diagnosis of optic neuritis (ON) secondary to COVID-19 vaccination; This is a literature report.  The authors report the case of a 39-year-old 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 optic neuritis (ON) was made and the authors 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 visual acuity (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. Humphrey visual field testing revealed global defect in the visual field of the right eye with normal left eye findings. In addition, NMO and MOG laboratory workup came back negative from her hospital stay, confirming her diagnosis of secondary ON. 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. 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. In this case, the authors 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.; Sender's Comments: As there is limited information in the case provided, the causal association between the Reported Event Optic neuritis and the suspect drug cannot be excluded. The case will be reassessed once new information is available. The impact of this report on the benefit/risk profile of the Pfizer drug is evaluated as part of Pfizer procedures for safety evaluation, including the review and analysis of aggregate data for adverse events. Any safety concern identified as part of this review, as well as any appropriate action in response, will be promptly notified to Regulatory Authorities, Ethics Committees, and Investigators, as appropriate. ,Linked Report(s) : US-PFIZER INC-202201346763 Same article, suspect vaccine, patient; different dose and events;