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Background Optical coherence tomography (OCT) is a promising tool for detecting subclinical changes in retinal nerve fiber layer (RNFL) and macular volume in multiple sclerosis (MS). Objectives The aim of the study was to assess the relationship of retinal changes in different MS subtypes with and without optic neuritis (ON) with clinical disability, duration of illness, and MRI results. Methods Twenty-four patients with relapsing-remitting subtype and 12 patients with secondary progressive subtype, of age range 16-55 years, with and without ON, and 16 age-matched and sex-matched healthy controls were enrolled in this study; in total, there were 15 male and 37 female participants. Patients were subjected to history, clinical evaluation, Extended Disability Status Score for disease severity, MRI brain with contrast, and OCT to assess the RNFL and macular volume of the optic nerve. The control group underwent OCT. Results RNFL thinning was highly correlated in both subtypes with and without ON in all field quadrants compared with the healthy controls. In addition, retinal and macular thickness inversely correlated with Extended Disability Status Score and disease duration in the progressive group than in the relapsing-remitting type. MRI with contrast inversely correlated with both macular and RNFL thickness in the progressive type. Conclusion Retinal axonal loss is more prominent in advanced stages of disease with proportionally greater thinning in eyes previously affected by clinically evident ON. In the absence of clinically evident ON, OCT is a promising potential biomarker of retinal pathology in MS subtypes. [ABSTRACT FROM AUTHOR]