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Abstract Objective Thinning of the peripapillary retinal nerve fiber layer (p‐RNFL), as measured by optical coherence tomography (OCT), was recently introduced as a promising marker for cerebral neuronal loss in people with epilepsy (PwE). However, its clinical implication remains to be elucidated. We thus aimed to (1) systematically characterize the extent of the retinal neuroaxonal loss in a broad spectrum of unselected PwE and (2) to evaluate the main clinical determinants. Methods In this prospective study, a spectral‐domain OCT evaluation was performed on 98 well‐characterized PwE and 85 healthy controls (HCs) (18–55 years of age). All inner retinal layers and the total macula volume were assessed. Group comparisons and linear regression analyses with stepwise backward selection were performed to identify relevant clinical and demographic modulators of the retinal neuroaxonal integrity. Results PwE (age: 33.7 ± 10.6 years; 58.2% female) revealed a significant neuroaxonal loss across all assessed retinal layers (global pRNFL, P = 0.001, Δ = 4.24 μm; macular RNFL, P

Objective: Thinning of the peripapillary retinal nerve fiber layer (p‐RNFL), as measured by optical coherence tomography (OCT), was recently introduced as a promising marker for cerebral neuronal loss in people with epilepsy (PwE). However, its clinical implication remains to be elucidated. We thus aimed to (1) systematically characterize the extent of the retinal neuroaxonal loss in a broad spectrum of unselected PwE and (2) to evaluate the main clinical determinants. Methods: In this prospective study, a spectral‐domain OCT evaluation was performed on 98 well‐characterized PwE and 85 healthy controls (HCs) (18–55 years of age). All inner retinal layers and the total macula volume were assessed. Group comparisons and linear regression analyses with stepwise backward selection were performed to identify relevant clinical and demographic modulators of the retinal neuroaxonal integrity. Results: PwE (age: 33.7 ± 10.6 years; 58.2% female) revealed a significant neuroaxonal loss across all assessed retinal layers (global pRNFL, P = 0.001, Δ = 4.24 μm; macular RNFL, P < 0.001, Δ = 0.05 mm3; ganglion cell inner plexiform layer, P < 0.001, Δ = 0.11 mm3; inner nuclear layer, INL, P = 0.03, Δ = 0.02 mm3) as well as significantly reduced total macula volumes (TMV, P < 0.001, Δ = 0.18 mm3) compared to HCs (age: 31.2 ± 9.0 years; 57.6% female). The extent of retinal neuroaxonal loss was associated with the occurrence and frequency of tonic–clonic seizures and the number of antiseizure medications, and was most pronounced in male patients. Significance: PwE presented an extensive retinal neuroaxonal loss, affecting not only the peripapillary but also macular structures. The noninvasive and economic measurement via OCT bears the potential to establish as a practical tool to inform patient management, as the extent of the retinal neuroaxonal loss reflects aspects of disease severity and sex‐specific vulnerability. Plain Language Summary: The retina is an extension of the brain and closely connected to it. Thus, cerebral alterations like atrophy reflect also on the retinal level. This is advantageous, as the retina is easily accessible and measureable with help of the optical coherence tomography. Here we report that adults with epilepsy have a significantly thinner retina than healthy persons. Especially people with many big seizures and a lot of medications have a thinner retina. We propose that measurement of the retina can be useful as a marker of disease severity and to inform patient management. [ABSTRACT FROM AUTHOR]