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

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.

Wilson’s disease: A review of what we have learned

“…Both manifestations may resolve with continued therapy [39] . Small fiber peripheral neuro pathy involving the corneal nerve plexus [40] , as well as neuronal degeneration involving the retina have also been described [41] , using novel techniques such as corneal confocal microscopy and spectral domain optical coherence tomography, respectively. Psychiatric abnormalities, which may be present before hepatic or neurological signs in up to one third of patients [42] , include decreased academic performance or personality changes, sexual exhibitionism, impulsiveness, labile mood, inappropriate behavior, depression, paranoia, and schizophrenia, leading also to suicide in a discrete number of cases [15,33,43,44] .…”

Alterations of the outer retina in non‐arteritic anterior ischaemic optic neuropathy detected using spectral‐domain optical coherence tomography

“…Aside from the small number of patients and the same patients having no serial OCT, another limitation of our work is the incomparability of the peripapillary and macular findings as the macular retinal layers were automatically detected, whereas the peripapillary retinal layers were manually measured using composite layers as previously described. [38][39][40] However, given the large number of multiple comparisons, we were required to use a general estimation equation as a conservative statistical model. To strike a balance between the level of significance and our study results, we designated P values of 0.05-0.1 as marginally statistically significant.…”

Role of the P-Type ATPases, ATP7A and ATP7B in brain copper homeostasis

“…The essential requirement for copper and ATP7B for retinal structure integrity is underscored by reduced thickness of total macula as well as ganglion cell and inner plexiform layer in WD patients. Up to 50% of WD patients have abnormal visual evoked potentials (VEPs; Albrecht et al, 2012). Immunohistochemical studies of mouse and human retina identified the presence of ATP7A in the retinal pigment epithelium (RPE), outer plexiform layer (OPL), and ganglion cell layer (GCL) of the BALB/c mouse retina (Krajacic et al, 2006).…”