Neuro-Ophthalmic Manifestations of COVID-19

Abstract and Introduction

Abstract

Purpose of Review: To provide a summary of the neuro-ophthalmic manifestations of coronavirus disease 19 (COVID-19), documented in the literature thus far.

Recent Findings: A small but growing literature documents cases of new onset neuro-ophthalmic disease, in the setting of COVID-19 infection. Patients with COVID-19 have experienced acute onset vision loss, optic neuritis, cranial neuropathies, and Miller Fisher syndrome. In addition, COVID-19 increases the risk of cerebrovascular diseases that can impact the visual system.

Summary: The literature on COVID-19 continues to evolve. Although COVID-19 primarily impacts the respiratory system, there are several reports of new onset neuro-ophthalmic conditions in COVID-infected patients. When patients present with new onset neuro-ophthalmic issues, COVID-19 should be kept on the differential. Testing for COVID-19 should be considered, especially when fever or respiratory symptoms are also present. When screening general patients for COVID-19-associated symptoms, frontline physicians can consider including questions about diplopia, eye pain, pain with extraocular movements, decreased vision, gait issues, and other neurologic symptoms. The presence of these symptoms may increase the overall probability of viral infection, especially when fever or respiratory symptoms are present. More research is needed to establish a causal relationship between COVID-19 and neuro-ophthalmic disease, and better understand pathogenesis.

Introduction

In December 2019, a novel coronavirus, severe acute respiratory syndrome 2 (SARS-COV-2) appeared on the international stage, first documented in Wuhan, China. Its associated disease, coronavirus disease 19 (COVID-19), gradually spread internationally, causing a global health emergency. By March 2020, a worldwide pandemic was declared by the WHO, and the international public health crisis persists at the time of writing of this article. The virus continues to ravage the world's community. Per the WHO, by late July there had been over 13.8 million documented cases worldwide and over 593 000 deaths.^[1] In the United States alone there were over 3.6 million cases, and 138 000 deaths.^[2] There is still limited understanding of the disease's pathogenesis, clinical presentation, natural course, and management. There is not yet a proven vaccine or cure for the disease.^[3]

COVID-19 prominently causes flu-like symptoms and respiratory disease. Early in the pandemic, health officials warned the public to be attentive to classic symptoms associated with the virus: fever, cough, and shortness of breath. The majority of hospitalized patients manifested respiratory complications such as pneumonia, and in severe cases acute respiratory distress syndrome.^[4] However, it has become clear that the virus can impact various additional systems of the body. A number of patients have presented with gastrointestinal symptoms such as anorexia, nausea, vomiting, and diarrhea, in the absence of respiratory symptoms; and SARS-COV-2 has been identified in fecal matter.^[5] Physicians have identified characteristic dermatologic signs in COVID-19-positive patients, including urticaria and 'COVID toes'.^[6,7] A significant number of COVID-positive hospitalized patients have developed coagulopathy, which can lead to venous and arterial thrombosis.^[8]

Neurological manifestations are common in those infected with COVID-19. In a retrospective case series conducted in Wuhan, China, of 214 patients infected with the virus, 36.4% had nervous system signs and symptoms including headache, dizziness, hypogeusia, hyposmia, muscle damage, ischemic and hemorrhagic stroke.^[9] A high percentage of COVID-19-positive patients experience the neurologic phenomena of anosmia and ageusia. In a study by Kaye et al.,^[10] 73% of participants experienced anosmia prior to COVID-19 diagnosis. There have been several cases of Guillain–Barre syndrome development in the context of COVID-19 infection, with at least eight patients described in the literature.^[11–14]

A notable number of patients with COVID-19 have experienced ischemic strokes, although the relationship between the virus and cerebrovascular accidents (CVAs) is not yet well understood.^[15] In a single-center, retrospective study in Wuhan, China carried out by Li et al.^[16] of 219 patients with COVID-19, 4.6% developed acute ischemic stroke. During the pandemic, it has come to light that young patients appear to be at risk for stroke when infected with COVID-19. A case series from a New York City Hospital reported five patients under the age of 50 who presented to the hospital over a 2-week period with large-vessel ischemic strokes, and were found to be COVID-19 positive.^[17] The authors noted that at the same medical center, during the prior 12 months, every 2 weeks, the average number of patients under 50 with large-vessel strokes was much lower at 0.73.

Ophthalmic signs and symptoms associated with COVID-19 infection have been documented in the literature as well. In animal models (murine, feline), coronaviruses have been shown to cause a variety of ophthalmic sequelae including conjunctivitis, anterior uveitis, retinitis, and optic neuritis.^[18] Physicians documented eye redness and irritation in patients relatively early in the pandemic, describing 'conjunctival congestion' in Wuhan, China.^[19] Eye pain is a common symptom of infection, and it is well documented that patients can develop viral follicular conjunctivitis in the context of COVID-19 infection as well. A significant portion of infected patients have had conjunctival swabs and tear samples that have tested positive for SARS-COV-2, raising the concern that the virus can be passed via contact with mucosal membranes.^[20] Characteristic retinal findings have been identified in patients with COVID-19. In a case series by Marinho et al.,^[21] all 12 patients included in the study exhibited hyper-reflective lesions at the level of the ganglion cell and inner plexiform layers. Given the ability of SARS-COV-2 to impact the neurological system, it comes as no surprise that the virus can manifest with neuro-ophthalmic signs and symptoms. A small number of case reports describe new onset neuro-ophthalmic diseases in patients with COVID-19. This review will focus on the neuro-ophthalmic manifestations of COVID-19 that have been documented in the literature thus far.