Retinal Neurodegeneration in Wilson’s Disease Revealed by Spectral Domain Optical Coherence Tomography

Philipp Albrecht,Gerd Geerling,Orhan Aktas,Axel Methner,Marius Ringelstein,Ann-Kristin Müller,Hans-Peter Hartung,David Finis,Eva Cohn,Harald Hefter,Pablo Villoslada

doi:10.1371/journal.pone.0049825

Abstract

Background/ObjectiveIn addition to cirrhosis of the liver, Wilson’s disease leads to copper accumulation and widespread degeneration of the nervous system. Delayed visual evoked potentials (VEPs) suggest changes to the visual system and potential structural changes of the retina.MethodsWe used the latest generation of spectral domain optical coherence tomography to assess the retinal morphology of 42 patients with Wilson’s disease and 76 age- and sex-matched controls. We measured peripapillary retinal nerve fiber layer (RNFL) thickness and total macular thickness and manually segmented all retinal layers in foveal scans of 42 patients with Wilson’s disease and 76 age- and sex-matched controls. The results were compared with VEPs and clinical parameters.ResultsThe mean thickness of the RNFL, paramacular region, retinal ganglion cell/inner plexiform layer and inner nuclear layer was reduced in Wilson’s disease. VEPs were altered with delayed N75 and P100 latencies, but the N140 latency and amplitude was unchanged. An analysis of the laboratory parameters indicated that the serum concentrations of copper and caeruloplasmin positively correlated with the thickness of the outer plexiform layer and with N75 and P100 VEP latencies.ConclusionNeuronal degeneration in Wilson’s disease involves the retina and changes can be quantified by optical coherence tomography. While the VEPs and the thickness of the outer plexiform layer appear to reflect the current copper metabolism, the thicknesses of the RNFL, ganglion cell/inner plexiform layer, inner nuclear layer and the total paramacular thickness may be the best indicators of chronic neuronal degeneration.

Highlights

Wilson’s disease is an autosomal recessively inherited disorder that leads to copper accumulation and, to hepatic damage and neuropsychological symptoms [1,2]
Common ocular findings of Wilson’s disease include the Kayser–Fleischer ring and sunflower cataracts. Both are due to copper deposition and do not cause visual impairment, suggesting that the observed pathologies in Visual evoked potentials (VEPs) may be explained by retroocular changes
The mean peripapillary retinal nerve fiber layer (RNFL) was significantly thinner compared to age and sex matched controls (Means 6 standard deviation (M6SD): Wilson’s disease 95.368.8 mm vs. controls 99.6610.4 mm, figure 1 A) as was the mean total macular thickness (M6SD: Wilson’s disease 311.2615.79 mm vs. controls 321.0614.8 mm, figure 1 B)

Summary

Introduction

Wilson’s disease is an autosomal recessively inherited disorder that leads to copper accumulation and, to hepatic damage and neuropsychological symptoms [1,2]. Visual evoked potentials (VEPs) have been reported to be abnormal in approximately 50% of symptomatic Wilson’s disease patients [10,11,14,15,16]. Common ocular findings of Wilson’s disease include the Kayser–Fleischer ring and sunflower cataracts. Both are due to copper deposition and do not cause visual impairment, suggesting that the observed pathologies in VEPs may be explained by retroocular changes. 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]

Methods

Results

Conclusion