Contrast Sensitivity and Color Vision as Biomarkers of the Preclinical Stage of Neurodegeneration in Huntington’s Disease

Abstract

The aim of the study was to investigate contrast sensitivity (CS) and color vision in Huntington's disease (HD), their correlation with clinical and genetic data, and the possibility of using the ophthalmological parameters as biomarkers of preclinical stage of neurodegeneration. Materials and Methods. Participants in the study were divided into two groups, which included 44 HD subjects (main group) and 31 apparently healthy volunteers (control). In the main group, 21 subjects had pre-manifest and 23 manifest HD stage. The groups were age-, sex-, intraocular pressure-, and mean refractive error-matched. CAG (cytosine-adenine-guanine) repeat expansion size in the huntingtin gene, disease duration, and a motor function score according to the UHDRS were evaluated in HD patients. All patients underwent a thorough neurological and ophthalmic examination including CS evaluation using Freiburg Vision Test (FrACT), color vision assessment using Rabkin plates, and computer-assisted campimetry based on ApWay.ru Web platform. Results. The range of the CAG repeat expansion size in the main group was 37-56 repeats (44.3±3.8), the UHDRS motor score 36.3±29.7, disease duration 13.7±7.2 years. CS in HD was reduced, there was a significant difference between the pre-manifest and manifest patients. The CS log inversely correlated with CAG repeat expansion size (r=-0.627; p=0.001). When reading Rabkin plates, HD patients made significantly more nonspecific mistakes than controls. Color differentiation thresholds in the HD group were higher than in the control group in red, green and blue colors. During computer-assisted campimetry, the manifest HD patients made significantly more mistakes in the stimulus shape differentiation giving oral answers than choosing on the screen. Color differentiation thresholds in green (r=0.489; p=0.003) and blue (r=0.416; p=0.014) correlated with the UHDRS score. When plotting ROC curves, the differentiation threshold for blue color had been established to have the best diagnostic value for distinguishing between the control and pre-manifest HD patients. Conclusion. The study results indicate visual sensory deprivation in HD. Color vision disturbances develop early at the pre-manifest HD stage, ahead of the CS decrease signifying early damage to the parvocellular vision pathway. Amnestic aphasia in the manifest HD patients makes it difficult to obtain correct oral answers during visual function evaluation. Color differentiation thresholds proved to be a promising biomarker for early diagnosis of neurodegenerative processes.