Abstract

Geometrical analysis of the photoreceptor mosaic can reveal subclinical ocular pathologies. In this paper, we describe a fully automatic algorithm to identify and segment photoreceptors in adaptive optics ophthalmoscope images of the photoreceptor mosaic. This method is an extension of our previously described closed contour segmentation framework based on graph theory and dynamic programming (GTDP). We validated the performance of the proposed algorithm by comparing it to the state-of-the-art technique on a large data set consisting of over 200,000 cones and posted the results online. We found that the GTDP method achieved a higher detection rate, decreasing the cone miss rate by over a factor of five.

© 2013 OSA

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    [CrossRef] [PubMed]

2012

R. S. Jonnal, O. P. Kocaoglu, Q. Wang, S. Lee, and D. T. Miller, “Phase-sensitive imaging of the outer retina using optical coherence tomography and adaptive optics,” Biomed. Opt. Express3(1), 104–124 (2012).
[CrossRef] [PubMed]

K. E. Stepien, W. M. Martinez, A. M. Dubis, R. F. Cooper, A. Dubra, and J. Carroll, “Subclinical photoreceptor disruption in response to severe head trauma,” Arch. Ophthalmol.130(3), 400–402 (2012).
[CrossRef] [PubMed]

S. J. Chiu, J. A. Izatt, R. V. O’Connell, K. P. Winter, C. A. Toth, and S. Farsiu, “Validated automatic segmentation of AMD pathology including drusen and geographic atrophy in SD-OCT images,” Invest. Ophthalmol. Vis. Sci.53(1), 53–61 (2012).
[CrossRef] [PubMed]

S. J. Chiu, C. A. Toth, C. Bowes Rickman, J. A. Izatt, and S. Farsiu, “Automatic segmentation of closed-contour features in ophthalmic images using graph theory and dynamic programming,” Biomed. Opt. Express3(5), 1127–1140 (2012).
[CrossRef] [PubMed]

X. Liu, Y. Zhang, and D. Yun, “An automated algorithm for photoreceptors counting in adaptive optics retinal images,” Proc. SPIE8419, 84191Z, 84191Z–5 (2012).
[CrossRef]

R. Garrioch, C. Langlo, A. M. Dubis, R. F. Cooper, A. Dubra, and J. Carroll, “Repeatability of in vivo parafoveal cone density and spacing measurements,” Optom. Vis. Sci.89(5), 632–643 (2012).
[CrossRef] [PubMed]

2011

F. LaRocca, S. J. Chiu, R. P. McNabb, A. N. Kuo, J. A. Izatt, and S. Farsiu, “Robust automatic segmentation of corneal layer boundaries in SDOCT images using graph theory and dynamic programming,” Biomed. Opt. Express2(6), 1524–1538 (2011).
[CrossRef] [PubMed]

R. F. Cooper, A. M. Dubis, A. Pavaskar, J. Rha, A. Dubra, and J. Carroll, “Spatial and temporal variation of rod photoreceptor reflectance in the human retina,” Biomed. Opt. Express2(9), 2577–2589 (2011).
[CrossRef] [PubMed]

A. Dubra and Y. Sulai, “Reflective afocal broadband adaptive optics scanning ophthalmoscope,” Biomed. Opt. Express2(6), 1757–1768 (2011).
[CrossRef] [PubMed]

A. Dubra, Y. Sulai, J. L. Norris, R. F. Cooper, A. M. Dubis, D. R. Williams, and J. Carroll, “Noninvasive imaging of the human rod photoreceptor mosaic using a confocal adaptive optics scanning ophthalmoscope,” Biomed. Opt. Express2(7), 1864–1876 (2011).
[CrossRef] [PubMed]

D. Merino, J. L. Duncan, P. Tiruveedhula, and A. Roorda, “Observation of cone and rod photoreceptors in normal subjects and patients using a new generation adaptive optics scanning laser ophthalmoscope,” Biomed. Opt. Express2(8), 2189–2201 (2011).
[CrossRef] [PubMed]

M. Pircher, J. S. Kroisamer, F. Felberer, H. Sattmann, E. Götzinger, and C. K. Hitzenberger, “Temporal changes of human cone photoreceptors observed in vivo with SLO/OCT,” Biomed. Opt. Express2(1), 100–112 (2011).
[CrossRef] [PubMed]

O. P. Kocaoglu, S. Lee, R. S. Jonnal, Q. Wang, A. E. Herde, J. C. Derby, W. Gao, and D. T. Miller, “Imaging cone photoreceptors in three dimensions and in time using ultrahigh resolution optical coherence tomography with adaptive optics,” Biomed. Opt. Express2(4), 748–763 (2011).
[CrossRef] [PubMed]

Y. Kitaguchi, S. Kusaka, T. Yamaguchi, T. Mihashi, and T. Fujikado, “Detection of photoreceptor disruption by adaptive optics fundus imaging and Fourier-domain optical coherence tomography in eyes with occult macular dystrophy,” Clin. Ophthalmol.5, 345–351 (2011).
[CrossRef] [PubMed]

S. Ooto, M. Hangai, K. Takayama, N. Arakawa, A. Tsujikawa, H. Koizumi, S. Oshima, and N. Yoshimura, “High-resolution photoreceptor imaging in idiopathic macular telangiectasia type 2 using adaptive optics scanning laser ophthalmoscopy,” Invest. Ophthalmol. Vis. Sci.52(8), 5541–5550 (2011).
[CrossRef] [PubMed]

S. Ooto, M. Hangai, K. Takayama, A. Sakamoto, A. Tsujikawa, S. Oshima, T. Inoue, and N. Yoshimura, “High-resolution imaging of the photoreceptor layer in epiretinal membrane using adaptive optics scanning laser ophthalmoscopy,” Ophthalmology118(5), 873–881 (2011).
[CrossRef] [PubMed]

2010

2009

J. Carroll, R. C. Baraas, M. Wagner-Schuman, J. Rha, C. A. Siebe, C. Sloan, D. M. Tait, S. Thompson, J. I. Morgan, J. Neitz, D. R. Williams, D. H. Foster, and M. Neitz, “Cone photoreceptor mosaic disruption associated with Cys203Arg mutation in the M-cone opsin,” Proc. Natl. Acad. Sci. U.S.A.106(49), 20948–20953 (2009).
[CrossRef] [PubMed]

C. Torti, B. Povazay, 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. Express17(22), 19382–19400 (2009).
[CrossRef] [PubMed]

M. Mujat, R. D. Ferguson, N. Iftimia, and D. X. Hammer, “Compact adaptive optics line scanning ophthalmoscope,” Opt. Express17(12), 10242–10258 (2009).
[CrossRef] [PubMed]

2008

T. Y. Chui, H. Song, and S. A. Burns, “Adaptive-optics imaging of human cone photoreceptor distribution,” J. Opt. Soc. Am. A25(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]

M. Pircher, R. J. Zawadzki, J. W. Evans, J. S. Werner, and C. K. Hitzenberger, “Simultaneous imaging of human cone mosaic with adaptive optics enhanced scanning laser ophthalmoscopy and high-speed transversal scanning optical coherence tomography,” Opt. Lett.33(1), 22–24 (2008).
[CrossRef] [PubMed]

J. Carroll, S. S. Choi, and D. R. Williams, “In vivo imaging of the photoreceptor mosaic of a rod monochromat,” Vision Res.48(26), 2564–2568 (2008).
[CrossRef] [PubMed]

S. S. Choi, R. J. Zawadzki, M. A. Greiner, J. S. Werner, and J. L. Keltner, “Fourier-domain optical coherence tomography and adaptive optics reveal nerve fiber layer loss and photoreceptor changes in a patient with optic nerve drusen,” J. Neuroophthalmol.28(2), 120–125 (2008).
[CrossRef] [PubMed]

M. K. Yoon, A. Roorda, Y. Zhang, C. Nakanishi, L. J. Wong, Q. Zhang, L. Gillum, A. Green, and J. L. Duncan, “Adaptive optics scanning laser ophthalmoscopy images in a family with the mitochondrial DNA T8993C mutation,” Invest. Ophthalmol. Vis. Sci.50(4), 1838–1847 (2008).
[CrossRef] [PubMed]

D. H. Wojtas, B. Wu, P. K. Ahnelt, P. J. Bones, and R. P. Millane, “Automated analysis of differential interference contrast microscopy images of the foveal cone mosaic,” J. Opt. Soc. Am. A25(5), 1181–1189 (2008).
[CrossRef] [PubMed]

2007

2006

D. Merino, C. Dainty, A. Bradu, and A. G. Podoleanu, “Adaptive optics enhanced simultaneous en-face optical coherence tomography and scanning laser ophthalmoscopy,” Opt. Express14(8), 3345–3353 (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. Express14(10), 4380–4394 (2006).
[CrossRef] [PubMed]

S. S. Choi, N. Doble, J. L. Hardy, S. M. Jones, J. L. Keltner, S. S. Olivier, and J. S. Werner, “In vivo imaging of the photoreceptor mosaic in retinal dystrophies and correlations with visual function,” Invest. Ophthalmol. Vis. Sci.47(5), 2080–2092 (2006).
[CrossRef] [PubMed]

J. I. Wolfing, M. Chung, J. Carroll, A. Roorda, and D. R. Williams, “High-resolution retinal imaging of cone-rod dystrophy,” Ophthalmology113(6), 1014–1019.e1 (2006).
[CrossRef] [PubMed]

2005

2004

J. Carroll, M. Neitz, H. Hofer, J. Neitz, and D. R. Williams, “Functional photoreceptor loss revealed with adaptive optics: an alternate cause of color blindness,” Proc. Natl. Acad. Sci. U.S.A.101(22), 8461–8466 (2004).
[CrossRef] [PubMed]

2002

1999

A. Roorda and D. R. Williams, “The arrangement of the three cone classes in the living human eye,” Nature397(6719), 520–522 (1999).
[CrossRef] [PubMed]

1997

1986

K.-Y. Liang and S. L. Zeger, “Longitudinal data analysis using generalized linear models,” Biometrika73(1), 13–22 (1986).
[CrossRef]

Ahnelt, P. K.

Andrews, M.

Arakawa, N.

S. Ooto, M. Hangai, K. Takayama, N. Arakawa, A. Tsujikawa, H. Koizumi, S. Oshima, and N. Yoshimura, “High-resolution photoreceptor imaging in idiopathic macular telangiectasia type 2 using adaptive optics scanning laser ophthalmoscopy,” Invest. Ophthalmol. Vis. Sci.52(8), 5541–5550 (2011).
[CrossRef] [PubMed]

Baraas, R. C.

J. Carroll, R. C. Baraas, M. Wagner-Schuman, J. Rha, C. A. Siebe, C. Sloan, D. M. Tait, S. Thompson, J. I. Morgan, J. Neitz, D. R. Williams, D. H. Foster, and M. Neitz, “Cone photoreceptor mosaic disruption associated with Cys203Arg mutation in the M-cone opsin,” Proc. Natl. Acad. Sci. U.S.A.106(49), 20948–20953 (2009).
[CrossRef] [PubMed]

R. C. Baraas, J. Carroll, K. L. Gunther, M. Chung, D. R. Williams, D. H. Foster, and M. Neitz, “Adaptive optics retinal imaging reveals S-cone dystrophy in tritan color-vision deficiency,” J. Opt. Soc. Am. A24(5), 1438–1447 (2007).
[CrossRef] [PubMed]

Bessho, K.

Y. Kitaguchi, K. Bessho, T. Yamaguchi, N. Nakazawa, T. Mihashi, and T. Fujikado, “In vivo measurements of cone photoreceptor spacing in myopic eyes from images obtained by an adaptive optics fundus camera,” Jpn. J. Ophthalmol.51(6), 456–461 (2007).
[CrossRef] [PubMed]

Biggs, D. S.

Bones, P. J.

Bower, B. A.

Bowes Rickman, C.

Bradu, A.

Branham, K. E.

J. L. Duncan, Y. Zhang, J. Gandhi, C. Nakanishi, M. Othman, K. E. Branham, A. Swaroop, and A. Roorda, “High-resolution imaging with adaptive optics in patients with inherited retinal degeneration,” Invest. Ophthalmol. Vis. Sci.48(7), 3283–3291 (2007).
[CrossRef] [PubMed]

Burns, S. A.

Campbell, M.

Carroll, J.

K. E. Stepien, W. M. Martinez, A. M. Dubis, R. F. Cooper, A. Dubra, and J. Carroll, “Subclinical photoreceptor disruption in response to severe head trauma,” Arch. Ophthalmol.130(3), 400–402 (2012).
[CrossRef] [PubMed]

R. Garrioch, C. Langlo, A. M. Dubis, R. F. Cooper, A. Dubra, and J. Carroll, “Repeatability of in vivo parafoveal cone density and spacing measurements,” Optom. Vis. Sci.89(5), 632–643 (2012).
[CrossRef] [PubMed]

R. F. Cooper, A. M. Dubis, A. Pavaskar, J. Rha, A. Dubra, and J. Carroll, “Spatial and temporal variation of rod photoreceptor reflectance in the human retina,” Biomed. Opt. Express2(9), 2577–2589 (2011).
[CrossRef] [PubMed]

A. Dubra, Y. Sulai, J. L. Norris, R. F. Cooper, A. M. Dubis, D. R. Williams, and J. Carroll, “Noninvasive imaging of the human rod photoreceptor mosaic using a confocal adaptive optics scanning ophthalmoscope,” Biomed. Opt. Express2(7), 1864–1876 (2011).
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C. Torti, B. Povazay, 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. Express17(22), 19382–19400 (2009).
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J. Carroll, R. C. Baraas, M. Wagner-Schuman, J. Rha, C. A. Siebe, C. Sloan, D. M. Tait, S. Thompson, J. I. Morgan, J. Neitz, D. R. Williams, D. H. Foster, and M. Neitz, “Cone photoreceptor mosaic disruption associated with Cys203Arg mutation in the M-cone opsin,” Proc. Natl. Acad. Sci. U.S.A.106(49), 20948–20953 (2009).
[CrossRef] [PubMed]

J. Carroll, S. S. Choi, and D. R. Williams, “In vivo imaging of the photoreceptor mosaic of a rod monochromat,” Vision Res.48(26), 2564–2568 (2008).
[CrossRef] [PubMed]

R. C. Baraas, J. Carroll, K. L. Gunther, M. Chung, D. R. Williams, D. H. Foster, and M. Neitz, “Adaptive optics retinal imaging reveals S-cone dystrophy in tritan color-vision deficiency,” J. Opt. Soc. Am. A24(5), 1438–1447 (2007).
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J. I. Wolfing, M. Chung, J. Carroll, A. Roorda, and D. R. Williams, “High-resolution retinal imaging of cone-rod dystrophy,” Ophthalmology113(6), 1014–1019.e1 (2006).
[CrossRef] [PubMed]

J. Carroll, M. Neitz, H. Hofer, J. Neitz, and D. R. Williams, “Functional photoreceptor loss revealed with adaptive optics: an alternate cause of color blindness,” Proc. Natl. Acad. Sci. U.S.A.101(22), 8461–8466 (2004).
[CrossRef] [PubMed]

Cense, B.

Chiu, S. J.

Choi, S.

Choi, S. S.

J. Carroll, S. S. Choi, and D. R. Williams, “In vivo imaging of the photoreceptor mosaic of a rod monochromat,” Vision Res.48(26), 2564–2568 (2008).
[CrossRef] [PubMed]

S. S. Choi, R. J. Zawadzki, M. A. Greiner, J. S. Werner, and J. L. Keltner, “Fourier-domain optical coherence tomography and adaptive optics reveal nerve fiber layer loss and photoreceptor changes in a patient with optic nerve drusen,” J. Neuroophthalmol.28(2), 120–125 (2008).
[CrossRef] [PubMed]

B. Xue, S. S. Choi, N. Doble, and J. S. Werner, “Photoreceptor counting and montaging of en-face retinal images from an adaptive optics fundus camera,” J. Opt. Soc. Am. A24(5), 1364–1372 (2007).
[CrossRef] [PubMed]

S. S. Choi, N. Doble, J. L. Hardy, S. M. Jones, J. L. Keltner, S. S. Olivier, and J. S. Werner, “In vivo imaging of the photoreceptor mosaic in retinal dystrophies and correlations with visual function,” Invest. Ophthalmol. Vis. Sci.47(5), 2080–2092 (2006).
[CrossRef] [PubMed]

Chui, T. Y.

T. Y. Chui, H. Song, and S. A. Burns, “Adaptive-optics imaging of human cone photoreceptor distribution,” J. Opt. Soc. Am. A25(12), 3021–3029 (2008).
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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).
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Chung, M.

Cooper, R. F.

R. Garrioch, C. Langlo, A. M. Dubis, R. F. Cooper, A. Dubra, and J. Carroll, “Repeatability of in vivo parafoveal cone density and spacing measurements,” Optom. Vis. Sci.89(5), 632–643 (2012).
[CrossRef] [PubMed]

K. E. Stepien, W. M. Martinez, A. M. Dubis, R. F. Cooper, A. Dubra, and J. Carroll, “Subclinical photoreceptor disruption in response to severe head trauma,” Arch. Ophthalmol.130(3), 400–402 (2012).
[CrossRef] [PubMed]

A. Dubra, Y. Sulai, J. L. Norris, R. F. Cooper, A. M. Dubis, D. R. Williams, and J. Carroll, “Noninvasive imaging of the human rod photoreceptor mosaic using a confocal adaptive optics scanning ophthalmoscope,” Biomed. Opt. Express2(7), 1864–1876 (2011).
[CrossRef] [PubMed]

R. F. Cooper, A. M. Dubis, A. Pavaskar, J. Rha, A. Dubra, and J. Carroll, “Spatial and temporal variation of rod photoreceptor reflectance in the human retina,” Biomed. Opt. Express2(9), 2577–2589 (2011).
[CrossRef] [PubMed]

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Deng, C.

Derby, J. C.

Doble, N.

B. Xue, S. S. Choi, N. Doble, and J. S. Werner, “Photoreceptor counting and montaging of en-face retinal images from an adaptive optics fundus camera,” J. Opt. Soc. Am. A24(5), 1364–1372 (2007).
[CrossRef] [PubMed]

S. S. Choi, N. Doble, J. L. Hardy, S. M. Jones, J. L. Keltner, S. S. Olivier, and J. S. Werner, “In vivo imaging of the photoreceptor mosaic in retinal dystrophies and correlations with visual function,” Invest. Ophthalmol. Vis. Sci.47(5), 2080–2092 (2006).
[CrossRef] [PubMed]

Donnelly, W.

Drexler, W.

Dubis, A. M.

K. E. Stepien, W. M. Martinez, A. M. Dubis, R. F. Cooper, A. Dubra, and J. Carroll, “Subclinical photoreceptor disruption in response to severe head trauma,” Arch. Ophthalmol.130(3), 400–402 (2012).
[CrossRef] [PubMed]

R. Garrioch, C. Langlo, A. M. Dubis, R. F. Cooper, A. Dubra, and J. Carroll, “Repeatability of in vivo parafoveal cone density and spacing measurements,” Optom. Vis. Sci.89(5), 632–643 (2012).
[CrossRef] [PubMed]

R. F. Cooper, A. M. Dubis, A. Pavaskar, J. Rha, A. Dubra, and J. Carroll, “Spatial and temporal variation of rod photoreceptor reflectance in the human retina,” Biomed. Opt. Express2(9), 2577–2589 (2011).
[CrossRef] [PubMed]

A. Dubra, Y. Sulai, J. L. Norris, R. F. Cooper, A. M. Dubis, D. R. Williams, and J. Carroll, “Noninvasive imaging of the human rod photoreceptor mosaic using a confocal adaptive optics scanning ophthalmoscope,” Biomed. Opt. Express2(7), 1864–1876 (2011).
[CrossRef] [PubMed]

Dubra, A.

Duncan, J. L.

D. Merino, J. L. Duncan, P. Tiruveedhula, and A. Roorda, “Observation of cone and rod photoreceptors in normal subjects and patients using a new generation adaptive optics scanning laser ophthalmoscope,” Biomed. Opt. Express2(8), 2189–2201 (2011).
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M. K. Yoon, A. Roorda, Y. Zhang, C. Nakanishi, L. J. Wong, Q. Zhang, L. Gillum, A. Green, and J. L. Duncan, “Adaptive optics scanning laser ophthalmoscopy images in a family with the mitochondrial DNA T8993C mutation,” Invest. Ophthalmol. Vis. Sci.50(4), 1838–1847 (2008).
[CrossRef] [PubMed]

J. L. Duncan, Y. Zhang, J. Gandhi, C. Nakanishi, M. Othman, K. E. Branham, A. Swaroop, and A. Roorda, “High-resolution imaging with adaptive optics in patients with inherited retinal degeneration,” Invest. Ophthalmol. Vis. Sci.48(7), 3283–3291 (2007).
[CrossRef] [PubMed]

Elsner, A. E.

Evans, J. W.

Farsiu, S.

Felberer, F.

Ferguson, D.

Ferguson, R. D.

Foster, D. H.

J. Carroll, R. C. Baraas, M. Wagner-Schuman, J. Rha, C. A. Siebe, C. Sloan, D. M. Tait, S. Thompson, J. I. Morgan, J. Neitz, D. R. Williams, D. H. Foster, and M. Neitz, “Cone photoreceptor mosaic disruption associated with Cys203Arg mutation in the M-cone opsin,” Proc. Natl. Acad. Sci. U.S.A.106(49), 20948–20953 (2009).
[CrossRef] [PubMed]

R. C. Baraas, J. Carroll, K. L. Gunther, M. Chung, D. R. Williams, D. H. Foster, and M. Neitz, “Adaptive optics retinal imaging reveals S-cone dystrophy in tritan color-vision deficiency,” J. Opt. Soc. Am. A24(5), 1438–1447 (2007).
[CrossRef] [PubMed]

Fujikado, T.

Y. Kitaguchi, S. Kusaka, T. Yamaguchi, T. Mihashi, and T. Fujikado, “Detection of photoreceptor disruption by adaptive optics fundus imaging and Fourier-domain optical coherence tomography in eyes with occult macular dystrophy,” Clin. Ophthalmol.5, 345–351 (2011).
[CrossRef] [PubMed]

Y. Kitaguchi, K. Bessho, T. Yamaguchi, N. Nakazawa, T. Mihashi, and T. Fujikado, “In vivo measurements of cone photoreceptor spacing in myopic eyes from images obtained by an adaptive optics fundus camera,” Jpn. J. Ophthalmol.51(6), 456–461 (2007).
[CrossRef] [PubMed]

Gandhi, J.

J. L. Duncan, Y. Zhang, J. Gandhi, C. Nakanishi, M. Othman, K. E. Branham, A. Swaroop, and A. Roorda, “High-resolution imaging with adaptive optics in patients with inherited retinal degeneration,” Invest. Ophthalmol. Vis. Sci.48(7), 3283–3291 (2007).
[CrossRef] [PubMed]

Gao, W.

Garrioch, R.

R. Garrioch, C. Langlo, A. M. Dubis, R. F. Cooper, A. Dubra, and J. Carroll, “Repeatability of in vivo parafoveal cone density and spacing measurements,” Optom. Vis. Sci.89(5), 632–643 (2012).
[CrossRef] [PubMed]

Gillum, L.

M. K. Yoon, A. Roorda, Y. Zhang, C. Nakanishi, L. J. Wong, Q. Zhang, L. Gillum, A. Green, and J. L. Duncan, “Adaptive optics scanning laser ophthalmoscopy images in a family with the mitochondrial DNA T8993C mutation,” Invest. Ophthalmol. Vis. Sci.50(4), 1838–1847 (2008).
[CrossRef] [PubMed]

Götzinger, E.

Green, A.

M. K. Yoon, A. Roorda, Y. Zhang, C. Nakanishi, L. J. Wong, Q. Zhang, L. Gillum, A. Green, and J. L. Duncan, “Adaptive optics scanning laser ophthalmoscopy images in a family with the mitochondrial DNA T8993C mutation,” Invest. Ophthalmol. Vis. Sci.50(4), 1838–1847 (2008).
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Greiner, M. A.

S. S. Choi, R. J. Zawadzki, M. A. Greiner, J. S. Werner, and J. L. Keltner, “Fourier-domain optical coherence tomography and adaptive optics reveal nerve fiber layer loss and photoreceptor changes in a patient with optic nerve drusen,” J. Neuroophthalmol.28(2), 120–125 (2008).
[CrossRef] [PubMed]

Gunther, K. L.

Hammer, D. X.

Hangai, M.

S. Ooto, M. Hangai, K. Takayama, N. Arakawa, A. Tsujikawa, H. Koizumi, S. Oshima, and N. Yoshimura, “High-resolution photoreceptor imaging in idiopathic macular telangiectasia type 2 using adaptive optics scanning laser ophthalmoscopy,” Invest. Ophthalmol. Vis. Sci.52(8), 5541–5550 (2011).
[CrossRef] [PubMed]

S. Ooto, M. Hangai, K. Takayama, A. Sakamoto, A. Tsujikawa, S. Oshima, T. Inoue, and N. Yoshimura, “High-resolution imaging of the photoreceptor layer in epiretinal membrane using adaptive optics scanning laser ophthalmoscopy,” Ophthalmology118(5), 873–881 (2011).
[CrossRef] [PubMed]

S. Ooto, M. Hangai, A. Sakamoto, A. Tsujikawa, K. Yamashiro, Y. Ojima, Y. Yamada, H. Mukai, S. Oshima, T. Inoue, and N. Yoshimura, “High-resolution imaging of resolved central serous chorioretinopathy using adaptive optics scanning laser ophthalmoscopy,” Ophthalmology117(9), 1800–1809, e1–e2 (2010).
[CrossRef] [PubMed]

Hardy, J. L.

S. S. Choi, N. Doble, J. L. Hardy, S. M. Jones, J. L. Keltner, S. S. Olivier, and J. S. Werner, “In vivo imaging of the photoreceptor mosaic in retinal dystrophies and correlations with visual function,” Invest. Ophthalmol. Vis. Sci.47(5), 2080–2092 (2006).
[CrossRef] [PubMed]

Hebert, T.

Herde, A. E.

Hitzenberger, C. K.

Hofer, B.

Hofer, H.

J. Carroll, M. Neitz, H. Hofer, J. Neitz, and D. R. Williams, “Functional photoreceptor loss revealed with adaptive optics: an alternate cause of color blindness,” Proc. Natl. Acad. Sci. U.S.A.101(22), 8461–8466 (2004).
[CrossRef] [PubMed]

Iftimia, N.

Inoue, T.

S. Ooto, M. Hangai, K. Takayama, A. Sakamoto, A. Tsujikawa, S. Oshima, T. Inoue, and N. Yoshimura, “High-resolution imaging of the photoreceptor layer in epiretinal membrane using adaptive optics scanning laser ophthalmoscopy,” Ophthalmology118(5), 873–881 (2011).
[CrossRef] [PubMed]

S. Ooto, M. Hangai, A. Sakamoto, A. Tsujikawa, K. Yamashiro, Y. Ojima, Y. Yamada, H. Mukai, S. Oshima, T. Inoue, and N. Yoshimura, “High-resolution imaging of resolved central serous chorioretinopathy using adaptive optics scanning laser ophthalmoscopy,” Ophthalmology117(9), 1800–1809, e1–e2 (2010).
[CrossRef] [PubMed]

Izatt, J. A.

Jones, S.

Jones, S. M.

S. S. Choi, N. Doble, J. L. Hardy, S. M. Jones, J. L. Keltner, S. S. Olivier, and J. S. Werner, “In vivo imaging of the photoreceptor mosaic in retinal dystrophies and correlations with visual function,” Invest. Ophthalmol. Vis. Sci.47(5), 2080–2092 (2006).
[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. Express13(21), 8532–8546 (2005).
[CrossRef] [PubMed]

Jonnal, R.

Jonnal, R. S.

Keltner, J. L.

S. S. Choi, R. J. Zawadzki, M. A. Greiner, J. S. Werner, and J. L. Keltner, “Fourier-domain optical coherence tomography and adaptive optics reveal nerve fiber layer loss and photoreceptor changes in a patient with optic nerve drusen,” J. Neuroophthalmol.28(2), 120–125 (2008).
[CrossRef] [PubMed]

S. S. Choi, N. Doble, J. L. Hardy, S. M. Jones, J. L. Keltner, S. S. Olivier, and J. S. Werner, “In vivo imaging of the photoreceptor mosaic in retinal dystrophies and correlations with visual function,” Invest. Ophthalmol. Vis. Sci.47(5), 2080–2092 (2006).
[CrossRef] [PubMed]

Kitaguchi, Y.

Y. Kitaguchi, S. Kusaka, T. Yamaguchi, T. Mihashi, and T. Fujikado, “Detection of photoreceptor disruption by adaptive optics fundus imaging and Fourier-domain optical coherence tomography in eyes with occult macular dystrophy,” Clin. Ophthalmol.5, 345–351 (2011).
[CrossRef] [PubMed]

Y. Kitaguchi, K. Bessho, T. Yamaguchi, N. Nakazawa, T. Mihashi, and T. Fujikado, “In vivo measurements of cone photoreceptor spacing in myopic eyes from images obtained by an adaptive optics fundus camera,” Jpn. J. Ophthalmol.51(6), 456–461 (2007).
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Kocaoglu, O. P.

Koizumi, H.

S. Ooto, M. Hangai, K. Takayama, N. Arakawa, A. Tsujikawa, H. Koizumi, S. Oshima, and N. Yoshimura, “High-resolution photoreceptor imaging in idiopathic macular telangiectasia type 2 using adaptive optics scanning laser ophthalmoscopy,” Invest. Ophthalmol. Vis. Sci.52(8), 5541–5550 (2011).
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Kuo, A. N.

Kusaka, S.

Y. Kitaguchi, S. Kusaka, T. Yamaguchi, T. Mihashi, and T. Fujikado, “Detection of photoreceptor disruption by adaptive optics fundus imaging and Fourier-domain optical coherence tomography in eyes with occult macular dystrophy,” Clin. Ophthalmol.5, 345–351 (2011).
[CrossRef] [PubMed]

Langlo, C.

R. Garrioch, C. Langlo, A. M. Dubis, R. F. Cooper, A. Dubra, and J. Carroll, “Repeatability of in vivo parafoveal cone density and spacing measurements,” Optom. Vis. Sci.89(5), 632–643 (2012).
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Laut, S.

Lee, S.

Li, K. Y.

K. Y. Li, P. Tiruveedhula, and A. Roorda, “Intersubject variability of foveal cone photoreceptor density in relation to eye length,” Invest. Ophthalmol. Vis. Sci.51(12), 6858–6867 (2010).
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K. Y. Li and A. Roorda, “Automated identification of cone photoreceptors in adaptive optics retinal images,” J. Opt. Soc. Am. A24(5), 1358–1363 (2007).
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Liang, J.

Liang, K.-Y.

K.-Y. Liang and S. L. Zeger, “Longitudinal data analysis using generalized linear models,” Biometrika73(1), 13–22 (1986).
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X. Liu, Y. Zhang, and D. Yun, “An automated algorithm for photoreceptors counting in adaptive optics retinal images,” Proc. SPIE8419, 84191Z, 84191Z–5 (2012).
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Martinez, W. M.

K. E. Stepien, W. M. Martinez, A. M. Dubis, R. F. Cooper, A. Dubra, and J. Carroll, “Subclinical photoreceptor disruption in response to severe head trauma,” Arch. Ophthalmol.130(3), 400–402 (2012).
[CrossRef] [PubMed]

McNabb, R. P.

Merino, D.

Mihashi, T.

Y. Kitaguchi, S. Kusaka, T. Yamaguchi, T. Mihashi, and T. Fujikado, “Detection of photoreceptor disruption by adaptive optics fundus imaging and Fourier-domain optical coherence tomography in eyes with occult macular dystrophy,” Clin. Ophthalmol.5, 345–351 (2011).
[CrossRef] [PubMed]

Y. Kitaguchi, K. Bessho, T. Yamaguchi, N. Nakazawa, T. Mihashi, and T. Fujikado, “In vivo measurements of cone photoreceptor spacing in myopic eyes from images obtained by an adaptive optics fundus camera,” Jpn. J. Ophthalmol.51(6), 456–461 (2007).
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Millane, R. P.

Miller, D.

Miller, D. T.

Morgan, J. I.

J. Carroll, R. C. Baraas, M. Wagner-Schuman, J. Rha, C. A. Siebe, C. Sloan, D. M. Tait, S. Thompson, J. I. Morgan, J. Neitz, D. R. Williams, D. H. Foster, and M. Neitz, “Cone photoreceptor mosaic disruption associated with Cys203Arg mutation in the M-cone opsin,” Proc. Natl. Acad. Sci. U.S.A.106(49), 20948–20953 (2009).
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Mujat, M.

Mukai, H.

S. Ooto, M. Hangai, A. Sakamoto, A. Tsujikawa, K. Yamashiro, Y. Ojima, Y. Yamada, H. Mukai, S. Oshima, T. Inoue, and N. Yoshimura, “High-resolution imaging of resolved central serous chorioretinopathy using adaptive optics scanning laser ophthalmoscopy,” Ophthalmology117(9), 1800–1809, e1–e2 (2010).
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Nakanishi, C.

M. K. Yoon, A. Roorda, Y. Zhang, C. Nakanishi, L. J. Wong, Q. Zhang, L. Gillum, A. Green, and J. L. Duncan, “Adaptive optics scanning laser ophthalmoscopy images in a family with the mitochondrial DNA T8993C mutation,” Invest. Ophthalmol. Vis. Sci.50(4), 1838–1847 (2008).
[CrossRef] [PubMed]

J. L. Duncan, Y. Zhang, J. Gandhi, C. Nakanishi, M. Othman, K. E. Branham, A. Swaroop, and A. Roorda, “High-resolution imaging with adaptive optics in patients with inherited retinal degeneration,” Invest. Ophthalmol. Vis. Sci.48(7), 3283–3291 (2007).
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Nakazawa, N.

Y. Kitaguchi, K. Bessho, T. Yamaguchi, N. Nakazawa, T. Mihashi, and T. Fujikado, “In vivo measurements of cone photoreceptor spacing in myopic eyes from images obtained by an adaptive optics fundus camera,” Jpn. J. Ophthalmol.51(6), 456–461 (2007).
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Neitz, J.

J. Carroll, R. C. Baraas, M. Wagner-Schuman, J. Rha, C. A. Siebe, C. Sloan, D. M. Tait, S. Thompson, J. I. Morgan, J. Neitz, D. R. Williams, D. H. Foster, and M. Neitz, “Cone photoreceptor mosaic disruption associated with Cys203Arg mutation in the M-cone opsin,” Proc. Natl. Acad. Sci. U.S.A.106(49), 20948–20953 (2009).
[CrossRef] [PubMed]

J. Carroll, M. Neitz, H. Hofer, J. Neitz, and D. R. Williams, “Functional photoreceptor loss revealed with adaptive optics: an alternate cause of color blindness,” Proc. Natl. Acad. Sci. U.S.A.101(22), 8461–8466 (2004).
[CrossRef] [PubMed]

Neitz, M.

J. Carroll, R. C. Baraas, M. Wagner-Schuman, J. Rha, C. A. Siebe, C. Sloan, D. M. Tait, S. Thompson, J. I. Morgan, J. Neitz, D. R. Williams, D. H. Foster, and M. Neitz, “Cone photoreceptor mosaic disruption associated with Cys203Arg mutation in the M-cone opsin,” Proc. Natl. Acad. Sci. U.S.A.106(49), 20948–20953 (2009).
[CrossRef] [PubMed]

R. C. Baraas, J. Carroll, K. L. Gunther, M. Chung, D. R. Williams, D. H. Foster, and M. Neitz, “Adaptive optics retinal imaging reveals S-cone dystrophy in tritan color-vision deficiency,” J. Opt. Soc. Am. A24(5), 1438–1447 (2007).
[CrossRef] [PubMed]

J. Carroll, M. Neitz, H. Hofer, J. Neitz, and D. R. Williams, “Functional photoreceptor loss revealed with adaptive optics: an alternate cause of color blindness,” Proc. Natl. Acad. Sci. U.S.A.101(22), 8461–8466 (2004).
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Nicholas, P.

Norris, J. L.

O’Connell, R. V.

S. J. Chiu, J. A. Izatt, R. V. O’Connell, K. P. Winter, C. A. Toth, and S. Farsiu, “Validated automatic segmentation of AMD pathology including drusen and geographic atrophy in SD-OCT images,” Invest. Ophthalmol. Vis. Sci.53(1), 53–61 (2012).
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Ojima, Y.

S. Ooto, M. Hangai, A. Sakamoto, A. Tsujikawa, K. Yamashiro, Y. Ojima, Y. Yamada, H. Mukai, S. Oshima, T. Inoue, and N. Yoshimura, “High-resolution imaging of resolved central serous chorioretinopathy using adaptive optics scanning laser ophthalmoscopy,” Ophthalmology117(9), 1800–1809, e1–e2 (2010).
[CrossRef] [PubMed]

Olivier, S.

Olivier, S. S.

S. S. Choi, N. Doble, J. L. Hardy, S. M. Jones, J. L. Keltner, S. S. Olivier, and J. S. Werner, “In vivo imaging of the photoreceptor mosaic in retinal dystrophies and correlations with visual function,” Invest. Ophthalmol. Vis. Sci.47(5), 2080–2092 (2006).
[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. Express13(21), 8532–8546 (2005).
[CrossRef] [PubMed]

Ooto, S.

S. Ooto, M. Hangai, K. Takayama, A. Sakamoto, A. Tsujikawa, S. Oshima, T. Inoue, and N. Yoshimura, “High-resolution imaging of the photoreceptor layer in epiretinal membrane using adaptive optics scanning laser ophthalmoscopy,” Ophthalmology118(5), 873–881 (2011).
[CrossRef] [PubMed]

S. Ooto, M. Hangai, K. Takayama, N. Arakawa, A. Tsujikawa, H. Koizumi, S. Oshima, and N. Yoshimura, “High-resolution photoreceptor imaging in idiopathic macular telangiectasia type 2 using adaptive optics scanning laser ophthalmoscopy,” Invest. Ophthalmol. Vis. Sci.52(8), 5541–5550 (2011).
[CrossRef] [PubMed]

S. Ooto, M. Hangai, A. Sakamoto, A. Tsujikawa, K. Yamashiro, Y. Ojima, Y. Yamada, H. Mukai, S. Oshima, T. Inoue, and N. Yoshimura, “High-resolution imaging of resolved central serous chorioretinopathy using adaptive optics scanning laser ophthalmoscopy,” Ophthalmology117(9), 1800–1809, e1–e2 (2010).
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S. Ooto, M. Hangai, K. Takayama, A. Sakamoto, A. Tsujikawa, S. Oshima, T. Inoue, and N. Yoshimura, “High-resolution imaging of the photoreceptor layer in epiretinal membrane using adaptive optics scanning laser ophthalmoscopy,” Ophthalmology118(5), 873–881 (2011).
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S. Ooto, M. Hangai, A. Sakamoto, A. Tsujikawa, K. Yamashiro, Y. Ojima, Y. Yamada, H. Mukai, S. Oshima, T. Inoue, and N. Yoshimura, “High-resolution imaging of resolved central serous chorioretinopathy using adaptive optics scanning laser ophthalmoscopy,” Ophthalmology117(9), 1800–1809, e1–e2 (2010).
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J. L. Duncan, Y. Zhang, J. Gandhi, C. Nakanishi, M. Othman, K. E. Branham, A. Swaroop, and A. Roorda, “High-resolution imaging with adaptive optics in patients with inherited retinal degeneration,” Invest. Ophthalmol. Vis. Sci.48(7), 3283–3291 (2007).
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D. Merino, J. L. Duncan, P. Tiruveedhula, and A. Roorda, “Observation of cone and rod photoreceptors in normal subjects and patients using a new generation adaptive optics scanning laser ophthalmoscope,” Biomed. Opt. Express2(8), 2189–2201 (2011).
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K. Y. Li, P. Tiruveedhula, and A. Roorda, “Intersubject variability of foveal cone photoreceptor density in relation to eye length,” Invest. Ophthalmol. Vis. Sci.51(12), 6858–6867 (2010).
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M. K. Yoon, A. Roorda, Y. Zhang, C. Nakanishi, L. J. Wong, Q. Zhang, L. Gillum, A. Green, and J. L. Duncan, “Adaptive optics scanning laser ophthalmoscopy images in a family with the mitochondrial DNA T8993C mutation,” Invest. Ophthalmol. Vis. Sci.50(4), 1838–1847 (2008).
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J. L. Duncan, Y. Zhang, J. Gandhi, C. Nakanishi, M. Othman, K. E. Branham, A. Swaroop, and A. Roorda, “High-resolution imaging with adaptive optics in patients with inherited retinal degeneration,” Invest. Ophthalmol. Vis. Sci.48(7), 3283–3291 (2007).
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S. Ooto, M. Hangai, A. Sakamoto, A. Tsujikawa, K. Yamashiro, Y. Ojima, Y. Yamada, H. Mukai, S. Oshima, T. Inoue, and N. Yoshimura, “High-resolution imaging of resolved central serous chorioretinopathy using adaptive optics scanning laser ophthalmoscopy,” Ophthalmology117(9), 1800–1809, e1–e2 (2010).
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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).
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K. E. Stepien, W. M. Martinez, A. M. Dubis, R. F. Cooper, A. Dubra, and J. Carroll, “Subclinical photoreceptor disruption in response to severe head trauma,” Arch. Ophthalmol.130(3), 400–402 (2012).
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Swaroop, A.

J. L. Duncan, Y. Zhang, J. Gandhi, C. Nakanishi, M. Othman, K. E. Branham, A. Swaroop, and A. Roorda, “High-resolution imaging with adaptive optics in patients with inherited retinal degeneration,” Invest. Ophthalmol. Vis. Sci.48(7), 3283–3291 (2007).
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S. Ooto, M. Hangai, K. Takayama, N. Arakawa, A. Tsujikawa, H. Koizumi, S. Oshima, and N. Yoshimura, “High-resolution photoreceptor imaging in idiopathic macular telangiectasia type 2 using adaptive optics scanning laser ophthalmoscopy,” Invest. Ophthalmol. Vis. Sci.52(8), 5541–5550 (2011).
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D. Merino, J. L. Duncan, P. Tiruveedhula, and A. Roorda, “Observation of cone and rod photoreceptors in normal subjects and patients using a new generation adaptive optics scanning laser ophthalmoscope,” Biomed. Opt. Express2(8), 2189–2201 (2011).
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S. Ooto, M. Hangai, A. Sakamoto, A. Tsujikawa, K. Yamashiro, Y. Ojima, Y. Yamada, H. Mukai, S. Oshima, T. Inoue, and N. Yoshimura, “High-resolution imaging of resolved central serous chorioretinopathy using adaptive optics scanning laser ophthalmoscopy,” Ophthalmology117(9), 1800–1809, e1–e2 (2010).
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S. S. Choi, N. Doble, J. L. Hardy, S. M. Jones, J. L. Keltner, S. S. Olivier, and J. S. Werner, “In vivo imaging of the photoreceptor mosaic in retinal dystrophies and correlations with visual function,” Invest. Ophthalmol. Vis. Sci.47(5), 2080–2092 (2006).
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J. Carroll, R. C. Baraas, M. Wagner-Schuman, J. Rha, C. A. Siebe, C. Sloan, D. M. Tait, S. Thompson, J. I. Morgan, J. Neitz, D. R. Williams, D. H. Foster, and M. Neitz, “Cone photoreceptor mosaic disruption associated with Cys203Arg mutation in the M-cone opsin,” Proc. Natl. Acad. Sci. U.S.A.106(49), 20948–20953 (2009).
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J. Carroll, M. Neitz, H. Hofer, J. Neitz, and D. R. Williams, “Functional photoreceptor loss revealed with adaptive optics: an alternate cause of color blindness,” Proc. Natl. Acad. Sci. U.S.A.101(22), 8461–8466 (2004).
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M. K. Yoon, A. Roorda, Y. Zhang, C. Nakanishi, L. J. Wong, Q. Zhang, L. Gillum, A. Green, and J. L. Duncan, “Adaptive optics scanning laser ophthalmoscopy images in a family with the mitochondrial DNA T8993C mutation,” Invest. Ophthalmol. Vis. Sci.50(4), 1838–1847 (2008).
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S. Ooto, M. Hangai, K. Takayama, A. Sakamoto, A. Tsujikawa, S. Oshima, T. Inoue, and N. Yoshimura, “High-resolution imaging of the photoreceptor layer in epiretinal membrane using adaptive optics scanning laser ophthalmoscopy,” Ophthalmology118(5), 873–881 (2011).
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S. Ooto, M. Hangai, A. Sakamoto, A. Tsujikawa, K. Yamashiro, Y. Ojima, Y. Yamada, H. Mukai, S. Oshima, T. Inoue, and N. Yoshimura, “High-resolution imaging of resolved central serous chorioretinopathy using adaptive optics scanning laser ophthalmoscopy,” Ophthalmology117(9), 1800–1809, e1–e2 (2010).
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M. K. Yoon, A. Roorda, Y. Zhang, C. Nakanishi, L. J. Wong, Q. Zhang, L. Gillum, A. Green, and J. L. Duncan, “Adaptive optics scanning laser ophthalmoscopy images in a family with the mitochondrial DNA T8993C mutation,” Invest. Ophthalmol. Vis. Sci.50(4), 1838–1847 (2008).
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J. L. Duncan, Y. Zhang, J. Gandhi, C. Nakanishi, M. Othman, K. E. Branham, A. Swaroop, and A. Roorda, “High-resolution imaging with adaptive optics in patients with inherited retinal degeneration,” Invest. Ophthalmol. Vis. Sci.48(7), 3283–3291 (2007).
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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. Express14(10), 4380–4394 (2006).
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Y. Zhang, J. Rha, R. Jonnal, and D. Miller, “Adaptive optics parallel spectral domain optical coherence tomography for imaging the living retina,” Opt. Express13(12), 4792–4811 (2005).
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Zhong, Z.

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Appl. Opt.

Arch. Ophthalmol.

K. E. Stepien, W. M. Martinez, A. M. Dubis, R. F. Cooper, A. Dubra, and J. Carroll, “Subclinical photoreceptor disruption in response to severe head trauma,” Arch. Ophthalmol.130(3), 400–402 (2012).
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Biomed. Opt. Express

A. Dubra, Y. Sulai, J. L. Norris, R. F. Cooper, A. M. Dubis, D. R. Williams, and J. Carroll, “Noninvasive imaging of the human rod photoreceptor mosaic using a confocal adaptive optics scanning ophthalmoscope,” Biomed. Opt. Express2(7), 1864–1876 (2011).
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A. Dubra and Y. Sulai, “Reflective afocal broadband adaptive optics scanning ophthalmoscope,” Biomed. Opt. Express2(6), 1757–1768 (2011).
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R. S. Jonnal, O. P. Kocaoglu, Q. Wang, S. Lee, and D. T. Miller, “Phase-sensitive imaging of the outer retina using optical coherence tomography and adaptive optics,” Biomed. Opt. Express3(1), 104–124 (2012).
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D. Merino, J. L. Duncan, P. Tiruveedhula, and A. Roorda, “Observation of cone and rod photoreceptors in normal subjects and patients using a new generation adaptive optics scanning laser ophthalmoscope,” Biomed. Opt. Express2(8), 2189–2201 (2011).
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M. Pircher, J. S. Kroisamer, F. Felberer, H. Sattmann, E. Götzinger, and C. K. Hitzenberger, “Temporal changes of human cone photoreceptors observed in vivo with SLO/OCT,” Biomed. Opt. Express2(1), 100–112 (2011).
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O. P. Kocaoglu, S. Lee, R. S. Jonnal, Q. Wang, A. E. Herde, J. C. Derby, W. Gao, and D. T. Miller, “Imaging cone photoreceptors in three dimensions and in time using ultrahigh resolution optical coherence tomography with adaptive optics,” Biomed. Opt. Express2(4), 748–763 (2011).
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R. F. Cooper, A. M. Dubis, A. Pavaskar, J. Rha, A. Dubra, and J. Carroll, “Spatial and temporal variation of rod photoreceptor reflectance in the human retina,” Biomed. Opt. Express2(9), 2577–2589 (2011).
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F. LaRocca, S. J. Chiu, R. P. McNabb, A. N. Kuo, J. A. Izatt, and S. Farsiu, “Robust automatic segmentation of corneal layer boundaries in SDOCT images using graph theory and dynamic programming,” Biomed. Opt. Express2(6), 1524–1538 (2011).
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S. J. Chiu, C. A. Toth, C. Bowes Rickman, J. A. Izatt, and S. Farsiu, “Automatic segmentation of closed-contour features in ophthalmic images using graph theory and dynamic programming,” Biomed. Opt. Express3(5), 1127–1140 (2012).
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Biometrika

K.-Y. Liang and S. L. Zeger, “Longitudinal data analysis using generalized linear models,” Biometrika73(1), 13–22 (1986).
[CrossRef]

Clin. Ophthalmol.

Y. Kitaguchi, S. Kusaka, T. Yamaguchi, T. Mihashi, and T. Fujikado, “Detection of photoreceptor disruption by adaptive optics fundus imaging and Fourier-domain optical coherence tomography in eyes with occult macular dystrophy,” Clin. Ophthalmol.5, 345–351 (2011).
[CrossRef] [PubMed]

Invest. Ophthalmol. Vis. Sci.

S. Ooto, M. Hangai, K. Takayama, N. Arakawa, A. Tsujikawa, H. Koizumi, S. Oshima, and N. Yoshimura, “High-resolution photoreceptor imaging in idiopathic macular telangiectasia type 2 using adaptive optics scanning laser ophthalmoscopy,” Invest. Ophthalmol. Vis. Sci.52(8), 5541–5550 (2011).
[CrossRef] [PubMed]

M. K. Yoon, A. Roorda, Y. Zhang, C. Nakanishi, L. J. Wong, Q. Zhang, L. Gillum, A. Green, and J. L. Duncan, “Adaptive optics scanning laser ophthalmoscopy images in a family with the mitochondrial DNA T8993C mutation,” Invest. Ophthalmol. Vis. Sci.50(4), 1838–1847 (2008).
[CrossRef] [PubMed]

J. L. Duncan, Y. Zhang, J. Gandhi, C. Nakanishi, M. Othman, K. E. Branham, A. Swaroop, and A. Roorda, “High-resolution imaging with adaptive optics in patients with inherited retinal degeneration,” Invest. Ophthalmol. Vis. Sci.48(7), 3283–3291 (2007).
[CrossRef] [PubMed]

S. S. Choi, N. Doble, J. L. Hardy, S. M. Jones, J. L. Keltner, S. S. Olivier, and J. S. Werner, “In vivo imaging of the photoreceptor mosaic in retinal dystrophies and correlations with visual function,” Invest. Ophthalmol. Vis. Sci.47(5), 2080–2092 (2006).
[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]

K. Y. Li, P. Tiruveedhula, and A. Roorda, “Intersubject variability of foveal cone photoreceptor density in relation to eye length,” Invest. Ophthalmol. Vis. Sci.51(12), 6858–6867 (2010).
[CrossRef] [PubMed]

S. J. Chiu, J. A. Izatt, R. V. O’Connell, K. P. Winter, C. A. Toth, and S. Farsiu, “Validated automatic segmentation of AMD pathology including drusen and geographic atrophy in SD-OCT images,” Invest. Ophthalmol. Vis. Sci.53(1), 53–61 (2012).
[CrossRef] [PubMed]

J. Neuroophthalmol.

S. S. Choi, R. J. Zawadzki, M. A. Greiner, J. S. Werner, and J. L. Keltner, “Fourier-domain optical coherence tomography and adaptive optics reveal nerve fiber layer loss and photoreceptor changes in a patient with optic nerve drusen,” J. Neuroophthalmol.28(2), 120–125 (2008).
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J. Opt. Soc. Am. A

R. C. Baraas, J. Carroll, K. L. Gunther, M. Chung, D. R. Williams, D. H. Foster, and M. Neitz, “Adaptive optics retinal imaging reveals S-cone dystrophy in tritan color-vision deficiency,” J. Opt. Soc. Am. A24(5), 1438–1447 (2007).
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R. D. Ferguson, Z. Zhong, D. X. Hammer, M. Mujat, A. H. Patel, C. Deng, W. Zou, and S. A. Burns, “Adaptive optics scanning laser ophthalmoscope with integrated wide-field retinal imaging and tracking,” J. Opt. Soc. Am. A27(11), A265–A277 (2010).
[CrossRef] [PubMed]

T. Y. Chui, H. Song, and S. A. Burns, “Adaptive-optics imaging of human cone photoreceptor distribution,” J. Opt. Soc. Am. A25(12), 3021–3029 (2008).
[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. A14(11), 2884–2892 (1997).
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S. A. Burns, R. Tumbar, A. E. Elsner, D. Ferguson, and D. X. Hammer, “Large-field-of-view, modular, stabilized, adaptive-optics-based scanning laser ophthalmoscope,” J. Opt. Soc. Am. A24(5), 1313–1326 (2007).
[CrossRef] [PubMed]

K. Y. Li and A. Roorda, “Automated identification of cone photoreceptors in adaptive optics retinal images,” J. Opt. Soc. Am. A24(5), 1358–1363 (2007).
[CrossRef] [PubMed]

B. Xue, S. S. Choi, N. Doble, and J. S. Werner, “Photoreceptor counting and montaging of en-face retinal images from an adaptive optics fundus camera,” J. Opt. Soc. Am. A24(5), 1364–1372 (2007).
[CrossRef] [PubMed]

D. H. Wojtas, B. Wu, P. K. Ahnelt, P. J. Bones, and R. P. Millane, “Automated analysis of differential interference contrast microscopy images of the foveal cone mosaic,” J. Opt. Soc. Am. A25(5), 1181–1189 (2008).
[CrossRef] [PubMed]

J. Vis.

A. Roorda and D. R. Williams, “Optical fiber properties of individual human cones,” J. Vis.2(5), 404–412 (2002).
[CrossRef] [PubMed]

Jpn. J. Ophthalmol.

Y. Kitaguchi, K. Bessho, T. Yamaguchi, N. Nakazawa, T. Mihashi, and T. Fujikado, “In vivo measurements of cone photoreceptor spacing in myopic eyes from images obtained by an adaptive optics fundus camera,” Jpn. J. Ophthalmol.51(6), 456–461 (2007).
[CrossRef] [PubMed]

Nature

A. Roorda and D. R. Williams, “The arrangement of the three cone classes in the living human eye,” Nature397(6719), 520–522 (1999).
[CrossRef] [PubMed]

Ophthalmology

J. I. Wolfing, M. Chung, J. Carroll, A. Roorda, and D. R. Williams, “High-resolution retinal imaging of cone-rod dystrophy,” Ophthalmology113(6), 1014–1019.e1 (2006).
[CrossRef] [PubMed]

S. Ooto, M. Hangai, K. Takayama, A. Sakamoto, A. Tsujikawa, S. Oshima, T. Inoue, and N. Yoshimura, “High-resolution imaging of the photoreceptor layer in epiretinal membrane using adaptive optics scanning laser ophthalmoscopy,” Ophthalmology118(5), 873–881 (2011).
[CrossRef] [PubMed]

S. Ooto, M. Hangai, A. Sakamoto, A. Tsujikawa, K. Yamashiro, Y. Ojima, Y. Yamada, H. Mukai, S. Oshima, T. Inoue, and N. Yoshimura, “High-resolution imaging of resolved central serous chorioretinopathy using adaptive optics scanning laser ophthalmoscopy,” Ophthalmology117(9), 1800–1809, e1–e2 (2010).
[CrossRef] [PubMed]

Opt. Express

S. J. Chiu, X. T. Li, P. Nicholas, C. A. Toth, J. A. Izatt, and S. Farsiu, “Automatic segmentation of seven retinal layers in SDOCT images congruent with expert manual segmentation,” Opt. Express18(18), 19413–19428 (2010).
[CrossRef] [PubMed]

M. Mujat, R. D. Ferguson, A. H. Patel, N. Iftimia, N. Lue, and D. X. Hammer, “High resolution multimodal clinical ophthalmic imaging system,” Opt. Express18(11), 11607–11621 (2010).
[CrossRef] [PubMed]

C. Torti, B. Povazay, 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. Express17(22), 19382–19400 (2009).
[CrossRef] [PubMed]

M. Mujat, R. D. Ferguson, N. Iftimia, and D. X. Hammer, “Compact adaptive optics line scanning ophthalmoscope,” Opt. Express17(12), 10242–10258 (2009).
[CrossRef] [PubMed]

A. Roorda, F. Romero-Borja, W. Donnelly, H. Queener, T. Hebert, and M. Campbell, “Adaptive optics scanning laser ophthalmoscopy,” Opt. Express10(9), 405–412 (2002).
[CrossRef] [PubMed]

Y. Zhang, J. Rha, R. Jonnal, and D. Miller, “Adaptive optics parallel spectral domain optical coherence tomography for imaging the living retina,” Opt. Express13(12), 4792–4811 (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. Express13(21), 8532–8546 (2005).
[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. Express14(8), 3345–3353 (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. Express14(10), 4380–4394 (2006).
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Opt. Lett.

Optom. Vis. Sci.

R. Garrioch, C. Langlo, A. M. Dubis, R. F. Cooper, A. Dubra, and J. Carroll, “Repeatability of in vivo parafoveal cone density and spacing measurements,” Optom. Vis. Sci.89(5), 632–643 (2012).
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Proc. Natl. Acad. Sci. U.S.A.

J. Carroll, R. C. Baraas, M. Wagner-Schuman, J. Rha, C. A. Siebe, C. Sloan, D. M. Tait, S. Thompson, J. I. Morgan, J. Neitz, D. R. Williams, D. H. Foster, and M. Neitz, “Cone photoreceptor mosaic disruption associated with Cys203Arg mutation in the M-cone opsin,” Proc. Natl. Acad. Sci. U.S.A.106(49), 20948–20953 (2009).
[CrossRef] [PubMed]

J. Carroll, M. Neitz, H. Hofer, J. Neitz, and D. R. Williams, “Functional photoreceptor loss revealed with adaptive optics: an alternate cause of color blindness,” Proc. Natl. Acad. Sci. U.S.A.101(22), 8461–8466 (2004).
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Proc. SPIE

X. Liu, Y. Zhang, and D. Yun, “An automated algorithm for photoreceptors counting in adaptive optics retinal images,” Proc. SPIE8419, 84191Z, 84191Z–5 (2012).
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Vision Res.

J. Carroll, S. S. Choi, and D. R. Williams, “In vivo imaging of the photoreceptor mosaic of a rod monochromat,” Vision Res.48(26), 2564–2568 (2008).
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Other

K. Loquin, I. Bloch, K. Nakashima, F. Rossant, P.-Y. Boelle, and M. Paques, “Automatic photoreceptor detection in in-vivo adaptive optics retinal images: statistical validation,” in Image Analysis and Recognition, A. Campilho and M. Kamel, eds. (Springer Berlin / Heidelberg, 2012), pp. 408–415.

A. Dubra and Z. Harvey, “Registration of 2D images from fast scanning ophthalmic instruments,” in Biomedical Image Registration, B. Fischer, B. Dawant, and C. Lorenz, eds. (Springer Berlin / Heidelberg, 2010), pp. 60–71.

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T. J. Holmes, S. Bhattacharyya, J. A. Cooper, D. Hanzel, V. Krishna-murthi, W. C. Lin, B. Roysam, D. Szarowski, and J. Turner, “Light microscopic images reconstructed by maximum likelihood deconvolution,” in Handbook of Biological Confocal Microscopy, J. B. Pawley, ed. (Plenum Press, 1995), pp. 389–402.

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Figures (6)

Fig. 1
Fig. 1

Cone photoreceptor segmentation using the quasi-polar transform. (a) Cartesian image containing the cone to segment. (b) Pilot estimate of the cone in (a). (c,d) Polar transformation of (a) and (b), respectively. The black regions in (c) are invalid points that lie outside the image in the Cartesian domain. (e,f) Images (c) and (d) column-wise shifted until the pilot estimate in (d) was flat. (g) Segmentation of (e) using GTDP (magenta). (h) Transformation of the segmentation in (g) back into the Cartesian domain (magenta).

Fig. 2
Fig. 2

Identification of cones missed by local maxima. (a) AOSLO image in log scale with missed cones shown inside the white boxes. (b) Cone photoreceptors segmented using local maxima initialization in black, and pilot estimates of missed cones found using deconvolution and local maxima are shown in white asterisks.

Fig. 3
Fig. 3

Qualitative GTDP segmentation result. Top row: (a) Higher quality AOSLO image of cone photoreceptors in log scale, (b) fully automatic segmentation result of (a) using GTDP for closed contour structures, and (c) centroid of each fully automatically segmented cone from (b). Bottom row: Lower quality AOSLO image (a) and its segmentation (b) and centroid (c) result.

Fig. 4
Fig. 4

Variable performance of the fully automatic cone identification algorithms. Left column: AOSLO image of the cone mosaic in log scale. Middle column: Garrioch et al. 2012 algorithm results (yellow: true positives; green: false negatives). Right column: GTDP algorithm results (magenta: true positives; green: false negatives; blue: false positives). Middle row: Typical (mean) performance by both algorithms. Top and bottom rows: Performance one standard deviation above and below the mean for both algorithms, respectively.

Fig. 5
Fig. 5

A closer look at the performance of the GTDP algorithm. (a) AOSLO image corresponding to Fig. 4(b) (left), and (b) automatic GTDP segmentation result (magenta: true positives; green: false negatives; blue: false positives). White boxes: locations where the algorithm “missed” a cone, even though there appears to be no cone present. Black box: location where the algorithm “erroneously added” a cone, although the original image seems to contain an added cone not identified by the gold standard.

Fig. 6
Fig. 6

Fully automatic identification of rods and cone photoreceptors. (a) AOSLO image of rods and cone photoreceptors in log scale (image taken from [54]). (b,c) Fully automatic segmentation (b) and identification (c) of rods and cones using GTDP for closed contour structures. (d) Histogram of the segmentations from (b). (e) Threshold of 27.7 µm2 used to classify the photoreceptors from (d) into rods (magenta) and cones (green).

Tables (2)

Tables Icon

Table 1 Cone Identification Performance of Fully Automatic Methods Compared to the Gold Standard Across All 840 Images

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Table 2 Reproducibility Comparison of Cone Density and Spacing Measurements

Equations (6)

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I c all =normalize(log(normalize( I c orig ,0.1,0.9)),0,1)
w ab =normalize(( g a LD + g b LD ),1,2)+ normalize(( g a DL + g b DL ),0,0.1)+ normalize( d ab ,0,0.05)+ w min ,
w ab =normalize(( g a LD + g b LD ),1,2)+ normalize(( g a DL + g b DL ),1,1.5)+ w min
N automatic  cones  identified = N true positive + N false positive and N gold  standard  cones  identified = N true positive + N false negative ,
w ab =normalize(( g a LD + g b LD ),1,2)+ normalize( i a + i b ,0.1,0.2)+ normalize( r a + r b ,0,0.05)+ normalize( d ab ,2,2.1)+ w min
w ab =normalize( i a + i b ,0.2,1)+ normalize( d ab ,0,0.1)+ w min

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