Skip to main content

Advertisement

SpringerLink
Log in

Retina Oculomics in Neurodegenerative Disease

  • Review
  • Published:
Annals of Biomedical Engineering Aims and scope Submit manuscript

Abstract

Ophthalmic biomarkers have long played a critical role in diagnosing and managing ocular diseases. Oculomics has emerged as a field that utilizes ocular imaging biomarkers to provide insights into systemic diseases. Advances in diagnostic and imaging technologies including electroretinography, optical coherence tomography (OCT), confocal scanning laser ophthalmoscopy, fluorescence lifetime imaging ophthalmoscopy, and OCT angiography have revolutionized the ability to understand systemic diseases and even detect them earlier than clinical manifestations for earlier intervention. With the advent of increasingly large ophthalmic imaging datasets, machine learning models can be integrated into these ocular imaging biomarkers to provide further insights and prognostic predictions of neurodegenerative disease. In this manuscript, we review the use of ophthalmic imaging to provide insights into neurodegenerative diseases including Alzheimer Disease, Parkinson Disease, Amyotrophic Lateral Sclerosis, and Huntington Disease. We discuss recent advances in ophthalmic technology including eye-tracking technology and integration of artificial intelligence techniques to further provide insights into these neurodegenerative diseases. Ultimately, oculomics opens the opportunity to detect and monitor systemic diseases at a higher acuity. Thus, earlier detection of systemic diseases may allow for timely intervention for improving the quality of life in patients with neurodegenerative disease.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. London, A., I. Benhar, and M. Schwartz. The retina as a window to the brain—from eye research to CNS disorders. Nat. Rev. Neurol. 9(1):44–53, 2013. https://doi.org/10.1038/nrneurol.2012.227.

    Article  CAS  PubMed  Google Scholar 

  2. Wagner, S. K., D. J. Fu, L. Faes, et al. Insights into systemic disease through retinal imaging-based oculomics. Transl. Vis. Sci. Technol. 9(2):6, 2020. https://doi.org/10.1167/tvst.9.2.6.

    Article  PubMed Central  PubMed  Google Scholar 

  3. Moreno-Ramos, T., J. Benito-Leon, A. Villarejo, and F. Bermejo-Pareja. Retinal nerve fiber layer thinning in dementia associated with Parkinson’s disease, dementia with Lewy bodies and Alzheimer’s disease. J. Alzheimers Dis. 34(3):659–664, 2013. https://doi.org/10.3233/JAD-121975.

    Article  CAS  PubMed  Google Scholar 

  4. Jo, T., K. Nho, and A. J. Saykin. Deep learning in Alzheimer’s disease: diagnostic classification and prognostic prediction using neuroimaging data. Front. Aging Neurosci. 11:220, 2019. https://doi.org/10.3389/fnagi.2019.00220.

    Article  PubMed Central  PubMed  Google Scholar 

  5. Majeed, A., B. Marwick, H. Yu, H. Fadavi, and M. Tavakoli. Ophthalmic biomarkers for Alzheimer’s disease: a review. Front. Aging Neurosci. 13:720167, 2021. https://doi.org/10.3389/fnagi.2021.720167.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  6. Ukalovic, K., S. Cao, S. Lee, et al. Drusen in the peripheral retina of the Alzheimer’s eye. Curr. Alzheimer Res. 15(8):743–750, 2018. https://doi.org/10.2174/1567205015666180123122637.

    Article  CAS  PubMed  Google Scholar 

  7. Chalkias, I. N., T. Tegos, F. Topouzis, and M. Tsolaki. Ocular biomarkers and their role in the early diagnosis of neurocognitive disorders. Eur. J. Ophthalmol. 31(6):2808–2817, 2021. https://doi.org/10.1177/11206721211016311.

    Article  PubMed  Google Scholar 

  8. Huang, D., E. A. Swanson, C. P. Lin, et al. Optical coherence tomography. Science. 254(5035):1178–1181, 1991. https://doi.org/10.1126/science.1957169.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  9. Koustenis, A., Jr., A. Harris, J. Gross, I. Januleviciene, A. Shah, and B. Siesky. Optical coherence tomography angiography: an overview of the technology and an assessment of applications for clinical research. Br. J. Ophthalmol. 101(1):16–20, 2017. https://doi.org/10.1136/bjophthalmol-2016-309389.

    Article  PubMed  Google Scholar 

  10. Macgillivray, T. J., E. Trucco, J. R. Cameron, B. Dhillon, J. G. Houston, and E. J. R. Van Beek. Retinal imaging as a source of biomarkers for diagnosis, characterization and prognosis of chronic illness or long-term conditions. Br. J. Radiol. 87(1040):20130832, 2014. https://doi.org/10.1259/bjr.20130832.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  11. Schweitzer, D., M. Hammer, F. Schweitzer, et al. In vivo measurement of time-resolved autofluorescence at the human fundus. J. Biomed. Opt. 9(6):1214–1222, 2004. https://doi.org/10.1117/1.1806833.

    Article  PubMed  Google Scholar 

  12. Kremers, J., D. J. McKeefry, I. J. Murray, and N. R. A. Parry. Developments in non-invasive visual electrophysiology. Vision Res. 174:50–56, 2020. https://doi.org/10.1016/j.visres.2020.05.003.

    Article  PubMed  Google Scholar 

  13. Barnes, D. E., and K. Yaffe. The projected effect of risk factor reduction on Alzheimer’s disease prevalence. Lancet Neurol. 10(9):819–828, 2011. https://doi.org/10.1016/S1474-4422(11)70072-2.

    Article  PubMed Central  PubMed  Google Scholar 

  14. Lim, J. K., Q. X. Li, Z. He, et al. The eye as a biomarker for Alzheimer’s disease. Front Neurosci. 10:536, 2016. https://doi.org/10.3389/fnins.2016.00536.

    Article  PubMed Central  PubMed  Google Scholar 

  15. Martins, R. N., V. Villemagne, H. R. Sohrabi, et al. Alzheimer’s disease: a journey from amyloid peptides and oxidative stress, to biomarker technologies and disease prevention strategies—gains from AIBL and DIAN cohort studies. J. Alzheimer Dis. 62(3):965–992, 2018. https://doi.org/10.3233/jad-171145.

    Article  CAS  Google Scholar 

  16. Thal, L. J., K. Kantarci, E. M. Reiman, et al. The role of biomarkers in clinical trials for Alzheimer disease. Alzheimer Dis. Assoc. Disord. 20(1):6–15, 2006. https://doi.org/10.1097/01.wad.0000191420.61260.a8.

    Article  PubMed Central  PubMed  Google Scholar 

  17. Albert, M. S., S. T. Dekosky, D. Dickson, et al. The diagnosis of mild cognitive impairment due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimer Dement. 7(3):270–279, 2011. https://doi.org/10.1016/j.jalz.2011.03.008.

    Article  Google Scholar 

  18. Granholm, E. L., M. S. Panizzon, J. A. Elman, et al. Pupillary responses as a biomarker of early risk for Alzheimer’s disease. J Alzheimers Dis. 56(4):1419–1428, 2017. https://doi.org/10.3233/JAD-161078.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  19. Tian, T., B. Zhang, Y. Jia, and Z. Li. Promise and challenge: the lens model as a biomarker for early diagnosis of Alzheimer’s disease. Dis. Mark. 2014:826503, 2014. https://doi.org/10.1155/2014/826503.

    Article  CAS  Google Scholar 

  20. Ornek, N., E. Dag, and K. Ornek. Corneal sensitivity and tear function in neurodegenerative diseases. Curr. Eye Res. 40(4):423–428, 2015. https://doi.org/10.3109/02713683.2014.930154.

    Article  PubMed  Google Scholar 

  21. Chaitanuwong, P., S. Jariyakosol, S. Apinyawasisuk, et al. Changes in ocular biomarkers from normal cognitive aging to Alzheimer’s disease: a pilot study. Eye Brain. 15:15–23, 2023. https://doi.org/10.2147/EB.S391608.

    Article  PubMed Central  PubMed  Google Scholar 

  22. Rehan, S., N. Giroud, F. Al-Yawer, W. Wittich, and N. Phillips. Visual performance and cortical atrophy in vision-related brain regions differ between older adults with (or at risk for) Alzheimer’s disease. J. Alzheimer Dis. 83(3):1125–1148, 2021. https://doi.org/10.3233/JAD-201521.

    Article  CAS  Google Scholar 

  23. Koronyo-Hamaoui, M., Y. Koronyo, A. V. Ljubimov, et al. Identification of amyloid plaques in retinas from Alzheimer’s patients and noninvasive in vivo optical imaging of retinal plaques in a mouse model. NeuroImage. 54:S204–S217, 2011. https://doi.org/10.1016/j.neuroimage.2010.06.020.

    Article  CAS  PubMed  Google Scholar 

  24. Klaver, C. C., A. Ott, A. Hofman, J. J. Assink, M. M. Breteler, and P. T. de Jong. Is age-related maculopathy associated with Alzheimer’s Disease? The Rotterdam study. Am J Epidemiol. 150(9):963–968, 1999. https://doi.org/10.1093/oxfordjournals.aje.a010105.

    Article  CAS  PubMed  Google Scholar 

  25. Tsai, C. S. Optic nerve head and nerve fiber layer in Alzheimer’s disease. Arch. Ophthalmol. 109(2):199, 1991. https://doi.org/10.1001/archopht.1991.01080020045040.

    Article  CAS  PubMed  Google Scholar 

  26. Lu, Y., Z. Li, X. Zhang, et al. Retinal nerve fiber layer structure abnormalities in early Alzheimer’s disease: evidence in optical coherence tomography. Neurosci. Lett. 480(1):69–72, 2010. https://doi.org/10.1016/j.neulet.2010.06.006.

    Article  CAS  PubMed  Google Scholar 

  27. Vij, R., and S. Arora. A systematic survey of advances in retinal imaging modalities for Alzheimer’s disease diagnosis. Metab. Brain Dis. 37(7):2213–2243, 2022. https://doi.org/10.1007/s11011-022-00927-4.

    Article  PubMed  Google Scholar 

  28. Danesh-Meyer, H. V., H. Birch, J. Y. Ku, S. Carroll, and G. Gamble. Reduction of optic nerve fibers in patients with Alzheimer disease identified by laser imaging. Neurology. 67(10):1852–1854, 2006. https://doi.org/10.1212/01.wnl.0000244490.07925.8b.

    Article  CAS  PubMed  Google Scholar 

  29. Kurna, S. A., G. Akar, A. Altun, Y. Agirman, E. Gozke, and T. Sengor. Confocal scanning laser tomography of the optic nerve head on the patients with Alzheimer’s disease compared to glaucoma and control. Int. Ophthalmol. 34(6):1203–1211, 2014. https://doi.org/10.1007/s10792-014-0004-z.

    Article  PubMed  Google Scholar 

  30. Koronyo, Y., D. Biggs, E. Barron, et al. Retinal amyloid pathology and proof-of-concept imaging trial in Alzheimer’s disease. JCI Insight. 2017. https://doi.org/10.1172/jci.insight.93621.

    Article  PubMed Central  PubMed  Google Scholar 

  31. Jentsch, S., D. Schweitzer, K. U. Schmidtke, et al. Retinal fluorescence lifetime imaging ophthalmoscopy measures depend on the severity of Alzheimer’s disease. Acta Ophthalmol. 93(4):e241–e247, 2015. https://doi.org/10.1111/aos.12609.

    Article  CAS  PubMed  Google Scholar 

  32. Sadda, S. R., E. Borrelli, W. Fan, et al. A pilot study of fluorescence lifetime imaging ophthalmoscopy in preclinical Alzheimer’s disease. Eye (Lond). 33(8):1271–1279, 2019. https://doi.org/10.1038/s41433-019-0406-2.

    Article  PubMed Central  PubMed  Google Scholar 

  33. Colligris, P., M. J. Perez de Lara, B. Colligris, and J. Pintor. Ocular manifestations of Alzheimer’s and other neurodegenerative diseases: the prospect of the eye as a tool for the early diagnosis of Alzheimer’s disease. J. Ophthalmol. 2018:8538573, 2018. https://doi.org/10.1155/2018/8538573.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  34. Budenz, D. L., D. R. Anderson, R. Varma, et al. Determinants of normal retinal nerve fiber layer thickness measured by stratus OCT. Ophthalmology. 114(6):1046–1052, 2007. https://doi.org/10.1016/j.ophtha.2006.08.046.

    Article  PubMed  Google Scholar 

  35. Cunha, J. P., R. Proenca, A. Dias-Santos, et al. OCT in Alzheimer’s disease: thinning of the RNFL and superior hemiretina. Graefes. Arch. Clin. Exp. Ophthalmol. 255(9):1827–1835, 2017. https://doi.org/10.1007/s00417-017-3715-9.

    Article  PubMed  Google Scholar 

  36. Berisha, F., G. T. Feke, C. L. Trempe, J. W. McMeel, and C. L. Schepens. Retinal abnormalities in early Alzheimer’s disease. Invest. Opthalmol. Vis. Sci. 48(5):2285, 2007. https://doi.org/10.1167/iovs.06-1029.

    Article  Google Scholar 

  37. Sánchez, D., M. Castilla-Marti, O. Rodríguez-Gómez, et al. Usefulness of peripapillary nerve fiber layer thickness assessed by optical coherence tomography as a biomarker for Alzheimer’s disease. Sci. Rep. 2018. https://doi.org/10.1038/s41598-018-34577-3.

    Article  PubMed Central  PubMed  Google Scholar 

  38. Den Haan, J., L. Csinscik, T. Parker, et al. Retinal thickness as potential biomarker in posterior cortical atrophy and typical Alzheimer’s disease. Alzheimer Res. Ther. 2019. https://doi.org/10.1186/s13195-019-0516-x.

    Article  Google Scholar 

  39. Zhang, Y. S., N. Zhou, B. M. Knoll, et al. Parafoveal vessel loss and correlation between peripapillary vessel density and cognitive performance in amnestic mild cognitive impairment and early Alzheimer’s disease on optical coherence tomography angiography. PLOS ONE. 14(4):e0214685, 2019. https://doi.org/10.1371/journal.pone.0214685.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  40. Zabel, P., J. J. Kaluzny, M. Wilkosc-Debczynska, et al. Comparison of retinal microvasculature in patients with Alzheimer’s disease and primary open-angle glaucoma by optical coherence tomography angiography. Invest. Ophthalmol. Vis. Sci. 60(10):3447–3455, 2019. https://doi.org/10.1167/iovs.19-27028.

    Article  PubMed  Google Scholar 

  41. Salobrar-Garcia, E., C. Mendez-Hernandez, R. Hoz, et al. Ocular vascular changes in mild Alzheimer’s disease patients: foveal avascular zone, choroidal thickness, and ONH hemoglobin analysis. J. Pers. Med. 2020. https://doi.org/10.3390/jpm10040231.

    Article  PubMed Central  PubMed  Google Scholar 

  42. Lopez-de-Eguileta, A., C. Lage, S. Lopez-Garcia, et al. Evaluation of choroidal thickness in prodromal Alzheimer’s disease defined by amyloid PET. PLoS One. 15(9):e0239484, 2020. https://doi.org/10.1371/journal.pone.0239484.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  43. Li, M., R. Li, J. H. Lyu, et al. Relationship between Alzheimer’s disease and retinal choroidal thickness: a cross-sectional study. J. Alzheimers Dis. 80(1):407–419, 2021. https://doi.org/10.3233/JAD-201142.

    Article  CAS  PubMed  Google Scholar 

  44. Querques, G., E. Borrelli, R. Sacconi, et al. Functional and morphological changes of the retinal vessels in Alzheimer’s disease and mild cognitive impairment. Sci. Rep. 2019. https://doi.org/10.1038/s41598-018-37271-6.

    Article  PubMed Central  PubMed  Google Scholar 

  45. Yoon, S. P., D. S. Grewal, A. C. Thompson, et al. Retinal microvascular and neurodegenerative changes in Alzheimer’s disease and mild cognitive impairment compared with control participants. Ophthalmol. Retina. 3(6):489–499, 2019. https://doi.org/10.1016/j.oret.2019.02.002.

    Article  PubMed Central  PubMed  Google Scholar 

  46. Song, A., N. Johnson, A. Ayala, and A. C. Thompson. Optical coherence tomography in patients with Alzheimer’s disease: what can it tell us? Eye Brain. 13:1–20, 2021. https://doi.org/10.2147/eb.s235238.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  47. Krasodomska, K., W. Lubinski, A. Potemkowski, and K. Honczarenko. Pattern electroretinogram (PERG) and pattern visual evoked potential (PVEP) in the early stages of Alzheimer’s disease. Doc. Ophthalmol. 121(2):111–121, 2010. https://doi.org/10.1007/s10633-010-9238-x.

    Article  PubMed Central  PubMed  Google Scholar 

  48. Liao, C., J. Xu, Y. Chen, and N. Y. Ip. Retinal dysfunction in Alzheimer’s disease and implications for biomarkers. Biomolecules. 2021. https://doi.org/10.3390/biom11081215.

    Article  PubMed Central  PubMed  Google Scholar 

  49. Samra, K., A. M. MacDougall, A. Bouzigues, et al. Genetic forms of primary progressive aphasia within the GENetic frontotemporal dementia initiative (GENFI) cohort: comparison with sporadic primary progressive aphasia. Brain Commun. 5(2):fcad036, 2023. https://doi.org/10.1093/braincomms/fcad036.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  50. Meeter, L. H., L. D. Kaat, J. D. Rohrer, and J. C. Van Swieten. Imaging and fluid biomarkers in frontotemporal dementia. Nat. Rev. Neurol. 13(7):406–419, 2017. https://doi.org/10.1038/nrneurol.2017.75.

    Article  CAS  PubMed  Google Scholar 

  51. Moinuddin, O., N. S. Khandwala, K. Z. Young, et al. Role of optical coherence tomography in identifying retinal biomarkers in frontotemporal dementia: a review. Neurol. Clin. Pract. 11(4):e516–e523, 2021. https://doi.org/10.1212/CPJ.0000000000001041.

    Article  PubMed Central  PubMed  Google Scholar 

  52. Hutchings, R., R. Palermo, J. Bruggemann, J. R. Hodges, O. Piguet, and F. Kumfor. Looking but not seeing: increased eye fixations in behavioural-variant frontotemporal dementia. Cortex. 103:71–81, 2018. https://doi.org/10.1016/j.cortex.2018.02.011.

    Article  PubMed  Google Scholar 

  53. Moon, S. Y., B. H. Lee, S. W. Seo, S. J. Kang, and D. L. Na. Slow vertical saccades in the frontotemporal dementia with motor neuron disease. J. Neurol. 255(9):1337–1343, 2008. https://doi.org/10.1007/s00415-008-0890-y.

    Article  CAS  PubMed  Google Scholar 

  54. Ferrari, L., S. C. Huang, G. Magnani, A. Ambrosi, G. Comi, and L. Leocani. Optical coherence tomography reveals retinal neuroaxonal thinning in frontotemporal dementia as in Alzheimer’s disease. J. Alzheimers Dis. 56(3):1101–1107, 2017. https://doi.org/10.3233/JAD-160886.

    Article  CAS  PubMed  Google Scholar 

  55. Kim, B. J., D. J. Irwin, D. Song, et al. Optical coherence tomography identifies outer retina thinning in frontotemporal degeneration. Neurology. 89(15):1604–1611, 2017. https://doi.org/10.1212/wnl.0000000000004500.

    Article  PubMed Central  PubMed  Google Scholar 

  56. Kim, B. J., M. Grossman, D. Song, et al. Persistent and progressive outer retina thinning in frontotemporal degeneration. Front. Neurosci. 13:298, 2019. https://doi.org/10.3389/fnins.2019.00298.

    Article  PubMed Central  PubMed  Google Scholar 

  57. Cofreces, P., S. D. Ofman, J. A. Estay, and P. D. Hermida. Enfermedad de Parkinson: una actualizacion bibliografica de los aspectos psicosociales. Rev. Fac. Cien. Med. Univ. Nac. Cordoba. 79(2):181–187, 2022. https://doi.org/10.31053/1853.0605.v79.n2.33610.

    Article  PubMed Central  PubMed  Google Scholar 

  58. Khan, M. A., N. Haider, T. Singh, et al. Promising biomarkers and therapeutic targets for the management of Parkinson’s disease: recent advancements and contemporary research. Metab Brain Dis. 38(3):873–919, 2023. https://doi.org/10.1007/s11011-023-01180-z.

    Article  CAS  PubMed  Google Scholar 

  59. Rekik, A., S. Mrabet, A. Nasri, et al. Eye movement study in essential tremor patients and its clinical correlates. J. Neural. Transm. (Vienna). 130(4):537–548, 2023. https://doi.org/10.1007/s00702-023-02614-9.

    Article  PubMed  Google Scholar 

  60. Davidsdottir, S., A. Cronin-Golomb, and A. Lee. Visual and spatial symptoms in Parkinson’s disease. Vision Res. 45(10):1285–1296, 2005. https://doi.org/10.1016/j.visres.2004.11.006.

    Article  PubMed  Google Scholar 

  61. Huang, J., Y. Li, J. Xiao, et al. Combination of multifocal electroretinogram and spectral-domain OCT can increase diagnostic efficacy of Parkinson’s disease. Parkinson’s Dis. 2018:1–7, 2018. https://doi.org/10.1155/2018/4163239.

    Article  Google Scholar 

  62. Unlu, M., D. Gulmez Sevim, M. Gultekin, and C. Karaca. Correlations among multifocal electroretinography and optical coherence tomography findings in patients with Parkinson’s disease. Neurol. Sci. 39(3):533–541, 2018. https://doi.org/10.1007/s10072-018-3244-2.

    Article  PubMed  Google Scholar 

  63. Stemplewitz, B., M. Keseru, D. Bittersohl, et al. Scanning laser polarimetry and spectral domain optical coherence tomography for the detection of retinal changes in Parkinson’s disease. Acta Ophthalmol. 93(8):e672–e677, 2015. https://doi.org/10.1111/aos.12764.

    Article  CAS  PubMed  Google Scholar 

  64. Chorostecki, J., N. Seraji-Bozorgzad, A. Shah, et al. Characterization of retinal architecture in Parkinson’s disease. J. Neurol. Sci. 355(1–2):44–48, 2015. https://doi.org/10.1016/j.jns.2015.05.007.

    Article  PubMed  Google Scholar 

  65. Devos, D., M. Tir, C. A. Maurage, et al. ERG and anatomical abnormalities suggesting retinopathy in dementia with Lewy bodies. Neurology. 65(7):1107–1110, 2005. https://doi.org/10.1212/01.wnl.0000178896.44905.33.

    Article  CAS  PubMed  Google Scholar 

  66. Alves, J. N., B. U. Westner, A. Højlund, R. S. Weil, and S. S. Dalal. Structural and functional changes in the retina in Parkinson’s disease. J Neurol Neurosurg Psychiatry. 2023. https://doi.org/10.1136/jnnp-2022-329342.

    Article  PubMed  Google Scholar 

  67. Kaur, M., R. Saxena, D. Singh, M. Behari, P. Sharma, and V. Menon. Correlation between structural and functional retinal changes in Parkinson disease. J Neuroophthalmol. 35(3):254–258, 2015. https://doi.org/10.1097/WNO.0000000000000240.

    Article  PubMed  Google Scholar 

  68. Sari, E. S., R. Koc, A. Yazici, G. Sahin, and S. S. Ermis. Ganglion cell-inner plexiform layer thickness in patients with Parkinson disease and association with disease severity and duration. J Neuroophthalmol. 35(2):117–121, 2015. https://doi.org/10.1097/WNO.0000000000000203.

    Article  PubMed  Google Scholar 

  69. Satue, M., J. Obis, R. Alarcia, et al. Retinal and choroidal changes in patients with Parkinson’s disease detected by swept-source optical coherence tomography. Curr. Eye Res. 43(1):109–115, 2018. https://doi.org/10.1080/02713683.2017.1370116.

    Article  PubMed  Google Scholar 

  70. Obis, J., M. Satue, R. Alarcia, L. E. Pablo, and E. Garcia-Martin. Actualizacion sobre alteraciones de funcion visual y espesores coriorretinianos en la enfermedad de Parkinson. Arch. Soc. Esp. Oftalmol. (Engl Ed). 93(5):231–238, 2018. https://doi.org/10.1016/j.oftal.2018.01.004.

    Article  CAS  PubMed  Google Scholar 

  71. Brown, G. L., M. L. Camacci, S. D. Kim, et al. Choroidal thickness correlates with clinical and imaging metrics of Parkinson’s disease: a pilot study. J. Parkinsons Dis. 11(4):1857–1868, 2021. https://doi.org/10.3233/JPD-212676.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  72. Moschos, M. M., and I. P. Chatziralli. Evaluation of choroidal and retinal thickness changes in Parkinson’s disease using spectral domain optical coherence tomography. Semin. Ophthalmol. 33(4):494–497, 2018. https://doi.org/10.1080/08820538.2017.1307423.

    Article  PubMed  Google Scholar 

  73. Eraslan, M., E. Cerman, S. Yildiz Balci, et al. The choroid and lamina cribrosa is affected in patients with Parkinson’s disease: enhanced depth imaging optical coherence tomography study. Acta Ophthalmol. 94(1):e68-75, 2016. https://doi.org/10.1111/aos.12809.

    Article  PubMed  Google Scholar 

  74. Kamata, Y., N. Hara, T. Satou, T. Niida, and K. Mukuno. Investigation of the pathophysiology of the retina and choroid in Parkinson’s disease by optical coherence tomography. Int. Ophthalmol. 42(5):1437–1445, 2022. https://doi.org/10.1007/s10792-021-02133-0.

    Article  PubMed  Google Scholar 

  75. Zhang, Y., L. Yang, Y. Gao, et al. Choroid and choriocapillaris changes in early-stage Parkinson’s disease: a swept-source optical coherence tomography angiography-based cross-sectional study. Alzheimers Res. Ther. 14(1):116, 2022. https://doi.org/10.1186/s13195-022-01054-z.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  76. Garcia-Martin, E., L. E. Pablo, M. P. Bambo, et al. Comparison of peripapillary choroidal thickness between healthy subjects and patients with Parkinson’s disease. PLoS One. 12(5):e0177163, 2017. https://doi.org/10.1371/journal.pone.0177163.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  77. Garcia-Martin, E., D. Rodriguez-Mena, M. Satue, et al. Electrophysiology and optical coherence tomography to evaluate Parkinson disease severity. Invest. Ophthalmol. Vis. Sci. 55(2):696–705, 2014. https://doi.org/10.1167/iovs.13-13062.

    Article  PubMed  Google Scholar 

  78. Moschos, M. M., G. Tagaris, I. Markopoulos, et al. Morphologic changes and functional retinal impairment in patients with Parkinson disease without visual loss. Eur. J. Ophthalmol. 21(1):24–29, 2011. https://doi.org/10.5301/ejo.2010.1318.

    Article  PubMed  Google Scholar 

  79. Kupersmith, M. J., E. Shakin, I. M. Siegel, and A. Lieberman. Visual system abnormalities in patients with Parkinson’s disease. Arch. Neurol. 39(5):284–286, 1982. https://doi.org/10.1001/archneur.1982.00510170026007.

    Article  CAS  PubMed  Google Scholar 

  80. Batum, M., A. K. Ak, M. S. Ari, H. Mayali, E. Kurt, and D. Selcuki. Evaluation of the visual system with visual evoked potential and optical coherence tomography in patients with idiopathic Parkinson’s disease and with multiple system atrophy. Doc. Ophthalmol. 145(2):99–112, 2022. https://doi.org/10.1007/s10633-022-09887-7.

    Article  PubMed  Google Scholar 

  81. Carrarini, C., M. Russo, G. Pagliaccio, et al. Visual evoked potential abnormalities in dementia with Lewy bodies. Neurophysiol. Clin. 51(5):425–431, 2021. https://doi.org/10.1016/j.neucli.2021.02.003.

    Article  PubMed  Google Scholar 

  82. Zhou, M., L. Wu, Q. Hu, et al. Visual impairments are associated with retinal microvascular density in patients with Parkinson’s disease. Front. Neurosci. 15:718820, 2021. https://doi.org/10.3389/fnins.2021.718820.

    Article  PubMed Central  PubMed  Google Scholar 

  83. Tuncer, Z., G. Dereli Can, H. Donmez Keklikoglu, F. A. Eren, F. Yulek, and O. Deniz. The Relationship between visual-evoked potential and optic coherence tomography and clinical findings in Parkinson patients. Parkinsons Dis. 2023:7739944, 2023. https://doi.org/10.1155/2023/7739944.

    Article  PubMed Central  PubMed  Google Scholar 

  84. Witkovsky, P. Dopamine and retinal function. Doc. Ophthalmol. 108(1):17–39, 2004. https://doi.org/10.1023/b:doop.0000019487.88486.0a.

    Article  PubMed  Google Scholar 

  85. Ikeda, H., G. M. Head, and C. J. Ellis. Electrophysiological signs of retinal dopamine deficiency in recently diagnosed Parkinson’s disease and a follow up study. Vision Res. 34(19):2629–2638, 1994. https://doi.org/10.1016/0042-6989(94)90248-8.

    Article  CAS  PubMed  Google Scholar 

  86. Gottlob, I., H. Weghaupt, C. Vass, and E. Auff. Effect of levodopa on the human pattern electroretinogram and pattern visual evoked potentials. Graefes. Arch. Clin. Exp. Ophthalmol. 227(5):421–427, 1989. https://doi.org/10.1007/BF02172892.

    Article  CAS  PubMed  Google Scholar 

  87. Christou, E. E., S. Konitsiotis, K. Pamporis, et al. Inner retinal layers’ alterations of the microvasculature in early stages of Parkinson’s disease: a cross sectional study. Int. Ophthalmol. 2023. https://doi.org/10.1007/s10792-023-02653-x.

    Article  PubMed  Google Scholar 

  88. Christou, E. E., I. Asproudis, C. Asproudis, A. Giannakis, M. Stefaniotou, and S. Konitsiotis. Macular microcirculation characteristics in Parkinson’s disease evaluated by OCT-angiography: a literature review. Semin. Ophthalmol. 37(3):399–407, 2022. https://doi.org/10.1080/08820538.2021.1987482.

    Article  PubMed  Google Scholar 

  89. Kwapong, W. R., H. Ye, C. Peng, et al. Retinal microvascular impairment in the early stages of Parkinson’s disease. Invest. Ophthalmol. Vis. Sci. 59(10):4115–4122, 2018. https://doi.org/10.1167/iovs.17-23230.

    Article  CAS  PubMed  Google Scholar 

  90. McGrath, M. S., R. Zhang, P. M. Bracci, A. Azhir, and B. D. Forrest. Regulation of the innate immune system as a therapeutic approach to supporting respiratory function in ALS. Cells. 2023. https://doi.org/10.3390/cells12071031.

    Article  PubMed Central  PubMed  Google Scholar 

  91. Verber, N., and P. J. Shaw. Biomarkers in amyotrophic lateral sclerosis: a review of new developments. Curr. Opin. Neurol. 33(5):662–668, 2020. https://doi.org/10.1097/wco.0000000000000854.

    Article  CAS  PubMed  Google Scholar 

  92. Mitsumoto, H., and T. Saito. A prognostic biomarker in amyotrophic lateral sclerosis. Rinsho Shinkeigaku. 58(12):729–736, 2018. https://doi.org/10.5692/clinicalneurol.cn-001220.

    Article  PubMed  Google Scholar 

  93. Youn, C. E., C. Lu, J. Cauchi, D. MacGowan, R. Morgenstern, and S. Scelsa. Oculomotor dysfunction in motor neuron disease. J. Neuromuscul. Dis. 2023. https://doi.org/10.3233/JND-221579.

    Article  PubMed  Google Scholar 

  94. Ringelstein, M., P. Albrecht, M. Südmeyer, et al. Subtle retinal pathology in amyotrophic lateral sclerosis. Ann. Clin. Transl. Neurol. 1(4):290–297, 2014. https://doi.org/10.1002/acn3.46.

    Article  PubMed Central  PubMed  Google Scholar 

  95. Mohanty, B., A. K. Misra, S. Kumar, et al. Retinal nerve fiber layer thinning found in amyotrophic lateral sclerosis—Correlation with disease duration and severity. Indian J. Ophthalmol. 71(2):369–378, 2023. https://doi.org/10.4103/ijo.IJO_1870_22.

    Article  PubMed Central  PubMed  Google Scholar 

  96. Zhang, Y., X. Liu, J. Fu, et al. Selective and inverse U-shaped curve alteration of the retinal nerve in amyotrophic lateral sclerosis: a potential mirror of the disease. Front. Aging Neurosci. 13:783431, 2021. https://doi.org/10.3389/fnagi.2021.783431.

    Article  CAS  PubMed  Google Scholar 

  97. Hubers, A., H. P. Muller, J. Dreyhaupt, et al. Retinal involvement in amyotrophic lateral sclerosis: a study with optical coherence tomography and diffusion tensor imaging. J. Neural. Transm. (Vienna). 123(3):281–287, 2016. https://doi.org/10.1007/s00702-015-1483-4.

    Article  CAS  PubMed  Google Scholar 

  98. Rohani, M., A. Meysamie, B. Zamani, M. M. Sowlat, and F. H. Akhoundi. Reduced retinal nerve fiber layer (RNFL) thickness in ALS patients: a window to disease progression. J. Neurol. 265(7):1557–1562, 2018. https://doi.org/10.1007/s00415-018-8863-2.

    Article  PubMed  Google Scholar 

  99. Nepal, G., S. Kharel, M. A. Coghlan, et al. Amyotrophic lateral sclerosis and retinal changes in optical coherence tomography: a systematic review and meta-analysis. Brain Behav. 12(9):e2741, 2022. https://doi.org/10.1002/brb3.2741.

    Article  PubMed Central  PubMed  Google Scholar 

  100. Yap, T. E., S. I. Balendra, M. T. Almonte, and M. F. Cordeiro. Retinal correlates of neurological disorders. Ther. Adv. Chronic Dis. 10:2040622319882205, 2019. https://doi.org/10.1177/2040622319882205.

    Article  PubMed Central  PubMed  Google Scholar 

  101. Abdelhak, A., A. Hübers, K. Böhm, A. C. Ludolph, J. Kassubek, and E. H. Pinkhardt. In vivo assessment of retinal vessel pathology in amyotrophic lateral sclerosis. J. Neurol. 265(4):949–953, 2018. https://doi.org/10.1007/s00415-018-8787-x.

    Article  CAS  PubMed  Google Scholar 

  102. Kolde, G., R. Bachus, and A. C. Ludolph. Skin involvement in amyotrophic lateral sclerosis. Lancet. 347(9010):1226–1227, 1996. https://doi.org/10.1016/s0140-6736(96)90737-0.

    Article  CAS  PubMed  Google Scholar 

  103. Cennamo, G., D. Montorio, F. P. Ausiello, et al. Correlation between retinal vascularization and disease aggressiveness in amyotrophic lateral sclerosis. Biomedicines. 2022. https://doi.org/10.3390/biomedicines10102390.

    Article  PubMed Central  PubMed  Google Scholar 

  104. Simonett, J. M., R. Huang, N. Siddique, et al. Macular sub-layer thinning and association with pulmonary function tests in Amyotrophic Lateral Sclerosis. Sci. Rep. 6(1):29187, 2016. https://doi.org/10.1038/srep29187.

    Article  PubMed Central  PubMed  Google Scholar 

  105. Imarisio, S., J. Carmichael, V. Korolchuk, et al. Huntington’s disease: from pathology and genetics to potential therapies. Biochem. J. 412(2):191–209, 2008. https://doi.org/10.1042/BJ20071619.

    Article  CAS  PubMed  Google Scholar 

  106. Zeun, P., R. I. Scahill, S. J. Tabrizi, and E. J. Wild. Fluid and imaging biomarkers for Huntington’s disease. Mol. Cell Neurosci. 97:67–80, 2019. https://doi.org/10.1016/j.mcn.2019.02.004.

    Article  CAS  PubMed  Google Scholar 

  107. Knapp, J., D. A. VanNasdale, K. Ramsey, and J. Racine. Retinal dysfunction in a presymptomatic patient with Huntington’s disease. Doc. Ophthalmol. 136(3):213–221, 2018. https://doi.org/10.1007/s10633-018-9632-3.

    Article  PubMed  Google Scholar 

  108. Amini, E., M. Moghaddasi, S. A. H. Habibi, et al. Huntington’s disease and neurovascular structure of retina. Neurol. Sci. 43(10):5933–5941, 2022. https://doi.org/10.1007/s10072-022-06232-3.

    Article  PubMed  Google Scholar 

  109. Gatto, E., V. Parisi, G. Persi, et al. Optical coherence tomography (OCT) study in Argentinean Huntington’s disease patients. Int. J. Neurosci. 128(12):1157–1162, 2018. https://doi.org/10.1080/00207454.2018.1489807.

    Article  PubMed  Google Scholar 

  110. Murueta-Goyena, A., R. Del Pino, M. Acera, et al. Retinal thickness as a biomarker of cognitive impairment in manifest Huntington’s disease. J. Neurol. 2023. https://doi.org/10.1007/s00415-023-11720-3.

    Article  PubMed Central  PubMed  Google Scholar 

  111. Kersten, H. M., H. V. Danesh-Meyer, D. H. Kilfoyle, and R. H. Roxburgh. Optical coherence tomography findings in Huntington’s disease: a potential biomarker of disease progression. J. Neurol. 262(11):2457–2465, 2015. https://doi.org/10.1007/s00415-015-7869-2.

    Article  CAS  PubMed  Google Scholar 

  112. Schmid, R. D., J. Remlinger, M. Abegg, et al. No optical coherence tomography changes in premanifest Huntington’s disease mutation carriers far from disease onset. Brain Behav. 12(6):e2592, 2022. https://doi.org/10.1002/brb3.2592.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  113. Andrade, C., J. Beato, A. Monteiro, et al. Spectral-domain optical coherence tomography as a potential biomarker in Huntington’s disease. Mov. Disord. 31(3):377–383, 2016. https://doi.org/10.1002/mds.26486.

    Article  PubMed  Google Scholar 

  114. Dusek, P., A. Kopal, M. Brichova, et al. Is retina affected in Huntington’s disease? Is optical coherence tomography a good biomarker? PLoS One. 18(2):e0282175, 2023. https://doi.org/10.1371/journal.pone.0282175.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  115. Di Maio, L. G., D. Montorio, S. Peluso, et al. Optical coherence tomography angiography findings in Huntington’s disease. Neurol. Sci. 42(3):995–1001, 2021. https://doi.org/10.1007/s10072-020-04611-2.

    Article  PubMed  Google Scholar 

  116. Mazur-Michalek, I., K. Kowalska, D. Zielonka, et al. Structural abnormalities of the optic nerve and retina in huntington’s disease pre-clinical and clinical settings. Int. J. Mol. Sci. 2022. https://doi.org/10.3390/ijms23105450.

    Article  PubMed Central  PubMed  Google Scholar 

  117. Li, M., D. Yasumura, A. A. K. Ma, et al. Intravitreal administration of HA-1077, a ROCK inhibitor, improves retinal function in a mouse model of Huntington disease. PLoS ONE. 8(2):e56026, 2013. https://doi.org/10.1371/journal.pone.0056026.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  118. Helmlinger, D., G. Yvert, S. Picaud, et al. Progressive retinal degeneration and dysfunction in R6 Huntington’s disease mice. Hum. Mol. Genet. 11(26):3351–3359, 2002. https://doi.org/10.1093/hmg/11.26.3351.

    Article  CAS  PubMed  Google Scholar 

  119. Kwon, J. Y., J. H. Yang, J. S. Han, and D. G. Kim. Analysis of the retinal nerve fiber layer thickness in Alzheimer disease and mild cognitive impairment. Korean J. Ophthalmol. 31(6):548–556, 2017. https://doi.org/10.3341/kjo.2016.0118.

    Article  PubMed Central  PubMed  Google Scholar 

Download references

Funding

NASA Grant [80NSSC20K183]: A Non-intrusive Ocular Monitoring Framework to Model Ocular Structure and Functional Changes due to Long-term Spaceflight.

Author information

Authors and Affiliations

  1. Tulane University School of Medicine, New Orleans, LA, USA

    Alex Suh

  2. Michigan Medicine, University of Michigan, Ann Arbor, MI, USA

    Joshua Ong

  3. Human-Machine Perception Laboratory, Department of Computer Science and Engineering, University of Nevada, Reno, Reno, NV, USA

    Sharif Amit Kamran, Nasif Zaman, Prithul Sarker & Alireza Tavakkoli

  4. University College Dublin School of Medicine, Belfield, Dublin, Ireland

    Ethan Waisberg

  5. Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

    Phani Paladugu

  6. Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, USA

    Phani Paladugu

  7. Center for Space Medicine, Baylor College of Medicine, Houston, TX, USA

    Andrew G. Lee

  8. Department of Ophthalmology, Blanton Eye Institute, Houston Methodist Hospital, 6560 Fannin St #450, Houston, TX, 77030, USA

    Andrew G. Lee

  9. The Houston Methodist Research Institute, Houston Methodist Hospital, Houston, TX, USA

    Andrew G. Lee

  10. Departments of Ophthalmology, Neurology and Neurosurgery, Weill Cornell Medicine, New York, NY, USA

    Andrew G. Lee

  11. Department of Ophthalmology, University of Texas Medical Branch, Galveston, TX, USA

    Andrew G. Lee

  12. University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Andrew G. Lee

  13. Texas A&M College of Medicine, Bryan, TX, USA

    Andrew G. Lee

  14. Department of Ophthalmology, The University of Iowa Hospitals and Clinics, Iowa City, IA, USA

    Andrew G. Lee

Authors
  1. Alex Suh
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Joshua Ong
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sharif Amit Kamran
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ethan Waisberg
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Phani Paladugu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Nasif Zaman
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Prithul Sarker
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Alireza Tavakkoli
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Andrew G. Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Alex Suh.

Ethics declarations

Conflict of interest

The authors declare no competing interests.

Additional information

Associate Editor Joel Stitzel oversaw the review of this article.

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Suh, A., Ong, J., Kamran, S.A. et al. Retina Oculomics in Neurodegenerative Disease. Ann Biomed Eng 51, 2708–2721 (2023). https://doi.org/10.1007/s10439-023-03365-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10439-023-03365-0

Keywords

Search

Navigation