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Although respiratory symptoms are the most frequent manifestation of COVID-19, multi-organ involvement has been demonstrated, including ocular manifestations. The author investigates how the eye can be affected.

 

The SARS-CoV-2 virus responsible for the COVID-19 pandemic has presented a significant public health challenge globally. As of 11 January 2021, it has resulted in over 80 million cases and 1.8 million deaths globally [1].

Common clinical manifestations of COVID-19 include fever, cough, fatigue and sore throat but in severe cases can progress to acute respiratory distress syndrome, which often requires ventilatory support and intensive care [2]. Although lung involvement is the most serious manifestation of COVID-19, the disease can lead to multi-organ dysfunction, including hypercoagulability, cortisol insufficiency, acute kidney injury, liver dysfunction, acute myocardial infarction, cerebrovascular disease and ocular complications [3]. This article will outline some of the commonly reported ocular manifestations of COVID-19.

Conjunctivitis

Conjunctivitis is one of the most commonly reported ocular manifestations of COVID-19. Wu et al. presented a case series from the Hubei province, China, of 38 patients with COVID-19, 12 of whom had ocular symptoms consistent with conjunctivitis including chemosis, conjunctival hyperaemia and epiphora. Two of these patients were reverse transcriptase polymerase chain reaction (RT-PCR) positive for SARS-CoV from both conjunctival and nasopharyngeal swabs. The authors also showed that patients with ocular symptoms were more likely to have severe COVID-19 infection as shown from laboratory investigations [4].

These findings were corroborated by Aggarwal et al. in a meta-analysis of the ocular surface manifestations of COVID-19. They analysed 16 studies with 2347 confirmed COVID-19 cases and reported that 11.6% of these patients had ocular surface manifestations, namely ocular pain, discharge, redness and follicular conjunctivitis. Some studies report follicular conjunctivitis as the first and sole manifestation of the disease [5]. Others have shown evidence of viral SARs-CoV-2 RNA in ocular samples [4,6,7,8] but the infectious potential of this and whether disease has resulted from ocular transmission remains unclear [9].

Retinal pathologies

COVID-19 has been implicated in the development of retinal microangiopathy. In a study of 27 asymptomatic individuals following COVID-19 pneumonia, Landecho et al. report retinal microangiopathy as cotton wool spots developing in 22% of individuals. Asymptomatic ocular microangiopathy is commonly seen in other vascular diseases such as diabetes and hypertension. It is theorised that SARS CoV-2 can cause ACE-2 downregulation leading to endothelial cell dysfunction and thus microvascular damage [10]. In another study, patients with severe COVID-19 infection were found to have acute vascular lesions of the inner retina, including cotton wool spots and flame shaped haemorrhages, however, these findings were not adjusted for co-morbidities [11].

“Several studies have shown evidence of viral SARs-CoV-2 RNA in ocular samples but the infectious potential of this and whether disease has resulted from ocular transmission remains uncertain”

Yahalomi et al. report a case of central retinal vein occlusion (CRVO) in a 33-year-old healthy male which occurred two weeks after his symptoms of COVID-19 infection resolved [12]. The pathogenesis of CRVO is multifactorial and risk factors include age, hyperlipidaemia and hypercoagulable states. We now know that COVID-19 is strongly associated with an increased risk of thromboembolic events [13]. Cases of paracentral acute middle maculopathy and acute macular neuroretinopathy have also been described in young individuals, which are thought to represent post-infectious complications of COVID-19 [14].

Neuro-ophthalmic manifestations

Optic neuritis in patients with COVID-19 infection is described in the literature [15], including a case of bilateral optic neuritis with myelin oligodendrocyte glycoprotein (MOG) antibodies whose production may have been triggered by the virus [16]. Guillain Barre Syndrome (GBS), an immune-mediated disorder, has been described in patients following COVID-19 infection and is hypothesised to occur secondary to molecular mimicry [17,18]. Miller Fisher syndrome, a variant of GBS, has been described in a 50-year-old COVID-19 patient who presented with vertical diplopia and ataxia, postulated to result from immune-mediated injury [19]. Cranial nerve palsies including third nerve palsies have notably been described by Belghmaidi et al., who report a pupil-sparing third nerve palsy in a 24-year-old patient with concurrent COVID-19 infection. Laboratory investigations and imaging revealed no underlying structural cause for the oculomotor nerve injury. One hypothesis is that the expression of ACE-2 receptors in nerve cells can explain the neurotropic effect of the virus, which may enter the nervous system through the cribriform lamina [20].

Conclusion

The most common ocular complications observed with COVID-19 are eye pain, redness and conjunctivitis. Although there is evidence of SARS-CoV-2 viral RNA in ocular fluid, the infectious potential and risk of transmission remain uncertain. Retinal and neuro-ophthalmic disease have also been reported in numerous case studies. However, it is unclear in many of these studies whether the SARS CoV-2 virus is responsible for these ocular manifestations. Further studies to explore the underlying pathological processes are required.

 

References

1. World Health Organisation (WHO). Weekly operation update on COVID-19, 11 January 2021:
www.who.int/publications/m/item/
weekly-operational-update-on-covid-19
---11-january-2021

(Last accessed February 2021).
2. Zhu N, Zhang D, Wang W, et al. A Novel Coronavirus from Patients with Pneumonia in China, 2019. N Engl J Med 2020;382(8):727-33.
3. Gavriatopoulou M, Korompoki E, Fotiou D, et al. Organ-specific manifestations of COVID-19 infection. Clin Exp Med 2020;20(4):493-506.
4. Wu P, Duan F, Luo C, et al. Characteristics of Ocular Findings of Patients With Coronavirus Disease 2019 (COVID-19) in Hubei Province, China. JAMA Ophthalmol 2020;138(5):575-8.
5. Aggarwal K, Agarwal A, Jaiswal N, et al. Ocular surface manifestations of coronavirus disease 2019 (COVID-19): A systematic review and meta-analysis. PloS One 2020;15(11):e0241661.
6. Zhang X, Chen X, Chen L, et al. The infection evidence of SARS-COV-2 in ocular surface: a single-center cross-sectional study. Public and Global Health 2020:
http://medrxiv.org/lookup/doi/
10.1101/2020.02.26.20027938

(Last accessed February 2021).
7. Chen L, Liu M, Zhang Z, et al. Ocular manifestations of a hospitalised patient with confirmed 2019 novel coronavirus disease. Br J Ophthalmol 2020;104(6):748‑51.
8. Colavita F, Lapa D, Carletti F, et al. SARS-CoV-2 Isolation From Ocular Secretions of a Patient With COVID-19 in Italy With Prolonged Viral RNA Detection. Ann Intern Med 2020;173(3):242-3.
9. Dockery DM, Rowe SG, Murphy MA, Krzystolik MG. The Ocular Manifestations and Transmission of COVID-19: Recommendations for Prevention. J Emerg Med 2020;59(1):137-40.
10. Landecho MF, Yuste JR, Gándara E, et al. COVID‐19 retinal microangiopathy as an in vivo biomarker of systemic vascular disease? J Intern Med 2021;289(1):116‑20.
11. Pereira LA, Soares LCM, Nascimento PA, et al. Retinal findings in hospitalised patients with severe COVID-19. Br J Ophthalmol 2020;Epub ahead of print.
12. Yahalomi T, Pikkel J, Arnon R, Pessach Y. Central retinal vein occlusion in a young healthy COVID-19 patient: A case report. Am J Ophthalmol Case Rep 2020;20:100992.
13. Malas MB, Naazie IN, Elsayed N, et al. Thromboembolism risk of COVID-19 is high and associated with a higher risk of mortality: A systematic review and meta-analysis. EClinicalMedicine 2020;29-30:100639.
14. Virgo J, Mohamed M. Paracentral acute middle maculopathy and acute macular neuroretinopathy following SARS-CoV-2 infection. Eye Lond Engl 2020;34(12):2352‑3.
15. Gold DM, Galetta SL. Neuro-ophthalmologic complications of coronavirus disease 2019 (COVID-19). Neurosci Lett 2021;742:135531.
16. Sawalha K, Adeodokun S, Kamoga G-R. COVID-19-Induced Acute Bilateral Optic Neuritis. J Investig Med High Impact Case Rep 2020;8:2324709620976018.
17. Sedaghat Z, Karimi N. Guillain Barre syndrome associated with COVID-19 infection: A case report. J Clin Neurosci Off J Neurosurg Soc Australas 2020;76:233-5.
18. Jacobs BC, Rothbarth PH, van der Meché FG, et al. The spectrum of antecedent infections in Guillain-Barré syndrome: a case-control study. Neurology 1998;51(4):1110-5.
19. Gutiérrez-Ortiz C, Méndez-Guerrero A, Rodrigo-Rey S, et al. Miller Fisher syndrome and polyneuritis cranialis in COVID-19. Neurology 2020;95(5):e601-5.
20. Belghmaidi S, Nassih H, Boutgayout S, et al. Third Cranial Nerve Palsy Presenting with Unilateral Diplopia and Strabismus in a 24-Year-Old Woman with COVID-19. Am J Case Rep 2020;21:e925897.


TAKE HOME MESSAGE
  • Most common ocular manifestations of COVID-19 are eye pain, redness, conjunctivitis.
  • SARS CoV-2 viral RNA has been found in ocular fluid but infectious potential is uncertain.
  • Retinal microangiopathy has been observed in some patients following COVID-19 infection.
  • Neuro-ophthalmic manifestations such as optic neuritis and cranial nerve palsies have been reported but underlying pathogenesis is unknown.



Declaration of competing interests: None declared.

 

 

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CONTRIBUTOR
Amal Minocha

Imperial College Healthcare Trust, UK.

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