Retinal involvement of coronavirus disease (COVID-19): A systematic review

Mohammad Eko Prayogo(1*), Angela Nurini Agni(2)

(1) Department of Ophthalmology, Faculty of Medicine, Public Health, and Nursing, Gadjah Mada University
(2) Department of Ophthalmology, Faculty of Medicine, Public Health, and Nursing, Gadjah Mada University
(*) Corresponding Author


COVID-19 has wide-ranging manifestations which involve various organs. Although COVID-19 is known to affect mainly the respiratory system, many patients suffered from ocular manifestations following SARS-CoV-2 infection, especially conjunctivitis. However, there was some evidence of broader ocular involvement, which could involve the retinal layer. This review aims to analyze the possible explanation of retinal involvement in COVID-19 and whether comorbidities increase the risk of retinal involvement in COVID-19. We conducted a systematic literature search during September 2020 using the PUBMED database and other additional sources (e.g., Google Scholar). There was no year of publication nor language restriction. Six papers are used in this literature review: two studies reported retinal lesions in COVID-19 patients, one study detected SARS-CoV-2 RNA in retinal biopsies and three studies proposed possible mechanisms of retinal involvement in COVID-19. Ocular structures express ACE-2, such as the aqueous humor, pigmented epithelium, and retina. This is supported by the finding of SARS-CoV-2 nucleic acid in postmortem patients. Retinal involvement in COVID-19 patients includes hyperreflective retina lesions, subtle cotton wool spots, and microhemorrhage. However, these findings do not necessarily indicate the specificity of retinal involvement. Diabetes mellitus may be associated with disease severity in patients with COVID-19. Some evidence of retinal involvement in SARS-CoV-2 infection involves the detection of retinal lesions, the expression of ACE-2 in the retina, and the role of comorbidities.


COVID-19; ocular manifestation; retinal manifestation; infection

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  1. World Health Organization (WHO). Weekly Operational Report on COVID-19 4 September 2020.[Internet] Cited 20 October 2020. Available from:
  2. Cui J, Li F, Shi ZL. Origin and evolution of pathogenic coronaviruses. Nat Rev Microbiol. 2019;17:181–192.
  3. World Health Organization. Archived: WHO Timeline – COVID-19. [Internet] Cited 20 October 2020. Available from:
  4. Yuki, K., Fujiogi, M., Koutsogiannaki, S. COVID-19 pathophysiology: a review. Clinical Immunology. 2020;215:108427.
  5. Lai CC, Shih TP, Ko WC, et al; Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease-2019 (COVID-19): the epidemic and the challenges. Int J Antimicrob Agents. 2020;55(3):105924.
  6. Wiersinga, WJ, Rhodes, A, Cheng, AC, Peacock, SJ, Prescott, HC. Pathophysiology, transmission, diagnosis and treatment of coronavirus disease 2019 (COVID-19): a review. JAMA. 2020;324(8):782-793.
  7. Mao R, Qiu Y, He JS, Tan JY, Li XH, Liang J, et al. Manifestations and prognosis of gastrointestinal and liver involvement in patients with COVID-19: A systematic review and meta-analysis. Lancet Gastroenterol Hepatol. 2020; 5(7):667-678.
  8. Guan WJ, Ni ZY, Hu Y, Liang W, Ou C, He J, et al; Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med. 2020;382(18):1708-1720.
  9. Garg S, Kim L, Whitaker M, O’Halloran A, Cummings C, Hostein R, et al. Hospitalization rates and characteristics of patients hospitalized with laboratory-confirmed coronavirus disease 2019—COVID-NET, 14 States, March 1-30, 2020. MMWR Morb Mortal Wkly Rep. 2020;69(15):458-464.
  10. Richardson S, Hirsch JS, Narasimhan M, Crawford JM, McGinn T, Davidson KW, et al. Presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with COVID-19 in the New York City area. JAMA. 2020;323(20):2052-2059.
  11. Docherty AB, Harrison EM, Green CA, Hardwick HE, Pius R, Norman L, et al. Features of 20 133 UK patients in hospital with COVID-19 using the ISARIC WHO Clinical Characterisation Protocol: prospective observational cohort study. BMJ. 2020;369:m1985.
  12. Grasselli G, Zangrillo A, Zanella A, Antonelli M, Cabrini L, Castelli A, et al; COVID-19 Lombardy ICU Network. Baseline characteristics and outcomes of 1591 patients infected with SARS-CoV-2 admitted to ICUs of the Lombardy Region, Italy. JAMA. 2020;323(16):1574-1581.
  13. Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395(10223):497-506. doi:10.1016/S0140-6736(20)30183-5
  14. Long B, Brady WJ, Koyfman A, Gottlieb M. Cardiovascular complications in COVID-19. Am J Emerg Med. 2020;38(7):1504-1507. doi:10.1016/j.ajem.2020.04.048
  15. Mao L, Jin H, Wang M, Hu Y, Chen S, He Q, et al. Neurologic manifestations of hospitalized patients with coronavirus disease 2019 in Wuhan, China. JAMA Neurol. 2020;77(6):1-9.
  16. Helms J, Kremer S, Merdji H, Clere-Jehl R, Schenck M, Kummerlen C, et al. Neurologic features in severe SARS-CoV-2 infection. N Engl J Med. 2020;382(23):2268-2270.
  17. Hendren NS, Drazner MH, Bozkurt B, Cooper LT. Description and proposed management of the acute COVID-19 cardiovascular syndrome. Circulation. 2020;141(23):1903-1914.
  18. Wu P, Duan F, Luo C, Liu Q, Qu X, Liang L, Wu K. Characteristics of ocular findings of patients with coronavirus disease 2019 (COVID-19) in Hubei Province, China. JAMA Ophthalmol. 2020;138(5):575-578.
  19. Aiello F, Afflitto GG, Mancino R, Li JO, 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(7):1206-1211.
  20. Marinho PM, Marcos AA, Romano AC, Nascimento H, Belfort R. Retinal findings in patients with COVID-19. Lancet 2020;395(10237):1610.
  21. Hoffmann M, Kleine-Weber H, Schroeder S, Kruger N, Herrler T, Erichsen S, et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell. 2020;181(2):271–280.
  22. Zou X, Chen K, Zou J, et al. Single-cell RNA-seq data analysis on the receptor ACE2 expression reveals the potential risk of different human organs vulnerable to 2019-nCoV infection, Front Med. 2020;14(2):185-192.
  23. Cristelo C, Azevedo C, Marques JM, Nunes R, Sarmento B. SARS-CoV-2 and diabetes: new challenges for the disease. Diabetes Res Clin Pract 2020;164:108228.
  24. Landecho MF, Yuste JR, Gándara E, Sunsundegui P, Quiroga J, Alcaide AB, et al. COVID-19 retinal microangiopathy as an in vivo biomarker of systemic vascular disease? J Intern Med. 2020;168:108395.
  25. Casagrande M, Fitzek A, Püschel K, Aleshcheva G, Schultheiss H-P, Berneking L, et al. Detection of SARS-CoV-2 in human retinal biopsies of deceased COVID-19 patients. Ocul Immunol Inflamm. 2020;28(5):721–725.
  26. Raony Í, Figueiredo CS. 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.
  27. Vavvas DG, Sarraf D, Sadda SR, Eliott D, Ehlers JP, Waheed NK, et al. Concerns about the interpretation of OCT and fundus findings in COVID-19 patients in recent Lancet publication. Eye Lond Engl. 2020;34(12):2153-2154.
  28. Aiello F, Gallo Afflitto G, 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.
  29. Huang I, Lim MA, Pranata R. Diabetes mellitus is associated with increased mortality and severity of disease in COVID-19 pneumonia - A systematic review, meta-analysis, and metaregression. Diabetes Metab Syndr. 2020;14:395-403. doi: 10.1016/j.dsx.2020.04.018
  30. Guo W, Li M, Dong Y, Zhou H, Zhang Z, Tian C, et al. Diabetes is a risk factor for the progression and prognosis of COVID-19. Diabetes Metab Res Rev 2020;e3319.
  31. Wang W, Lo AC. Diabetic retinopathy: pathophysiology and treatments. Int J Mol Sci 2018;19(6):1816.
  32. Ye Q, Wang B, Mao J. The pathogenesis and treatment of the ‘cytokine storm’ in COVID-19. J Infect 2020;80(6):607–613.
  33. Cristelo C, Azevedo C, Marques JM, Nunes R, Sarmento B. SARS-CoV-2 and diabetes: New challenges for the disease. Diabetes Res Clin Pract 2020;164:108228.
  34. Soro-Paavonen A, Gordin D, Forsblom C, et al. Circulating ACE2 activity is increased in patients with type 1 diabetes and vascular complications. J Hypertens 2012;30(2):375–383.
  35. Fang L, Karakiulakis G, Roth M. Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection? Lancet Respirat Med 2020;8(4):e21.


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