NEURO-OPHTHALMOLOGY Physiological evidence for impairment in autosomal dominant optic atrophy at the pre-ganglion level Aldina Reis & Catarina Mateus & Teresa Viegas & Ralph Florijn & Arthur Bergen & Eduardo Silva & Miguel Castelo-Branco Received: 21 January 2012 / Revised: 8 June 2012 / Accepted: 2 July 2012 / Published online: 4 August 2012 # Springer-Verlag 2012 Abstract Background Functional studies in patients with autosomal dominant optic atrophy (ADOA) are usually confined to analysis of physiological and clinical impact at the ganglion cell (GG) and post GC levels. Here we aimed to investigate the impact of the disease at a pre-GC level and its correla- tion with GC/post-GC related measures. Methods Visual function was assessed in a population of 22 subjects (44 eyes) from 13 families with ADOA submitted to OPA1 mutation analysis. Quantitative psychophysical methods were used to assess konio and parvocellular chro- matic pathways (Cambridge Colour Test) and distinct ach- romatic spatial frequency channels (Metropsis Contrast Sensitivity Test). Preganglionic and GC measures were assessed with the Multifocal Electroretinogram (mfERG) and Pattern Electroretinogram (PERG) respectively. Global Pattern and Multifocal VEP (visual evoked potentials) were used to assess retinocortical processing, in order to charac- terize impaired processing at the post GC level. Perimetric sensitivity, retinal and ganglion cell nerve fibre layer (RNFL) thickness measurements were also obtained. Results Chromatic thresholds were significantly increased for protan, deutan and tritan axes (p <<0.001 for all comparisons) and achromatic contrast sensitivity (CS) was reduced for all studied six spatial frequency channels (p <<0.001). We ob- served significant decreases in peripapillary (p ≤ 0.0008), mac- ular (ring2: p 0 0.02; ring 3: p <0.0001) RNFL, as well as in overall retinal thickness (p <0.0001 in all regions, except the central one). Interestingly, we found significant decreases in pre-ganglionic multifocal ERG response amplitudes (P1- wave: p ≤ 0.005) that were correlated with retinal thickness (ring 2: r 0 0.512; p 0 0.026/ring 3: r 0 0.583; p 0 0.011) and visual acuity (r 0 0.458; p 0 0.03, central ring 1). Reductions in GC and optic nerve responses amplitude (PERG: p <0.0001, P50 and N95 components; Pattern VEP: p <0.0001, P100) were accompanied by abnormalities of the MfVEP, primarily in central locations (ring 1: p 0 0.0007; ring 2: p 0 0.012). Conclusions In the ADOA model of ganglion cell damage, parvo-, konio- and magnocellular pathways are concomi- tantly affected. Structural changes and physiological impair- ment also occurs at a preganglionic level, suggesting a retrograde damage mechanism with a significant clinical The authors have full control of all primary data, and they agree to allow Graefe’ s Archive for Clinical and Experimental Ophthalmology to review their data upon request. A. Reis : C. Mateus : T. Viegas : E. Silva : M. Castelo-Branco Visual Neuroscience Laboratory, Institute of Biomedical Research on Light and Image (IBILI), Faculty of Medicine, University of Coimbra, Coimbra, Portugal A. Reis : E. Silva Coimbra University Hospital, Coimbra, Portugal R. Florijn : A. Bergen The Netherlands Institute for Neuroscience (NIN), Royal Netherlands Academy of Arts and Sciences (KNAW), Amsterdam, The Netherlands A. Bergen Department of Ophthalmology, Academic Medical Centre (AMC), Amsterdam, The Netherlands A. Bergen Department of Clinical Genetics, AMC, Amsterdam, The Netherlands A. Reis (*) : M. Castelo-Branco (*) Visual Neuroscience Laboratory, IBILI, Azinhaga de Santa Comba, Celas, 3000-548 Coimbra, Portugal e-mail: aldinareis@gmail.com e-mail: mcbranco@ibili.uc.pt Graefes Arch Clin Exp Ophthalmol (2013) 251:221–234 DOI 10.1007/s00417-012-2112-7