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.

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.

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.

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.

Intensive ocular sampling for the detection of subclinical canine herpesvirus-1 shedding in dogs with experimentally-induced latent infection.

Latent canine herpesvirus-1 (CaHV-1) infections are common in domestic dogs, but viral shedding patterns in dogs are poorly understood. Previous research failed to detect spontaneous subclinical ocular CaHV-1 shedding in dogs following ocular infection, a situation that is fundamentally distinct from many of the alphaherpesviruses closely related to CaHV-1. One possible explanation for this finding is that the sampling interval in the prior studies evaluating ocular shedding patterns was too infrequent to detect rapidly cleared, brief ocular viral shedding episodes. To evaluate for this potential viral shedding scenario, 10 laboratory beagles recovered from experimental primary ocular CaHV-1 infection and with latent CaHV-1infection were intensively monitored for viral reactivation and shedding for 28 days. Clinical ophthalmic examinations were performed daily. Ocular swab samples were collected for CaHV-1 polymerase chain reaction 3 times daily and CaHV-1 virus neutralizing antibody assays were evaluated at 2-week intervals. No abnormalities suggestive of recurrent CaHV-1 ocular disease were observed during clinical ophthalmic examination in the dogs during the study. Ocular CaHV-1 shedding was not detected by polymerase chain reaction and CaHV-1 virus neutralizing antibody titers remained stable in all dogs for the study duration. In the present study utilizing frequent multiple daily sample collections, no evidence of subclinical ocular CaHV-1 shedding was detected in mature dogs with experimentally-induced latent CaHV-1 infection.

A Patient With Bilateral Conjunctivitis Positive for SARS-CoV-2 RNA in a Conjunctival Sample.

PURPOSE: To present a patient with bilateral conjunctivitis, testing positive for viral RNA of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in both nasopharyngeal and conjunctival samples. METHODS: A 40-year-old man with bilateral acute conjunctivitis and suspicious signs of coronavirus disease 2019 (COVID-19) presented to the hospital. A detailed ophthalmic examination was performed. Samples obtained from conjunctival and nasopharyngeal swabs were tested by reverse transcription PCR (RT-PCR) for the detection of SARS-CoV-2 virus. Ocular findings and duration of the presence of viral RNA in the conjunctival specimens were evaluated at follow-up visits. RESULTS: Slit-lamp biomicroscopy revealed bilateral acute follicular conjunctivitis. The RT-PCR assay demonstrated the presence of viral RNA in the nasopharyngeal and conjunctival specimens at the initial visit and at the 4-day follow-up. Conjunctivitis findings were decreased after 4 days and recovered completely without any sequelae within10 days. The PCR results of both nasopharyngeal and conjunctiva specimens were negative for the viral RNA at 10 days. CONCLUSIONS: Bilateral conjunctivitis is rare in patients infected with COVID-19. Although it is difficult to detect viral RNA from conjunctival swabs, conjunctival secretions may be a source of contamination, and protective measures must be taken.

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.

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.

Corticosteroids Versus Cyclosporine for Subepithelial Infiltrates Secondary to Epidemic Keratoconjunctivitis: A Prospective Randomized Double-Blind Study.

PURPOSE: To compare efficiency and tolerance between topical 0.5% cyclosporine A (CSA) and fluorometholone (FML) for subepithelial infiltrates (SEI) complicating epidemic keratoconjunctivitis. METHODS: We conducted a prospective double-blind randomized study involving 72 eyes with SEI. Thirty-eight eyes were treated with topical FML (FML group) and 34 eyes with CSA 0.5% eye drops (CSA group). Treatment was considered successful in case of SEI reduction and visual acuity improvement. Tolerance was evaluated by Schirmer test value, burning on eye drops instillation, and conjunctival injection. RESULTS: Baseline characteristics of both groups were similar (P > 0.05). After 3 months of the regimen, resolution of SEI was 3 times more observed in the FML group than that in the CSA group (P = 0.026). After 6 months, resolution of SEI was observed in 70% of the FML group and in 47% of the CSA group (P = 0.068). The recurrence of SEI was almost twice higher in the FML group than that in the CSA group (16% vs. 9%). FML was better tolerated during the first 3 months: a higher Schirmer test value (P = 0.0003), less burning on instillation (P = 0.242), and less conjunctival injection (P = 0.003). For the rest of the follow-up period, the 2 groups were comparable in tolerance. No ocular hypertension was noted. CONCLUSIONS: Epidemic keratoconjunctivitis can evolve favorably under both FML and CSA. The effect of FML is faster and CSA is more durable with fewer recurrences. Both are safe therapeutic options for long-term control of SEI.

[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.

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.

Ocular Features and Associated Systemic Findings in SARS-CoV-2 Infection.

PURPOSES: To describe the prevalence of ocular features among COVID-19 patients and their relationship with clinical data, inflammatory markers and respiratory support therapy (including CPAP); to investigate SARS-CoV-2 in ocular secretions of symptomatic patients. METHODS: 172 COVID-19 patients were evaluated for presence of ocular manifestations. Clinical and laboratory data were also reviewed. Conjunctival swabs were analyzed for SARS-CoV-2 by RT-PCR. RESULTS: Forty-five patients (26.2%) reported ocular manifestations. Patients treated with CPAP were more likely to have ocular abnormalities (p <.01). The presence of ocular symptoms was not associated with more significant alterations on blood tests. Conjunctival swabs from patients with suspect conjunctivitis yielded negative results for SARS-CoV-2. CONCLUSIONS: Ocular features are not infrequent in COVID-19 patients, but the presence of SARS-CoV-2 in ocular secretions is low. Ocular manifestations in hospitalized COVID-19 patients can also be a consequence of respiratory support therapy. Prevention of possible transmission through ocular secretions is still recommended.

Ophthalmic manifestations of coronavirus disease 2019 and ocular side effects of investigational pharmacologic agents.

PURPOSE OF REVIEW: To compile and report the ocular manifestations of coronavirus disease 2019 (COVID-19) infection and summarize the ocular side effects of investigational treatments of this disease. RECENT FINDINGS: Conjunctivitis is by far the most common ocular manifestation of COVID-19 with viral particles being isolated from tears/secretions of infected individuals. Multiple therapeutic options are being explored across a variety of medication classes with diverse ocular side effects. SUMMARY: Eye care professionals must exercise caution, as conjunctivitis may be the presenting or sole finding of an active COVID-19 infection. While no currently studied therapeutic agents have been found to reliably treat COVID-19, early vaccination trials are progressing and show promise. A video abstract is available for a more detailed summary. VIDEO ABSTRACT: http://links.lww.com/COOP/A36.

Natural protection of ocular surface from viral infections - A hypothesis.

A pandemic outbreak of a viral respiratory infection (COVID-19) caused by a coronavirus (SARS-CoV-2) prompted a multitude of research focused on various aspects of this disease. One of the interesting aspects of the clinical manifestation of the infection is an accompanying ocular surface viral infection, viral conjunctivitis. Although occasional reports of viral conjunctivitis caused by this and the related SARS-CoV virus (causing the SARS outbreak in the early 2000s) are available, the prevalence of this complication among infected people appears low (~1%). This is surprising, considering the recent discovery of the presence of viral receptors (ACE2 and TMPRSS2) in ocular surface tissue. The discrepancy between the theoretically expected high rate of concurrence of viral ocular surface inflammation and the observed relatively low occurrence can be explained by several factors. In this work, we discuss the significance of natural protective factors related to anatomical and physiological properties of the eyes and preventing the deposition of large number of virus-loaded particles on the ocular surface. Specifically, we advance the hypothesis that the standing potential of the eye plays an important role in repelling aerosol particles (microdroplets) from the surface of the eye and discuss factors associated with this hypothesis, possible ways to test it and its implications in terms of prevention of ocular infections.

SARS-COV-2 in Ophthalmology: Current Evidence and Standards for Clinical Practice.

INTRODUCTION: COVID-19 is caused by the coronavirus SARS-CoV-2. Ocular manifestations have been reported including conjunctivitis and retinal changes. Therefore, it is of the utmost importance to clarify eye involvement in COVID-19 in order to help with its diagnosis and to further prevent its transmission. The purpose of this review is to describe the structure and transmission of SARS-CoV-2, reported ocular findings and protection strategies for ophthalmologists. MATERIAL AND METHODS: Literature search on PubMed for relevant articles using the keywords 'COVID-19', 'coronavirus', and 'SARS-CoV-2' in conjunction with 'ophthalmology' and 'eye'. Moreover, official recommendations of ophthalmological societies were reviewed. RESULTS: Although the conjunctiva is directly exposed to extraocular pathogens, and the mucosa of the ocular surface and upper respiratory tract are connected by the nasolacrimal duct, the eye is rarely involved in human SARS-CoV-2 infection and the SARS-CoV-2 RNA positive rate by RT-PCR test in tears and conjunctival secretions from patients with COVID-19 is also extremely low. DISCUSSION: The eye can be affected by SARS-CoV-2, which is supported by some reports of conjunctivitis and retinal changes, but its role in the spread of the disease is still unknown. CONCLUSION: Given the current scarce evidence, more research is needed to clarify the relationship between SARS-CoV-2 and the eye.

Introdução: COVID-19 é o nome atribuído à doença causada pelo novo coronavírus - SARS-CoV-2. Esta infeção rapidamente atingiu uma disseminação mundial, face ao aumento da globalização e adaptação do vírus a ambientes distintos. Foram descritas manifestações oftalmológicas em doentes com COVID-19, nomeadamente, conjuntivite e alterações retinianas. Assim, é fundamental esclarecer o envolvimento ocular na COVID-19, contribuindo para o seu diagnóstico precoce e limitando a sua transmissão. O objetivo desta revisão é descrever a estrutura e o modo de transmissão do SARS-CoV-2, assim como manifestações oculares reportadas e estratégias de proteção para oftalmologistas. Material e Métodos: Revisão dos artigos relevantes publicados na PubMed usando as palavras-chave 'COVID-19', 'coronavirus' e 'SARS-CoV-2' em associação com as palavras 'ophthalmology' e 'eye'. Além disso, foi feita uma revisão das recomendações oficiais de várias sociedades oftalmológicas a nível mundial. Resultados: Apesar da conjuntiva estar diretamente exposta a patógenos exógenos, e da mucosa da superfície ocular e do trato respiratório superior estarem conectados pelo canal nasolacrimal, o olho raramente parece ser afetado pelo SARS-CoV-2. A infeção por SARS-CoV-2 e a taxa de positividade para a pesquisa do RNA do SARS-CoV-2 pelo teste de RT-PCR em lágrimas e secreções conjuntivais de pacientes com COVID-19 também são extremamente baixas. Discussão: O olho pode ser afetado pelo SARS-CoV-2, dada a descrição de casos de conjuntivite e alterações retinianas, mas o seu papel na disseminação da doença ainda é desconhecido. Conclusão: Dada a escassa evidência atual, são necessários mais estudos para esclarecer a relação entre o SARS-CoV-2 e o globo ocular.

Relapsing viral keratoconjunctivitis in COVID-19: a case report.

BACKGROUND: Since the outbreak of Coronavirus Disease 2019 (COVID-19) in December 2019, many studies have reported the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the conjunctival sac of patients infected with this virus, with several patients displaying symptoms of viral conjunctivitis. However, to our best knowledge, there is no in-depth report on the course of patients with COVID-19 complicated by relapsing viral conjunctivitis or keratoconjunctivitis. CASE PRESENTATION: A 53-year-old man confirmed with COVID-19 developed symptoms of viral conjunctivitis in the left eye approximately 10 days after the onset of COVID-19. The results of a nucleic acid test were positive for SARS-CoV-2 in the conjunctival sac of the left eye. The symptoms were relieved 6 days after treatment. However, the patient was subsequently diagnosed with viral keratoconjunctivitis in both eyes 5 days after the symptoms in the left eye were satisfactorily relieved. The disease progressed rapidly, with spot staining observed at the periphery of the corneal epithelium. Although SARS-CoV-2 could not be detected in conjunctival secretions, the levels of inflammatory factors, such as interleukin-6, were increased in both eyes. Both eyes were treated with glucocorticoids, and symptoms were controlled within 5 days. There was no recurrence. CONCLUSIONS: In this case report, the pathogenesis, clinical manifestations, treatment, and outcome of a case with COVID-19 complicated by relapsing viral keratoconjunctivitis is described, and the involvement of topical cytokine surge in the pathogenesis of COVID-19 as it relates to viral keratoconjunctivitis is reported.