Optic neuritis is an inflammatory demyelinating condition of the optic nerve typically characterised by subacute, unilateral decreased vision and periorbital pain worse with eye movement. Optic neuritis is often the first presenting sign of multiple sclerosis (MS), and thus warrants a thorough evaluation for MS including MRI brain and orbits with contrast as well as laboratory testing [9]. Less commonly, optic neuritis has been known to be a complication of both viral infection and vaccination. There have been reported cases of optic neuritis following influenza, mumps, varicella zoster, cytomegalovirus, and Epstein-Barr infection, as well as following inoculation with influenza, rabies, measles, mumps, rubella (MMR), hepatitis A and B vaccinations [10]. The pathophysiology is likely related to an autoimmune reaction triggered in patients with an underlying predisposition, rather than via direct bacterial or viral spread to the optic nerve [10].

Since the beginning of the COVID-19 pandemic, optic neuritis has been described in many cases of COVID-19 infection, as well as following several cases of COVID-19 vaccination. Both unilateral [11,12,13] and bilateral [6, 7] cases of optic neuritis have been reported, and have occurred in patients with symptoms ranging from mild to severe. The most common presenting symptoms have included pain with eye movements, decreased visual acuity, and headache. This case was unique in that the patient did not have any visual symptoms, perhaps reflecting a subclinical or mild form of optic neuritis that did not impact visual acuity. However, she did exhibit pain with eye movement and optic nerve enhancement.

This patient was likewise unique in that she exhibited restrictions in extraocular motility, which one would not typically see in optic neuritis. Motility deficits have been seen in other inflammatory conditions of the eye that have been associated with COVID-19 infection, including orbital inflammatory pseudotumor and orbital apex syndrome, a syndrome characterized by dysfunction of the optic nerve (II), oculomotor nerve (III), trochlear nerve (IV), abducens nerve (VI), and the first division of the trigeminal nerve (V). Case reports of COVID-19 related orbital inflammatory disease or orbital apex syndrome have been rare [14, 15]. The most common symptoms in these cases have included vision loss, ptosis, periorbital pain, and ophthalmoplegia. Cases of COVID-19 related orbital apex syndrome have most often been associated with concurrent orbital cellulitis or mucormycosis coinfection, which our patient did not have. Moreover, orbital apex syndrome is commonly associated with enhancement in the orbital apex area on MRI, which was not seen in our patient. In our case, the patient’s restrictions in eye movement were limited to right eye supraduction, and may have been related to concomitant cranial nerve involvement, though less likely given her isolated deficit, or more likely, due to extraocular muscle involvement.

This is also the first case to the authors’ knowledge of optic neuritis occurring after both recent COVID infection and booster vaccination. Moreover, our patient began experiencing symptoms of pressure-like eye pain with eye movement within two hours after receiving her booster. This is much quicker than previously documented cases of COVID-19 related optic neuritis, which have occurred days to weeks after initial infection [12, 13], or several weeks after vaccination [8]. Though it is difficult to know precisely what led to this patient’s case of optic neuritis, COVID-19 infection, vaccination, or the combination of the two, the authors suspect that the combination of a recent COVID infection and booster vaccination may have contributed to the hyperacute presentation of her optic neuritis. The patient likely mounted an initial immune response, developing her own antibodies and memory B-cells against COVID-19 after contracting the virus, thus priming her against future exposures. Vaccination with the booster dose may have then triggered a rapid secondary inflammatory reaction that led to her optic neuritis. This is supported by studies demonstrating that COVID-19 recovered patients achieve a higher antibody and memory B-cell response to vaccination compared to COVID-19 naïve patients [16].

Moreover, it is well known that COVID-19 immunity is strongest initially after infection and wanes over time. Thus, the fact that she received her COVID-19 booster shortly after initial infection may have predisposed her to mounting a robust immune reaction, whereby viral antigens from the vaccine immediately triggered an immune response toward host myelin proteins in the central nervous system leading to optic neuritis. To date, there are no other reports of optic neuritis or other systemic immune reactions associated with COVID-19 vaccination after recent COVID-19 infection, and thus it is difficult to know for certain if this relationship is truly responsible for our patient’s presentation. The most recent recommendations by the Centres for Disease Control (CDC) allow for COVID-19 vaccination or booster vaccination as soon as 10 days after COVID-19 infection, which is much sooner than our patient received her COVID-19 booster following infection.

Ultimately, this case represents a rare neuro-ophthalmologic complication of COVID-19, and highlights the importance of considering SARS-CoV-2 infection in patients presenting with new onset visual and inflammatory ophthalmologic symptoms. High clinical suspicion is needed, and multidisciplinary evaluation including by the primary, neurology, and ophthalmology teams are required to determine appropriate treatment, often with high dose corticosteroids. Prognosis and visual recovery are typically good.

In conclusion, the patient presented in this study developed a hyperacute optic neuritis with a mild clinical presentation after receiving her COVID-19 booster vaccination. This case is unique in that the patient was exposed to both the virus and the vaccine prior to her presentation. Though it is difficult to know exactly what caused her presentation, it is possible that the initial exposure to the COVID-19 virus primed the patient’s immune system, leading to a rapid inflammatory response upon COVID vaccination. As our understanding of COVID-19 continues to grow, likely so will our knowledge of the various neuro-ophthalmological sequalae of SARS-CoV-2 infection.