Retinal axonal degeneration in Niemann-Pick type C disease

J Neurol. 2020 Jul;267(7):2070-2082. doi: 10.1007/s00415-020-09796-2. Epub 2020 Mar 28.


Objective: Niemann-Pick disease type C1 (NPC1) is a rare autosomal-recessive lysosomal storage disorder presenting with a broad clinical spectrum ranging from a severe infantile-onset neurovisceral disorder to late-onset neurodegenerative disease. Optical coherence tomography (OCT) is established to detect retinal degeneration in vivo. We examined NPC1-patients (NPC1-P), clinically asymptomatic NPC1-mutation carriers (NPC1-MC), and healthy controls (HC) to (1) identify retinal degeneration in NPC1-disease and (2) to investigate possible subclinical retinal degeneration in NPC1-MC.

Methods: Fourteen NPC1-P, 17 NPC1-MC, and 31 age-matched HC were examined using spectral-domain OCT. Neurological examinations, clinical scales [modified Disability Rating Scale (mDRS); Scale for the Rating and Assessment of Ataxia (SARA); Spinocerebellar Ataxia Functional Index (SCAFI)], and video-oculography (VOG) were correlated with OCT data.

Results: Macular retinal nerve fiber layer and volumes of combined ganglion cell and inner plexiform layer were significantly lower in NPC1-P compared to HC [mRNFL (µm):0.13 ± 0.01 vs. 0.14 ± 0.02; p = 0.01; GCIPL (mm3):0.60 ± 0.05 vs. 0.62 ± 0.04; p = 0.04]. No significant differences were found in NPC1-MC in comparison to HC. In NPC1-P, the amplitude of upward vertical saccades showed positive associations with peripapillary RNFL (ρ = 0.645; p < 0.05), and thinned GCIP (ρ = 0.609; p < 0.05), but not in NPC1-MC. In NPC1-P correlations between combined outer plexiform layer and outer nuclear layer (OPONL) with mDRS (r = - 0.617; p < 0.05) and GCIP with SARA (r = - 0.622; p < 0.05) were observed. Furthermore, in NPC1-MC, motor scores were negatively associated with pRNFL (ρ = - 0.677; p < 0.01).

Conclusions: Using OCT, we showed retinal degeneration in NPC1-P and significant correlation between retinal neuroaxonal degeneration with clinical measurements. We observed a non-significant trend of retinal degeneration in NPC1-MC correlating with subclinical motor abnormalities. Based on these preliminary data, OCT may be an important marker of neurodegeneration in NPC1-disease after onset of clinical symptoms.

Keywords: Clinical biomarker; Heterozygosity; Niemann–Pick type C; Optical coherence tomography; Retinal neuroaxonal degeneration.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Axons / pathology*
  • Axons / ultrastructure
  • Biomarkers
  • Child
  • Eye Movements / physiology
  • Eye-Tracking Technology
  • Female
  • Heterozygote
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Macula Lutea / pathology
  • Macula Lutea / ultrastructure
  • Male
  • Middle Aged
  • Nerve Degeneration / diagnostic imaging
  • Nerve Degeneration / genetics
  • Nerve Degeneration / pathology*
  • Nerve Degeneration / physiopathology
  • Niemann-Pick C1 Protein
  • Niemann-Pick Disease, Type C / diagnostic imaging
  • Niemann-Pick Disease, Type C / genetics*
  • Niemann-Pick Disease, Type C / pathology*
  • Niemann-Pick Disease, Type C / physiopathology
  • Retinal Degeneration / diagnostic imaging
  • Retinal Degeneration / genetics
  • Retinal Degeneration / pathology*
  • Retinal Degeneration / physiopathology
  • Retinal Ganglion Cells / pathology
  • Retinal Ganglion Cells / ultrastructure
  • Tomography, Optical Coherence
  • Young Adult


  • Biomarkers
  • Intracellular Signaling Peptides and Proteins
  • NPC1 protein, human
  • Niemann-Pick C1 Protein