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Optic neuritis secondary to the Pfizer-BioNTech-162b2 COVID-19 vaccine managed with plasmapheresis: A case report and review
Paras P Shah1, Samuel Gelnick2, Daniel Zhu1, Amanda Wong1, Rashmi Verma3
1 Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Great Neck, NY, USA
2 Department of Ophthalmology, Northwell Health, Great Neck, NY, USA
3 Donald and Barbara Zucker School of Medicine at Hofstra/Northwell; Department of Ophthalmology, Northwell Health, Great Neck, NY, USA
|Date of Submission||30-Nov-2021|
|Date of Decision||16-Apr-2022|
|Date of Acceptance||21-Jun-2022|
|Date of Web Publication||03-Aug-2022|
4300 Hempstead Turnpike, Bethpage, NY 11714
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Keywords: BNT162b2, COVID-19, optic neuritis, side effect, vaccine
|How to cite this URL:|
Shah PP, Gelnick S, Zhu D, Wong A, Verma R. Optic neuritis secondary to the Pfizer-BioNTech-162b2 COVID-19 vaccine managed with plasmapheresis: A case report and review. Oman J Ophthalmol [Epub ahead of print] [cited 2022 Aug 10]. Available from: https://www.ojoonline.org/preprintarticle.asp?id=353268
| Introduction|| |
The 2019 novel coronavirus (COVID-19) pandemic has had a devastating public health impact globally, claiming upwards of 5 million lives globally at the time of this report. Safe and effective vaccination has become critical to limiting the spread of the disease. The safety and efficacy profiles of the vaccine are well documented, with a low occurrence of significant adverse events in both the treatment and placebo groups.
In August 2021, the Pfizer COVID-19 vaccine became the first of its type approved by the U.S. Food and Drug Administration, which even suggested benefit of a third dose for certain groups, further promoting its safety and effectiveness. With time, however, additional adverse events have been reported possibly linked to the COVID-19 vaccine, including acute thrombotic events, myocarditis, and corneal transplant rejection. While vaccination for other viruses in the last century has been associated with optic neuritis (ON), to our knowledge, it has yet to be described as an isolated event for a COVID-19 vaccine., Although the mechanism by which these events occur is poorly understood, the underlying pathophysiology seems to include a heightened auto-immunologic response.
As COVID-19 vaccination becomes more widespread, it is important for the medical community to be aware of all available data on possible adverse effects to appropriately advise and treat patients.
| Case Report|| |
We report the case of a 39-year-old African − American female with no significant past medical history who presented to the emergency department (ED) complaining of severe, worsening headaches, and vision loss in the right eye for 3 days. She was sent by an outpatient ophthalmologist, who noted a swollen optic nerve and 20/400 vision in the right eye. She denied changes of vision with position, light sensitivity, fevers, chills, history of autoimmune diseases, weakness, numbness, tingling in extremities, personal or family history of multiple sclerosis or any other demyelinating disorders. Upon further questioning, she stated that she had received her first dose of the Pfizer COVID-19 vaccine 4 weeks earlier and second dose 1 week earlier. She had also contracted COVID-19 infection 3 weeks prior, 1 week after her first vaccine dose. In the ED, the patient had unremarkable routine laboratories, including complete blood count, coagulation time, serum electrolytes, and kidney/liver function tests, and computed tomography of the head without contrast showing no signs of acute pathology. A routine COVID-19 polymerase chain reaction (PCR) test was also negative.
Neuro-ophthalmologic examination of the right eye revealed grade 3+ afferent pupillary defect (APD), pain on extraocular movements (EOM), best-corrected visual acuity (VA) of 20/400, confrontational visual field with generalized constriction, and loss of color vision (0/12). Dilated fundus examination (DFE) revealed swelling in the superior quadrant of the optic nerve with blurring of the disc margin in the right eye. The remainder of the ophthalmological and focused neurological examinations was normal. A preliminary diagnosis of ON was made and we recommended the patient to start 1 g of methylprednisolone intravenously (IV) once daily for 3 days followed by an oral prednisone taper.
Magnetic resonance imaging of the brain revealed no abnormal enhancement intracranially and no acute intracranial pathology. Mild edema and subtle enhancement of the terminal portion of the intraorbital segment of the right optic nerve was noted, extending into the canalicular segment, consistent with the diagnosis of ON. The patient's laboratory workup, including lumbar puncture with cerebrospinal fluid analysis, chest X-ray, erythrocyte sedimentation rate, Lyme antibody, fluorescent treponemal antibody-absorption, and rapid plasma reagin tests were all negative. A repeat ophthalmological examination was stable from prior. A diagnosis of ON secondary to COVID-19 vaccination, as opposed to clinically isolated ON, was considered. The patient was advised to continue the 1 g of IV methylprednisolone daily followed by 11 days of 1 mg/kg oral prednisone.
After the third dose of methylprednisolone, the patient failed to report improvement in her vision or pain in her right eye, and it was decided to continue the 1 mg of IV methylprednisolone daily for two additional days before starting the prednisone taper. Examination revealed that her VA had progressed to no light perception (NLP) in the right eye, and pain was present with EOM in all directions. The examination was otherwise stable from prior. She also reported a new onset of right-sided throbbing headaches, ranging from five to eight on a scale of 10. At this time the diagnoses of neuromyelitis optica (NMO) and myelin oligodendrocyte glycoprotein (MOG) were considered due to the worsening degree of vision loss despite three doses of IV steroids. It was recommended to start plasmapheresis (PLEX) should the patient not improve after the fifth dose of methylprednisolone. A lumbar puncture was also performed which revealed clear fluid and resulted negative for the signs of inflammation or demyelinating disease.
On the 6th day after admission, the patient did not report improvements in her symptoms nor were her examination findings improved. In an effort to rescue her vision in the right eye, the patient was started on PLEX therapy, one session every other day for five sessions. Plasma volume with 5% albumin was the replacement fluid. The patient tolerated the procedure well.
Following the initial PLEX session, the patient reported improvement of pain with EOM's in the right eye, but examination still revealed VA of NLP and 4+ APD in the right eye. In addition, examination revealed worsened nasal optic disc edema in the right eye. After the second PLEX procedure, examination of the right eye revealed improved APD with slow constriction in response to light, and pain on EOM was now only present on right gaze. Just prior to the third PLEX procedure, there was no pain with EOMs in all directions in both eyes. Following the fourth PLEX session, the patient was found to have bare light perception, which had improved to counting fingers at 3 feet in her superior field of view by the fifth PLEX procedure. Given negative findings on the examination and ongoing laboratory workup, the patient was discharged on oral prednisone 60 mg taper and instructed to follow-up in the outpatient setting.
The patient was seen 2 weeks later for follow-up. Examination of the right eye revealed 2+ APD and grade 2 disc edema. VA measured in the office was now hand motion in the right eye and stable in the left eye. Optical coherence tomography (OCT) imaging of the retinal nerve fiber layer (RNFL) in the right eye revealed increased RNFL [Figure 1]. Humphrey visual field testing revealed global defect in the visual field of the right eye with normal left eye findings [Figure 2]. In addition, NMO and MOG laboratory workup came back negative from her hospital stay, confirming her diagnosis of secondary ON.
|Figure 1: Two weeks following hospital discharge, the patient's optical coherence tomography of the retinal nerve fiber layer showed residual optic nerve edema and retinal nerve fiber layer thickening in the right eye, with normal left eye findings. OD: Right eye, OS: Left eye, RNFL: Retinal nerve fiber layer; OCT: Optical coherence tomography, ILM: Inner limiting membrane, S: Superior, T: Temporal, I: Inferior, N: Nasa|
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|Figure 2: Two weeks following hospital discharge, the patient's Humphrey visual field testing revealed a global defect in visual field of the right eye, with normal left eye findings|
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The patient was again seen 6 weeks later for routine follow-up. Examination of the right eye revealed 2+ APD and hand motion VA with the ability to count fingers in the far superior field of vision, stable from prior examination. DFE and fundus photography was notable for significant pallor of the right optic disc [Figure 3]. OCT was positive for near complete thinning of the RNFL sparing the inferonasal portion. All findings were consistent with her previous episode of ON, now with signs of atrophy of the right optic nerve.
|Figure 3: Fundus photography at the 6-week follow-up after hospital discharge revealed significant pallor of the optic disc in the right eye|
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| Discussion|| |
ON is a multifaceted disease, involving inflammation of one or both of the optic nerves, with an estimated prevalence of 1.15 per 1,000 population. Its etiology is not entirely understood. Although adult-onset ON is usually idiopathic, it can sometimes present in the context of chronic autoimmune disease (typically multiple sclerosis), recent infection, or recent vaccination against viral infection. In fact, studies have shown that up to 37% of individuals with multiple sclerosis show signs of ON during their disease process, and as such, this is the most notorious cause of ON.
While no causal relationship between vaccines and ON has been established to date, there are many documented reports of ON in temporal association with various vaccines. Our PubMed literature search of the phrase “'optic neuritis” and “vaccine'” from 1951 to 2021 revealed 77 results, which collectively included 38 detailed cases of ON post vaccination, with the most common vaccines being Hepatitis B (seven cases), Measles, Mumps, and Rubella (six cases), and influenza (five cases). In fact, a recent review of ocular side-effects following vaccination found that ON was the most implicated adverse event over the past decade (2010–2020), with 23 reports; the mean time from inoculation to onset of symptoms was 10.8 days. Another literature review of both the Vaccine Adverse Event Reporting System and PubMed from 1966 to 2003 found 100 reports of ON following hepatitis B immunization. Clearly, the notion that vaccinations may be followed by acute ON is not a novel finding; however, the ocular side effects of COVID-19 mRNA vaccination have not been well elucidated.
In this case, we describe a 39-year-old female who experienced the symptoms of ON 3 days following her second dose of the COVID-19 vaccination. She did not have any history of demyelinating disease and workup for other causes of ON was negative. However, she did test positive for COVID-19 infection 23 days before her diagnosis, which leads us to consider whether the ON was related to COVID-19 vaccination or COVID-19 infection.
We found six published reports of ON in temporal proximity to COVID-19 infection. However, in order to fully evaluate this association, it is critical to understand the timeline between COVID-19 diagnosis and the development of symptoms of ON such as loss of vision and pain with EOMs. Of these six cases, two patients actually tested positive for COVID-19 after the onset of symptoms of ON,, while the rest tested positive 2 days, 4 days, or 7 days, before the onset of symptoms. In the patient described in this case, the onset of symptoms occurred a full 17 days after the last confirmed positive COVID-19 PCR test. In addition, the patient tested negative for COVID-19 on the 1st day of her admission to the hospital, as a part of routine screening, and in fact her examination findings and symptoms worsened after admission. Given the temporal proximity of her symptoms to the second COVID-19 vaccine as opposed to COVID-19 infection, and a negative workup eliminating any other known etiology, we hypothesize that our patient developed ON secondary to COVID-19 vaccination.
On a pathophysiological level, the immunological response following COVID-19 vaccination does in fact align with the aforementioned timeline. COVID-19 mRNA vaccination triggers a relatively intense immunological response; antibody markers including total immunoglobulins (Ig), anti-SARS-COV-2 spike protein receptor-binding domain (RBD), anti-S1/S2 (spike proteins), and anti-RBD IgG can increase by over 350 times in the 21 days after initial vaccination, before reaching a plateau. However, after the second vaccination, these antibody markers can rise up to 30 times further, peaking at 14 days after second dose. In our patient, the examination findings and symptoms deteriorated in correlation with these time points, as her symptoms had reached a nadir at exactly 14 days after her second COVID-19 vaccine, which prompted us to initiate PLEX therapy.
Finally, although there have been limited prior reports of ON following COVID-19 vaccination, these patients' symptoms were not isolated to just ON and neither case required the use of PLEX., One case involved a patient who developed NMO while another case described a patient who developed acute thyroiditis in addition to ON.
| Conclusions|| |
To our knowledge, this is the first reported case of isolated ON secondary to COVID-19 vaccination treated with PLEX. Clinicians should be aware of this severe complication, despite its rarity, and be prepared to treat it. However, the risk must be weighed and should not preclude the extensive benefits of vaccination.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3]