Ocular manifestations of Monkeypox virus (MPXV) infection with viral persistence in ocular samples - a case series.

OBJECTIVE: We describe the clinical presentation and ocular viral dynamics in patients with Monkeypox virus-related ophthalmic disease (MPXROD). METHODS: In this case series, we investigated five consecutive patients with confirmed mpox, diagnosed through a positive Monkeypox virus (MPXV) Polymerase Chain Reaction (PCR) test and presenting with ocular symptoms. They were referred from the Reference Center for Sexually Transmitted Infections in São Paulo (CRT) to the Uveitis Sector at the Federal University of São Paulo, between August and December 2022. We performed PCR testing on ocular samples and culture supernatants for MPXV in all patients. Viral sequencing was conducted in one of the cases. RESULTS: Replicating MPXV was identified in at least one ocular sample of all patients, between day 31 and day 145 after the onset of skin lesions. All patients presented with keratitis, 3 with uveitis (60%) and two exhibited hypopyon (40%). The onset of ocular symptoms occurred at a mean of 21,2 days after the appearance of the first skin lesion and persisted, on average, for 61,6 days, with a worsening trend observed until the initiation of tecovirimat treatment. Tecovirimat treatment was administered to all patients, with initiation occurring between 31 and 145 days after the onset of skin lesions. MPXV genome sequencing of an isolate from one patient classified it as belonging to lineage B1 in clade IIb. CONCLUSION: This study reveals a late onset and persistence of sight threatening ocular disease, along with potential viral infectivity even after systemic resolution in mpox cases. These findings highlight the risk of ongoing transmission from individuals with prolonged ocular manifestations, particularly through ocular discharge.

SARS-CoV-2 and the ocular surface: test accuracy and viral load / SARS-CoV-2 e a superfície ocular: acurácia dos testes e carga viral

ABSTRACT Purpose: This study aimed to evaluate the pre-sence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA in the ocular surface of individuals clinically suspected of coronavirus disease 2019 (COVID-19) and determine the accuracy of different approaches of molecular testing on the ocular surface based on the nasopharyngeal positivity status for COVID-19. Methods: A total of 152 individuals with suspected COVID-19 symptoms who simultaneously underwent nasopharyngeal and two different tear film collection techniques for quantitative reverse-transcriptase polymerase chain reaction (RT-qPCR) were included. Tears were collected and randomized: one eye had the filter strip for the Schirmer test and the contralateral eye had conjunctival swab/cytology in the inferior fornix. All patients underwent slit lamp biomicroscopy. The accuracy of various ocular surface collection techniques used for the detection of SARS-CoV-2 RNA was determined. Results: Of the 152 patients enrolled in the study, 86 (56.6%) had COVID-19 confirmed by nasopharyngeal PCR. Both tear film collection techniques detected viral particles: the Schirmer test was positive in 16.3% (14/86) and the conjunctival swab/cytology in 17.4% (15/86), with no statistically significant differences. No positive ocular tests were found among those with negative nasopharyngeal PCR tests. The overall agreement of the ocular tests was 92.7%, and in combination, the sensitivity would increase to 23.2%. The mean cycle threshold values in the nasopharyngeal, Schirmer, and conjunctival swab/cytology tests were 18.2 ± 5.3, 35.6 ± 1.4, and 36.4 ± 3.9, respectively. Compared with the nasopharyngeal test, the Schirmer (p=0.001) and conjunctival swab/cytology (p<0.001) tests had significantly different Ct values. Conclusion: The Schirmer (16.3%) and conjunctival swab (17.4%) tests were comparably capable of detecting SARS-CoV-2 RNA in the ocular surface by RT-PCR accurately based on nasopharyngeal status and demonstrated indistinct sensitivity and specificity. Simultaneous specimen sampling and processing from the nasopharyngeal, Schirmer, and conjunctival swab/cytology tests demonstrated significantly lower viral load in both ocular surface approaches than in the nasopharyngeal test. Ocular manifestations detected by slit lamp biomicroscopy were not associated with ocular RT-PCR positivity.

RESUMO Objetivo: Avaliar a presença de RNA de coronavírus 2 causador de síndrome respiratória aguda grave (SARS-CoV-2) na superfície ocular de indivíduos clinicamente suspeitos com COVID-19 e determinar a precisão de diferentes abordagens de testes moleculares na superfície ocular com base no status de positividade do RT-qPCR de nasofaringe para COVID-19. Métodos: 152 indivíduos com sintomas suspeitos para a COVID-19 foram submetidos a coleta de reação em cadeia da polimerase de nasofaringe simultaneamente a duas técnicas diferentes de coleta de filme lacrimal para RT-qPCR: aleatoriamente, um olho com a tira filtro do teste de Schirmer e, o olho contralateral, com citologia (swab) conjuntival no fórnice inferior. Todos os indivíduos foram submetidos à biomicroscopia com lâmpada de fenda. Resultados: Dos 152 pacientes, 86 (56,6%) tiveram a COVID-19 confirmada por PCR de nasofaringe. Ambas as técnicas de coleta detectaram partículas virais: o teste de Schirmer foi positivo em 16,3% (14/86) e a citologia conjuntival em 17,4% (15/86), sem diferenças estatisticamente significativas. Não houve testes oculares positivos entre aqueles com reação em cadeia da polimerase de nasofaringe negativo. A concordância geral dos testes oculares foi de 92,7% e, em combinação, a sensibilidade aumentaria para 23,2%. Os valores médios do limiar de ciclo nos testes de nasofaringe, Schirmer e citologia conjuntival foram 18,2 ± 5,3, 35,6 ± 1,4 e 36,4 ± 3,9, respectivamente. Conclusão: Os testes de Schirmer (16,3%) e swab conjuntival (17,4%) foram igualmente capazes de detectar RNA de SARS-CoV-2 na superfície ocular por RT-PCR e demonstraram sensibilidade e especificidade indistintas. A coleta simultânea de amostras ao processamento dos testes de RT-PCR de nasofaringe, Schirmer e citologia (swab) conjuntival demonstraram carga viral significativamente menor em ambas as abordagens da superfície ocular em comparação com o teste de nasofaringe. As manifestações oculares detectadas pela biomicroscopia com lâmpada de fenda não foram claramente associadas à positividade do RT-PCR ocular.

Masquerade syndrome in ocular surface squamous neoplasia / Síndrome mascarada em neoplasia escamosa da superfície ocular

ABSTRACT The aim of this study was to alert the ophthalmic community to an atypical manifestation of ocular surface squamous neoplasia, which may delay diagnosis and treatment and result in a guarded visual prognosis and significant sequelae. A 61-year-old immunocompetent man presented with an initial diagnosis of necrotizing scleritis in the right eye for 3 months. He was treated with systemic prednisone but experienced persistent pain and low visual acuity. Conjunctival biopsy of the affected region confirmed the diagnosis of invasive ocular surface squamous neoplasia, which progressed with intraocular and orbital invasion; thus, exenteration was performed. Masquerade syndrome should be suspected in patients with nodulo-ulcerative lesions of the conjunctiva and sclera. This clinical can be more aggressive, with a greater likelihood of intraocular and orbital involvement. The earlier the diagnosis and treatment, the better the patient prognosis.

RESUMO O objetivo é alertar a comunidade oftalmológica sobre uma manifestação atípica de neoplasia escamosa da superfície ocular (OSSN) que pode levar a um atraso no diagnóstico e tratamento, evoluindo com prognóstico reservado e significativas sequelas. Homem, imunocompetente, 61 anos com diagnóstico inicial de esclerite necrosante em olho direito há 3 meses, em tratamento com prednisona sistêmica porém com persistência da dor e baixa acuidade visual. Realizado biópsia conjuntival em região acometida e diagnosticado como neoplasia escamosa da superfície ocular invasiva. Evolui com invasão intraocular e orbital sendo submetido a exenteração. Assim sendo, deve-se suspeitar de síndrome mascarada frente a um paciente com lesões nódulo-ulcerativas da conjuntiva e esclera. Essa forma clínica pode ser mais agressiva, com maior chance de comprometimento intraocular e orbital. Quanto mais precoces o diagnóstico e o tratamento, melhor o prognóstico para o paciente.

SARS-CoV-2 and the ocular surface: test accuracy and viral load.

PURPOSE: This study aimed to evaluate the pre-sence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA in the ocular surface of individuals clinically suspected of coronavirus disease 2019 (COVID-19) and determine the accuracy of different approaches of molecular testing on the ocular surface based on the nasopharyngeal positivity status for COVID-19. METHODS: A total of 152 individuals with suspected COVID-19 symptoms who simultaneously underwent nasopharyngeal and two different tear film collection techniques for quantitative reverse-transcriptase polymerase chain reaction (RT-qPCR) were included. Tears were collected and randomized: one eye had the filter strip for the Schirmer test and the contralateral eye had conjunctival swab/cytology in the inferior fornix. All patients underwent slit lamp biomicroscopy. The accuracy of various ocular surface collection techniques used for the detection of SARS-CoV-2 RNA was determined. RESULTS: Of the 152 patients enrolled in the study, 86 (56.6%) had COVID-19 confirmed by nasopharyngeal PCR. Both tear film collection techniques detected viral particles: the Schirmer test was positive in 16.3% (14/86) and the conjunctival swab/cytology in 17.4% (15/86), with no statistically significant differences. No positive ocular tests were found among those with negative nasopharyngeal PCR tests. The overall agreement of the ocular tests was 92.7%, and in combination, the sensitivity would increase to 23.2%. The mean cycle threshold values in the nasopharyngeal, Schirmer, and conjunctival swab/cytology tests were 18.2 ± 5.3, 35.6 ± 1.4, and 36.4 ± 3.9, respectively. Compared with the nasopharyngeal test, the Schirmer (p=0.001) and conjunctival swab/cytology (p<0.001) tests had significantly different Ct values. CONCLUSION: The Schirmer (16.3%) and conjunctival swab (17.4%) tests were comparably capable of detecting SARS-CoV-2 RNA in the ocular surface by RT-PCR accurately based on nasopharyngeal status and demonstrated indistinct sensitivity and specificity. Simultaneous specimen sampling and processing from the nasopharyngeal, Schirmer, and conjunctival swab/cytology tests demonstrated significantly lower viral load in both ocular surface approaches than in the nasopharyngeal test. Ocular manifestations detected by slit lamp biomicroscopy were not associated with ocular RT-PCR positivity.

Masquerade syndrome in ocular surface squamous neoplasia.

The aim of this study was to alert the ophthalmic community to an atypical manifestation of ocular surface squamous neoplasia, which may delay diagnosis and treatment and result in a guarded visual prognosis and significant sequelae. A 61-year-old immunocompetent man presented with an initial diagnosis of necrotizing scleritis in the right eye for 3 months. He was treated with systemic prednisone but experienced persistent pain and low visual acuity. Conjunctival biopsy of the affected region confirmed the diagnosis of invasive ocular surface squamous neoplasia, which progressed with intraocular and orbital invasion; thus, exenteration was performed. Masquerade syndrome should be suspected in patients with nodulo-ulcerative lesions of the conjunctiva and sclera. This clinical can be more aggressive, with a greater likelihood of intraocular and orbital involvement. The earlier the diagnosis and treatment, the better the patient prognosis.

Impact of COVID-19 on corneal esthesiometry.

Individuals with suspected COVID-19 symptoms (n=202) were tested using nasopharyngeal RT-qPCR. All individuals underwent corneal esthesiometry measurements using the Cochet-Bonnet esthesiometer during their first visit; 50 participants underwent an additional measurement at a mean interval of 32.5 (17.8) days. COVID-19 was confirmed in 101 subjects (50%) using nasopharyngeal PCR. The mean time from symptom onset to disease diagnosis and corneal esthesiometry was 4.2 (2.1) days. Mean corneal esthesiometry findings based on the positive and negative PCR status indicated no statistical difference. This study demonstrated that COVID-19 had no effect on corneal esthesiometry in individuals with acute-phase COVID-19.

Necrotizing Streptococcus pyogenes Infiltrating Conjunctiva and Tenon's Capsule: A Case Report.

We report a case of a patient with necrotizing infection of the conjunctiva and Tenon's capsule caused by Streptococcus pyogenes, a rare and atypical ophthalmologic condition. A 50-years-old male patient with acute red-eye, purulent discharge, and pain diagnosed with post-septal cellulitis presented with a yellowish and dense membrane covering the ocular surface with necrotic Tenon's capsule. Patient was hospitalized, and intravenous antibiotics were initiated (ceftriaxone and clindamycin). Topical antibiotics and corticosteroids were also administered, and the infection was eradicated in 2 weeks. Ancillary exams excluded rheumatologic involvement. Conjunctival culture confirmed Streptococcus pyogenes growth. Tenon's biopsy revealed unspecific acute inflammatory necrosis. This is an uncommon condition in daily ophthalmological clinic. Literature review reported 3 cases associated with previous ocular surgery.

SARS-COV-2 and Ocular Surface: From Physiology to Pathology, a Route to Understand Transmission and Disease.

Coronaviruses gained public attention during the severe acute respiratory syndrome (SARS) outbreak in East Asia in 2003 and spread of Middle Eastern respiratory syndrome (MERS) in 2012. Direct human-to-human contact and droplet are the main methods of transmission. Viral stability in aerosols on different surfaces supports evidence on indirect viral acquisition from fomites through the mucous membranes of the mouth, nose, and eyes. Given the pandemic circumstances, the level of evidence in COVID-19 and ophthalmology regarding eye infection, conjunctival transmission, and viral shedding through tears is insufficient. Presently, conjunctival transmission of coronaviruses has not been confirmed and remains controversial. Considering the physiology of the lacrimal system and ocular surface, the eyes are considered an immunoprotective site, with several antiviral molecules and anti-inflammatory proteins. Nevertheless, they represent an interface with the exterior world and face daily putative aggressors. Understanding the host's ocular surface immunological and protective environment is crucial to clarify the potential of the conjunctiva as an entry route for SARS-CoV-2 and as part of this viral infection. We will discuss hypothetical ocular surface transmission mechanisms and related counterarguments addressed to both angiotensin-converting enzyme 2 receptors found on the conjunctival and corneal epithelia and lactoferrin, lysozyme, lipocalin and secretory IgA levels in the tear film. Hopefully, we will promote better understanding of this organ in COVID-19 infection and the potential transmission route that can be helpful in setting recommendations on best practices and protective guidelines to mitigate the disease spread.