A systematic review and meta-analysis of OCT-based ophthalmic changes in amyotrophic lateral sclerosis.

Asmar Ahsan; Ju-Chi Ou; Pritha Majumder; Yung-Hsiao Chiang; Jeffrey K Huang; Chi-Chen Sarah Huang

doi:10.1016/j.jneuroim.2026.579028

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A systematic review and meta-analysis of OCT-based ophthalmic changes in amyotrophic lateral sclerosis.

Asmar Ahsan·Ju-Chi Ou·Pritha Majumder·Yung-Hsiao Chiang·Jeffrey K Huang·Chi-Chen Sarah Huang

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Abstract

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease marked by motor decline and respiratory failure. Optical coherence tomography (OCT), a non-invasive imaging technique, has been explored for detecting retinal structural changes that may reflect neurodegeneration in ALS. While some studies report thinning of retinal layers, findings remain inconsistent. Therefore, a meta-analysis is needed to clarify the extent of retinal involvement and the potential of OCT as a biomarker in ALS. METHODS: A systematic literature search was conducted across PubMed, EMBASE, and Cochrane databases for studies published between 2010 and May 2025. Study quality was assessed using the Newcastle-Ottawa Scale (NOS), and publication bias was evaluated through funnel plot asymmetry and Egger's test. Pooled effect sizes were calculated using random-effects models to account for between-study heterogeneity, and differences in OCT parameters between ALS patients and healthy controls were expressed as standardized mean differences (SMD) with 95% confidence intervals (CI). Statistical heterogeneity was quantified using the I2 statistic. RESULTS: A total of 17 studies were included in the present meta-analysis. The primary unadjusted global model demonstrated significant reduction of retinal nerve fibre layer (RNFL) thickness in ALS patients compared to controls (unadjusted SMD = -0.295, 95% CI: -0.522, -0.068). Upon applying a Design Effect variance inflation model to address fellow-eye non-independence, the pooled estimate remained robustly significant across a conservative range of intraclass correlations (SMD ranged from -0.256 to -0.249). Subgroup analyses revealed that RNFL thinning was particularly pronounced in spinal-onset ALS (SMD = -0.54, 95% CI: (-0.98, -0.10). When studies were stratified by the region of conduct, RNFL and macular thinning reached statistical significance only within the non-Asian subgroup, though the formal test for subgroup differences was not significant. CONCLUSION: This meta-analysis demonstrates significant bilateral RNFL thinning in ALS, with relative preservation of the Inner Nuclear Layer and Ganglion Cell Layer - Inner Plexiform Layer, supporting retinal neurodegeneration as a feature of this multisystem disorder. SYSTEMATIC REVIEW REGISTRATION: PROSPERO identifier CRD420251076035.

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Humans Amyotrophic Lateral Sclerosis Tomography, Optical Coherence Retina Amyotrophic lateral sclerosis Biomarker Optical coherence tomography Retinal nerve fibre layer Journal Article Systematic Review Meta-Analysis

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Asmar Ahsan, Ju-Chi Ou, Pritha Majumder, Yung-Hsiao Chiang, Jeffrey K Huang, Chi-Chen Sarah Huang. 2026-07-24. A systematic review and meta-analysis of OCT-based ophthalmic changes in amyotrophic lateral sclerosis.. https://doi.org/10.1016/j.jneuroim.2026.579028

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Amyotrophic Lateral Sclerosis subject Humans subject Journal Article subject Journal Article; Systematic Review; Meta-Analysis resource Meta-Analysis subject Optical coherence tomography subject Systematic reviews study

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