Abstract
Background
To evaluate and compare the ability of two Fourier-domain optical coherence tomography (OCT) devices to detect retinal and retinal nerve fibre layer (RNFL) atrophy in patients with Alzheimer’s disease (AD) compared with healthy subjects; to test the intra-session reliability of two OCT devices in AD patients and healthy subjects.
Methods
AD patients (n=75) and age-matched healthy subjects (n=75) underwent three Macular Cube 200 × 200 protocols using the Cirrus and Spectralis OCT devices and three 360° circular scans centred on the optic disc using the Cirrus OCT device, the classic glaucoma application, and the new Nsite Axonal Analytics application of the Spectralis OCT instrument. Differences between healthy and AD eyes were compared, and measurements provided by each OCT protocol were compared. Reliability was measured using intraclass correlation coefficients and coefficients of variation. Correlations between OCT measurements and disease duration and severity were also analysed.
Results
Retinal thinning was observed in AD eyes in all areas except the fovea using both OCT devices. RNFL atrophy was detected in AD eyes with all three protocols, but the Nsite Axonal application was the most sensitive. Measurements by the two OCT devices were correlated, but differed significantly. Reliability was good using all protocols, but better with the glaucoma application of Spectralis. Mean RNFL thickness provided by the Nsite Axonal application correlated with disease duration.
Conclusions
Fourier-domain OCT is a valid and reliable technique for detecting subclinical RNFL and retinal atrophy in AD, especially using the Nsite Axonal application. RNFL thickness decreased with disease duration.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
References
Georges J . Giving a voice to people with dementia. Dementia in Europe: The Alzheimer Europe Magazine 2012; 4: 1.
Wimo A, Winblad B, Jonsson L . The worldwide societal costs of dementia: estimates for 2009. Alzheimers Dement 2010; 6 (2): 98–103.
Sadun AA, Borchert M, De Vita E, Hinton DR, Bassi CJ . Assessment of visual impairment in patients with Alzheimer’s disease. Am J Ophthalmol 1987; 104: 113–120.
Lewis DA, Campbell MJ, Terry RD, Morrison JH . Laminar and regional distributions of neurofibrillary tangles and neuritic plaques in Alzheimer’s disease: a quantitative study of visual and auditory cortices. J Neurosc 1987; 7: 1799–1808.
Hof PR, Morrison JH . Quantitative analysis of a vulnerable subset of pyramidal neurons in Alzheimer’s disease: II. Primary and secondary visual cortex. J Comp Neurol 1990; 301: 55–64.
Berisha F, Feke GT, Trempe CL, McMeel JW, Schepens CL . Retinal abnormalities in early Alzheimer’s disease. Invest Ophthalmol Vis Sci 2007; 48 (5): 2285–2289.
Iseri PK, Altinaş O, Tokay T, Yüksel N . Relationship between cognitive impairment and retinal morphological and visual functional abnormalities in Alzheimer disease. J Neuro-Ophthalmol 2006; 26 (1): 18–24.
Kesler A, Vakhapova V, Korczyn AD, Naftaliev E, Neudorfer M . Retinal thickness in patients with mild cognitive impairment and Alzheimer's disease. Clin Neurol Neurosurg 2011; 113 (7): 523–526.
Schuman JS, Pedut-Kloizman T, Hertzmark E, Hee MR, Wilkins JR, Coker JG et al. Reproducibility of nerve fibre layer thickness measurements using optical coherence tomography. Ophthalmology 1996; 103 (11): 1889–1898.
Garcia-Martin E, Rodriguez-Mena D, Herrero R, Almarcegui C, Dolz I, Martin J et al. Neuro-ophthalmologic evaluation, quality of life, and functional disability in patients with MS. Neurology 2013; 81 (1): 76–83.
Garcia-Martin E, Satue M, Fuertes I, Otin S, Alarcia R, Herrero R et al. Ability and reproducibility of Fourier-domain optical coherence tomography to detect retinal nerve fiber layer atrophy in Parkinson’s disease. Ophthalmology 2012; 119 (10): 2161–2167.
Valenti DA . Alzheimer’s disease and glaucoma: imaging the biomarkers of neurodegenerative disease. Int J Alzheimers 2011; 2010: 793931.
Garcia-Martin E, Pablo LE, Herrero R, Satue M, Polo V, Larrosa JM et al. Diagnostic ability of a linear discriminant function for Spectral domain optical coherence tomography in multiple sclerosis patients. Ophthalmology 2012; 119 (8): 1705–1711.
Ratchford JN, Quigg ME, Conger A, Frohman T, Frohman E, Balcer LJ et al. Optical coherence tomography helps differentiate neuromyelitis optica and MS optic neuropathies. Neurology 2009; 73: 302–308.
Aaker GD, Myung JS, Ehrlich JR, Mohammed M, Henchcliffe C, Kiss S . Detection of retinal changes in Parkinson's disease with spectral-domain optical coherence tomography. Clin Ophthalmol 2010; 4: 1427–1432.
Satue M, Garcia-Martin E, Fuertes I, Otin S, Alarcia R, Herrero R et al. Use of Fourier-domain OCT to detect retinal nerve fiber layer degeneration in Parkinson’s disease patients. Eye 2013; 27 (4): 507–514.
McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM . Clinical diagnosis of Alzheimer’s disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer’s Disease. Neurology 1984; 34: 939–944.
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) 4th ed. American Psychiatric Association: Washington, DC, USA, 1994.
Gupta PK, Asrani S, Freedman SF, El-Dairi M, Bhatti MT . Differentiating glaucomatous from non-glaucomatous optic nerve cupping by optical coherence tomography. Open Neurol J 2011; 5: 1–7.
Wu Z, Huang J, Dustin L, Sadda SR . Signal strength is an important determinant of accuracy of nerve fiber layer thickness measurement by optical coherence tomography. J Glaucoma 2009; 18: 213–216.
Early Treatment Diabetic Retinopathy Study Research Group. Photocoagulation for diabetic macular edema. Early Treatment Diabetic Retinopathy Study Report No. 1 1985; 103: 1796–1806.
Folstein MF, Folstein SE, McHugh PR . ‘Mini-Mental State Examination: a practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975; 12: 189–198.
Rebok G, Brandt J, Folstein M . Longitudinal cognitive decline in patients with Alzheimer’s disease. J Geriat Psychiat Neurol 1990; 3: 91–97.
Garcia-Martin E, Pueyo V, Pinilla I, Ara JR, Martin J, Fernandez J . Fourier-domain OCT in multiple sclerosis patients: reproducibility and ability to detect retinal nerve fiber layer atrophy. Invest Ophthalmol Vis Sci 2011; 52: 4124–4131.
Parikh RS, Parikh SR, Sekhar GC, Prabakaran S, Babu JG, Thomas R . Normal age-related decay of retinal nerve fiber layer thickness. Ophthalmology 2007; 114: 921–926.
Garcia-Martin E, Pueyo V, Almarcegui C, Martin J, Ara JR, Sancho E . Risk factors for progressive axonal degeneration of the retinal nerve fibre layer in multiple sclerosis patients. Br J Ophthalmol 2011; 95: 1577–1582.
Vizzeri G, Balasubramanian M, Bowd C, Weinreb RN, Medeiros FA, Zangwill LM . Spectral domain-optical coherence tomography to detect localized retinal nerve fiber layer defects in glaucomatous eyes. Opt Express 2009; 17: 4004–4018.
Armstrong RA . Visual field defects in Alzheimeŕs disease patients may reflect differential pathology in the primary visual cortex. Optom Vis Sci 1996; 73: 677–682.
Blanks JC, Torigoe Y, Hinton DR, Blanks RH . Retinal pathology in Alzheimer disease. I. Ganglion cell loss in foveal/parafoveal retina. Neurobiol Aging 1996; 17: 377–384.
Blanks JC, Schmidt SY, Torigoe Y, Porrello KV, Hinton DR, Blanks RH . Retinal pathology in Alzheimeŕs disease. II. Regional neuron loss and glial changes in GCL. Neurobiol Aging 1996; 17: 385–395.
Ewers M, Sperling RA, Klunk WE, Weiner MW, Hampel H . Neuroimaging markers for the prediction and early diagnosis of Alzheimeŕs disease dementia. Trends Neurosci 2011; 34 (8): 430–442.
Gordon-Lipkin E, Chodkowski B, Reich DS, Smith SA, Pulicken M, Balcer LJ et al. Retinal nerve fiber layer is associated with brain atrophy in multiple sclerosis. Neurology 2007; 69: 1603–1609.
Pulicken M, Gordon-Lipkin E, Balcer LJ, Frohman E, Cutter G, Calabresi PA . Optical coherence tomography and disease subtype in multiple sclerosis. Neurology 2007; 69: 2085–2092.
Inzelberg R, Ramirez JA, Nisipeanu P, Ophir A . Retinal nerve fiber layer thinning in Parkinson disease. Vision Res 2004; 44: 2793–2797.
Grazioli E, Zivadinov R, Weinstock-Guttman B, Lincoff N, Baier M, Wong JR et al. Retinal nerve fiber layer thickness is associated with brain MRI outcomes in multiple sclerosis. J Neurol Sci 2008; 268: 12–17.
Fortune B, Cull GA, Burgoyne CF . Relative course of retinal nerve fiber layer birefringence and thickness and retinal function changes after optic nerve transection. Invest Ophthalmol Vis Sci 2008; 49: 4444–4452.
Knight OJ, Chang RT, Feuer WJ, Budenz DL . Comparison of retinal nerve fiber layer measurements using time domain and spectral domain optical coherent tomography. Ophthalmology 2009; 116: 1271–1277.
Leung CK, Cheung CY, Weinreb RN, Qiu Q, Liu S, Li H et al. Retinal nerve fiber layer imaging with spectral-domain optical coherence tomography: a variability and diagnostic performance study. Ophthalmology 2009; 116: 1257–1263.
Acknowledgements
This work was supported in part by the Fundación Mutua Madrileña grant FMMA 02/12. We thank the Federación Aragonesa de Asociaciones de Familiares de Alzheimer y otras demencias (FARAL) for helping with the patient inclusion.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Competing interests
The authors declare no conflict of interest.
Rights and permissions
About this article
Cite this article
Polo, V., Garcia-Martin, E., Bambo, M. et al. Reliability and validity of Cirrus and Spectralis optical coherence tomography for detecting retinal atrophy in Alzheimer’s disease. Eye 28, 680–690 (2014). https://doi.org/10.1038/eye.2014.51
Received:
Accepted:
Published:
Issue date:
DOI: https://doi.org/10.1038/eye.2014.51
This article is cited by
-
Ability of Swept-source OCT and OCT-angiography to detect neuroretinal and vasculature changes in patients with Parkinson disease and essential tremor
Eye (2023)
-
Thickness measurements taken with the spectralis OCT increase with decreasing signal strength
BMC Ophthalmology (2022)
-
A systematic survey of advances in retinal imaging modalities for Alzheimer’s disease diagnosis
Metabolic Brain Disease (2022)
-
Multimodal Coherent Imaging of Retinal Biomarkers of Alzheimer’s Disease in a Mouse Model
Scientific Reports (2020)
-
Evaluation of macular thickness and volume tested by optical coherence tomography as biomarkers for Alzheimer’s disease in a memory clinic
Scientific Reports (2020)