SLE is a multisystemic disorder that has a very complex pathogenesis comprising multiple factors including gender and environment. These factors cause the formation of both antibodies and immune complexes, which can lead to a systemic, global inflammatory reaction involving multiple organs . In 2019, European Alliance of Associations for Rheumatology/American College of Rheumatology (EULAR/ACR) classified SLE based on positive ANA as an obligatory criterion; in addition to seven clinical (constitutional, hematologic, neuropsychiatric, mucocutaneous, serosal, musculoskeletal, renal) and three immunological (antiphospholipid antibodies, complement proteins, SLE-specific antibodies) domains, and clarified a scoring system of a “weight from 2 to 10.” A patient who has ≥ 10 points will be classified as SLE . Our patient scored 24 points according to the updated criteria. Occular involvement such as keratoconjunctivitis sicca, iridocyclitis, retinal vasculitis, vasoocclusive disease, choroidopathy, and optic neuropathy can be presenting features of SLE . However, it is worth mentioning that there are some differences between SLE-associated optic neuritis and optic neuropathy. Optic neuritis is characterized by the acute unilateral painful loss of vision due to infarction of the optic nerve secondary to arteriolar fibrinoid necrosis, whereas optic neuropathy associated with SLE presents as bilateral, painless vision loss, with or without optic disc swelling due to an ischemic process affecting the optic nerve head and retrobulbar nerve [14, 15]. For SLE-induced optic neuritis or optic neuropathy, advanced testing such as fundus fluorescein angiography (FFA), visual field test, and MRI of orbit with gadolinium scan can be done for differentiation between the diseases [11, 16]. Our patient presented with bilateral acute painless loss of vision with optic disc swelling that was in favor of ischemic optic neuropathy related to SLE-induced vasculitis. In addition, our patient suffered the first attack of transverse myelitis, which was clinically more suggestive of NMO, evidenced by the presence of highly specific anti-NMO IgG antibodies in high titer along with the longitudinally extensive lesions in both cervical and dorsal spinal cord. Moreover, paraparesis and sensory abnormality improved after giving methylprednisolone; however, her vision did not improve substantially. Mehta et al.  reported a case of SLE where the patient suffered recurrent transverse myelitis without optic neuritis due to NMO, evidenced by positive anti-NMO-antibody and longitudinally extensive lesion in the spinal cord. Sequential or concomitant attacks of transverse myelitis and optic neuritis, with contiguous spinal cord MRI lesions extending over three or more vertebral segments with the presence of anti-aquaporin 4 antibodies (AQ4 Ab) not only define NMOSD but also differentiate it from multiple sclerosis [3, 12]. Relapsing–remitting multiple sclerosis (RRMS) is a strong differential of NMOSD. Sometimes it is difficult to distinguish both diseases by clinical features only. A typical MRI pattern of multiple sclerosis is at least one lesion on a T2-weighted scan (which could be T2 spin echo or fluid-attenuated imaging) in both the inferior temporal lobe and adjacent to the lateral ventricle, or either a subcortical lesion with a U-fiber-type morphology (s-shaped or curved) or an ovoid lesion perpendicular to the lateral ventricle (Dawson’s fingers). In the spinal cord, the lesion will be a short segment. This radiological criterion has 92% sensitivity and 96.2% specificity. On the contrary, the presence of anti-aquaporin 4 antibodies with longitudinally extensive lesions in the spinal cord (T2 and FLAIR) goes more in favor of NMOSD . It is clear that our patient had active SLE [fever, oral ulceration, arthralgia, raised erythrocyte sedimentation rate (ESR), high titer anti-ds-DNA, low C3 and C4, and ischemic optic neuropathy] but it is very unlikely that SLE causes longitudinally extensive spinal cord lesion and anti-NMO antibody. That is why we considered NMO as the cause of typical MRI lesions in the spinal cord. To the best of our knowledge, this is the first case in Bangladesh where SLE with acute ischemic optic neuropathy (AION) was associated with NMO; which is extremely rare. For SLE-associated ocular disease, immunosuppressive medications are the mainstay of treatment . High-dose intravenous methylprednisolone (1 g/day for 3 days) followed by oral prednisone (1 mg/kg/day) is the first line of treatment for SLE-associated optic neuropathy . Currently, the first-line therapy for severe NMO is azathioprine or rituximab, second-line therapy is azathioprine to rituximab or vice versa, or mycophenolate mofetil, methotrexate, or mitoxantrone in case of side effects or poor response. However, third-line therapy tocilizumab should be started if disease progression occurs and/or the above treatments fail . In our patient, intravenous methylprednisolone 1 gm was given for five consecutive days followed by oral prednisolone 60 mg per day, hydroxychloroquine 300 mg per day, and mycophenolate mofetil 2 gm per day. The outcome of optic neuropathy related to SLE is variable. Jabs et al.  described that four of their seven patients partially improved following treatment with corticosteroids. Rosenbaum mentioned in their observational study that four patients suffered SLE-associated ischemic optic neuropathy; visual acuity improved only in two of them on intravenous cyclophosphamide therapy because of early presentations and young age . In our patient, visual acuity did not improve adequately, probably because of late presentation (more than 96 hours) and not receiving cyclophosphamide. We believe that early initiation of intravenous cyclophosphamide in conjunction with methylprednisolone is the best treatment option for neuro-ophthalmic manifestations of SLE.