Relations between the ocular surface and SARS-CoV-2 / Relações entre superfície ocular e SARS-CoV-2

ABSTRACT Introduction: The SARS-CoV-2 pandemic has been a major challenge for the international scientific community. Since its inception, studies aiming to describe pathophysiological aspects and clinical manifestations of the disease have been conducted, raising hypotheses and confirming possible associations. One aspect of this scientific medical production is the role of the ocular surface as a means of transmission and clinical presentation of viral syndrome. Objectives: To analyze the role of the ocular surface in transmission, pathophysiology, and clinical manifestations of SARS-CoV-2, by means of a systematic review. Methods: The search was carried out in three databases: Cochrane, PubMed Central Journals and MEDLINE, using the following descriptors: "COVID-19, ophthalmology". The filters last five years and studies on humans resulted in 32 studies; in that 12 were excluded for not meeting the purpose of the study. Results: There are still few published studies on the relation between SARS-CoV-2 and the ocular route. Most studies showed an association between the presence of nonspecific ocular manifestations and infection by the new coronavirus, with limitations in the number of patients analyzed and the methodology adopted. Hypotheses about the pathophysiological role are largely anchored in the association of SARS-CoV and the ocular surface evaluated in the past. Comments: The results found are still not sufficient to confirm the role of the ocular surface in the pathophysiology of the disease. Most of these preliminary studies are of considerable importance in raising hypotheses based on the medical analysis of the patients studied. However, larger studies with standardized methodology for diagnostic protocol and laboratory analysis of the individuals assessed are required.

RESUMO Introdução: A pandemia da SARS-CoV-2 tem sido um grande desafio para a comunidade científica internacional. Desde seu surgimento, estudos com a intenção de descrever os aspectos fisiopatológicos e as manifestações clínicas da doença vêm sendo conduzidos, levantando hipóteses e confirmando possíveis associações. Um dos temas dessa produção médica científica é o papel da superfície ocular como meio de transmissão e apresentação clínica da síndrome viral. Objetivo: Analisar o papel da superfície ocular na transmissão, na fisiopatologia e nas manifestações clínicas de SARS-CoV-2, através de uma revisão sistemática. Realizou-se a busca em três bancos de dados Cochrane Database, PubMed® e MEDLINE®, utilizando os descritores "COVID-19 e ophthalmology". Foram definidos como filtros o artigo ter sido publicado nos últimos 5 anos e estudo realizado em humanos, tendo sido encontrados 32 artigos. Destes, foram excluídos 12 por não corresponderem ao objetivo do estudo. Resultados: Ainda são poucos os estudos publicados sobre a relação entre o coronavírus 2 da síndrome respiratória aguda grave (SARS-CoV-2) e a via ocular. A maioria dos estudos mostrou associação entre a presença de manifestações oculares inespecíficas e a infecção pelo novo coronavírus, com limitações no número de pacientes analisados e na metodologia adotada. Hipóteses sobre o papel fisiopatológico se ancoram, em grande parte, na associação estudada entre o SARS-CoV-2 e a superfície ocular no passado. Comentários: Os resultados encontrados ainda não são suficientes para confirmar o papel da superfície ocular na fisiopatologia da doença. Grande parte desses estudos preliminares têm importância considerável ao levantar hipóteses baseadas na análise clínica dos pacientes estudados. No entanto, são necessários estudos maiores e com metodologia padronizada para protocolo diagnóstico e análise laboratorial dos indivíduos avaliados.

COVID-19 pandemic from an ophthalmology point of view.

Coronavirus disease 2019 (COVID-19) is caused by a highly contagious RNA virus termed as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Ophthalmologists are at high-risk due to their proximity and short working distance at the time of slit-lamp examination. Eye care professionals can be caught unaware because conjunctivitis may be one of the first signs of COVID-19 at presentation, even precluding the emergence of additional symptoms such as dry cough and anosmia. Breath and eye shields as well as N95 masks, should be worn while examining patients with fever, breathlessness, or any history of international travel or travel from any hotspot besides maintaining hand hygiene. All elective surgeries need to be deferred. Adults or children with sudden-onset painful or painless visual loss, or sudden-onset squint, or sudden-onset floaters or severe lid oedema need a referral for urgent care. Patients should be told to discontinue contact lens wear if they have any symptoms of COVID-19. Cornea retrieval should be avoided in confirmed cases and suspects, and long-term preservation medium for storage of corneas should be encouraged. Retinal screening is unnecessary for coronavirus patients taking chloroquine or hydroxychloroquine as the probability of toxic damage to the retina is less due to short-duration of drug therapy. Tele-ophthalmology and artificial intelligence should be preferred for increasing doctor-patient interaction.

SARS-COV-2 viral load in tears of patients with COVID-19 in the early symptomatic stages: comparison of two different tear sampling methods.

PURPOSE: To evaluate the presence of SARS-CoV-2 virus in tears of patients with COVID-19 in the early symptomatic stages and to compare two different sampling methods. MATERIALS AND METHOD: In this cross-sectional study, tears sampling was performed in COVID-19 patients admitted within the first 7 days of symptom onset. The samples were collected with both conjunctival swabs and Schirmer strips. Each specimen was analyzed via RT-PCR. The viral load was evaluated in terms of the cycle threshold value. Ocular and systemic symptoms and comorbidities of the patients were also recorded. RESULTS: Forty patients were included. The average time from the initiation of symptoms was 3.15 days. Unilateral conjunctivitis has been observed in 5% of patients and foreign body sensation in 7.5% of patients. No viral RNA was detected in the tear samples of the patients with ocular findings. The positivity rate for SARS-CoV-2 in tears was 2.5% (n = 1). None of the samples collected by Schirmer test strips yielded positive polymerase chain reaction result for SARS-COV-2. The Ct value of the positive conjunctival swab was 36.03 and the nasopharyngeal Ct value of the same patient was 25.68. CONCLUSION: The SARS-CoV-2 viral shedding rate has been determined as 2.5% in the tears of early symptomatic stage COVID-19 patients. The viral load of the tears was lower than the naso-oropharynx. The conjunctival swab method is recommended in tear collection to evaluate the presence of SARS-CoV-2 by RT-PCR analysis in low viral load tears.

Ocular transmissibility of COVID-19: possibilities and perspectives.

Since the initial outbreak of coronavirus disease 2019 (COVID-19), extensive research has emerged from across the globe to understand the pathophysiology of this novel coronavirus. Transmission of this virus is a subject of particular interest as researchers work to understand which protective and preventative measures are most effective. Despite the well understood model of aerosol-respiratory mediated transmission, the exact mechanism underlying the inoculation, infection and spread of COVID-19 is currently unknown. Given anatomical positioning and near constant exposure to aerosolized pathogens, the eye may be a possible gateway for COVID-19 infection. This critical review explores the possibility of an ocular-systemic or ocular-nasal-pulmonic pathway of COVID-19 infection and includes novel insights into the possible immunological mechanisms leading to cytokine surge.

COVID-19 and the Eye: Ocular Manifestations, Treatment and Protection Measures.

The novel pandemic coronavirus disease 2019 (COVID-19) leading to health and economic problems worldwide is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although COVID-19 mainly occurs as a lower respiratory tract infection, there is multiorgan involvement in infected patients. The disease is transmitted from person to person through air droplets or contact with contaminated surfaces. SARS-CoV-2 leads to this systemic involvement by attaching to angiotensin-converting enzyme 2 (ACE2) receptors located on several human cells. Since SARS-CoV-2 RNA has been found in tears of infected patients, ocular surface may allow the virus to transmit to nasopharynx via the nasolacrimal duct. This narrative review aims to sum up all segmental ocular complications, ocular adverse effects of COVID-19 treatment, and preventive measures suggested to minimize the SARS-CoV-2 transmission between patients and ophthalmologists by reviewing currently available literature.

Transcriptomic analysis revealed increased expression of genes involved in keratinization in the tears of COVID-19 patients.

Recent studies have focused their attention on conjunctivitis as one of the symptoms of coronavirus disease 2019 (COVID-19). Therefore, tear samples were taken from COVID-19 patients and the presence of SARS-CoV-2 was evidenced using Real Time reverse transcription polymerase chain reaction. The main aim of this study was to analyze mRNA expression in the tears of patients with COVID-19 compared with healthy subjects using Next Generation Sequencing (NGS). The functional evaluation of the transcriptome highlighted 25 genes that differ statistically between healthy individuals and patients affected by COVID-19. In particular, the NGS analysis identified the presence of several genes involved in B cell signaling and keratinization. In particular, the genes involved in B cell signaling were downregulated in the tears of COVID-19 patients, while those involved in keratinization were upregulated. The results indicated that SARS-CoV-2 may induce a process of ocular keratinization and a defective B cell response.

Novel Insights into the Transmission of SARS-CoV-2 Through the Ocular Surface and its Detection in Tears and Conjunctival Secretions: A Review.

SARS-CoV-2 is a highly transmissible virus that spreads mainly via person-to-person contact through respiratory droplets, or through contact with contaminated objects or surfaces from an infected person. At present we are passing through a phase of slow and painful understanding of the origin, epidemiological profile, clinical spectrum, and risk profile of the virus. To the best of our knowledge there is only limited and contradictory evidence concerning SARS-CoV-2 transmission through other routes. Importantly, the eye may constitute not only a potential site of virus replication but also an alternative transmission route of the virus from the ocular surface to the respiratory and gastrointestinal tract. It is therefore imperative to gain a better insight into the potential ophthalmological transmission route of the virus and establish directions on best practice and future models of care for ophthalmological patients. This review article critically evaluates available evidence on the ophthalmological mode of viral transmission and the value of earlier identification of the virus on the eye. More evidence is urgently needed to better evaluate the need for protective measures and reliable ocular diagnostic tests to diminish further pandemic spread.

Identification of SARS-CoV-2 on the ocular surface in a cohort of COVID-19 patients from Brazil.

In this cross-sectional study, we investigate the presence of Severe Acute Respiratory Syndrome Coronavirus 2 Ribonucleic Acid (SARS-CoV-2 RNA) in the tears of hospitalized COVID-19 patients. After laboratory confirmation of SARS-CoV-2 infection by reverse transcription polymerase chain reaction (RT-PCR) analysis, tear samples from both eyes of each patient were collected using conjunctival swab for RT-PCR. Detailed demographic profile, systemic and ocular symptoms, comorbidities, clinical, ancillary, and ocular manifestations were evaluated. Of the 83 patients enrolled in the study, 7 (8.43%) had SARS-CoV-2 RNA detected in the tear samples. Neutrophils' count, C-reactive protein, and D-dimer were higher in patients with SARS-CoV-2 detected in tears than in patients without virus in ocular surface samples. One patient with SARS-CoV-2 in tears showed mild ocular eyelid edema, hyperemia, and chemosis. No relevant ocular manifestations were detected in the other patients. Although the levels of viral RNA on ocular surface samples were low for most patients (5/7), with positivity only for gene N and CT higher than 30, two patients were positive for all viral targets tested (N, E, and RpRd), with viral load near 1 × 105 ePFU/mL, indicating that the ocular transmission of SARS-CoV-2 is a possibility that needs to be considered, especially in the hospital environment. Further studies need to be conducted to demonstrate whether infective viral particles could be isolated from tears.

An Eye on COVID-19: A Meta-analysis of Positive Conjunctival Reverse Transcriptase-Polymerase Chain Reaction and SARS-CoV-2 Conjunctivitis Prevalence.

SIGNIFICANCE: This analysis and review demonstrate that, although emerging data indicate that the prevalence of severe acute respiratory coronavirus 2 (SARS-CoV-2) on the ocular surface and coronavirus disease 2019 (COVID-19) conjunctivitis is rare, the ocular surface remains of interest as a potential inoculation and transmission site for SARS-CoV-2. Continued safety precautions should be taken as more data become available.COVID-19, caused by SARS-CoV-2, is a novel, global pandemic that has infected millions and, up to this point, caused more than two million fatalities worldwide. The ocular surface has become of interest as a possible vector for transmission by acting as a direct inoculation site, being a conduit for the virus into the respiratory system or as a method of transmission from potentially infected conjunctiva or tears. The components necessary for SARS-CoV-2 to theoretically infect ocular tissues are present: binding receptors (angiotensin-converting enzyme 2 and cluster of differentiation 147) and mechanisms for cell entry (transmembrane protease serine 2 and cathepsin L). This meta-analysis of COVID-19 prevalence data indicates that SARS-CoV-2 RNA has been infrequently found in conjunctival samples when tested with reverse transcriptase-polymerase chain reaction. This review estimates the prevalence of SARS-CoV-2 on the ocular surface and prevalence of conjunctivitis in patients with laboratory-confirmed COVID-19. There is much to be learned regarding ocular tropism of SARS-CoV-2.

Comparative Evaluation of Tears and Nasopharyngeal Swab for SARS-CoV-2 in COVID-19 Dedicated Intensive Care Unit Patients.

Purpose: To compare the cycle threshold (Ct) values of tears and nasopharyngeal (NP) swab in severe COVID-19 ICU patients with positive NP swabs.Procedure: A cross-sectional study for the detection of SARS-CoV-2 by real-time RT-PCR on simultaneously collected NP swabs and tears was performed. Detailed demographic profile, including comorbidities, ocular, and systemic features were analyzed.Results: In the 78 cases, the mean tear positivity was 26.92% (21/78), 2 tear samples being positive despite a negative NP swab. The mean Ct value of tears and NP were 28.17 ± 4.76 and 23.71 ± 6.19, respectively (p= .003). None of the cases had ocular findings or relationship between tear positivity and comorbidity.Conclusions: The viral load of tears is less than the NP secretions with the possibility of prolonged shedding in tears. Tears act as an additional source of contact transmission in ICU that can possibly be decreased by frequent hand hygiene by the patient.Abbreviations: SARS-CoV-2: Severe acute respiratory syndrome coronavirus; RT-PCR: Real-time Reverse transcriptase-polymerase chain reaction; COVID-19: Corona virus disease 2019; ICU: Intensive care unit; RdRp: RNA-dependent RNA polymerase; ORF 1b: Open reading frame 1b; AIIR: Airborne infection isolation room; HCW: Health care workers; VTM: viral transport media; NP: Nasopharyngeal swab; PPE: Personal protective equipment.

Ocular Surface and Conjunctival Cytology Findings in Patients With Confirmed COVID-19.

PURPOSE: To assess the effect of severe acute respiratory syndrome coronavirus-2 infection on the conjunctiva and tear film. METHODS: Thirty-eight patients with confirmed COVID-19 and 31 healthy controls were included in this prospective and observational study. Individuals with COVID-19 formed the patient group, and healthy individuals formed the control group. Conjunctival impression cytology (CIC), TBUT, Schirmer II test, and ocular surface disease index were evaluated in all participants. RESULTS: No significant difference was observed regarding the mean age and gender between the groups (P=0.786 and P=0.122, respectively). The mean TBUT and Schirmer II test results did not differ between the two groups (P=0.496 and P=0.447, respectively). The CIC results revealed decreased density and cell size of goblet cells and moderate to high enlargement, squamous changes, and increased nucleocytoplasmic ratio in nongoblet epithelial cells in the COVID-19 group compared with the control group. Based on the Nelson classification in CIC samples, 60.6% of the COVID-19 group and 19.4% of the control group had changes consistent with grade 2 or above. The presence of neutrophils in CIC was significantly higher in the COVID-19 group (P<0.001), whereas the presence of lymphocyte was similar between the two groups (P=0.247). CONCLUSION: This study revealed the pathological conjunctival alterations in patients with COVID-19 and demonstrated that pathological ocular surface alterations may present even at the beginning of COVID-19 without clinically significant ocular manifestation.

SARS-CoV-2 on Ocular Surfaces in a Cohort of Patients With COVID-19 From the Lombardy Region, Italy.

Importance: Since February 2020, coronavirus disease 2019 (COVID-19) has spread rapidly all over the world, with an epidemiological cluster in Lombardy, Italy. The viral communicability may be mediated by various body fluids, but insufficient information is available on the presence of the virus in human tears. Objectives: To investigate the rate of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in tears collected from patients with COVID-19 by means of real-time reverse transcriptase-polymerase chain reaction (rRT-PCR) assay and to assess the association of virus presence with concomitant clinical conditions. Design, Setting, and Participants: Cross-sectional study conducted between April 9 and May 5, 2020. The setting was intensive care units at Azienda Socio-Sanitaria Territoriale (ASST) Sette-Laghi Hospital, University of Insubria, in Varese, Lombardy, Italy. A conjunctival swab was performed in 91 patients hospitalized for COVID-19, which was clinically diagnosed by rRT-PCR assay on nasopharyngeal swabs and by radiological imaging. Conjunctival swabs from 17 additional healthy volunteer participants with no symptoms of COVID-19 were examined to evaluate the availability and applicability of the conjunctival swab test. Exposure: SARS-CoV-2 detection by means of rRT-PCR assay performed on the collected samples obtained by conjunctival swabs. Main Outcomes and Measures: Conjunctival swab and nasopharyngeal swab results are reported, as well as demographic and clinical data. Results: A total of 108 participants (mean [SD] age, 58.7 [14.2] years; 55 female and 53 male) were tested for SARS-CoV-2 using rRT-PCR assay, including 91 patients hospitalized with COVID-19 and 17 were healthy volunteers. SARS-CoV-2 was found on the ocular surface in 52 of 91 patients with COVID-19 (57.1%; 95% CI, 46.3%-67.5%), with a wide variability in the mean viral load from both eyes. Among a subset of 41 patients, concordance of 63.0% (95% CI, 41.0%-81.0%) was found between positive conjunctival and nasopharyngeal swab test results when performed within 2 days of each other. In 17 of these patients, nasopharyngeal swab results were negative for SARS-CoV-2. In 10 of these 17 patients, conjunctival swab results were positive for the virus. Conclusions and Relevance: In this study, SARS-CoV-2 RNA was found on the ocular surface in a large part of this cohort of patients with COVID-19, although the infectivity of this material could not be determined. Because patients may have positive test results with a conjunctival swab and negative results with a nasopharyngeal swab, use of the slightly invasive conjunctival swab may be considered as a supplementary diagnostic test.

Conjunctivitis as sole symptom of COVID-19: A case report and review of literature.

INTRODUCTION: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel virus causing an ongoing pandemic in 2020. Although the symptomatic patients infected by SARS-CoV-2 generally show respiratory distress, atypical manifestations such as conjunctivitis are also observed. A series of cases are reported in which reverse transcriptase polymerase chain reaction (RT-PCR) testing on tears had demonstrated the presence of the virus. However, the transmission of the virus through ocular fluids remains unknown. CASE DESCRIPTION: In this case report, the development of conjunctivitis is presented as the sole symptom of a new coronavirus disease 2019 (COVID-19) in an emergency health care worker. The patient's first application was to the ophthalmology clinic due to redness, stinging, tearing, and photophobia for one day in the right eye. The patient had no symptoms of fever, cough, shortness of breath, or fatigue. Two days later, the RT-PCR test, blood analysis, and chest computed tomography (CT) were applied to the patient for being in contact with a COVID positive patient. Conjunctival swabs did not identify SARS-CoV-2 by RT-PCR. However, nasopharyngeal swab and blood test confirmed the diagnosis of COVID-19. Chest CT did not show pneumonia. CONCLUSION: This phenomenon shows that conjunctivitis may occur as a sole manifestation of COVID-19 which needs to be carefully evaluated by health care workers and eye care professionals during the pandemic.

Progress in research on the detection of the novel coronavirus in human samples of different groups.

OBJECTIVE: Among the illnesses that may develop from COVID-19, the disease caused by the novel coronavirus (SARS-CoV-2), is pneumonia, a severe acute respiratory infectious disease. SARS-CoV-2 continues to spread worldwide and has caused hundreds of thousands of deaths thus far and has disrupted the world economy. PATIENTS AND METHODS: This review summarized the reported distributions of SARS-CoV-2 in 13 biological samples of the human body, including nose, feces, sperm, tears, breast milk, cerebrospinal fluid, urine, organs, sputum, cell lines, bronchial brush, blood, throat, and bronchoalveolar lavage fluid. Moreover, this review briefly describes the detection of SARS-CoV-2 in human body samples of five other coronaviruses. CONCLUSIONS: This review offers several recommendations for controlling the spread of SARS-CoV-2 control, specifically, sample collection from suspected cases from foreign countries and risk assessment of imported special goods (biological materials).

Implications of COVID-19 for Ophthalmologists.

PURPOSE: To describe and explain the implications of coronavirus disease 2019 (COVID-19) for ophthalmologists considering the rapid developments in our understanding of the virology, transmission, and ocular involvement. DESIGN: Evidence-based perspective. METHODS: Review and synthesis of pertinent literature. RESULTS: Retrospective studies highlight that <1% of patients display COVID-19-related conjunctivitis. However, prospective studies suggest the rate is higher (~6%). Viral RNA has been identified in tears and conjunctival secretions in patients with active conjunctivitis as well as asymptomatic cases. Overall, conjunctival swabs are positive in 2.5%. Samples taken earlier in the disease course are more likely to demonstrate positive virus. Viral transmission through ocular tissues has not been substantiated. Ophthalmologists are in the high-risk category for COVID-19 infection for several reasons: high-volume clinics, close proximity with patients, equipment-intense clinics, and direct contact with patients' conjunctival mucosal surfaces. COVID-19 is predominantly contracted through direct or airborne transmission by inhalation of respiratory droplets. Evidence that aerosol transmission occurs is increasing in particularly prolonged exposure to high concentrations in a relatively closed environment. Based on the current evidence, ophthalmologists should consider measures that include social distancing, wearing masks, sterilization techniques, and managing clinic volumes. CONCLUSIONS: A major challenge to containing COVID-19 is that many infected people are asymptomatic. Droplet spread, contaminated environmental surfaces, and shared medical devices are areas that require management by ophthalmologists. More studies are required to explore the role of the conjunctiva and ocular tissues in the transmission of disease.

Detection of Coronavirus in Tear Samples of Hospitalized Patients With Confirmed SARS-CoV-2 From Oropharyngeal Swabs.

PURPOSE: This study was designed to detect CoV-RNA in the tears of polymerase chain reaction (PCR)-confirmed SARS-CoV-2 positive patients. METHODS: We performed a prospective case series study of hospitalized patients who have been confirmed SARS-CoV-2 positive by oropharyngeal swab within the previous 5 days. Tear samples obtained with a laboratory capillary and oropharyngeal swabs were analyzed by real-time PCR using the Altona SARS-CoV-2 Assay or the Roche SARS-CoV-2 LightMix PCR, depending on the availability. Patient history was documented, and ophthalmoscopy was used to assess for ocular surface disease. RESULTS: Of all 18 patients recruited in April 2020, 5 suffered from respiratory failure and were submitted to an intensive care unit. None of our patients had signs of viral conjunctivitis although all patients in intensive care showed chemosis and conjunctival hyperemia because of third-spacing or fluid overload. The presence of coronavirus RNA was confirmed by PCR in 5 of 18 patients (28%) in tears and 72% for oropharyngeal swabs. CONCLUSIONS: Using a tear fluid sampling technique similar to oropharyngeal lavage presents a higher percentage of SARS-CoV-2 positive tears in contrast to earlier reports that used a conjunctival swab. This does not automatically indicate viral shedding in ocular tissue or contagiousness of tear fluid.

A review on human body fluids for the diagnosis of viral infections: scope for rapid detection of COVID-19.

Introduction: The unprecedented outbreaks of corona virus disease of 2019 (COVID-19) have highlighted the necessity of readily available, reliable, precise, and faster techniques for its detection. Nasopharyngeal swab has been the gold standard for the diagnosis of COVID-19. However, it is not an ideal screening procedure for massive screening as it implicates the patient's stay in the hospital or at home until diagnosis, thus causing crowding of the specimen at the diagnostic centers. Present study deal with the exploration of potential application of different body fluids using certain highly objective techniques (Optical and e-Nose) for faster detection of molecular markers thereby diagnosing viral infections.Areas covered: This report presents an evaluation of different body fluids, and their advantages for the rapid detection of COVID-19, coupled with highly sensitive optical techniques for the detection of molecular biomarkers.Expert opinion: Tears, saliva, and breath samples can provide valuable information about viral infections. Our brief review strongly recommends the application of saliva/tears and exhaled breath as clinical samples using technics such as high-performance liquid chromatography-laser-induced fluorescence, photoacoustic spectroscopy, and e-Nose, respectively, for the fast diagnosis of viral infections.

Ocular surface manifestations of coronavirus disease 2019 (COVID-19): A systematic review and meta-analysis.

PURPOSE: This study was performed to determine the occurrence of ocular surface manifestations in patients diagnosed with coronavirus disease 2019 (COVID-19) due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: A systematic search of electronic databases i.e. PubMed, Web of Science, CINAHL, OVID and Google scholar was performed using a comprehensive search strategy. The searches were current through 31st May 2020. Pooled data from cross-sectional studies was used for meta-analysis and a narrative synthesis was conducted for studies where a meta-analysis was not feasible. RESULTS: A total of 16 studies reporting 2347 confirmed COVID-19 cases were included. Pooled data showed that 11.64% of COVID-19 patients had ocular surface manifestations. Ocular pain (31.2%), discharge (19.2%), redness (10.8%), and follicular conjunctivitis (7.7%) were the main features. 6.9% patients with ocular manifestations had severe pneumonia. Viral RNA was detected from the ocular specimens in 3.5% patients. CONCLUSION: The most common reported ocular presentations of COVID-19 included ocular pain, redness, discharge, and follicular conjunctivitis. A small proportion of patients had viral RNA in their conjunctival/tear samples. The available studies show significant publication bias and heterogeneity. Prospective studies with methodical collection and data reporting are needed for evaluation of ocular involvement in COVID-19.