Research Review Article Ocular Manifestations of COVID-19: A Systematic Review and Meta-analysis

Research Review Article

Ocular Manifestations of COVID-19: A Systematic
Review and Meta-analysis

Naser Nasiri1, MS; Hamid Sharifi1, PhD; Azam Bazrafshan2, MS; Atefeh Noori3, MS
Mohammad Karamouzian1,4, MS; Ali Sharifi5, MD

1HIV/STI Surveillance Research Center, and WHO Collaborating Center for HIV Surveillance, Institute for Futures Studies in
Health, Kerman University of Medical Sciences, Kerman, Iran

2Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran
3Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada

4School of Population and Public Health, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada
5Department of Ophthalmology, Shafa Hospital, Afzalipour School of Medicine, Kerman University of Medical Sciences,

Kerman, Iran

ORCID:
Naser Nasiri: https://orcid.org/0000-0002-1505-0866
Ali Sharifi: https://orcid.org/0000-0003-0713-088X

Abstract
Several studies have reported the characteristics of Coronavirus disease 2019 (COVID-19), yet
there is a gap in our understanding of the ocular manifestations of COVID-19. In this systematic
review and meta-analysis, we investigated the prevalence of ocular manifestations in COVID-19
patients. We searched Pubmed, Embase, Scopus, Web of Science, and medRxiv from December
1, 2019 to August 11, 2020. Two independent reviewers screened the articles, abstracted the data,
and assessed the quality of included studies in duplicate. Thirty-eight studies were eligible after
screening of 895 unique articles, with a total of 8,219 COVID-19 patients (55.3% female; n = 3,486
out of 6,308 patients). Using data extracted from cross-sectional studies, we performed random-
effects meta-analyses to estimate the pooled prevalence of ocular symptoms along with 95%
confidence interval (CI). The prevalence of ocular manifestations was estimated to be 11.03% (95%
CI: 5.71–17.72). In the studies that reported the details of observed ocular symptoms, the most
common ocular manifestations were dry eye or foreign body sensation (n = 138, 16%), redness (n
= 114, 13.3%), tearing (n = 111, 12.8%), itching (n = 109, 12.6%), eye pain (n = 83, 9.6%) and discharge
(n = 76, 8.8%). Moreover, conjunctivitis had the highest rate among reported ocular diseases
in COVID-19 patients (79 out of 89, 88.8%). The results suggest that approximately one out of
ten COVID-19 patients show at least one ocular symptom. Attention to ocular manifestations,
especially conjunctivitis, can increase the sensitivity of COVID-19 detection among patients.

Keywords: Conjunctivitis; COVID-19; Meta-analysis; Ocular Manifestations; Systematic Review

J Ophthalmic Vis Res 2021; 16 (1): 103–112

Correspondence to:

Ali Sharifi, MD. Department of Ophthalmology, Shafa
Hospital, Afzalipour School of Medicine, Kerman
University of Medical Sciences, Kerman, Iran.
E-mail: a_sharifi@kmu.ac.ir; sharifialim2@gmail.com
Received: 01-10-2020 Accepted: 28-12-2020

Access this article online

Website:
https://knepublishing.com/index.php/JOVR

DOI:
10.18502/jovr.v16i1.8256

INTRODUCTION

Severe acute respiratory syndrome coronavirus
2 (SARS-CoV-2) was initially detected in late
This is an open access journal, and articles are distributed under the terms of
the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which
allows others to remix, tweak, and build upon the work non-commercially, as
long as appropriate credit is given and the new creations are licensed under the
identical terms.

How to cite this article: Nasiri N, Sharifi H, Bazrafshan A, Noori A,
Karamouzian M, Sharifi A. Ocular Manifestations of COVID-19: A Systematic
Review and Meta-analysis. J Ophthalmic Vis Res 2021;16:103–112.

© 2021 JOURNAL OF OPHTHALMIC AND VISION RESEARCH | PUBLISHED BY KNOWLEDGE E 103

http://crossmark.crossref.org/dialog/?doi=10.18502/jovr.v16i1.8256&domain=pdf&date_stamp=2019-07-17

https://knepublishing.com/index.php/JOVR

Ocular Manifestations of COVID-19; Nasiri et al

2019 in Wuhan, China,[1] and Coronavirus disease
2019 (COVID-19) swiftly spread across the globe,
and was declared a pandemic on March 11,
2020.[2] By August 14, 2020, 21,092,096 people
were infected with SARS-CoV-2, 757,727 of whom
passed away due to COVID-19 or its adverse health
consequences.[3]

COVID-19 may pose challenges in clinical
diagnosis because there is no pathognomonic
symptom to detect the disease. Several clinical
symptoms have been frequently reported among
COVID-19 patients including but not limited to
cough, fever, fatigue, sore throat, nasal obstruction,
shortness of breath, headache, sputum production,
and hemoptysis.[4] Moreover, while some patients
show a wider range of gastrointestinal symptoms
such as diarrhea, abdominal pain, low appetite,
and vomit,[5] others have shown renal and ocular
symptoms.[6]

Most clinical research about SARS-CoV-2 have
focused on respiratory manifestations; however,
a growing body of evidence has raised concerns
about the ocular complications caused by SARS-
CoV-2.[7] The reported ocular manifestations of
the infection vary greatly and include dry eye,
foreign body sensation, itching, blurring of vision,
conjunctivitis, chemosis, and photophobia.[8] Some
studies have even reported conjunctivitis as an
early sign for COVID-19 diagnosis.[9] Knowing
the prevalence and type of ocular manifestations
of COVID-19 can help physicians diagnose the
infection better and sooner in the course of
the disease. Therefore, we aimed to summarize
the relevant published literature on the ocular
manifestations of the COVID-19 patients.

METHODS

We completed our systematic review in
accordance with the preferred reporting items for
systematic reviews and meta-analyses (PRISMA)
guideline (See Supplementary file S1 for PRISMA
checklist).[10]

For this systematic review and meta-analysis,
we searched Pubmed, Embase, Scopus, Web
of Science, and medRxiv preprint server from
December 1, 2019 to August 11, 2020 for studies
published in English (See Supplementary file S2
for a sample search strategy). We also searched
the reference lists of related systematic reviews for
potentially eligible studies.

Inclusion Criteria and Study Selection

We included empirical observational studies
including cohort, case-control, cross-sectional,
case-reports, or case-series that reported about
ocular manifestations in COVID-19 patients. We
excluded editorials, commentaries, letters to
editors, and reviews. Two reviewers (NN and HSH)
independently, and in duplicate, screened the
titles and abstracts of identified citations, and
assessed the full-text of potentially eligible studies
for inclusion in the data synthesis. The reviewers
resolved the disagreements on the process of
study selection through feedback and discussion
with the senior author (ASH).

Data Collection

Two authors (NN and AB) independently, and in
duplicate, extracted data from each eligible study,
including study characteristics (e.g., first author,
publication date, study type, location, and total
sample size) and patients’ information (e.g., age,
sex, and ocular manifestations such as conjunctival
hyperemia, clear secretions, conjunctivitis, follicles,
petechia, and chemosis).

Quality Assessment of the Evidence

Two independent reviewers evaluated the quality
of included studies duplicate using the Joanna
Briggs Institute critical appraisal tool.[11] The
criteria suggested by Joanna Briggs to assess
quality include eight items for case-report studies,
nine items for cross-sectional studies, and ten
items for case-series. Reviewers resolved the
disagreements by adjudication or feedback from
the senior author.

Statistical Analysis

Data were presented using descriptive statistics
(i.e., mean, median, and standard deviation
[SD] for continuous variables and frequency
and percentage for categorical variables). To
assess the proportion of patients with a particular
manifestation, we calculated the sum of the
patients with a particular manifestation in different
papers and divided them to the number of
included patients. To account for the different
study designs included in the study, we only

104 JOURNAL OF OPHTHALMIC AND VISION RESEARCH VOLUME 16, ISSUE 1, JANUARY-MARCH 2021

Ocular Manifestations of COVID-19; Nasiri et al

considered cross-sectional studies in our meta-
analysis. Using random-effects meta-analysis,
we calculated the pooled estimated prevalence
and 95% confidence interval (95% CI) of ocular
manifestations, using metaprop command in Stata
version 14.2. We also assessed the heterogeneity
among the included studies using I2 and the
Q-statistic. A value of ≥50% of I2 and a P-
value of <0.1 for the Q-statistic was perceived as considerable heterogeneity. We then ran a meta-regression to assess the potential sources of heterogeneity. The following variables were included in the meta-regression: Method of COVID-19 diagnosis (polymerase chain reaction [PCR] or computed tomography scan [CT scan] vs clinical signs), the quality of studies (quality score < 4 vs quality score ≥ 4), the mean age of patients (age ≤ 45 years vs age > 45 years),
the method of examination by ophthalmologist
(standard ophthalmic exam vs non-standard
ophthalmic exam), and the recruited sample size
(sample size > 500 vs sample size ≤ 500). Based
on the reported information in the papers, we
also aimed to assess whether the reported ocular
manifestations preceded or followed the presence
of systemic symptoms. To do so, we calculated the
lag between ocular manifestation and systemic
disease as well as the lag between systemic
disease and ocular manifestation. All statistical
analyses were performed in Stata version 14.2
and all comparisons were two-tailed, with a
threshold P-value of 0.05.

RESULTS

Out of the 895 unique publications that were
assessed, 38 studies[12–49] were included
in this review (Figure 1). Overall, 13 studies
were case reports,[37–49] six were case-series
study,[13, 15, 18, 25, 28, 36] and the remaining 19 studies
were cross-sectional.[12, 14, 16, 17, 19–24, 26, 27, 29–35]
Twenty-four studies reported aggregate-level[12–35]
and fourteen[36–49]reported individual-level
information about ocular manifestations. Out
of the 38 studies, 1 study[16] was conducted among
healthcare providers (see Supplementary file S3
for type of study, sex, mean age, and main ocular
manifestations; Supplementary file S4 for location,
publication data, patient population, and chronic
disease). Moreover, out of the 38 included studies,
32 (3,719 out of 8,219 patients) were among
inpatients, four among outpatients (2,353 out of

8,219 patients), and two included outpatient and
inpatient individuals, simultaneously (2,147 out of
8,129 patients).

Demographic and clinical characteristics of
COVID-19 patients included in the reviewed
studies are presented in Table 1. A total of 8,219
patients with COVID-19 were enrolled in the
included studies. Across all COVID-19 studies,
6,308 reported sex distribution, 1,532 reported
other comorbidities with COVID-19, and 1,021
were at the individual level and reported ocular
symptoms and signs. The number of enrolled
patients in the included studies ranged from 1 to
1,452, most patients were female (n = 3,486 out of
6,308 patients, 55.3%), and the mean age of the
participants ranged between 7 and 65.8 years. The
diagnosis of SARS-CoV-2 was confirmed in 4,039
(49.1%) and 4,180 (50.9) patients using clinical signs
and CT scans. The most detected comorbidities
in patients were hypertension (593 out of 1,532),
diabetes mellitus (294 out of 1,532), respiratory
diseases (219 out of 1,532), and cardiovascular and
cerebrovascular diseases (188 out of 1,532).

Quality Assessment of Included Studies

Joanna Briggs Institute’s critical appraisal scores
ranged from 2 to 6 for case reports (out of 8
possible points), and 0 to 5 for prevalence (cross-
sectional) studies (out of 9 possible points), and 3
to 7 (out of 10 possible points) for single case-series
included in the review. Quality assessment tools
were different based on study design; therefore,
scores could not be directly compared (See
Supplementary file S5).

The Pooled Prevalence of Ocular
Manifestations

We included 19 cross-sectional studies
corresponding to 7,300 individuals for meta-
analysis of ocular manifestations among patients
with COVID-19. The pooled prevalence of all
ocular manifestations among COVID -19 patients
was 11.03% (95% CI: 5.71 to 17.72) (Figure 2), The
most prevalent ocular manifestations were dry
eye or foreign body sensation (n = 138, 16.0%),
redness (n = 114, 13.3%), tearing (n = 111, 12.8%),
itching (n = 109, 12.6%), eye pain (n = 83, 9.6%),
and discharge (n = 76, 8.8%). The most prevalent
ocular disease was conjunctivitis (n = 79, 88.8%).

JOURNAL OF OPHTHALMIC AND VISION RESEARCH VOLUME 16, ISSUE 1, JANUARY-MARCH 2021 105

Ocular Manifestations of COVID-19; Nasiri et al

Records identified through

database search

(n = 1,225)

S
c
re

e
n
in

g

In
c
lu

d
e
d

E

li
g

ib
il
it
y

Id

e
n
ti
fi
c
a
ti
o

n

Records identified through other

sources

(n = 25)

Records after duplicates removed

(n = 895)

Records screened

(n = 895)

Records excluded

(n = 815)

Full-text articles

assessed for eligibility

(n = 80)

Full-text articles excluded, with

reasons

(n = 11)

Reports were editorial,

commentaries or reviews

(n = 23)

Full text not found (n = 2)

Reported only Tear PCR (n =

4)

Study did not report any

information about ocular

manifestation COVID-19- (n =

2)

Studies included in

qualitative synthesis

(n = 38)

Figure 1. Flowchart of studies included in the systematic review of COVID-19 ocular manifestation

Other rare conditions such as keratitis (n = 2, 2.2%),
episcleritis (n = 2, 2.2%), keratoconjunctivitis (n =
2, 2.2%), hordeolum (n = 2, 2.2%), pingueculitis
(n = 1, 1.1%), posterior ischemic optic neuropathy
(n = 1, 1.1%) were also reported (Table 2). No
significant source of heterogeneity from the
included variables in the meta-regression was
detected (Table 3).

Five studies reported the lag between ocular
manifestation and systemic disease; however, nine
studies reported the lag between systemic disease

and ocular manifestation. Weighted mean between
onset ocular manifestations and systemic disease
was 0.04 days (range, 1 to 3 days). However,
weighted mean between systemic disease and
ocular manifestation was 1.5 days (range, 2 to 21
days).

DISCUSSION

This systematic review and meta-analysis included
38 studies with a total of 8,219 COVID-19 patients.

106 JOURNAL OF OPHTHALMIC AND VISION RESEARCH VOLUME 16, ISSUE 1, JANUARY-MARCH 2021

Ocular Manifestations of COVID-19; Nasiri et al

Figure 2. Pooled prevalence of ocular manifestation among patients with COVID-19

Based on the existing evidence, we found the
pooled prevalence of all ocular symptoms to be
11.03% (95% CI: 5.71 to 17.72) among COVID-
19 patients. Dry eye or foreign body sensation
was the most common reported ocular symptoms
(16.0%), followed by redness (13.3%) and tearing
(12.8%). The most prevalent ocular disease was
conjunctivitis (88.8%).

This study showed that approximately one out
of ten COVID-19 patients included in this study
showed at least one ocular manifestations.
Although these manifestations may not be
frequent, they should not be overlooked by
physicians and ophthalmologists.[50] These

findings are comparable with the findings
of previous studies on COVID-19 or other
coronaviruses. For example, Vabret et al in a
study in a French hospital, from November 2002
to April 2003, reported that ocular manifestations
were 16.7% (3 out of 18) in patients diagnosed
with human coronavirus NL63.[51] Moreover, Ulhaq
et al in a systematic review study up to April
4, 2020 reported that ocular manifestations in
COVID-19 patients were 5.5%.[52] The reason for
ocular manifestations among patients diagnosed
with COVID-19 and other coronaviruses could be
related to the presence of ACE2 receptor, the cell
receptor for coronaviruses and SARS-CoV-2, in

JOURNAL OF OPHTHALMIC AND VISION RESEARCH VOLUME 16, ISSUE 1, JANUARY-MARCH 2021 107

Ocular Manifestations of COVID-19; Nasiri et al

Table 1. Demographic and clinical characteristics of COVID-19 infection included in the reviewed studies

Characteristics N (%)

Diagnostic approach (n = 8,219)

Only clinical signs and CT Scan 4,180 (50.9)

PCR laboratory confirmed 4,039 (49.1)

Sex (n = 6,308)

Male 2,822 (44.7)

Female 3,486 (55.3)

Comorbidity with COVID-19 (n = 1, 532)

Hypertension 593 (38.7)

Diabetes 294 (19.2)

Respiratory system disease 219 (14.3)

Cardiovascular and cerebrovascular diseases 188 (12.3)

Cancer 60 (3.9)

Disease of immune system 59 (3.9)

Hepatitis 54 (3.5)

Liver disease 33 (2.1)

Kidney disease 32 (2.1)

the eye cells.[8] Transmission of SARS-CoV-2 by
tear is not unlikely,[53] and the eye can be a way
for entering the infection droplets to the body.[54]
Therefore, protecting eyes is essential for people,
especially for healthcare providers to protect
themselves against SARS-CoV-2.

The most important ocular manifestations in
COVID-19 patients were dry eye or foreign body
sensation, redness, tearing, itching, eye pain,
and discharge. The mechanism of dry eye or
foreign body sensation is unclear in COVID-
19 patients and may not be directly associated
with SARS-CoV-2. Indeed, the occurrence of dry
eye during the COVID-19 epidemic could be
due to wearing face masks and directing the
expiratory air current toward eyes, especially when
masks are loose against the face and nose.
The stream of air against ocular surface causes
accelerated evaporation of the tear and may
create dry eye symptoms. In persons with pre-
existing dry eye or poor-quality tear film, the
symptoms can be more common and prominent.
Limitation of access to lubricating agents in fear
of contamination of hands and drug containers
also deteriorates dry eye manifestations.[55, 56]
Furthermore, since the beginning of the pandemic,
people spend more time looking at screens that
may exacerbate dry eye sensation.[57, 58] While

screen watching, the rate and intensity of blinks is
significantly diminished, exacerbating the dry eye
symptoms. Loss of follow-up visits and reduced
seeking care in patients with previous dry eye
condition could be other factors that may have
contributed to increased dry eye symptoms during
the pandemic.[55, 56]

Conjunctivitis was the most common eye
disease in patients. Conjunctivitis could be
developed by certain viruses (e.g., Haemophilus
influenzae and Herpes simplex), bacteria
(e.g., Staphylococcal species, Streptococcus
pneumoniae, and Neisseria gonorrhoeae), and
allergies (e.g., pollen and animal dander).[59]
Conjunctivitis could also be developed by
coronavirus and SARS-CoV-2.[60, 61] In a study
in Iran among 142 COVID-19 patients, the
most prevalent ocular finding was conjunctival
hyperemia (44 persons; 31%); however, the
most prevalent ocular manifestation among
ICU-admitted patients was chemosis (17 out of
28 admitted to ICU; 60.7%), and 50.0% of the
patients admitted to ICU (14 of the 28) showed
conjunctival hyperemia.[23] Scalinci et al in a study
among five Italian COVID-19 patients reported
that conjunctivitis remained through the course
of the disease among COVID-19 patients.[38]
Hong et al in a study in China showed that some

108 JOURNAL OF OPHTHALMIC AND VISION RESEARCH VOLUME 16, ISSUE 1, JANUARY-MARCH 2021

Ocular Manifestations of COVID-19; Nasiri et al

Table 2. Symptoms and diseases of ocular in COVID-19 infection included in the reviewed studies (n = 1,021)

Characteristics N (%)

Symptom and sign (n = 932)

Dry eyes or foreign body sensation 138 (16.0)

Redness 114 (13.3)

Tearing 111 (12.8)

Itching 109 (12.6)

Eye pain 83 (9.6)

Discharge 76 (8.8)

Blurred vision or decreased vision 71 (8.2)

Photophobia 62 (7.2)

Chemosis 42 (4.9)

Irritation 21 (2.4)

Gritty feeling 14 (1.6)

Burning sensation 8 (0.9)

Lid edema 8 (0.9)

Subconjunctival hemorrhage 3 (0.3)

Pseudomembrane and hemorrhage 2 (0.2)

Pseudodendrite 1 (0.1)

Subepithelial infiltrates 1 (0.1)

Water secretion 1 (0.1)

Disease (n = 89)

Conjunctivitis 79 (88.8)

Keratitis 2 (2.2)

Episcleritis 2 (2.2)

Keratoconjunctivitis 2 (2.2)

Pingueculitis 1 (1.1)

Hordeolum 2 (2.2)

Posterior ischemic optic neuropathy 1 (1.1)

Table 3. Meta-regression analysis of the effect of the factors on the ocular manifestations of the COVID-19 patients

Variables Multivariable meta-regression

Coefficient P-value [95% conf. Interval]

Quality of the included papers (quality ≥4 vs
quality < 4) 0.02 0.59 –0.07 – 0.11 The mean age of the patients (≤ 45 years vs > 45
years

–0.11 0.29 –0.35 – 0.13

Clinical examination (standard ophthalmic exam vs
non-standard ophthalmic exam

0.12 0.33 –0.17 – 0.42

Diagnostic method (PCR vs CT Scan and clinical
signs)

–0.22 0.09 –0.50 – 0.05

The recruited sample size (sample size > 500 vs
sample size ≤ 500)

–0.22 0.13 –0.52 – 0.09

conf., confidence

JOURNAL OF OPHTHALMIC AND VISION RESEARCH VOLUME 16, ISSUE 1, JANUARY-MARCH 2021 109

Ocular Manifestations of COVID-19; Nasiri et al

patients reported conjunctivitis after admission for
treatment of COVID-19.[19] Chen et al in a cross-
sectional study in Wuhan China reported that some
patients had conjunctivitis as their first symptom
and others reported conjunctivitis after the clinical
symptom of COVID-19 had begun.[21] In a study
in Canada, an association between conjunctivitis
with corneal subepithelial infiltrations, corneal
epithelial defects, development of tender
preauricular lymphadenopathy, and conjunctival
follicular reaction was observed among COVID-
19 patients.[44] Navel et al reported tarsal
hemorrhage mucous filaments and tarsal
pseudomembranous in one COVID-19 patient.
They observed the eyelids were irritated by
numerous sticky secretions accumulating around
the eyelashes, and described mucous filaments,
tarsal pseudomembranous, and superficial
punctuate keratitis.[39]

Assessing and observing the symptoms and
ocular manifestations of COVID-19 patients could
improve clinicians’ diagnosis of the disease. During
the ongoing pandemic, ophthalmologists should
consider COVID-19 as a potential diagnosis when
observing ocular manifestations and conjunctivitis,
especially with other manifestations of COVID-
19-like respiratory signs or fever.[60] Incidence of
ocular symptoms may happen a few hours or days
before the onset of COVID-19 systemic signs such
as fever and cough.[18, 19, 36]

Ophthalmologists are at a high risk for SARS-
CoV-2 given their close contact with patients.
Although the transmission of SARS-CoV-2 via
tear is not unlikely[53] and the mechanism is
uncertain,[8, 62] there exists a risk of transmission,[54]
and ophthalmologists and other healthcare
providers should adhere to recommendations
about wearing eye protective gears in addition
to face masks and other protective devises
during clinical examinations.[63] This is particularly
important when it comes to interactions with
asymptomatic COVID-19 patients.[1]

We acknowledge the limitations of our study.
First, ocular manifestations were measured by
an ophthalmologist in some studies and through
patient self-reports in others. Second, given
the significant variations between the studies,
we could not merge the results of different study
designs. Third, most studies had a low sample size,
and the quality of the included studies was low,
and most were case reports and cross-sectional
studies. Lastly, most COVID-19 patients are

asymptomatic, but all patients enrolled in studies
were symptomatic which could overestimate the
infection’s manifestations.

SUMMARY

Attention to ocular manifestations in combination
with other COVID-19 manifestations could help
improve COVID-19 diagnosis. The main ocular
manifestations were dry eye, tearing, itching,
redness, eye pain, and foreign body sensation. It is
recommended that healthcare providers especially
ophthalmologists who are in close contacts with
patients wear eye protective goggles in addition to
other recommended protective equipment.

Financial Support and Sponsorship

Nil.

Conflicts of Interest

There are no conflicts of interest.

REFERENCES

1. Veritti D, Sarao V, Bandello F, Lanzetta P. Infection
control measures in ophthalmology during the COVID-19
outbreak: a narrative review from an early experience in
Italy. Eur J Ophthalmol 2020;30:621–628.

2. Khalili M, Karamouzian M, Nasiri N, Javadi S, Mirzazadeh
A, Sharifi H. Epidemiological characteristics of COVID-19:
a systematic review and meta-analysis. Epidemiol Infect
2020;148:e130.

3. Worldometer. COVID-19 coronavirus pandemic
[Internet]. Worldometer; 2020. Available from:
https://www.worldometers.info/coronavirus/

4. Jin X, Lian JS, Hu JH, Gao J, Zheng L, Zhang YM, et al.
Epidemiological, clinical and virological characteristics of
74 cases of coronavirus-infected disease 2019 (COVID-19)
with gastrointestinal symptoms. Gut 2020;69:1002–1009.

5. Han C, Duan C, Zhang S, Spiegel B, Shi H, Wang W,
et al. Digestive symptoms in COVID-19 patients with mild
disease severity: clinical presentation, stool viral RNA
testing, and outcomes. Am J Gastroenterol 2020;115:916–
923.

6. Renu K, Prasanna PL, Valsala Gopalakrishnan A.
Coronaviruses pathogenesis, comorbidities and multi-
organ damage – a review. Life Sci 2020;255:117839.

7. Seah I, Agrawal R. Can the Coronavirus Disease 2019
(COVID-19) affect the eyes? A review of Coronaviruses and
ocular implications in humans and animals. Ocul Immunol
Inflamm 2020;28:391–395.

8. Ho D, Low R, Tong L, Gupta V, Veeraraghavan A,
Agrawal R. COVID-19 and the ocular surface: a review of
transmission and manifestations. Ocul Immunol Inflamm
2020;28:726–734.

110 JOURNAL OF OPHTHALMIC AND VISION RESEARCH VOLUME 16, ISSUE 1, JANUARY-MARCH 2021

https://www.worldometers.info/coronavirus/

Ocular Manifestations of COVID-19; Nasiri et al

9. Mahayana IT, Angsana NC, Kamila A, Fatiha NN, Sunjaya
DZ, Andajana W, et al. Literature review of conjunctivitis,
conjunctival swab and chloroquine effect in the eyes: a
current updates on COVID-19 and ophthalmology. J Med
Sci 2020;52:21–28.

10. Moher D, Liberati A, Tetzlaff J, Altman DG, Group
P. Preferred reporting items for systematic reviews
and meta-analyses: the PRISMA statement. PLOS Med
2009;6:e1000097.

11. Joanna Briggs Institute. The Joanna Briggs Institute
Critical Appraisal tools for use in JBI systematic
reviews checklist for prevalence studies [Internet].
Joanna Briggs Institute; 2017. Available from:
http://joannabriggs.org/research/critical-appraisal-
tools.html

12. Zhang X, Chen X, Chen L, Deng C, Zou X, Liu W, et al. The
evidence of SARS-CoV-2 infection on ocular surface. Ocul
Surf 2020;18:360–362.

13. Xia J, Tong J, Liu M, Shen Y, Guo D. Evaluation of
coronavirus in tears and conjunctival secretions of patients
with SARS-CoV-2 infection. J Med Virol 2020;92:589–
594.

14. Wu P, Duan F, Luo C, Liu Q, Qu X, Liang L, et al.
Characteristics of ocular findings of patients with
Coronavirus Disease 2019 (COVID-19) in Hubei Province,
China. JAMA Ophthalmol 2020;138:575–578.

15. Valente P, Iarossi G, Federici M, Petroni S, Palma
P, Cotugno N, et al. Ocular manifestations and viral
shedding in tears of pediatric patients with coronavirus
disease 2019: a preliminary report. J AAPOS 2020:S1091–
8531(20)30115-4.

16. Tostmann A, Bradley J, Bousema T, Yiek WK, Holwerda M,
Bleeker-Rovers C, et al. Strong associations and moderate
predictive value of early symptoms for SARS-CoV-2 test
positivity among healthcare workers, the Netherlands,
March 2020. Euro Surveill 2020;25:2000508.

17. Kumar K, Prakash AA, Gangasagara SB, Rathod SBL, Ravi
K, Rangaiah A, et al. Presence of viral RNA of SARS-CoV-
2 in conjunctival swab specimens of COVID-19 patients.
Indian J Ophthalmol 2020;68:1015–1017.

18. Karimi S, Arabi A, Shahraki T, Safi S. Detection of
severe acute respiratory syndrome Coronavirus-2 in
the tears of patients with Coronavirus disease 2019.
Eye 2020;34:1220–1223.

19. Hong N, Yu W, Xia J, Shen Y, Yap M, Han W.
Evaluation of ocular symptoms and tropism of SARS-CoV-
2 in patients confirmed with COVID-19. Acta Ophthalmol
2020;26:10.1111/aos.14445.

20. Güemes-Villahoz N, Burgos-Blasco B, Arribi-Vilela A,
Arriola-Villalobos P, Rico-Luna CM, Cuiña-Sardiña R, et al.
Detecting SARS-CoV-2 RNA in conjunctival secretions: is
it a valuable diagnostic method of COVID-19? J Med Virol
2020:10.1002/jmv.26219.

21. Chen L, Deng C, Chen X, Zhang X, Chen B, Yu H, et al.
Ocular manifestations and clinical characteristics of 535
cases of COVID-19 in Wuhan, China: a cross-sectional
study. Acta Ophthalmol 2020;10.1111/aos.14472.

22. Bostanci Ceran B, Ozates S. Ocular manifestations
of coronavirus disease 2019. Graefes Arch Clin Exp
Ophthalmol 2020:258:1959–1963.

23. Abrishami M, Tohidinezhad F, Daneshvar R, Omidtabrizi
A, Amini M, Sedaghat A, et al. Ocular manifestations of

hospitalized patients with COVID-19 in Northeast of Iran.
Ocul Immunol Inflamm 2020:28:739–744.

24. Lapostolle F, Schneider E, Vianu I, Dollet G, Roche B,
Berdah J, et al. Clinical features of 1487 COVID-19 patients
with outpatient management in the Greater Paris: the
COVID-call study. Intern Emerg Med 2020:15:813–817.

25. Ye Y, Song Y, Yan M, Hu C, Chen X, Yu J, et al.
Novel coronavirus pneumonia combined with
conjunctivitis: three cases report. Zhonghua Shiyan
Yanke …