Ocular Implications of SARS-CoV-2 Infections

The ocular surface has emerged as both a potential route of SARS-CoV-2 entry and a site of diverse clinical manifestations. Early in the pandemic, tear fluid and conjunctival swabs revealed viral RNA in a small proportion of patients, and mild conjunctivitis was recognised as an occasional presentation. Deeper involvement has been described through subtle retinal changes on imaging—such as hyperreflective inner retinal lesions—and vascular complications including microhaemorrhages and vein occlusion. The distribution of viral entry factors, ACE2 and TMPRSS2, in conjunctival, limbal and corneal epithelia suggests direct surface susceptibility, while post-systemic exposure the virus can breach the blood–retinal barrier, triggering retinal inflammation and microvasculopathy. Immune-mediated neuroinflammation within the eye adds further complexity, with potential long-term sequelae for visual function. In parallel, pandemic restrictions and infection risks profoundly disrupted ophthalmic care, leading to underutilisation of services and delayed treatment for vision-threatening diseases. Understanding these ocular implications has informed infection control measures in eye clinics, guided screening for ocular involvement, and stimulated research on interventional strategies to mitigate visual morbidity. Globally, these findings underscore the need for integrated ophthalmic surveillance in COVID-19 management and highlight the eye’s dual role as a gateway for viral transmission and a target for systemic and local inflammation.

Research from Nature Portfolio

Recent studies have quantified the impact of the pandemic on ophthalmic service delivery. One large-scale analysis used registry data from tens of millions of patient encounters to model expected care utilisation and documented sustained reductions in visits for both routine and emergent eye conditions during and after the initial hiatus, with the greatest declines observed in non-urgent services but concerning deficits in vision-threatening care. In parallel, experimental inoculation studies in non-human primates demonstrated that conjunctival exposure to SARS-CoV-2 can establish infection, with detectable viral loads in the nasolacrimal pathway and evidence of mild pulmonary pathology. These findings collectively emphasise the conjunctiva as a viable route of entry and the wider ramifications of care disruption on ocular health.

Ocular Implications of SARS-CoV-2 Infections publication trend

The graph below shows the total number of articles in ocular implications of sars-cov-2 infections across all publications each year (not limited to Nature Index journals).

Technical terms

Conjunctivitis: inflammation of the conjunctival membrane of the eye, characterised by redness, tearing and discharge.

Blood–retinal barrier (BRB): a selective physiological barrier formed by retinal vascular endothelium and retinal pigment epithelium that regulates molecular exchange between the bloodstream and neural retina.

ACE2 receptor: angiotensin-converting enzyme 2, a cell-surface protein that mediates SARS-CoV-2 attachment and entry.

TMPRSS2 protease: transmembrane serine protease 2, a host cell enzyme that primes the viral spike protein, facilitating membrane fusion.

Viral tropism: the specificity of a virus for particular host tissues or cell types based on receptor expression and cellular factors.

Neuroinflammation: inflammatory response within neural tissues, often characterised by activation of resident immune cells and cytokine release.

References

1. Shifts in ophthalmic care utilization during the COVID-19 pandemic in the US. Communications Medicine (2023).
2. SARS-CoV-2 infects cells lining the blood-retinal barrier and induces a hyperinflammatory immune response in the retina via systemic exposure. PLOS Pathogens (2024).
3. Characteristics of Ocular Findings of Patients With Coronavirus Disease 2019 (COVID-19) in Hubei Province, China. JAMA Ophthalmology (2020).
4. Ocular conjunctival inoculation of SARS-CoV-2 can cause mild COVID-19 in rhesus macaques. Nature Communications (2020).
5. 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. The Ocular Surface (2020).
6. Ocular surface manifestations of coronavirus disease 2019 (COVID-19): A systematic review and meta-analysis. PLOS ONE (2020).