# Analysis of retinal markers and incident amyotrophic lateral sclerosis: An optical coherence tomography-based cohort study

## TL;DR

This study finds that thinner photoreceptor layers and thicker retinal pigment epithelium in the retina may predict future ALS risk, suggesting potential early diagnostic clues.

## Contribution

The study identifies specific retinal biomarkers (PRL and RPE thickness) associated with increased ALS risk using OCT data from a large cohort.

## Key findings

- A thinner photoreceptor layer (PRL) was linked to a 19% increased ALS risk.
- A thicker retinal pigment epithelium (RPE) was associated with a 20% higher ALS risk.
- Findings were more pronounced in smokers and consistent across sensitivity analyses.

## Abstract

Biomarkers are widely recognized as crucial breakthroughs in tackling amyotrophic lateral sclerosis (ALS). Among them, retina markers may hold promise due to the close retina-brain connection and non-invasive, portable detection methods. Thus, using optical coherence tomography (OCT), we investigated the link between baseline cell-level retinal features and future ALS risk.

Participants from the UK Biobank underwent OCT scans to assess retinal layers, macula, and optic disc parameters. Follow-up commenced two years after the baseline period (2006–2010), during which ALS cases were identified using International Classification of Diseases (ICD) codes from medical and assessment records. Cox proportional hazards models were applied to examine the relationship between retinal markers and incident ALS. Over a median follow-up of 14.11 years, 70 ALS cases occurred among 53,824 participants (incidence 10.58 per 100,000 person-years). Most participants were White (94.6%), 44.8% male, with a median age of 58 years. After adjusting for demographics and comorbidities affecting the retina, a standard deviation (SD) decrease of 15.19 µm in photoreceptor layer (PRL) thickness was associated with a 19% (95% confidence interval [7, 29]; p = 0.002) increased risk of ALS, while a SD increase of 26.11 µm in retinal pigment epithelium (RPE) thickness corresponded to a 20% (95% CI [7, 34]; p = 0.002) higher risk. Sensitivity analyses excluding follow-ups of less than 4 and 6 years yielded consistent results. Subgroup analyses showed these findings were more pronounced in smokers. The main limitation of this study is its single time point observational design.

A thinner PRL and thicker RPE may precede the clinical diagnosis of ALS, offering potential clues for early diagnosis and insights into the disease’s pathogenesis.

Amyotrophic lateral sclerosis (ALS) has limited diagnostic and treatment options, creating an urgent need for biomarkers to advance management.

Retinal biomarkers may be emerging for ALS diagnosis due to retina-brain links and non-invasive detection.

Current evidence on early retinal features in ALS is limited.

Cell-level retinal features were assessed using optical coherence tomography (OCT) data from 53,824 participants.

Their association with future ALS risk was investigated over a median follow-up of 14.11 years.

A thinner photoreceptor layer (PRL) and a thicker retinal pigment epithelium (RPE) were found to potentially precede the clinical diagnosis of ALS.

OCT-based assessment of PRL and RPE thickness may offer valuable clues for early ALS diagnosis and insights into its pathogenesis.

The main limitation of this study is its single time point observational design.

Using optical coherence tomography, Chunyang Pang, Yaojia Li and colleagues investigate the link between baseline cell-level retinal features and future amyotrophic lateral sclerosis risk.