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.

Phlyctenular Keratoconjunctivitis in a Patient With COVID-19 Infection.

ABSTRACT: The coronavirus disease 2019 global pandemic is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Several ophthalmic manifestations have been reported to be associated with SARS-CoV-2 infection, including conjunctivitis, acute sixth nerve palsy, and multiple cranial neuropathies. We present a unique case of unilateral phlyctenular keratoconjunctivitis in a 5-year-old boy in the setting of SARS-CoV-2 infection.

[Viral conjunctivitis as the first sign of COVID-19 infection (clinical observation)]. / Virusnyi kon"yunktivit kak pervyi priznak koronavirusnoi infektsii COVID-19 (klinicheskoe nablyudenie).

The article presents a case of complicated viral conjunctivitis. Conjunctivitis was the initial sign of the new coronavirus infection (COVID-19) in the patient. The disease had a fairly long course and led to symmetrical scarring in the form of partial external symblepharon and dry eye syndrome. Ophthalmologists should be aware about this disease and its complications. Early treatment with corticosteroids in combination with symptomatic therapy can contribute to prevention of the development of conjunctival scarring. In addition to conjunctival scarring, this disease can possibly potentiate the development of keratitis, optic neuritis, and uveitis.

The COVID-19 Pandemic from an Ophthalmologist's Perspective.

The current coronavirus disease 2019 (COVID-19) pandemic is rapidly spreading around the world. The first doctor to report this new disease was an ophthalmologist: this exemplifies the role of ophthalmologists in an infectious disease pandemic. Here we review how severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) affects the eye and discuss implications for ophthalmologists.

COVID-19 pandemic: Impact on the rate of viral conjunctivitis.

OBJECTIVE: The COVID-19 pandemic led Spain to order a state of alert with the cessation of non-essential activities on 14 March 2020, and to implement public health interventions (such as home confinement) and other health recommendations to prevent the spread of the SARS-CoV-2 virus (hand washing and the obligation to wear face-masks). These factors could have influenced the rate of viral conjunctivitis. METHOD: In this retrospective, noninterventional, descriptive study, the incidence of viral conjunctivitis in an emergency department of a national hospital is compared over two distinct time periods: pre-COVID (13 March-30 September 2019, one year before the start of the pandemic) and COVID (13 March-30 September 2020). RESULTS: In the first period there were 436 cases of conjunctivitis, of which 168 (38.5%) were confirmed cases of viral conjunctivitis 168 (38.5%), while in the second period there were 121 recorded cases, of which the most frequent were allergic and traumatic (23 cases; 19% each group), bacterial (15 cases; 12.3%) and viral (15 cases; 12.3%). The diagnosis of viral conjunctivitis is the one that suffered the most significant relative reduction (48.5%), while other types of conjunctivitis hardly changed their relative frequency between these two periods of time. CONCLUSIONS: Viral conjunctivitis is the most frequent infectious disease of the eye and has a transmission rate similar to that of coronavirus, so the measures implemented could positively affect its incidence.

Herpes Zoster Ophthalmicus After COVID-19 Vaccination: Chance Occurrence or More?

ABSTRACT: As the understanding of COVID-19 infection becomes better, it is being recognized as a complex multisystem pathology rather than just affecting the lungs. Several ocular findings have been documented by researchers in individuals infected with COVID-19, and ocular symptoms may even be the first presenting feature of COVID-19 infection in 2.26% individuals. Several countries have started vaccination with inactivated or live vaccines to combat this pandemic, and varied side effects have been reported after vaccination. Few cases of herpes zoster have previously been reported in elderly patients with comorbidities after receiving COVID-19 vaccines. In this article, the authors described 2 interesting cases of herpes zoster ophthalmicus (HZO) after receiving a live COVID-19 vaccine. The first case was a 35-year-old immunocompetent man who developed HZO 3 days postvaccine. The second case was a 40-year-old immunocompetent man who developed HZO 28 days postvaccine. To the best of our knowledge, no literature to date has described HZO after live vaccine.

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.

COVID-19 Ocular Manifestations in the Early Phase of Disease.

Purpose: To evaluate and establishe the number of patients with ocular manifestations in the early phase of systemic COVID-19 infection.Methods: A cross-sectional study was performed in a COVID-19 referral center regarding ocular findings in patients with COVID-19 in the first few days of the disease. The patients were submitted to a clinical examination, an ophthalmic exam and a RT-PCR for SARS-COV-2.Results: Out of 1740 patients, we reported 108 patients with ocular manifestations. Forty-nine with markedly conjunctivitis had conjunctival swab positive for SARS-COV-2, four of them developed keratitis. There were mostly no evidence of retinopathy nor decrease in visual acuity. They had no marked clinical symptoms, which can contribute and demonstrate that the virus may cause ocular disease as an only finding or in the very early stage of the infection.Conclusion: Patients were in the first days of COVID-19 infection, presented ocular manifestations suggested to be related to the virus and need to be aware of the pathways of transmissions.

A dermatologic perspective on multisystem inflammatory syndrome in children.

As of May 2020, an emerging immune-mediated syndrome mainly affecting children has been detected primarily in Europe and the United States. The incidence of this syndrome appears to mirror the initial infectious assault, with a delay of several weeks. This syndrome has been termed "multisystem inflammatory syndrome in children" (MIS-C) and is observed in association with the coronavirus disease 2019 (COVID-19). The phenotypes of presentation include several characteristic features, including prolonged fever, skin eruption, neck stiffness, and gastrointestinal manifestations with pronounced abdominal pain. Shock and organ dysfunction on presentation are frequent but inconsistent, whereas respiratory distress is typically and notably absent. We have reviewed recently published data aiming to better understand MIS-C, with a focus on its mucocutaneous manifestations.

[Ocular manifestations of viral diseases]. / Atteintes ophtalmologiques des infections virales.

Viral infections may involve all ocular tissues and may have short and long-term sight-threatening consequences. Among them, ocular infections caused by herpesviruses are the most frequent. HSV-1 keratitis and kerato-uveitis affect approximately are the leading cause of infectious blindness in the Western world, mainly because of corneal opacification caused by recurrences. For this reason, they may warrant long-term antiviral prophylaxis. Herpes zoster ophthalmicus, accounts for 10 to 20% of all shingles locations and can be associated with severe ocular involvement (keratitis, kerato-uveitis) of which a quarter becomes chronic/recurrent. Post herpetic neuralgias in the trigeminal territory can be particularly debilitating. Necrotizing retinitis caused by herpesviruses (HSV, VZV, CMV) are seldom, but must be considered as absolute visual emergencies, requiring urgent intravenous and intravitreal antiviral treatment. Clinical pictures depend on the immune status of the host. Adenovirus are the most frequent cause of infectious conjunctivitis. These most often benign infections are highly contagious and may be complicated by visually disabling corneal lesions that may last over months or years. Some arboviruses may be associated with inflammatory ocular manifestations. Among them, congenital Zika infections may cause macular or optic atrophy. Conjunctivitis is frequent during the acute phase of Ebola virus disease. Up to 15% of survivors present with severe chronic inflammatory ocular conditions caused by viral persistence in uveal tissues. Finally, COVID-19-associated conjunctivitis can precede systemic disease, or even be the unique manifestation of the disease. Utmost caution must be taken because of viral shedding in tears.

The Presence of SARS-CoV-2 in Conjunctival Secretions of COVID-19 Patients.

Purpose: To evaluate the presence of SARS-CoV-2 in conjunctival secretions of COVID-19 patients.Material and Methods: In this retrospective study, the records were examined of patients who were treated in the hospital with the diagnosis of COVID-19 between March-May 2020 and were referred to the eye clinic due to ocular symptoms. Conjunctival swabs from both confirmed and suspected COVID-19 cases during hospitalization were analyzed.Results: A total of 35 patients (22 suspected, 13 laboratory-confirmed COVID-19) were referred to the eye clinic. Conjunctival swab samples from 3 patients yielded positive PCR results. These three patients were being treated in the intensive care unit, and all were suspected COVID-19 patients.Conclusion: SARS-CoV-2 may be detected in patients with suspected COVID-19. Even with conjunctivitis findings, SARS-CoV-2 may not be detected in most conjunctiva swab samples of COVID-19 patients.

Ocular findings in patients with coronavirus disease 2019 (COVID-19) in an outbreak hospital.

PURPOSE: The aim of this study was to investigate the ocular findings observed in patients with coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 and to present the relationship between ocular involvement, systemic findings, and laboratory results. MATERIAL AND METHODS: This cross-sectional study was carried out between 1 May and 30 June 2020. The study included 359 patients diagnosed with COVID-19 and assessed by clinical evaluation, nasopharyngeal polymerase chain reaction, and lung computed tomography. RESULTS: One hundred ninety-seven (54.9%) of the patients were male and 162 (45.1%) were female. The mean age of the patients was 58.5 years (20-91). Two hundred ninety-four (81.9%) patients were treated in the inpatient clinic and 65 (18.1%) patients were treated in the intensive care unit. Various ocular diseases were observed in 16 (4.5%) of the patients. Although the rate of ocular disease was 12 out of 294 (4.1%) in patients followed up in the inpatient clinic, this rate was 4 out of 65 (6.2%) in intensive care patients. There was no systemic problem in one patient, in whom conjunctival hyperemia was the first and only reason for admission to the hospital. Four patients followed up in the inpatient clinic had conjunctivitis at the time of admission, and conjunctivitis occurred in three patients during hospitalization. Subconjunctival hemorrhage occurred in five patients and vitreous hemorrhage in one patient. CONCLUSION: Ocular diseases are uncommon in COVID-19 patients but may occur during the first period of the disease or during follow-up. Ocular diseases may be the initial or only sign of COVID-19 infection.

Detecting SARS-CoV-2 RNA in conjunctival secretions: Is it a valuable diagnostic method of COVID-19?

The main purpose of this study is to evaluate the presence of viral RNA of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in conjunctival swab specimen of coronavirus disease 2019 (COVID-19) patients with and without conjunctivitis to establish the diagnostic value of reverse transcription-polymerase chain reaction (RT-PCR) in each case and to describe its clinical characteristics. A cross-sectional study was conducted at the Hospital Clinico San Carlos of Madrid, Spain. Thirty-six subjects from the COVID admission unit with laboratory-confirmed SARS-CoV-2 infection were included. Conjunctival swabs were collected from 18 patients with conjunctivitis and 18 patients without conjunctivitis and RT-PCR was performed. Conjunctival swab was collected from both eyes of 36 patients (72 eyes), detecting SARS-CoV-2 RNA in conjunctival swab of two patients (5.5%). Among the 18 patients with conjunctivitis, only one of them (5.5%) showed positive results. Likewise, SARS-CoV-2 RNA was detected in one patient without conjunctivitis (5.5%). The mean age of the 36 patients was 67.9 years (range, 28-92 years) and the male-to-female ratio was 0.44 (16:20). The mean days since the onset of COVID-19 symptoms until conjunctivitis manifestation was 8 (range, 1-24 days). The mean duration of the conjunctivitis was 3 days (range, 1-7 days). SARS-CoV-2 RNA may be detected in conjunctival swabs of both patients with and without conjunctivitis. This study revealed the same rate of positive results amongst the group with and without conjunctivitis, suggesting that detecting SARS-CoV-2 in ocular fluids is not conditioned on the presence of conjunctivitis. The presence of SARS-CoV-2 RNA in ocular samples highlights the role of the eye as a possible route of transmission of the disease.

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.

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.

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.