkin et al. reported two cases of a 36-year-old male and a 71-year-old female, who presented with diplopia and ophthalmoparesis. There was associated leg paresthesia and areflexia. This points to a picture of polyneuropathy, again highlighting the neurotropism of the virus.

  Conclusions Top

Although conjunctivitis is the most common ocular presentation of COVID-19 viral infection, other parts of the eye including the retina and the optic nerve may be affected. With the passage of time, there are increasing reports of the virus affecting the retina and neuroophthalmological manifestations are being reported with increasing frequency. A conjunctivitis may precede or may not be followed by any systemic manifestations; therefore, it is very important to consider the possibility of COVID-19 in every case of red eye. A detailed travel history and a history of fever and cough are extremely important. Conjunctival swabs may help to confirm the diagnosis in suspicious cases, but they may be negative in a high proportion of cases. Conjunctival congestion is seen more often in severe COVID-19 infection, thus a red eye in a proven COVID-19 patient may be the harbinger of severe systemic symptoms. Hand–eye contact has been noted to be an important factor in the pathogenesis of COVID-19 conjunctivitis, underlining the importance of hand hygiene and frequent handwashing. The viral RNA has been detected in the conjunctiva of patients with COVID-19 having conjunctivitis; thus, ophthalmologists are particularly prone to get infected. Special precautionary measures should be adopted when examining patients presenting with red eye. Vision testing is also important in these patients to rule out posterior segment affection. The ophthalmologist during the time of the pandemic should keep his eyes open to the possibility of the SARS-CoV2 virus affecting every part of the eye. As the vaccine seems within reach and with increasing knowledge about the virus, the sense of panic and fear among populations may abate, but until then, it is best to take care, stay safe, and practice hand hygiene and social distancing to overcome this challenging situation.

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Conflicts of interest

There are no conflicts of interest.

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  [Table 1], [Table 2], [Table 3]


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