Systematic review and meta-analysis of retinal biomarkers in frontotemporal dementia and Alzheimer disease
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Key Takeaway
Consider that retinal thinning may differ between frontotemporal dementia and Alzheimer disease, but evidence is preliminary.
This is a systematic review and meta-analysis of retinal biomarkers measured by optical coherence tomography (OCT) and OCT angiography in individuals with frontotemporal dementia (FTD), Alzheimer disease (AD), mild cognitive impairment, TDP-43 proteinopathy, tauopathy, and controls. The analysis included 139 individuals with FTD, 87 with AD, 29 with mild cognitive impairment, 14 with TDP-43 proteinopathy, 5 with tauopathy, and 255 controls.
The authors synthesized findings on retinal nerve fiber layer (RNFL) thickness and ganglion cell layer-inner plexiform layer (GCL-IPL) thickness. For RNFL thickness, the meta-analysis found it was significantly thinner in individuals with FTD compared with AD, with a standardized mean difference (SMD) of -0.61 (95% CI -0.98, -0.24). For GCL-IPL thickness, it was significantly thinner in individuals with FTD compared with controls, with an SMD of -0.55 (95% CI -1.02, -0.08). Pooled analyses across multiple retinal biomarkers were non-significant (SMD -0.19, 95% CI -0.52, 0.14).
The authors acknowledge key limitations, including the need for larger longitudinal studies with standardized OCT/OCTA protocols to determine the diagnostic and prognostic utility of retinal biomarkers in FTD. Follow-up duration and safety data were not reported.
Practice relevance was not reported, and the findings should be interpreted as preliminary evidence from a meta-analysis, not as a basis for clinical decision-making.
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View Original Abstract ↓
Background: Frontotemporal dementia (FTD) lacks widely accessible disease-specific biomarkers. Optical coherence tomography (OCT) and OCT angiography (OCTA) may provide non-invasive measures of retinal changes associated with neurodegeneration. We conducted a systematic review and meta-analysis evaluating retinal biomarkers in FTD compared with Alzheimer disease (AD) and controls. Methods: A systematic search of PubMed and Embase was conducted through April 25, 2026 according to PRISMA guidelines. Studies evaluating OCT/OCTA biomarkers in FTD with comparator groups were included. Inverse weighted random-effects models, publication bias assessments, and meta-regressions were performed. Results: Ten studies involving 139 individuals with FTD, 87 with AD, 29 with mild cognitive impairment, 14 with TDP-43 proteinopathy, 5 with tauopathy, and 255 controls were included in the systematic review; five studies were eligible for meta-analysis. Compared with AD, individuals with FTD demonstrated significantly thinner retinal nerve fiber layer (RNFL) thickness (SMD = -0.61, 95% CI -0.98, -0.24). Compared with controls, individuals with FTD exhibited significantly thinner ganglion cell layer-inner plexiform layer (GCL-IPL) thickness (SMD = -0.55, 95% CI -1.02, -0.08), whereas pooled analyses across multiple retinal biomarkers were non-significant (SMD = -0.19, 95% CI -0.52, 0.14). RNFL thickness correlated negatively with female % in FTD and positively with age in both AD and controls. Conclusions: Individuals with FTD exhibit lower RNFL thickness than AD and lower GCL-IPL thickness than controls, suggesting retinal alterations may reflect neurodegeneration. However, larger longitudinal studies with standardized OCT/OCTA protocols are needed to determine the diagnostic and prognostic utility of retinal biomarkers in FTD
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