Abstract

Diagnostic classification techniques used to diagnose cataracts, the world’s leading cause of blindness, are currently based on subjective methods. Here, we present optical coherence tomography as a noninvasive tool for volumetric visualization of lesions formed in the crystalline lens. A custom-made swept-source optical coherence tomography (SS-OCT) system was utilized to investigate the murine crystalline lens. In addition to imaging cataractous lesions in aged wildtype mice, we studied the structure and shape of cataracts in a mouse model of Alzheimer’s disease. Hyperscattering opacifications in the crystalline lens were observed in both groups. Post mortem histological analysis were performed to correlate findings in the anterior and posterior part of the lens to 3D OCT in vivo imaging. Our results showcase the capability of OCT to rapidly visualize cataractous lesions in the murine lens and suggest that OCT might be a valuable tool that provides additional insight for preclinical studies of cataract formation.

© 2020 Optical Society of America under the terms of the OSA Open Access Publishing Agreement

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2019 (3)

P. Eugui, D. J. Harper, A. Lichtenegger, M. Augustin, C. W. Merkle, A. Woehrer, C. K. Hitzenberger, and B. Baumann, “Polarization-sensitive imaging with simultaneous bright-and dark-field optical coherence tomography,” Opt. Lett. 44(16), 4040–4043 (2019).
[Crossref]

J. Gesperger, A. Lichtenegger, T. Roetzer, M. Augustin, D. J. Harper, P. Eugui, C. W. Merkle, C. K. Hitzenberger, A. Woehrer, and B. Baumann, “Comparison of intensity-and polarization-based contrast in amyloid-beta plaques as observed by optical coherence tomography,” Appl. Sci. 9(10), 2100 (2019).
[Crossref]

C. S. Lee, E. B. Larson, L. E. Gibbons, A. Y. Lee, S. M. McCurry, J. D. Bowen, W. C. McCormick, and P. K. Crane, “Associations between recent and established ophthalmic conditions and risk of Alzheimer’s disease,” Alzheimers Dement. 15(1), 34–41 (2019).
[Crossref]

2018 (8)

C. Poroy and A. A. Yücel, “Optical coherence tomography: Is really a new biomarker for Alzheimer’s disease?” Annals Indian Acad. Neurol. 21(2), 119 (2018).
[Crossref]

A. Lichtenegger, M. Muck, P. Eugui, D. J. Harper, M. Augustin, K. Leskovar, C. K. Hitzenberger, A. Woehrer, and B. Baumann, “Assessment of pathological features in Alzheimer’s disease brain tissue with a large field-of-view visible-light optical coherence microscope,” Neurophotonics 5(03), 1 (2018).
[Crossref]

I. Grulkowski, S. Manzanera, L. Cwiklinski, F. Sobczuk, K. Karnowski, and P. Artal, “Swept source optical coherence tomography and tunable lens technology for comprehensive imaging and biometry of the whole eye,” Optica 5(1), 52–59 (2018).
[Crossref]

B. Baumann, M. Augustin, A. Lichtenegger, D. J. Harper, M. Muck, P. Eugui, A. Wartak, M. Pircher, and C. K. Hitzenberger, “Polarization-sensitive optical coherence tomography imaging of the anterior mouse eye,” J. Biomed. Opt. 23(08), 1 (2018).
[Crossref]

A. de Castro, A. Benito, S. Manzanera, J. Mompeán, B. Canizares, D. Martínez, J. M. Marín, I. Grulkowski, and P. Artal, “Three-dimensional cataract crystalline lens imaging with swept-source optical coherence tomography,” Invest. Ophthalmol. Visual Sci. 59(2), 897–903 (2018).
[Crossref]

I. Grulkowski, S. Manzanera, L. Cwiklinski, J. Mompeán, A. de Castro, J. M. Marin, and P. Artal, “Volumetric macro-and micro-scale assessment of crystalline lens opacities in cataract patients using long-depth-range swept source optical coherence tomography,” Biomed. Opt. Express 9(8), 3821–3833 (2018).
[Crossref]

P. Eugui, A. Lichtenegger, M. Augustin, D. J. Harper, M. Muck, T. Roetzer, A. Wartak, T. Konegger, G. Widhalm, C. K. Hitzenberger, A. Woehrer, and B. Baumann, “Beyond backscattering: optical neuroimaging by BRAD,” Biomed. Opt. Express 9(6), 2476–2494 (2018).
[Crossref]

M. Ang, M. Baskaran, R. M. Werkmeister, J. Chua, D. Schmidl, V. A. dos Santos, G. Garhoefer, J. S. Mehta, and L. Schmetterer, “Anterior segment optical coherence tomography,” Prog. Retinal Eye Res. 66, 132–156 (2018).
[Crossref]

2017 (2)

S. R. Flaxman, R. R. Bourne, S. Resnikoff, P. Ackland, T. Braithwaite, M. V. Cicinelli, A. Das, J. B. Jonas, J. Keeffe, J. Kempen, H. Leasher, H. Limburg, K. Naidoo, K. Pesudovs, A. Silvester, G. Stevens, N. Tahhan, T. Y. Wong, and H. R. Taylor, “Global causes of blindness and distance vision impairment 1990–2020: a systematic review and meta-analysis,” The Lancet Glob. Heal. 5(12), e1221–e1234 (2017).
[Crossref]

C. Panthier, J. Burgos, H. Rouger, A. Saad, and D. Gatinel, “New objective lens density quantification method using swept-source optical coherence tomography technology: Comparison with existing methods,” J. Cataract Refractive Surg. 43(12), 1575–1581 (2017).
[Crossref]

2016 (1)

J. P. Cunha, N. Moura-Coelho, R. P. Proença, A. Dias-Santos, J. Ferreira, C. Louro, and A. Castanheira-Dinis, “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. 254(11), 2079–2092 (2016).
[Crossref]

2015 (4)

G. Coppola, A. Di Renzo, L. Ziccardi, F. Martelli, A. Fadda, G. Manni, P. Barboni, F. Pierelli, A. A. Sadun, and V. Parisi, “Optical coherence tomography in Alzheimer’s disease: a meta-analysis,” PLoS One 10(8), e0134750 (2015).
[Crossref]

A. Lozzi, A. Agrawal, A. Boretsky, C. G. Welle, and D. X. Hammer, “Image quality metrics for optical coherence angiography,” Biomed. Opt. Express 6(7), 2435–2447 (2015).
[Crossref]

P. Pérez-Merino, M. Velasco-Ocana, E. Martinez-Enriquez, and S. Marcos, “OCT-based crystalline lens topography in accommodating eyes,” Biomed. Opt. Express 6(12), 5039–5054 (2015).
[Crossref]

J. P. Su, Y. Li, M. Tang, L. Liu, A. D. Pechauer, D. Huang, and G. Liu, “Imaging the anterior eye with dynamic-focus swept-source optical coherence tomography,” J. Biomed. Opt. 20(12), 126002 (2015).
[Crossref]

2014 (5)

T. C. Chan, E. Y. Li, and J. C. Yau, “Application of anterior segment optical coherence tomography to identify eyes with posterior polar cataract at high risk for posterior capsule rupture,” J. Cataract Refractive Surg. 40(12), 2076–2081 (2014).
[Crossref]

X. Weiner, M. Baumeister, T. Kohnen, and J. Bühren, “Repeatability of lens densitometry using Scheimpflug imaging,” J. Cataract Refractive Surg. 40(5), 756–763 (2014).
[Crossref]

S. A. Lim, J. Hwang, K.-Y. Hwang, and S.-H. Chung, “Objective assessment of nuclear cataract: comparison of double-pass and Scheimpflug systems,” J. Cataract Refractive Surg. 40(5), 716–721 (2014).
[Crossref]

R. Chakraborty, K. D. Lacy, C. C. Tan, H. na Park, and M. T. Pardue, “Refractive index measurement of the mouse crystalline lens using optical coherence tomography,” Exp. Eye Res. 125, 62–70 (2014).
[Crossref]

R. Michael, C. Otto, A. Lenferink, E. Gelpi, G. A. Montenegro, J. Rosandić, F. Tresserra, R. I. Barraquer, and G. F. Vrensen, “Absence of amyloid-beta in lenses of Alzheimer patients: a confocal Raman microspectroscopic study,” Exp. Eye Res. 119, 44–53 (2014).
[Crossref]

2013 (1)

M. Adhi and J. S. Duker, “Optical coherence tomography–current and future applications,” Curr. opinion ophthalmology 24(3), 213–221 (2013).
[Crossref]

2012 (2)

G. Jun, J. A. Moncaster, C. Koutras, S. Seshadri, J. Buros, A. C. McKee, G. Levesque, P. A. Wolf, P. S. George-Hyslop, L. E. Goldstein, and L. A. Farrar, “δ-catenin is genetically and biologically associated with cortical cataract and future Alzheimer-related structural and functional brain changes,” PLoS One 7(9), e43728 (2012).
[Crossref]

M. F. Kraus, B. Potsaid, M. A. Mayer, R. Bock, B. Baumann, J. J. Liu, J. Hornegger, and J. G. Fujimoto, “Motion correction in optical coherence tomography volumes on a per a-scan basis using orthogonal scan patterns,” Biomed. Opt. Express 3(6), 1182–1199 (2012).
[Crossref]

2011 (4)

T.-H. Chou, O. P. Kocaoglu, D. Borja, M. Ruggeri, S. R. Uhlhorn, F. Manns, and V. Porciatti, “Postnatal elongation of eye size in DBA/2J mice compared with C57BL/6J mice: in vivo analysis with whole-eye OCT,” Invest. Ophthalmol. Visual Sci. 52(6), 3604–3612 (2011).
[Crossref]

S. Bassnett, Y. Shi, and G. F. Vrensen, “Biological glass: structural determinants of eye lens transparency,” Philos. Trans. R. Soc., B 366(1568), 1250–1264 (2011).
[Crossref]

R. Michael and A. Bron, “The ageing lens and cataract: a model of normal and pathological ageing,” Philos. Trans. R. Soc., B 366(1568), 1278–1292 (2011).
[Crossref]

M. A. Bermudez, A. F. Vicente, M. C. Romero, M. D. Arcos, J. M. Abalo, and F. Gonzalez, “Time course of cold cataract development in anesthetized mice,” Curr. Eye Res. 36(3), 278–284 (2011).
[Crossref]

2010 (3)

2009 (3)

J. L. B. Ramos, Y. Li, and D. Huang, “Clinical and research applications of anterior segment optical coherence tomography–a review,” Clin. & Exp. Ophthalmol. 37(1), 81–89 (2009).
[Crossref]

D. S. Grewal, G. S. Brar, and S. P. S. Grewal, “Correlation of nuclear cataract lens density using Scheimpflug images with Lens Opacities Classification System III and visual function,” Ophthalmology 116(8), 1436–1443 (2009).
[Crossref]

P. Rosales and S. Marcos, “Pentacam Scheimpflug quantitative imaging of the crystalline lens and intraocular lens,” J. Cataract Refractive Surg. 25(5), 421–428 (2009).
[Crossref]

2007 (1)

Y. Verma, K. Rao, M. Suresh, H. Patel, and P. Gupta, “Measurement of gradient refractive index profile of crystalline lens of fisheye in vivo using optical coherence tomography,” Appl. Phys. B 87(4), 607–610 (2007).
[Crossref]

2006 (3)

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2003 (3)

L. E. Goldstein, J. A. Muffat, R. A. Cherny, R. D. Moir, M. H. Ericsson, X. Huang, C. Mavros, J. A. Coccia, K. Y. Faget, K. A. Fitch, C. Masters, R. E. Tanzi, L. T. Chylack, and A. I. Bush, “Cytosolic β-amyloid deposition and supranuclear cataracts in lenses from people with Alzheimer’s disease,” Lancet 361(9365), 1258–1265 (2003).
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2002 (1)

1999 (1)

C. D. DiCarlo, W. P. Roach, D. A. Gagliano, S. A. Boppart, D. X. Hammer, A. B. Cox, and J. G. Fujimoto, “Comparison of optical coherence tomography imaging of cataracts with histopathology,” J. Biomed. Opt. 4(4), 450–459 (1999).
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1993 (3)

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1986 (1)

L. Calderone, P. Grimes, and M. Shalev, “Acute reversible cataract induced by xylazine and by ketamine-xylazine anesthesia in rats and mice,” Exp. Eye Res. 42(4), 331–337 (1986).
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1985 (1)

S. Remtulla and P. Hallett, “A schematic eye for the mouse, and comparisons with the rat,” Vision Res. 25(1), 21–31 (1985).
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1981 (1)

M. Campbell and A. Hughes, “An analytic, gradient index schematic lens and eye for the rat which predicts aberrations for finite pupils,” Vision Res. 21(7), 1129–1148 (1981).
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1969 (1)

B. Philipson, “Distribution of protein within the normal rat lens,” Invest. Ophthalmol. Visual Sci. 8, 258–270 (1969).

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G. Coppola, A. Di Renzo, L. Ziccardi, F. Martelli, A. Fadda, G. Manni, P. Barboni, F. Pierelli, A. A. Sadun, and V. Parisi, “Optical coherence tomography in Alzheimer’s disease: a meta-analysis,” PLoS One 10(8), e0134750 (2015).
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J. Gesperger, A. Lichtenegger, T. Roetzer, M. Augustin, D. J. Harper, P. Eugui, C. W. Merkle, C. K. Hitzenberger, A. Woehrer, and B. Baumann, “Comparison of intensity-and polarization-based contrast in amyloid-beta plaques as observed by optical coherence tomography,” Appl. Sci. 9(10), 2100 (2019).
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A. Lichtenegger, M. Muck, P. Eugui, D. J. Harper, M. Augustin, K. Leskovar, C. K. Hitzenberger, A. Woehrer, and B. Baumann, “Assessment of pathological features in Alzheimer’s disease brain tissue with a large field-of-view visible-light optical coherence microscope,” Neurophotonics 5(03), 1 (2018).
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B. Baumann, M. Augustin, A. Lichtenegger, D. J. Harper, M. Muck, P. Eugui, A. Wartak, M. Pircher, and C. K. Hitzenberger, “Polarization-sensitive optical coherence tomography imaging of the anterior mouse eye,” J. Biomed. Opt. 23(08), 1 (2018).
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M. A. Bermudez, A. F. Vicente, M. C. Romero, M. D. Arcos, J. M. Abalo, and F. Gonzalez, “Time course of cold cataract development in anesthetized mice,” Curr. Eye Res. 36(3), 278–284 (2011).
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Boppart, S. A.

C. D. DiCarlo, W. P. Roach, D. A. Gagliano, S. A. Boppart, D. X. Hammer, A. B. Cox, and J. G. Fujimoto, “Comparison of optical coherence tomography imaging of cataracts with histopathology,” J. Biomed. Opt. 4(4), 450–459 (1999).
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Boretsky, A.

Borja, D.

T.-H. Chou, O. P. Kocaoglu, D. Borja, M. Ruggeri, S. R. Uhlhorn, F. Manns, and V. Porciatti, “Postnatal elongation of eye size in DBA/2J mice compared with C57BL/6J mice: in vivo analysis with whole-eye OCT,” Invest. Ophthalmol. Visual Sci. 52(6), 3604–3612 (2011).
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S. R. Flaxman, R. R. Bourne, S. Resnikoff, P. Ackland, T. Braithwaite, M. V. Cicinelli, A. Das, J. B. Jonas, J. Keeffe, J. Kempen, H. Leasher, H. Limburg, K. Naidoo, K. Pesudovs, A. Silvester, G. Stevens, N. Tahhan, T. Y. Wong, and H. R. Taylor, “Global causes of blindness and distance vision impairment 1990–2020: a systematic review and meta-analysis,” The Lancet Glob. Heal. 5(12), e1221–e1234 (2017).
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C. S. Lee, E. B. Larson, L. E. Gibbons, A. Y. Lee, S. M. McCurry, J. D. Bowen, W. C. McCormick, and P. K. Crane, “Associations between recent and established ophthalmic conditions and risk of Alzheimer’s disease,” Alzheimers Dement. 15(1), 34–41 (2019).
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S. R. Flaxman, R. R. Bourne, S. Resnikoff, P. Ackland, T. Braithwaite, M. V. Cicinelli, A. Das, J. B. Jonas, J. Keeffe, J. Kempen, H. Leasher, H. Limburg, K. Naidoo, K. Pesudovs, A. Silvester, G. Stevens, N. Tahhan, T. Y. Wong, and H. R. Taylor, “Global causes of blindness and distance vision impairment 1990–2020: a systematic review and meta-analysis,” The Lancet Glob. Heal. 5(12), e1221–e1234 (2017).
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D. S. Grewal, G. S. Brar, and S. P. S. Grewal, “Correlation of nuclear cataract lens density using Scheimpflug images with Lens Opacities Classification System III and visual function,” Ophthalmology 116(8), 1436–1443 (2009).
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R. Michael and A. Bron, “The ageing lens and cataract: a model of normal and pathological ageing,” Philos. Trans. R. Soc., B 366(1568), 1278–1292 (2011).
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Bühren, J.

X. Weiner, M. Baumeister, T. Kohnen, and J. Bühren, “Repeatability of lens densitometry using Scheimpflug imaging,” J. Cataract Refractive Surg. 40(5), 756–763 (2014).
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Bullimore, M. A.

L. T. Chylack, J. K. Wolfe, D. M. Singer, M. C. Leske, M. A. Bullimore, I. L. Bailey, J. Friend, D. McCarthy, and S.-Y. Wu, “The lens opacities classification system III,” Arch. Ophthalmol. 111(6), 831–836 (1993).
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Burgos, J.

C. Panthier, J. Burgos, H. Rouger, A. Saad, and D. Gatinel, “New objective lens density quantification method using swept-source optical coherence tomography technology: Comparison with existing methods,” J. Cataract Refractive Surg. 43(12), 1575–1581 (2017).
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Bush, A. I.

L. E. Goldstein, J. A. Muffat, R. A. Cherny, R. D. Moir, M. H. Ericsson, X. Huang, C. Mavros, J. A. Coccia, K. Y. Faget, K. A. Fitch, C. Masters, R. E. Tanzi, L. T. Chylack, and A. I. Bush, “Cytosolic β-amyloid deposition and supranuclear cataracts in lenses from people with Alzheimer’s disease,” Lancet 361(9365), 1258–1265 (2003).
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Calderone, L.

L. Calderone, P. Grimes, and M. Shalev, “Acute reversible cataract induced by xylazine and by ketamine-xylazine anesthesia in rats and mice,” Exp. Eye Res. 42(4), 331–337 (1986).
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Calhoun, M. E.

R. Radde, T. Bolmont, S. A. Kaeser, J. Coomaraswamy, D. Lindau, L. Stoltze, M. E. Calhoun, F. Jäggi, H. Wolburg, S. Gengler, C. Haass, B. Ghetti, C. Czech, C. Holscher, P. M. Matthews, and M. Jucker, “Aβ42-driven cerebral amyloidosis in transgenic mice reveals early and robust pathology,” EMBO Rep. 7(9), 940–946 (2006).
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Campbell, M.

M. Campbell and A. Hughes, “An analytic, gradient index schematic lens and eye for the rat which predicts aberrations for finite pupils,” Vision Res. 21(7), 1129–1148 (1981).
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A. de Castro, A. Benito, S. Manzanera, J. Mompeán, B. Canizares, D. Martínez, J. M. Marín, I. Grulkowski, and P. Artal, “Three-dimensional cataract crystalline lens imaging with swept-source optical coherence tomography,” Invest. Ophthalmol. Visual Sci. 59(2), 897–903 (2018).
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J. P. Cunha, N. Moura-Coelho, R. P. Proença, A. Dias-Santos, J. Ferreira, C. Louro, and A. Castanheira-Dinis, “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. 254(11), 2079–2092 (2016).
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R. Chakraborty, K. D. Lacy, C. C. Tan, H. na Park, and M. T. Pardue, “Refractive index measurement of the mouse crystalline lens using optical coherence tomography,” Exp. Eye Res. 125, 62–70 (2014).
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T. C. Chan, E. Y. Li, and J. C. Yau, “Application of anterior segment optical coherence tomography to identify eyes with posterior polar cataract at high risk for posterior capsule rupture,” J. Cataract Refractive Surg. 40(12), 2076–2081 (2014).
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Cherny, R. A.

L. E. Goldstein, J. A. Muffat, R. A. Cherny, R. D. Moir, M. H. Ericsson, X. Huang, C. Mavros, J. A. Coccia, K. Y. Faget, K. A. Fitch, C. Masters, R. E. Tanzi, L. T. Chylack, and A. I. Bush, “Cytosolic β-amyloid deposition and supranuclear cataracts in lenses from people with Alzheimer’s disease,” Lancet 361(9365), 1258–1265 (2003).
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Chou, T.-H.

T.-H. Chou, O. P. Kocaoglu, D. Borja, M. Ruggeri, S. R. Uhlhorn, F. Manns, and V. Porciatti, “Postnatal elongation of eye size in DBA/2J mice compared with C57BL/6J mice: in vivo analysis with whole-eye OCT,” Invest. Ophthalmol. Visual Sci. 52(6), 3604–3612 (2011).
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M. Ang, M. Baskaran, R. M. Werkmeister, J. Chua, D. Schmidl, V. A. dos Santos, G. Garhoefer, J. S. Mehta, and L. Schmetterer, “Anterior segment optical coherence tomography,” Prog. Retinal Eye Res. 66, 132–156 (2018).
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Chung, S.-H.

S. A. Lim, J. Hwang, K.-Y. Hwang, and S.-H. Chung, “Objective assessment of nuclear cataract: comparison of double-pass and Scheimpflug systems,” J. Cataract Refractive Surg. 40(5), 716–721 (2014).
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Chylack, L. T.

L. E. Goldstein, J. A. Muffat, R. A. Cherny, R. D. Moir, M. H. Ericsson, X. Huang, C. Mavros, J. A. Coccia, K. Y. Faget, K. A. Fitch, C. Masters, R. E. Tanzi, L. T. Chylack, and A. I. Bush, “Cytosolic β-amyloid deposition and supranuclear cataracts in lenses from people with Alzheimer’s disease,” Lancet 361(9365), 1258–1265 (2003).
[Crossref]

L. T. Chylack, J. K. Wolfe, D. M. Singer, M. C. Leske, M. A. Bullimore, I. L. Bailey, J. Friend, D. McCarthy, and S.-Y. Wu, “The lens opacities classification system III,” Arch. Ophthalmol. 111(6), 831–836 (1993).
[Crossref]

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S. R. Flaxman, R. R. Bourne, S. Resnikoff, P. Ackland, T. Braithwaite, M. V. Cicinelli, A. Das, J. B. Jonas, J. Keeffe, J. Kempen, H. Leasher, H. Limburg, K. Naidoo, K. Pesudovs, A. Silvester, G. Stevens, N. Tahhan, T. Y. Wong, and H. R. Taylor, “Global causes of blindness and distance vision impairment 1990–2020: a systematic review and meta-analysis,” The Lancet Glob. Heal. 5(12), e1221–e1234 (2017).
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L. E. Goldstein, J. A. Muffat, R. A. Cherny, R. D. Moir, M. H. Ericsson, X. Huang, C. Mavros, J. A. Coccia, K. Y. Faget, K. A. Fitch, C. Masters, R. E. Tanzi, L. T. Chylack, and A. I. Bush, “Cytosolic β-amyloid deposition and supranuclear cataracts in lenses from people with Alzheimer’s disease,” Lancet 361(9365), 1258–1265 (2003).
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R. Radde, T. Bolmont, S. A. Kaeser, J. Coomaraswamy, D. Lindau, L. Stoltze, M. E. Calhoun, F. Jäggi, H. Wolburg, S. Gengler, C. Haass, B. Ghetti, C. Czech, C. Holscher, P. M. Matthews, and M. Jucker, “Aβ42-driven cerebral amyloidosis in transgenic mice reveals early and robust pathology,” EMBO Rep. 7(9), 940–946 (2006).
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Coppola, G.

G. Coppola, A. Di Renzo, L. Ziccardi, F. Martelli, A. Fadda, G. Manni, P. Barboni, F. Pierelli, A. A. Sadun, and V. Parisi, “Optical coherence tomography in Alzheimer’s disease: a meta-analysis,” PLoS One 10(8), e0134750 (2015).
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Cox, A. B.

C. D. DiCarlo, W. P. Roach, D. A. Gagliano, S. A. Boppart, D. X. Hammer, A. B. Cox, and J. G. Fujimoto, “Comparison of optical coherence tomography imaging of cataracts with histopathology,” J. Biomed. Opt. 4(4), 450–459 (1999).
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Crane, P. K.

C. S. Lee, E. B. Larson, L. E. Gibbons, A. Y. Lee, S. M. McCurry, J. D. Bowen, W. C. McCormick, and P. K. Crane, “Associations between recent and established ophthalmic conditions and risk of Alzheimer’s disease,” Alzheimers Dement. 15(1), 34–41 (2019).
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Cunha, J. P.

J. P. Cunha, N. Moura-Coelho, R. P. Proença, A. Dias-Santos, J. Ferreira, C. Louro, and A. Castanheira-Dinis, “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. 254(11), 2079–2092 (2016).
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Cwiklinski, L.

Czech, C.

R. Radde, T. Bolmont, S. A. Kaeser, J. Coomaraswamy, D. Lindau, L. Stoltze, M. E. Calhoun, F. Jäggi, H. Wolburg, S. Gengler, C. Haass, B. Ghetti, C. Czech, C. Holscher, P. M. Matthews, and M. Jucker, “Aβ42-driven cerebral amyloidosis in transgenic mice reveals early and robust pathology,” EMBO Rep. 7(9), 940–946 (2006).
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Das, A.

S. R. Flaxman, R. R. Bourne, S. Resnikoff, P. Ackland, T. Braithwaite, M. V. Cicinelli, A. Das, J. B. Jonas, J. Keeffe, J. Kempen, H. Leasher, H. Limburg, K. Naidoo, K. Pesudovs, A. Silvester, G. Stevens, N. Tahhan, T. Y. Wong, and H. R. Taylor, “Global causes of blindness and distance vision impairment 1990–2020: a systematic review and meta-analysis,” The Lancet Glob. Heal. 5(12), e1221–e1234 (2017).
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de Boer, J. F.

de Castro, A.

Di Renzo, A.

G. Coppola, A. Di Renzo, L. Ziccardi, F. Martelli, A. Fadda, G. Manni, P. Barboni, F. Pierelli, A. A. Sadun, and V. Parisi, “Optical coherence tomography in Alzheimer’s disease: a meta-analysis,” PLoS One 10(8), e0134750 (2015).
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J. P. Cunha, N. Moura-Coelho, R. P. Proença, A. Dias-Santos, J. Ferreira, C. Louro, and A. Castanheira-Dinis, “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. 254(11), 2079–2092 (2016).
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DiCarlo, C. D.

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R. Michael, C. Otto, A. Lenferink, E. Gelpi, G. A. Montenegro, J. Rosandić, F. Tresserra, R. I. Barraquer, and G. F. Vrensen, “Absence of amyloid-beta in lenses of Alzheimer patients: a confocal Raman microspectroscopic study,” Exp. Eye Res. 119, 44–53 (2014).
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R. Chakraborty, K. D. Lacy, C. C. Tan, H. na Park, and M. T. Pardue, “Refractive index measurement of the mouse crystalline lens using optical coherence tomography,” Exp. Eye Res. 125, 62–70 (2014).
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Supplementary Material (1)

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» Visualization 1       Video showing a volumetric dataset of an opacification formed in the anterior lens.

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Figures (6)

Fig. 1.
Fig. 1. OCT imaging system and experimental protocol. The anesthetized mice were imaged in vivo with the OCT device depicted on the left. The eyes were extracted post mortem for histological processing as described on the right. MEMS: Microelectromechanical scanner.
Fig. 2.
Fig. 2. Crystalline lens imaging with OCT. a) Illustration of the mouse eye. b) Whole OCT section of a wildtype mouse eye where the two focus locations selected for this experiment are indicated with a red box (anterior lens surface) and a green box (posterior lens surface). The scale bar on the right indicates the anatomical axial lengths of the different ocular components [31]. Note that the images were not corrected for light refraction by the individual structures. The retina appears flipped over the zero delay in this image due to the available imaging range such that the vitreous length appears reduced. c) Zoom-in on the anterior lens pole of a wildtype mouse (age 23 months) where an opacity has formed as indicated by the yellow arrow. The bright artifact at the corneal epithelium is due to a strong backreflection at the air-tissue interface. d) Zoom-in to the posterior part of the lens of the corresponding mouse. e) Zoom-in to the anterior lens part of a transgenic mouse of the same age where an opaque region can be observed posterior to the lens surface. f) Posterior lens surface of the transgenic mouse. Images were not corrected for light refraction. g) Pie chart representing the presence of lesions for the total number of eyes imaged. Four datasets were discarded due to poor image quality or eye condition. h) Pie chart representing the number of eyes with opacity lesions observed for wildtype and transgenic mice.
Fig. 3.
Fig. 3. Examples of different cataract manifestations in OCT. Details of the anterior lens (a-d) and the corresponding counterparts in the posterior lens (e-h) are shown. a) Representative B-scan of an anterior lens devoid of opacities. b) Diffuse cataract in the anterior part of the lens. Increased scattering can be observed across the anterior lens capsule. c) Bubble-shaped opacity formation close to the anterior lens surface. d) Cataract located in the lens nucleus. No opacity can be observed at the lens surface. e-h) Corresponding B-scans focusing on the posterior part of the lens. e) Only a weak scattering signal can be observed in the posterior lens. The retina is located at the bottom of the image. f-g) Diffuse opacifications with increased scattering signal formed in the lens cortex. Red arrows indicate opacification. Images were not corrected for light refraction. The horizontal lines in panels (a-d) are artifacts caused by a reflection within the system optics that could not be entirely removed by post processing. Scale bars correspond to 0.5 mm.
Fig. 4.
Fig. 4. Lenticular lesion in a 23-month old wildtype mouse investigated using the SS-OCT system. a) B-scan of a mouse anterior lens which exhibits a bubble-shaped lesion. b) Corresponding histological section of the imaged area. The lesion is indicated by an arrow. c) Depth intensity projection over 500 µm in the lesion region. d) 3D reconstruction of the anterior segment. The investigated bubble-shaped lesion can be observed right beneath the lens surface. OCT images were not corrected for light refraction. e) Measured sizes of the 6 bubble lesions observed in the 3D datasets.
Fig. 5.
Fig. 5. The figure below shows representative lesions we observed in the lens of an APPPS1$^{-/-}$ mouse. Both anterior subcapsular cataract (ASC) and posterior subcapsular cataract (PSC) were observed. Anterior and posterior sutures were composed of enlarged fiber cells around the suture, fragmenting into eosinic globules (Morgagnian globules, arrowheads) and subcapsular vacuoles filled with debris (asterisks). Clods of cortical material are indicated with arrows.
Fig. 6.
Fig. 6. Analysis of grade and contrast of the lens opacifications. a) Histogram distributions of the opacification gradings given for wildtype and transgenic mice. b) Weber contrast for wildtype and transgenic mouse groups. c) Weber contrast for adult (17/18 months) and old (23/24 months) mouse groups. d) Comparison of the Weber contrast values retrieved from the data and the blind visual grades. A tendency to increased WC values in high grades can be observed.

Equations (1)

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W C = μ c μ b μ b