Abstract

The ability to resolve single cells noninvasively in the living retina has important applications for the study of normal retina, diseased retina, and the efficacy of therapies for retinal disease. We describe a new instrument for high-resolution, in vivo imaging of the mammalian retina that combines the benefits of confocal detection, adaptive optics, multispectral, and fluorescence imaging. The instrument is capable of imaging single ganglion cells and their axons through retrograde transport in ganglion cells of fluorescent dyes injected into the monkey lateral geniculate nucleus (LGN). In addition, we demonstrate a method involving simultaneous imaging in two spectral bands that allows the integration of very weak signals across many frames despite inter-frame movement of the eye. With this method, we are also able to resolve the smallest retinal capillaries in fluorescein angiography and the mosaic of retinal pigment epithelium (RPE) cells with lipofuscin autofluorescence.

© 2006 Optical Society of America

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  1. W. Drexler, U. Morgner, R. K. Ghanta, F. X. Kartner, J. S. Schuman, and J. G. Fujimoto, “Ultrahigh-resolution ophthalmic optical coherence tomography,” Nat. Med 7, 502–507 (2001).
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  42. N. Lois, A. S. Halfyard, A. C. Bird, and F. W. Fitzke, “Quantitative evaluation of fundus autofluorescence imaged “in vivo” in eyes with retinal disease,” Br. J. Ophthalmol. 84, 741–745 (2000).
    [Crossref] [PubMed]
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2006 (4)

H. Hofer, J. Carroll, J. Neitz, M. Neitz, and D. R. Williams, “Organization of the human trichromatic cone mosaic,” J. Neurosci. 26, 722–722 (2006).

D. X. Hammer, R. D. Ferguson, C. E. Bigelow, N. V. Iftimia, and T. E. Ustun, “Adaptive optics scanning laser ophthalmoscope for stabilized retinal imaging,” Opt. Express 14, 3354–3367 (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, 3345–3353 (2006).
[Crossref] [PubMed]

J. I. Wolfing, M. Chung, J. Carroll, A. Roorda, and D. R. Williams, “High-resolution retinal imaging of cone-rod dystrophy,” Ophthalmology 113, 1014–1019 (2006).
[Crossref]

2005 (6)

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

E. J. Fernandez, 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, 3432–3444 (2005).
[Crossref] [PubMed]

R. J. Zawadzki, S. M. Jones, S. S. Olivier, M. T. 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, 8532–8546 (2005).
[Crossref] [PubMed]

N. M. Putnam, H. J. Hofer, N. Doble, L. Chen, J. Carroll, and D. R. Williams, “The locus of fixation and the foveal cone mosaic,” J. Vis. 5, 632–639 (2005).
[Crossref] [PubMed]

O. Strauss, “The retinal pigment epithelium in visual function,” Physiol. Rev. 85, 845–881 (2005).
[Crossref] [PubMed]

J. M. Burke and L. M. Hjelmeland, “Mosaicism of the retinal pigment epithelium: seeing the small picture,” Mol. Interv. 5, 241–249 (2005).
[Crossref] [PubMed]

2004 (10)

N. Lois, A. S. Halfyard, A. C. Bird, G. E. Holder, and F. W. Fitzke, “Fundus autofluorescence in Stargardt macular dystrophy-fundus flavimaculatus,” Am. J. Ophthalmol. 138, 55–63 (2004).
[Crossref] [PubMed]

A. Bindewald, J. J. Jorzik, A. Loesch, F. Schutt, and F. G. Holz, “Visualization of retinal pigment epithelial cells in vivo using digital high-resolution confocal scanning laser ophthalmoscopy,” Am. J. Opthalmol. 137, 556–558 (2004).
[Crossref]

M. F. Cordeiro, L. Guo, V. Luong, G. Harding, W. Wang, H. E. Jones, S. E. Moss, A. M. Sillito, and F. W. Fitzke, “Real-time imaging of single nerve cell apoptosis in retinal neurodegeneration,” Proc. Natl. Acad. Sci. U.S.A. 101, 13352–13356 (2004).
[Crossref] [PubMed]

Y. Imanishi, D. W. Piston, W. Baehr, and K. Palczewski, “Noninvasive two-photon imaging reveals retinyl ester storage structures in the eye,” J. Cell. Biol. 164, 373–383 (2004).
[Crossref] [PubMed]

B. Hermann, E. J. Fernandez, A. Unterhuber, H. Sattmann, A. F. Fercher, W. Drexler, P. M. Prieto, and P. Artal, “Adaptive-optics ultrahigh-resolution optical coherence tomography,” Opt. Lett. 29, 2142–2144 (2004).
[Crossref] [PubMed]

R. a. Leitgeb, W. Drexler, A. Unterhuber, B. Hermann, T. Bajraszewski, T. Le, A. Stingl, and A. F. Fercher, “Ultrahigh resolution Fourier domain optical coherence tomography,” Opt. Express 12, 2156–2165 (2004).
[Crossref] [PubMed]

B. Cense and N. A. Nassif, “Ultrahigh-resolution high-speed retinal imaging using spectral-domain optical coherence tomography,” Opt. Express 12, 2435–2447 (2004).
[Crossref] [PubMed]

M. Wojtkowski, V. J. Srinivasan, T. H. Ko, J. G. Fujimoto, A. Kowalczyk, and J. S. Duker, “Ultrahigh-resolution, high-speed, Fourier domain optical coherence tomography and methods for dispersion compensation,” Opt. Express 12, 2404–2422 (2004).
[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, 8461–8466 (2004).
[Crossref] [PubMed]

M. Glanc, E. Gendron, F. Lacombe, D. Lafaille, J. F. Le Gargasson, and P. Lena, “Towards wide-field retinal imaging with adaptive optics,” Opt. Commun. 230, 225–238 (2004).
[Crossref]

2003 (3)

A. Pallikaris, D. R. Williams, and H. Hofer, “The Reflectance of Single Cones in the Living Human Eye,” Invest. Opthalmol. Vis. Sci. 44, 4580–4492 (2003).
[Crossref]

D. M. Dacey, B. B. Peterson, F. R. Robinson, and P. D. Gamlin, “Fireworks in the primate retina: In vitro photodynamics reveals diverse LGN-projecting ganglion cell types,” Neuron 37, 15–27 (2003).
[Crossref] [PubMed]

J. Cushion, F. N. Reinholz, and B. A. Patterson, “General purpose control system for scanning laser ophthalmoscopes,” Clin Experiment Ophthalmol 31, 241–245 (2003).
[Crossref] [PubMed]

2002 (3)

D. M. Snodderly, M. M. Sandstrom, I. Y. F. Leung, C. I. Zucker, and M. Neuringer, “Retinal pigment epithelial cell distribution in central retina of rhesus monkeys,” Invest. Ophthalmol. Visual Sci. 43, 2815–2818 (2002).

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

A. Roorda, F. Romero-Borja, W. J. Donnelly, H. Queener, T. J. Hebert, and M. C. W. Campbell, “Adaptive optics scanning laser ophthalmoscopy,” Opt. Express 10, 405–412 (2002).
[PubMed]

2001 (7)

G. Yoon, H. Hofer, L. Chen, B. Singer, J. Porter, Y. Yamauchi, N. Doble, and D. R. Williams, “Dynamic correction of the eye’s aberration with the Rochester 2nd generation adaptive optics system.," Invest. Ophthalmol. Visual Sci. 42, S99–S99 (2001).

H. Hofer, L. Chen, G. Y. Yoon, B. Singer, Y. Yamauchi, and D. R. Williams, “Improvement in retinal image quality with dynamic correction of the eye’s aberrations,” J. Opt. Soc. Am. A 8, 631–643 (2001).

A. Roorda, A. B. Metha, P. Lennie, and D. R. Williams, “Packing arrangement of the three cone classes in primate retina,” Vision Res. 41, 1291–1306 (2001).
[Crossref] [PubMed]

W. Drexler, U. Morgner, R. K. Ghanta, F. X. Kartner, J. S. Schuman, and J. G. Fujimoto, “Ultrahigh-resolution ophthalmic optical coherence tomography,” Nat. Med 7, 502–507 (2001).
[Crossref] [PubMed]

F. G. Holz, C. Bellman, S. Staudt, F. Schutt, and H. E. Volcker, “Fundus autofluorescence and development of geographic atrophy in age-related macular degeneration,” Invest. Ophthalmol. Visual Sci. 42, 1051–1056 (2001).

F. C. Delori, D. G. Goger, and C. K. Dorey, “Age-related accumulation and spatial distribution of lipofuscin in RPE of normal subjects,” Invest. Ophthalmol. Visual Sci. 42, 1855–1866 (2001).

H. Hofer, P. Artal, B. Singer, J. L. Aragon, and D. R. Williams, “Dynamics of the eye’s wave aberration,” J. Opt. Soc. Am. A 18, 497–506 (2001).
[Crossref]

2000 (1)

N. Lois, A. S. Halfyard, A. C. Bird, and F. W. Fitzke, “Quantitative evaluation of fundus autofluorescence imaged “in vivo” in eyes with retinal disease,” Br. J. Ophthalmol. 84, 741–745 (2000).
[Crossref] [PubMed]

1999 (2)

F. Reinholz, R. A. Ashman, and R. H. Eikelboom, “Simultaneous three wavelength imaging with a scanning laser ophthalmoscope,” Cytometry 37, 165–170 (1999).
[Crossref] [PubMed]

A. Roorda and D. R. Williams, “The arrangement of the three cone classes in the living human eye,” Nature 397, 520–522 (1999).
[Crossref] [PubMed]

1998 (1)

1997 (2)

1995 (5)

D. T. Miller, D. R. Williams, G. M. Morris, and J. Liang, “Images of Cone Photoreceptors in the Living Human Eye,” Invest. Ophthalmol. Visual Sci. 36, S188–S188 (1995).

P. M. Bischoff, H. J. Niederberger, B. Torok, and P. Speiser, “Simultaneous Indocyanine Green and Fluorescein Angiography,” Retina 15, 91–99 (1995).
[Crossref] [PubMed]

F. C. Delori, C. K. Dorey, G. Staurenghi, O. Arend, D. G. Goger, and J. J. Weiter, “In vivo fluorescence of the ocular fundus exhibits retinal pigment epithelium lipofuscin characteristics,” Invest. Ophthalmol. Visual Sci. 36, 718–729 (1995).

A. von Ruckmann, F. W. Fitzke, and A. C. Bird, “Distribution of fundus autofluorescence with a scanning laser ophthalmoscope,” Br. J. Ophthalmol. 79, 407–412 (1995).
[Crossref] [PubMed]

R. S. Weinhaus, J. M. Burke, F. C. Delori, and D. M. Snodderly, “Comparison of Fluorescein Angiography with Microvascular Anatomy of Macaque Retinas,” Exp. Eye Res. 61, 1–16 (1995).
[Crossref] [PubMed]

1994 (1)

1990 (1)

C. A. Curcio, K. R. Sloan, R. E. Kalina, and A. E. Hendrickson, “Human Photoreceptor Topography,” J. Comp. Neurol. 292, 497–523 (1990).
[Crossref] [PubMed]

1989 (2)

O. Packer, a. E. Hendrickson, and C. a. Curcio, “Photoreceptor Topography of the Retina in the Adult Pigtail Macaque (Macaca-Nemestrina),” J. Comp. Neurol. 288, 165–183 (1989).
[Crossref] [PubMed]

P. Artal and R. Navarro, “High-resolution imaging of the living human fovea: measurement of the intercenter cone distance by speckle interferometry,” Opt. Lett. 14, 1098–1100 (1989).
[Crossref] [PubMed]

1986 (1)

N. J. Coletta and D. R. Williams, “Psychophysical Estimate of Parafoveal Cone Spacing,” J. Opt. Soc. Am. A Opt. Image Sci. Vis. 3, P92–P93 (1986).

1984 (1)

L. Feeney-Burns, E. S. Hilderbrand, and S. Eldridge, “Aging Human Rpe - Morphometric Analysis of Macular, Equatorial, and Peripheral Cells,” Invest. Ophthl. Vis. Sci. 25, 195–200 (1984).

1966 (1)

A. F. Fuchs and R. A. Robinson, “A method for measuring horizontal and vertical eye movement chronically in the monkey,” J. Appl. Physiol. 21, 1068–1070 (1966).
[PubMed]

Ahnelt, P.

E. J. Fernandez, 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, 3432–3444 (2005).
[Crossref] [PubMed]

Aragon, J. L.

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Artal, P.

Ashman, R. A.

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Y. Imanishi, D. W. Piston, W. Baehr, and K. Palczewski, “Noninvasive two-photon imaging reveals retinyl ester storage structures in the eye,” J. Cell. Biol. 164, 373–383 (2004).
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Bellman, C.

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A. Bindewald, J. J. Jorzik, A. Loesch, F. Schutt, and F. G. Holz, “Visualization of retinal pigment epithelial cells in vivo using digital high-resolution confocal scanning laser ophthalmoscopy,” Am. J. Opthalmol. 137, 556–558 (2004).
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N. Lois, A. S. Halfyard, A. C. Bird, G. E. Holder, and F. W. Fitzke, “Fundus autofluorescence in Stargardt macular dystrophy-fundus flavimaculatus,” Am. J. Ophthalmol. 138, 55–63 (2004).
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J. M. Burke and L. M. Hjelmeland, “Mosaicism of the retinal pigment epithelium: seeing the small picture,” Mol. Interv. 5, 241–249 (2005).
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R. S. Weinhaus, J. M. Burke, F. C. Delori, and D. M. Snodderly, “Comparison of Fluorescein Angiography with Microvascular Anatomy of Macaque Retinas,” Exp. Eye Res. 61, 1–16 (1995).
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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, 8461–8466 (2004).
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Chen, L.

N. M. Putnam, H. J. Hofer, N. Doble, L. Chen, J. Carroll, and D. R. Williams, “The locus of fixation and the foveal cone mosaic,” J. Vis. 5, 632–639 (2005).
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H. Hofer, L. Chen, G. Y. Yoon, B. Singer, Y. Yamauchi, and D. R. Williams, “Improvement in retinal image quality with dynamic correction of the eye’s aberrations,” J. Opt. Soc. Am. A 8, 631–643 (2001).

Choi, S.

Chung, M.

J. I. Wolfing, M. Chung, J. Carroll, A. Roorda, and D. R. Williams, “High-resolution retinal imaging of cone-rod dystrophy,” Ophthalmology 113, 1014–1019 (2006).
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M. F. Cordeiro, L. Guo, V. Luong, G. Harding, W. Wang, H. E. Jones, S. E. Moss, A. M. Sillito, and F. W. Fitzke, “Real-time imaging of single nerve cell apoptosis in retinal neurodegeneration,” Proc. Natl. Acad. Sci. U.S.A. 101, 13352–13356 (2004).
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C. A. Curcio, K. R. Sloan, R. E. Kalina, and A. E. Hendrickson, “Human Photoreceptor Topography,” J. Comp. Neurol. 292, 497–523 (1990).
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J. Cushion, F. N. Reinholz, and B. A. Patterson, “General purpose control system for scanning laser ophthalmoscopes,” Clin Experiment Ophthalmol 31, 241–245 (2003).
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D. M. Dacey, B. B. Peterson, F. R. Robinson, and P. D. Gamlin, “Fireworks in the primate retina: In vitro photodynamics reveals diverse LGN-projecting ganglion cell types,” Neuron 37, 15–27 (2003).
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Delori, F. C.

F. C. Delori, D. G. Goger, and C. K. Dorey, “Age-related accumulation and spatial distribution of lipofuscin in RPE of normal subjects,” Invest. Ophthalmol. Visual Sci. 42, 1855–1866 (2001).

F. C. Delori, C. K. Dorey, G. Staurenghi, O. Arend, D. G. Goger, and J. J. Weiter, “In vivo fluorescence of the ocular fundus exhibits retinal pigment epithelium lipofuscin characteristics,” Invest. Ophthalmol. Visual Sci. 36, 718–729 (1995).

R. S. Weinhaus, J. M. Burke, F. C. Delori, and D. M. Snodderly, “Comparison of Fluorescein Angiography with Microvascular Anatomy of Macaque Retinas,” Exp. Eye Res. 61, 1–16 (1995).
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F. C. Delori, “Spectrophotometer for noninvasive measurement of intrinsic fluorescence and reflectance of the ocular fundus.,” Appl. Opt. 33, 7439–7452 (1994).
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N. M. Putnam, H. J. Hofer, N. Doble, L. Chen, J. Carroll, and D. R. Williams, “The locus of fixation and the foveal cone mosaic,” J. Vis. 5, 632–639 (2005).
[Crossref] [PubMed]

G. Yoon, H. Hofer, L. Chen, B. Singer, J. Porter, Y. Yamauchi, N. Doble, and D. R. Williams, “Dynamic correction of the eye’s aberration with the Rochester 2nd generation adaptive optics system.," Invest. Ophthalmol. Visual Sci. 42, S99–S99 (2001).

Donnelly, W. J.

Dorey, C. K.

F. C. Delori, D. G. Goger, and C. K. Dorey, “Age-related accumulation and spatial distribution of lipofuscin in RPE of normal subjects,” Invest. Ophthalmol. Visual Sci. 42, 1855–1866 (2001).

F. C. Delori, C. K. Dorey, G. Staurenghi, O. Arend, D. G. Goger, and J. J. Weiter, “In vivo fluorescence of the ocular fundus exhibits retinal pigment epithelium lipofuscin characteristics,” Invest. Ophthalmol. Visual Sci. 36, 718–729 (1995).

Drexler, W.

E. J. Fernandez, 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, 3432–3444 (2005).
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Duker, J. S.

Eikelboom, R. H.

F. Reinholz, R. A. Ashman, and R. H. Eikelboom, “Simultaneous three wavelength imaging with a scanning laser ophthalmoscope,” Cytometry 37, 165–170 (1999).
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L. Feeney-Burns, E. S. Hilderbrand, and S. Eldridge, “Aging Human Rpe - Morphometric Analysis of Macular, Equatorial, and Peripheral Cells,” Invest. Ophthl. Vis. Sci. 25, 195–200 (1984).

Feeney-Burns, L.

L. Feeney-Burns, E. S. Hilderbrand, and S. Eldridge, “Aging Human Rpe - Morphometric Analysis of Macular, Equatorial, and Peripheral Cells,” Invest. Ophthl. Vis. Sci. 25, 195–200 (1984).

Fercher, A. F.

Ferguson, R. D.

Fernandez, E. J.

E. J. Fernandez, 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, 3432–3444 (2005).
[Crossref] [PubMed]

B. Hermann, E. J. Fernandez, A. Unterhuber, H. Sattmann, A. F. Fercher, W. Drexler, P. M. Prieto, and P. Artal, “Adaptive-optics ultrahigh-resolution optical coherence tomography,” Opt. Lett. 29, 2142–2144 (2004).
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M. F. Cordeiro, L. Guo, V. Luong, G. Harding, W. Wang, H. E. Jones, S. E. Moss, A. M. Sillito, and F. W. Fitzke, “Real-time imaging of single nerve cell apoptosis in retinal neurodegeneration,” Proc. Natl. Acad. Sci. U.S.A. 101, 13352–13356 (2004).
[Crossref] [PubMed]

N. Lois, A. S. Halfyard, A. C. Bird, G. E. Holder, and F. W. Fitzke, “Fundus autofluorescence in Stargardt macular dystrophy-fundus flavimaculatus,” Am. J. Ophthalmol. 138, 55–63 (2004).
[Crossref] [PubMed]

N. Lois, A. S. Halfyard, A. C. Bird, and F. W. Fitzke, “Quantitative evaluation of fundus autofluorescence imaged “in vivo” in eyes with retinal disease,” Br. J. Ophthalmol. 84, 741–745 (2000).
[Crossref] [PubMed]

A. von Ruckmann, F. W. Fitzke, and A. C. Bird, “Distribution of fundus autofluorescence with a scanning laser ophthalmoscope,” Br. J. Ophthalmol. 79, 407–412 (1995).
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Gamlin, P. D.

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[Crossref] [PubMed]

Gaun, C.

W. Jiang, N. Ling, Y. Zhang, Y. Zeping, R. Xuejun, C. Gaun, C. Wang, L. Xue, and E. Li, “Medical and Industrial Application of Adaptive Optics in Institute of Optics and Electronics, Chinese Academy of Sciences,” in 5th International Workshop on Adaptive Optics for Industry and Medicine, (2005)

Gendron, E.

M. Glanc, E. Gendron, F. Lacombe, D. Lafaille, J. F. Le Gargasson, and P. Lena, “Towards wide-field retinal imaging with adaptive optics,” Opt. Commun. 230, 225–238 (2004).
[Crossref]

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W. Drexler, U. Morgner, R. K. Ghanta, F. X. Kartner, J. S. Schuman, and J. G. Fujimoto, “Ultrahigh-resolution ophthalmic optical coherence tomography,” Nat. Med 7, 502–507 (2001).
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M. Glanc, E. Gendron, F. Lacombe, D. Lafaille, J. F. Le Gargasson, and P. Lena, “Towards wide-field retinal imaging with adaptive optics,” Opt. Commun. 230, 225–238 (2004).
[Crossref]

Goger, D. G.

F. C. Delori, D. G. Goger, and C. K. Dorey, “Age-related accumulation and spatial distribution of lipofuscin in RPE of normal subjects,” Invest. Ophthalmol. Visual Sci. 42, 1855–1866 (2001).

F. C. Delori, C. K. Dorey, G. Staurenghi, O. Arend, D. G. Goger, and J. J. Weiter, “In vivo fluorescence of the ocular fundus exhibits retinal pigment epithelium lipofuscin characteristics,” Invest. Ophthalmol. Visual Sci. 36, 718–729 (1995).

Guo, L.

M. F. Cordeiro, L. Guo, V. Luong, G. Harding, W. Wang, H. E. Jones, S. E. Moss, A. M. Sillito, and F. W. Fitzke, “Real-time imaging of single nerve cell apoptosis in retinal neurodegeneration,” Proc. Natl. Acad. Sci. U.S.A. 101, 13352–13356 (2004).
[Crossref] [PubMed]

Halfyard, A. S.

N. Lois, A. S. Halfyard, A. C. Bird, G. E. Holder, and F. W. Fitzke, “Fundus autofluorescence in Stargardt macular dystrophy-fundus flavimaculatus,” Am. J. Ophthalmol. 138, 55–63 (2004).
[Crossref] [PubMed]

N. Lois, A. S. Halfyard, A. C. Bird, and F. W. Fitzke, “Quantitative evaluation of fundus autofluorescence imaged “in vivo” in eyes with retinal disease,” Br. J. Ophthalmol. 84, 741–745 (2000).
[Crossref] [PubMed]

Hammer, D. X.

Harding, G.

M. F. Cordeiro, L. Guo, V. Luong, G. Harding, W. Wang, H. E. Jones, S. E. Moss, A. M. Sillito, and F. W. Fitzke, “Real-time imaging of single nerve cell apoptosis in retinal neurodegeneration,” Proc. Natl. Acad. Sci. U.S.A. 101, 13352–13356 (2004).
[Crossref] [PubMed]

Hebert, T. J.

Hendrickson, A. E.

C. A. Curcio, K. R. Sloan, R. E. Kalina, and A. E. Hendrickson, “Human Photoreceptor Topography,” J. Comp. Neurol. 292, 497–523 (1990).
[Crossref] [PubMed]

O. Packer, a. E. Hendrickson, and C. a. Curcio, “Photoreceptor Topography of the Retina in the Adult Pigtail Macaque (Macaca-Nemestrina),” J. Comp. Neurol. 288, 165–183 (1989).
[Crossref] [PubMed]

Hermann, B.

Hilderbrand, E. S.

L. Feeney-Burns, E. S. Hilderbrand, and S. Eldridge, “Aging Human Rpe - Morphometric Analysis of Macular, Equatorial, and Peripheral Cells,” Invest. Ophthl. Vis. Sci. 25, 195–200 (1984).

Hjelmeland, L. M.

J. M. Burke and L. M. Hjelmeland, “Mosaicism of the retinal pigment epithelium: seeing the small picture,” Mol. Interv. 5, 241–249 (2005).
[Crossref] [PubMed]

Hofer, H.

H. Hofer, J. Carroll, J. Neitz, M. Neitz, and D. R. Williams, “Organization of the human trichromatic cone mosaic,” J. Neurosci. 26, 722–722 (2006).

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, 8461–8466 (2004).
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A. Pallikaris, D. R. Williams, and H. Hofer, “The Reflectance of Single Cones in the Living Human Eye,” Invest. Opthalmol. Vis. Sci. 44, 4580–4492 (2003).
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G. Yoon, H. Hofer, L. Chen, B. Singer, J. Porter, Y. Yamauchi, N. Doble, and D. R. Williams, “Dynamic correction of the eye’s aberration with the Rochester 2nd generation adaptive optics system.," Invest. Ophthalmol. Visual Sci. 42, S99–S99 (2001).

H. Hofer, L. Chen, G. Y. Yoon, B. Singer, Y. Yamauchi, and D. R. Williams, “Improvement in retinal image quality with dynamic correction of the eye’s aberrations,” J. Opt. Soc. Am. A 8, 631–643 (2001).

H. Hofer, P. Artal, B. Singer, J. L. Aragon, and D. R. Williams, “Dynamics of the eye’s wave aberration,” J. Opt. Soc. Am. A 18, 497–506 (2001).
[Crossref]

Hofer, H. J.

N. M. Putnam, H. J. Hofer, N. Doble, L. Chen, J. Carroll, and D. R. Williams, “The locus of fixation and the foveal cone mosaic,” J. Vis. 5, 632–639 (2005).
[Crossref] [PubMed]

Holder, G. E.

N. Lois, A. S. Halfyard, A. C. Bird, G. E. Holder, and F. W. Fitzke, “Fundus autofluorescence in Stargardt macular dystrophy-fundus flavimaculatus,” Am. J. Ophthalmol. 138, 55–63 (2004).
[Crossref] [PubMed]

Holz, F. G.

A. Bindewald, J. J. Jorzik, A. Loesch, F. Schutt, and F. G. Holz, “Visualization of retinal pigment epithelial cells in vivo using digital high-resolution confocal scanning laser ophthalmoscopy,” Am. J. Opthalmol. 137, 556–558 (2004).
[Crossref]

F. G. Holz, C. Bellman, S. Staudt, F. Schutt, and H. E. Volcker, “Fundus autofluorescence and development of geographic atrophy in age-related macular degeneration,” Invest. Ophthalmol. Visual Sci. 42, 1051–1056 (2001).

Iftimia, N. V.

Imanishi, Y.

Y. Imanishi, D. W. Piston, W. Baehr, and K. Palczewski, “Noninvasive two-photon imaging reveals retinyl ester storage structures in the eye,” J. Cell. Biol. 164, 373–383 (2004).
[Crossref] [PubMed]

Izatt, J. A.

Jiang, W.

W. Jiang, N. Ling, Y. Zhang, Y. Zeping, R. Xuejun, C. Gaun, C. Wang, L. Xue, and E. Li, “Medical and Industrial Application of Adaptive Optics in Institute of Optics and Electronics, Chinese Academy of Sciences,” in 5th International Workshop on Adaptive Optics for Industry and Medicine, (2005)

Jones, H. E.

M. F. Cordeiro, L. Guo, V. Luong, G. Harding, W. Wang, H. E. Jones, S. E. Moss, A. M. Sillito, and F. W. Fitzke, “Real-time imaging of single nerve cell apoptosis in retinal neurodegeneration,” Proc. Natl. Acad. Sci. U.S.A. 101, 13352–13356 (2004).
[Crossref] [PubMed]

Jones, S. M.

Jonnal, R. S.

Jorzik, J. J.

A. Bindewald, J. J. Jorzik, A. Loesch, F. Schutt, and F. G. Holz, “Visualization of retinal pigment epithelial cells in vivo using digital high-resolution confocal scanning laser ophthalmoscopy,” Am. J. Opthalmol. 137, 556–558 (2004).
[Crossref]

Kalina, R. E.

C. A. Curcio, K. R. Sloan, R. E. Kalina, and A. E. Hendrickson, “Human Photoreceptor Topography,” J. Comp. Neurol. 292, 497–523 (1990).
[Crossref] [PubMed]

Kartner, F. X.

W. Drexler, U. Morgner, R. K. Ghanta, F. X. Kartner, J. S. Schuman, and J. G. Fujimoto, “Ultrahigh-resolution ophthalmic optical coherence tomography,” Nat. Med 7, 502–507 (2001).
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Ko, T. H.

Kowalczyk, A.

Lacombe, F.

M. Glanc, E. Gendron, F. Lacombe, D. Lafaille, J. F. Le Gargasson, and P. Lena, “Towards wide-field retinal imaging with adaptive optics,” Opt. Commun. 230, 225–238 (2004).
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Lafaille, D.

M. Glanc, E. Gendron, F. Lacombe, D. Lafaille, J. F. Le Gargasson, and P. Lena, “Towards wide-field retinal imaging with adaptive optics,” Opt. Commun. 230, 225–238 (2004).
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Le, T.

Le Gargasson, J. F.

M. Glanc, E. Gendron, F. Lacombe, D. Lafaille, J. F. Le Gargasson, and P. Lena, “Towards wide-field retinal imaging with adaptive optics,” Opt. Commun. 230, 225–238 (2004).
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Leitgeb, R.

E. J. Fernandez, 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, 3432–3444 (2005).
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Leitgeb, R. a.

Lena, P.

M. Glanc, E. Gendron, F. Lacombe, D. Lafaille, J. F. Le Gargasson, and P. Lena, “Towards wide-field retinal imaging with adaptive optics,” Opt. Commun. 230, 225–238 (2004).
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Li, E.

W. Jiang, N. Ling, Y. Zhang, Y. Zeping, R. Xuejun, C. Gaun, C. Wang, L. Xue, and E. Li, “Medical and Industrial Application of Adaptive Optics in Institute of Optics and Electronics, Chinese Academy of Sciences,” in 5th International Workshop on Adaptive Optics for Industry and Medicine, (2005)

Liang, J.

Ling, N.

W. Jiang, N. Ling, Y. Zhang, Y. Zeping, R. Xuejun, C. Gaun, C. Wang, L. Xue, and E. Li, “Medical and Industrial Application of Adaptive Optics in Institute of Optics and Electronics, Chinese Academy of Sciences,” in 5th International Workshop on Adaptive Optics for Industry and Medicine, (2005)

Loesch, A.

A. Bindewald, J. J. Jorzik, A. Loesch, F. Schutt, and F. G. Holz, “Visualization of retinal pigment epithelial cells in vivo using digital high-resolution confocal scanning laser ophthalmoscopy,” Am. J. Opthalmol. 137, 556–558 (2004).
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Lois, N.

N. Lois, A. S. Halfyard, A. C. Bird, G. E. Holder, and F. W. Fitzke, “Fundus autofluorescence in Stargardt macular dystrophy-fundus flavimaculatus,” Am. J. Ophthalmol. 138, 55–63 (2004).
[Crossref] [PubMed]

N. Lois, A. S. Halfyard, A. C. Bird, and F. W. Fitzke, “Quantitative evaluation of fundus autofluorescence imaged “in vivo” in eyes with retinal disease,” Br. J. Ophthalmol. 84, 741–745 (2000).
[Crossref] [PubMed]

Luong, V.

M. F. Cordeiro, L. Guo, V. Luong, G. Harding, W. Wang, H. E. Jones, S. E. Moss, A. M. Sillito, and F. W. Fitzke, “Real-time imaging of single nerve cell apoptosis in retinal neurodegeneration,” Proc. Natl. Acad. Sci. U.S.A. 101, 13352–13356 (2004).
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Metha, A. B.

A. Roorda, A. B. Metha, P. Lennie, and D. R. Williams, “Packing arrangement of the three cone classes in primate retina,” Vision Res. 41, 1291–1306 (2001).
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D. T. Miller, Associate Professor of Optometry, Indian University School of Optometry, 800 E. Atwater Ave, Bloomington, IN 47405 (Personal Communication, 2006).

Morgner, U.

W. Drexler, U. Morgner, R. K. Ghanta, F. X. Kartner, J. S. Schuman, and J. G. Fujimoto, “Ultrahigh-resolution ophthalmic optical coherence tomography,” Nat. Med 7, 502–507 (2001).
[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,” Invest. Ophthalmol. Visual Sci. 36, S188–S188 (1995).

Moss, S. E.

M. F. Cordeiro, L. Guo, V. Luong, G. Harding, W. Wang, H. E. Jones, S. E. Moss, A. M. Sillito, and F. W. Fitzke, “Real-time imaging of single nerve cell apoptosis in retinal neurodegeneration,” Proc. Natl. Acad. Sci. U.S.A. 101, 13352–13356 (2004).
[Crossref] [PubMed]

Nassif, N. A.

Navarro, R.

Neitz, J.

H. Hofer, J. Carroll, J. Neitz, M. Neitz, and D. R. Williams, “Organization of the human trichromatic cone mosaic,” J. Neurosci. 26, 722–722 (2006).

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, 8461–8466 (2004).
[Crossref] [PubMed]

Neitz, M.

H. Hofer, J. Carroll, J. Neitz, M. Neitz, and D. R. Williams, “Organization of the human trichromatic cone mosaic,” J. Neurosci. 26, 722–722 (2006).

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, 8461–8466 (2004).
[Crossref] [PubMed]

Neuringer, M.

D. M. Snodderly, M. M. Sandstrom, I. Y. F. Leung, C. I. Zucker, and M. Neuringer, “Retinal pigment epithelial cell distribution in central retina of rhesus monkeys,” Invest. Ophthalmol. Visual Sci. 43, 2815–2818 (2002).

Niederberger, H. J.

P. M. Bischoff, H. J. Niederberger, B. Torok, and P. Speiser, “Simultaneous Indocyanine Green and Fluorescein Angiography,” Retina 15, 91–99 (1995).
[Crossref] [PubMed]

Olivier, S. S.

Packer, O.

O. Packer, a. E. Hendrickson, and C. a. Curcio, “Photoreceptor Topography of the Retina in the Adult Pigtail Macaque (Macaca-Nemestrina),” J. Comp. Neurol. 288, 165–183 (1989).
[Crossref] [PubMed]

Palczewski, K.

Y. Imanishi, D. W. Piston, W. Baehr, and K. Palczewski, “Noninvasive two-photon imaging reveals retinyl ester storage structures in the eye,” J. Cell. Biol. 164, 373–383 (2004).
[Crossref] [PubMed]

Pallikaris, A.

A. Pallikaris, D. R. Williams, and H. Hofer, “The Reflectance of Single Cones in the Living Human Eye,” Invest. Opthalmol. Vis. Sci. 44, 4580–4492 (2003).
[Crossref]

Patterson, B. A.

J. Cushion, F. N. Reinholz, and B. A. Patterson, “General purpose control system for scanning laser ophthalmoscopes,” Clin Experiment Ophthalmol 31, 241–245 (2003).
[Crossref] [PubMed]

Peterson, B. B.

D. M. Dacey, B. B. Peterson, F. R. Robinson, and P. D. Gamlin, “Fireworks in the primate retina: In vitro photodynamics reveals diverse LGN-projecting ganglion cell types,” Neuron 37, 15–27 (2003).
[Crossref] [PubMed]

Piston, D. W.

Y. Imanishi, D. W. Piston, W. Baehr, and K. Palczewski, “Noninvasive two-photon imaging reveals retinyl ester storage structures in the eye,” J. Cell. Biol. 164, 373–383 (2004).
[Crossref] [PubMed]

Podoleanu, A. G.

Porter, J.

G. Yoon, H. Hofer, L. Chen, B. Singer, J. Porter, Y. Yamauchi, N. Doble, and D. R. Williams, “Dynamic correction of the eye’s aberration with the Rochester 2nd generation adaptive optics system.," Invest. Ophthalmol. Visual Sci. 42, S99–S99 (2001).

Povazay, B.

E. J. Fernandez, 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, 3432–3444 (2005).
[Crossref] [PubMed]

Prieto, P. M.

Putnam, N. M.

N. M. Putnam, H. J. Hofer, N. Doble, L. Chen, J. Carroll, and D. R. Williams, “The locus of fixation and the foveal cone mosaic,” J. Vis. 5, 632–639 (2005).
[Crossref] [PubMed]

Queener, H.

Reinholz, F.

F. Reinholz, R. A. Ashman, and R. H. Eikelboom, “Simultaneous three wavelength imaging with a scanning laser ophthalmoscope,” Cytometry 37, 165–170 (1999).
[Crossref] [PubMed]

Reinholz, F. N.

J. Cushion, F. N. Reinholz, and B. A. Patterson, “General purpose control system for scanning laser ophthalmoscopes,” Clin Experiment Ophthalmol 31, 241–245 (2003).
[Crossref] [PubMed]

Rha, J. T.

Robinson, F. R.

D. M. Dacey, B. B. Peterson, F. R. Robinson, and P. D. Gamlin, “Fireworks in the primate retina: In vitro photodynamics reveals diverse LGN-projecting ganglion cell types,” Neuron 37, 15–27 (2003).
[Crossref] [PubMed]

Robinson, R. A.

A. F. Fuchs and R. A. Robinson, “A method for measuring horizontal and vertical eye movement chronically in the monkey,” J. Appl. Physiol. 21, 1068–1070 (1966).
[PubMed]

Romero-Borja, F.

Roorda, A.

J. I. Wolfing, M. Chung, J. Carroll, A. Roorda, and D. R. Williams, “High-resolution retinal imaging of cone-rod dystrophy,” Ophthalmology 113, 1014–1019 (2006).
[Crossref]

A. Roorda, F. Romero-Borja, W. J. Donnelly, H. Queener, T. J. Hebert, and M. C. W. Campbell, “Adaptive optics scanning laser ophthalmoscopy,” Opt. Express 10, 405–412 (2002).
[PubMed]

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

A. Roorda, A. B. Metha, P. Lennie, and D. R. Williams, “Packing arrangement of the three cone classes in primate retina,” Vision Res. 41, 1291–1306 (2001).
[Crossref] [PubMed]

A. Roorda and D. R. Williams, “The arrangement of the three cone classes in the living human eye,” Nature 397, 520–522 (1999).
[Crossref] [PubMed]

Sandstrom, M. M.

D. M. Snodderly, M. M. Sandstrom, I. Y. F. Leung, C. I. Zucker, and M. Neuringer, “Retinal pigment epithelial cell distribution in central retina of rhesus monkeys,” Invest. Ophthalmol. Visual Sci. 43, 2815–2818 (2002).

Sattmann, H.

E. J. Fernandez, 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, 3432–3444 (2005).
[Crossref] [PubMed]

B. Hermann, E. J. Fernandez, A. Unterhuber, H. Sattmann, A. F. Fercher, W. Drexler, P. M. Prieto, and P. Artal, “Adaptive-optics ultrahigh-resolution optical coherence tomography,” Opt. Lett. 29, 2142–2144 (2004).
[Crossref] [PubMed]

Schuman, J. S.

W. Drexler, U. Morgner, R. K. Ghanta, F. X. Kartner, J. S. Schuman, and J. G. Fujimoto, “Ultrahigh-resolution ophthalmic optical coherence tomography,” Nat. Med 7, 502–507 (2001).
[Crossref] [PubMed]

Schutt, F.

A. Bindewald, J. J. Jorzik, A. Loesch, F. Schutt, and F. G. Holz, “Visualization of retinal pigment epithelial cells in vivo using digital high-resolution confocal scanning laser ophthalmoscopy,” Am. J. Opthalmol. 137, 556–558 (2004).
[Crossref]

F. G. Holz, C. Bellman, S. Staudt, F. Schutt, and H. E. Volcker, “Fundus autofluorescence and development of geographic atrophy in age-related macular degeneration,” Invest. Ophthalmol. Visual Sci. 42, 1051–1056 (2001).

Sillito, A. M.

M. F. Cordeiro, L. Guo, V. Luong, G. Harding, W. Wang, H. E. Jones, S. E. Moss, A. M. Sillito, and F. W. Fitzke, “Real-time imaging of single nerve cell apoptosis in retinal neurodegeneration,” Proc. Natl. Acad. Sci. U.S.A. 101, 13352–13356 (2004).
[Crossref] [PubMed]

Singer, B.

G. Yoon, H. Hofer, L. Chen, B. Singer, J. Porter, Y. Yamauchi, N. Doble, and D. R. Williams, “Dynamic correction of the eye’s aberration with the Rochester 2nd generation adaptive optics system.," Invest. Ophthalmol. Visual Sci. 42, S99–S99 (2001).

H. Hofer, L. Chen, G. Y. Yoon, B. Singer, Y. Yamauchi, and D. R. Williams, “Improvement in retinal image quality with dynamic correction of the eye’s aberrations,” J. Opt. Soc. Am. A 8, 631–643 (2001).

H. Hofer, P. Artal, B. Singer, J. L. Aragon, and D. R. Williams, “Dynamics of the eye’s wave aberration,” J. Opt. Soc. Am. A 18, 497–506 (2001).
[Crossref]

Sloan, K. R.

C. A. Curcio, K. R. Sloan, R. E. Kalina, and A. E. Hendrickson, “Human Photoreceptor Topography,” J. Comp. Neurol. 292, 497–523 (1990).
[Crossref] [PubMed]

Snodderly, D. M.

D. M. Snodderly, M. M. Sandstrom, I. Y. F. Leung, C. I. Zucker, and M. Neuringer, “Retinal pigment epithelial cell distribution in central retina of rhesus monkeys,” Invest. Ophthalmol. Visual Sci. 43, 2815–2818 (2002).

R. S. Weinhaus, J. M. Burke, F. C. Delori, and D. M. Snodderly, “Comparison of Fluorescein Angiography with Microvascular Anatomy of Macaque Retinas,” Exp. Eye Res. 61, 1–16 (1995).
[Crossref] [PubMed]

Speiser, P.

P. M. Bischoff, H. J. Niederberger, B. Torok, and P. Speiser, “Simultaneous Indocyanine Green and Fluorescein Angiography,” Retina 15, 91–99 (1995).
[Crossref] [PubMed]

Srinivasan, V. J.

Staudt, S.

F. G. Holz, C. Bellman, S. Staudt, F. Schutt, and H. E. Volcker, “Fundus autofluorescence and development of geographic atrophy in age-related macular degeneration,” Invest. Ophthalmol. Visual Sci. 42, 1051–1056 (2001).

Staurenghi, G.

F. C. Delori, C. K. Dorey, G. Staurenghi, O. Arend, D. G. Goger, and J. J. Weiter, “In vivo fluorescence of the ocular fundus exhibits retinal pigment epithelium lipofuscin characteristics,” Invest. Ophthalmol. Visual Sci. 36, 718–729 (1995).

Stiles, W. S.

G. Wyszecki and W. S. Stiles, Color Science: Concepts and Methods, Quantitative Data and Formulas (John Wiley & Sons, Inc., New York, 1982), Chap. 2.

Stingl, A.

Strauss, O.

O. Strauss, “The retinal pigment epithelium in visual function,” Physiol. Rev. 85, 845–881 (2005).
[Crossref] [PubMed]

Torok, B.

P. M. Bischoff, H. J. Niederberger, B. Torok, and P. Speiser, “Simultaneous Indocyanine Green and Fluorescein Angiography,” Retina 15, 91–99 (1995).
[Crossref] [PubMed]

Unterhuber, A.

Ustun, T. E.

Vargas-Martin, F.

Volcker, H. E.

F. G. Holz, C. Bellman, S. Staudt, F. Schutt, and H. E. Volcker, “Fundus autofluorescence and development of geographic atrophy in age-related macular degeneration,” Invest. Ophthalmol. Visual Sci. 42, 1051–1056 (2001).

von Ruckmann, A.

A. von Ruckmann, F. W. Fitzke, and A. C. Bird, “Distribution of fundus autofluorescence with a scanning laser ophthalmoscope,” Br. J. Ophthalmol. 79, 407–412 (1995).
[Crossref] [PubMed]

Wang, C.

W. Jiang, N. Ling, Y. Zhang, Y. Zeping, R. Xuejun, C. Gaun, C. Wang, L. Xue, and E. Li, “Medical and Industrial Application of Adaptive Optics in Institute of Optics and Electronics, Chinese Academy of Sciences,” in 5th International Workshop on Adaptive Optics for Industry and Medicine, (2005)

Wang, W.

M. F. Cordeiro, L. Guo, V. Luong, G. Harding, W. Wang, H. E. Jones, S. E. Moss, A. M. Sillito, and F. W. Fitzke, “Real-time imaging of single nerve cell apoptosis in retinal neurodegeneration,” Proc. Natl. Acad. Sci. U.S.A. 101, 13352–13356 (2004).
[Crossref] [PubMed]

Weinhaus, R. S.

R. S. Weinhaus, J. M. Burke, F. C. Delori, and D. M. Snodderly, “Comparison of Fluorescein Angiography with Microvascular Anatomy of Macaque Retinas,” Exp. Eye Res. 61, 1–16 (1995).
[Crossref] [PubMed]

Weiter, J. J.

F. C. Delori, C. K. Dorey, G. Staurenghi, O. Arend, D. G. Goger, and J. J. Weiter, “In vivo fluorescence of the ocular fundus exhibits retinal pigment epithelium lipofuscin characteristics,” Invest. Ophthalmol. Visual Sci. 36, 718–729 (1995).

Werner, J. S.

Williams, D. R.

J. I. Wolfing, M. Chung, J. Carroll, A. Roorda, and D. R. Williams, “High-resolution retinal imaging of cone-rod dystrophy,” Ophthalmology 113, 1014–1019 (2006).
[Crossref]

H. Hofer, J. Carroll, J. Neitz, M. Neitz, and D. R. Williams, “Organization of the human trichromatic cone mosaic,” J. Neurosci. 26, 722–722 (2006).

N. M. Putnam, H. J. Hofer, N. Doble, L. Chen, J. Carroll, and D. R. Williams, “The locus of fixation and the foveal cone mosaic,” J. Vis. 5, 632–639 (2005).
[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, 8461–8466 (2004).
[Crossref] [PubMed]

A. Pallikaris, D. R. Williams, and H. Hofer, “The Reflectance of Single Cones in the Living Human Eye,” Invest. Opthalmol. Vis. Sci. 44, 4580–4492 (2003).
[Crossref]

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

H. Hofer, L. Chen, G. Y. Yoon, B. Singer, Y. Yamauchi, and D. R. Williams, “Improvement in retinal image quality with dynamic correction of the eye’s aberrations,” J. Opt. Soc. Am. A 8, 631–643 (2001).

A. Roorda, A. B. Metha, P. Lennie, and D. R. Williams, “Packing arrangement of the three cone classes in primate retina,” Vision Res. 41, 1291–1306 (2001).
[Crossref] [PubMed]

G. Yoon, H. Hofer, L. Chen, B. Singer, J. Porter, Y. Yamauchi, N. Doble, and D. R. Williams, “Dynamic correction of the eye’s aberration with the Rochester 2nd generation adaptive optics system.," Invest. Ophthalmol. Visual Sci. 42, S99–S99 (2001).

H. Hofer, P. Artal, B. Singer, J. L. Aragon, and D. R. Williams, “Dynamics of the eye’s wave aberration,” J. Opt. Soc. Am. A 18, 497–506 (2001).
[Crossref]

A. Roorda and D. R. Williams, “The arrangement of the three cone classes in the living human eye,” Nature 397, 520–522 (1999).
[Crossref] [PubMed]

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

J. Liang and D. R. Williams, “Aberrations and retinal image quality of the normal human eye,” J. Opt. Soc. Am. A 14, 2873–2883 (1997).
[Crossref]

D. T. Miller, D. R. Williams, G. M. Morris, and J. Liang, “Images of Cone Photoreceptors in the Living Human Eye,” Invest. Ophthalmol. Visual Sci. 36, S188–S188 (1995).

N. J. Coletta and D. R. Williams, “Psychophysical Estimate of Parafoveal Cone Spacing,” J. Opt. Soc. Am. A Opt. Image Sci. Vis. 3, P92–P93 (1986).

Wojtkowski, M.

Wolfing, J. I.

J. I. Wolfing, M. Chung, J. Carroll, A. Roorda, and D. R. Williams, “High-resolution retinal imaging of cone-rod dystrophy,” Ophthalmology 113, 1014–1019 (2006).
[Crossref]

Wyszecki, G.

G. Wyszecki and W. S. Stiles, Color Science: Concepts and Methods, Quantitative Data and Formulas (John Wiley & Sons, Inc., New York, 1982), Chap. 2.

Xue, L.

W. Jiang, N. Ling, Y. Zhang, Y. Zeping, R. Xuejun, C. Gaun, C. Wang, L. Xue, and E. Li, “Medical and Industrial Application of Adaptive Optics in Institute of Optics and Electronics, Chinese Academy of Sciences,” in 5th International Workshop on Adaptive Optics for Industry and Medicine, (2005)

Xuejun, R.

W. Jiang, N. Ling, Y. Zhang, Y. Zeping, R. Xuejun, C. Gaun, C. Wang, L. Xue, and E. Li, “Medical and Industrial Application of Adaptive Optics in Institute of Optics and Electronics, Chinese Academy of Sciences,” in 5th International Workshop on Adaptive Optics for Industry and Medicine, (2005)

Yamauchi, Y.

G. Yoon, H. Hofer, L. Chen, B. Singer, J. Porter, Y. Yamauchi, N. Doble, and D. R. Williams, “Dynamic correction of the eye’s aberration with the Rochester 2nd generation adaptive optics system.," Invest. Ophthalmol. Visual Sci. 42, S99–S99 (2001).

H. Hofer, L. Chen, G. Y. Yoon, B. Singer, Y. Yamauchi, and D. R. Williams, “Improvement in retinal image quality with dynamic correction of the eye’s aberrations,” J. Opt. Soc. Am. A 8, 631–643 (2001).

Yoon, G.

G. Yoon, H. Hofer, L. Chen, B. Singer, J. Porter, Y. Yamauchi, N. Doble, and D. R. Williams, “Dynamic correction of the eye’s aberration with the Rochester 2nd generation adaptive optics system.," Invest. Ophthalmol. Visual Sci. 42, S99–S99 (2001).

Yoon, G. Y.

H. Hofer, L. Chen, G. Y. Yoon, B. Singer, Y. Yamauchi, and D. R. Williams, “Improvement in retinal image quality with dynamic correction of the eye’s aberrations,” J. Opt. Soc. Am. A 8, 631–643 (2001).

Zawadzki, R. J.

Zeping, Y.

W. Jiang, N. Ling, Y. Zhang, Y. Zeping, R. Xuejun, C. Gaun, C. Wang, L. Xue, and E. Li, “Medical and Industrial Application of Adaptive Optics in Institute of Optics and Electronics, Chinese Academy of Sciences,” in 5th International Workshop on Adaptive Optics for Industry and Medicine, (2005)

Zhang, Y.

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

W. Jiang, N. Ling, Y. Zhang, Y. Zeping, R. Xuejun, C. Gaun, C. Wang, L. Xue, and E. Li, “Medical and Industrial Application of Adaptive Optics in Institute of Optics and Electronics, Chinese Academy of Sciences,” in 5th International Workshop on Adaptive Optics for Industry and Medicine, (2005)

Zhao, M. T.

Zinn, K. M.

K. M. Zinn and J. V. Benjamin-Henkind, “Anatomy of the human retinal pigment epithelium”, in The Retinal Pigment Epithelium, K. M. Zinn and M. F. Marmor (Harvard University Press, Cambridge, 1979).

K. M. Zinn and J. V. Benjamin-Henkind, “Anatomy of the human retinal pigment epithelium”, in The Retinal Pigment Epithelium, K. M. Zinn and M. F. Marmor (Harvard University Press, Cambridge, 1979).

Zucker, C. I.

D. M. Snodderly, M. M. Sandstrom, I. Y. F. Leung, C. I. Zucker, and M. Neuringer, “Retinal pigment epithelial cell distribution in central retina of rhesus monkeys,” Invest. Ophthalmol. Visual Sci. 43, 2815–2818 (2002).

Am. J. Ophthalmol. (1)

N. Lois, A. S. Halfyard, A. C. Bird, G. E. Holder, and F. W. Fitzke, “Fundus autofluorescence in Stargardt macular dystrophy-fundus flavimaculatus,” Am. J. Ophthalmol. 138, 55–63 (2004).
[Crossref] [PubMed]

Am. J. Opthalmol. (1)

A. Bindewald, J. J. Jorzik, A. Loesch, F. Schutt, and F. G. Holz, “Visualization of retinal pigment epithelial cells in vivo using digital high-resolution confocal scanning laser ophthalmoscopy,” Am. J. Opthalmol. 137, 556–558 (2004).
[Crossref]

Appl. Opt. (1)

Br. J. Ophthalmol. (2)

A. von Ruckmann, F. W. Fitzke, and A. C. Bird, “Distribution of fundus autofluorescence with a scanning laser ophthalmoscope,” Br. J. Ophthalmol. 79, 407–412 (1995).
[Crossref] [PubMed]

N. Lois, A. S. Halfyard, A. C. Bird, and F. W. Fitzke, “Quantitative evaluation of fundus autofluorescence imaged “in vivo” in eyes with retinal disease,” Br. J. Ophthalmol. 84, 741–745 (2000).
[Crossref] [PubMed]

Clin Experiment Ophthalmol (1)

J. Cushion, F. N. Reinholz, and B. A. Patterson, “General purpose control system for scanning laser ophthalmoscopes,” Clin Experiment Ophthalmol 31, 241–245 (2003).
[Crossref] [PubMed]

Cytometry (1)

F. Reinholz, R. A. Ashman, and R. H. Eikelboom, “Simultaneous three wavelength imaging with a scanning laser ophthalmoscope,” Cytometry 37, 165–170 (1999).
[Crossref] [PubMed]

Exp. Eye Res. (1)

R. S. Weinhaus, J. M. Burke, F. C. Delori, and D. M. Snodderly, “Comparison of Fluorescein Angiography with Microvascular Anatomy of Macaque Retinas,” Exp. Eye Res. 61, 1–16 (1995).
[Crossref] [PubMed]

Invest. Ophthalmol. Visual Sci. (6)

F. G. Holz, C. Bellman, S. Staudt, F. Schutt, and H. E. Volcker, “Fundus autofluorescence and development of geographic atrophy in age-related macular degeneration,” Invest. Ophthalmol. Visual Sci. 42, 1051–1056 (2001).

F. C. Delori, D. G. Goger, and C. K. Dorey, “Age-related accumulation and spatial distribution of lipofuscin in RPE of normal subjects,” Invest. Ophthalmol. Visual Sci. 42, 1855–1866 (2001).

F. C. Delori, C. K. Dorey, G. Staurenghi, O. Arend, D. G. Goger, and J. J. Weiter, “In vivo fluorescence of the ocular fundus exhibits retinal pigment epithelium lipofuscin characteristics,” Invest. Ophthalmol. Visual Sci. 36, 718–729 (1995).

D. M. Snodderly, M. M. Sandstrom, I. Y. F. Leung, C. I. Zucker, and M. Neuringer, “Retinal pigment epithelial cell distribution in central retina of rhesus monkeys,” Invest. Ophthalmol. Visual Sci. 43, 2815–2818 (2002).

D. T. Miller, D. R. Williams, G. M. Morris, and J. Liang, “Images of Cone Photoreceptors in the Living Human Eye,” Invest. Ophthalmol. Visual Sci. 36, S188–S188 (1995).

G. Yoon, H. Hofer, L. Chen, B. Singer, J. Porter, Y. Yamauchi, N. Doble, and D. R. Williams, “Dynamic correction of the eye’s aberration with the Rochester 2nd generation adaptive optics system.," Invest. Ophthalmol. Visual Sci. 42, S99–S99 (2001).

Invest. Ophthl. Vis. Sci. (1)

L. Feeney-Burns, E. S. Hilderbrand, and S. Eldridge, “Aging Human Rpe - Morphometric Analysis of Macular, Equatorial, and Peripheral Cells,” Invest. Ophthl. Vis. Sci. 25, 195–200 (1984).

Invest. Opthalmol. Vis. Sci. (1)

A. Pallikaris, D. R. Williams, and H. Hofer, “The Reflectance of Single Cones in the Living Human Eye,” Invest. Opthalmol. Vis. Sci. 44, 4580–4492 (2003).
[Crossref]

J. Appl. Physiol. (1)

A. F. Fuchs and R. A. Robinson, “A method for measuring horizontal and vertical eye movement chronically in the monkey,” J. Appl. Physiol. 21, 1068–1070 (1966).
[PubMed]

J. Cell. Biol. (1)

Y. Imanishi, D. W. Piston, W. Baehr, and K. Palczewski, “Noninvasive two-photon imaging reveals retinyl ester storage structures in the eye,” J. Cell. Biol. 164, 373–383 (2004).
[Crossref] [PubMed]

J. Comp. Neurol. (2)

C. A. Curcio, K. R. Sloan, R. E. Kalina, and A. E. Hendrickson, “Human Photoreceptor Topography,” J. Comp. Neurol. 292, 497–523 (1990).
[Crossref] [PubMed]

O. Packer, a. E. Hendrickson, and C. a. Curcio, “Photoreceptor Topography of the Retina in the Adult Pigtail Macaque (Macaca-Nemestrina),” J. Comp. Neurol. 288, 165–183 (1989).
[Crossref] [PubMed]

J. Neurosci. (1)

H. Hofer, J. Carroll, J. Neitz, M. Neitz, and D. R. Williams, “Organization of the human trichromatic cone mosaic,” J. Neurosci. 26, 722–722 (2006).

J. Opt. Soc. Am. A (5)

J. Opt. Soc. Am. A Opt. Image Sci. Vis. (1)

N. J. Coletta and D. R. Williams, “Psychophysical Estimate of Parafoveal Cone Spacing,” J. Opt. Soc. Am. A Opt. Image Sci. Vis. 3, P92–P93 (1986).

J. Vis. (2)

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

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Nature (1)

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Neuron (1)

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Supplementary Material (1)

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Figures (6)

Fig. 1.
Fig. 1.

The fluorescence Adaptive Optics Scanning Laser Ophthalmoscope. L: lenses, M: spherical mirrors, FM: fold mirrors, CM: cold mirrors, FC: fiber collimators, DBS: dichroic beam splitters, CP: confocal pinholes, LD: 830-nm fiber coupled laser diode, LDB: laser diode beacon, BS 1: 90/10 parallel plate AR coated beam splitter, DM: MEMS deformable mirror, TL: ophthalmic trial lens, PBS: pellicle beam splitter, VS: vertical scanner (26 Hz), HS: horizontal scanner (15.1 kHz), F: band pass fluorescence filter, PMT: photomultiplier tube, APD: avalanche photodiode, LEI Box: scanner control electronics.

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Fig. 2.
Fig. 2.

(a) Ganglion cell bodies and axons labeled with rhodamine dextran dye. The image was taken at an eccentricity of approximately 17 degrees nasal and 5 degrees inferior, with the optic disk to the upper right of the image. (b) Ganglion cells labeled with rhodamine dextran dye at an eccentricity of approximately 10 degrees inferior along the vertical meridian. (c) Ganglion cells labeled with alexa 594 dye at an eccentricity of approximately 10 degrees infero-nasal, 37 days after labeling. (d) From the same location, taken 77 days after image (c) showing at least four ganglion cells that remained labeled. (a, b, c) taken without AO correction, (d) with closed loop AO correction, (a, b) taken without dual registration and (c, d) taken with dual registration. The images were constructed from (a) 500 frames, (b) 200 frames, (c) 512 frames, (d) 1000 frames. Scale bars: (a, b) 100 μm, (c, d) 50 μm.

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Fig. 3.
Fig. 3.

(a) Located at an eccentricity of approximately 19 degrees nasal and 7 degrees inferior, ganglion cells labeled with rhodamine dextran dye. The image was taken before exposure to intense light, and cells were excited at 530 nm. The green box shows the approximate size of the exposed region (b). Increased intensity of cell fluorescence due to a 20-minute exposure of a 1-degree square area with 530-nm excitation. Both images were taken without adaptive optics or dual registration. 300 frames were used to create both images. Scale bars are 100 μm.

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Fig. 4.
Fig. 4.

RPE cells imaged at two retinal locations: (a) At an eccentricity of approximately 10 degrees infero-nasal at the same location as ganglion cells in Fig. 2 (c) and (d). (b) Centered at the fovea. Both images taken with the use of adaptive optics, dual registration, and were created with 1000 frames. Scale bars are 75 μm.

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Fig. 5.
Fig. 5.

(a) Two-dimensional power spectrum corresponding to the RPE mosaic in Fig. 4 (a). (b) Two-dimensional power spectrum corresponding to the RPE mosaic in Fig. 4 (b).

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Fig. 6.
Fig. 6.

Intravenous injection of sodium fluorescein dye centered at the fovea with a 3.5-degree field of view. The image was taken without adaptive optics, and 1918 fluorescence frames were dual registered. See linked (2 MB) movie file for real time filling of the vasculature. Scale bar is 150 μm. [Media 1]

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