COVID and the Eye: Medical Research Findings 5 Years On

The COVID-19 pandemic has impacted nearly every aspect of human health and society since it emerged in 2019. While primarily known as a respiratory illness, mounting evidence shows that SARS-CoV-2, the virus that causes COVID-19, can affect multiple organ systems — including the eyes.¹ As the gateway to our visual world, the eyes play a critical role in our daily lives and overall well-being. Five years ago, in March 2020, we first started referring to the threat this virus caused as a pandemic. Since then, researchers have uncovered much about COVID and the eye.  From short-term symptoms, such as conjunctivitis, to potential long-term effects on the retina and optic nerve, COVID-19 can affect various ocular systems.^1,2

The eye’s intricate structure provides multiple potential sites for viral infection and damage.² The cornea and conjunctiva on the eye’s surface may serve as an entry point for the virus. Deeper structures, such as the retina and its rich blood supply, could be affected by the systemic inflammation and vascular changes seen in severe COVID-19. Even the visual pathways in the brain may be impacted by the neurological effects of the disease.³ “Virus-induced inflammation is treatable, but in severe cases of retinal pathological changes, only personalized and symptomatic treatments are available to manage the conditions,” explained Pawan Singh, PhD, Assistant Professor of Ophthalmology at the University of Missouri School of Medicine. 

In the 5 years since the start of the pandemic, researchers have built a wealth of knowledge regarding COVID and the eye, from common short-term symptoms to emerging evidence of long-term and potentially permanent changes. 

Short-Term Ocular Manifestations of COVID-19

Conjunctivitis: Conjunctivitis has emerged as likely the most common ocular manifestation of COVID-19. Recent studies show a higher prevalence of ocular symptoms than initially thought, with a meta-analysis reporting a pooled prevalence of 11.03% for ocular manifestations among COVID-19 patients.^3,4 Conjunctivitis accounts for most of these cases, with some studies indicating it comprises up to 88.8% of all ocular manifestations.⁴

The symptoms of COVID-19-related conjunctivitis can range from mild to severe. Common symptoms include:⁴

• Eye redness
• Foreign body sensation
• Ocular irritation
• Tearing
• Mucoid discharge
• Eyelid swelling
• Chemosis

In some cases, more severe symptoms,  such as photophobia, tarsal hemorrhage, and pseudomembrane formation, have been reported.³ The onset of conjunctivitis can vary, with some patients experiencing it as an early symptom and others developing it later in the course of the disease.³ Ocular symptoms typically last 4 to 14 days, are generally mild, heal quickly, and do not cause sight-threatening complications.¹

Interestingly, conjunctivitis can sometimes present as the initial or even the sole manifestation of COVID-19. In a study of 38 hospitalized COVID-19 patients, one individual presented with epiphora as the first symptom of the disease.⁴ Other studies have reported that ocular symptoms were the first presenting complaint or sole manifestation of COVID-19 in 0.9% of patients.¹ These cases highlight the importance of considering COVID-19 in patients presenting with conjunctivitis, even in the absence of other typical symptoms.

Other Acute Ocular Symptoms: Dry eye or foreign body sensation is a common ocular symptom associated with COVID-19, with studies reporting a prevalence of up to 16% among affected patients.^3,4 This symptom can contribute to ocular discomfort and may be accompanied by other manifestations of conjunctivitis. The influence of SARS-CoV-2 infection on the systemic immune system can damage the ocular surface or affect the structure and stability of the tear film, predisposing the eye to secondary infections.¹

Excessive tearing, or epiphora, is another frequently reported ocular symptom in COVID-19 patients. Studies have shown a prevalence of around 12.8% for this symptom.^3,4 In some cases, epiphora may be the presenting symptom of COVID-19, emphasizing the need for healthcare providers to be aware of this potential early sign of infection.

Photophobia, or light sensitivity, has been observed in some COVID-19 patients with ocular involvement. While less common than conjunctivitis or dry eye, photophobia can be a significant source of discomfort for affected individuals. It may occur in conjunction with other ocular symptoms or as part of more severe ocular manifestations of COVID-19.^3,4 

While these ocular symptoms are generally self-limiting and resolve spontaneously or with supportive treatment, they can significantly affect a patient’s quality of life during the acute phase of the infection. Moreover, the presence of ocular symptoms may have implications for disease transmission, as the virus has been detected in the ocular secretions of some patients.⁴ 

Research has also revealed that SARS-CoV-2 can potentially breach the blood-retinal barrier, even in otherwise healthy individuals.⁵ This finding suggests that the virus may have more profound effects on ocular health than previously thought, potentially leading to long-term consequences in the eye. As such, it is recommended that COVID-19 patients, even those who were asymptomatic, undergo ophthalmological examinations to check for signs of retinal changes or other ocular complications.⁵

While respiratory symptoms remain the hallmark of COVID-19, ocular manifestations, particularly conjunctivitis and related symptoms, are increasingly recognized as important aspects of the disease. Their presence can aid in early diagnosis and may have implications for patient management and infection control measures.

Long-Term Ocular Effects of COVID-19

The long-term ocular effects of COVID-19 have become an area of increasing concern as research reveals the virus’s far-reaching effects beyond the respiratory system. In fact, its ability to penetrate the blood-retinal barrier can potentially lead to various complications in the retina as well as other parts of the eye. This ability of SARS-CoV-2 to breach the protective barrier puts the retina at risk, even in cases where the infection doesn’t directly enter through the eye’s surface.⁶ “The eye is an immune-privileged organ where host-induced persistent inflammation can cause more damage than the invading pathogen alone,” said Dr Singh.

One of the most significant areas of concern regarding COVID and the eye in the long term is retinal involvement.⁶ 

“Our studies show that SARS-CoV-2 can cause a hyperinflammatory response in the retina via systemic or lung infection,” said Dr Singh. “In COVID-19 cases, if the virus reaches the eye, it can cause inflammatory damage to the retina and may cause these symptoms.” 

Prolonged exposure to viral remnants in the eye increases the risk of damage to the retina and visual function. Complications such as retinal artery and vein occlusion, often described as an “eye stroke,” have been reported in COVID-19 patients.⁷ Other observed issues include retinal microaneurysms, where tiny blood vessels in the retina swell and leak, and vascular leakage in the eyes.⁶ “Prolonged exposure to viral remnants in the eye increases the risk of damage to the retina and visual function,” noted Dr Singh. “In long-COVID patients, viral remnants like spike antigens may exacerbate retinal damage, leading to conditions such as vascular leakage and ischemia.”

Microvascular changes in the retina are among the most common manifestations of COVID-19. These include cotton wool spots and retinal microhemorrhages. Many patients maintain preserved visual acuity and pupillary reflexes, but there have been instances where patients developed visual field defects.^8,9 The SARS-CoV-2 infection has also been associated with new-onset paracentral acute middle maculopathy (PAMM) and acute macular neuroretinopathy (AMN), although a definitive relationship between these conditions and COVID-19 is yet to be established.¹⁰

Central retinal vein occlusion (CRVO) has been identified as an important complication of COVID-19, requiring early detection and treatment for improved prognosis. The infection is known to cause endothelial disruption, complement activation, and inflammation, leading to a hypercoagulable state that increases the risk of thrombus formation.¹¹ Symptoms of CRVO, such as decreased and blurred vision, can start from 5 days to 6 weeks after the initial onset of fever.¹²

In addition to retinal complications, COVID-19 has been associated with various forms of ocular inflammation, including anterior and posterior uveitis.¹³ Cases of optic neuropathy, both ischemic optic neuropathy (ION) and optic neuritis (ON), have been reported in COVID-19 patients.¹⁴ These conditions can lead to long-term visual impairment if not properly managed.¹⁵

Research also shows that COVID-19 can affect the cornea and ocular surface. Studies have reported a significant reduction in corneal nerve fiber density in patients who have recovered from COVID-19, particularly in those with persistent symptoms.^16,17 Some patients have experienced persistent dry eye symptoms and changes in tear osmolarity following COVID-19 infection.¹⁸ 

While these ocular complications have been observed in COVID-19 patients, their prevalence and long-term impact are still being studied. Some research suggests that retinal involvement may be more common in patients with severe COVID-19, but it has also been observed in those with mild or asymptomatic cases.¹⁹ 

“Current literature, patient data from clinics, and our experimental studies indicate COVID-19 may induce retinal thromboembolic events, including retinal arteries and vein occlusion, retinal volume and microvascular loss, and loss of vision,” explained Dr Singh. “Currently, retinal pathologies are more commonly reported in severely ill individuals; however, mild or asymptomatic patients can also show COVID-induced retinal damage. We have an asymptomatic juvenile patient at our clinic with COVID-19-induced retinal changes.”

As research continues, the understanding of the long-term ocular effects of COVID-19 will likely evolve, potentially leading to improved strategies for preventing and treating these complications. Given the potential for long-term ocular damage, routine eye exams are essential for post-COVID care. “A routine eye exam is crucial in detecting early onset of any ocular conditions,” advised Dr Singh. 

Permanent Ocular Changes From COVID

COVID-19 has been shown to potentially cause permanent ocular changes in some patients, affecting both the structure and function of various eye tissues. Structural alterations in ocular tissues have been observed, particularly in the retina and cornea.^20,21 Retinal scarring has been reported in some severe cases, often associated with vascular complications such as retinal artery and vein occlusions.²² These vascular events can permanently damage the retinal tissue, potentially resulting in long-term vision impairment.^22,23 “The retina is a neuronal tissue, and the damage could be irreversible,” said Dr Singh. Additionally, studies have found evidence of persistent retinal microaneurysms and vascular leakage in some recovered COVID-19 patients, which may contribute to ongoing retinal damage.²⁰ 

“In our experimental studies, we detect the shedding of live virus for up to 16 weeks, the viral remnants can stay even longer,” said Dr Singh. “In long-COVID patients, viral remnants such as spike antigens may cause acute or permanent damage to the retina.”.

Corneal changes have also been documented in COVID-19 patients. Research has revealed significant alterations to the cornea, including corneal nerve loss and increased corneal dendritic cell density in recovered patients, particularly those with long COVID symptoms. These changes in corneal nerve morphology may persist for extended periods, with one study finding alterations in corneal nerve parameters for longer than 20 months after acute infection.²⁴ Such long-term changes to the corneal structure could potentially affect visual function and ocular surface health. 

How COVID Can Damage Vision 

Functional changes in vision have been reported in some COVID-19 patients, both during active infection and in the post-infection period. Visual acuity loss has been observed in various cases, ranging from mild to severe. In some instances, vision loss has been associated with complications such as optic neuritis, which can lead to permanent visual impairment if not promptly treated.^15,25 Color vision deficits have also been noted in some recovered COVID-19 patients. A study found that patients who had recovered from COVID-19 exhibited higher contrast thresholds and worse color sensitivity for almost all color mechanisms studied, suggesting potential impairment in visual perception.²⁶

Visual field changes have been reported in some cases, particularly in patients who developed complications such as retinal vein occlusions or optic nerve involvement.¹⁵ These changes can manifest as scotomas or other visual field defects, which may persist even after recovery from the acute infection.

Research investigating the permanent ocular effects of COVID-19 continues, but many uncertainties remain. Current studies focus on long-term follow-up of recovered patients to better understand the persistence and progression of ocular changes. For instance, researchers are using advanced imaging techniques like optical coherence tomography angiography (OCT-A) to assess long-term changes in retinal vasculature and potentially use these findings as biomarkers for COVID-19 complications.²⁰

However, determining long-term outcomes presents several challenges. The relatively recent emergence of COVID-19 means that truly permanent data are still limited. Additionally, the presence of comorbidities in many COVID-19 patients, such as diabetes and hypertension, can confound the interpretation of ocular findings.²⁰ The wide range of disease severity and the potential impact of different treatment regimens make it difficult to generalize outcomes across all patients. 

While evidence suggests that COVID-19 can cause permanent ocular changes in some patients, affecting both ocular structure and function, much remains to be learned about the infection’s long-term consequences on eye health. Ongoing research and long-term follow-up studies will be crucial in fully understanding the permanent ocular effects of COVID-19 and developing appropriate management strategies for affected patients.

Ongoing Research Into COVID And The Eye

Like with other systemic viral infections, COVID and the eye have a complex relationship. As research continues to unfold new evidence, it is clear that SARS-CoV-2 can affect the eyes in the short and long term, with the potential for permanent changes. The virus’s ability to penetrate ocular barriers and induce inflammation highlights the need for heightened awareness among healthcare providers regarding ocular symptoms as potential early indicators of COVID-19.

Short-term manifestations such as conjunctivitis and dry eye are relatively common and usually self-limiting, yet they can significantly affect a patient’s quality of life and may aid in early diagnosis. More concerning are the long-term effects, including retinal involvement and vascular complications, which could lead to lasting visual impairment. The potential for permanent structural changes in ocular tissues, such as retinal scarring and corneal nerve loss, necessitates ongoing monitoring and research.

Given these findings, routine ophthalmological examinations should be considered an integral part of post-COVID care, even for asymptomatic individuals. This proactive approach could help detect early signs of ocular complications, allowing for timely intervention and potentially mitigating long-term damage. 

As our understanding of COVID-19‘s effect on ocular health evolves, developing comprehensive strategies to manage these effects and improve outcomes for affected patients will be crucial.

This article originally appeared on Ophthalmology Advisor