Did not report vision problems with his left eye and the ophthalmologic examination revealed no pathology of the left eye, with a corrected visual acuity of 90 .Optical Coherence Tomography in Wilsons’s DiseaseFigure 5. Correlations between layers, VEP parameters and laboratory. A The significant correlations between the laboratory parameters and the mean thickness of the retinal layers and VEP parameters of both eyes are shown and the Pearson or Spearman r is indicated (p,0.05 including the outlier, all comparisons were made using a Pearson analysis except for the Wilson Score, which was analyzed using a Spearman analysis). A The continuous lines resemble linear regressions including, and the dotted lines excluding, an outlier with beginning hepatic failure (the outlier is marked as unfilled dot, Pearson r is indicated considering the outlier). doi:10.1371/journal.pone.0049825.gHowever, the laboratory parameters were indicative of a beginning hepatic failure, with changes of the liver parameters, and he was later diagnosed with a hepatocellular carcinoma. It is possible that changes of the visual pathway due to the hepatic failure, which were not accessible to the ophthalmologic exam, accounted for the prolonged VEP latencies in this patient. The case of this patient stresses the fact that marked changes in VEP latencies can be indicative of a beginning hepatic encephalopathy Zamir, 2002 #422 and should prompt further investigations. We observed no correlation between the OCT parameters and visual acuity using Snellen charts. To analyze the functional consequence of the structural changes observed, studies 1480666 using more sensitive parameters such as analysis of the flicker fusion threshold or low contrast letter recognition are warranted. When discussing the results of the correlations performed in our study, one must bear in mind that even though the single correlations may be significant with a p,0.05, the overall risk of a type I error (false positive result) increases with the number of correlations. Thus, the significant correlations should be interpreted with caution and ideally verified with an independent study. To obtain a more conservative measure of correlation we therefore performed Bonferroni corrections, though this simultaneously increased the risk of a type II error (false negative result). After the Bonferroni correction, only the correlations between macular thickness with GCIP, INL and ONL and between urine copper and serum caeruloplasmin remained significant, which is not astonishing as the macular thickness is greatly influenced 1407003 bythese layers and urine copper and serum caeruloplasmin concentrations are closely linked. Using a linear order 478-01-3 regression based approach, we identified age as the only significant influence on macular thickness as the major retinal parameter, with female sex being MedChemExpress 60940-34-3 associated with thinner macular thickness. Males and females did not differ in age, excluding an age-related artifact. Although a higher macular thickness in males compared to females has been reported before [35?7], the macular thickness in our control cohort did not differ between males and females. A possible explanation for the differences observed in our patients could be that the small differences between men and women, which are most likely hormone mediated, may be accentuated by the elevated copper levels in Wilson’s disease. The fact that the laboratory parameters did not serve as predictors for retinal degeneration measured.Did not report vision problems with his left eye and the ophthalmologic examination revealed no pathology of the left eye, with a corrected visual acuity of 90 .Optical Coherence Tomography in Wilsons’s DiseaseFigure 5. Correlations between layers, VEP parameters and laboratory. A The significant correlations between the laboratory parameters and the mean thickness of the retinal layers and VEP parameters of both eyes are shown and the Pearson or Spearman r is indicated (p,0.05 including the outlier, all comparisons were made using a Pearson analysis except for the Wilson Score, which was analyzed using a Spearman analysis). A The continuous lines resemble linear regressions including, and the dotted lines excluding, an outlier with beginning hepatic failure (the outlier is marked as unfilled dot, Pearson r is indicated considering the outlier). doi:10.1371/journal.pone.0049825.gHowever, the laboratory parameters were indicative of a beginning hepatic failure, with changes of the liver parameters, and he was later diagnosed with a hepatocellular carcinoma. It is possible that changes of the visual pathway due to the hepatic failure, which were not accessible to the ophthalmologic exam, accounted for the prolonged VEP latencies in this patient. The case of this patient stresses the fact that marked changes in VEP latencies can be indicative of a beginning hepatic encephalopathy Zamir, 2002 #422 and should prompt further investigations. We observed no correlation between the OCT parameters and visual acuity using Snellen charts. To analyze the functional consequence of the structural changes observed, studies 1480666 using more sensitive parameters such as analysis of the flicker fusion threshold or low contrast letter recognition are warranted. When discussing the results of the correlations performed in our study, one must bear in mind that even though the single correlations may be significant with a p,0.05, the overall risk of a type I error (false positive result) increases with the number of correlations. Thus, the significant correlations should be interpreted with caution and ideally verified with an independent study. To obtain a more conservative measure of correlation we therefore performed Bonferroni corrections, though this simultaneously increased the risk of a type II error (false negative result). After the Bonferroni correction, only the correlations between macular thickness with GCIP, INL and ONL and between urine copper and serum caeruloplasmin remained significant, which is not astonishing as the macular thickness is greatly influenced 1407003 bythese layers and urine copper and serum caeruloplasmin concentrations are closely linked. Using a linear regression based approach, we identified age as the only significant influence on macular thickness as the major retinal parameter, with female sex being associated with thinner macular thickness. Males and females did not differ in age, excluding an age-related artifact. Although a higher macular thickness in males compared to females has been reported before [35?7], the macular thickness in our control cohort did not differ between males and females. A possible explanation for the differences observed in our patients could be that the small differences between men and women, which are most likely hormone mediated, may be accentuated by the elevated copper levels in Wilson’s disease. The fact that the laboratory parameters did not serve as predictors for retinal degeneration measured.
