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Roshanshad A, Ali Ashraf M, Roshanshad R, Kharmandar A, Alireza Zomorodian S, Ashraf H. Ocular Manifestations of Patients with Coronavirus Disease 2019: A Comprehensive Review. JOVR [Internet]. 2021Apr.29 [cited 2024Jun.30];16(2):234–247. Available from: https://knepublishing.com/index.php/JOVR/article/view/9087
https://doi.org/10.18502/jovr.v16i2.9087
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Amirhossein Roshanshad
Amirhossein Roshanshad
Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran
-
Mohammad Ali Ashraf
Mohammad Ali Ashraf
Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran
-
Romina Roshanshad
Romina Roshanshad
Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran
-
Ali Kharmandar
Ali Kharmandar
Non-communicable Disease Research Center, Fasa University of Medical Sciences, Fasa, Iran
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Seyed Alireza Zomorodian
Seyed Alireza Zomorodian
Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran
-
Hossein Ashraf
Hossein Ashraf
Poostchi Ophthalmology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
Published Date
- Apr 29, 2021
Ocular Manifestations of Patients with Coronavirus Disease 2019: A Comprehensive Review
Abstract
Apart from conjunctival involvement which is the most well-known ocular manifestation of coronavirus infectious disease 2019 (COVID-19), there are multiple reports of the involvement of other ocular structures by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We comprehensively reviewed PubMed, Scopus, Embase, and Google Scholar for available evidence regarding COVID-19 various ocular manifestations, with special focus on less known and unusual ocular findings. We then categorized the findings based on the parts of the eye which was involved. In anterior sections of the eye, the involvement of the eyelid (tarsadenitis), conjunctiva and cornea (follicular conjunctivitis, pseudomembranous conjunctivitis, and keratoconjunctivitis), episclera (nodular episcleritis), uvea (anterior uveitis) were reported. Also, third, fourth, and sixth nerve palsy, retinal vasculitis, retinal optical coherence tomography (OCT) changes (hyper-reflective lesions and increased retinal nerve fiber layer thickness [RNFLT]), optic neuritis, papillophlebitis, Miller Fisher syndrome, posterior reversible leukoencephalopathy (PRES), ophthalmic artery and central retinal artery occlusion, and polyneuritis cranialis were reported in different studies. Postmortem evaluation of COVID-19 patients detected no viral RNA in different anterior and posterior segments of the eyes. However, another study revealed a 21.4% positivity of the retinal biopsies of dead patients. The results of this study can help ophthalmologists to be vigilant when they see these findings in a suspected case of COVID-19. In addition, wearing face masks and protective goggles or eye shields are recommended, especially in high-risk contacts.
Keywords:
Coronavirus, COVID-19, Manifestations, Ocular, Ophthalmologic
References
1. Chou R, Dana T, Buckley DI, Selph S, Fu R, Totten AM. Epidemiology of and risk factors for coronavirus infection in health care workers. Ann Intern Med 2020;173:120–136.
2. Douglas KAA, Douglas VP, Moschos MM. Ocular manifestations of COVID-19 (SARS-CoV-2): a critical review of current literature. In vivo 2020;34:1619–1628.
3. Rothan HA, Byrareddy SN. The epidemiology and pathogenesis of coronavirus disease (COVID-19) outbreak. J Autoimmun 2020:102433.
4. Santarpia JL, Rivera DN, Herrera VL, Morwitzer MJ, Creager HM, Santarpia GW, et al. Aerosol and surface contamination of SARS-CoV-2 observed in quarantine and isolation care. Sci Rep 2020;10:12732.
5. Xia J, Tong J, Liu M, Shen Y, Guo D. Evaluation of coronavirus in tears and conjunctival secretions of patients with SARS-CoV-2 infection. J medical virology 2020;92(??):589-594.
6. Lai THT, Tang EWH, Chau SKY, Fung KSC, Li KKW. Stepping up infection control measures in ophthalmology during the novel coronavirus outbreak: an experience from Hong Kong. Graefes Arch Clin Exp Ophthalmol 2020;258:1049–1055.
7. Cadet J. Harmless effects of sterilizing 222-nm far-UV radiation on mouse skin and eye tissues. Photochem Photobiol 2020;96:949–950.
8. Aytoğan H, Ayintap E, Yilmaz NÖ. Detection of coronavirus disease 2019 viral material on environmental surfaces of an ophthalmology examination room. JAMA Ophthalmol 2020;138:990–993.
9. Wu P, Duan F, Luo C, Liu Q, Qu X, Liang L, et al. Characteristics of ocular findings of patients with coronavirus disease 2019 (COVID-19) in Hubei Province, China. JAMA Ophthalmol 2020;138:575.
10. Wan Y, Shang J, Graham R, Baric RS, Li F. Receptor recognition by the novel coronavirus from Wuhan: an analysis based on decade-long structural studies of SARS coronavirus. J Virol 2020;94:e00127–e00200.
11. Li W, Moore MJ, Vasilieva N, Sui J, Wong SK, Berne MA, et al. Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature 2003;426:450– 454.
12. Letko M, Marzi A, Munster V. Functional assessment of cell entry and receptor usage for SARS-CoV-2 and other lineage B betacoronaviruses. Nat Microbiol 2020;5:562–569.
13. Zou X, Chen K, Zou J, Han P, Hao J, Han Z. Single-cell RNAseq data analysis on the receptor ACE2 expression reveals the potential risk of different human organs vulnerable to 2019-nCoV infection. Front Med 2020;14:185–192.
14. Zhou L, Xu Z, Castiglione GM, Soiberman US, Eberhart CG, Duh EJ. ACE2 and TMPRSS2 are expressed on the human ocular surface, suggesting susceptibility to SARS-CoV-2 infection. Ocul Surf 2020;18:537–544.
15. Senanayake Pd, Drazba J, Shadrach K, Milsted A, Rungger- Brandle E, Nishiyama K, et al. Angiotensin II and its receptor subtypes in the human retina. Invest Ophthalmol Vis Sci 2007;48:3301–3311.
16. Holappa M, Valjakka J, Vaajanen A. Angiotensin (1- 7) and ACE2,“the hot spots” of renin-angiotensin system, detected in the human aqueous humor. Open J Ophthalmol 2015;9:28.
17. Collin J, Queen R, Zerti D, Dorgau B, Georgiou M, Djidrovski I, et al. Co-expression of SARS-CoV-2 entry genes in the superficial adult human conjunctival, limbal and corneal epithelium suggests an additional route of entry via the ocular surface. Ocul Surf 2020;19:190–200.
18. Critical appraisal tools | Joanna Briggs Institute [Internet]. Joannabriggs.org; 2020 [cited 2020 December 4]. Available from: https://joannabriggs.org/critical-appraisaltools
19. Xu M, Zhang H, Niu X. COVID-19 patient firstly visiting eye doctor due to tarsadenitis and subconjunctival hemorrhage: a case report. Zhonghua Shiyan Yanke Zazhi/Chinese Journal of Experimental Ophthalmology 2020;38:374–376.
20. Megarbane B, Tadayoni R. Cluster of chalazia in nurses using eye protection while caring for critically ill patients with COVID-19 in intensive care. Occup Environ Med 2020;77:584–585.
21. McCulley JP, Dougherty JM, Deneau DG. Classification of chronic blepharitis. Ophthalmology 1982;89:1173–1180.
22. McCulley JP, Dougherty J. Bacterial aspects of chronic blepharitis. Trans Ophthalmol Soc UK 1986;105:314–318.
23. Terpos E, Ntanasis-Stathopoulos I, Elalamy I, Kastritis E, Sergentanis TN, Politou M, et al. Hematological findings and complications of COVID-19. Am J Hematol 2020;95:834–847.
24. Knop E, Knop N, Millar T, Obata H, Sullivan DA. The international workshop on meibomian gland dysfunction: report of the subcommittee on anatomy, physiology, and pathophysiology of the meibomian gland. Invest Ophthalmol Vis Sci 2011;52:1938–1978.
25. Bostanci Ceran B, Ozates S. Ocular manifestations of coronavirus disease 2019. Graefes Arch Clin Exp Ophthalmol 2020;258:1959–1963.
26. WHO. Report of the WHO–China joint mission on coronavirus disease 2019 (COVID-19). WHO; 2020.
27. Sarma P, Kaur H, Kaur H, Bhattacharyya J, Prajapat M, Shekhar N, et al. Ocular manifestations and tear or conjunctival swab PCR positivity for 2019-nCoV in patients with COVID-19: a systematic review and meta-analysis. SSRN 2020. Available from: https://ssrn.com/abstract= 3566161
28. Loffredo L, Pacella F, Pacella E, Tiscione G, Oliva A, Violi F. Conjunctivitis and COVID-19: a meta-analysis. J Med Virol 2020;92:1413–1414.
29. Chen L, Deng C, Chen X, Zhang X, Chen B, Yu H, et al. Ocular manifestations and clinical characteristics of 535 cases of COVID-19 in Wuhan, China: a cross-sectional study. Acta Ophthalmol 2020;98:e951–e959.
30. Navel V, Chiambaretta F, Dutheil F. Haemorrhagic conjunctivitis with pseudomembranous related to SARSCoV- 2. Am J Ophthalmol Case Rep 2020:100735.
31. Chen L, Liu M, Zhang Z, Qiao K, Huang T, Chen M, et al. Ocular manifestations of a hospitalised patient with confirmed 2019 novel coronavirus disease. Br J Ophthalmol 2020;104:748–751.
32. Colavita F, Lapa D, Carletti F, Lalle E, Bordi L, Marsella P, et al. SARS-CoV-2 isolation from ocular secretions of a patient with COVID-19 in Italy with prolonged viral RNA detection. Ann Int Med 2020;173:242–243.
33. Aiello F, Afflitto GG, Mancino R, Li J-PO, Cesareo M, Giannini C, et al. Coronavirus disease 2019 (SARS-CoV- 2) and colonization of ocular tissues and secretions: a systematic review. Eye 2020;34:1206–1211.
34. Corman VM, Landt O, Kaiser M, Molenkamp R, Meijer A, Chu DK, et al. Detection of 2019 novel coronavirus (2019-nCoV) by real-time RT-PCR. Eurosurveillance 2020;25:2000045.
35. Lin C, Ye R, Xia Y. A meta-analysis to evaluate the effectiveness of real-time PCR for diagnosing novel coronavirus infections. Genet Mol Res 2015;14:15634– 15641.
36. Raboud J, Shigayeva A, McGeer A, Bontovics E, Chapman M, Gravel D, et al. Risk factors for SARS transmission from patients requiring intubation: a multicentre investigation in Toronto, Canada. PLoS ONE 2010;5:e10717.
37. Qing H, Li Z, Yang Z, Shi M, Huang Z, Song J, et al. The possibility of COVID-19 transmission from eye to nose. Acta Ophthalmol 2020;98:e388.
38. Cheema M, Aghazadeh H, Nazarali S, Ting A, Hodges J, McFarlane A, et al. Keratoconjunctivitis as the initial medical presentation of the novel coronavirus disease 2019 (COVID-19). Can J Ophthalmol 2020;55:e125–e129.
39. Mendez Mangana C, Barraquer Kargacin A, Barraquer RI. Episcleritis as an ocular manifestation in a patient with COVID-19. Acta Ophthalmol 2020;98:e1056–e1057.
40. Bettach E, Zadok D, Weill Y, Brosh K, Hanhart J. Bilateral anterior uveitis as a part of a multisystem inflammatory syndrome secondary to COVID-19 infection. J Med Virol 2020;93:139–140.
41. Doherty M. Ocular manifestations of feline infectious peritonitis. Amer Vet Med Ass J 1971;159:417–424.
42. Seah I, Agrawal R. Can the coronavirus disease 2019 (COVID-19) affect the eyes? A review of coronaviruses and ocular implications in humans and animals. Ocul Immunol Inflamm 2020;28:391–395.
43. Amano S, Oshika T, Kaji Y, Numaga J, Matsubara M, Araie M. Herpes simplex virus in the trabeculum of an eye with corneal endotheliitis. Am J Ophthalmol 1999;127:721–722.
44. Carmichael A. Cytomegalovirus and the eye. Eye 2012;26:237–240.
45. Choi JA, Kim KS, Jung Y, Park HYL, Park CK. Cytomegalovirus as a cause of hypertensive anterior uveitis in immunocompetent patients. J Ophthalmic Inflamm Infect 2016;6:32.
46. Chee S, Jap A. Cytomegalovirus anterior uveitis: outcome of treatment. Br J Ophthalmol 2010;94:1648–1652.
47. Accorinti M, Gilardi M, Pirraglia M, Amorelli G, Nardella C, Abicca I, et al. Cytomegalovirus anterior uveitis: long-term follow-up of immunocompetent patients. Graefes Arch Clin Exp Ophthalmol 2014;252:1817–1824.
48. Varkey JB, Shantha JG, Crozier I, Kraft CS, Lyon GM, Mehta AK, et al. Persistence of Ebola virus in ocular fluid during convalescence. N Engl J Med 2015;372:2423–2427.
49. Dinkin M, Gao V, Kahan J, Bobker S, Simonetto M, Wechsler P, et al. COVID-19 presenting with ophthalmoparesis from cranial nerve palsy. Neurology 2020;95:221–223.
50. Gala F. Magnetic resonance imaging of optic nerve. Indian J Radiol Imaging 2015;25:421.
51. Zhao H, Shen D, Zhou H, Liu J, Chen S. Guillain-Barré syndrome associated with SARS-CoV-2 infection: causality or coincidence? Lancet Oncol 2020;19:383–384.
52. Falcone MM, Rong AJ, Salazar H, Redick DW, Falcone S, Cavuoto KM. Acute abducens nerve palsy in a patient with the novel coronavirus disease (COVID-19). J AAPOS 2020;24:216–217.
53. de Oliveira RDMC, Santos DH, Olivetti BC, Takahashi JT. Bilateral trochlear nerve palsy due to cerebral vasculitis related to covid-19 infection. Arquivos de Neuro- Psiquiatria 2020;78:385–386.
54. Chwalisz BK, Dinkin MJ. Disease of the year: COVID-19 and its neuro-ophthalmic complications. J Neuroophthalmol 2020;40:283–284.
55. Casagrande M, Fitzek A, Puschel K, Aleshcheva G, Schultheiss HP, Berneking L, et al. Detection of SARSCoV- 2 in human retinal biopsies of deceased COVID-19 patients. Ocul Immunol Inflamm 2020;28:721–725.
56. Marinho PM, Marcos AAA, Romano AC, Nascimento H, Belfort R Jr. Retinal findings in patients with COVID-19. Lancet 2020;395:1610.
57. Seah I, Agrawal R. Can the coronavirus disease 2019 (COVID-19) affect the eyes? A review of coronaviruses and ocular implications in humans and animals. Ocul Immunol Inflamm 2020;28:391–395.
58. Wang Y, Detrick B, Yu Z-X, Zhang J, Chesky L, Hooks JJ. The role of apoptosis within the retina of coronavirus infected mice. Invest Ophthalmol Vis Sci 2000;41:3011–3018.
59. Quintana-Castanedo L, Feito-Rodríguez M, Fernández- Alcalde C, Granados-Fernández M, Montero-Vega D, Mayor-Ibarguren A, et al. Concurrent chilblains and retinal vasculitis in a child with COVID-19. J Eur Acad Dermatol Venereol 2020;34:e764–e766.
60. Burgos-Blasco B, Güemes-Villahoz N, Donate-Lopez J, Vidal-Villegas B, García-Feijóo J. Optic nerve analysis in COVID-19 patients. J Med Virol 2020;93:190–191.
61. Insausti-García A, Reche-Sainz JA, Ruiz-Arranz C, López Vázquez Á, Ferro-Osuna M. Papillophlebitis in a COVID- 19 patient: inflammation and hypercoagulable state. Eur J Ophthalmol 2020:1120672120947591.
62. Raony Í, Saggioro de Figueiredo C. Retinal outcomes of COVID-19: possible role of CD147 and cytokine storm in infected patients with diabetes mellitus. Diabetes Res Clin Pract 2020;165:108280.
63. Rohl A, Kalhorn A, Singh J, Mandava N. Decreased retinal detachments during a COVID-19 lockdown period in Colorado. Acta Ophthalmol 2020. Available from: https: //doi.org/10.1111/aos.14570
64. Awad M, Poostchi A, Orr G, Kumudhan D, Zaman A, Wilde C. Delayed presentation and increased prevalence of proliferative vitreoretinopathy for primary rhegmatogenous retinal detachments presenting during the COVID-19 pandemic lockdown. Eye 2020:1–2.
65. Poyser A, Deol SS, Osman L, Sivagnanasithiyar T, Kuht HJ, Manrique R, et al. Impact of COVID-19 pandemic and lockdown on retinal detachments. Eye 2020:1–2.
66. Netland J, Meyerholz DK, Moore S, Cassell M, Perlman S. Severe acute respiratory syndrome coronavirus infection causes neuronal death in the absence of encephalitis in mice transgenic for human ACE2. J Virol 2008;82:7264– 7275.
67. Wrapp D, Wang N, Corbett KS, Goldsmith JA, Hsieh C-L, Abiona O, et al. Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science 2020;367:1260– 1263.
68. Toscano G, Palmerini F, Ravaglia S, Ruiz L, Invernizzi P, Cuzzoni MG, et al. Guillain–Barré syndrome associated with SARS-CoV-2. N Engl J Med 2020;382:2574–2576.
69. Nordvig AS, Rimmer KT, Willey JZ, Thakur KT, Boehme AK, Vargas WS, et al. Potential neurological manifestations of COVID-19. Neurol Clin Pract 2020. Available from: https: //doi.org/10.1212/CPJ.0000000000000897
70. Gutiérrez-Ortiz C, Méndez A, Rodrigo-Rey S, San Pedro- Murillo E, Bermejo-Guerrero L, Gordo-Mañas R, et al. Miller Fisher Syndrome and polyneuritis cranialis in COVID-19. Neurology 2020;95:e601–e605.
71. Lantos JE, Strauss SB, Lin E. COVID-19-associated Miller Fisher Syndrome: MRI findings. AJNR 2020;41:1184–1186.
72. Conde G, Pájaro LDQ, Marzola IDQ, Villegas YR, Salazar LRM. Neurotropism of SARS-CoV 2: Mechanisms and manifestations. J Neurol Sci 2020;412:116824.
73. Kaya Y, Kara S, Akinci C, Kocaman AS. Transient cortical blindness in COVID-19 pneumonia; a PRES-like syndrome: Case report. J Neurol Sci 2020;413:116858.
74. Doo FX, Kassim G, Lefton DR, Patterson S, Pham H, Belani P. Rare presentations of COVID-19: PRESlike leukoencephalopathy and carotid thrombosis. Clin Imaging 2020.
75. Agarwal S, Jain R, Dogra S, Krieger P, Lewis A, Nguyen V, et al. Cerebral microbleeds and leukoencephalopathy in critically Ill patients with COVID-19. Stroke 2020;51:2649–2655.
76. Cariddi LP, Damavandi PT, Carimati F, Banfi P, Clemenzi A, Marelli M, et al. Reversible Encephalopathy Syndrome (PRES) in a COVID-19 patient. J Neurol 2020;267:3157–3160.
77. Parauda SC, Gao V, Gewirtz AN, Parikh NS, Merkler AE, Lantos J, et al. Posterior reversible encephalopathy syndrome in patients with COVID-19. J Neurol Sci 2020;416:117019.
78. Zhou S, Jones-Lopez EC, Soneji DJ, Azevedo CJ, Patel VR. Myelin Oligodendrocyte glycoprotein antibody-associated optic neuritis and myelitis in COVID-19. J Neuroophthalmol 2020;40:398–402.
79. Dumitrascu OM, Volod O, Bose S, Wang Y, Biousse V, Lyden PD. Acute ophthalmic artery occlusion in a COVID-19 patient on apixaban. J Stroke Cerebrovasc Dis 2020;29:104982.
80. Acharya S, Diamond M, Anwar S, Glaser A, Tyagi P. Unique case of central retinal artery occlusion secondary to COVID-19 disease. ID Cases 2020;21:e00867.
81. Giannis D, Ziogas IA, Gianni P. Coagulation disorders in coronavirus infected patients: COVID-19, SARS-CoV- 1, MERS-CoV and lessons from the past. J Clin Virol 2020;127:104362.
82. Tang N, Bai H, Chen X, Gong J, Li D, Sun Z. Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy. J Thromb Haemost 2020;18:1094–1099.
83. Han H, Yang L, Liu R, Liu F, Wu K-l, Li J, et al. Prominent changes in blood coagulation of patients with SARS-CoV- 2 infection. Clin Chem Lab Med 2020;1(ahead-of-print).
84. Barnes GD, Burnett A, Allen A, Blumenstein M, Clark NP, Cuker A, et al. Thromboembolism and anticoagulant therapy during the COVID-19 pandemic: interim clinical guidance from the anticoagulation forum. J Thromb Thrombolysis 2020;50:72–81.
85. Barrett CD, Moore HB, Yaffe MB, Moore EE. ISTH interim guidance on recognition and management of coagulopathy in COVID-19: a comment. J Thromb Haemost 2020;18:2060–2063.
86. Löffler KU, Reinhold A, Herwig-Carl MC, Tzankov A, Holz FG, Scholl HPN, et al. Ocular post-mortem findings in patients having died from COVID-19. Ophthalmologe 2020;117:648–651.
87. Bayyoud T, Iftner A, Iftner T, Bartz-Schmidt KU, Rohrbach JM, Ueffing M, et al. Absence of Severe Acute Respiratory Syndrome-Coronavirus-2 RNA in human corneal tissues. Cornea 2020;40:342–347.
88. Bayyoud T, Iftner A, Iftner T, Bartz-Schmidt KU, Ueffing M, Schindler M, et al. Absence of Severe Acute Respiratory Syndrome-Coronavirus-2 RNA in ocular tissues. Am J Ophthalmol Case Rep 2020;19:100805.
89. Fuest M, Boor P, Knuechel R, Walter P, Salla S. Postmortem conjunctival and nasopharyngeal swabs in SARS-CoV-2 infected and uninfected patients. Acta Ophthalmol 2020.
90. Luhtala S, Vaajanen A, Oksala O, Valjakka J, Vapaatalo H. Activities of angiotensin-converting enzymes ACE1 and ACE2 and inhibition by bioactive peptides in porcine ocular tissues. J Ocul Pharmacol Ther 2009;25:23–28.
91. Tikellis C, Johnston C, Forbes JM, Burns WC, Thomas MC, Lew RA, et al. Identification of angiotensin converting enzyme 2 in the rodent retina. Curr Eye Res 2004;29:419–427.
2. Douglas KAA, Douglas VP, Moschos MM. Ocular manifestations of COVID-19 (SARS-CoV-2): a critical review of current literature. In vivo 2020;34:1619–1628.
3. Rothan HA, Byrareddy SN. The epidemiology and pathogenesis of coronavirus disease (COVID-19) outbreak. J Autoimmun 2020:102433.
4. Santarpia JL, Rivera DN, Herrera VL, Morwitzer MJ, Creager HM, Santarpia GW, et al. Aerosol and surface contamination of SARS-CoV-2 observed in quarantine and isolation care. Sci Rep 2020;10:12732.
5. Xia J, Tong J, Liu M, Shen Y, Guo D. Evaluation of coronavirus in tears and conjunctival secretions of patients with SARS-CoV-2 infection. J medical virology 2020;92(??):589-594.
6. Lai THT, Tang EWH, Chau SKY, Fung KSC, Li KKW. Stepping up infection control measures in ophthalmology during the novel coronavirus outbreak: an experience from Hong Kong. Graefes Arch Clin Exp Ophthalmol 2020;258:1049–1055.
7. Cadet J. Harmless effects of sterilizing 222-nm far-UV radiation on mouse skin and eye tissues. Photochem Photobiol 2020;96:949–950.
8. Aytoğan H, Ayintap E, Yilmaz NÖ. Detection of coronavirus disease 2019 viral material on environmental surfaces of an ophthalmology examination room. JAMA Ophthalmol 2020;138:990–993.
9. Wu P, Duan F, Luo C, Liu Q, Qu X, Liang L, et al. Characteristics of ocular findings of patients with coronavirus disease 2019 (COVID-19) in Hubei Province, China. JAMA Ophthalmol 2020;138:575.
10. Wan Y, Shang J, Graham R, Baric RS, Li F. Receptor recognition by the novel coronavirus from Wuhan: an analysis based on decade-long structural studies of SARS coronavirus. J Virol 2020;94:e00127–e00200.
11. Li W, Moore MJ, Vasilieva N, Sui J, Wong SK, Berne MA, et al. Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature 2003;426:450– 454.
12. Letko M, Marzi A, Munster V. Functional assessment of cell entry and receptor usage for SARS-CoV-2 and other lineage B betacoronaviruses. Nat Microbiol 2020;5:562–569.
13. Zou X, Chen K, Zou J, Han P, Hao J, Han Z. Single-cell RNAseq data analysis on the receptor ACE2 expression reveals the potential risk of different human organs vulnerable to 2019-nCoV infection. Front Med 2020;14:185–192.
14. Zhou L, Xu Z, Castiglione GM, Soiberman US, Eberhart CG, Duh EJ. ACE2 and TMPRSS2 are expressed on the human ocular surface, suggesting susceptibility to SARS-CoV-2 infection. Ocul Surf 2020;18:537–544.
15. Senanayake Pd, Drazba J, Shadrach K, Milsted A, Rungger- Brandle E, Nishiyama K, et al. Angiotensin II and its receptor subtypes in the human retina. Invest Ophthalmol Vis Sci 2007;48:3301–3311.
16. Holappa M, Valjakka J, Vaajanen A. Angiotensin (1- 7) and ACE2,“the hot spots” of renin-angiotensin system, detected in the human aqueous humor. Open J Ophthalmol 2015;9:28.
17. Collin J, Queen R, Zerti D, Dorgau B, Georgiou M, Djidrovski I, et al. Co-expression of SARS-CoV-2 entry genes in the superficial adult human conjunctival, limbal and corneal epithelium suggests an additional route of entry via the ocular surface. Ocul Surf 2020;19:190–200.
18. Critical appraisal tools | Joanna Briggs Institute [Internet]. Joannabriggs.org; 2020 [cited 2020 December 4]. Available from: https://joannabriggs.org/critical-appraisaltools
19. Xu M, Zhang H, Niu X. COVID-19 patient firstly visiting eye doctor due to tarsadenitis and subconjunctival hemorrhage: a case report. Zhonghua Shiyan Yanke Zazhi/Chinese Journal of Experimental Ophthalmology 2020;38:374–376.
20. Megarbane B, Tadayoni R. Cluster of chalazia in nurses using eye protection while caring for critically ill patients with COVID-19 in intensive care. Occup Environ Med 2020;77:584–585.
21. McCulley JP, Dougherty JM, Deneau DG. Classification of chronic blepharitis. Ophthalmology 1982;89:1173–1180.
22. McCulley JP, Dougherty J. Bacterial aspects of chronic blepharitis. Trans Ophthalmol Soc UK 1986;105:314–318.
23. Terpos E, Ntanasis-Stathopoulos I, Elalamy I, Kastritis E, Sergentanis TN, Politou M, et al. Hematological findings and complications of COVID-19. Am J Hematol 2020;95:834–847.
24. Knop E, Knop N, Millar T, Obata H, Sullivan DA. The international workshop on meibomian gland dysfunction: report of the subcommittee on anatomy, physiology, and pathophysiology of the meibomian gland. Invest Ophthalmol Vis Sci 2011;52:1938–1978.
25. Bostanci Ceran B, Ozates S. Ocular manifestations of coronavirus disease 2019. Graefes Arch Clin Exp Ophthalmol 2020;258:1959–1963.
26. WHO. Report of the WHO–China joint mission on coronavirus disease 2019 (COVID-19). WHO; 2020.
27. Sarma P, Kaur H, Kaur H, Bhattacharyya J, Prajapat M, Shekhar N, et al. Ocular manifestations and tear or conjunctival swab PCR positivity for 2019-nCoV in patients with COVID-19: a systematic review and meta-analysis. SSRN 2020. Available from: https://ssrn.com/abstract= 3566161
28. Loffredo L, Pacella F, Pacella E, Tiscione G, Oliva A, Violi F. Conjunctivitis and COVID-19: a meta-analysis. J Med Virol 2020;92:1413–1414.
29. Chen L, Deng C, Chen X, Zhang X, Chen B, Yu H, et al. Ocular manifestations and clinical characteristics of 535 cases of COVID-19 in Wuhan, China: a cross-sectional study. Acta Ophthalmol 2020;98:e951–e959.
30. Navel V, Chiambaretta F, Dutheil F. Haemorrhagic conjunctivitis with pseudomembranous related to SARSCoV- 2. Am J Ophthalmol Case Rep 2020:100735.
31. Chen L, Liu M, Zhang Z, Qiao K, Huang T, Chen M, et al. Ocular manifestations of a hospitalised patient with confirmed 2019 novel coronavirus disease. Br J Ophthalmol 2020;104:748–751.
32. Colavita F, Lapa D, Carletti F, Lalle E, Bordi L, Marsella P, et al. SARS-CoV-2 isolation from ocular secretions of a patient with COVID-19 in Italy with prolonged viral RNA detection. Ann Int Med 2020;173:242–243.
33. Aiello F, Afflitto GG, Mancino R, Li J-PO, Cesareo M, Giannini C, et al. Coronavirus disease 2019 (SARS-CoV- 2) and colonization of ocular tissues and secretions: a systematic review. Eye 2020;34:1206–1211.
34. Corman VM, Landt O, Kaiser M, Molenkamp R, Meijer A, Chu DK, et al. Detection of 2019 novel coronavirus (2019-nCoV) by real-time RT-PCR. Eurosurveillance 2020;25:2000045.
35. Lin C, Ye R, Xia Y. A meta-analysis to evaluate the effectiveness of real-time PCR for diagnosing novel coronavirus infections. Genet Mol Res 2015;14:15634– 15641.
36. Raboud J, Shigayeva A, McGeer A, Bontovics E, Chapman M, Gravel D, et al. Risk factors for SARS transmission from patients requiring intubation: a multicentre investigation in Toronto, Canada. PLoS ONE 2010;5:e10717.
37. Qing H, Li Z, Yang Z, Shi M, Huang Z, Song J, et al. The possibility of COVID-19 transmission from eye to nose. Acta Ophthalmol 2020;98:e388.
38. Cheema M, Aghazadeh H, Nazarali S, Ting A, Hodges J, McFarlane A, et al. Keratoconjunctivitis as the initial medical presentation of the novel coronavirus disease 2019 (COVID-19). Can J Ophthalmol 2020;55:e125–e129.
39. Mendez Mangana C, Barraquer Kargacin A, Barraquer RI. Episcleritis as an ocular manifestation in a patient with COVID-19. Acta Ophthalmol 2020;98:e1056–e1057.
40. Bettach E, Zadok D, Weill Y, Brosh K, Hanhart J. Bilateral anterior uveitis as a part of a multisystem inflammatory syndrome secondary to COVID-19 infection. J Med Virol 2020;93:139–140.
41. Doherty M. Ocular manifestations of feline infectious peritonitis. Amer Vet Med Ass J 1971;159:417–424.
42. Seah I, Agrawal R. Can the coronavirus disease 2019 (COVID-19) affect the eyes? A review of coronaviruses and ocular implications in humans and animals. Ocul Immunol Inflamm 2020;28:391–395.
43. Amano S, Oshika T, Kaji Y, Numaga J, Matsubara M, Araie M. Herpes simplex virus in the trabeculum of an eye with corneal endotheliitis. Am J Ophthalmol 1999;127:721–722.
44. Carmichael A. Cytomegalovirus and the eye. Eye 2012;26:237–240.
45. Choi JA, Kim KS, Jung Y, Park HYL, Park CK. Cytomegalovirus as a cause of hypertensive anterior uveitis in immunocompetent patients. J Ophthalmic Inflamm Infect 2016;6:32.
46. Chee S, Jap A. Cytomegalovirus anterior uveitis: outcome of treatment. Br J Ophthalmol 2010;94:1648–1652.
47. Accorinti M, Gilardi M, Pirraglia M, Amorelli G, Nardella C, Abicca I, et al. Cytomegalovirus anterior uveitis: long-term follow-up of immunocompetent patients. Graefes Arch Clin Exp Ophthalmol 2014;252:1817–1824.
48. Varkey JB, Shantha JG, Crozier I, Kraft CS, Lyon GM, Mehta AK, et al. Persistence of Ebola virus in ocular fluid during convalescence. N Engl J Med 2015;372:2423–2427.
49. Dinkin M, Gao V, Kahan J, Bobker S, Simonetto M, Wechsler P, et al. COVID-19 presenting with ophthalmoparesis from cranial nerve palsy. Neurology 2020;95:221–223.
50. Gala F. Magnetic resonance imaging of optic nerve. Indian J Radiol Imaging 2015;25:421.
51. Zhao H, Shen D, Zhou H, Liu J, Chen S. Guillain-Barré syndrome associated with SARS-CoV-2 infection: causality or coincidence? Lancet Oncol 2020;19:383–384.
52. Falcone MM, Rong AJ, Salazar H, Redick DW, Falcone S, Cavuoto KM. Acute abducens nerve palsy in a patient with the novel coronavirus disease (COVID-19). J AAPOS 2020;24:216–217.
53. de Oliveira RDMC, Santos DH, Olivetti BC, Takahashi JT. Bilateral trochlear nerve palsy due to cerebral vasculitis related to covid-19 infection. Arquivos de Neuro- Psiquiatria 2020;78:385–386.
54. Chwalisz BK, Dinkin MJ. Disease of the year: COVID-19 and its neuro-ophthalmic complications. J Neuroophthalmol 2020;40:283–284.
55. Casagrande M, Fitzek A, Puschel K, Aleshcheva G, Schultheiss HP, Berneking L, et al. Detection of SARSCoV- 2 in human retinal biopsies of deceased COVID-19 patients. Ocul Immunol Inflamm 2020;28:721–725.
56. Marinho PM, Marcos AAA, Romano AC, Nascimento H, Belfort R Jr. Retinal findings in patients with COVID-19. Lancet 2020;395:1610.
57. Seah I, Agrawal R. Can the coronavirus disease 2019 (COVID-19) affect the eyes? A review of coronaviruses and ocular implications in humans and animals. Ocul Immunol Inflamm 2020;28:391–395.
58. Wang Y, Detrick B, Yu Z-X, Zhang J, Chesky L, Hooks JJ. The role of apoptosis within the retina of coronavirus infected mice. Invest Ophthalmol Vis Sci 2000;41:3011–3018.
59. Quintana-Castanedo L, Feito-Rodríguez M, Fernández- Alcalde C, Granados-Fernández M, Montero-Vega D, Mayor-Ibarguren A, et al. Concurrent chilblains and retinal vasculitis in a child with COVID-19. J Eur Acad Dermatol Venereol 2020;34:e764–e766.
60. Burgos-Blasco B, Güemes-Villahoz N, Donate-Lopez J, Vidal-Villegas B, García-Feijóo J. Optic nerve analysis in COVID-19 patients. J Med Virol 2020;93:190–191.
61. Insausti-García A, Reche-Sainz JA, Ruiz-Arranz C, López Vázquez Á, Ferro-Osuna M. Papillophlebitis in a COVID- 19 patient: inflammation and hypercoagulable state. Eur J Ophthalmol 2020:1120672120947591.
62. Raony Í, Saggioro de Figueiredo C. Retinal outcomes of COVID-19: possible role of CD147 and cytokine storm in infected patients with diabetes mellitus. Diabetes Res Clin Pract 2020;165:108280.
63. Rohl A, Kalhorn A, Singh J, Mandava N. Decreased retinal detachments during a COVID-19 lockdown period in Colorado. Acta Ophthalmol 2020. Available from: https: //doi.org/10.1111/aos.14570
64. Awad M, Poostchi A, Orr G, Kumudhan D, Zaman A, Wilde C. Delayed presentation and increased prevalence of proliferative vitreoretinopathy for primary rhegmatogenous retinal detachments presenting during the COVID-19 pandemic lockdown. Eye 2020:1–2.
65. Poyser A, Deol SS, Osman L, Sivagnanasithiyar T, Kuht HJ, Manrique R, et al. Impact of COVID-19 pandemic and lockdown on retinal detachments. Eye 2020:1–2.
66. Netland J, Meyerholz DK, Moore S, Cassell M, Perlman S. Severe acute respiratory syndrome coronavirus infection causes neuronal death in the absence of encephalitis in mice transgenic for human ACE2. J Virol 2008;82:7264– 7275.
67. Wrapp D, Wang N, Corbett KS, Goldsmith JA, Hsieh C-L, Abiona O, et al. Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science 2020;367:1260– 1263.
68. Toscano G, Palmerini F, Ravaglia S, Ruiz L, Invernizzi P, Cuzzoni MG, et al. Guillain–Barré syndrome associated with SARS-CoV-2. N Engl J Med 2020;382:2574–2576.
69. Nordvig AS, Rimmer KT, Willey JZ, Thakur KT, Boehme AK, Vargas WS, et al. Potential neurological manifestations of COVID-19. Neurol Clin Pract 2020. Available from: https: //doi.org/10.1212/CPJ.0000000000000897
70. Gutiérrez-Ortiz C, Méndez A, Rodrigo-Rey S, San Pedro- Murillo E, Bermejo-Guerrero L, Gordo-Mañas R, et al. Miller Fisher Syndrome and polyneuritis cranialis in COVID-19. Neurology 2020;95:e601–e605.
71. Lantos JE, Strauss SB, Lin E. COVID-19-associated Miller Fisher Syndrome: MRI findings. AJNR 2020;41:1184–1186.
72. Conde G, Pájaro LDQ, Marzola IDQ, Villegas YR, Salazar LRM. Neurotropism of SARS-CoV 2: Mechanisms and manifestations. J Neurol Sci 2020;412:116824.
73. Kaya Y, Kara S, Akinci C, Kocaman AS. Transient cortical blindness in COVID-19 pneumonia; a PRES-like syndrome: Case report. J Neurol Sci 2020;413:116858.
74. Doo FX, Kassim G, Lefton DR, Patterson S, Pham H, Belani P. Rare presentations of COVID-19: PRESlike leukoencephalopathy and carotid thrombosis. Clin Imaging 2020.
75. Agarwal S, Jain R, Dogra S, Krieger P, Lewis A, Nguyen V, et al. Cerebral microbleeds and leukoencephalopathy in critically Ill patients with COVID-19. Stroke 2020;51:2649–2655.
76. Cariddi LP, Damavandi PT, Carimati F, Banfi P, Clemenzi A, Marelli M, et al. Reversible Encephalopathy Syndrome (PRES) in a COVID-19 patient. J Neurol 2020;267:3157–3160.
77. Parauda SC, Gao V, Gewirtz AN, Parikh NS, Merkler AE, Lantos J, et al. Posterior reversible encephalopathy syndrome in patients with COVID-19. J Neurol Sci 2020;416:117019.
78. Zhou S, Jones-Lopez EC, Soneji DJ, Azevedo CJ, Patel VR. Myelin Oligodendrocyte glycoprotein antibody-associated optic neuritis and myelitis in COVID-19. J Neuroophthalmol 2020;40:398–402.
79. Dumitrascu OM, Volod O, Bose S, Wang Y, Biousse V, Lyden PD. Acute ophthalmic artery occlusion in a COVID-19 patient on apixaban. J Stroke Cerebrovasc Dis 2020;29:104982.
80. Acharya S, Diamond M, Anwar S, Glaser A, Tyagi P. Unique case of central retinal artery occlusion secondary to COVID-19 disease. ID Cases 2020;21:e00867.
81. Giannis D, Ziogas IA, Gianni P. Coagulation disorders in coronavirus infected patients: COVID-19, SARS-CoV- 1, MERS-CoV and lessons from the past. J Clin Virol 2020;127:104362.
82. Tang N, Bai H, Chen X, Gong J, Li D, Sun Z. Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy. J Thromb Haemost 2020;18:1094–1099.
83. Han H, Yang L, Liu R, Liu F, Wu K-l, Li J, et al. Prominent changes in blood coagulation of patients with SARS-CoV- 2 infection. Clin Chem Lab Med 2020;1(ahead-of-print).
84. Barnes GD, Burnett A, Allen A, Blumenstein M, Clark NP, Cuker A, et al. Thromboembolism and anticoagulant therapy during the COVID-19 pandemic: interim clinical guidance from the anticoagulation forum. J Thromb Thrombolysis 2020;50:72–81.
85. Barrett CD, Moore HB, Yaffe MB, Moore EE. ISTH interim guidance on recognition and management of coagulopathy in COVID-19: a comment. J Thromb Haemost 2020;18:2060–2063.
86. Löffler KU, Reinhold A, Herwig-Carl MC, Tzankov A, Holz FG, Scholl HPN, et al. Ocular post-mortem findings in patients having died from COVID-19. Ophthalmologe 2020;117:648–651.
87. Bayyoud T, Iftner A, Iftner T, Bartz-Schmidt KU, Rohrbach JM, Ueffing M, et al. Absence of Severe Acute Respiratory Syndrome-Coronavirus-2 RNA in human corneal tissues. Cornea 2020;40:342–347.
88. Bayyoud T, Iftner A, Iftner T, Bartz-Schmidt KU, Ueffing M, Schindler M, et al. Absence of Severe Acute Respiratory Syndrome-Coronavirus-2 RNA in ocular tissues. Am J Ophthalmol Case Rep 2020;19:100805.
89. Fuest M, Boor P, Knuechel R, Walter P, Salla S. Postmortem conjunctival and nasopharyngeal swabs in SARS-CoV-2 infected and uninfected patients. Acta Ophthalmol 2020.
90. Luhtala S, Vaajanen A, Oksala O, Valjakka J, Vapaatalo H. Activities of angiotensin-converting enzymes ACE1 and ACE2 and inhibition by bioactive peptides in porcine ocular tissues. J Ocul Pharmacol Ther 2009;25:23–28.
91. Tikellis C, Johnston C, Forbes JM, Burns WC, Thomas MC, Lew RA, et al. Identification of angiotensin converting enzyme 2 in the rodent retina. Curr Eye Res 2004;29:419–427.