Ocular Manifestations of COVID-19: A Systematic Review and Meta-Analysis
Several studies have reported the characteristics of Coronavirus disease 2019 (COVID-19), yet there is a gap in our understanding of the ocular manifestations of COVID-19. In this systematic review and meta-analysis, we investigated the prevalence of ocular manifestations in COVID-19 patients. We searched Pubmed, Embase, Scopus, Web of Science, and medRxiv from December 1, 2019 to August 11, 2020. Two independent reviewers screened the articles, abstracted the data, and assessed the quality of included studies in duplicate. Thirty-eight studies were eligible after screening of 895 unique articles, with a total of 8,219 COVID-19 patients (55.3% female; n = 3,486 out of 6,308 patients). Using data extracted from cross-sectional studies, we performed randomeffects meta-analyses to estimate the pooled prevalence of ocular symptoms along with 95% confidence interval (CI). The prevalence of ocular manifestations was estimated to be 11.03% (95% CI: 5.71–17.72). In the studies that reported the details of observed ocular symptoms, the most common ocular manifestations were dry eye or foreign body sensation (n = 138, 16%), redness (n = 114, 13.3%), tearing (n = 111, 12.8%), itching (n = 109, 12.6%), eye pain (n = 83, 9.6%) and discharge (n = 76, 8.8%). Moreover, conjunctivitis had the highest rate among reported ocular diseases in COVID-19 patients (79 out of 89, 88.8%). The results suggest that approximately one out of ten COVID-19 patients show at least one ocular symptom. Attention to ocular manifestations, especially conjunctivitis, can increase the sensitivity of COVID-19 detection among patients.
Conjunctivitis, COVID-19, Meta-analysis, Ocular Manifestations, Systematic Review
1. Veritti D, Sarao V, Bandello F, Lanzetta P. Infection control measures in ophthalmology during the COVID-19 outbreak: a narrative review from an early experience in Italy. Eur J Ophthalmol 2020;30:621–628.
2. Khalili M, Karamouzian M, Nasiri N, Javadi S, Mirzazadeh A, Sharifi H. Epidemiological characteristics of COVID-19: a systematic review and meta-analysis. Epidemiol Infect 2020;148:e130.
3. Worldometer. COVID-19 coronavirus pandemic [Internet]. Worldometer; 2020. Available from: https://www.worldometers.info/coronavirus/
4. Jin X, Lian JS, Hu JH, Gao J, Zheng L, Zhang YM, et al. Epidemiological, clinical and virological characteristics of 74 cases of coronavirus-infected disease 2019 (COVID-19) with gastrointestinal symptoms. Gut 2020;69:1002–1009.
5. Han C, Duan C, Zhang S, Spiegel B, Shi H, Wang W, et al. Digestive symptoms in COVID-19 patients with mild disease severity: clinical presentation, stool viral RNA testing, and outcomes. Am J Gastroenterol 2020;115:916– 923.
6. Renu K, Prasanna PL, Valsala Gopalakrishnan A. Coronaviruses pathogenesis, comorbidities and multiorgan damage – a review. Life Sci 2020;255:117839.
7. 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.
8. Ho D, Low R, Tong L, Gupta V, Veeraraghavan A, Agrawal R. COVID-19 and the ocular surface: a review of transmission and manifestations. Ocul Immunol Inflamm 2020;28:726–734.
9. Mahayana IT, Angsana NC, Kamila A, Fatiha NN, Sunjaya DZ, Andajana W, et al. Literature review of conjunctivitis, conjunctival swab and chloroquine effect in the eyes: a current updates on COVID-19 and ophthalmology. J Med Sci 2020;52:21–28.
10. Moher D, Liberati A, Tetzlaff J, Altman DG, Group P. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLOS Med 2009;6:e1000097.
11. Joanna Briggs Institute. The Joanna Briggs Institute Critical Appraisal tools for use in JBI systematic reviews checklist for prevalence studies [Internet]. Joanna Briggs Institute; 2017. Available from: http://joannabriggs.org/research/critical-appraisaltools. HTML
12. Zhang X, Chen X, Chen L, Deng C, Zou X, Liu W, et al. The evidence of SARS-CoV-2 infection on ocular surface. Ocul Surf 2020;18:360–362.
13. 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 Med Virol 2020;92:589– 594.
14. 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;138:575–578.
15. Valente P, Iarossi G, Federici M, Petroni S, Palma P, Cotugno N, et al. Ocular manifestations and viral shedding in tears of pediatric patients with coronavirus disease 2019: a preliminary report. J AAPOS 2020:S1091– 8531(20)30115-4.
16. Tostmann A, Bradley J, Bousema T, Yiek WK, Holwerda M, Bleeker-Rovers C, et al. Strong associations and moderate predictive value of early symptoms for SARS-CoV-2 test positivity among healthcare workers, the Netherlands, March 2020. Euro Surveill 2020;25:2000508.
17. Kumar K, Prakash AA, Gangasagara SB, Rathod SBL, Ravi K, Rangaiah A, et al. Presence of viral RNA of SARS-CoV- 2 in conjunctival swab specimens of COVID-19 patients. Indian J Ophthalmol 2020;68:1015–1017.
18. Karimi S, Arabi A, Shahraki T, Safi S. Detection of severe acute respiratory syndrome Coronavirus-2 in the tears of patients with Coronavirus disease 2019. Eye 2020;34:1220–1223.
19. Hong N, Yu W, Xia J, Shen Y, Yap M, Han W. Evaluation of ocular symptoms and tropism of SARS-CoV- 2 in patients confirmed with COVID-19. Acta Ophthalmol 2020;26:10.1111/aos.14445.
20. Güemes-Villahoz N, Burgos-Blasco B, Arribi-Vilela A, Arriola-Villalobos P, Rico-Luna CM, Cuiña-Sardiña R, et al. Detecting SARS-CoV-2 RNA in conjunctival secretions: is it a valuable diagnostic method of COVID-19? J Med Virol 2020:10.1002/jmv.26219.
21. 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;10.1111/aos.14472.
22. Bostanci Ceran B, Ozates S. Ocular manifestations of coronavirus disease 2019. Graefes Arch Clin Exp Ophthalmol 2020:258:1959–1963.
23. Abrishami M, Tohidinezhad F, Daneshvar R, Omidtabrizi A, Amini M, Sedaghat A, et al. Ocular manifestations of hospitalized patients with COVID-19 in Northeast of Iran. Ocul Immunol Inflamm 2020:28:739–744.
24. Lapostolle F, Schneider E, Vianu I, Dollet G, Roche B, Berdah J, et al. Clinical features of 1487 COVID-19 patients with outpatient management in the Greater Paris: the COVID-call study. Intern Emerg Med 2020:15:813–817.
25. Ye Y, Song Y, Yan M, Hu C, Chen X, Yu J, et al. Novel coronavirus pneumonia combined with conjunctivitis: three cases report. Zhonghua Shiyan Yanke Zazhi/Chinese J Exp Ophthalmol 2020;38:242–244.
26. Seah IYJ, Anderson DE, Kang AEZ, Wang L, Rao P, Young BE, et al. Assessing viral shedding and infectivity of tears in Coronavirus Disease 2019 (COVID-19) patients. Ophthalmology 2020;127:977–979.
27. Deng C, Yang Y, Chen H, Chen W, Chen Z, Ma K, et al. Ocular dectection of SARS-CoV-2 in 114 cases of COVID-19 pneumonia in Wuhan, China: an observational study [Internet]. SSRN; 2020. Available from: http://www. ssrn.com/abstract=3543587
28. Xu L, Zhang X, Song W, Sun B, Mu J, Wang B, et al. Conjunctival polymerase chain reaction-tests of 2019 novel coronavirus in patients in Shenyang, China [Internet]. SSRN; 2020. Available from: https://www.ssrn. com/abstract=3543592
29. Guan W-j, Ni Z-y, Hu Y, Liang W-h, Ou C-q, He J-x, et al. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med 2020;382:1708–1720.
30. Zhou Y, Duan C, Zeng Y, Tong Y, Nie Y, Yang Y, et al. Ocular findings and proportion with conjunctival SARS-COV-2 in COVID-19 patients. Ophthalmology 2020;127:982–983.
31. Lechien JR, Chiesa-Estomba CM, Place S, Van Laethem Y, Cabaraux P, Mat Q, et al. Clinical and epidemiological characteristics of 1420 European patients with mildto- moderate coronavirus disease 2019. J Intern Med 2020;288:335–344.
32. Pardhan S, Vaughan M, Zhang J, Smith L, Chichger H. Type and frequency of ocular and other known symptoms experienced by people who self diagnosed as suffering from COVID-19 in the UK. medRxiv 2020.
33. Liang L, Wu P. There may be virus in conjunctival secretion of patients with COVID-19. Acta Ophthalmol 2020;98:223.
34. Sindhuja K, Lomi N, Asif MI, Tandon R. Clinical profile and prevalence of conjunctivitis in mild COVID-19 patients in a tertiary care COVID-19 hospital: a retrospective crosssectional study. Indian J Ophthalmol 2020;68:1546–1550.
35. Wu F, Zhou Y, Wang Z, Xie M, Shi Z, Tang Z, et al. Clinical characteristics of COVID-19 infection in chronic obstructive pulmonary disease: a multicenter, retrospective, observational study. J Thorac Dis 2020;12:1811–1823.
36. Huang L, Zhang X, Zhang X, Wei Z, Zhang L, Xu J, et al. Rapid asymptomatic transmission of COVID-19 during the incubation period demonstrating strong infectivity in a cluster of youngsters aged 16-23 years outside Wuhan and characteristics of young patients with COVID-19: a prospective contact-tracing study. J Infect 2020;80:e1– e13.
37. Selvaraj V, Sacchetti D, Finn A, Dapaah-Afriyie K. Acute vision loss in a patient with COVID-19. R I Med J 2020;103:37–38.
38. Scalinci SZ, Trovato Battagliola E. Conjunctivitis can be the only presenting sign and symptom of COVID-19. IDCases 2020;20:e00774.
39. Navel V, Chiambaretta F, Dutheil F. Haemorrhagic conjunctivitis with pseudomembranous related to SARSCoV- 2. Am J Ophthalmol Case Rep 2020;19:100735.
40. Li X, Wang M, Dai J, Wang W, Yang Y, Jin W. Novel coronavirus disease with conjunctivitis and conjunctivitis as first symptom: two cases report. [Zhonghua Shiyan Yanke Zazhi] Chinese J Exp Ophthalmol 2020;38:318–321.
41. Lan QQ, Zeng SM, Liao X, Xu F, Qi H, Li M. [Screening for novel coronavirus related conjunctivitis among the patients with corona virus disease-19]. [Zhonghua yan ke za zhi] Chinese J Ophthalmol 2020;56:E009.
42. Daruich A, Martin D, Bremond-Gignac D. Ocular manifestation as first sign of Coronavirus Disease 2019 (COVID-19): interest of telemedicine during the pandemic context. J Fr Ophtalmol 2020;43:389–391.
43. 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.
44. 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.
45. Chavis A, Bakken H, Ellenby M, Hasan R. Coronavirus Disease-2019 and telehealth: prevention of exposure in a medically complex patient with a mild presentation. J Adolesc Health 2020;67:456–458.
46. Ozturker ZK. Conjunctivitis as sole symptom of COVID- 19: a case report and review of literature [published online ahead of print, 2020, Jul 24]. Eur J Ophthalmol 2020;1120672120946287.
47. Nayak B, Poddar C, Panigrahi MK, Tripathy S, Mishra B. Late manifestation of follicular conjunctivitis in ventilated patient following COVID-19 positive severe pneumonia. Indian J Ophthalmol 2020;68:1675–1677.
48. Guo D, Xia J, Wang Y, Zhang X, Shen Y, Tong JP. Relapsing viral keratoconjunctivitis in COVID-19: a case report. Virol J 2020;17:97.
49. Salducci M, La Torre G. COVID-19 emergency in the cruise’s ship: a case report of conjunctivitis. Clin Ter 2020;171:e189–e91.
50. Lai C-C, Ko W-C, Lee P-I, Jean S-S, Hsueh P-R. Extrarespiratory manifestations of COVID-19. Int J Antimicrob Agents 2020;56:106024.
51. Vabret A, Mourez T, Dina J, van der Hoek L, Gouarin S, Petitjean J, et al. Human coronavirus NL63, France. Emerg Infect Dis 2005;11:1225–1229.
52. Ulhaq ZS, Soraya GV. The prevalence of ophthalmic manifestations in COVID-19 and the diagnostic value of ocular tissue/fluid. Graefes Arch Clin Exp Ophthalmol 2020;258:1351–1352.
53. Abobaker A, Raba AA, Alzwi A. Extrapulmonary and atypical clinical presentations of COVID-19. J Med Virol 2020;10.1002/jmv.26157.
54. Dockery DM, Rowe SG, Murphy MA, Krzystolik MG. The ocular manifestations and transmission of COVID- 19: recommendations for prevention. J Emerg Med 2020;59:137–140.
55. Giannaccare G, Vaccaro S, Mancini A, Scorcia V. Dry eye in the COVID-19 era: how the measures for controlling pandemic might harm ocular surface. Graefes Arch Clin Exp Ophthalmol 2020;258:2567–2568.
56. Patel S, Henderson R, Bradley L, Galloway B, Hunter L. Effect of visual display unit use on blink rate and tear stability. Optom Vis Sci 1991;68:888–892.
57. Marinova E, Dabov D, Zdravkov Y. Ophthalmic complaints in face-mask wearing: prevalence, treatment, and prevention with a potential protective effect against SARSCoV- 2. Biotechnol Biotechnol Equip 2020;34:1323–1336.
58. Moshirfar M, West WB, Marx DP. Face mask-associated ocular irritation and dryness. Ophthalmol Ther 2020;9:397–400.
59. Azari AA, Barney NP. Conjunctivitis: a systematic review of diagnosis and treatment. JAMA 2013;310:1721–1729.
60. Amesty MA, Alió del Barrio JL, Alió JL. COVID-19 disease and ophthalmology: an update. Ophthalmol Ther 2020;9:1–12.
61. Guo D, Xia J, Shen Y, Tong J. SARS-CoV-2 may be related to conjunctivitis but not necessarily spread through the conjunctiva SARS-CoV-2 and conjunctiva. J Med Virol 2020;10.1002/jmv.25856.
62. Loon SC, Teoh SC, Oon LL, Se-Thoe SY, Ling AE, Leo YS, et al. The severe acute respiratory syndrome coronavirus in tears. Br J Ophthalmol 2004;88:861–863.
63. Chen X, Yu H, Mei T, Chen B, Chen L, Li S, et al. SARSCoV- 2 on the ocular surface: is it truly a novel transmission route? Br J Ophthalmol 2020;bjophthalmol-2020-316263.