Optical Coherence Tomography in Neurodegenerative Disorders

Abstract

Purpose Ophthalmic findings, including abnormalities of the optic nerve and retina, are common features of a number of neurodegenerative disorders. These ophthalmic abnormalities have emerged as potential biomarkers of disease progression in several neurodegenerative conditions. In addition, anterior visual system changes have clinical relevance because they can be a significant cause of disability. Optical coherence tomography (OCT) allows for rapid, non-invasive imaging and quantitative analysis of the optic nerve and retina. Over the past 15 years, OCT has been widely used to investigate axonal and neuronal degeneration in the eye, and the relationship with disease severity in multiple sclerosis, neuromyelitis optica Alzheimer’s disease and Parkinson’s disease. OCT is now frequently utilised in observational studies, clinical practice and therapeutic trials of potential neuroprotective agents. The objectives of the studies outlined in this research thesis were twofold: Firstly, to investigate the morphology of the optic nerve head and retina, using OCT, in patients with neurodegenerative disorders, and to determine the relationship between OCT measurements and disease duration and severity. Methods Subjects with neurodegenerative disorders including muscular dystrophies, Huntington’s disease, Parkinson’s disease, motor neuron disease, ataxias and hereditary spastic paraplegia were recruited. All participants underwent a complete neuro-ophthalmic assessment including retinal photography and OCT examination of the peripapillary retinal nerve fibre layer (RNFL) and macula. Ophthalmic findings were compared with those from a healthy control group. Additionally, neurological assessment was undertaken in order to be able to assess the relationship between OCT findings and disease severity. Results OCT examination was performed in patients with a diverse range of neurodegenerative disorders. There was preferential thinning of the temporal RNFL in the Huntington’s disease and cerebellar ataxia neuropathy vestibular areflexia syndrome (CANVAS) cohorts. Global RNFL thickness was reduced in the Friedreich’s ataxia and hereditary spastic paraplegia (HSP) groups. In the myotonic dystrophy type 1 (DM1), Parkinson’s disease, motor neuron disease and facioscapulohumeral muscular dystrophy (FSHD) groups, there was no significant difference in RNFL thickness between patients and controls. Macular thickness was greater in the myotonic dystrophy type 1 group compared with controls. This was due to a high prevalence of epiretinal membrane, detected with OCT examination. Macular volume was significantly reduced in the Freidreich’s ataxia patient group. There was no significant difference in macular thickness or volume between patients and controls in the Parkinson’s disease, motor neuron disease, Huntington’s disease, CANVAS, FSHD or HSP groups. In the Huntington’s disease group there was a significant correlation between disease duration and both temporal RNFL thickness and macular volume, and a significant relationship between motor assessment scores and macular volume. There was no significant relationship between symptom duration, measures of disability and/or cognitive function and OCT findings in the DM1, Parkinson’s disease, motor neuron disease, CANVAS, HSP, Friedreich’s ataxia or FSHD groups. Conclusions OCT measurements may be potential biomarkers of disease progression in Huntington’s disease patients. The preferential thinning of the temporal RNFL in Huntington’s disease may be due to mitochondrial dysfunction. In addition, OCT assessment has a role in the clinical assessment of patients with myotonic dystrophy, in the detection and monitoring of patients with epiretinal membranes. Larger, longitudinal studies are required in order to determine the relationship between ophthalmic and neurological findings in neurodegenerative disorders, and to further investigate the utility of OCT measurements as potential biomarkers of disease progression in these conditions.