Advances in ophthalmic imaging research on retinal biomarkers of Alzheimer’s disease_Chinese Journal of Ocular Fundus Diseases

Authors：

Li Luyao , He Hailong ,  Jin Zibing

Beijing Tongren Hospital, Capital Medical University, Beijing Tongren Eye Center, Beijing Institute of Ophthalmology, National Engineering Research Center for Ophthalmology, Beijing 100730, China;

Corresponding?author：

Jin Zibing, Email: jinzb502@ccmu.edu.cn

Keywords：

Alzheimer’s disease; Ophthalmic imaging; Retina; Biomarker; Review

DOI：

10.3760/cma.j.cn511434-20250603-00239

Video：

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Abstract Full text Figures/Tables Video References Cited by

Alzheimer's disease (AD) is a neurodegenerative disorder with insidious onset and poor prognosis, and it is the primary cause of senile dementia. Its early diagnosis is challenging, and existing methods mostly rely on high-cost and invasive examinations. As an integral part of the central nervous system, the retina provides a non-invasive and efficient observation window for AD diagnosis. In recent years, with the development of ophthalmic imaging technologies such as optical coherence tomography, optical coherence tomography angiography, and hyperspectral imaging, a growing number of studies have revealed that AD patients exhibit retinal structural changes, structural and functional abnormalities of retinal blood vessels, and that amyloid-beta and Tau deposits can be detected via specific imaging methods—suggesting that these changes may occur prior to brain lesions. Meanwhile, the integrated analysis of multimodal imaging shows promising prospects in identifying retinal biomarkers and predicting AD risk, demonstrates the significant potential of retinal imaging technology in the early screening, diagnosis, and disease progression monitoring of AD, and provides a new source of biomarkers and potential clinical applications for AD research.

Citation： Li Luyao, He Hailong, Jin Zibing. Advances in ophthalmic imaging research on retinal biomarkers of Alzheimer’s disease. Chinese Journal of Ocular Fundus Diseases, 2026, 42(3): 253-258. doi: 10.3760/cma.j.cn511434-20250603-00239 Copy

1.
2.
3.
4.
5.	Jiang X, Xie M, Ma L, et al. International publication trends in the application of artificial intelligence in ophthalmology research: an updated bibliometric analysis[J/OL]. Ann Transl Med, 2023, 11(5): 219[2023-03-09]. https://pubmed.ncbi.nlm.nih.gov/37007552/. DOI: 10.21037/atm-22-3773.
6.
7.	Chan VTT, Ran AR, Wagner SK, et al. Value proposition of retinal imaging in Alzheimer's disease screening: a review of eight evolving trends[J/OL]. Prog Retin Eye Res, 2024, 103: 101290[2024-08-22]. https://pubmed.ncbi.nlm.nih.gov/39173942/. DOI: 10.1016/j.preteyeres.2024.101290.
8.
9.	Ge YJ, Xu W, Ou YN, et al. Retinal biomarkers in Alzheimer's disease and mild cognitive impairment: a systematic review and meta-analysis[J/OL]. Ageing Res Rev, 2021, 69: 101361[2021-05-14]. https://pubmed.ncbi.nlm.nih.gov/34000463/. DOI: 10.1016/j.arr.2021.101361.
10.
11.	Grimaldi A, Pediconi N, Oieni F, et al. Neuroinflammatory processes, A1 astrocyte activation and protein aggregation in the retina of Alzheimer's disease patients, possible biomarkers for early diagnosis[J/OL]. Front Neurosci, 2019, 13: 925[2019-09-04]. https://pubmed.ncbi.nlm.nih.gov/31551688/. DOI: 10.3389/fnins.2019.00925.
12.	Georgevsky D, Retsas S, Raoufi N, et al. A longitudinal assessment of retinal function and structure in the APP/PS1 transgenic mouse model of Alzheimer's disease[J/OL]. Transl Neurodegener, 2019, 8: 30[2019-10-01]. https://pubmed.ncbi.nlm.nih.gov/31592131/. DOI: 10.1186/s40035-019-0170-z.
13.
14.
15.	Choi SH, Park SJ, Kim NR. Macular ganglion cell-inner plexiform layer thickness is associated with clinical progression in mild cognitive impairment and Alzheimers disease[J/OL]. PLoS One, 2016, 11(9): e0162202[2016-09-06]. https://pubmed.ncbi.nlm.nih.gov/27598262/. DOI: 10.1371/journal.pone.0162202.
16.
17.
18.
19.	Lian TH, Jin Z, Qu YZ, et al. The relationship between retinal nerve fiber layer thickness and clinical symptoms of Alzheimer's disease[J/OL]. Front Aging Neurosci, 2020, 12: 584244[2021-01-29]. https://pubmed.ncbi.nlm.nih.gov/33584241/. DOI: 10.3389/fnagi.2020.584244.
20.	Kim JI, Kang BH. Decreased retinal thickness in patients with Alzheimer's disease is correlated with disease severity[J/OL]. PLoS One, 2019, 14(11): e0224180[2019-11-15]. https://pubmed.ncbi.nlm.nih.gov/31689310/. DOI: 10.1371/journal.pone.0224180.
21.
22.	álvarez-Rodríguez L, Pueyo A, de Moura J, et al. Fully automatic deep convolutional approaches for the screening of neurodegeneratives diseases using multi-view OCT images[J/OL]. Artif Intell Med, 2024, 158: 103006[2024-11-01]. https://pubmed.ncbi.nlm.nih.gov/39504622/. DOI: 10.1016/j.artmed.2024.103006.
23.	Lee MW, Park KS, Lim HB, et al. Long-term reproducibility of GC-IPL thickness measurements using spectral domain optical coherence tomography in eyes with high myopia[J/OL]. Sci Rep, 2018, 8(1): 11037[2018-07-23]. https://pubmed.ncbi.nlm.nih.gov/30038425/. DOI: 10.1038/s41598-018-29466-8.
24.
25.
26.
27.	Frost S, Kanagasingam Y, Sohrabi H, et al. Retinal vascular biomarkers for early detection and monitoring of Alzheimer's disease[J/OL]. Transl Psychiatry, 2013, 3(2): e233[2013-02-26]. https://pubmed.ncbi.nlm.nih.gov/23443359/. DOI: 10.1038/tp.2012.150.
28.	Golzan M, Goozee K, Georgevsky D, et al. Retinal vascular and structural changes are associated with amyloid burden in the elderly: ophthalmic biomarkers of preclinical Alzheimer's disease[J/OL]. Alzheimers Res Ther, 2017, 9(1): 13[2017-03-01]. https://pubmed.ncbi.nlm.nih.gov/28253913/. DOI: 10.1186/s13195-017-0239-9.
29.
30.	Cheung CY, Ran AR, Wang S, et al. A deep learning model for detection of Alzheimer's disease based on retinal photographs: a retrospective, multicentre case-control study[J/OL]. Lancet Digit Health, 2022, 4(11): e806-e815[2022-09-30]. https://pubmed.ncbi.nlm.nih.gov/36192349/. DOI: 10.1016/S2589-7500(22)00169-8.
31.	Pead E, Thompson AC, Grewal DS, et al. Retinal vascular changes in Alzheimer's dementia and mild cognitive impairment: a pilot study using ultra-widefield imaging[J/OL]. Transl Vis Sci Technol, 2023, 12(1): 13[2023-01-03]. https://pubmed.ncbi.nlm.nih.gov/36622689/. DOI: 10.1167/tvst.12.1.13.
32.
33.	Querques G, Borrelli E, Sacconi R, et al. Functional and morphological changes of the retinal vessels in Alzheimer's disease and mild cognitive impairment[J/OL]. Sci Rep, 2019, 9(1): 63[2019-01-11]. https://pubmed.ncbi.nlm.nih.gov/30635610/. DOI: 10.1038/s41598-018-37271-6.
34.
35.	Hui J, Zhao Y, Yu S, et al. Detection of retinal changes with optical coherence tomography angiography in mild cognitive impairment and Alzheimer's disease patients: a meta-analysis[J/OL]. PLoS One, 2021, 16(8): e0255362[2021-08-11]. https://pubmed.ncbi.nlm.nih.gov/34379663/. DOI: 10.1371/journal.pone.0255362.
36.	Chua J, Hu Q, Ke M, et al. Retinal microvasculature dysfunction is associated with Alzheimer's disease and mild cognitive impairment[J/OL]. Alzheimers Res Ther, 2020, 12(1): 161[2020-12-04]. https://pubmed.ncbi.nlm.nih.gov/33276820/. DOI: 10.1186/s13195-020-00724-0.
37.	Yoon JM, Lim CY, Noh H, et al. Enhancing foveal avascular zone analysis for Alzheimer's diagnosis with AI segmentation and machine learning using multiple radiomic features[J/OL]. Sci Rep, 2024, 14(1): 1841[2024-01-22]. https://pubmed.ncbi.nlm.nih.gov/38253722/. DOI: 10.1038/s41598-024-51612-8.
38.	Liu S, Zhang Z, Gu Y, et al. Beyond the eye: a relational model for early dementia detection using retinal OCTA images[J/OL]. Med Image Anal, 2025, 102: 103513[2025-02-26]. https://pubmed.ncbi.nlm.nih.gov/40022853/. DOI: 10.1016/j.media.2025.103513.
39.
40.
41.
42.	Koronyo Y, Biggs D, Barron E, et al. Retinal amyloid pathology and proof-of-concept imaging trial in Alzheimer's disease[J/OL]. JCI Insight, 2017, 2(16): e93621[2017-08-17]. https://pubmed.ncbi.nlm.nih.gov/28814675/. DOI: 10.1172/jci.insight.93621.
43.	Ngolab J, Donohue M, Belsha A, et al. Feasibility study for detection of retinal amyloid in clinical trials: the anti-amyloid treatment in asymptomatic Alzheimer's disease (A4) trial[J/OL]. Alzheimers Dement (Amst), 2021, 13(1): e12199[2021-08-17]. https://pubmed.ncbi.nlm.nih.gov/34430703/. DOI: 10.1002/dad2.12199.
44.	Qiu Y, Jin T, Mason E, et al. Predicting thioflavin fluorescence of retinal amyloid deposits associated with Alzheimer's disease from their polarimetric properties[J/OL]. Transl Vis Sci Technol, 2020, 9(2): 47[2020-08-14]. https://pubmed.ncbi.nlm.nih.gov/32879757/. DOI: 10.1167/tvst.9.2.47.
45.
46.
47.	Hadoux X, Hui F, Lim JKH, et al. Non-invasive in vivo hyperspectral imaging of the retina for potential biomarker use in Alzheimer's disease[J/OL]. Nat Commun, 2019, 10(1): 4227[2019-09-17]. https://pubmed.ncbi.nlm.nih.gov/31530809/. DOI: 10.1038/s41467-019-12242-1.
48.	Du X, Koronyo Y, Mirzaei N, et al. Label-free hyperspectral imaging and deep-learning prediction of retinal amyloid β-protein and phosphorylated tau[J/OL]. PNAS Nexus, 2022, 1(4): pgac164[2022-08-19]. https://pubmed.ncbi.nlm.nih.gov/36157597/. DOI: 10.1093/pnasnexus/pgac164.
49.
50.
51.
52.	Sch?n C, Hoffmann NA, Ochs SM, et al. Long-term in vivo imaging of fibrillar tau in the retina of P301S transgenic mice[J/OL]. PLoS One, 2012, 7(12): e53547[2012-12-31]. https://pubmed.ncbi.nlm.nih.gov/23300938/. DOI: 10.1371/journal.pone.0053547.
53.
54.

1.
2.
3.
4.
5. Jiang X, Xie M, Ma L, et al. International publication trends in the application of artificial intelligence in ophthalmology research: an updated bibliometric analysis[J/OL]. Ann Transl Med, 2023, 11(5): 219[2023-03-09]. https://pubmed.ncbi.nlm.nih.gov/37007552/. DOI: 10.21037/atm-22-3773.
6.
7. Chan VTT, Ran AR, Wagner SK, et al. Value proposition of retinal imaging in Alzheimer's disease screening: a review of eight evolving trends[J/OL]. Prog Retin Eye Res, 2024, 103: 101290[2024-08-22]. https://pubmed.ncbi.nlm.nih.gov/39173942/. DOI: 10.1016/j.preteyeres.2024.101290.
8.
9. Ge YJ, Xu W, Ou YN, et al. Retinal biomarkers in Alzheimer's disease and mild cognitive impairment: a systematic review and meta-analysis[J/OL]. Ageing Res Rev, 2021, 69: 101361[2021-05-14]. https://pubmed.ncbi.nlm.nih.gov/34000463/. DOI: 10.1016/j.arr.2021.101361.
10.
11. Grimaldi A, Pediconi N, Oieni F, et al. Neuroinflammatory processes, A1 astrocyte activation and protein aggregation in the retina of Alzheimer's disease patients, possible biomarkers for early diagnosis[J/OL]. Front Neurosci, 2019, 13: 925[2019-09-04]. https://pubmed.ncbi.nlm.nih.gov/31551688/. DOI: 10.3389/fnins.2019.00925.
12. Georgevsky D, Retsas S, Raoufi N, et al. A longitudinal assessment of retinal function and structure in the APP/PS1 transgenic mouse model of Alzheimer's disease[J/OL]. Transl Neurodegener, 2019, 8: 30[2019-10-01]. https://pubmed.ncbi.nlm.nih.gov/31592131/. DOI: 10.1186/s40035-019-0170-z.
13.
14.
15. Choi SH, Park SJ, Kim NR. Macular ganglion cell-inner plexiform layer thickness is associated with clinical progression in mild cognitive impairment and Alzheimers disease[J/OL]. PLoS One, 2016, 11(9): e0162202[2016-09-06]. https://pubmed.ncbi.nlm.nih.gov/27598262/. DOI: 10.1371/journal.pone.0162202.
16.
17.
18.
19. Lian TH, Jin Z, Qu YZ, et al. The relationship between retinal nerve fiber layer thickness and clinical symptoms of Alzheimer's disease[J/OL]. Front Aging Neurosci, 2020, 12: 584244[2021-01-29]. https://pubmed.ncbi.nlm.nih.gov/33584241/. DOI: 10.3389/fnagi.2020.584244.
20. Kim JI, Kang BH. Decreased retinal thickness in patients with Alzheimer's disease is correlated with disease severity[J/OL]. PLoS One, 2019, 14(11): e0224180[2019-11-15]. https://pubmed.ncbi.nlm.nih.gov/31689310/. DOI: 10.1371/journal.pone.0224180.
21.
22. álvarez-Rodríguez L, Pueyo A, de Moura J, et al. Fully automatic deep convolutional approaches for the screening of neurodegeneratives diseases using multi-view OCT images[J/OL]. Artif Intell Med, 2024, 158: 103006[2024-11-01]. https://pubmed.ncbi.nlm.nih.gov/39504622/. DOI: 10.1016/j.artmed.2024.103006.
23. Lee MW, Park KS, Lim HB, et al. Long-term reproducibility of GC-IPL thickness measurements using spectral domain optical coherence tomography in eyes with high myopia[J/OL]. Sci Rep, 2018, 8(1): 11037[2018-07-23]. https://pubmed.ncbi.nlm.nih.gov/30038425/. DOI: 10.1038/s41598-018-29466-8.
24.
25.
26.
27. Frost S, Kanagasingam Y, Sohrabi H, et al. Retinal vascular biomarkers for early detection and monitoring of Alzheimer's disease[J/OL]. Transl Psychiatry, 2013, 3(2): e233[2013-02-26]. https://pubmed.ncbi.nlm.nih.gov/23443359/. DOI: 10.1038/tp.2012.150.
28. Golzan M, Goozee K, Georgevsky D, et al. Retinal vascular and structural changes are associated with amyloid burden in the elderly: ophthalmic biomarkers of preclinical Alzheimer's disease[J/OL]. Alzheimers Res Ther, 2017, 9(1): 13[2017-03-01]. https://pubmed.ncbi.nlm.nih.gov/28253913/. DOI: 10.1186/s13195-017-0239-9.
29.
30. Cheung CY, Ran AR, Wang S, et al. A deep learning model for detection of Alzheimer's disease based on retinal photographs: a retrospective, multicentre case-control study[J/OL]. Lancet Digit Health, 2022, 4(11): e806-e815[2022-09-30]. https://pubmed.ncbi.nlm.nih.gov/36192349/. DOI: 10.1016/S2589-7500(22)00169-8.
31. Pead E, Thompson AC, Grewal DS, et al. Retinal vascular changes in Alzheimer's dementia and mild cognitive impairment: a pilot study using ultra-widefield imaging[J/OL]. Transl Vis Sci Technol, 2023, 12(1): 13[2023-01-03]. https://pubmed.ncbi.nlm.nih.gov/36622689/. DOI: 10.1167/tvst.12.1.13.
32.
33. Querques G, Borrelli E, Sacconi R, et al. Functional and morphological changes of the retinal vessels in Alzheimer's disease and mild cognitive impairment[J/OL]. Sci Rep, 2019, 9(1): 63[2019-01-11]. https://pubmed.ncbi.nlm.nih.gov/30635610/. DOI: 10.1038/s41598-018-37271-6.
34.
35. Hui J, Zhao Y, Yu S, et al. Detection of retinal changes with optical coherence tomography angiography in mild cognitive impairment and Alzheimer's disease patients: a meta-analysis[J/OL]. PLoS One, 2021, 16(8): e0255362[2021-08-11]. https://pubmed.ncbi.nlm.nih.gov/34379663/. DOI: 10.1371/journal.pone.0255362.
36. Chua J, Hu Q, Ke M, et al. Retinal microvasculature dysfunction is associated with Alzheimer's disease and mild cognitive impairment[J/OL]. Alzheimers Res Ther, 2020, 12(1): 161[2020-12-04]. https://pubmed.ncbi.nlm.nih.gov/33276820/. DOI: 10.1186/s13195-020-00724-0.
37. Yoon JM, Lim CY, Noh H, et al. Enhancing foveal avascular zone analysis for Alzheimer's diagnosis with AI segmentation and machine learning using multiple radiomic features[J/OL]. Sci Rep, 2024, 14(1): 1841[2024-01-22]. https://pubmed.ncbi.nlm.nih.gov/38253722/. DOI: 10.1038/s41598-024-51612-8.
38. Liu S, Zhang Z, Gu Y, et al. Beyond the eye: a relational model for early dementia detection using retinal OCTA images[J/OL]. Med Image Anal, 2025, 102: 103513[2025-02-26]. https://pubmed.ncbi.nlm.nih.gov/40022853/. DOI: 10.1016/j.media.2025.103513.
39.
40.
41.
42. Koronyo Y, Biggs D, Barron E, et al. Retinal amyloid pathology and proof-of-concept imaging trial in Alzheimer's disease[J/OL]. JCI Insight, 2017, 2(16): e93621[2017-08-17]. https://pubmed.ncbi.nlm.nih.gov/28814675/. DOI: 10.1172/jci.insight.93621.
43. Ngolab J, Donohue M, Belsha A, et al. Feasibility study for detection of retinal amyloid in clinical trials: the anti-amyloid treatment in asymptomatic Alzheimer's disease (A4) trial[J/OL]. Alzheimers Dement (Amst), 2021, 13(1): e12199[2021-08-17]. https://pubmed.ncbi.nlm.nih.gov/34430703/. DOI: 10.1002/dad2.12199.
44. Qiu Y, Jin T, Mason E, et al. Predicting thioflavin fluorescence of retinal amyloid deposits associated with Alzheimer's disease from their polarimetric properties[J/OL]. Transl Vis Sci Technol, 2020, 9(2): 47[2020-08-14]. https://pubmed.ncbi.nlm.nih.gov/32879757/. DOI: 10.1167/tvst.9.2.47.
45.
46.
47. Hadoux X, Hui F, Lim JKH, et al. Non-invasive in vivo hyperspectral imaging of the retina for potential biomarker use in Alzheimer's disease[J/OL]. Nat Commun, 2019, 10(1): 4227[2019-09-17]. https://pubmed.ncbi.nlm.nih.gov/31530809/. DOI: 10.1038/s41467-019-12242-1.
48. Du X, Koronyo Y, Mirzaei N, et al. Label-free hyperspectral imaging and deep-learning prediction of retinal amyloid β-protein and phosphorylated tau[J/OL]. PNAS Nexus, 2022, 1(4): pgac164[2022-08-19]. https://pubmed.ncbi.nlm.nih.gov/36157597/. DOI: 10.1093/pnasnexus/pgac164.
49.
50.
51.
52. Sch?n C, Hoffmann NA, Ochs SM, et al. Long-term in vivo imaging of fibrillar tau in the retina of P301S transgenic mice[J/OL]. PLoS One, 2012, 7(12): e53547[2012-12-31]. https://pubmed.ncbi.nlm.nih.gov/23300938/. DOI: 10.1371/journal.pone.0053547.
53.
54.

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