Introduction Optic neuritis (ON) is a blinding inflammatory disease of the optic nerve, typically affecting young adults as described in the Optic Neuritis Treatment Trial (ONTT). However, there is limited information describing ON in patients older than 45 years of age. The aim of this study was to determine the clinical profile of ON in this age group in Malaysia. Methods A retrospective case series study was performed between January 2014 and December 2018 among patients older than 45 years old, treated as ON in Hospital Universiti Sains Malaysia, Kelantan, Malaysia. Clinical features, visual acuity, imaging, laboratory results, aetiologies, and visual outcomes were analyzed. Results This study comprised 17 patients (20 eyes) with a gender distribution of eight males and nine females. The mean age of ON onset was 55.8 ± 7.7 years (46-80 years). Most patients (94.1%) presented with reduced vision and retroorbital pain, and three patients (17.6%) had bilateral eye involvement. Papillitis was observed in 13 eyes (65%), retrobulbar ON in five eyes (25%), and optic atrophy in two eyes. Presenting visual acuity was moderately correlated with final visual outcome (rs= 0.47, n = 20, p < 0.05). Post-treatment visual improvement (good and slight) was reported in 14 eyes (70%), four (20%) had no improvement while the remaining two eyes (10%) had worsening best-corrected visual acuity (BCVA). Infective causes accounted for 23.5% of cases (one ocular syphilis, two ocular tuberculosis, and one case of toxoplasmosis). Most cases (70.6%) were idiopathic ON, and only one case was diagnosed with neuromyelitis optica spectrum disorder (NMOSD). Conclusion ON in Malaysian patients older than 45 years of age has no gender predilection and is most likely to be idiopathic; however, infective ON must still be ruled out. Overall visual outcomes were satisfactory. Among the infective causes, ocular tuberculosis caused poor visual recovery as compared with syphilitic and toxoplasmosis-related ON cases.