The spread of coronavirus disease that originated in Wuhan, China, led to a global pandemic affecting people in different ways. COVID-19 causes pulmonary problems and impacts other systems of the human body, including cardiovascular/circulatory, digestive, immune, and sensory nervous. Various forms of ophthalmic manifestations of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) occur as a result of the immune response to the virus and might be used for differential diagnosis. The following literature review will investigate the sources of evidence and discuss the prevalence and examples of eye-related COVID-19 symptoms, as well as the pathogenesis of the disease. The results of the five studies also create implications for research and clinical practice, which will be considered.
Prevalence and Examples of Ocular Manifestations
Specific data on the prevalence and distinct forms of ophthalmic symptoms is important because it might help healthcare workers ensure timely and accurate diagnosis of SARS-CoV-2. The systematic review by Nasiri et al. (2021) aimed to eliminate the gap in the understanding of the ocular symptoms of COVID-19. The researchers examined 895 articles available in several major databases (Pubmed, Embase, Web of Science, Scopus, and medRxiv) and discovered that the prevalence of ocular manifestations was 11.03%. Similarly, Wu et al. (2020) reported that 11 of 38 COVID-positive patients monitored during their research had ocular abnormalities, while 2 had positive results from conjunctival swabs. The estimated prevalence of viral nucleotides in conjunctival samples was relatively low (5.2%). In contrast to the findings discussed above, Lawrenson and Buckley (2020) maintain that viral conjunctivitis and other ophthalmic symptoms are rare complications of COVID-19 with an average prevalence of 4% or less. The experts state that the reports of positive SARS-CoV-2 patients reveal insufficient use of conjunctival swabs and doubt the existence of the causal relationship between COVID-19 and ocular symptoms.
The researchers aimed to identify and describe distinct ophthalmic symptoms that might be used for diagnostic purposes. According to Nasiri et al. (2021), the most common symptoms are dry eye or foreign object sensation, redness, itching, tearing, and pain. Chen et al. (2020) conducted experimentation on animal models and concluded that eye infections, such as conjunctivitis, uveitis, retinitis, and optic neuritis, might be additional signs of coronavirus infection. Wu et al. (2020) also discovered that conjunctival hyperemia, epiphora, chemosis, and excessive eye discharge contribute to the list of ophthalmic manifestations. The researchers did not observe the instances of blurred vision in COVID-19 patients, while epiphora appeared to be the first symptom of the infection in one instance.
Pathogenic Mechanisms
The examination of pathogenesis in relation to ocular manifestations of COVID-19 might provide valuable insights into the problem of the infectious disease. Willcox et al. (2020) stated that several types of coronaviruses, including SARS-CoV-2, employ the spike protein to bind to host cell receptors and replicate. Chen et al. (2020) noticed that the angiotensin-converting enzyme 2 (ACE2) is a receptor associated with coronavirus infection that is present in the human conjunctiva, retina, cornea, and aqueous humor. Moreover, Lawrenson and Buckley (2020) discovered that the priming protease TMPRSS2 facilitates the binding of the virus to the ACE2 receptors. The authors proposed that SARS-CoV-2 targets the receptors located in different eye tissues, causing conjunctivitis, anterior uveitis, retinitis, and optic neuritis. ACE2 is also present in the kidneys, heart, and liver, which might explain the coincidence of severe ocular symptoms with organ damage. The researchers mentioned above agree that ACE2 is the main receptor involved in coronavirus pathogenesis.
There are opposing views on the ophthalmic origin of COVID-19, as the studies of ocular manifestations demonstrated a low prevalence of SARS-CoV-2 fragments (nucleotides) in conjunctival specimens. Wu et al. (2020) reported only one patient whose primary symptom was conjunctivitis. Furthermore, the initial reports from Wuhan, China, 17 studies from Singapore, and 32 international cases did not list conjunctivitis or other ocular manifestations as COVID-19 symptoms (Willcox et al., 2020). Conjunctival inoculation is associated with mild cases of lung infection in comparison with trachea inoculation (Willcox et al., 2020). Therefore, conjunctival testing might be ineffective for confirming COVID-19, which makes nasopharyngeal swabs and blood samples the primary diagnostic methods.
Implications for Research and Clinical Practice
The research findings related to the ophthalmic manifestations of coronavirus disease may promote further research and support the development of effective prevention and treatment strategies. Thus, the experts addressed the problem of ocular symptoms to identify its potential for application in clinical practice. The ocular surface is a possible target for viral infections, which means that retinopathy in COVID-19 patients may correlate with the degree of microvascular lesions and predict damage in other organs (Chen et al., 2020). It should be noted that the fragments of the original SARS-CoV, which is 79.5% genetically consistent with the novel coronavirus, were detected in tears of individuals with the acute respiratory syndrome (Chen et al., 2020). Based on the univariate analysis of 38 COVID-positive patients, Wu et al. (2020) concluded that individuals with ocular symptoms experienced higher neutrophil and white blood cell counts than patients without ophthalmologic manifestations. The researchers also reported higher C-reactive protein, procalcitonin, and lactate hydrogenase in these patients. The findings suggest that ocular abnormalities may serve as early indicators of coronavirus disease, as they are consistent with severe systemic symptoms and blood test results.
The articles also provide implications for ophthalmologic and epidemiologic practice and research. The eye is considered a possible site of coronavirus infection due to the risk of exposure to airborne droplets transmitted during person-to-person contact. Additionally, respiratory tract infection can facilitate the migration of the virus through the nasolacrimal duct to the ocular surface (Willcox et al., 2020). The article by Wu et al. (2020) confirms the idea and shows that unprotected eyes can increase the risk of viral transmission, which implies that COVID-19 might spread through the eye. Notably, animal studies identified SARS-CoV-2 RNA on the ocular surface of rhesus monkeys shortly after an infection, and the highest antibody levels were detected on day 14 (Willcox et al., 2020). Despite the possibility of ocular transmission, the literature review conducted by Willcox et al. (2020) indicates that contact lenses and other forms of vision correction are safe if proper hygiene is practiced. It can be concluded that coronavirus attaches to ocular surface cells, which explains its potential to cause conjunctivitis.
Conclusion
The review of the articles contributed valuable information on the prevalence of ocular manifestations, examples, and pathogenic mechanisms of COVID-19. The authors reported different percentages of ophthalmic symptom prevalence, while the ACE2 receptor was assumed to play a significant role in the pathogenesis. According to some authors, the manifestations may be considered as indicators of organ damage, while others doubt the effectiveness of the conjunctival testing. The ocular surface was described as the target for the infection, which indicated the possibility of ocular transmission. Therefore, the research findings provided several implications for clinical practice and academic research, which might improve diagnostic procedures and treatment options.
References
Chen, J., Pan, S., Chen, G., & Sun, H. (2020). A review of COVID-19 related eye disease. Social Science Research Network. Web.
Lawrenson, J. G., & Buckley, R. J. (2020). COVID‐19 and the eye. Ophthalmic and Physiological Optics. Web.
Nasiri, N., Sharifi, H., Bazrafshan, A., Noori, A., Karamouizan, M., & Sharifi, A. (2021). Ocular manifestations of COVID-19: A systematic review and meta-analysis. Journal of Ophthalmic and Vision Research, 16(1), 103-112. Web.
Willcox, M., Walsh, K., Nichols, J. J. Morgan, P. B., & Jones, L. W. (2020). The ocular surface, coronaviruses and COVID-19. Clinical and Experimental Optometry, 103(4), 418-424. Web.
Wu, P., Duan, F., Luo, C., Liu, Q., Qu, X., Liang, L., & Wu, K. (2020). Characteristics of ocular findings of patients with coronavirus disease 2019 (COVID-19) in Hubei Province, China. JAMA Ophthalmology, 138(5), 575-578. Web.