A 30-year-old male, diagnosed with AQP4-positive NMOSD 1.5 years previously after a longitudinally extensive transverse myelitis found to have 1:1000 titer of AQP-4 antibody. He was adherent to Ravulizumab since that time with the longest variation from the ideal infusion date being 5 days. He then presented for 1 month of right vision loss. Exam found finger counting visual acuity OD with color vision loss and a large central scatoma. MRI revealed subtle enhancement in the right optic nerve. Free C5 levels are not commercially available, so Functional C5 Total C5 and C5a were tested. Functional C5 was reduced but not completely eliminated (13.8 normal range > 23), and C5a was normal, possibly indicating some successful breakdown of C5 into C5a and C5b consistent with incomplete complement inhibition.  There was a significant amount of weight gained during observation period.

Acute treatment involved high-dose intravenous corticosteroids for 5 days followed by plasmapheresis for 5 days, leading to only partial visual improvement (20/200 OD). Given the objective evidence of incomplete complement inhibition and the breakthrough disease, the patient opted to transition from Ravulizumab to Eculizumab for long-term management. Further C5a level monitoring is planned to guide ongoing therapy.