Background Schizophrenia is associated with visual perception and early processing deficits. Retinal optical coherence tomography (OCT) parameters can be biomarkers of neural pathology and disease progression by detecting neurodegenerative changes. Purpose The aim of this study was to detect neurodegenerative changes in schizophrenic patients by OCT and to correlate them to the severity and duration of schizophrenia. Patients and methods This is a comparative case–control study that included 60 participants: 30 male schizophrenics compared with 30 age-matched and sex-matched healthy persons. Both groups were subjected to ophthalmic examination, including visual assessment, anterior-segment examination using slit lamp, and posterior-segment examination by indirect ophthalmoscopy. Schizophrenic patients were subjected to psychometric evaluation using Positive and Negative Syndrome Scale. Then, OCT imaging was done for all participants. Results The schizophrenic group showed thinning of the retinal nerve fiber layer (RNFL) compared with the controls. The difference was statistically significant regarding the average, superior, and nasal quadrants (P=0.002, P