Peripheral Retinal Imaging Biomarkers for Alzheimer's Disease: A Pilot Study

Lajos Csincsik, Thomas J MacGillivray, Erin Flynn, Enrico Pellegrini, Giorgos Papanastasiou, Neda Barzegar-Befroei, Adrienne Csutak, Alan C Bird, Craig W Ritchie, Tunde Peto, Imre Lengyel

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Abstract

PURPOSE: To examine whether ultra-widefield (UWF) retinal imaging can identify biomarkers for Alzheimer's disease (AD) and its progression.

METHODS: Images were taken using a UWF scanning laser ophthalmoscope (Optos P200C AF) to determine phenotypic variations in 59 patients with AD and 48 healthy controls at baseline (BL). All living participants were invited for a follow-up (FU) after 2 years and imaged again (if still able to participate). All participants had blood taken for genotyping at BL. Images were graded for the prevalence of age-related macular degeneration-like pathologies and retinal vascular parameters. Comparison between AD patients and controls was made using the Student t test and the χ2 test.

RESULTS: Analysis at BL revealed a significantly higher prevalence of a hard drusen phenotype in the periphery of AD patients (14/55; 25.4%) compared to controls (2/48; 4.2%) [χ2 = 9.9, df = 4, p = 0.04]. A markedly increased drusen number was observed at the 2-year FU in patients with AD compared to controls. There was a significant increase in venular width gradient at BL (zone C: 8.425 × 10-3 ± 2.865 × 10-3 vs. 6.375 × 10-3 ± 1.532 × 10-3, p = 0.008; entire image: 8.235 × 10-3 ± 2.839 × 10-3 vs. 6.050 × 10-3 ± 1.414 × 10-3, p = 0.004) and a significant decrease in arterial fractal dimension in AD at BL (entire image: 1.250 ± 0.086 vs. 1.304 ± 0.089, p = 0.049) with a trend for both at FU.

CONCLUSIONS: UWF retinal imaging revealed a significant association between AD and peripheral hard drusen formation and changes to the vasculature beyond the posterior pole, at BL and after clinical progression over 2 years, suggesting that monitoring pathological changes in the peripheral retina might become a valuable tool in AD monitoring.

Original languageEnglish
JournalOphthalmic Research
Early online date05 Apr 2018
DOIs
Publication statusEarly online date - 05 Apr 2018

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Alzheimer Disease
Biomarkers
Ophthalmoscopes
Retinal Vessels
Fractals
Macular Degeneration
Disease Progression
Retina
Lasers
Pathology
Students
Phenotype

Keywords

  • Journal Article

Cite this

Csincsik, Lajos ; MacGillivray, Thomas J ; Flynn, Erin ; Pellegrini, Enrico ; Papanastasiou, Giorgos ; Barzegar-Befroei, Neda ; Csutak, Adrienne ; Bird, Alan C ; Ritchie, Craig W ; Peto, Tunde ; Lengyel, Imre. / Peripheral Retinal Imaging Biomarkers for Alzheimer's Disease: A Pilot Study. In: Ophthalmic Research. 2018.
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abstract = "PURPOSE: To examine whether ultra-widefield (UWF) retinal imaging can identify biomarkers for Alzheimer's disease (AD) and its progression.METHODS: Images were taken using a UWF scanning laser ophthalmoscope (Optos P200C AF) to determine phenotypic variations in 59 patients with AD and 48 healthy controls at baseline (BL). All living participants were invited for a follow-up (FU) after 2 years and imaged again (if still able to participate). All participants had blood taken for genotyping at BL. Images were graded for the prevalence of age-related macular degeneration-like pathologies and retinal vascular parameters. Comparison between AD patients and controls was made using the Student t test and the χ2 test.RESULTS: Analysis at BL revealed a significantly higher prevalence of a hard drusen phenotype in the periphery of AD patients (14/55; 25.4{\%}) compared to controls (2/48; 4.2{\%}) [χ2 = 9.9, df = 4, p = 0.04]. A markedly increased drusen number was observed at the 2-year FU in patients with AD compared to controls. There was a significant increase in venular width gradient at BL (zone C: 8.425 × 10-3 ± 2.865 × 10-3 vs. 6.375 × 10-3 ± 1.532 × 10-3, p = 0.008; entire image: 8.235 × 10-3 ± 2.839 × 10-3 vs. 6.050 × 10-3 ± 1.414 × 10-3, p = 0.004) and a significant decrease in arterial fractal dimension in AD at BL (entire image: 1.250 ± 0.086 vs. 1.304 ± 0.089, p = 0.049) with a trend for both at FU.CONCLUSIONS: UWF retinal imaging revealed a significant association between AD and peripheral hard drusen formation and changes to the vasculature beyond the posterior pole, at BL and after clinical progression over 2 years, suggesting that monitoring pathological changes in the peripheral retina might become a valuable tool in AD monitoring.",
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Csincsik, L, MacGillivray, TJ, Flynn, E, Pellegrini, E, Papanastasiou, G, Barzegar-Befroei, N, Csutak, A, Bird, AC, Ritchie, CW, Peto, T & Lengyel, I 2018, 'Peripheral Retinal Imaging Biomarkers for Alzheimer's Disease: A Pilot Study', Ophthalmic Research. https://doi.org/10.1159/000487053

Peripheral Retinal Imaging Biomarkers for Alzheimer's Disease: A Pilot Study. / Csincsik, Lajos; MacGillivray, Thomas J; Flynn, Erin; Pellegrini, Enrico; Papanastasiou, Giorgos; Barzegar-Befroei, Neda; Csutak, Adrienne; Bird, Alan C; Ritchie, Craig W; Peto, Tunde; Lengyel, Imre.

In: Ophthalmic Research, 05.04.2018.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Peripheral Retinal Imaging Biomarkers for Alzheimer's Disease: A Pilot Study

AU - Csincsik, Lajos

AU - MacGillivray, Thomas J

AU - Flynn, Erin

AU - Pellegrini, Enrico

AU - Papanastasiou, Giorgos

AU - Barzegar-Befroei, Neda

AU - Csutak, Adrienne

AU - Bird, Alan C

AU - Ritchie, Craig W

AU - Peto, Tunde

AU - Lengyel, Imre

N1 - © 2018 S. Karger AG, Basel.

PY - 2018/4/5

Y1 - 2018/4/5

N2 - PURPOSE: To examine whether ultra-widefield (UWF) retinal imaging can identify biomarkers for Alzheimer's disease (AD) and its progression.METHODS: Images were taken using a UWF scanning laser ophthalmoscope (Optos P200C AF) to determine phenotypic variations in 59 patients with AD and 48 healthy controls at baseline (BL). All living participants were invited for a follow-up (FU) after 2 years and imaged again (if still able to participate). All participants had blood taken for genotyping at BL. Images were graded for the prevalence of age-related macular degeneration-like pathologies and retinal vascular parameters. Comparison between AD patients and controls was made using the Student t test and the χ2 test.RESULTS: Analysis at BL revealed a significantly higher prevalence of a hard drusen phenotype in the periphery of AD patients (14/55; 25.4%) compared to controls (2/48; 4.2%) [χ2 = 9.9, df = 4, p = 0.04]. A markedly increased drusen number was observed at the 2-year FU in patients with AD compared to controls. There was a significant increase in venular width gradient at BL (zone C: 8.425 × 10-3 ± 2.865 × 10-3 vs. 6.375 × 10-3 ± 1.532 × 10-3, p = 0.008; entire image: 8.235 × 10-3 ± 2.839 × 10-3 vs. 6.050 × 10-3 ± 1.414 × 10-3, p = 0.004) and a significant decrease in arterial fractal dimension in AD at BL (entire image: 1.250 ± 0.086 vs. 1.304 ± 0.089, p = 0.049) with a trend for both at FU.CONCLUSIONS: UWF retinal imaging revealed a significant association between AD and peripheral hard drusen formation and changes to the vasculature beyond the posterior pole, at BL and after clinical progression over 2 years, suggesting that monitoring pathological changes in the peripheral retina might become a valuable tool in AD monitoring.

AB - PURPOSE: To examine whether ultra-widefield (UWF) retinal imaging can identify biomarkers for Alzheimer's disease (AD) and its progression.METHODS: Images were taken using a UWF scanning laser ophthalmoscope (Optos P200C AF) to determine phenotypic variations in 59 patients with AD and 48 healthy controls at baseline (BL). All living participants were invited for a follow-up (FU) after 2 years and imaged again (if still able to participate). All participants had blood taken for genotyping at BL. Images were graded for the prevalence of age-related macular degeneration-like pathologies and retinal vascular parameters. Comparison between AD patients and controls was made using the Student t test and the χ2 test.RESULTS: Analysis at BL revealed a significantly higher prevalence of a hard drusen phenotype in the periphery of AD patients (14/55; 25.4%) compared to controls (2/48; 4.2%) [χ2 = 9.9, df = 4, p = 0.04]. A markedly increased drusen number was observed at the 2-year FU in patients with AD compared to controls. There was a significant increase in venular width gradient at BL (zone C: 8.425 × 10-3 ± 2.865 × 10-3 vs. 6.375 × 10-3 ± 1.532 × 10-3, p = 0.008; entire image: 8.235 × 10-3 ± 2.839 × 10-3 vs. 6.050 × 10-3 ± 1.414 × 10-3, p = 0.004) and a significant decrease in arterial fractal dimension in AD at BL (entire image: 1.250 ± 0.086 vs. 1.304 ± 0.089, p = 0.049) with a trend for both at FU.CONCLUSIONS: UWF retinal imaging revealed a significant association between AD and peripheral hard drusen formation and changes to the vasculature beyond the posterior pole, at BL and after clinical progression over 2 years, suggesting that monitoring pathological changes in the peripheral retina might become a valuable tool in AD monitoring.

KW - Journal Article

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DO - 10.1159/000487053

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JO - Ophthalmic Research

JF - Ophthalmic Research

SN - 0030-3747

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Csincsik L, MacGillivray TJ, Flynn E, Pellegrini E, Papanastasiou G, Barzegar-Befroei N et al. Peripheral Retinal Imaging Biomarkers for Alzheimer's Disease: A Pilot Study. Ophthalmic Research. 2018 Apr 5. https://doi.org/10.1159/000487053