Complications of Adenoviral Keratoconjunctivitis in Ophthalmologists and Orthoptists: Epidemiology and Risk Factor, A Retrospective Questionnaire Analysis.

PURPOSE: The purpose of this study was to assess the medical history of adenoviral keratoconjunctivitis (AK) and subepithelial infiltrates (SEIs) among French ophthalmologists and orthoptists and the frequency of unreported occupational diseases. We also described short-term and long-term consequences of AK and evaluated associated factors. METHODS: The REDCap questionnaire was diffused online several times over 7 consecutive months, from October 2019 to May 2020, through mailing lists (French Society of Ophthalmology, residents, and hospital departments), social networks, and by word of mouth. RESULTS: Seven hundred ten participants were included with a response rate of 6.2% for ophthalmologists, 3.8% for orthoptists, and 28.3% for ophthalmology residents. The medical history of AK was found in 24.1% (95% confidence interval 21%-27.2%) of respondents and SEI in 43.9% (36.5%-51.3%) of the AK population. In total, 87.1% (82.1%-92.1%) of AK occupational diseases were not declared. In total, 57.7% of respondents took 9.4 ± 6.2 days of sick leave, mostly unofficial, and 95.7% stopped surgeries for 13.0 ± 6.6 days. Among the AK population, 39.8% had current sequelae, with 17.5% having persistent SEIs, 19.9% using current therapy, and 16.4% experiencing continuing discomfort. SEIs were associated with wearing contact lenses (odds ratio 3.31, 95% confidence interval 1.19-9.21) and smoking (4.07, 1.30-12.8). Corticosteroid therapy was associated with a greater number of sequelae (3.84, 1.51-9.75). CONCLUSIONS: AK and SEI affect a large proportion of ophthalmologists and orthoptists, possibly for years, with high morbidity leading to occupational discomfort. Few practitioners asked for either to be recognized as an occupational disease. Associated factors would require a dedicated study.

LOW VULNERABILITY OF THE POSTERIOR EYE SEGMENT TO SARS-COV-2 INFECTION: Chorioretinal SARS-CoV-2 Vulnerability.

PURPOSE: Retinal manifestations have been described in COVID-19 patients, but it is unknown whether SARS-CoV-2, the causal agent in COVID-19, can directly infect posterior ocular tissues. Here, we investigate SARS-CoV-2 host factor gene expression levels and their distribution across retinal and choroidal cell types. METHODS: Query of single-cell RNA sequencing data from human retina and choroid. RESULTS: We find no relevant expression of two key genes involved in SARS-CoV-2 entry, ACE2 and TMPRSS2, in retinal cell types. By contrast, scarce expression levels could be detected in choroidal vascular cells. CONCLUSION: Given the current understanding of viral host cell entry, these findings suggest a low vulnerability of the posterior eye segment to SARS-CoV-2 with a potential weak spot in the vasculature, which could play a putative causative role in ocular lesions in COVID-19 patients. This may qualify the vasculature of the human posterior eye segment as an in vivo biomarker for life-threatening vascular occlusions in COVID-19 patients.

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.

Ophthalmic manifestations in the COVID-19 clinical spectrum.

PURPOSE: The aim of this study was to determine the frequency and various types of ophthalmic manifestation of patients with COVID-19. METHODS: This is a prospective observational study conducted on patients with SARS-Co-V-2 infection, at a dedicated tertiary COVID-19 hospital in South India from April 1 to July 31, 2020. At the time of their admission to the COVID hospital, demographic data such as name, age, sex was recorded. A thorough history regarding the onset, duration, progression, nature of symptoms and its associated factors, medication history, treatment history were elicited and documented. Ocular examination was performed under torchlight by an ophthalmologist posted for COVID duty. Further investigations including imaging were sought for, depending on clinical indications. Serial follow-up examinations of all patients were carried out every 72 hours or when patients complained of any ocular symptoms whichever earlier, until discharge. All relevant data were compiled and statistically analyzed. RESULTS: A total of 2742 patients were examined. Of them, 1461 (53.28%) were males and 1281 (46.72%) were females. The mean age (±SD) was 39.46 ± 17.63 years. None of the patients in our study had any ocular symptoms or signs as the presenting complaint at the time of their admission. On subsequent follow-up, only 20 (0.72%) developed ocular manifestations, of which 19 (95%) had features suggestive of Bilateral viral conjunctivitis. However, 1 (5%) patient had orbital cellulitis secondary to pansinusitis. CONCLUSION: Ophthalmic manifestations in the clinical spectrum of COVID-19 infection are uncommon and unlikely to be the presenting clinical impression. However, it has broadened our view to a wider spectrum of COVID-19 presentations enhancing our clinical acumen for staunch detection of COVID-19 suspects in our daily practice, augmenting early diagnosis and management and also break the chain of transmission for the greater good of humanity.

COVID-19 and Eye: A Review of Ophthalmic Manifestations of COVID-19.

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has had health implications of unprecedented magnitude. The infection can range from asymptomatic, mild to life threatening respiratory distress. It can affect almost every organ of the body. Ophthalmologists world over are reporting various manifestations of the infection in the eye. This review was undertaken to help ophthalmologists recognize the possible manifestations and the stage of the viral disease when they commonly appear. Literature search was performed for the publications on ophthalmic manifestations of coronavirus disease-19 (COVID-19) between January 1, 2020 and January 31, 2021. 46 case reports, 8 case series, 11 cross sectional/cohort observational studies, 5 prospective interventional studies, 3 animal models/autopsy studies and 6 reviews/meta-analysis were included. Conjunctivitis is the most common manifestation and can develop at any stage of the disease. Direct effect due to virus, immune mediated tissue damage, activation of the coagulation cascade and prothrombotic state induced by the viral infection, the associated comorbidities and drugs used in the management are responsible for the findings in the eye. The viral ribonucleic acid (RNA) has been isolated from ocular tissues but the role of eye as a route for infection is yet to be substantiated. Ophthalmic manifestations may be the presenting feature of COVID-19 infection or they may develop several weeks after recovery. Ophthalmologists should be aware of the possible associations of ocular diseases with SARS-CoV-2 in order to ask relevant history, look for specific signs, advise appropriate tests and thereby mitigate the spread of infection as well as diagnose and initiate early treatment for life and vision threatening complications.

Ocular manifestations of emerging viral diseases.

Emerging infectious diseases (EIDs) are an increasing threat to public health on a global scale. In recent times, the most prominent outbreaks have constituted RNA viruses, spreading via droplets (COVID-19 and Influenza A H1N1), directly between humans (Ebola and Marburg), via arthropod vectors (Dengue, Zika, West Nile, Chikungunya, Crimean Congo) and zoonotically (Lassa fever, Nipah, Rift Valley fever, Hantaviruses). However, specific approved antiviral therapies and vaccine availability are scarce, and public health measures remain critical. Patients can present with a spectrum of ocular manifestations. Emerging infectious diseases should therefore be considered in the differential diagnosis of ocular inflammatory conditions in patients inhabiting or returning from endemic territories, and more general vigilance is advisable in the context of a global pandemic. Eye specialists are in a position to facilitate swift diagnosis, improve clinical outcomes, and contribute to wider public health efforts during outbreaks. This article reviews those emerging viral diseases associated with reports of ocular manifestations and summarizes details pertinent to practicing eye specialists.

Ocular Symptoms of SARS-CoV-2: Indication of Possible Ocular Transmission or Viral Shedding.

The recently identified novel coronavirus (CoV), the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), causes the coronavirus disease 2019 (COVID-19). While published data about other highly infectious human COVs [that is, the severe acute respiratory syndrome coronavirus (SARS-CoV) and the Middle East respiratory syndrome coronavirus (MERS-CoV)] provide helpful information about the infectivity of SARS-CoV-2, there is limited understanding surrounding knowledge of ocular manifestation of the virus. This paper reviews published data which reveal the presence of SARS-CoV-2 RNA in tears and conjunctival scrappings of some COVID-19 patients by real-time-polymerase chain reaction assay, although the detection rate is low compared to samples from respiratory sites. Nevertheless, the ocular complications from SARS-CoV-2 infection are uncommon. The evidence partly supports the eye as a portal of entry for SARS-CoV-2 to infect respiratory cells or viral shedding from respiratory cells via the nasolacrimal duct unto the ocular surface. The possibility of ocular secretions as source for SARS-CoV-2 to spread externally has substantial public health implications.

SARS-CoV-2 and COVID-19 for the ophthalmologist.

The COVID-19 pandemic has had an unprecedented impact on ophthalmology. This review compiles general aspects of the novel coronavirus and COVID-19, further dissects the most recent data on the role of the eye regarding disease transmission and manifestations, and summarizes preventive measures in the particular context of eye care.

Acute Onset of Bilateral Follicular Conjunctivitis in two Patients with Confirmed SARS-CoV-2 Infections.

PURPOSE: To report bilateral follicular conjunctivitis in two confirmed Coronavirus (COVID-19) patients with the presence of Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) in conjunctival swab specimens. PARTICIPANTS AND METHODS: Two unrelated patients with confirmed SARS-CoV-2 infection and bilateral acute conjunctivitis were examined. Conjunctival swabs were assessed for the presence of SARS-CoV-2 by quantitative real-time polymerase chain reaction (RT-PCR) and viral culture. RESULTS: Both patients developed eye redness 3 days after the onset of COVID-19 symptoms. Slit lamp examination showed bilateral acute follicular conjunctivitis, which was resolved within 6 days. RT-PCR demonstrated the presence of viral RNA in conjunctival specimens from both eyes, which was unrelated to viral RNA from throat swabs. CONCLUSION: SARS-CoV-2 may cause ocular manifestations such as viral conjunctivitis. Conjunctival sampling may be useful for infected patients with conjunctivitis and fever. Precautionary measures are recommended when examining infected patients throughout the clinical course of the infection.

SARS-CoV-2 Targeting the Retina: Host-virus Interaction and Possible Mechanisms of Viral Tropism.

Background: Coronavirus disease 2019 (COVID-19) is caused by Severe Acute Respiratory Syndrome Coronavirus 2 10 (SARS-CoV-2). Recent studies demonstrated not only retinal impairments but also detected SARS-CoV-2 in the retina of patients with COVID-19. Purpose: This letter discusses the retinal tropism of SARS-CoV-2, describing possible routes for this coronavirus to reach the retina and cellular mechanisms involved in the retinal cell infection. Conclusions: Determining how SARS-CoV-2 can affect the retinal tissue is essential for the development of new therapeutic strategies and preventive measures, as well as for understanding the possible relationship between COVID-19 damage to the retina and to the brain.

Ocular involvement in coronavirus disease 2019 (COVID-19): a clinical and molecular analysis.

PURPOSE: Coronavirus disease 2019 (COVID-19) caused a global pandemic with millions infected worldwide. Little is known on the ocular involvement associated with the disease. The aim of this study was to assess the clinical and molecular ocular involvement among patients with confirmed COVID-19 admitted to a tertiary care facility. METHODS: Consecutive patients admitted to the COVID-19 Ward of the Shamir Medical Center in Israel during March and April, 2020 were included. The control group included patients negative for COVID-19 admitted during a similar period to a different ward. Patients were examined by trained Ophthalmologists. SARS-CoV-2 conjunctival swab samples were obtained. RESULTS: Included were 48 patients, 16 with confirmed COVID-19 and 32 controls. Median patient age was 68.5 (interquartile range: 31.5, mean: 63 ± 21) years and 48% were male. Active conjunctival injection was present in three patients (19%) with COVID-19, compared to none in the controls (p = 0.034). Patients with COVID-19 were more likely to complain of foreign body sensation (31.3% vs 3.1%, p = 0.005) and redness of the eye (25% vs 0%, p = 0.003). Conjunctival injection was associated with loss of smell and taste (75% vs 7.7%, p = 0.018). Viral conjunctival swab tests all showed negative results for all three viral genes tested (E, N, and RdRp). CONCLUSIONS: Among patients admitted to a tertiary referral center with confirmed COVID-19, active conjunctival injection was noted in one out of five cases, and was associated with loss of smell and taste. Conjunctival swabs for viral RNA were negative in patients with and without ocular involvement.

Ocular tropism of coronavirus (CoVs): a comparison of the interaction between the animal-to-human transmitted coronaviruses (SARS-CoV-1, SARS-CoV-2, MERS-CoV, CoV-229E, NL63, OC43, HKU1) and the eye.

PURPOSE: Several studies have reported conflicting results on ocular manifestations and transmission of coronavirus disease 2019 (COVID-19) whose causative virus, SARS-CoV-2, belongs to the coronavirus family, the seventh recognized as a human pathogen and the third causing a severe clinical syndrome. COVID-19 primarily affects the lungs, similar to the other human coronaviruses. Comparing the relation between the animal-to-human transmitted coronaviruses (SARS-CoV-1, SARS-Cov-2, MERS-CoV, CoV-229E, NL63, OC43, HKU1) and the eye may contribute to determining their actual eye-tissue tropism and risk of ocular transmission. METHODS: Literature review was conducted via Pubmed.gov, Google Scholar and medRixv using the following keywords: COVID-19, SARS-CoV-2, SARS-CoV-1, MERS-CoV, CoV-229E, NL63, OC43, HKU1, conjunctivitis, tear swab, ocular expression, ocular symptoms and human angiotensin converting enzyme-2 expression. Studies with lack in methodology were excluded. RESULTS: Sixteen observational studies were selected. The range for detection of viral RNA in tears was 0-8% for SARS-CoV-1 and 0-5.3% for SARS-CoV-2, while no reports were found for other coronaviruses. Ocular manifestations have been reported for NL63 and SARS-CoV-2. Ocular symptoms in the form of conjunctivitis/conjunctival congestion predominantly were detected in 65 (3.17%) out of 2048 reported patients with COVID-19 (range of 0.8-32%). Eye symptoms were not reported for the other coronaviruses. CONCLUSIONS: Data aggregation for coronaviruses shows a relatively low eye-tissue tropism. Conjunctival congestion is an uncommon manifestation of COVID-19 similar to all human coronaviruses' infections. In a low percentage of patients, the virus can be excreted in ocular fluids at different stages of the infection, regardless of positive SARS-Cov-2 throat swab. Albeit high viral loads in ocular tissue seem to have relatively low prevalence, the eye should be regarded as a potential source of infection dissemination for COVID-19.

Conjunctivitis in COVID-19 patients: frequency and clinical presentation.

PURPOSE: The purpose of this study was to evaluate the frequency and clinical presentation of conjunctivitis in hospitalized patients with COVID-19. METHODS: A cross-sectional study was conducted at the Hospital Clinico San Carlos of Madrid, Spain. A total of 301 subjects from the COVID admission unit with laboratory-confirmed SARS-CoV-2 infection were included. The presence and clinical characteristics of conjunctivitis were evaluated. Laboratory, radiological, and clinical results in patients with and without conjunctivitis stratified by sex were analyzed. RESULTS: Of the 301 subjects included, 180 patients (59.8%) were male and the median age was 72 years (IQ 59-82). Overall, 35 patients (11.6%) were diagnosed with acute conjunctivitis. We found no relationship between the COVID-19 severity score and the presence of conjunctivitis (P = 0.17). However, conjunctivitis was more frequent in males with moderate clinical severity and in women classified as clinically mild. The natural history of the disease seems to be a rapid self-limited conjunctivitis that improves without treatment and does not affect visual acuity nor associate short-term complications. CONCLUSIONS: Approximately, 1 out of 10 hospitalized non-critical COVID-19 patients presents conjunctivitis during the disease. Compared with other viral conjunctivitis, we found distinctive clinical findings that could guide defining and differentiating conjunctivitis in COVID-19 patients. TRIAL REGISTRATION NUMBER: 20/336_E_COVID.

SARS-CoV-2 on the ocular surface: is it truly a novel transmission route?

Since December 2019, the novel COVID-19 outbreak has spread rapidly around the globe and infected millions of people. Although the major transmission route of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is considered to be airborne droplets and close contact, the ocular transmission route has been reported with great concern. The current work summarises the characteristics of SARS-CoV-2, the ocular distribution of the major SARS-CoV-2 binding protein, and the experimental and clinical evidence of the ocular transmission route. Although it seems that the likelihood of the ocular surface being an infection gateway is low, SARS-CoV-2 infection or transmission via the ocular surface may cause conjunctivitis and other ocular discomfort. Therefore, good eye protection is an essential safeguard procedure, especially for medical staff.

Clinical profile and prevalence of conjunctivitis in mild COVID-19 patients in a tertiary care COVID-19 hospital: A retrospective cross-sectional study.

PURPOSE: To find the clinical profile and prevalence of conjunctivitis and other ocular manifestations in mild COVID-19 positive patients in a nodal COVID-19 hospital. METHODS: A retrospective cross-sectional, single-center study conducted in 127 mild cases of COVID-19 positive patients admitted between 27th March and 19th April 2020 in a tertiary care COVID-19 hospital in north India. From the hospital records, demographic data is collected. Ocular history and ocular examinations were done by face-to-face survey during ward rounds. RESULTS: A total of 127 patients were included in the study with a median age of 38.8 years. Forty-eight (37.80%) patients had upper respiratory tract symptoms, 20 (15.75%) patients had systemic illness, 18 (14.17%) patients were using spectacles, and 50 (39.37%) patients had history of hand-eye contact. Out of 12 (9.45%) patients who had ocular complaints, 11 (8.66%) had ocular manifestation after admission. Among 11 patients, eight (6.29%) had conjunctival congestion. Three (3/8) patients had developed conjunctival congestion even before the manifestation of definite COVID-19 symptoms. Five patients (5/8) patients had no other associated ocular symptoms other than congestion. Six patients (6/8) had symptoms of upper respiratory tract infection. CONCLUSION: Mild conjunctivitis manifesting as conjunctival congestion is common and is one of the major ocular manifestations in COVID-19 positive patients even with milder disease.

The eye: "An organ that must not be forgotten in coronavirus disease 2019 (COVID-2019) pandemic".

The coronavirus family is a group of zoonotic viruses with some recognized reservoirs particularly some bats. A novel coronavirus emerged in the province of Wuhan (China) in December of 2019.The number of infected patient with serious respiratory infection quickly spread around the world to become a global pandemic. The clinical presentation and viral pathogenesis of the coronavirus disease named COVID-19 indicated that the virus is transmitted from person to person through infected droplets entering the respiratory mucosa. Close contact with infected individuals particularly in crowded environments has characterized the rapid spread of the infection. Clinical manifestations of the viral infection have mentioned the presence of some ocular findings such as conjunctival congestion, conjunctivitis and even corneal injury associated with the classical COVID-19 infection. Some animal models of different coronaviruses eye infections have described the viral pathogenesis through tear and conjunctival sampling. On the other hand, we are recommended protective measure to prevent contagion and limit the spread of the virus in health care professionals and contact lenses wearers.