A large-scale cohort study identified specific retinal changes that may be linked to future development of amyotrophic lateral sclerosis. The findings support the potential use of noninvasive retinal imaging for early detection.
Led by Chunyang Pang and Yaojia Li of the First Affiliated Hospital of Wenzhou Medical University in China, the researchers analyzed optical coherence tomography (OCT) scans from 53,824 UK Biobank participants. They found that 70 participants developed amyotrophic lateral sclerosis (ALS) during a median follow-up period of 14.11 years. This proportion of patients corresponded to an incidence rate of 10.58 per 100,000 person-years.
A thinner photoreceptor layer (PRL) and a thicker retinal pigment epithelium (RPE) were independently associated with higher ALS risk. Each standard deviation (SD) decrease in PRL thickness was linked to a 19% increased risk, while each SD increase in RPE thickness corresponded to a 20% increase. These associations remained statistically significant after adjusting for demographic, socioeconomic, and clinical factors.
OCT scans were conducted between 2006 and 2010 using a standardized imaging protocol. Measurements from both eyes were averaged, and the lowest-quality 20% of scans were excluded. Participants with ALS at baseline or less than 2 years of follow-up were also excluded.
The associations remained consistent in sensitivity analyses, including after excluding participants with short follow-up periods and those with ocular conditions. The associations were stronger among participants with a history of smoking.
To assess disease specificity, researchers also examined OCT markers in relation to Alzheimer’s disease, Parkinson’s disease, and frontotemporal dementia. No similar associations were found, which suggested that PRL and RPE changes may be specific to ALS.
Due to its structural and developmental similarities to the brain, the retina is increasingly being studied as a site for noninvasive biomarkers in neurodegenerative disease. OCT enables cellular-level imaging and may serve as a useful tool for large-scale risk assessment.
Despite the study’s strengths—large sample size and long follow-up—limitations include its observational design and use of a single time-point OCT measurement. The researchers noted the need for longitudinal and mechanistic studies to clarify whether retinal changes precede ALS onset or reflect early disease activity, as well as explorations into choroidal disease as an additional biomarker for neurodegenerative diseases. "Prospective studies with dynamic retinal monitoring throughout ALS progression may help determine the timing, location, and clinical relevance of retinal changes, as well as their potential role in disease assessment and subtype stratification," the authors concluded.
These findings add to growing evidence that supports the retina as a biomarker site.
The authors reported no conflicts of interest.
Source: PLOS Medicine