Subclinical Ocular Changes Following Mild COVID-19 in Young Adults


The Coronavirus Disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has evolved into a global pandemic with a spectrum of clinical manifestations, ranging from mild viral illness to severe respiratory distress and multi-organ failure [1].

Beyond the respiratory system, COVID-19 has been associated with various extrapulmonary manifestations, including ocular effects that span from conjunctivitis to more severe conditions like vasculitic retinal vein occlusion and optic neuritis [2], [3], [4], [5].

Prevalence and Clinical Presentation:

Studies conducted in different regions demonstrate a spectrum of ocular manifestations in Covid-19 patients. A systematic study of 2347 cases in 2020 revealed that 11.64% of patients exhibited ocular surface manifestations, with pain being the most prevalent symptom at 31.2%. Meta-analyses reported pooled prevalence rates of 11.03%, with conjunctivitis, dry eye, redness, tearing, and itching being the most common ocular signs.

In a case series of 38 patients, 12 hospitalized individuals presented with conjunctivitis, hyperemia, chemosis, and increased secretions. Notably, one patient showed conjunctivitis as the first symptom. The presence of ocular manifestations was associated with elevated white blood cells, neutrophils, and C-reactive protein levels.

Cross-sectional studies in Wuhan and Iraq reported varying prevalence rates of conjunctival congestion, ocular pain, discharge, epiphora, and photophobia, with a higher occurrence in severe cases of Covid-19. A meta-analysis by Cao et al. involving 1930 participants suggested a net prevalence rate of 8% for conjunctivitis/conjunctival congestion, with only 1% presenting ocular symptoms initially. The positive rate of conjunctival swab samples was 3%.

Neuro-Ophthalmological Involvement:

Beyond surface manifestations, Covid-19 has been implicated in neuro-ophthalmological disorders. Reports indicate cranial nerve palsy, polyneuritis cranialis, and Miller-Fisher syndrome associated with the virus. A case study demonstrated isolated abducent nerve palsy without an identifiable lesion, highlighting the complexity of ocular involvement in Covid-19.

Optic neuritis cases have been documented, emphasizing the need for awareness of ocular symptoms in Covid-19 patients. Additionally, rare occurrences of bilateral optic nerve affection with retinal hemorrhages have been reported, prompting considerations of a potential link between ocular manifestations and Covid-19.

Vascular Complications:

Several studies have explored vascular complications associated with Covid-19, including central retinal artery occlusion (CRAO). Case reports suggest that hypercoagulability in severe infections may lead to CRAO, emphasizing the need for careful monitoring and further investigation into treatment options.

Detection of the Virus in Ocular Secretions:

The presence of the virus in ocular secretions has been a subject of investigation. A cross-sectional study revealed that 7.1% of hospitalized patients had positive conjunctival swabs, suggesting the potential for ocular transmission. Another multicenter study detected viral RNA in conjunctival swabs for nearly 12 days after disease onset, indicating the prolonged presence of the virus in ocular tissues.

Effects of Medications and Vaccines:

Ocular manifestations are not limited to the direct effects of the virus but extend to medications and vaccines used in Covid-19 management. Some medications, such as chloroquine, hydroxychloroquine, ribavirin, and corticosteroids, have been associated with ocular toxicities, emphasizing the importance of monitoring and careful administration.

Reports of ocular manifestations following Covid-19 vaccination have emerged, with anterior and posterior segment involvements. Corneal graft rejection has been identified as a common anterior segment manifestation, while posterior segment effects include microangiopathy, localized vasculitis, and demyelination. Although these manifestations are rare, further research is needed to establish a definitive relationship between Covid-19 vaccines and ocular complications.

ACE2 Receptors and TMPRSS2 in Ocular Tissues:

The entry of SARS-CoV-2 into host cells relies on the binding of viral spike proteins to angiotensin-converting enzyme-2 (ACE2) receptors and the involvement of type II transmembrane serine protease (TMPRSS2). These key structures have been identified in ocular tissues, particularly in the cornea, raising concerns about the potential for ocular transmission of the virus [6], [7], [8]. An immunohistochemical study demonstrated the expression of ACE2 and TMPRSS2 in both the cornea and conjunctival epithelium, suggesting the ocular surface as a possible route for SARS-CoV-2 transmission [9].

Ocular Transmission Risk and Corneal Transplants:

The risk of SARS-CoV-2 transmission through corneal transplants has been highlighted, as evidenced by the expression of viral entry factors in corneal tissues. This underscores the importance of considering the potential transmission risk in corneal transplant procedures [10]. Furthermore, a prevalence study revealed the presence of SARS-CoV-2 RNA and proteins in ocular tissues of COVID-19 donors, prompting questions about the origin of the infection and whether it occurs primarily on the ocular surface or results from the transport of viral particles via the nasolacrimal duct [11].

Subclinical Changes in Corneal Structures:

Despite the absence of pathological findings in the corneal epithelium and endothelium of COVID-19 patients, the expression of ACE2 receptors raises the possibility of subclinical changes. Monitoring for these subtle alterations is crucial, as they may have implications for long-term ophthalmological health. The aim of the current study is to investigate and document these subclinical ocular changes in young adults who experienced mild COVID-19.


The study employs corneal topography to evaluate corneal curvature and specular microscopy to assess the endothelial layer. These techniques allow for the early detection of subclinical changes that may occur in the absence of overt pathological findings.

Potential Consequences and Implications:

Early detection of subclinical changes in corneal structures may facilitate timely clinical management to prevent or mitigate chronic ophthalmological conditions. Possible consequences include corneal edema due to endothelial insufficiency, corneal graft failures, alterations in the course of ectatic diseases, changes in refractive status, and retinal vascular and inflammatory changes.


In light of the potential ocular involvement in COVID-19, investigating subclinical changes in corneal structures becomes imperative for comprehensive patient care. This study aims to contribute valuable insights into the ocular effects of mild COVID-19, shedding light on the need for vigilant monitoring and early intervention to safeguard the long-term ocular health of affected individuals.

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