Visual dysfunction may quietly precede the first neurological symptoms of Alzheimer's, Huntington's, MS, and more.
A recent systematic review of 53 studies covering 32 distinct diseases revealed that the eyes may act as an early warning system for a wide range of neurodevelopmental and neurodegenerative conditions.
Researchers at The Warren Alpert Medical School of Brown University and Weill Cornell Medicine categorized 13 neurodevelopmental and 19 neurodegenerative disorders. Across these groups, they consistently found that various visual impairments—detected through noninvasive eye examinations—were present prior to or alongside neurological symptoms. These manifestations included retinal nerve fiber thinning, optic atrophy, abnormal eye movements, and changes in retinal blood flow.
In Alzheimer’s disease, several studies observed structural retinal changes that were linked to cognitive decline. One study of 75 patients found that reduced retinal nerve fiber layer thickness correlated with smaller brain volumes, including the hippocampus and amygdala. Additional studies showed that patients with Alzheimer’s and mild cognitive impairment had lower retinal vessel density and reduced blood perfusion, which correlated with poorer cognitive and executive function.
The researchers noted similar trends in patients with Huntington’s disease. A study that compared patients with healthy controls found significant thinning in specific retinal layers. Thinning of the macular inner nuclear layer was closely associated with cognitive performance, suggesting that retinal measurements may serve as biomarkers for cognitive function.
In Parkinson’s disease, visual changes extended beyond motor symptoms. Studies reported reduced contrast sensitivity, impaired visual acuity, and thicker retinal photoreceptor layers, particularly in patients with visual hallucinations. Additional findings indicated that patients with different forms of synucleinopathies could be classified based on combined motor and visual symptoms.
Patients with Joubert syndrome demonstrated significant associations between retinal dystrophy and intellectual disability. Half of the children studied showed retinal dysfunction through abnormal electroretinography and visual evoked potentials, even when fundus examinations appeared normal.
In multiple sclerosis, visual symptoms were widespread. One large cohort study reported disturbances in 80% of 5,478 patients that increased with longer disease duration. In amyotrophic lateral sclerosis, ocular movement abnormalities were present in 64.2% of patients, with distinct patterns in spinal vs bulbar onset forms.
Other disorders, including Fragile-X associated tremor/ataxia syndrome, Gaucher’s disease, neuronal ceroid lipofuscinoses, and leukodystrophies, also showed measurable visual impairments. Abnormal eye movements, retinal degeneration, and optic atrophy were frequently reported across these conditions.
The review authors concluded that noninvasive imaging techniques such as optical coherence tomography, electroretinography, and visual evoked potentials can detect subtle retinal changes that reflect early or ongoing central nervous system pathology. The retina’s accessibility allows repeated measurements over time, which can provide a valuable window into neurological health.
While further longitudinal studies are needed to validate these findings across larger populations and to "uncover the underlying mechanisms of visual dysfunction in neurological conditions," the authors wrote, evidence suggests that ocular assessments may play a growing role in the early detection, monitoring, and management of neurological diseases.
The authors reported no conflicts of interest.
Source: Eye and Brain
