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.

Outbreak of Adenovirus in a Neonatal Intensive Care Unit: Critical Importance of Equipment Cleaning During Inpatient Ophthalmologic Examinations.

PURPOSE: Outbreaks of adenovirus in neonatal intensive care units (NICUs) can lead to widespread transmission and serious adverse outcomes. We describe the investigation, response, and successful containment of an adenovirus outbreak in a NICU associated with contaminated handheld ophthalmologic equipment used during retinopathy of prematurity (ROP) screening. DESIGN: Epidemiologic outbreak investigation. PARTICIPANTS: A total of 23 hospitalized neonates, as well as NICU staff and parents of affected infants. MAIN OUTCOME MEASURES: Routine surveillance identified an adenovirus outbreak in a level IV NICU in August 2016. Epidemiologic investigation followed, including chart review, staff interviews, and observations. Cases were defined as hospital-acquired adenovirus identified from any clinical specimen (NICU patient or employee) or compatible illness in a family member. Real-time polymerase chain reaction (PCR) and partial- and whole-genome sequencing assays were used for testing of clinical and environmental specimens. RESULTS: We identified 23 primary neonatal cases and 9 secondary cases (6 employees and 3 parents). All neonatal case-patients had respiratory symptoms. Of these, 5 developed pneumonia and 12 required increased respiratory support. Less than half (48%) had ocular symptoms. All neonatal case-patients (100%) had undergone a recent ophthalmologic examination, and 54% of neonates undergoing examinations developed adenovirus infection. All affected employees and parents had direct contact with infected neonates. Observations revealed inconsistent disinfection of bedside ophthalmologic equipment and limited glove use. Sampling of 2 handheld lenses and 2 indirect ophthalmoscopes revealed adenovirus serotype 3 DNA on each device. Sequence analysis of 16 neonatal cases, 2 employees, and 2 lenses showed that cases and equipment shared 100% identity across the entire adenovirus genome. Infection control interventions included strict hand hygiene, including glove use; isolation precautions; enhanced cleaning of lenses and ophthalmoscopes between all examinations; and staff furlough. We identified no cases of secondary transmission among neonates. CONCLUSIONS: Adenovirus outbreaks can result from use of contaminated ophthalmologic equipment. Even equipment that does not directly contact patients can facilitate indirect transmission. Patient-to-patient transmission can be prevented with strict infection control measures and equipment cleaning. Ophthalmologists performing inpatient examinations should take measures to avoid adenoviral spread from contaminated handheld equipment.

A Polymerase Chain Reaction-Based Algorithm to Detect and Prevent Transmission of Adenoviral Conjunctivitis in Hospital Employees.

PURPOSE: To devise and implement a practice algorithm that would enable rapid detection and appropriate furlough of hospital employees with adenoviral conjunctivitis in order to prevent healthcare-associated epidemic keratoconjunctivitis. DESIGN: Evaluation of an ongoing quality assurance/improvement initiative. METHODS: Employees of Johns Hopkins Hospital with signs and symptoms of adenoviral conjunctivitis underwent evaluation by nurse practitioners in Occupational Health and rapid diagnostic testing by real-time polymerase chain reaction (PCR). Sequencing was used to determine serotype when adenovirus was detected. Signs, symptoms, diagnosis, and disposition of employees with eye complaints as well as PCR and serotype results were recorded. RESULTS: Over a 36-month period approximately 18% of initial employee visits were due to unique, eye-related complaints. Viral conjunctivitis was suspected in 542 of 858 employees with eye complaints (62%); adenovirus was detected by PCR in 44 of 542 suspected viral conjunctivitis cases (8%) or 44 of 858 employees with any eye concern (5%). Fourteen of the 44 employees had adenoviral serotypes and clinical presentation consistent with epidemic keratoconjunctivitis (type 37 [n = 6], 8 [n = 4], 4 [n = 3], 19 [n = 1]). Other serotypes found in individuals with less severe conjunctivitis were 3 (n = 5), 4 (n = 5), 56 (n = 4), 1 (n = 2), 42 (n = 1), and 7 (n = 1). No healthcare-associated adenoviral conjunctivitis outbreaks occurred after algorithm implementation, and fewer employees required furlough than had clinical diagnosis alone been used. CONCLUSIONS: The algorithm is an effective infection prevention tool that minimizes productivity loss compared to clinical diagnosis and allows for determination of prevalence and serotype characterization of adenoviral conjunctivitis in hospital employees.

Risk of blood splashes to the eye during surgery.

BACKGROUND: With the advent of a new infectious era involving the HIV and hepatitis B and C viruses, concern has arisen about transmission of these viruses through ocular blood splashes during surgery. The purpose of the study was to determine the risk of ocular blood splashes to surgeons and their assistants during surgery. METHOD: Surgeons and assistants in several surgical disciplines were requested to wear facemasks with a transparent plastic visor. The visors were collected postoperatively and inspected for macroscopic and microscopic blood splashes. RESULTS: Fifty-nine per cent of the surgeons and assistants refused to wear facemasks with a visor. The incidence of blood splashes in those who participated was 45%. There was a trend for blood splashes to be more common during major surgery and during elective surgery. Surgeons and assistants were subject to similar risk. CONCLUSION: This study confirms the significant risk of ocular blood splashes during surgery, while also suggesting that both surgeons and assistants lack appreciation of the risk.

Ocular contamination during lesional surgery-a hazard for the plastic surgeon.

UNLABELLED: Protective glasses reduce the risk of transconjunctival virus transmission although this has never been characterised for local anaesthetic skin lesion surgery. This study investigated the use of, and need for, protective eyewear during Plastic Surgery and the surgeons' attitude to risk. MATERIALS AND METHODS: Study 1. A multi-center questionnaire recorded the attitudes of Plastic Surgeons' regarding google use and ocular viral transmission. Study 2. A single surgeon performed local anaesthetic skin lesion surgery over 8 months whilst wearing clean goggles. After each procedure the goggles were inspected for macroscopic splashes ans a record made of whether the operator had been aware of the splash occurrence. RESULTS: Study 1. There were 36 respondents to the questionnaire (response rate of 84%). All grades recognised the risk of conjunctival contamination but most respondents did not wear goggles. Respondents changed their behavior, however, in 'high risk' cases. Study 2. 143 procedures resulted in 42 splashes. The surgeon was only aware of the splash in 6 cases. CONCLUSION: Despite widespread recognition of the importance of eye protection, goggle use is still infrequent. Our study stresses the frequency of potential splashes to the eye and need for routine use of goggles to prevent viral transmission.

Detection of hepatitis C virus in the corneas of seropositive donors.

PURPOSE: There have been no reported cases of hepatitis C virus (HCV) transmission by corneal transplantation. Previous studies have also shown no correlation between HCV seropositivity and the presence of HCV RNA in the corneal tissues. This study aims to investigate such correlation and to provide further evidence to the possible transmissibility of HCV via corneal grafts. METHODS: Of the 1,619 potential corneal donors to the Eye Bank of Canada over a 1-year period, 15 tested HCV-positive by the second-generation Abbott HCV enzyme immunoassay (EIA) 2.0 assay. Their sera were further tested with second-generation radio-immunoblot assay (RIBA-II), and their corneas (29 altogether) were processed for identification of HCV RNA using polymerase chain reaction (PCR). RESULTS: Of the 29 corneas from seropositive donors, HCV RNA was detected in 7 (24.1%). CONCLUSION: This is the first study in the literature that demonstrates a significant correlation between HCV seropositivity and the presence of HCV in the corneas. Routine HCV serologic testing for all potential corneal donors and rejection of corneal tissues based on HCV seropositivity is certainly justifiable.

The survival of adenovirus in multidose bottles of topical fluorescein.

PURPOSE: To determine if common ocular adenovirus serotypes survive in vitro in multidose bottles of topical fluorescein (Fluress; Pilkington Barnes Hind, Inc, Sunnyvale, California). METHODS: Clinical isolates of adenovirus types 8 and 19 were inoculated separately into 10 bottles each of Fluress and maintained at room temperature (25 C). All bottles were titered for adenovirus on A549 cell monolayers at 0, 7, 14, 21, 28, and 49 days. RESULTS: Adenovirus was recovered from Fluress for up to 21 days for adenovirus type 19 and 28 days for adenovirus type 8. CONCLUSION: A multidose bottle of Fluress contaminated with adenovirus can be a potential source of adenoviral transmission in an ophthalmic office setting.

HIV and AIDS and the eye in developing countries: a review.

An estimated 30 million people worldwide have been infected with the human immunodeficiency virus, the causative agent of the acquired immunodeficiency syndrome. Of these, 90% live in developing countries from where there is relatively little published information about the ocular manifestations of human immunodeficiency virus and acquired immunodeficiency syndrome. We review the information available from Africa, Latin America, and Asia. The prevailing ocular manifestations differ in some developing countries compared with those in the industrialized countries. These differences most likely result from different socioeconomic conditions and basic health care availability and from different patterns of endemic disease present before the human immunodeficiency virus epidemic.

Should antibody to hepatitis B core antigen be tested in routine screening of donor corneas for transplant?

PURPOSE: A review of the literature on transfusion-transmitted infectious diseases shows that antibody to hepatitis B core antigen (anti-HBc) is not presently viewed as helpful for hepatitis C or hepatitis non-ABC screening of blood donors. Its utility as a screen for hepatitis B or human immunodeficiency virus-1 (HIV-1) is controversial among experts. METHODS: We compare relevant aspects of the screening of blood donations and the screening of cornea transplant donors to assess implications for the screening of donor corneas. CONCLUSION: We conclude that there is not sufficient evidence to warrant introducing anti-HBc as a routine screening test for cornea donors.

Possible consequences of shaking hands with your patients with epidemic keratoconjunctivitis.

PURPOSE: We evaluated patients' hands as a possible vector for the spread of epidemic kerato-conjunctivitis. METHODS: The hands and conjunctivitis of 26 patients with epidemic keratoconjunctivitis and the hands of 26 uninfected control patients were cultured for infectious adenovirus. RESULTS: In 12 (46%) of 26 patients with epidemic keratoconjunctivitis, cultures from the hands were positive for adenovirus, whereas cultures from the hands of all uninfected control patients were negative. CONCLUSIONS: Simultaneous coinfection of patients' hands and eyes with adenovirus may contribute to office epidemics. Ophthalmologists and coworkers should not shake the hands of patients suspected of having epidemic keratoconjunctivitis unless properly gloved.

AIDS and the contact lens practice.

The probability of the ophthalmologist and office personnel coming into direct contact with a patient infected with the human immunodeficiency virus (HIV) is extremely high. HIV has been recovered from the ocular tissues, tears, and soft contact lenses of patients with acquired immunodeficiency syndrome. All ophthalmic offices, especially those with a contact lens practice, must be aware of any potential risk of transmission of HIV to both the office staff and to other patients from HIV-infected patients through the use of trial contact lenses. To date, there has been no documented case of HIV transmission through human tears or contact lenses, and the risk of such a transmission is extremely low.

Review of the risk of HIV infection through corneal transplantation in the United States.

BACKGROUND: Human immunodeficiency virus (HIV), the pathogen that causes acquired immunodeficiency syndrome (AIDS), has been isolated in the corneal epithelium of some HIV-positive patients. This observation raises concern about the risk of HIV transmission through corneal transplantation surgery (penetrating keratoplasty). METHODS: A comprehensive review of the literature of the ocular transmission of HIV, screening of donor corneas, and the potential of HIV transmission through penetrating keratoplasty was conducted and analyzed to review and interpret the relative risk of HIV infection through corneal transplantation. RESULTS: No cases of HIV transmission were found as a result of routine eye care or ophthalmic surgical procedures, including HIV-serp-negative recipients who inadvertently received HIV-seropositive corneas. CONCLUSIONS: While ocular transmission of HIV appears to be remote, there are still relative risks of HIV transmission due to ophthalmic surgical procedures. Careful screening of donors for HIV infection affords an important increase in the margin of safety for corneal transplantation recipients.