Neurodegeneration in the retina of motoneuron diseases: a longitudinal study in amyotrophic lateral sclerosis and Kennedy's disease

Abstract

Background: To what extent retinal atrophy in neurodegenerative diseases reflects the severity and/or the chronicity of brain pathology or is a local independent phenomenon remains to be clarified. Moreover, whether retinal atrophy has a clinical (diagnostic and prognostic) value in these diseases remains unclear.

Objective: To add light on the pathological significance and clinical value of retinal atrophy in patients with amyotrophic lateral sclerosis (ALS) and Kennedy's disease (KD).

Methods: Thirty-five ALS, thirty-seven KD, and forty-nine age-matched healthy controls (HC) were included in a one-year longitudinal study. Spectrum-domain optical coherence tomography (OCT) was performed at study entry (T0) and after 12 months (T1). Disease duration and functional rating scale (FRS) for ALS and KD patients were correlated to retinal thicknesses.

Results: Compared to HC, peripapillary retinal nerve fiber layer (pRNFL) thickness was significantly thinner in both ALS (p = 0.034) and KD (p = 0.003). pRNFL was thinner in KD compared to ALS, but the difference was not significant. In KD, pRNFL atrophy significantly correlated with both disease severity (r = 0.296, p = 0.035) and disease duration (r = - 0.308, p = 0.013) while no significant correlation was found in ALS (disease severity: r = 0.147, p = 0.238; disease duration: r = - 0.093, p = 0.459). During the follow-up, pRNFL thickness remained stable in KD while significantly decreased in ALS (p = 0.043).

Conclusions: Our study provides evidence of retinal atrophy in both ALS and KD and suggests that retinal thinning is a primary local phenomenon in motoneuron diseases. The clinical value of pRNFL atrophy in KD is worthy of further investigation.

Keywords: Amyotrophic lateral sclerosis; Biomarker; Kennedy’s disease; Motoneuron disease; Neurodegeneration; Optical coherence tomography.

Fig. 1

Bloxplots showing baseline comparisons between HC, ALS, and KD in peripapillary RNFL G, PMB, T/N ratio, and pRNFL sectors (thickness in μm), as well as macular GCIPL, INL, OPNL, RPE, IRL (volume in mm³). *indicates p < 0.05. pRNFL G thickness was significantly lower in both ALS (p = 0.034) and KD (p = 0.003) compared to HC. Sectorial analysis revealed that this significant thinning was localized in the whole temporal sectors (pRNFL N/T, T, TS, and TI) and PMB for ALS, and restricted to the TI sector in KD

Fig. 2

a Spearman correlation analysis between disease severity (based on ALSFRS-R and SBMA-FRS) and pRNFL G, respectively in ALS and KD patients. b Pearson correlation between pRNFL G and disease duration, expressed respectively in months (m) for ALS, and in years (y) for KD. r indicates either Spearman’s rho or Pearson r; p indicates significance. In KD, pRNFL G atrophy significantly correlated with both disease severity (r = 0.296, p = 0.035), and disease duration (r = – 0.308, p = 0.013)

Fig. 3

T0–T1 mean change in retinal pRNFL G thickness and GCIPL, INL, OPNL, RPE, IRL volume for ALS (orange bar) and KD (yellow bar). *indicates p < 0.05. pRNFL G thickness exhibited a stable annual trend in KD (from 97.85 ± 6.53 to 98.11 ± 7.66 μm; mean change of + 0.26 μm), while decreased in ALS (from 100.33 ± 7.95 to 99.60 ± 7.83 μm; mean change of – 0.73 μm), and the thickness change resulted significantly different between the two groups (p = 0.043)