Retinal Imaging in Motor Neuron Disease – Amyotrophic Lateral Sclerosis: A Systematic Review

Motor neuron disease (MND) is a rapidly progressive neurodegenerative disorder characterised by motor neuron death resulting in limb and bulbar paralysis with death from respiratory failure within 2-3 years of diagnosis in most individuals. The commonest subtype, accounting for 80% of individuals, is amyotrophic lateral sclerosis (ALS). There is an urgent need for sensitive and specific biomarkers for diagnosis and disease monitoring. Recent studies suggest retinal abnormalities may arise in MND offering the opportunity for retinal imaging as a non-invasive and scalable biomarker. We conducted a systematic review and narrative summary of studies evaluating retinal imaging modalities (optical coherence tomography [OCT], fundus photography, scanning laser ophthalmoscopy and OCT angiography) in adults with MND. We identified 18 studies in the 25 years between 2000–2024. Most studies reported thinning in the retinal nerve fibre layer, nuclear layers, and choroid in MND compared to healthy controls with a few reporting thickening or vascular changes. Nine studies linked retinal measures to disease severity or duration. Preliminary data support the potential utility of retinal imaging in MND with the need for larger longitudinal studies to investigate further.