Anticipating the Long-term Ocular Effects of COVID-19
Although it may feel as if COVID-19 has been in our lives for much longer, the first cases appeared in Wuhan, China, only at the very end of December. As such, information on the natural course of the illness is limited. The virus’ acute effects have certainly become better recognized, but its long-term effects remain largely unknown. The ocular manifestations of this disease are no exception. While COVID-19 is not strongly associated with any acute ocular findings, it is possible that additional symptoms may develop in the later phases of the disease.
Here we will consider four different approaches that might be helpful in anticipating COVID-19’s potential long-term ocular effects: (1) identifying known sequelae of acute ocular manifestations of COVID-19; (2) considering the chronic ocular effects of other viruses; (3) analyzing the long-term ocular manifestations of coronaviruses in animal models; and (4) extrapolating the systemic effects of COVID-19 to the eye.
What We Know About COVID-19’s Acute Ocular Manifestations
Conjunctivitis is the most common acute ocular finding in COVID-19, although it is still somewhat rare, with a prevalence of approximately 1%-5%. There are no specific distinguishing factors in COVID-19; it presents in the typical fashion for a viral conjunctivitis.
If conjunctivitis appeared as the initial clinical sign of COVID-19, it would be especially noteworthy, but this is not supported by current evidence. In one large study, conjunctival congestion mostly (72%) appeared after the development of other symptoms. There is a case report of bilateral conjunctivitis as the initial presenting symptom of COVID-19, but in that scenario the conjunctivitis only preceded the other symptoms by a few hours.
In a study of more than 500 patients, the three most common ocular symptoms associated with COVID-19 were dry eye (20.97%), blurred vision (12.73%), and foreign-body sensation (11.80%), none of which were associated with significant ocular pathology in the anterior or posterior segment.
Retinal findings may also be associated with acute COVID-19 infection. A recent case series reported on 12 patients (6 men, 6 women) with confirmed COVID-19 infection who developed retinal findings between 11 and 33 days after the onset of illness. All were found to have hyperreflective lesions at the ganglion cell and inner plexiform layers, which were primarily localized to the papillomacular bundle. Additionally, four had cotton wool spots and microhemorrhages. There have also been separate reports of two patients who developed paracentral acute middle maculopathy (PAMM) and acute macular neuroretinopathy (AMN) during COVID-19.
When considering the sequelae of conjunctivitis, the most common acute ocular finding of COVID-19, it seems unlikely that major long-term effects will occur secondary to this usually self-limited condition.
The acute retinal findings, however, have more potential to affect the eye over the long term. Cotton wool spots and hemorrhages resolve without major retinal disruption, but PAMM and AMN can lead to retinal atrophy and reduced vision or scotomas.
Other Viruses’ Long-term Ocular Effects
SARS-CoV-2, the virus that causes COVID-19, is in the family of coronaviruses that cause diseases such as severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). In attempting to predict COVID-19’s long-term ocular effects, it is worthwhile to consider how these other coronaviruses affect the eye.
Other coronaviruses may rarely cause acute conjunctivitis, but no ocular complications were documented in the MERS and SARS epidemics. The approximate number of patients who contracted MERS and SARS was relatively small (2500 and 8500, respectively) compared with COVID-19. With limited patients to draw from, establishing these viruses’ long-term ocular effects is difficult. As COVID-19 numbers continue to rise globally, it is possible that it will yet be associated with new ocular effects.
Other viruses outside of the coronavirus family, such as Ebola and Zika, are notorious for causing both acute and chronic ocular effects, including conjunctivitis, conjunctival hemorrhaging, and uveitis. Perhaps the most worrying ocular effect of Ebola was its ability to cause an intense and severe uveitis, even months after the systemic symptoms had resolved.
It is too soon to know whether uveitis might develop in COVID-19 patients in the later autoimmune phase of the disease. The SARS-CoV-2 virus is not exceedingly similar to either the Ebola or Zika virus, both of which had the potential to significantly impact the long-term integrity of the eye in ways that were not initially anticipated.
Ocular Effects of Coronavirus in Animals
An awareness of the chronic effects of coronavirus in animal models may provide useful information about what ocular tissues could be targeted by the virus in humans.
Murine coronavirus can generate experimental COVID retinopathy, which has disastrous consequences on the eye. It can affect all retinal tissues, including the photoreceptors and retinal pigment epithelium. The murine coronavirus infects multiple retinal layers and can lead to retinal fibrosis and atrophy. It is suspected that the coronavirus facilitates the breakdown of the blood-ocular barrier, resulting in widespread inflammation throughout the eye.
These effects have not been noted acutely in humans, but it is possible that the chronic inflammation that persists in murine coronavirus might manifest as chronic ocular inflammation, such as uveitis, in humans.
Systemic Effects of COVID-19 May Predict Long-term Ocular Effects
COVID-19 has been demonstrated to induce a hypercoagulable state and has also been implicated in other clotting abnormalities. The risk for venous thromboembolism, including deep venous thrombosis and pulmonary embolism, is increased in patients with COVID-19. All of these conditions can affect the eye owing to the highly sensitive vasculature of the retina.
Retinal venous occlusions and retinal artery occlusions could occur secondary to the coagulability changes induced by COVID-19. Symptoms that might indicate the presence of a venous or artery occlusion, such as decreased vision, a scotoma, or amaurosis fugax, could potentially go unnoticed by patients in the acute phase of COVID-19 due to the severity of their other symptoms.
Neurocognitive effects have also been documented with COVID-19 and may affect the eye and vision as well. After the acute phase of the illness, some patients with a prolonged recovery time (greater than 3-6 weeks) have reported vision changes. The exact mechanism of these changes is not known. More than one third of patients hospitalized with COVID-19 in Wuhan, China, ultimately had some level of neurocognitive effects, so this symptom may not be uncommon.
Many viruses affect children in ways that are distinct from adult manifestations, which might be the case with the long-term ocular effects of COVID-19. COVID-19 can produce a condition known as multisystem inflammatory syndrome in children (MIS-C), which is clinically similar to Kawasaki disease. Approximately 50% of patients with MIS-C exhibit conjunctivitis acutely, but this condition might also have the potential to produce long-term ocular complications. Anterior uveitis is common in Kawasaki disease but typically resolves in the first 2 months. It is possible that in MIS-C, the uveitis might be more chronic or severe than it is in Kawasaki disease. Rare side effects of Kawasaki disease include vasculitis and neuropathies, conditions that might also develop in patients with MIS-C.
Wait and See
Even after considering the available evidence — the acute ocular findings, the behavior of other coronaviruses in the eye, the retinal infection caused by murine coronavirus, and its impact on circulation and inflammation — we cannot yet predict whether COVID-19 will largely spare the eye or target the delicate ocular tissues later in the course of the disease or months to years afterward. Like so much else with this pandemic, we will have to watch closely and hope for the best.
Brianne N. Hobbs, OD, is associate director of exam innovation at the National Board of Examiners in Optometry in Charlotte, North Carolina. She is currently engaged with the creation of a new clinical skills exam for optometry. She has spent most of her career in academia and has also worked in a hospital-based setting.
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