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The impact of various neurodegenerative diseases on the retina has been investigated in recent years using optical coherence tomography (OCT). Epilepsy, classified as a neurodegenerative disorder, has been indicated to affect the structural integrity of the retina. Moreover, there is ongoing debate regarding the relative contribution of the disease pathogenesis and the consumption of anti-epileptic drugs (AEDs) to these retinal changes. The lack of systematic reviews has hindered our understanding of the true effects of epilepsy and AEDs on retinal health, as well as the efficacy of OCT in detecting these alterations. To comprehensively review the impact of epilepsy and AEDs on the structure of retina, we thoroughly searched the PubMed, EMBASE, and Web of Science databases to identify relevant articles published until July 7, 2024, and performed a meta-analysis. We updated our search in November, 2024. Random effect models have been used to calculate pooled effect estimates. Nineteen studies with a total number of 1851 eyes were identified. Adult patients showed significant reduction with respect of retinal nerve fiber layer (RNFL) thickness; average, as well as all quadrants. Significant reductions were also detected in all quadrants of ganglion cell complex (GCC). Conversely, average GCC and central macular thickness did not differ significantly between cases and controls. Additionally, in terms of various volume measurements in the retina, significant losses were observed in macular RNFL, ganglion cell-inner plexiform layer and total macula volumes in adult patients. In contrast, the inner nuclear layer volume remained comparable between the 2 groups. In pediatric patients with epilepsy receiving valproic acid, significant reductions was observed in the average RNFL thickness, as well as in the nasal and inferior quadrants; however, there were no significant changes in the thickness of the superior and temporal quadrants of RNFL, nor in foveal thickness. The analysis of pediatric patients receiving levetiracetam indicated no significant changes in retinal structural measurements across various RNFL categories, or in foveal thickness. This meta-analysis revealed the structural retinal alterations following AEDs administration in patients with epilepsy (PwE). OCT appears to be a reliable device that reflects retinal toxicity with AED consumption in PwE., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2025 Elsevier Inc. All rights reserved.)