Bilateral immune-mediated optic neuritis following HPV vaccination in an adolescent: diagnostic challenges and a rare clinical presentation

BACKGROUND: Optic neuritis (ON) is an inflammatory condition of the optic nerve that causes damage to the myelin sheath and nerve fibers, leading to acute visual impairment. While often idiopathic, ON is increasingly recognized in association with immune-mediated triggers, including post-vaccination phenomena. The proposed pathophysiology involves molecular mimicry, where vaccine-induced antigens trigger a cross-reactive immune response against myelin basic protein. Distinguishing vaccine-associated ON from primary demyelinating diseases, such as Multiple Sclerosis (MS) or Neuromyelitis Optica Spectrum Disorder (NMOSD), poses as significant diagnostic challenge, particularly in adolescents. Prompt differentiation is essential to guide clinical management and therapeutic interventions. CASE PRESENTATION: We report a case of a previously healthy 15-year-old female who presented with a two week history of painful visual loss in the right eye, occurring seven days after quadrivalent HPV vaccination. Examination revealed marked asymmetry in visual acuity and a right-sided relative afferent pupillary defect (RAPD). Other cranial nerves (III-XII), motor, sensory, and cerebellar examinations were unremarkable; no papilledema was noted. Laboratory investigations and cerebrospinal fluid (CSF) analysis were normal, except for mild microcytic anemia. MRI of the brain, orbits, and spine demonstrated bilateral optic nerve and perineural enhancement without evidence of demyelinating plaques, confirming bilateral optic neuritis. Autoimmune serology and metabolic panels (ANA, B12, folate, zinc) were within normal limits; serum AQP4-IgG and MOG-IgG were not available at the time of writing the report. The patient received five days of intravenous methylprednisolone, resulting in substantial visual recovery at follow-up. CONCLUSION: This case demonstrates the diagnostic complexity of optic neuritis in adolescents and highlights the necessity of maintaining a high index of clinical suspicion for vaccine-associated immune-mediated events. Although bilateral optic neuritis temporally associated with vaccination is rare and the precise pathophysiological link remains a subject of ongoing debate, a thorough assessment of the clinical chronology and temporal relationship to immunization can facilitate a prompt diagnosis. Timely intervention with corticosteroids is essential to mitigate progression and prevent permanent visual sequelae. However, long-term longitudinal surveillance is mandatory to distinguish such monophasic episodes from the initial manifestation of a chronic demyelinating disease.