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OCT in Alzheimer’s disease: thinning of the RNFL and superior hemiretina

  • João Paulo Cunha
  • Rita Proença
  • Arnaldo Dias-Santos
  • Rita Almeida
  • Helena Águas
  • Marta Alves
  • Ana Luísa Papoila
  • Carlota Louro
  • António Castanheira-Dinis
Neurophthalmology

Abstract

Background

Peripapillary retinal nerve fiber layer (pRNFL) and internal macular layer thinning have been demonstrated in Alzheimer’s disease (AD) with optical coherence tomography (OCT) studies. The purpose of this study is to compare the pRNFL thickness and overall retinal thickness (RT) in AD patients with non-AD patients, using spectral domain optical coherence tomography (SD-OCT) and determine the sectors most characteristically affected in AD.

Methods

A cross-sectional study was performed to determine the pRNFL and overall macular RT thicknesses in AD and non-AD patients, attending a tertiary hospital center. For pRNFL, the global and six peripapillary quadrants were calculated, and for overall RT values, the nine Early Treatment Diabetic Retinopathy Study (ETDRS) areas were used. A multiple regression analysis was applied to assess the effects of disease, age, gender, spherical equivalent, visual acuity, intraocular pressure, axial length and blood pressure on pRNFL and overall macular RT.

Results

A total of 202 subjects, including 50 eyes of 50 patients with mild AD (mean age 73.10; SD = 5.36 years) and 152 eyes of 152 patients without AD (mean age 71.03; SD = 4.62 years). After Bonferroni correction, the pRNFL was significantly thinner for the AD group globally and in the temporal superior quadrant (10.76 μm and 20.09 μm mean decrease, respectively). The RT thickness was also decreased in superior sectors S3 and S6 (mean thinning of 9.92 μm and 11.65 μm, respectively). Spearman’s correlation coefficient showed a direct association between pRNFL in the temporal superior quadrant and RT in superior S6 and S3 sectors (rS = 0.41; p < 0.001 and rS = 0.28; p < 0.001, respectively).

Conclusions

Patients with AD showed a significant thickness reduction in global and temporal superior quadrants in pRNFL and in superior pericentral and peripheral sectors of RT. These findings may reflect a peripapillary and retinal changes characteristic of AD, suggesting the importance of SD-OCT as a potential adjuvant in early diagnosis of AD. Further studies are needed to understand which retinal layers and macular sectors are more useful as potential ocular biomarker over time in AD.

Keywords

Alzheimer’s disease Spectral domain optical coherence tomography RNFL Retina Macula 

Notes

Acknowledgements

We would like to thank Bruno Oliveira-Santos for the helpful cooperation in collecting the OCT data. We thank Dr. Paula Mota and Dr. Joana Tavares-Ferreira for the detailed reading and comments on the manuscript.

Compliance with ethical standards

Funding

No funding was received for this research.

Conflict of Interest

All authors certify that they have no affiliationswith or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript.

Ethical approval

All procedures performed in studies involving humanparticipants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individualparticipants included in the study.

Financial disclosure

None of the authors have any conflict of interest.

Supplementary material

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Supplemental Table 1 (DOCX 21 kb).
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Supplemental Table 2 (DOCX 24 kb).
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Supplemental Table 3 (DOCX 24 kb).
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Supplemental Table 4 (DOCX 24 kb).
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Supplemental Table 5 (DOCX 24 kb).
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Supplemental Table 6 (DOCX 24 kb).

References

  1. 1.
    Association A (2012) 2012 Alzheimer ’ s disease facts and figures. Alzheimer’s Dementia 8:131–168. doi: 10.1016/j.jalz.2012.02.001 CrossRefGoogle Scholar
  2. 2.
    Perl DP, Perl DP (2010) Neuropathology of Alzheimer ’ s Disease Address Correspondence to : 32–42. doi: 10.1002/MSJ
  3. 3.
    Burns A, Iliffe S (2009) Alzheimer’s disease. BMJ 338:b158. doi: 10.1136/bmj.b158 CrossRefPubMedGoogle Scholar
  4. 4.
    Querfurth HW, LaFerla FM (2010) Alzheimer’s disease. N Engl J Med 362:329–344. doi: 10.1056/NEJMra0909142 CrossRefPubMedGoogle Scholar
  5. 5.
    Hinton DR, Sadun AA, Blanks JC, Miller CA (1986) Optic-nerve degeneration in Alzheimer’s disease. N Engl J Med 315:485–487. doi: 10.1056/NEJM198608213150804 CrossRefPubMedGoogle Scholar
  6. 6.
    Hinton DR, Sadun AA, Blanks JC, Miller CA (2010) Optic nerve degeneration in Alzheimer’s disease. N Engl J Med 315:485–487CrossRefGoogle Scholar
  7. 7.
    Blanks JC, Torigoe Y, Hinton DR, Blanks RHI (1996) Retinal pathology in Alzheimer’s disease. I. Ganglion cell loss in foveal/parafoveal retina. Neurobiol Aging 17:377–384. doi: 10.1016/0197-4580(96)00010-3 CrossRefPubMedGoogle Scholar
  8. 8.
    Blanks JC, Hinton DR, Sadun AA, Miller CA (1989) Retinal ganglion cell degeneration in Alzheimer’s disease. Brain Res 501:364–372Google Scholar
  9. 9.
    Parisi V, Restuccia R, Fattapposta F, et al (2001) Morphological and functional retinal impairment in Alzheimer’s disease patients. 112:1860–1867Google Scholar
  10. 10.
    Berisha F, Feke GT, Trempe CL, et al (2007) Retinal Abnormalities in Early Alzheimer ’ s Disease. 48:6–10. doi:  10.1167/iovs.06-1029
  11. 11.
    Hedges TR, Perez Galves R, Speigelman D et al (1996) Retinal nerve fiber layer abnormalities in Alzheimer’s disease. Acta Ophthalmol Scand 74:271–275CrossRefPubMedGoogle Scholar
  12. 12.
    Tsai C, Ritch R, Schwartz B et al (1991) Optic nerve head and nerve fiber layer in Alzheimer’s disease. Arch Ophthalmol 109:199–204CrossRefPubMedGoogle Scholar
  13. 13.
    Danesh-Meyer HV, Birch H, Ku JY et al (2006) Reduction of optic nerve fibers in patients with Alzheimer disease identified by laser imaging. Neurology 67:1852–1854CrossRefPubMedGoogle Scholar
  14. 14.
    Iseri PK, Tokay T (2006) Relationship between Cognitive Impairment and Retinal Morphological and Visual Functional Abnormalities in Alzheimer Disease. 26:18–24Google Scholar
  15. 15.
    Kirbas S, Turkyilmaz K, Anlar O et al (2013) Retinal nerve fiber layer thickness in patients with Alzheimer disease. J Neuroophthalmol 33:58–61. doi: 10.1097/WNO.0b013e318267fd5f CrossRefPubMedGoogle Scholar
  16. 16.
    Salobrar-garcia E, Hoz R De, Rojas B, et al (2015) Findings in Mild Alzheimer ’ s Disease. 2015:17–19. doi:  10.1155/2015/736949
  17. 17.
    Ascaso FJ, Cruz N, Modrego PJ, Cristo A (2014) Retinal alterations in mild cognitive impairment and Alzheimer ’ s disease : an optical coherence tomography study. 1522–1530. doi:  10.1007/s00415-014-7374-z
  18. 18.
    Moschos M, Markopoulos I, Chatziralli I et al (2012) Structural and functional impairment of the retina and optic nerve in Alzheimer’s disease. Curr Alzheimer Res 9:782–788. doi: 10.2174/156720512802455340 CrossRefPubMedGoogle Scholar
  19. 19.
    Gao L, Liu Y, Li X et al (2015) Abnormal retinal nerve fiber layer thickness and macula lutea in patients with mild cognitive impairment and Alzheimer ’ s disease. Arch Gerontol Geriatr 60:162–167. doi: 10.1016/j.archger.2014.10.011 CrossRefPubMedGoogle Scholar
  20. 20.
    Williams MA, Mcgowan AJ, Cardwell CR et al (2015) Retinal microvascular network attenuation in Alzheimer ’ s disease. Alzheimer’s Dement Diagnosis, Assess Dis Monit 1:229–235. doi: 10.1016/j.dadm.2015.04.001 Google Scholar
  21. 21.
    Marziani E, Pomati S, Ramolfo P, et al (2016) Evaluation of Retinal Nerve Fiber Layer and Ganglion Cell Layer Thickness in Alzheimer ’ s Disease Using Spectral- Domain Optical Coherence Tomography. doi:  10.1167/iovs.13-12046
  22. 22.
    Ong Y, Ong Y, Ikram MK, et al (2014) Potential Applications of Spectral-Domain Optical Coherence Tomography ( SD-OCT ) in the Study of Alzheimer ’ s Disease. 23:74–83Google Scholar
  23. 23.
    Garcia-Martin ES, Rojas B, Ramirez AI et al (2014) Macular Thickness as a Potential Biomarker of Mild Alzheimer’s Disease. Ophthalmology 121:1149–1151.e3. doi: 10.1016/j.ophtha.2013.12.023 CrossRefPubMedGoogle Scholar
  24. 24.
    Group ETDRSR (1991) Early Photocoagulation for Diabetic Retinopathy. Ophthalmology 98:766–785. doi: 10.1016/S0161-6420(13)38011-7 CrossRefGoogle Scholar
  25. 25.
    Salobrar-Garcia E, Hoyas I, Leal M, et al (2015) Analysis of Retinal Peripapillary Segmentation in Early Alzheimer ’ s Disease Patients. doi:  10.1155/2015/636548
  26. 26.
    Ozdemir E, Eda O, Seda D (2015) The relationship between the degree of cognitive impairment and retinal nerve fiber layer thickness. Neurol Sci:1141–1146. doi: 10.1007/s10072-014-2055-3
  27. 27.
    Bambo MP, Garcia-Martin E, Pinilla J et al (2014) Detection of retinal nerve fiber layer degeneration in patients with Alzheimer’s disease using optical coherence tomography: searching new biomarkers. Acta Ophthalmol 92:e581–e582. doi: 10.1111/aos.12374 CrossRefPubMedGoogle Scholar
  28. 28.
    Paquet C, Roger F, Dighiero P, et al (2007) Abnormal retinal thickness in patients with mild cognitive impairment and Alzheimer ’ s disease. 420:97–99. doi:  10.1016/j.neulet.2007.02.090
  29. 29.
    Kesler A, Vakhapova V, Korczyn AD et al (2011) Retinal thickness in patients with mild cognitive impairment and Alzheimer ’ s disease. Clin Neurol Neurosurg 113:523–526. doi: 10.1016/j.clineuro.2011.02.014 CrossRefPubMedGoogle Scholar
  30. 30.
    Tzekov R, Mullan M (2014) Vision function abnormalities in Alzheimer disease. Surv Ophthalmol 59:414–433. doi: 10.1016/j.survophthal.2013.10.002 CrossRefPubMedGoogle Scholar
  31. 31.
    Coppola G, Renzo A Di, Ziccardi L, Martelli F (2015) Optical Coherence Tomography in Alzheimer ’ s Disease : A Meta-Analysis. 1–14. doi: 10.1371/journal.pone.0134750Google Scholar
  32. 32.
    Cunha JP, Moura-Coelho N, Proença RP, et al (2016) Alzheimer’s disease: A review of its visual system neuropathology. Optical coherence tomography—a potential role as a study tool in vivo. Graefe’s Arch Clin Exp Ophthalmol. doi:  10.1007/s00417-016-3430-y
  33. 33.
    Thomson KL, Yeo JM, Waddell B et al (2015) A systematic review and meta-analysis of retinal nerve fiber layer change in dementia, using optical coherence tomography. Alzheimer’s Dement Diagnosis, Assess Dis Monit 1:136–143. doi: 10.1016/j.dadm.2015.03.001 Google Scholar
  34. 34.
    He X-F, Liu Y-T, Peng C et al (2012) Optical coherence tomography assessed retinal nerve fiber layer thickness in patients with Alzheimer’s disease: A meta-analysis. Int J Ophthalmol 5:401–405. doi: 10.3980/j.issn.2222-3959.2012.03.30 PubMedPubMedCentralGoogle Scholar
  35. 35.
    Cheung CY, Ting Y, Ikram MK et al (2014) Microvascular network alterations in the retina of patients with Alzheimer ’ s disease. Alzheimer’s Dement 10:135–142. doi: 10.1016/j.jalz.2013.06.009 CrossRefGoogle Scholar
  36. 36.
    Pillai JA, Bermel R, Bonner-Jackson A, et al (2016) Retinal Nerve Fiber Layer Thinning in Alzheimer’s Disease: A Case-Control Study in Comparison to Normal Aging, Parkinson’s Disease, and Non-Alzheimer’s Dementia. Am J Alzheimers Dis Other Demen. doi:  10.1177/1533317515628053
  37. 37.
    Trick GL, Trick LR, Morris P, Wolf M (1995) Visual field loss in senile dementia of the Alzheimer’s type. Neurol 45:68–74. doi: 10.1212/WNL.45.1.68 CrossRefGoogle Scholar
  38. 38.
    Armstrong RA (1996) Visual field defects in Alzheimer’s disease patients may reflect differential pathology in the primary visual cortex. Optom Vis Sci 73:677–682CrossRefPubMedGoogle Scholar
  39. 39.
    Jack CR, Knopman DS, Jagust WJ et al (2010) Hypothetical model of dynamic biomarkers of the Alzheimer’s pathological cascade. Lancet Neurol 9:119–128. doi: 10.1016/S1474-4422(09)70299-6 CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Damoiseaux JS, Prater KE, Miller BL, Greicius MD (2012) Functional connectivity tracks clinical deterioration in Alzheimer ’ s disease. NBA 33:828.e19–828.e30. doi: 10.1016/j.neurobiolaging.2011.06.024 Google Scholar
  41. 41.
    Hafkemeijer A, Möller C, Dopper EGP, Jiskoot LC (2015) Resting state functional connectivity differences between behavioral variant frontotemporal dementia and Alzheimer ’ s disease. 9:1–12. doi:  10.3389/fnhum.2015.00474
  42. 42.
    Hafkemeijer A, Christiane M (2017) A Longitudinal Study on Resting State Functional Connectivity in Behavioral Variant Frontotemporal Dementia and Alzheimer ’ s Disease. 55:521–537. doi:  10.3233/JAD-150695

Copyright information

© Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  • João Paulo Cunha
    • 1
    • 2
    • 3
  • Rita Proença
    • 1
  • Arnaldo Dias-Santos
    • 1
  • Rita Almeida
    • 4
  • Helena Águas
    • 4
  • Marta Alves
    • 5
  • Ana Luísa Papoila
    • 2
    • 5
    • 6
  • Carlota Louro
    • 2
  • António Castanheira-Dinis
    • 7
  1. 1.Department of OphthalmologyCentral Lisbon Hospital CenterLisbonPortugal
  2. 2.NOVA Medical SchoolUniversidade NOVA de LisboaLisbonPortugal
  3. 3.Department of Neuro-OphthalmologyCentral Lisbon Hospital CenterLisboaPortugal
  4. 4.Department of NeurologyCentral Lisbon Hospital CenterLisbonPortugal
  5. 5.Epidemiology and Statistics Unit, Research CentreCentral Lisbon Hospital CenterLisbonPortugal
  6. 6.CEAUL (Center of Statistics and Applications)Lisbon UniversityLisbonPortugal
  7. 7.Visual Sciences Study Center, Faculty of MedicineLisbon UniversityLisbonPortugal

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