Purpose: To determine if clinical and histopathologic findings were present in the eyes of patients with amyotrophic lateral sclerosis (ALS) and explore correlations to an animal model of ALS.
Methods: Two patients with ALS were studied histopathologically as well as the retinas of ALS/dementia transgenic mice with dysfunctional ubiquilin2, UBQLN2(P497H). Clinical study 1, an observational, cross-sectional study, was performed using optical coherence tomography (OCT) to obtain and compare mean total macular thickness and average and quadrant specific peripapillary retinal nerve fiber layer (pRNFL) scans from 16 patients with ALS to controls. Correlation analysis was performed to evaluate the association with disease duration. Clinical study 2 consisted of measuring visual acuity, color vision, contrast sensitivity, and quality of life in 12 patients.
Results: Histopathologic studies demonstrated intraretinal inclusions in one patient and loss of ganglion cell axons in another. Mouse eyes had intraretinal inclusions in the inner plexiform layers. Total macular volume was thinner in patients compared to controls (P<.05), and 37.5% of patients with ALS had an average pRNFL below the 1st percentile. Total macular and pRNFL thickness correlated inversely with disease duration.
Conclusions: Histopathologic analysis of ALS eyes and mice with the UBQLN2(P497H) mutation, as well as OCT measurements, supports involvement of the anterior visual pathway. We identified pathologies, including intraretinal deposits and axonal loss. pRNFL and total macular thinning found on OCT correlated with disease duration. A pattern of vision loss specific for ALS was not identified. This study confirms ocular involvement in patients and transgenic animals with ALS/dementia.