Abstract

Cone photoreceptors in the living human eye have recently been imaged with micron-scale resolution in all three spatial dimensions using adaptive optics optical coherence tomography. While these advances have allowed non-invasive study of the three-dimensional structure of living human cones, studies of their function and physiology are still hampered by the difficulties to monitor the same cells over time. The purpose of this study is to demonstrate the feasibility of cone monitoring using ultrahigh-resolution adaptive optics optical coherence tomography. Critical to this is incorporation of a high speed CMOS camera (125 KHz) and a novel feature-based, image registration/dewarping algorithm for reducing the deleterious effects of eye motion on volume images. Volume movies were acquired on three healthy subjects at retinal eccentricities from 0.5° to 6°. Image registration/dewarping reduced motion artifacts in the movies from 15 μm to 1.3 μm root mean square, the latter sufficient for identifying and tracking cones. Cone row-to-row spacing and outer segment lengths were consistent with that reported in the literature. Cone length analysis demonstrates that UHR-AO-OCT is sufficiently sensitive to measure real length differences between cones in the same 0.5° retinal patch, and requires no more than five measurements of OS length to achieve 95% confidence. We know of no other imaging modality that can monitor foveal or parafoveal cones over time with comparable resolution in all three dimensions.

©2011 Optical Society of America

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2010 (5)

2009 (4)

2008 (6)

R. J. Zawadzki, B. Cense, Y. Zhang, S. S. Choi, D. T. Miller, and J. S. Werner, “Ultrahigh-resolution optical coherence tomography with monochromatic and chromatic aberration correction,” Opt. Express 16(11), 8126–8143 (2008).
[Crossref] [PubMed]

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[Crossref] [PubMed]

T. Y. Chui, H. Song, and S. A. Burns, “Adaptive-optics imaging of human cone photoreceptor distribution,” J. Opt. Soc. Am. A 25(12), 3021–3029 (2008).
[Crossref] [PubMed]

T. Y. Chui, H. Song, and S. A. Burns, “Individual variations in human cone photoreceptor packing density: variations with refractive error,” Invest. Ophthalmol. Vis. Sci. 49(10), 4679–4687 (2008).
[Crossref] [PubMed]

B. Potsaid, I. Gorczynska, V. J. Srinivasan, Y. Chen, J. Jiang, A. Cable, and J. G. Fujimoto, “Ultrahigh speed spectral / Fourier domain OCT ophthalmic imaging at 70,000 to 312,500 axial scans per second,” Opt. Express 16(19), 15149–15169 (2008).
[Crossref] [PubMed]

V. J. Srinivasan, B. K. Monson, M. Wojtkowski, R. A. Bilonick, I. Gorczynska, R. Chen, J. S. Duker, J. S. Schuman, and J. G. Fujimoto, “Characterization of outer retinal morphology with high-speed, ultrahigh-resolution optical coherence tomography,” Invest. Ophthalmol. Vis. Sci. 49(4), 1571–1579 (2008).
[Crossref] [PubMed]

2007 (3)

2006 (6)

2005 (4)

M. Wojtkowski, V. Srinivasan, J. G. Fujimoto, T. Ko, J. S. Schuman, A. Kowalczyk, and J. S. Duker, “Three-dimensional retinal imaging with high-speed ultrahigh-resolution optical coherence tomography,” Ophthalmology 112(10), 1734–1746 (2005).
[Crossref] [PubMed]

Y. Zhang, J. Rha, R. Jonnal, and D. T. Miller, “Adaptive optics parallel spectral domain optical coherence tomography for imaging the living retina,” Opt. Express 13(12), 4792–4811 (2005).
[Crossref] [PubMed]

E. J. Fernández, B. Povazay, B. Hermann, A. Unterhuber, H. Sattmann, P. M. Prieto, R. Leitgeb, P. Ahnelt, P. Artal, and W. Drexler, “Three-dimensional adaptive optics ultrahigh-resolution optical coherence tomography using a liquid crystal spatial light modulator,” Vision Res. 45(28), 3432–3444 (2005).
[Crossref] [PubMed]

R. J. Zawadzki, S. M. Jones, S. S. Olivier, M. Zhao, B. A. Bower, J. A. Izatt, S. Choi, S. Laut, and J. S. Werner, “Adaptive-optics optical coherence tomography for high-resolution and high-speed 3D retinal in vivo imaging,” Opt. Express 13(21), 8532–8546 (2005).
[Crossref] [PubMed]

2004 (2)

2002 (1)

M. Wojtkowski, R. Leitgeb, A. Kowalczyk, T. Bajraszewski, and A. F. Fercher, “In vivo human retinal imaging by Fourier domain optical coherence tomography,” J. Biomed. Opt. 7(3), 457–463 (2002).
[Crossref] [PubMed]

1997 (1)

1996 (1)

D. T. Miller, D. R. Williams, G. M. Morris, and J. Liang, “Images of cone photoreceptors in the living human eye,” Vision Res. 36(8), 1067–1079 (1996).
[Crossref] [PubMed]

1987 (1)

C. A. Curcio, K. R. Sloan, O. Packer, A. E. Hendrickson, and R. E. Kalina, “Distribution of cones in human and monkey retina: individual variability and radial asymmetry,” Science 236(4801), 579–582 (1987).
[Crossref] [PubMed]

1982 (1)

J. I. Yellott., “Spectral analysis of spatial sampling by photoreceptors: topological disorder prevents aliasing,” Vision Res. 22(9), 1205–1210 (1982).
[Crossref] [PubMed]

1973 (1)

A. W. Snyder and C. Pask, “The Stiles-Crawford effect--explanation and consequences,” Vision Res. 13(6), 1115–1137 (1973).
[Crossref] [PubMed]

1954 (1)

Ahnelt, P.

E. J. Fernández, B. Povazay, B. Hermann, A. Unterhuber, H. Sattmann, P. M. Prieto, R. Leitgeb, P. Ahnelt, P. Artal, and W. Drexler, “Three-dimensional adaptive optics ultrahigh-resolution optical coherence tomography using a liquid crystal spatial light modulator,” Vision Res. 45(28), 3432–3444 (2005).
[Crossref] [PubMed]

Ahnelt, P. K.

Arathorn, D. W.

Armington, J. C.

Artal, P.

E. J. Fernández, A. Unterhuber, B. Považay, B. Hermann, P. Artal, and W. Drexler, “Chromatic aberration correction of the human eye for retinal imaging in the near infrared,” Opt. Express 14(13), 6213–6225 (2006).
[Crossref] [PubMed]

E. J. Fernández, B. Povazay, B. Hermann, A. Unterhuber, H. Sattmann, P. M. Prieto, R. Leitgeb, P. Ahnelt, P. Artal, and W. Drexler, “Three-dimensional adaptive optics ultrahigh-resolution optical coherence tomography using a liquid crystal spatial light modulator,” Vision Res. 45(28), 3432–3444 (2005).
[Crossref] [PubMed]

Bajraszewski, T.

M. Wojtkowski, R. Leitgeb, A. Kowalczyk, T. Bajraszewski, and A. F. Fercher, “In vivo human retinal imaging by Fourier domain optical coherence tomography,” J. Biomed. Opt. 7(3), 457–463 (2002).
[Crossref] [PubMed]

Baumann, B.

Besecker, J.

O. P. Kocaoglu, B. Cense, Q. Wang, J. Bruestle, J. Besecker, W. Gao, R. Jonnal, and D. T. Miller, “Imaging retinal nerve fiber bundles at ultrahigh-speed and ultrahigh-resolution using OCT with adaptive optics,” Proc. SPIE 7550(755010), 755010, 755010-5 (2010).
[Crossref]

Besecker, J. R.

Bigelow, C. E.

Bilonick, R. A.

V. J. Srinivasan, B. K. Monson, M. Wojtkowski, R. A. Bilonick, I. Gorczynska, R. Chen, J. S. Duker, J. S. Schuman, and J. G. Fujimoto, “Characterization of outer retinal morphology with high-speed, ultrahigh-resolution optical coherence tomography,” Invest. Ophthalmol. Vis. Sci. 49(4), 1571–1579 (2008).
[Crossref] [PubMed]

Bloom, B.

Bouma, B.

Bower, B. A.

Bradu, A.

Brown, J. M.

Bruestle, J.

O. P. Kocaoglu, B. Cense, Q. Wang, J. Bruestle, J. Besecker, W. Gao, R. Jonnal, and D. T. Miller, “Imaging retinal nerve fiber bundles at ultrahigh-speed and ultrahigh-resolution using OCT with adaptive optics,” Proc. SPIE 7550(755010), 755010, 755010-5 (2010).
[Crossref]

Burns, S. A.

Cable, A.

Carroll, J.

J. T. McAllister, A. M. Dubis, D. M. Tait, S. Ostler, J. Rha, K. E. Stepien, C. G. Summers, and J. Carroll, “Arrested development: high-resolution imaging of foveal morphology in albinism,” Vision Res. 50(8), 810–817 (2010).
[Crossref] [PubMed]

C. Torti, B. Považay, B. Hofer, A. Unterhuber, J. Carroll, P. K. Ahnelt, and W. Drexler, “Adaptive optics optical coherence tomography at 120,000 depth scans/s for non-invasive cellular phenotyping of the living human retina,” Opt. Express 17(22), 19382–19400 (2009).
[Crossref] [PubMed]

Cense, B.

R. S. Jonnal, J. R. Besecker, J. C. Derby, O. P. Kocaoglu, B. Cense, W. Gao, Q. Wang, and D. T. Miller, “Imaging outer segment renewal in living human cone photoreceptors,” Opt. Express 18(5), 5257–5270 (2010).
[Crossref] [PubMed]

O. P. Kocaoglu, B. Cense, Q. Wang, J. Bruestle, J. Besecker, W. Gao, R. Jonnal, and D. T. Miller, “Imaging retinal nerve fiber bundles at ultrahigh-speed and ultrahigh-resolution using OCT with adaptive optics,” Proc. SPIE 7550(755010), 755010, 755010-5 (2010).
[Crossref]

B. Cense, W. Gao, J. M. Brown, S. M. Jones, R. S. Jonnal, M. Mujat, B. H. Park, J. F. de Boer, and D. T. Miller, “Retinal imaging with polarization-sensitive optical coherence tomography and adaptive optics,” Opt. Express 17(24), 21634–21651 (2009).
[Crossref] [PubMed]

B. Cense, E. Koperda, J. M. Brown, O. P. Kocaoglu, W. Gao, R. S. Jonnal, and D. T. Miller, “Volumetric retinal imaging with ultrahigh-resolution spectral-domain optical coherence tomography and adaptive optics using two broadband light sources,” Opt. Express 17(5), 4095–4111 (2009).
[Crossref] [PubMed]

R. J. Zawadzki, B. Cense, Y. Zhang, S. S. Choi, D. T. Miller, and J. S. Werner, “Ultrahigh-resolution optical coherence tomography with monochromatic and chromatic aberration correction,” Opt. Express 16(11), 8126–8143 (2008).
[Crossref] [PubMed]

Y. Zhang, B. Cense, J. Rha, R. S. Jonnal, W. Gao, R. J. Zawadzki, J. S. Werner, S. Jones, S. Olivier, and D. T. Miller, “High-speed volumetric imaging of cone photoreceptors with adaptive optics spectral-domain optical coherence tomography,” Opt. Express 14(10), 4380–4394 (2006).
[Crossref] [PubMed]

B. Cense, N. Nassif, T. Chen, M. Pierce, S. H. Yun, B. Park, B. Bouma, G. Tearney, and J. de Boer, “Ultrahigh-resolution high-speed retinal imaging using spectral-domain optical coherence tomography,” Opt. Express 12(11), 2435–2447 (2004).
[Crossref] [PubMed]

Chen, R.

V. J. Srinivasan, B. K. Monson, M. Wojtkowski, R. A. Bilonick, I. Gorczynska, R. Chen, J. S. Duker, J. S. Schuman, and J. G. Fujimoto, “Characterization of outer retinal morphology with high-speed, ultrahigh-resolution optical coherence tomography,” Invest. Ophthalmol. Vis. Sci. 49(4), 1571–1579 (2008).
[Crossref] [PubMed]

Chen, T.

Chen, Y.

Choi, S.

Choi, S. S.

Chui, T. Y.

T. Y. Chui, H. Song, and S. A. Burns, “Individual variations in human cone photoreceptor packing density: variations with refractive error,” Invest. Ophthalmol. Vis. Sci. 49(10), 4679–4687 (2008).
[Crossref] [PubMed]

T. Y. Chui, H. Song, and S. A. Burns, “Adaptive-optics imaging of human cone photoreceptor distribution,” J. Opt. Soc. Am. A 25(12), 3021–3029 (2008).
[Crossref] [PubMed]

Curcio, C. A.

C. A. Curcio, K. R. Sloan, O. Packer, A. E. Hendrickson, and R. E. Kalina, “Distribution of cones in human and monkey retina: individual variability and radial asymmetry,” Science 236(4801), 579–582 (1987).
[Crossref] [PubMed]

Dainty, C.

de Boer, J.

de Boer, J. F.

Derby, J. C.

Drexler, W.

Dubis, A. M.

J. T. McAllister, A. M. Dubis, D. M. Tait, S. Ostler, J. Rha, K. E. Stepien, C. G. Summers, and J. Carroll, “Arrested development: high-resolution imaging of foveal morphology in albinism,” Vision Res. 50(8), 810–817 (2010).
[Crossref] [PubMed]

Duker, J. S.

V. J. Srinivasan, B. K. Monson, M. Wojtkowski, R. A. Bilonick, I. Gorczynska, R. Chen, J. S. Duker, J. S. Schuman, and J. G. Fujimoto, “Characterization of outer retinal morphology with high-speed, ultrahigh-resolution optical coherence tomography,” Invest. Ophthalmol. Vis. Sci. 49(4), 1571–1579 (2008).
[Crossref] [PubMed]

M. Wojtkowski, V. Srinivasan, J. G. Fujimoto, T. Ko, J. S. Schuman, A. Kowalczyk, and J. S. Duker, “Three-dimensional retinal imaging with high-speed ultrahigh-resolution optical coherence tomography,” Ophthalmology 112(10), 1734–1746 (2005).
[Crossref] [PubMed]

Fercher, A. F.

M. Wojtkowski, R. Leitgeb, A. Kowalczyk, T. Bajraszewski, and A. F. Fercher, “In vivo human retinal imaging by Fourier domain optical coherence tomography,” J. Biomed. Opt. 7(3), 457–463 (2002).
[Crossref] [PubMed]

Ferguson, R. D.

Fernández, E. J.

Fujimoto, J. G.

V. J. Srinivasan, B. K. Monson, M. Wojtkowski, R. A. Bilonick, I. Gorczynska, R. Chen, J. S. Duker, J. S. Schuman, and J. G. Fujimoto, “Characterization of outer retinal morphology with high-speed, ultrahigh-resolution optical coherence tomography,” Invest. Ophthalmol. Vis. Sci. 49(4), 1571–1579 (2008).
[Crossref] [PubMed]

B. Potsaid, I. Gorczynska, V. J. Srinivasan, Y. Chen, J. Jiang, A. Cable, and J. G. Fujimoto, “Ultrahigh speed spectral / Fourier domain OCT ophthalmic imaging at 70,000 to 312,500 axial scans per second,” Opt. Express 16(19), 15149–15169 (2008).
[Crossref] [PubMed]

M. Wojtkowski, V. Srinivasan, J. G. Fujimoto, T. Ko, J. S. Schuman, A. Kowalczyk, and J. S. Duker, “Three-dimensional retinal imaging with high-speed ultrahigh-resolution optical coherence tomography,” Ophthalmology 112(10), 1734–1746 (2005).
[Crossref] [PubMed]

Gao, W.

Gorczynska, I.

V. J. Srinivasan, B. K. Monson, M. Wojtkowski, R. A. Bilonick, I. Gorczynska, R. Chen, J. S. Duker, J. S. Schuman, and J. G. Fujimoto, “Characterization of outer retinal morphology with high-speed, ultrahigh-resolution optical coherence tomography,” Invest. Ophthalmol. Vis. Sci. 49(4), 1571–1579 (2008).
[Crossref] [PubMed]

B. Potsaid, I. Gorczynska, V. J. Srinivasan, Y. Chen, J. Jiang, A. Cable, and J. G. Fujimoto, “Ultrahigh speed spectral / Fourier domain OCT ophthalmic imaging at 70,000 to 312,500 axial scans per second,” Opt. Express 16(19), 15149–15169 (2008).
[Crossref] [PubMed]

Götzinger, E.

Hammer, D. X.

Hendrickson, A. E.

C. A. Curcio, K. R. Sloan, O. Packer, A. E. Hendrickson, and R. E. Kalina, “Distribution of cones in human and monkey retina: individual variability and radial asymmetry,” Science 236(4801), 579–582 (1987).
[Crossref] [PubMed]

Hermann, B.

Hitzenberger, C. K.

Hofer, B.

Hubel, D. H.

S. Martinez-Conde, S. L. Macknik, and D. H. Hubel, “The role of fixational eye movements in visual perception,” Nat. Rev. Neurosci. 5(3), 229–240 (2004).
[Crossref] [PubMed]

Iftimia, N. V.

Izatt, J. A.

Jiang, J.

Jones, S.

Jones, S. M.

Jonnal, R.

O. P. Kocaoglu, B. Cense, Q. Wang, J. Bruestle, J. Besecker, W. Gao, R. Jonnal, and D. T. Miller, “Imaging retinal nerve fiber bundles at ultrahigh-speed and ultrahigh-resolution using OCT with adaptive optics,” Proc. SPIE 7550(755010), 755010, 755010-5 (2010).
[Crossref]

Y. Zhang, J. Rha, R. Jonnal, and D. T. Miller, “Adaptive optics parallel spectral domain optical coherence tomography for imaging the living retina,” Opt. Express 13(12), 4792–4811 (2005).
[Crossref] [PubMed]

Jonnal, R. S.

Kalina, R. E.

C. A. Curcio, K. R. Sloan, O. Packer, A. E. Hendrickson, and R. E. Kalina, “Distribution of cones in human and monkey retina: individual variability and radial asymmetry,” Science 236(4801), 579–582 (1987).
[Crossref] [PubMed]

Ko, T.

M. Wojtkowski, V. Srinivasan, J. G. Fujimoto, T. Ko, J. S. Schuman, A. Kowalczyk, and J. S. Duker, “Three-dimensional retinal imaging with high-speed ultrahigh-resolution optical coherence tomography,” Ophthalmology 112(10), 1734–1746 (2005).
[Crossref] [PubMed]

Kocaoglu, O. P.

Kolbitsch, C.

Koperda, E.

Kowalczyk, A.

M. Wojtkowski, V. Srinivasan, J. G. Fujimoto, T. Ko, J. S. Schuman, A. Kowalczyk, and J. S. Duker, “Three-dimensional retinal imaging with high-speed ultrahigh-resolution optical coherence tomography,” Ophthalmology 112(10), 1734–1746 (2005).
[Crossref] [PubMed]

M. Wojtkowski, R. Leitgeb, A. Kowalczyk, T. Bajraszewski, and A. F. Fercher, “In vivo human retinal imaging by Fourier domain optical coherence tomography,” J. Biomed. Opt. 7(3), 457–463 (2002).
[Crossref] [PubMed]

Laut, S.

Leitgeb, R.

E. J. Fernández, B. Povazay, B. Hermann, A. Unterhuber, H. Sattmann, P. M. Prieto, R. Leitgeb, P. Ahnelt, P. Artal, and W. Drexler, “Three-dimensional adaptive optics ultrahigh-resolution optical coherence tomography using a liquid crystal spatial light modulator,” Vision Res. 45(28), 3432–3444 (2005).
[Crossref] [PubMed]

M. Wojtkowski, R. Leitgeb, A. Kowalczyk, T. Bajraszewski, and A. F. Fercher, “In vivo human retinal imaging by Fourier domain optical coherence tomography,” J. Biomed. Opt. 7(3), 457–463 (2002).
[Crossref] [PubMed]

Leitgeb, R. A.

Liang, J.

J. Liang, D. R. Williams, and D. T. Miller, “Supernormal vision and high-resolution retinal imaging through adaptive optics,” J. Opt. Soc. Am. A 14(11), 2884–2892 (1997).
[Crossref] [PubMed]

D. T. Miller, D. R. Williams, G. M. Morris, and J. Liang, “Images of cone photoreceptors in the living human eye,” Vision Res. 36(8), 1067–1079 (1996).
[Crossref] [PubMed]

Macknik, S. L.

S. Martinez-Conde, S. L. Macknik, and D. H. Hubel, “The role of fixational eye movements in visual perception,” Nat. Rev. Neurosci. 5(3), 229–240 (2004).
[Crossref] [PubMed]

Martinez-Conde, S.

S. Martinez-Conde, S. L. Macknik, and D. H. Hubel, “The role of fixational eye movements in visual perception,” Nat. Rev. Neurosci. 5(3), 229–240 (2004).
[Crossref] [PubMed]

McAllister, J. T.

J. T. McAllister, A. M. Dubis, D. M. Tait, S. Ostler, J. Rha, K. E. Stepien, C. G. Summers, and J. Carroll, “Arrested development: high-resolution imaging of foveal morphology in albinism,” Vision Res. 50(8), 810–817 (2010).
[Crossref] [PubMed]

Merino, D.

Miller, D. T.

O. P. Kocaoglu, B. Cense, Q. Wang, J. Bruestle, J. Besecker, W. Gao, R. Jonnal, and D. T. Miller, “Imaging retinal nerve fiber bundles at ultrahigh-speed and ultrahigh-resolution using OCT with adaptive optics,” Proc. SPIE 7550(755010), 755010, 755010-5 (2010).
[Crossref]

R. S. Jonnal, J. R. Besecker, J. C. Derby, O. P. Kocaoglu, B. Cense, W. Gao, Q. Wang, and D. T. Miller, “Imaging outer segment renewal in living human cone photoreceptors,” Opt. Express 18(5), 5257–5270 (2010).
[Crossref] [PubMed]

B. Cense, W. Gao, J. M. Brown, S. M. Jones, R. S. Jonnal, M. Mujat, B. H. Park, J. F. de Boer, and D. T. Miller, “Retinal imaging with polarization-sensitive optical coherence tomography and adaptive optics,” Opt. Express 17(24), 21634–21651 (2009).
[Crossref] [PubMed]

B. Cense, E. Koperda, J. M. Brown, O. P. Kocaoglu, W. Gao, R. S. Jonnal, and D. T. Miller, “Volumetric retinal imaging with ultrahigh-resolution spectral-domain optical coherence tomography and adaptive optics using two broadband light sources,” Opt. Express 17(5), 4095–4111 (2009).
[Crossref] [PubMed]

R. J. Zawadzki, B. Cense, Y. Zhang, S. S. Choi, D. T. Miller, and J. S. Werner, “Ultrahigh-resolution optical coherence tomography with monochromatic and chromatic aberration correction,” Opt. Express 16(11), 8126–8143 (2008).
[Crossref] [PubMed]

J. Rha, R. S. Jonnal, K. E. Thorn, J. Qu, Y. Zhang, and D. T. Miller, “Adaptive optics flood-illumination camera for high speed retinal imaging,” Opt. Express 14(10), 4552–4569 (2006).
[Crossref] [PubMed]

Y. Zhang, B. Cense, J. Rha, R. S. Jonnal, W. Gao, R. J. Zawadzki, J. S. Werner, S. Jones, S. Olivier, and D. T. Miller, “High-speed volumetric imaging of cone photoreceptors with adaptive optics spectral-domain optical coherence tomography,” Opt. Express 14(10), 4380–4394 (2006).
[Crossref] [PubMed]

Y. Zhang, J. Rha, R. Jonnal, and D. T. Miller, “Adaptive optics parallel spectral domain optical coherence tomography for imaging the living retina,” Opt. Express 13(12), 4792–4811 (2005).
[Crossref] [PubMed]

J. Liang, D. R. Williams, and D. T. Miller, “Supernormal vision and high-resolution retinal imaging through adaptive optics,” J. Opt. Soc. Am. A 14(11), 2884–2892 (1997).
[Crossref] [PubMed]

D. T. Miller, D. R. Williams, G. M. Morris, and J. Liang, “Images of cone photoreceptors in the living human eye,” Vision Res. 36(8), 1067–1079 (1996).
[Crossref] [PubMed]

Monson, B. K.

V. J. Srinivasan, B. K. Monson, M. Wojtkowski, R. A. Bilonick, I. Gorczynska, R. Chen, J. S. Duker, J. S. Schuman, and J. G. Fujimoto, “Characterization of outer retinal morphology with high-speed, ultrahigh-resolution optical coherence tomography,” Invest. Ophthalmol. Vis. Sci. 49(4), 1571–1579 (2008).
[Crossref] [PubMed]

Morris, G. M.

D. T. Miller, D. R. Williams, G. M. Morris, and J. Liang, “Images of cone photoreceptors in the living human eye,” Vision Res. 36(8), 1067–1079 (1996).
[Crossref] [PubMed]

Mujat, M.

Nassif, N.

Oliver, S. S.

Olivier, S.

Olivier, S. S.

Ostler, S.

J. T. McAllister, A. M. Dubis, D. M. Tait, S. Ostler, J. Rha, K. E. Stepien, C. G. Summers, and J. Carroll, “Arrested development: high-resolution imaging of foveal morphology in albinism,” Vision Res. 50(8), 810–817 (2010).
[Crossref] [PubMed]

Packer, O.

C. A. Curcio, K. R. Sloan, O. Packer, A. E. Hendrickson, and R. E. Kalina, “Distribution of cones in human and monkey retina: individual variability and radial asymmetry,” Science 236(4801), 579–582 (1987).
[Crossref] [PubMed]

Park, B.

Park, B. H.

Parker, A.

Pask, C.

A. W. Snyder and C. Pask, “The Stiles-Crawford effect--explanation and consequences,” Vision Res. 13(6), 1115–1137 (1973).
[Crossref] [PubMed]

Pierce, M.

Pircher, M.

Podoleanu, A. G.

Potsaid, B.

Povazay, B.

E. J. Fernández, B. Povazay, B. Hermann, A. Unterhuber, H. Sattmann, P. M. Prieto, R. Leitgeb, P. Ahnelt, P. Artal, and W. Drexler, “Three-dimensional adaptive optics ultrahigh-resolution optical coherence tomography using a liquid crystal spatial light modulator,” Vision Res. 45(28), 3432–3444 (2005).
[Crossref] [PubMed]

Považay, B.

Prieto, P. M.

E. J. Fernández, B. Povazay, B. Hermann, A. Unterhuber, H. Sattmann, P. M. Prieto, R. Leitgeb, P. Ahnelt, P. Artal, and W. Drexler, “Three-dimensional adaptive optics ultrahigh-resolution optical coherence tomography using a liquid crystal spatial light modulator,” Vision Res. 45(28), 3432–3444 (2005).
[Crossref] [PubMed]

Qu, J.

Ratliff, F.

Rha, J.

Riggs, L. A.

Roorda, A.

Sattmann, H.

Schmoll, T.

Schuman, J. S.

V. J. Srinivasan, B. K. Monson, M. Wojtkowski, R. A. Bilonick, I. Gorczynska, R. Chen, J. S. Duker, J. S. Schuman, and J. G. Fujimoto, “Characterization of outer retinal morphology with high-speed, ultrahigh-resolution optical coherence tomography,” Invest. Ophthalmol. Vis. Sci. 49(4), 1571–1579 (2008).
[Crossref] [PubMed]

M. Wojtkowski, V. Srinivasan, J. G. Fujimoto, T. Ko, J. S. Schuman, A. Kowalczyk, and J. S. Duker, “Three-dimensional retinal imaging with high-speed ultrahigh-resolution optical coherence tomography,” Ophthalmology 112(10), 1734–1746 (2005).
[Crossref] [PubMed]

Sloan, K. R.

C. A. Curcio, K. R. Sloan, O. Packer, A. E. Hendrickson, and R. E. Kalina, “Distribution of cones in human and monkey retina: individual variability and radial asymmetry,” Science 236(4801), 579–582 (1987).
[Crossref] [PubMed]

Snyder, A. W.

A. W. Snyder and C. Pask, “The Stiles-Crawford effect--explanation and consequences,” Vision Res. 13(6), 1115–1137 (1973).
[Crossref] [PubMed]

Song, H.

T. Y. Chui, H. Song, and S. A. Burns, “Individual variations in human cone photoreceptor packing density: variations with refractive error,” Invest. Ophthalmol. Vis. Sci. 49(10), 4679–4687 (2008).
[Crossref] [PubMed]

T. Y. Chui, H. Song, and S. A. Burns, “Adaptive-optics imaging of human cone photoreceptor distribution,” J. Opt. Soc. Am. A 25(12), 3021–3029 (2008).
[Crossref] [PubMed]

Srinivasan, V.

M. Wojtkowski, V. Srinivasan, J. G. Fujimoto, T. Ko, J. S. Schuman, A. Kowalczyk, and J. S. Duker, “Three-dimensional retinal imaging with high-speed ultrahigh-resolution optical coherence tomography,” Ophthalmology 112(10), 1734–1746 (2005).
[Crossref] [PubMed]

Srinivasan, V. J.

V. J. Srinivasan, B. K. Monson, M. Wojtkowski, R. A. Bilonick, I. Gorczynska, R. Chen, J. S. Duker, J. S. Schuman, and J. G. Fujimoto, “Characterization of outer retinal morphology with high-speed, ultrahigh-resolution optical coherence tomography,” Invest. Ophthalmol. Vis. Sci. 49(4), 1571–1579 (2008).
[Crossref] [PubMed]

B. Potsaid, I. Gorczynska, V. J. Srinivasan, Y. Chen, J. Jiang, A. Cable, and J. G. Fujimoto, “Ultrahigh speed spectral / Fourier domain OCT ophthalmic imaging at 70,000 to 312,500 axial scans per second,” Opt. Express 16(19), 15149–15169 (2008).
[Crossref] [PubMed]

Stepien, K. E.

J. T. McAllister, A. M. Dubis, D. M. Tait, S. Ostler, J. Rha, K. E. Stepien, C. G. Summers, and J. Carroll, “Arrested development: high-resolution imaging of foveal morphology in albinism,” Vision Res. 50(8), 810–817 (2010).
[Crossref] [PubMed]

Summers, C. G.

J. T. McAllister, A. M. Dubis, D. M. Tait, S. Ostler, J. Rha, K. E. Stepien, C. G. Summers, and J. Carroll, “Arrested development: high-resolution imaging of foveal morphology in albinism,” Vision Res. 50(8), 810–817 (2010).
[Crossref] [PubMed]

Tait, D. M.

J. T. McAllister, A. M. Dubis, D. M. Tait, S. Ostler, J. Rha, K. E. Stepien, C. G. Summers, and J. Carroll, “Arrested development: high-resolution imaging of foveal morphology in albinism,” Vision Res. 50(8), 810–817 (2010).
[Crossref] [PubMed]

Tearney, G.

Thorn, K. E.

Tiruveedhula, P.

Torti, C.

Unterhuber, A.

Ustun, T. E.

Vogel, C. R.

Wang, Q.

O. P. Kocaoglu, B. Cense, Q. Wang, J. Bruestle, J. Besecker, W. Gao, R. Jonnal, and D. T. Miller, “Imaging retinal nerve fiber bundles at ultrahigh-speed and ultrahigh-resolution using OCT with adaptive optics,” Proc. SPIE 7550(755010), 755010, 755010-5 (2010).
[Crossref]

R. S. Jonnal, J. R. Besecker, J. C. Derby, O. P. Kocaoglu, B. Cense, W. Gao, Q. Wang, and D. T. Miller, “Imaging outer segment renewal in living human cone photoreceptors,” Opt. Express 18(5), 5257–5270 (2010).
[Crossref] [PubMed]

Werner, J. S.

Williams, D. R.

J. Liang, D. R. Williams, and D. T. Miller, “Supernormal vision and high-resolution retinal imaging through adaptive optics,” J. Opt. Soc. Am. A 14(11), 2884–2892 (1997).
[Crossref] [PubMed]

D. T. Miller, D. R. Williams, G. M. Morris, and J. Liang, “Images of cone photoreceptors in the living human eye,” Vision Res. 36(8), 1067–1079 (1996).
[Crossref] [PubMed]

Wojtkowski, M.

V. J. Srinivasan, B. K. Monson, M. Wojtkowski, R. A. Bilonick, I. Gorczynska, R. Chen, J. S. Duker, J. S. Schuman, and J. G. Fujimoto, “Characterization of outer retinal morphology with high-speed, ultrahigh-resolution optical coherence tomography,” Invest. Ophthalmol. Vis. Sci. 49(4), 1571–1579 (2008).
[Crossref] [PubMed]

M. Wojtkowski, V. Srinivasan, J. G. Fujimoto, T. Ko, J. S. Schuman, A. Kowalczyk, and J. S. Duker, “Three-dimensional retinal imaging with high-speed ultrahigh-resolution optical coherence tomography,” Ophthalmology 112(10), 1734–1746 (2005).
[Crossref] [PubMed]

M. Wojtkowski, R. Leitgeb, A. Kowalczyk, T. Bajraszewski, and A. F. Fercher, “In vivo human retinal imaging by Fourier domain optical coherence tomography,” J. Biomed. Opt. 7(3), 457–463 (2002).
[Crossref] [PubMed]

Yang, Q.

Yellott, J. I.

J. I. Yellott., “Spectral analysis of spatial sampling by photoreceptors: topological disorder prevents aliasing,” Vision Res. 22(9), 1205–1210 (1982).
[Crossref] [PubMed]

Yun, S. H.

Zawadzki, R. J.

Zhang, Y.

Zhao, M.

Invest. Ophthalmol. Vis. Sci. (2)

T. Y. Chui, H. Song, and S. A. Burns, “Individual variations in human cone photoreceptor packing density: variations with refractive error,” Invest. Ophthalmol. Vis. Sci. 49(10), 4679–4687 (2008).
[Crossref] [PubMed]

V. J. Srinivasan, B. K. Monson, M. Wojtkowski, R. A. Bilonick, I. Gorczynska, R. Chen, J. S. Duker, J. S. Schuman, and J. G. Fujimoto, “Characterization of outer retinal morphology with high-speed, ultrahigh-resolution optical coherence tomography,” Invest. Ophthalmol. Vis. Sci. 49(4), 1571–1579 (2008).
[Crossref] [PubMed]

J. Biomed. Opt. (1)

M. Wojtkowski, R. Leitgeb, A. Kowalczyk, T. Bajraszewski, and A. F. Fercher, “In vivo human retinal imaging by Fourier domain optical coherence tomography,” J. Biomed. Opt. 7(3), 457–463 (2002).
[Crossref] [PubMed]

J. Opt. Soc. Am. (1)

J. Opt. Soc. Am. A (4)

Nat. Rev. Neurosci. (1)

S. Martinez-Conde, S. L. Macknik, and D. H. Hubel, “The role of fixational eye movements in visual perception,” Nat. Rev. Neurosci. 5(3), 229–240 (2004).
[Crossref] [PubMed]

Ophthalmology (1)

M. Wojtkowski, V. Srinivasan, J. G. Fujimoto, T. Ko, J. S. Schuman, A. Kowalczyk, and J. S. Duker, “Three-dimensional retinal imaging with high-speed ultrahigh-resolution optical coherence tomography,” Ophthalmology 112(10), 1734–1746 (2005).
[Crossref] [PubMed]

Opt. Express (20)

Y. Zhang, J. Rha, R. Jonnal, and D. T. Miller, “Adaptive optics parallel spectral domain optical coherence tomography for imaging the living retina,” Opt. Express 13(12), 4792–4811 (2005).
[Crossref] [PubMed]

B. Cense, N. Nassif, T. Chen, M. Pierce, S. H. Yun, B. Park, B. Bouma, G. Tearney, and J. de Boer, “Ultrahigh-resolution high-speed retinal imaging using spectral-domain optical coherence tomography,” Opt. Express 12(11), 2435–2447 (2004).
[Crossref] [PubMed]

B. Potsaid, I. Gorczynska, V. J. Srinivasan, Y. Chen, J. Jiang, A. Cable, and J. G. Fujimoto, “Ultrahigh speed spectral / Fourier domain OCT ophthalmic imaging at 70,000 to 312,500 axial scans per second,” Opt. Express 16(19), 15149–15169 (2008).
[Crossref] [PubMed]

T. Schmoll, C. Kolbitsch, and R. A. Leitgeb, “Ultra-high-speed volumetric tomography of human retinal blood flow,” Opt. Express 17(5), 4166–4176 (2009).
[Crossref] [PubMed]

R. J. Zawadzki, B. Cense, Y. Zhang, S. S. Choi, D. T. Miller, and J. S. Werner, “Ultrahigh-resolution optical coherence tomography with monochromatic and chromatic aberration correction,” Opt. Express 16(11), 8126–8143 (2008).
[Crossref] [PubMed]

E. J. Fernández, B. Hermann, B. Považay, A. Unterhuber, H. Sattmann, B. Hofer, P. K. Ahnelt, and W. Drexler, “Ultrahigh resolution optical coherence tomography and pancorrection for cellular imaging of the living human retina,” Opt. Express 16(15), 11083–11094 (2008).
[Crossref] [PubMed]

B. Cense, E. Koperda, J. M. Brown, O. P. Kocaoglu, W. Gao, R. S. Jonnal, and D. T. Miller, “Volumetric retinal imaging with ultrahigh-resolution spectral-domain optical coherence tomography and adaptive optics using two broadband light sources,” Opt. Express 17(5), 4095–4111 (2009).
[Crossref] [PubMed]

C. Torti, B. Považay, B. Hofer, A. Unterhuber, J. Carroll, P. K. Ahnelt, and W. Drexler, “Adaptive optics optical coherence tomography at 120,000 depth scans/s for non-invasive cellular phenotyping of the living human retina,” Opt. Express 17(22), 19382–19400 (2009).
[Crossref] [PubMed]

B. Cense, W. Gao, J. M. Brown, S. M. Jones, R. S. Jonnal, M. Mujat, B. H. Park, J. F. de Boer, and D. T. Miller, “Retinal imaging with polarization-sensitive optical coherence tomography and adaptive optics,” Opt. Express 17(24), 21634–21651 (2009).
[Crossref] [PubMed]

E. J. Fernández, A. Unterhuber, B. Považay, B. Hermann, P. Artal, and W. Drexler, “Chromatic aberration correction of the human eye for retinal imaging in the near infrared,” Opt. Express 14(13), 6213–6225 (2006).
[Crossref] [PubMed]

Q. Yang, D. W. Arathorn, P. Tiruveedhula, C. R. Vogel, and A. Roorda, “Design of an integrated hardware interface for AOSLO image capture and cone-targeted stimulus delivery,” Opt. Express 18(17), 17841–17858 (2010).
[Crossref] [PubMed]

R. S. Jonnal, J. R. Besecker, J. C. Derby, O. P. Kocaoglu, B. Cense, W. Gao, Q. Wang, and D. T. Miller, “Imaging outer segment renewal in living human cone photoreceptors,” Opt. Express 18(5), 5257–5270 (2010).
[Crossref] [PubMed]

J. Rha, R. S. Jonnal, K. E. Thorn, J. Qu, Y. Zhang, and D. T. Miller, “Adaptive optics flood-illumination camera for high speed retinal imaging,” Opt. Express 14(10), 4552–4569 (2006).
[Crossref] [PubMed]

M. Pircher, B. Baumann, E. Götzinger, H. Sattmann, and C. K. Hitzenberger, “Simultaneous SLO/OCT imaging of the human retina with axial eye motion correction,” Opt. Express 15(25), 16922–16932 (2007).
[Crossref] [PubMed]

M. Pircher, E. Götzinger, H. Sattmann, R. A. Leitgeb, and C. K. Hitzenberger, “In vivo investigation of human cone photoreceptors with SLO/OCT in combination with 3D motion correction on a cellular level,” Opt. Express 18(13), 13935–13944 (2010).
[Crossref] [PubMed]

R. J. Zawadzki, S. M. Jones, S. S. Olivier, M. Zhao, B. A. Bower, J. A. Izatt, S. Choi, S. Laut, and J. S. Werner, “Adaptive-optics optical coherence tomography for high-resolution and high-speed 3D retinal in vivo imaging,” Opt. Express 13(21), 8532–8546 (2005).
[Crossref] [PubMed]

Y. Zhang, B. Cense, J. Rha, R. S. Jonnal, W. Gao, R. J. Zawadzki, J. S. Werner, S. Jones, S. Olivier, and D. T. Miller, “High-speed volumetric imaging of cone photoreceptors with adaptive optics spectral-domain optical coherence tomography,” Opt. Express 14(10), 4380–4394 (2006).
[Crossref] [PubMed]

D. Merino, C. Dainty, A. Bradu, and A. G. Podoleanu, “Adaptive optics enhanced simultaneous en-face optical coherence tomography and scanning laser ophthalmoscopy,” Opt. Express 14(8), 3345–3353 (2006).
[Crossref] [PubMed]

D. X. Hammer, R. D. Ferguson, C. E. Bigelow, N. V. Iftimia, T. E. Ustun, and S. A. Burns, “Adaptive optics scanning laser ophthalmoscope for stabilized retinal imaging,” Opt. Express 14(8), 3354–3367 (2006).
[Crossref] [PubMed]

C. R. Vogel, D. W. Arathorn, A. Roorda, and A. Parker, “Retinal motion estimation in adaptive optics scanning laser ophthalmoscopy,” Opt. Express 14(2), 487–497 (2006).
[Crossref] [PubMed]

Proc. SPIE (1)

O. P. Kocaoglu, B. Cense, Q. Wang, J. Bruestle, J. Besecker, W. Gao, R. Jonnal, and D. T. Miller, “Imaging retinal nerve fiber bundles at ultrahigh-speed and ultrahigh-resolution using OCT with adaptive optics,” Proc. SPIE 7550(755010), 755010, 755010-5 (2010).
[Crossref]

Science (1)

C. A. Curcio, K. R. Sloan, O. Packer, A. E. Hendrickson, and R. E. Kalina, “Distribution of cones in human and monkey retina: individual variability and radial asymmetry,” Science 236(4801), 579–582 (1987).
[Crossref] [PubMed]

Vision Res. (5)

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Supplementary Material (4)

» Media 1: AVI (3362 KB)     
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» Media 3: AVI (2562 KB)     
» Media 4: AVI (1715 KB)     

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Figures (11)

Fig. 1
Fig. 1 Procedure for axially registering UHR-AO-OCT volume movies. Shown is a projected slow B-scan (each column is the average of a single fast B-scan) at various stages of the process: (left) before axial registration; (center) segmentation of CC (red line) and determination of its mean height (yellow line); and (right) axial shifting of fast B-scans to align CC (red line in (center)) to their mean height (yellow line in (center)). Green rectangle denotes the region of interest (PL and RPE complex) that is cropped and used for further processing. OS: outer segment of cone photoreceptors.

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Fig. 2
Fig. 2 Procedure for lateral registration of cone photoreceptors in en face projections from UHR-AO-OCT volumes. ●: landmark cones, ◌: reference positions of landmark cones. (left) Landmark cones are selected and their reference positions determined in the first frame of the movie that had little to no apparent motion artifacts. (center) Each subsequent frame in the volume movie is segmented into 10 to 15 narrow strips whose long dimension is parallel to the fast scan direction. The border of each strip is defined by two landmark cones. (right) To register a strip, landmark cones are repositioned to their original (reference) positions using two linear transformations: scaling (shrinking and expanding) in slow scan direction and shearing in fast scan direction. After registration of the strips, the strips are reassembled to form a registered image. Note that the top and bottom strips are not registered as two landmark cones are needed to do so. The registration process is fully automated once the landmark cone coordinates are found. See text for additional details.

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Fig. 3
Fig. 3 Representative en face images of cone photoreceptors of S3 at 0.5°, 1.5°, 3°, 4.5°, and 6° temporal to the fovea. Scale bars indicate 50 μm. N, T, S, and I denote nasal, temporal, superior, and inferior directions at the retina.

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Fig. 4
Fig. 4 (top row) Cone photoreceptor images of S3 at 1.5°, 3°, and 6° temporal to the fovea. N, T, S, and I denote nasal, temporal, superior, and inferior directions at the retina. (middle row) Cross-sectional images (fast B-scans) of the PL-RPE complex are shown for the same three retinal eccentricities with location indicated by the yellow lines on the en face images. Media 1 shows movie versions that depict the yellow lines sliding on the en face images and corresponding B-scans for the entire UHR-AO-OCT volumes. (bottom row) Power spectra were computed from the corresponding en face images. Rings of concentrated power and centered on zero spatial frequency are visible. Note that the en face images (top row) are rotated 90° relative to the images in Fig. 3. The rotation was necessary for alignment to the fast B-scans (middle row).

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Fig. 5
Fig. 5 Comparison of cone photoreceptor spacing measured with UHR-AO-OCT, AO-SLO [24], and histology [37]. All measurements are temporal of the fovea. Error bars represent ± 1 standard deviation.

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Fig. 6
Fig. 6 Average of 15 0.5°x0.5° en face images from the same volume video (left) before and (center and right) after registration/dewarping. Images were acquired from subject S3 at 3° temporal to the fovea. Registration/dewarping was based on (center) three subframe strips (4 landmark cones marked with red crosses) and (right) 13 subframe strips (14 landmark cones marked with red crosses). Media 2 shows the corresponding movie versions of each image. Scale bars indicate 50 μm.

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Fig. 7
Fig. 7 Average of 15 en face images from the same volume movies of S3 at (left) 1.5°, (center) 3°, and (right) 6° temporal to the fovea after registration/dewarping. Registration/dewarping was based on (left) 12, (center) 13, and (right) 12 subframe strips (13, 14, and 13 landmark cones, respectively). Media 3 shows the registered en face UHR-AO-OCT movies from which the average images were computed. Retinal motion for the three videos are comparable with an en face motion RMS of 2.2 μm, 1.2 μm, 0.97 μm for 1.5°, 3°, and 6°, respectively. For comparison, RMS retinal motion before registration were 14.4 μm, 14.7 μm, 10.6 μm. Scale bars indicate 50 μm.

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Fig. 8
Fig. 8 (left column) An en face frame from the volume movie at 3° temporal to the fovea. Red crosses mark the locations of 14 landmark cones used for registration. Color-coded squares mark the locations of 11 cones that were tracked during the volume video. 10 of the cones were randomly selected but present in all frames, while one was intentionally selected as a landmark cone (red). (center column) Traces of en face position of the 11 cones and RMS magnitude of each cone (landmark cone is red) are shown without registration. (right column) Traces of en face position and RMS magnitude of the same 11 cones are shown with registration/dewarping. Registration/dewarping used 13 strips (14 landmark cones).

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Fig. 9
Fig. 9 Lateral motion of the retina during UHR-AO-OCT image acquisition before and after registration/dewarping. Averages are shown for each subject (S1, S2, and S3). Each bar represents the average RMS of five cones selected in volume videos at 3°. Error bars represesent ± 1 standard deviation of the five cone measurements.

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Fig. 10
Fig. 10 (left) Averaged en face image of S3 at 3° temporal to the fovea after registration and (right) cross-sectional images of individual cones. En face locations of cross-sectional images are marked by colored squares (yellow, blue, green, violet, red). Landmark cones used for registration are marked with red crosses. The cross-sectional cone images shown in red are landmark cones. Media 4 shows the registered en face UHR-AO-OCT movie from which the average image was computed along with cross-sectional movies of the six cones selected. Scale bars on the projection and cross-sectional images indicate 50 μm and 5 μm, respectively.

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Fig. 11
Fig. 11 UHR-AO-OCT measurement of cone OS length. (left) Average OS length of individual cones at 1.5°, 3°, and 6° temporal to the fovea and for the three subjects (four cones per eccentricity per subject). Error bars represent ± 1 standard deviation of 10 to 15 (14.2, on average) OS length measurements (intra-cone variability). (right) Average OS length of four cones at the same retinal eccentricity and same subject. Error bars represent ±1 standard deviation of OS length measurements over the four cones (inter-cone variability).

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Tables (1)

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Table 1 List of subjects’ age, refractive error, best-corrected visual acuity, and axial length a

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