D the toxic accumulation of copper primarily in the brain and

D the toxic accumulation of copper primarily in the brain and liver (reviewed in [3] and [4]). Intracellular copper deposits impede inhibitor of apoptosis proteins (IAPs), which eventually causes apoptotic cell death [5]. The clinical presentation varies from predominantly hepatic to predominantly neurologic and shows great heterogeneity regarding severity, age of onset and initial symptoms [6]. Wilson’s disease results in severe disability and death if untreated. The key neurological features comprise extrapyramidal symptoms, ataxia, dystonia, seizures and psychiatric symptoms, such as personalitychanges, depression and psychosis (reviewed in [7]). Structural changes in the brain of Wilson’s disease patients have been well documented by magnetic resonance imaging (MRI), which has revealed lesions of the basal ganglia, midbrain, pons and cerebellum and widespread cortical atrophy and white matter changes [8,9]. Histological studies have reported necrosis, gliosis and cystic changes in the brainstem, thalamus, cerebellum and cerebral cortex of Wilson’s disease patients [4]. The functional consequences of these structural changes have been demonstrated in the acoustic, sensory, motor and visual systems and are reflected by disordered multimodality evoked potentials [10?3]. Visual evoked potentials (VEPs) have been reported to be abnormal in approximately 50 of symptomatic Wilson’s disease patients [10,11,14?6]. Common ocular findings of Wilson’s disease include the Kayser leischer ring and sunflower cataracts. Both are due to copper deposition and do not cause visual impairment, suggesting that the observed pathologies in VEPs may beOptical Coherence 58-49-1 Tomography in Wilsons’s Diseaseexplained by retroocular changes. However, [DTrp6]-LH-RH web altered flash electroretinograms in Wilson’s disease are indicative of a retinal pathology [12]. Optical coherence tomography is a fast and non-invasive technique and the latest generation 15755315 of OCT devices is capable of depicting retinal changes at nearly the cellular level [17?5]. In this study, we used up-to-date OCT technology to analyze the retinal changes in Wilson’s disease patients. We compared the morphological changes measured by a state-of-theart spectral domain OCT device with VEPs as functional parameters and correlated these findings with laboratory parameters and a clinical Wilson’s disease score [26].Materials and Methods Ethics StatementThe work was conducted in accordance with the declaration of Helsinki. Written informed consent was obtained from all patients and the study was approved by the local ethics committee, the “Ethikkommission der Heinrich Heine Universitat, Dusseldorf”. ??PatientsWe examined 42 patients with Wilson’s disease and 76 control patients without ophthalmologic, inflammatory or degenerative neurological disease. All Wilson’s disease patients were clinically diagnosed following the established criteria [27], underwent longterm follow-up examinations (mean follow up period 1061 years) and were under therapy with D-penicillamine, trientine, tetrathiomolybdate and/or zinc. The copper and caeruloplasmin concentrations in serum and the 24 h urine copper excretion were measured at the time of the ocular exam and the patients were scored using an established clinical score [26]. All patients underwent formal ophthalmologic exams to rule out confounding ocular pathologies and three eyes were excluded due to central serous retinopathy, vitreomacular traction or paramacular scars. Patients w.D the toxic accumulation of copper primarily in the brain and liver (reviewed in [3] and [4]). Intracellular copper deposits impede inhibitor of apoptosis proteins (IAPs), which eventually causes apoptotic cell death [5]. The clinical presentation varies from predominantly hepatic to predominantly neurologic and shows great heterogeneity regarding severity, age of onset and initial symptoms [6]. Wilson’s disease results in severe disability and death if untreated. The key neurological features comprise extrapyramidal symptoms, ataxia, dystonia, seizures and psychiatric symptoms, such as personalitychanges, depression and psychosis (reviewed in [7]). Structural changes in the brain of Wilson’s disease patients have been well documented by magnetic resonance imaging (MRI), which has revealed lesions of the basal ganglia, midbrain, pons and cerebellum and widespread cortical atrophy and white matter changes [8,9]. Histological studies have reported necrosis, gliosis and cystic changes in the brainstem, thalamus, cerebellum and cerebral cortex of Wilson’s disease patients [4]. The functional consequences of these structural changes have been demonstrated in the acoustic, sensory, motor and visual systems and are reflected by disordered multimodality evoked potentials [10?3]. Visual evoked potentials (VEPs) have been reported to be abnormal in approximately 50 of symptomatic Wilson’s disease patients [10,11,14?6]. Common ocular findings of Wilson’s disease include the Kayser leischer ring and sunflower cataracts. Both are due to copper deposition and do not cause visual impairment, suggesting that the observed pathologies in VEPs may beOptical Coherence Tomography in Wilsons’s Diseaseexplained by retroocular changes. However, altered flash electroretinograms in Wilson’s disease are indicative of a retinal pathology [12]. Optical coherence tomography is a fast and non-invasive technique and the latest generation 15755315 of OCT devices is capable of depicting retinal changes at nearly the cellular level [17?5]. In this study, we used up-to-date OCT technology to analyze the retinal changes in Wilson’s disease patients. We compared the morphological changes measured by a state-of-theart spectral domain OCT device with VEPs as functional parameters and correlated these findings with laboratory parameters and a clinical Wilson’s disease score [26].Materials and Methods Ethics StatementThe work was conducted in accordance with the declaration of Helsinki. Written informed consent was obtained from all patients and the study was approved by the local ethics committee, the “Ethikkommission der Heinrich Heine Universitat, Dusseldorf”. ??PatientsWe examined 42 patients with Wilson’s disease and 76 control patients without ophthalmologic, inflammatory or degenerative neurological disease. All Wilson’s disease patients were clinically diagnosed following the established criteria [27], underwent longterm follow-up examinations (mean follow up period 1061 years) and were under therapy with D-penicillamine, trientine, tetrathiomolybdate and/or zinc. The copper and caeruloplasmin concentrations in serum and the 24 h urine copper excretion were measured at the time of the ocular exam and the patients were scored using an established clinical score [26]. All patients underwent formal ophthalmologic exams to rule out confounding ocular pathologies and three eyes were excluded due to central serous retinopathy, vitreomacular traction or paramacular scars. Patients w.