Superior ophthalmic vein and cavernous sinus thrombosis associated with COVID-19: a case report / Trombose de veia oftálmica superior e seio cavernoso associada à COVID-19: relato de caso

ABSTRACT Cavernous sinus and superior ophthalmic vein thrombosis is a rare clinical condition, and little described in the literature. The clinical presentation is nonspecific and highly variable, and symptoms may include red eye, ophthalmoplegia, coma, and death. The main etiology results from infection of the paranasal sinuses. The final diagnosis must be made through imaging tests such as magnetic resonance imaging. We describe a case of cavernous sinus and superior ophthalmic vein thrombosis after COVID-19 infection in a 64-year-old patient with persistent ocular hyperemia and pain on eye movement. Ophthalmological examination showed preserved visual acuity, conjunctival hyperemia, dilation of episcleral vessels and retinal vascular tortuosity in the right eye. Magnetic resonance imaging confirmed the diagnosis. The association with the COVID-19 was raised, excluding other infectious causes. Enoxaparin and Warfarin were started with significant improvement in the ocular clinical presentation and maintenance of initial visual acuity after 12 months of follow-up.

RESUMO A trombose de seio cavernoso e veia oftálmica superior é uma condição clínica rara e pouco descrita na literatura. A apresentação clínica é inespecífica e altamente variável. Os sintomas podem incluir olho vermelho, oftalmoplegia, coma e morte. A etiologia principal resulta da infecção dos seios paranasais. O diagnóstico final deve ser efetuado por meio de exames de imagem, como ressonância magnética. Descrevemos um caso de trombose de seio cavernoso e veia oftálmica superior após COVID-19 em paciente de 64 anos e com quadro de hiperemia ocular persistente e dor à movimentação ocular. Ao exame oftalmológico, observou-se acuidade visual preservada, hiperemia conjuntival, dilatação de vasos episclerais e tortuosidade vascular retiniana em olho direito. A ressonância confirmou o diagnóstico. A associação com a COVID-19 foi levantada, excluindo-se demais causas infecciosas. Prescrevemos enoxaparina e varfarina, com melhora do quadro clínico ocular e manutenção da acuidade visual inicial após 12 meses de acompanhamento.

Autoimmune Epithelitis and Chronic Inflammation in Sjögren's Syndrome-Related Dry Eye Disease.

Autoimmune epithelitis and chronic inflammation are one of the characteristic features of the immune pathogenesis of Sjögren's syndrome (SS)-related dry eye disease. Autoimmune epithelitis can cause the dysfunction of the excretion of tear fluid and mucin from the lacrimal glands and conjunctival epithelia and meibum from the meibomian glands. The lacrimal gland and conjunctival epithelia express major histocompatibility complex class II or human leukocyte antigen-DR and costimulatory molecules, acting as nonprofessional antigen-presenting cells for T cell and B cell activation in SS. Ocular surface epithelium dysfunction can lead to dry eye disease in SS. Considering the mechanisms underlying SS-related dry eye disease, this review highlights autoimmune epithelitis of the ocular surface, chronic inflammation, and several other molecules in the tear film, cornea, conjunctiva, lacrimal glands, and meibomian glands that represent potential targets in the treatment of SS-related dry eye disease.

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.

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 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.

In the eye of the storm: SARS-CoV-2 infection and replication at the ocular surface?

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) first emerged in December 2019 and spread quickly causing the coronavirus disease 2019 (COVID-19) pandemic. Recent single cell RNA-Seq analyses have shown the presence of SARS-CoV-2 entry factors in the human corneal, limbal, and conjunctival superficial epithelium, leading to suggestions that the human ocular surface may serve as an additional entry gateway and infection hub for SARS-CoV-2. In this article, we review the ocular clinical presentations of COVID-19 and the features of the ocular surface that may underline the overall low ocular SARS-CoV-2 infection. We critically evaluate the studies performed in nonhuman primates, ex vivo organ culture ocular models, stem cell derived eye organoids and the differences in infection efficiency observed in different parts of human ocular surface epithelium. Finally, we highlight the additional work that needs to be carried out to understand the immune response of the ocular surface to SARS-CoV-2 infection, which can be translated into prophylactic treatments that may be applied to other organ systems.

Evaluation of Nasopharyngeal and Conjunctival Swab Samples of Hospitalised Patients with Confirmed COVID-19.

PURPOSE: To evaluate the results of conjunctival and nasopharyngeal swab tests in patients with confirmed COVID-19. METHODS: This prospective study included 45 patients who were hospitalized for confirmed COVID-19. Nasopharyngeal swab samples were obtained from the patients before hospitalization. Only one eye of each patient was randomly selected for-conjunctival sampling. All participants underwent a complete slit-lamp examination. Conjunctival and nasopharyngeal swab samples were analyzed by reversetranscriptase-polymerase-chain reaction (RT-PCR). RESULTS: Twenty seven (60%) of the patients were male and 18 (40%) were female. Conjunctival swab was positive in only one (2.22%) patient. None of the COVID-19 patients showed ocular changes and symptoms. There were no abnormalities of the ocular surface, anterior chamber or posterior segment at slit-lamp examination. CONCLUSIONS: The RT-PCR was not high positive in the conjunctiva as in nasopharyngeal swabs. Ocular changes were not common in COVID-19 patients.

High expression of SARS-CoV-2 entry factors in human conjunctival goblet cells.

The angiotensin-converting enzyme 2 (ACE2) receptor has been proved for SARS-CoV-2 cell entry after auxiliary cellular protease priming by transmembrane protease serine 2 (TMPRSS2), but the co-effect of this molecular mechanism was unknown. Here, single-cell sequencing was performed with human conjunctiva and the results have shown that ACE2 and TMPRSS2 were highly co-expressed in the goblet cells with genes involved in immunity process. This identification of conjunctival cell types which are permissive to virus entry would help to understand the process by which SARS-CoV-2 infection was established. These finding might be suggestive for COVID-19 control and protection.

Expression of the COVID-19 receptor ACE2 in the human conjunctiva.

SARS-CoV-2 is assumed to use angiotensin-converting enzyme 2 (ACE2) and other auxiliary proteins for cell entry. Recent studies have described conjunctival congestion in 0.8% of patients with laboratory-confirmed severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), and there has been speculation that SARS-CoV-2 can be transmitted through the conjunctiva. However, it is currently unclear whether conjunctival epithelial cells express ACE2 and its cofactors. In this study, a total of 38 conjunctival samples from 38 patients, including 12 healthy conjunctivas, 12 melanomas, seven squamous cell carcinomas, and seven papilloma samples, were analyzed using high-throughput RNA sequencing to assess messenger RNA (mRNA) expression of the SARS-CoV-2 receptor ACE2 and its cofactors including TMPRSS2, ANPEP, DPP4, and ENPEP. ACE2 protein expression was assessed in eight healthy conjunctival samples using immunohistochemistry. Our results show that the SARS-CoV-2 receptor ACE2 is not substantially expressed in conjunctival samples on the mRNA (median: 0.0 transcripts per million [TPM], min: 0.0 TPM, max: 1.7 TPM) and protein levels. Similar results were obtained for the transcription of other auxiliary molecules. In conclusion, this study finds no evidence for a significant expression of ACE2 and its auxiliary mediators for cell entry in conjunctival samples, making conjunctival infection with SARS-CoV-2 via these mediators unlikely.

Conjunctivitis Related to not Severe COVID-19: A Case Report.

PURPOSE: The purpose of this article is to report a bilateral conjunctivitis case in a patient with confirmed 2019 novel coronavirus disease (COVID-19). CASE REPORT/OBSERVATIONS: A 24-year-old healthy man developed severe conjunctivitis in his right eye, followed by his left eye 4 days after fever and myalgia. He reported yellowish conjunctival discharge, foreign body sensation, redness, and tearing, and those symptoms were resolved in 10 days. Analyses of nasopharyngeal secretions identified SARS-CoV-2 by polymerase chain reaction (PCR). CONCLUSION: Mild COVID-19 can cause severe bilateral conjunctivitis. The ophthalmologist may be aware of conjunctival secretions, a possible path of infection, during eye checkup.

[Is conjunctival congestion in patients infected with 2019 novel coronavirus definitely related to the novel coronavirus].

This article was published ahead of print on the official website of Chinese Journal of Ophthalmology on April 14, 2020. Currently, it is commonly reported that coronavirus disease 2019 (COVID-19) patients are associated with conjunctival congestion and other symptoms, and the transmission route and high-risk eye diseases and high-risk working status are speculated. Are conjunctival congestion and conjunctiva-related symptoms in patients with 2019 novel coronavirus definitely related to the novel coronavirus? Conjunctival congestion is one of the common clinical signs of various types of conjunctivitis. The symptoms and signs of conjunctivitis in COVID-19 patients may be attributed to a variety of factors. Therefore, conjunctival symptoms should not be linked to 2019 novel coronavirus without evidence. ( Chin J Ophthalmol, 2020, 56: 571-572).

COVID-19 emergency in the cruise's ship: a case report of conjunctivitis.

Little is known about the Covid-19 transmission through ocular tissue, and more research needs to be carried out in order to confirm its ability to infect ocular tissue and its pathogenic mechanisms. Covid-19 may be detected in the tears and conjunctival secretions in novel coronavirus pneumonia patients with conjunctivitis. This case report shows a severe viral conjunctivitis in a patient diagnosed with Covid-19 on the Diamond Princess ship, characterized by both red, irritated and swollen eyes, with transparent serous secretions, conjunctival chemosis, pseudomembranes of fibrin and inflammatory cells on the tarsal conjunctiva accompanied by preauricular lymph nodes and enlarged submaxillaries.