Acta MedPort2020Sep;33(9):593-600 Recebido: 13demaio de2020- Aceite: 016dejunho2020 |  2. DepartmentofSurgeryandPhysiology. FacultyofMedicine.UniversityPorto.Portugal. 1. DepartmentofOphthalmology. CentroHospitalarUniversitáriodeSãoJoão.Porto.Portugal. re closely was pathogen new this that suggested was it (SARS-CoV-2). 2 rus coronavi syndrome respiratory acute severe called coronavirus, later of type novel a as disease this of causative vention (CDC) isolated through a throat swab the pathogen Pre and Control Disease for Centre Chinese the 2020, ary related be to the South to China Seafood Market. confirmed On the 7 were people infected the of Most China. Province, Hubei Wuhan, in happening pneumonia plained unex of cases 41 of cluster a of notified was (WHO) zation INTRODUCTION RESUMO Sónia TORRES-COSTA ABSTRACT Recomendações paraaPráticaClínica SARS-COV-2 emOftalmologia:Evidência Atual e Standards forClinicalPractice SARS-COV-2 inOphthalmology:CurrentEvidenceand Autor correspondente:ManuelFalcã[email protected] Palavras-chave: ocular. Conclusão: papel nadisseminaçãodadoençaaindaédesconhecido. Discussão: conjuntivais depacientescomCOVID-19tambémsãoextremamentebaixas. secreções e RT-PCRlágrimas de em teste SARS-CoV-2RNApelo do do pesquisa a para positividade de taxa a SARS-CoV-2e por SARS-CoV-2.pelo afetado Aser infeção parece raramente olho o nasolacrimal, canal pelo conectados estarem superior respiratório Resultados: de váriassociedadesoftalmológicasanívelmundial. oficiais recomendações das revisão uma feita foi ‘eye’. disso, ‘ophthalmology’e Além palavras as ‘SARS-CoV-2’com associação em Material eMétodos: de proteçãoparaoftalmologistas. visão é descrever a estrutura e o modo de transmissão do SARS-CoV-2, assim como manifestações oculares reportadas e estratégias re desta objetivo O transmissão. sua a limitando e precoce diagnóstico seu o para contribuindo COVID-19, na ocular envolvimento o ções oftalmológicas em doentes com COVID-19, nomeadamente, conjuntivite e alterações retinianas. Assim, é fundamental esclarecer uma disseminação mundial, face ao aumento da globalização e adaptação do vírus a ambientes distintos. Foram descritas manifesta Introdução: Keywords: Conclusion: its roleinthespreadofdiseaseisstillunknown. Discussion: RNA positiveratebyRT-PCR testintearsandconjunctivalsecretionsfrompatientswithCOVID-19isalsoextremelylow. SARS-CoV-2the and SARS-CoV-2infection human in involved rarely is eye the duct, nasolacrimal the by connected are tract ratory Results: reviewed. were societies ophthalmological of recommendations official Moreover, ‘eye’. and ‘ophthalmology’ with conjunction ‘SARS-CoV-2’in Material and Methods: ported ocularfindingsandprotectionstrategiesforophthalmologists. re SARS-CoV-2, of transmission and structure the describe to is review this of purpose The transmission. its prevent further to and and retinal changes. Therefore, it is of the utmost importance to clarify eye involvement in COVID-19 in order to help with its diagnosis Introduction: On the 31 the On Although the conjunctiva is directly exposed to extraocular pathogens, and the mucosa of the ocular surface and upper respi Conjunctivitis;CoronavirusInfections;COVID-19;EyeDiseases;Ophthalmology;SARS-COV O olho pode ser afetado pelo SARS-CoV-2, dada a descrição de casos de conjuntivite e alterações retinianas, mas o seu Dada a escassa evidência atual, são necessários mais estudos para esclarecer a relação entre o SARS-CoV-2 e o globo COVID-19 é o nome atribuído à doença causada pelo novo coronavírus - SARS-CoV-2. Esta infeção rapidamente atingiu The eye can be affected by SARS-CoV-2, which is supported by some reports of conjunctivitis and retinal changes, but changes, retinal and conjunctivitis of reports some by supported is SARS-CoV-2,which by affected be can eye The st Apesar da conjuntiva estar diretamente exposta a patógenos exógenos, e da mucosa da superfície ocular e do trato do e ocular superfície da mucosa da e exógenos, patógenos a exposta diretamente estar conjuntiva da Apesar Given the current scarce evidence, more research is needed to clarify the relationship between SARS-CoV-2 and the eye. December 2019, the World Health Organi Health World the 2019, December COVID-19 is caused by the coronavirus SARS-CoV-2. Ocular manifestations have been reported including conjunctivitis Conjuntivite;COVID-19;InfecçõesporCoronavírus;Oftalmologia; Oftalmopatias;SARS-COV Revisão dos artigos relevantes publicados na PubMed usando as palavras-chave ‘COVID-19’, ‘coronavirus’ e ‘coronavirus’ ‘COVID-19’, palavras-chave as usando PubMed na publicados relevantes artigos dos Revisão 1,2 Based on phylogenomic analysis, analysis, phylogenomic on Based 1 ieaue erh n uMd o rlvn atce uig h kyod ‘OI-9, crnvrs, and ‘coronavirus’, ‘COVID-19’, keywords the using articles relevant for PubMed on search Literature , MárioLIMA-FONTES ica da Ordem dos Médicos www m o c . a s e u g u t r o p a c i d e m a t c a w. w w s o c i d é M s o d m e d r O a d a c fi í t n e i C a t s i v e R ▪

https://doi.org/10.20344/amp.14118 Copyright ©Ordemdos Médicos2020 1 , FernandoFALCÃO-REIS th Janu ------593 nesadn o oua mnfsain o ptet with patients of manifestations ocular of understanding eye. the and SARS-CoV-2 between ship relation direct a identify that literature medical the in ports deaths. 256 323 in sulting re globally, people 186 893 4 in identified was COVID-19 21 the On pandemic. a as COVID-19 ognized sively all over the world. On the 11 (COVID-19) and continued to spread in China and progres 2019 disease coronavirus named was SARS-CoV-2 with ancestor.common a sharing ably prob bats, in isolated were that coronavirus two to lated 1,2 , ManuelFALCÃO 4 urnl, hr ae oe re some are there Currently,  3 -2 th The disease associated disease The March 2020, WHO rec 1,2 -2 2,5-9 Therefore, the Therefore, st May 2020, May ------

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------27 29,30 A re 19-22 28 Other symptoms include Despite this vast array of 18 24 25,26

23 18 SARS-COV-2 transmission could happen 17 The spike (S) protein of coronaviruses facilitates 19 31 Acta Med Port 2020 Sep;33(9):593-600 Port 2020 Acta Med In the current pandemic of SARS-CoV-2, there are al It is known that infection by different coronaviruses may different by infection that known is It was isolated for In the 2004, firstHCoV-NL63 time from MERS-CoV in reported been not has involvement Ocular The biochemical interactions and the pathogenesis of The most common symptoms of infection are fever, A A similar assessment was performed in a study published positive demonstrate to failed it However, year. same the in results for in SARS-CoV-1 RNA the tears of the tested pa tients. ready some reports of ocular infection. A member of Chinese the national expert panel on pneumonia conjunctivitis during developed an inspection of Wuhan and later test gowned fully being despite SARS-CoV-2, the for positive ed cough and shortness of breath. nasal congestion, headache, sore throat, sputum produc tion, fatigue, myalgias, arthralgias, nausea, vomiting, diar rhoea, anosmia and ageusia. symptoms, a significant number of infected individuals may be asymptomatic. Coronavirus family and ocular disease lead to ocular involvement. a 7-month-old child with bronchiolitis and conjunctivitis. The association between this coronavirus and conjunctivi tis was corroborated in 2015, in France, by a retrospective study that found an incidence of 17% for conjunctivitis in a population of children infected with HCoV-NL63. and infection. SARS-CoV-1 Nevertheless, in 2004, a study was conducted to assess the presence RNA in tears of of infected patients by Three SARS-CoV-1 RT-PCR. out of 36 patients tested positive which led to the hypothesis that the conjunctiva could be a direct inoculation site of the vi rus from infected droplets; other options included migration from the upper respiratory tract through the nasolacrimal duct; or hematogenous infection via the lacrimal gland. fected fected patients, raising the possibility of a faecal/oral trans mission route. in asymptomatic carrier patients, making the prevention of infection challenging. COVID-19 SARS-CoV-2 are believed to be similar to those of SARS- CoV-1. viral entry into target cells. Entry depends on binding of the which receptor, cellular a to protein S the of S1, unit, surface facilitates viral attachment to the surface of target cells. In addition, entry requires S protein priming by cellular pro teases, which entails spike protein cleavage at the S1/S2 mem cellular and viral of fusion allows and site S2’ the and branes, a process driven by the S2 subunit. It was known engages that angiotensin-converting SARS-CoV-1 enzyme 2 (ACE2) as the entry receptor and employs the serine protease cellular TMPRSS2 for S protein priming. SARS-CoV-2 that reported lines cell human with study cent uses the same mechanism to infect cells and that inhibition of TMPRSS2 blocks viral entry. Moreover, sera from con valescent SARS-CoV-1 patients cross-neutralized SARS- entry. CoV-2-driven

594 ------15 16 co 10,11 The , and 15

Coronaviri Respiratory gamma 14 13 , Similarly, the 13 beta , 15 of the order Nidovirales. alpha R e v i s ta C i e n tífi c a d a Or d e m d o s M é d i c o s w w w.a c ta m e d i c a p o r tu g u e s a .c o m Torres-Costa S, et al. SARS-COV-2 in ophthalmology, in ophthalmology, SARS-COV-2 S, et al. Torres-Costa In 2002 – 2003, the severe acute res Coronaviridae 12 family and SARS-CoV-2 structure family and SARS-CoV-2

- based on their genomic structure and affect birds , which means crown and its characteristic structure is , in the family Viral RNA has also been found in stool samples from in from samples stool in found been also has RNA Viral While animals are considered the original source, Up to December 2019, only six different coronaviruses Coronaviruses get their name from the Latin word We We performed a literature search on PubMed for rele virus unless aerosols are created. In those circumstances, the virus could spread more than 2 meters and additional protective measures should be taken. periods. Viral particles could be absorbed via the respira tory mucosa and potentially across the conjunctivae. coronavirus is not currently considered to be an airborne CoV-2 CoV-2 is also plausible and when smaller respiratory par Airborne transmission occurs should not be neglected. ticles (generally < 5 µm) circulate in the air for prolonged virus may remain viable from hours to days. particles may be spread while breathing, speaking, cough ing Aerosol or and sneezing. fomite transmission of SARS- person through larger respiratory droplets, generally above 5 µm diameter, which are subject to gravitational forces. These droplets can be directly inhaled by other people or land on surfaces that others may contact with, where the SARS-CoV-2 transmission SARS-CoV-2 SARS-CoV-2 is believed to spread primarily via person-to- CoV) caused a devastating epidemic in 2012, rate. 2400 cases reported and a 37% mortality with over was responsible for 774 deaths in 26 countries, affecting more than 8000 people around the world. Middle East respiratory syndrome coronavirus (MERS- whilst the other two have caused notorious epidemics in the in epidemics notorious caused have two other the whilst past two decades. piratory syndrome coronavirus (now termed SARS-CoV-1) were known to infect humans. Four of these (HCoV-NL63, HCoV-229E, HCoV-OC43 and HKU1) usually caused mild common cold-type symptoms in immunocompetent people and mammals. Coronaviruses may obtain mutations which facilitate the transmission from animal species to humans concern. of pathogens zoonotic them made has this and nae They have four main subgroups - delta rona pos These envelope. viral the on projections surface to due subfamily the to belong viruses RNA itive-sense cal societies were systematically reviewed. cal societies were systematically Coronavirus vant articles using the keywords ‘COVID-19’, ‘coronavirus’, and in ‘SARS-CoV-2’ conjunction with ‘ophthalmology’ and ophthalmologi of recommendations official Moreover, ‘eye’. MATERIAL AND METHODS MATERIAL pose of this review is to describe the SARS-CoV-2 structure, SARS-CoV-2 the describe to is review this of pose protection and manifestations ocular reported transmission, for ophthalmologists. strategies COVID-19 COVID-19 by ophthalmologists and others may help in the pur The transmission. disease of prevention and diagnosis

ARTIGO DE REVISÃO published evidence demonstrated consistent expression of expression consistent demonstrated evidence published pigment retinal the and retina the as such eye, the of tissues posterior the in expressed mainly was ACE2 that thought was it Although tract. respiratory the of infection of mechanism SARS-CoV-1 the with larity simi in tissues ocular infect coronavirus to receptors new ACE2 use could this that theorized been has it system, geal swabs). nasopharyn from also (and swabs conjunctival from PCR RT- on SARS-CoV-2 for results positive had two only and swabs nasopharyngeal from RT-PCR on SARS-CoV-2 for results positive had 11 abnormalities, ocular with patients 12 the From prognosis. worse a predict could which toms, symp ocular without patients than dehydrogenase lactate and protein, C-reactive procalcitonin, of levels higher and counts neutrophil and cell blood white higher have to likely more were symptoms ocular with Patients them. of one in COVID-19 of symptom first the was Conjunctivitis cretions. se increased or epiphora, chemosis, hyperaemia, junctival con including conjunctivitis, with ocular consistent manifestations showed patients (31.6%) Twelve swabs. junctival con their in SARS-CoV-2 for positive testing two only but swabs nasopharyngeal RT-PCRfrom on Covid-19 for ings on February 8, 2020), with 28 patients yielding positive find China of Commission Health National the by published nia Pneumo Coronavirus Novel the of Control and Prevention cases (based on the 5 Covid-19 confirmed 38 of sample a analysed study second conjunctivitis. of signs showed who one only the be to happened which them, of one only in tears in test PCR RT-positive a reported study and patients infected first 30 evaluated The patients. infected of surface ocular the in a studyin55924laboratoryconfirmedcases. on based 0.8%, at congestion conjunctival of incidence the transmission. SARS-CoV-2of route alternative possible a as infection lar ocu into research for call a in resulted and protection eye of importance the for China in professionals healthcare ed respirator.N95 and suit protective a with SD: standarddeviation; IQR:interquartilerange;RT-PCR: reverse-transcription polymerasechainreaction Table 1 PositiveRT- PCRinnasopharyngeal swabs PositiveRT-PCR insputum PositiveRT-PCR inconjunctival swabs PositiveRT-PCR intears Conjunctivitis Male Age Severe-typepatients Total patients Study ic te ua ee a is w renin-angiotensin own its has eye human the Since SARS-CoV-2RNAof presence the studied Twopapers estimated COVID-19 on Mission Joint WHO-China The , years(mean±SD/median+IQR) –DatacomparisonbetweenXia , n(%) 7 Bothstudiesarecomparedin Table 1. , n , n(%) , n(%) th edition of the National Guideline on Torres-Costa S,etal.SARS-COV-2 inophthalmology, ica da Ordem dos Médicos www m o c . a s e u g u t r o p a c i d e m a t c a w. w w s o c i d é M s o d m e d r O a d a c fi í t n e i C a t s i v e R , n(%) , n(%) et al epithelium , n(%) (2020)andWu 8 This report alert report This , n(%) 9

recently, , 2 The et al (2020)studiesaboutocularfindingsinCOVID-19 ------595 rior chamber inflammation were detected. Fundoscopy was ante or corneal the on lesions No observed. were branes pseudomem or haemorrhage subconjunctival No noted. follicles and tender palpable preauricular lymph nodes were conjunctival palpebral inferior discharge, watery conjunctival injection, moderate bilateral examination, lamp slit At vision. blurred without eyes both in tearing and sensation body foreign redness, reported patient the symptoms), first the being diarrhoea and throat sore (with onset disease ter af days Thirteen detail. more in COVID-19 confirmed with described the ocular manifestations of a hospitalized patient paper One conjunctivitis. COVID-19 of characteristics the tract. respiratory the into duct nasolacrimal the through drained are tears in particles viral when occur could droplets from may beadirectinfectionroutetoSARS-CoV-2. surface ocular the that theory the support could evidence SARS-CoV-2.for point entry an as work could face sur ocular the that possibility the reintroducing mouses, of pterygium and cells conjunctival the in genes TMPRSS2 and ACE2 cotton wool spots and microhaemorrhages along the retinal subtle presented patients four Furthermore, eyes. both in bundle papillomacular the in prominent more were which sions at the level of ganglion cell and inner plexiform layers, le hyper-reflective showed (OCT) tomography coherence optical patients, all In SARS-CoV-2. with infected patients 12 in findings retinal reported authors The published. was COVID-19 with patients in conjunctivitis than other tations manifes ocular on paper first the 2020, May In COVID-19. to linked uveitis about or involvement corneal or sequela surface ocular about found was evidence No ommended. rec be should measures supportive general treatments, specific of knowledge no is there Since conjunctivitis. ated associ COVID-19 of duration the of report first the is This picture. clinical ocular the of resolution the with correlated which one last the except positive tested samples tient’s pa the 19. All and 17 14, 13, days on collected RNAwere SARS-CoV-2of detection for swabs Conjunctival illness. of 19 day by resolved signs and symptoms ocular normal. All Despite all the described evidence, little is known about known is little evidence, described the all Despite transmission indirect that defends theory different One Acta MedPort2020Sep;33(9):593-600 34

cells from patients with Xia 54.50 ±14.17 29 (97%) 21 (70%) 9 (30%) et al 1 (3%) 1 (3%) 30 - - , 2020 pterygium Wu Wu 68 (53to76) 28 (74%) 12 (32%) 25 (66%) 15 (39%) et al 2 (5%) and in corneas 38 - - , 2020 32,33 This ------6

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44 Adequate 47 Respiratory protec 44 In the United States 48 March 2020, a survey of The American equivalent Therefore, in the event of th 49 44 If in contact with a suspected or con and the 12 One Italian ophthalmologist reported 48 th 46 To protect healthcare workers protect healthcare PPE; with To Environmental cleaning and disinfection in healthcare in disinfection and cleaning Environmental To prevent virus spread between patients and health and patients between spread virus prevent To Acta Med Port 2020 Sep;33(9):593-600 Port 2020 Acta Med Healthcare workers should strictly follow the procedures the follow strictly should workers Healthcare Between Between the 10 The strategies adopted during the pandemic could be 1. 2. 3. (1) Personal protective equipment Although, there was some controversy initially regard tory viruses such as influenza. widespread community transmission leading to shortages the necessarily prioritize approach would rational a PPE, of use of FFP2/3 or N95 respirators for care activities involv ing a higher perceived risk of transmission, such as during aerosol generating procedures or in intensive care. for putting on (donning) and safely removing (doffing) PPE in the correct sequence. Active assistance during donning recommend the use of masks, long sleeved gowns, gog gles and breath shields, and gloves. tion could be subdivided into surgical masks (which tect pro against infectious agents transmitted by droplets) and facial filtering piece (FFP) respirators (which prevent the wearer from inhaling aerosols). In Europe, tors are FFP classified in respira three classes based on filter efficacy and face adhesion: FFP 1, 2 and 3 with 80%, filter 94%, efficacy and of 99%, respectively. of America, the respirator classification is subdivided in N (not resistant to oil-aerosols), R (somewhat resistant to oil- aerosols) and S (resistant to oil-aerosols) series, and each 95%, of efficiency filter minimum a have should these of one 99% and 99.97%, respectively. of the FFP2 is the N95. This respirator blocks at least 95 percent of very small (0.3 micron) test particles. Regarding the potential viral spread by asymptomatic COVID-19 car riers, surgical masks are recommended for all patients and healthcare workers. firmed COVID-19 case, healthcare workers should if wear, available, an FFP2 or N95 respirator tested for fitting or, a surgical mask, if no respirator is available. With the excep tion of aerosol generating procedures, it is unclear whether than protection better provide 3) or 2 (class respirators FFP surgical masks against other coronaviruses and respira guidance COVID-19 current on practitioners ophthalmology at three major UK eye hospitals was performed. It showed a lack of confidence and understanding of COVID-19 Pub lic Health guidance amongst practicing ophthalmologists, the in risk exposure regarding anxiety significant with along ophthalmic setting. the dramatic conditions experienced, where adequate per sonal protective equipment (PPE) was missing. protection in healthcare workers, including gists, is essential. ophthalmolo types of measures: divided in three different care workers; facilities. ing the appropriate PPE for ophthalmologists during their clinical practice, several organizations currently agree and

596 ------36 24,26,37,38 In fact, 45 ; other possi 41,42 This receptor has Other severe neu 36 36 Curiously, one of the of one Curiously, 44 R e v i s ta C i e n tífi c a d a Or d e m d o s M é d i c o s w w w.a c ta m e d i c a p o r tu g u e s a .c o m Torres-Costa S, et al. SARS-COV-2 in ophthalmology, in ophthalmology, SARS-COV-2 S, et al. Torres-Costa Hypothesized mechanisms of the Therefore, the infection mechanisms

5 35 43 Other studies reported several categories several reported studies Other 36,38,39 36 ; movement of the virus to the brain via the supported by symptoms of hyposmia and 36 40 Reported non-specific and systemic neurological systemic and non-specific Reported 36 By the end of March 2020, up to 10% of the reported Due to neuroinvasive and neurotrophic properties, we Currently, there is increasing evidence that SARS-Cov-2 that evidence increasing is there Currently, Chinese ophthalmologist caring for patients in Wuhan. He died at age 34 years allegedly from the disease. ophthalmologists are a risk group due to their proximity to the patient during observation in the slit lamp. cases in China and up to 9% of all cases in Italy have been have Italy in cases all of 9% to up China and in cases workers. healthcare among identified first alarms about COVID-19 was made by LiWenliang, a The risks of COVID-19 to ophthalmologists and patients and ophthalmologists COVID-19 to risks of The and to the autonomic system. However, as far as we know, and as to far the as autonomic we system. know, However, struc neuronal ocular of involvement of reports no are there tures. may hypothesize that SARS-CoV-2 may affect other neu sub-ba nerve, optic the including eye the in structures ronal muscles extraocular the to nerves plexus, nerve corneal sal endothelium; this could lead to blood-brain barrier damage the through involvement (CNS) system nervous central and circulatory system. been detected in neurons and glial cells, which make it S a SARS-CoV-2 Moreover, SARS-CoV-2. for target potential proteins may interact ACE2 with expressed in the capillary ble mechanisms are the hematological pathway ACE2 and has been shown to use the receptors. In fact, SARS-CoV-2 ACE2 receptor as a cellular entry way. ethmoid bone olfactory bulb hypogeusia reported in COVID-19 patients ing encephalopathy, meningitis, encephalitis and Guillain- Barré syndrome. neuro-invasion and manifestations on the nervous system include dissemination across the cribriform plate of the sciousness disorders, several categories of cerebrovascu lar events, such as, intra-cerebral haemorrhage, ischemic necrotiz acute also and thrombosis venous cerebral stroke, common in severe stages of disease. rologic manifestations, recently, reported patients are encephalopathy, epilepsy, in paralysis and con COVID-19 These symptoms range from 30% to 45.5%, and are more symptoms included headache, myalgia, dizziness, fatigue and hyposmia, hypogeusia and visual dysfunction. COVID-19 developed neurological symptoms or secondary events. cerebral COVID-19 in disorders neurological peripheral and central of patients. like MERS and SARS-CoV could be seen in SARS-CoV-2. in seen be could SARS-CoV and MERS like Regarding the clinical features, a previous study in Wuhan, for hospitalised (36%) patients 214 of 77 that demonstrated that neurotropic potential is one common coronavirus feature family. of the and neurotropism previously found for other coronaviruses tion were detected. tion were can involve the nervous system. Recent studies suggested arcades. Visual acuity and pupillary reflexes were normal in normal were reflexes pupillary and acuity Visual arcades. inflamma intraocular of signs or symptoms no and eyes, all

ARTIGO DE REVISÃO to remain at least two meters apart from one another.The one from apart meters two least at remain to caregiver should also disinfect his hands and wear a mask. necessary,the is caregiver a which in situations entrance. special In main the at wait must friends or members ily Fam hospital. the enter can patient the Only patient. the to hands disinfected, and a surgical face mask should be given measured, be should temperature entrance, main hospital the At resolve. symptoms until days 14 isolation in stay to recommended and home, sent be should criteria, any fulfil that Patients COVID-19. confirmed or suspected with tact con close (3) watering; sensation, body foreign pruritus, symptoms; gastrointestinal (2) symptoms of conjunctivitis including red eye, myalgia, headache, anosmia, wheezing, breath, of shortness throat, sore hoarseness, cough, ous of COVID-19: (1) fever, acute onset or persistent or continu entrance, hospital main about the presence of risks factors the or symptoms suggestive at survey, a answer should ophthalmologists. trained subspeciality by observation for patient the guide and symptoms, neuro-ophthalmological or retinal disease, corneal as such disease, ocular specific a identify even or cases, telemedicine may allow ophthalmologists to suspect other In recommendations. treatment make to enough be may information telehealth cases, some In exposure. vider pro limiting and travel patient decreasing screening, tive effec an allows system This alternative. an be could crisis health public COVID-19 the during telemedicine of use the with measurestoavoidcontactpatients. provided or area risk lower a condi to allocated be health should tions) underlying with those and immunosup people pressed women, pregnant (including risk increased Ophthalmology. of Society Portuguese the by recommended as risk, infection imize segregated teams, keeping them separated in order to min general health. or functioning, material vision, patient’s the to risk stantive sub without months two for postponed be can that cedure pro or appointment an as it defines (AAO) Ophthalmology of Academy American the ophthalmologists, between vary formed. Regarding the definition of ‘elective’, although it can per be should surgeries or appointments urgent and gent emer Only authorities. health public of recommendation upon rescheduled be only should procedures and ments appoint These cases. procedural and surgical elective all delaying and appointments nonurgent delay and elective recommended all ing have worldwide institutions Many and healthcareprofessionals removal ofPPE. con the after immediately washed be should Hands tamination. ofaccidental risk the minimize help will doffing and ptamlg wiig om Avs sae patients seated Advise room: waiting Ophthalmology appointment an to come who Patients triage: Patient Teleophthalmology: In the case of routine appointments, three or two into staff the Tosplit reorganization: Staff surgeries: and appointments non-urgent all Deferred (2) Preventing spread of the virusbetweenpatients 50 44

50 Torres-Costa S,etal.SARS-COV-2 inophthalmology, ica da Ordem dos Médicos www m o c . a s e u g u t r o p a c i d e m a t c a w. w w s o c i d é M s o d m e d r O a d a c fi í t n e i C a t s i v e R 51 n atclr clege with colleagues particular, In 48 48 ------597

including controls and accompanying breath lamps, shields, should Slit use. after gloves the discard and surfaces ing should wear disposable gloves when cleaning and disinfect workers Healthcare observation. patient each after fected tion recommendations healthcare both workers andpatients. for solutions gel alcoholic with regularly clinical decision. a making to critical when requested be only should sound, ultra topography, corneal tomography, coherence optical procedures essential should be performed. Special tests such as visual field test, Only minimized. the be observe should to patient required time The observation. slit-lamp the during speak to not patients their inform should gists ophthalmolo and examination during masks wear should patients all possible, If recommended. is barriers slit-lamp gists should wear PPE, as described previously. The use of healthcare workersshouldregularlydisinfectsurfaces. flammatory activity, involvement of the posterior segment, posterior the of involvement activity, flammatory in intraocular the on depending basis, case-by-case strategy a on therapeutic the individualize to disease: inflam matory ophthalmological known with patients in mended recom are measures following the (FOIS), Society mation Inflam Foster Ocular the and (IOIS) Society Inflammation Ocular International the (IUSG), Group Study Uveitis tional Interna the with line in and Inflammation Ocular of Group Therapy adjustmentinocularinflammatorydisease is prudenttosuspenditsuse. it therefore, and microaerosols, of source potential a is etry nozzles. disposable with tonometer retropulsion the using preferably or tips tonometer posable dis single-use, recommends case, AAO necessary.that In strictly cases to limited be should tonometry transmission, nometer tips. 70% alcohol solutions should be effective for disinfecting to Therefore, alcohol. to resistant more much are that ruses mendations. EPArecom the in seen be can SARS-CoV-2 against use for recommended currently disinfectants registered (EPA) Agency Protection Environment Stated United common er water and alcohol solutions with at least 70% alcohol. hold bleach 5 tablespoons bleach per gallon/per 3.8 litres of house diluted include COVID-19 to specific disinfectants examination. cal clini the after alcohol ethyl 70% with disinfected be should probes, b-scan and lamps slit as such tissues, ocular with tice of several centres, all shared equipment having contact be disinfected,immediatelyaftereachpatientevaluation. om ad ntuet sol b toogl disin thoroughly be should instruments and Rooms (3) Environmentalcleaningandequipmentdisinfec hands washing recommends WHO The hygiene: Hand Ophthalmolo examination: ophthalmological During codn t te eomnain o te Portuguese the of recommendations the to According adenovi unlike virus, enveloped an is SARS-CoV-2 prac current and recommendations WHO to According Acta MedPort2020Sep;33(9):593-600 53 50

However, considering the risk of conjunctival 3,52 The current CDC recommendations for recommendations CDC current The 50

50 o-otc tonom Non-contact 50 Oth ------

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- - - - 60

62 63,64 59 In Portugal, although the HCQ as treat 56 In France, initially, 600 mg/day of HCQ for 10 In France, initially, 61 : Acta Med Port 2020 Sep;33(9):593-600 Port 2020 Acta Med The lack of observed benefit of HCQ associated with in- with associated HCQ of benefit observed of lack The Although CQ and HCQ are still used in many countries, The AAO recommended a maximum daily HCQ use of ≤ 5.0 mg/kg of real weight, with risk of toxicity being associated associated with neither a greatly lowered or increased risk or death. of intubation hospital following mortality, adjustment for pre-existing dis with consistent is admission, on illness of severity and ease recently reported data from other observational studies. Regarding the dose and duration of treatment, there of course 10-day a China, in instance, For variations. some are 500 mg CQ twice or daily, 400 mg HCQ four times daily is being used. days was used. ment for COVID-19 has been suspended, at the beginning of this pandemic, HCQ was prescribed as 400 daily for followed mg one by day, 200 mg twice daily for twice five or course. disease the patient’s 10 days according to taking into account the latest data reported by recent stud ies that suggested the absence of benefit or evencreased risk an in of mortality associated with HCQ, at the end of May 2020, several European countries, namely France, Belgium, Italy and Portugal have suspended HCQ as treatment for COVID-19. the use of

598 - - - - - In cases L and without recent increase in dose drugs; L 54 ; μ μL Additional recommendations recommendations Additional 54 R e v i s ta C i e n tífi c a d a Or d e m d o s M é d i c o s w w w.a c ta m e d i c a p o r tu g u e s a .c o m Torres-Costa S, et al. SARS-COV-2 in ophthalmology, in ophthalmology, SARS-COV-2 S, et al. Torres-Costa 55 Treatment has been authorized despite warn despite authorized been has Treatment Temporary interruption of Temporary immunomodulatory treatment, (conventional or biological) until complete recovery of COVID-19 infection; guaranteed; the minimum time required for tapering should be In systemic corticotherapy, The maintenance option of interferon or tocilizumab should be mandatorily discussed with the doctor responsible for the treatment of COVID-19 infection. Blood count should be monitored; To discuss with the doctor responsible for monitoring immunomodulatory therapy; of SARS-CoV-2 infection the need to infection; will be desirable screening for SARS-CoV-2 Testing reduce or suspension of 55-58 Symptomatic patients with confirmed COVID-19 infection: ------the other hand, a beneficial effect on the eventual prevention and treatment of ‘Cytokine storm syndrome’ that characterizes stage III of COVID-19 (with emphasis on interferon and tocilizumab) could be seen. Asymptomatic patients suspected of having a COVID-19 infection Leukocyte count should stay above 4000/ without patients in intervals harvest spacing necessary, whenever toxicity pharmacological monitor to study analytical an Repeat > 4000/ with leukocytes evidence of toxicity, Prioritize, if possible, harvests in a location close to the patient. Immunomodulatory therapy can theoretically compromise the response immune system in the early stages of COVID-19. On Under oral prednisolone > 5 mg / day associated with another immunomodulatory drug Under oral prednisolone > 5 mg / day associated in the last 6 months. Administration of cyclophosphamide or rituximab In patients undergoing dose titration, if possible, interrupt dose reduction and maintain the minimum dose previously effective, risk and normalization of evaluation conditions for patients; ideally until the disappearance of pandemic switching or starting new immunomodulatory treatments until that the pandemic is controlled. Avoid Under oral prednisolone > 20 mg/day (or 0.5 mg / kg / day) for more than 4 weeks, Under oral prednisolone > 20 mg/day (or 0.5 Under two or more drugs, co-morbidity, Immunosuppressants associated with another – Recommendations for evaluation and therapy management in non-infectious uveitis on immunomodulatory therapy during • • • • • • • • • • • • • An observational study of 1376 patients with COVID-19 Chloroquine (CQ) and hydroxychloroquine (HCQ) were Clinic compatible with COVID-19 infection Analytical study How to manage immunomodulatory therapy Non-infectious uveitis previously on immunomodulatory therapy Non-infectious uveitis previously on immunomodulatory if: Patients are under higher infectious risk Table Table 2 Group of Ocular Inflammation COVID-19 pandemics based on Portuguese who had been admitted to a large medical centre in New York City demonstrated that HCQ administration was not ings from scientific advisers about the lack of randomized efficacy and safety drugs’ these supporting trials controlled in this population. Drug Administration (FDA) based on limited in-vitro and an and in-vitro limited on based (FDA) Administration Drug ecdotal clinical data and is being used as off-label in many countries. Chloroquine and hydroxychloroquine as treatment as treatment of and hydroxychloroquine Chloroquine of the ophthalmologist COVID-19: the role approved as treatment for COVID-19 by the US Food and concerning non-infectious uveitis under immunomodulatory under uveitis non-infectious concerning 2. Table in treatment can be found treatment. treatment. Local corticosteroid therapy has not been asso accord infection, COVID-19 of risk increased an with ciated evidence. available the to ing instead of systemic immunomodulatory agents. of increased risk of secondary ocular hypertension, consid local after therapy eye topical hypotensive of prescription er chronicity, risk of functional chronicity, loss and state of the other eye; to prefer topical therapy and/or local corticosteroid therapy

ARTIGO DE REVISÃO 17. 16. 15. 14. 13. 12. 11. 10. 9. 8. 7. 6. 5. 4. 3. 2. 1. REFERENCES with patients in conjunctivitis of reports some by supported CONCLUSION garding CQorHCQusageforCOVID-19. re concern serious a not is retinopathy that public physicians the and reassure should ophthalmologists Therefore, counterproductive. be would tests screening questionable of performance the equipment, and personnel medical of shortages world-wide with pandemic of time a in Besides, retinal damage is remarkably low even with high dosages. of probability the therapy,because anti-viral as weeks two than less for HCQ or CQ take who patients COVID-19 for necessary not is screening ophthalmic that suggested MF AAO, even if for a short period of time. the by recommended those than higher are used dosages of treatment. Nevertheless, in order to treat COVID- 19, the years more or 10 before seen rarely is retinopathy dosage, use. of duration and dose daily on dependent compared withSARS-CoV-1. NEnglJ Med.2020;382:1564-7.. as SARS-CoV-2 of stability surface and Aerosol al. et BN, Williamson pandemic -anarrativereview. Anaesthesia. 2020;75:920-7.. Dis. Infect Emerg transmission. 2020;26:191. coronavirus syndrome respiratory syndrome. NEnglJMed.2003;349:2431-41. far. so know we Pathogens. 2020;9. what 2019: disease coronavirus and SARS-CoV-2 bat origin.Nature.2018;556:255-8. of coronavirus HKU2-related an by caused syndrome diarrhoea acute Rev Microbiol.2019;17:181-92. cov-2-through-ocular-fluids/. https://www.cebm.net/covid-19/spreading-sars-from: 10]. Available Apr surface mustnotbeignored.Lancet.2020;395:e39. Hubei Province,China.JAMA Ophthalmol.2020;138:575-8. ocular findings of patients with coronavirus disease 2019 (COVID-19) in 10.1136/ doi: bjophthalmol-2020-316304. novel press). (in 2019 2020 Ophthalmol. confirmed J Br with disease. coronavirus patient hospitalised a of manifestations Retinal findingsinpatientswithCOVID-19.Lancet.2020;395:1610. Available reports/20200521-covid-19-sitrep-122.pdf?sfvrsn=24f20e05_2:1-17. 30]. https://www.who.int/docs/default-source/coronaviruse/situation- May 2020 [accessed from: 2020. 122. – Report Situation coronavirus. ClinInfectDis.2020(inpress).doi:10.1093/cid/ciaa1 J Med Virol. 2020.;92:589-94.. infection. SARS-CoV-2 with patients of secretions conjunctival and Virol. Med 2020;92:401-2. J miracle. the and mystery The China: Wuhan, in etiology Holshue ML, DeBolt C, Lindquist S, Lofy KH, Wiesman J, Bruce H, et al. COVID-19 the A, Gamble MG, Holbrook DH, T,Morris Bushmaker during N, Doremalen van equipment protective Personal TM. Cook East Middle TW. John IG, Susan MM, Claire MB, Holly EK, Marie Peiris JS, Yuen KY, Osterhaus AD, Stöhr K. The severe acute respiratory AD. Al-Nasser DM, Salameh GA, Kasasbeh MS, Zoubi Al FA, Rabi swine Fatal al. et W, WF,Zhang Shi XL, T,YangLan H, P,Fan Zhou Cui J, Li F, Shi ZL. Origin and evolution of pathogenic coronaviruses. Nat 2020 [accessed 2020. fluids. ocular through SARS-CoV-2 Spreading ocular the through transmission 2019-nCoV ZF. Jia XF, Liu CW, Lu of Characteristics al. et L, Liang X, Qu Q, Liu C, Luo F, Duan P,Wu Ocular al. et M, Chen T, Huang K, Qiao Z, Zhang M, Liu L, Chen Jr. R Belfort H, Nascimento AC, Romano AA, Marcos PM, Marinho (COVID-19) 2019 disease Coronavirus Organization. Health World Zhang L, Shen FM, Chen F, Lin Z. Origin and evolution of the 2019 novel tears in coronavirus Y,TongShen J, of M, Xia Evaluation Liu D. J, Guo unknown of pneumonia of Outbreak YW. Tang CW, Stratton H, Lu is which disease, new this by affected be can eye The Torres-Costa S,etal.SARS-COV-2 inophthalmology, ica da Ordem dos Médicos www m o c . a s e u g u t r o p a c i d e m a t c a w. w w s o c i d é M s o d m e d r O a d a c fi í t n e i C a t s i v e R 61 Therefore, Marmor 61

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