BRIEF COMMUNICATION Reduction in retinal nerve fiber layer thickness in tuberous sclerosis complex Leonardo Emberti Gialloreti 1,2 & Romina Moavero 3,4 & Sara Marciano 3 & Matteo Pardini 5,6 & Francesca Benassi 2 & Maria Giulia Mutolo 7 & Paolo Curatolo 3 Received: 21 December 2014 /Accepted: 5 April 2015 # Springer-Verlag Berlin Heidelberg 2015 Abstract Purpose The aim of our study was to non-invasively investi- gate central nervous system axonal integrity in patients with tuberous sclerosis complex (TSC). Diffuse microstructural white matter abnormalities reflecting axonal disorganization, reduced/altered myelination, or gliosis have been described in individuals with TSC. Optical coherence tomography (OCT) is a fast, easy-to-perform, non-invasive, and cost-efficient method to assess retinal morphology in vivo and to measure the thickness of the retinal nerve fiber layer (RNFL). Methods In order to assess central nervous system axonal in- tegrity, eight subjects with TSC have been investigated by OCT to evaluate RNFL and they have been compared with matched healthy controls. Results When comparing mean overall RNFL thicknesses of the TSC group with those of the control group, the TSC group presented with significantly lower RNFL values, compared to the control group, in the temporal quadrant (62.5±6.9 vs. 76.9 ±5.4; t =14.438; p <0.0001). Conclusions Since a reduced RNFL thickness might be seen as an indicator of chronic axonal degeneration or lack of appropriate neuronal development, our results support the presence of axonal alterations in TSC and also that white matter disorganization could be much more diffuse than originally thought. Since axonal alterations directly derive from mammalian target of rapamycin (mTOR) overactivation, which occurs early during fetus devel- opment, the RNFL thinning we observed could represent one of the facets of such early neurodevelopmental abnormalities. Keywords Tuberous sclerosis complex . Retinal nerve fiber layer thickness . Optical coherence tomography (OCT) . White matter . Axons . mTOR Introduction Tuberous sclerosis complex (TSC) is an autosomal dominant multisystem disease affecting about 1 child in 6000 newborns and causing benign, circumscribed lesions in almost all organs and tissues, such as the brain, skin, eyes, heart, kidneys, lungs, and liver [1]. It is caused by the mutation in one of the two genes TSC1 (chromosome 9q34) or TSC2 (chromosome 16p13.3), respectively encoding for hamartin and tuberin, leading to an overactivation of the so-called mammalian target of rapamycin (mTOR) signaling pathway and subsequent al- teration of cell proliferation and differentiation [2]. The central nervous system (CNS) is almost invariably involved with the presence of cortical/subcortical tubers, subependymal nodules and/or giant cell astrocytomas, and * Paolo Curatolo curatolo@uniroma2.it 1 Department of Biomedicine and Prevention, University of Rome BTor Vergata^, Rome, Italy 2 Centre for Communication and Neurorehabilitation Research—CNAPP, Rome, Italy 3 Systems Medicine Department, Child Neurology and Psychiatry Unit, Tor Vergata University Hospital of Rome, Via Montpellier, 1, 00133 Rome, Italy 4 Neuroscience Department, Child Neurology Unit, Bambino Gesù Children’ s Hospital, IRCCS, Rome, Italy 5 Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics and Maternal and Child Health, University of Genoa, Genoa, Italy 6 Department of Magnetic Resonance Research Centre on Nervous System Diseases, University of Genoa, Genoa, Italy 7 Department of Ophthalmology, University of Rome BSapienza^, Sant’Andrea Hospital, Rome, Italy Childs Nerv Syst DOI 10.1007/s00381-015-2702-x