BackgroundProgressive neurodegeneration is a common consequence of epilepsy, which has a negative impact on the patient’s quality of life. This study aimed to predict neurodegeneration in patients with epilepsy (PwE) through assessment of the retinal nerve fiber layer (RNFL), ganglion cell complex (GCC) thickness, and central macular thickness (CMT) using optical coherence tomography (OCT).ResultsA cross-sectional study was done on 60 patients with idiopathic epilepsy and 30 healthy volunteers. They were subjected to a full neurological examination, ophthalmological assessment, and OCT for assessment of retinal layers, and cognitive examination using Addenbrooke’s scale. PwE had lower cognitive scores, including memory (13.97 ± 2.52), attention (15.95 ± 1.85), language (24.08 ± 1.71), and fluency (6.10 ± 2.05), compared to controls (20.53 ± 3.5), (17.13 ± 1.53), (24.83 ± 0.99), and (8.87 ± 2.39), respectively. There was a significant thinning in average RNFL thickness (84.27 ± 7.66), inferior RNFL thickness (99.33 ± 10.19), average GCC thickness (83.17 ± 9.76), and superior GCC thickness (84.83 ± 7.27) in the epilepsy group compared to controls (105.70 ± 8.73), (104.93 ± 9.75), (101.50 ± 4.84), and (100.53 ± 4.09), respectively. PwE had significantly higher focal macular volume loss (1.17 ± 1.22) versus (0.11 ± 0.21) and a higher insignificant global macular volume loss (1.88 ± 2.32) versus (1.37 ± 0.65) in controls, respectively. Superior GCC thickness was significantly lower in the uncontrolled patients (82.53 ± 6.23) compared to the controlled patients (87.13 ± 7.60), while CMT was significantly lower in the polytherapy group compared to the monotherapy group. There was a significant positive correlation between the age of epilepsy onset and verbal fluency (r = 0.382, p = 0.003). Epilepsy duration had significant negative correlations with memory (r = − 0.364, p = 0.004), inferior RNFL thickness (r = − 0.324, p = 0.012), perifoveal thickness (r = − 0.353, p = 0.006), and inferior (perifoveal) thickness (r = − 0.365, p = 0.004).ConclusionPwE receiving anti-seizure medications (ASMs) have reduced GCC, RNFL, and CMT and lower cognitive functions compared to controls. OCT may be a useful tool for detection of neurodegeneration in PwE.