Abstract

Non-invasive reflectance imaging of the human RPE cell mosaic is demonstrated using a modified confocal adaptive optics scanning light ophthalmoscope (AOSLO). The confocal circular aperture in front of the imaging detector was replaced with a combination of a circular aperture 4 to 16 Airy disks in diameter and an opaque filament, 1 or 3 Airy disks thick. This arrangement reveals the RPE cell mosaic by dramatically attenuating the light backscattered by the photoreceptors. The RPE cell mosaic was visualized in all 7 recruited subjects at multiple retinal locations with varying degrees of contrast and cross-talk from the photoreceptors. Various experimental settings were explored for improving the visualization of the RPE cell boundaries including: pinhole diameter, filament thickness, illumination and imaging pupil apodization, unmatched imaging and illumination focus, wavelength and polarization. None of these offered an obvious path for enhancing image contrast. The demonstrated implementation of dark-field AOSLO imaging using 790 nm light requires low light exposures relative to light safety standards and it is more comfortable for the subject than the traditional autofluorescence RPE imaging with visible light. Both these factors make RPE dark-field imaging appealing for studying mechanisms of eye disease, as well as a clinical tool for screening and monitoring disease progression.

© 2013 OSA

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    [PubMed]

2013

R. F. Cooper, C. S. Langlo, A. Dubra, and J. Carroll, “Automatic detection of modal spacing (Yellott’s ring) in adaptive optics scanning light ophthalmoscope images,” Ophthalmic Physiol. Opt.33(4), 540–549 (2013).
[CrossRef] [PubMed]

2012

Y. U. Shin and B. R. Lee, “Retro-mode Imaging for retinal pigment epithelium alterations in central serous chorioretinopathy,” Am. J. Ophthalmol154, 155–163 (2012).

Y. N. Sulai and A. Dubra, “Adaptive optics scanning ophthalmoscopy with annular pupils,” Biomed. Opt. Express3(7), 1647–1661 (2012).
[CrossRef] [PubMed]

T. Y. Chui, D. A. Vannasdale, and S. A. Burns, “The use of forward scatter to improve retinal vascular imaging with an adaptive optics scanning laser ophthalmoscope,” Biomed. Opt. Express3(10), 2537–2549 (2012).
[CrossRef] [PubMed]

J. Ambati and B. J. Fowler, “Mechanisms of age-related macular degeneration,” Neuron75(1), 26–39 (2012).
[CrossRef] [PubMed]

V. C. Greenstein, T. Duncker, K. Holopigian, R. E. Carr, J. P. Greenberg, S. H. Tsang, and D. C. Hood, “Structural and functional changes associated with normal and abnormal fundus autofluorescence in patients with retinitis pigmentosa,” Retina32(2), 349–357 (2012).
[CrossRef] [PubMed]

2011

R. F. Spaide and C. A. Curcio, “Anatomical correlates to the bands seen in the outer retina by optical coherence tomography: literature review and model,” Retina31(8), 1609–1619 (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]

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

2010

H. Tanna, A. M. Dubis, N. Ayub, D. M. Tait, J. Rha, K. E. Stepien, and J. Carroll, “Retinal imaging using commercial broadband optical coherence tomography,” Br. J. Ophthalmol.94(3), 372–376 (2010).
[CrossRef] [PubMed]

U. Kellner, S. Kellner, and S. Weinitz, “Fundus autofluorescence (488 NM) and near-infrared autofluorescence (787 NM) visualize different retinal pigment epithelium alterations in patients with age-related macular degeneration,” Retina30(1), 6–15 (2010).
[CrossRef] [PubMed]

R. Simó, M. Villarroel, L. Corraliza, C. Hernández, and M. Garcia-Ramírez, “The retinal pigment epithelium: something more than a constituent of the blood-retinal barrier--implications for the pathogenesis of diabetic retinopathy,” J. Biomed. Biotechnol.2010, 190724 (2010).
[CrossRef] [PubMed]

2009

U. Kellner, S. Kellner, B. H. Weber, B. Fiebig, S. Weinitz, and K. Ruether, “Lipofuscin- and melanin-related fundus autofluorescence visualize different retinal pigment epithelial alterations in patients with retinitis pigmentosa,” Eye (Lond.)23(6), 1349–1359 (2009).
[CrossRef] [PubMed]

2008

S. Schmitz-Valckenberg, F. G. Holz, A. C. Bird, and R. F. Spaide, “Fundus autofluorescence imaging: review and perspectives,” Retina28(3), 385–409 (2008).
[CrossRef] [PubMed]

M. Fleckenstein, P. Charbel Issa, H. M. Helb, S. Schmitz-Valckenberg, R. P. Finger, H. P. Scholl, K. U. Loeffler, and F. G. Holz, “High-resolution spectral domain-OCT imaging in geographic atrophy associated with age-related macular degeneration,” Invest. Ophthalmol. Vis. Sci.49(9), 4137–4144 (2008).
[CrossRef] [PubMed]

J. I. W. Morgan, J. J. Hunter, B. Masella, R. Wolfe, D. C. Gray, W. H. Merigan, F. C. Delori, and D. R. Williams, “Light-induced retinal changes observed with high-resolution autofluorescence imaging of the retinal pigment epithelium,” Invest. Ophthalmol. Vis. Sci.49(8), 3715–3729 (2008).
[CrossRef] [PubMed]

J. I. Morgan, A. Dubra, R. Wolfe, W. H. Merigan, and D. R. Williams, “In vivo autofluorescence imaging of the human and macaque retinal pigment epithelial cell mosaic,” Invest. Ophthalmol. Vis. Sci.50(3), 1350–1359 (2008).
[CrossRef] [PubMed]

2007

2006

2005

A. V. Cideciyan, S. G. Jacobson, T. S. Aleman, D. Gu, S. E. Pearce-Kelling, A. Sumaroka, G. M. Acland, and G. D. Aguirre, “In vivo dynamics of retinal injury and repair in the rhodopsin mutant dog model of human retinitis pigmentosa,” Proc. Natl. Acad. Sci. U.S.A.102(14), 5233–5238 (2005).
[CrossRef] [PubMed]

2002

L. C. Glazer and T. P. Dryja, "Understanding the etiology of Stargardt's disease," Ophthalmol. Clin. North. Am.15, 93-100 (2002).

1998

A. Yoshida, S. Ishiko, J. Akiba, N. Kitaya, and T. Nagaoka, “Radiating retinal folds detected by scanning laser ophthalmoscopy using a diode laser in a dark-field mode in idiopathic macular holes,” Graefes Arch. Clin. Exp. Ophthalmol.236(6), 445–450 (1998).
[CrossRef] [PubMed]

1997

F. Marlhens, C. Bareil, J. M. Griffoin, E. Zrenner, P. Amalric, C. Eliaou, S. Y. Liu, E. Harris, T. M. Redmond, B. Arnaud, M. Claustres, and C. P. Hamel, “Mutations in RPE65 cause Leber’s congenital amaurosis,” Nat. Genet.17(2), 139–141 (1997).
[CrossRef] [PubMed]

1996

A. E. Elsner, S. A. Burns, J. J. Weiter, and F. C. Delori, “Infrared imaging of sub-retinal structures in the human ocular fundus,” Vision Res.36(1), 191–205 (1996).
[CrossRef] [PubMed]

1990

C. F. Blodi and E. M. Stone, “Best’s vitelliform dystrophy,” Ophthalmic Paediatr. Genet.11(1), 49–59 (1990).
[PubMed]

1989

C. K. Dorey, G. Wu, D. Ebenstein, A. Garsd, and J. J. Weiter, “Cell loss in the aging retina. Relationship to lipofuscin accumulation and macular degeneration,” Invest. Ophthalmol. Vis. Sci.30(8), 1691–1699 (1989).
[PubMed]

1987

1985

D. Bok, “Retinal photoreceptor-pigment epithelium interactions. Friedenwald lecture,” Invest. Ophthalmol. Vis. Sci.26(12), 1659–1694 (1985).
[PubMed]

R. H. Steinberg, “Interactions between the retinal pigment epithelium and the neural retina,” Doc. Ophthalmol.60(4), 327–346 (1985).
[CrossRef] [PubMed]

1970

M. Spitznas and M. J. Hogan, “Outer segments of photoreceptors and the retinal pigment epithelium. Interrelationship in the human eye,” Arch. Ophthalmol.84(6), 810–819 (1970).
[CrossRef] [PubMed]

1933

W. Stiles and B. Crawford, “The luminous efficiency of rays entering the eye pupil at different points,” Proc. R. Soc. Lond. B Biol. Sci.112(778), 428–450 (1933).
[CrossRef]

Acland, G. M.

A. V. Cideciyan, S. G. Jacobson, T. S. Aleman, D. Gu, S. E. Pearce-Kelling, A. Sumaroka, G. M. Acland, and G. D. Aguirre, “In vivo dynamics of retinal injury and repair in the rhodopsin mutant dog model of human retinitis pigmentosa,” Proc. Natl. Acad. Sci. U.S.A.102(14), 5233–5238 (2005).
[CrossRef] [PubMed]

Aguirre, G. D.

A. V. Cideciyan, S. G. Jacobson, T. S. Aleman, D. Gu, S. E. Pearce-Kelling, A. Sumaroka, G. M. Acland, and G. D. Aguirre, “In vivo dynamics of retinal injury and repair in the rhodopsin mutant dog model of human retinitis pigmentosa,” Proc. Natl. Acad. Sci. U.S.A.102(14), 5233–5238 (2005).
[CrossRef] [PubMed]

Ahamd, K.

Akiba, J.

A. Yoshida, S. Ishiko, J. Akiba, N. Kitaya, and T. Nagaoka, “Radiating retinal folds detected by scanning laser ophthalmoscopy using a diode laser in a dark-field mode in idiopathic macular holes,” Graefes Arch. Clin. Exp. Ophthalmol.236(6), 445–450 (1998).
[CrossRef] [PubMed]

Aleman, T. S.

A. V. Cideciyan, S. G. Jacobson, T. S. Aleman, D. Gu, S. E. Pearce-Kelling, A. Sumaroka, G. M. Acland, and G. D. Aguirre, “In vivo dynamics of retinal injury and repair in the rhodopsin mutant dog model of human retinitis pigmentosa,” Proc. Natl. Acad. Sci. U.S.A.102(14), 5233–5238 (2005).
[CrossRef] [PubMed]

Amalric, P.

F. Marlhens, C. Bareil, J. M. Griffoin, E. Zrenner, P. Amalric, C. Eliaou, S. Y. Liu, E. Harris, T. M. Redmond, B. Arnaud, M. Claustres, and C. P. Hamel, “Mutations in RPE65 cause Leber’s congenital amaurosis,” Nat. Genet.17(2), 139–141 (1997).
[CrossRef] [PubMed]

Ambati, J.

J. Ambati and B. J. Fowler, “Mechanisms of age-related macular degeneration,” Neuron75(1), 26–39 (2012).
[CrossRef] [PubMed]

Arnaud, B.

F. Marlhens, C. Bareil, J. M. Griffoin, E. Zrenner, P. Amalric, C. Eliaou, S. Y. Liu, E. Harris, T. M. Redmond, B. Arnaud, M. Claustres, and C. P. Hamel, “Mutations in RPE65 cause Leber’s congenital amaurosis,” Nat. Genet.17(2), 139–141 (1997).
[CrossRef] [PubMed]

Ayub, N.

H. Tanna, A. M. Dubis, N. Ayub, D. M. Tait, J. Rha, K. E. Stepien, and J. Carroll, “Retinal imaging using commercial broadband optical coherence tomography,” Br. J. Ophthalmol.94(3), 372–376 (2010).
[CrossRef] [PubMed]

Baraas, R. C.

Bareil, C.

F. Marlhens, C. Bareil, J. M. Griffoin, E. Zrenner, P. Amalric, C. Eliaou, S. Y. Liu, E. Harris, T. M. Redmond, B. Arnaud, M. Claustres, and C. P. Hamel, “Mutations in RPE65 cause Leber’s congenital amaurosis,” Nat. Genet.17(2), 139–141 (1997).
[CrossRef] [PubMed]

Bird, A. C.

S. Schmitz-Valckenberg, F. G. Holz, A. C. Bird, and R. F. Spaide, “Fundus autofluorescence imaging: review and perspectives,” Retina28(3), 385–409 (2008).
[CrossRef] [PubMed]

Blodi, C. F.

C. F. Blodi and E. M. Stone, “Best’s vitelliform dystrophy,” Ophthalmic Paediatr. Genet.11(1), 49–59 (1990).
[PubMed]

Bok, D.

D. Bok, “Retinal photoreceptor-pigment epithelium interactions. Friedenwald lecture,” Invest. Ophthalmol. Vis. Sci.26(12), 1659–1694 (1985).
[PubMed]

Burns, S. A.

T. Y. Chui, D. A. Vannasdale, and S. A. Burns, “The use of forward scatter to improve retinal vascular imaging with an adaptive optics scanning laser ophthalmoscope,” Biomed. Opt. Express3(10), 2537–2549 (2012).
[CrossRef] [PubMed]

A. E. Elsner, S. A. Burns, J. J. Weiter, and F. C. Delori, “Infrared imaging of sub-retinal structures in the human ocular fundus,” Vision Res.36(1), 191–205 (1996).
[CrossRef] [PubMed]

Carr, R. E.

V. C. Greenstein, T. Duncker, K. Holopigian, R. E. Carr, J. P. Greenberg, S. H. Tsang, and D. C. Hood, “Structural and functional changes associated with normal and abnormal fundus autofluorescence in patients with retinitis pigmentosa,” Retina32(2), 349–357 (2012).
[CrossRef] [PubMed]

Carroll, J.

R. F. Cooper, C. S. Langlo, A. Dubra, and J. Carroll, “Automatic detection of modal spacing (Yellott’s ring) in adaptive optics scanning light ophthalmoscope images,” Ophthalmic Physiol. Opt.33(4), 540–549 (2013).
[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]

H. Tanna, A. M. Dubis, N. Ayub, D. M. Tait, J. Rha, K. E. Stepien, and J. Carroll, “Retinal imaging using commercial broadband optical coherence tomography,” Br. J. Ophthalmol.94(3), 372–376 (2010).
[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]

Charbel Issa, P.

M. Fleckenstein, P. Charbel Issa, H. M. Helb, S. Schmitz-Valckenberg, R. P. Finger, H. P. Scholl, K. U. Loeffler, and F. G. Holz, “High-resolution spectral domain-OCT imaging in geographic atrophy associated with age-related macular degeneration,” Invest. Ophthalmol. Vis. Sci.49(9), 4137–4144 (2008).
[CrossRef] [PubMed]

Chui, T. Y.

Chung, M.

Cideciyan, A. V.

A. V. Cideciyan, S. G. Jacobson, T. S. Aleman, D. Gu, S. E. Pearce-Kelling, A. Sumaroka, G. M. Acland, and G. D. Aguirre, “In vivo dynamics of retinal injury and repair in the rhodopsin mutant dog model of human retinitis pigmentosa,” Proc. Natl. Acad. Sci. U.S.A.102(14), 5233–5238 (2005).
[CrossRef] [PubMed]

Claustres, M.

F. Marlhens, C. Bareil, J. M. Griffoin, E. Zrenner, P. Amalric, C. Eliaou, S. Y. Liu, E. Harris, T. M. Redmond, B. Arnaud, M. Claustres, and C. P. Hamel, “Mutations in RPE65 cause Leber’s congenital amaurosis,” Nat. Genet.17(2), 139–141 (1997).
[CrossRef] [PubMed]

Cooper, R. F.

R. F. Cooper, C. S. Langlo, A. Dubra, and J. Carroll, “Automatic detection of modal spacing (Yellott’s ring) in adaptive optics scanning light ophthalmoscope images,” Ophthalmic Physiol. Opt.33(4), 540–549 (2013).
[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]

Corraliza, L.

R. Simó, M. Villarroel, L. Corraliza, C. Hernández, and M. Garcia-Ramírez, “The retinal pigment epithelium: something more than a constituent of the blood-retinal barrier--implications for the pathogenesis of diabetic retinopathy,” J. Biomed. Biotechnol.2010, 190724 (2010).
[CrossRef] [PubMed]

Crawford, B.

W. Stiles and B. Crawford, “The luminous efficiency of rays entering the eye pupil at different points,” Proc. R. Soc. Lond. B Biol. Sci.112(778), 428–450 (1933).
[CrossRef]

Curcio, C. A.

R. F. Spaide and C. A. Curcio, “Anatomical correlates to the bands seen in the outer retina by optical coherence tomography: literature review and model,” Retina31(8), 1609–1619 (2011).
[CrossRef] [PubMed]

Delori, F. C.

J. I. W. Morgan, J. J. Hunter, B. Masella, R. Wolfe, D. C. Gray, W. H. Merigan, F. C. Delori, and D. R. Williams, “Light-induced retinal changes observed with high-resolution autofluorescence imaging of the retinal pigment epithelium,” Invest. Ophthalmol. Vis. Sci.49(8), 3715–3729 (2008).
[CrossRef] [PubMed]

F. C. Delori, R. H. Webb, D. H. Sliney, and American National Standards Institute, “Maximum permissible exposures for ocular safety (ANSI 2000), with emphasis on ophthalmic devices,” J. Opt. Soc. Am. A24(5), 1250–1265 (2007).
[CrossRef] [PubMed]

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C. K. Dorey, G. Wu, D. Ebenstein, A. Garsd, and J. J. Weiter, “Cell loss in the aging retina. Relationship to lipofuscin accumulation and macular degeneration,” Invest. Ophthalmol. Vis. Sci.30(8), 1691–1699 (1989).
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L. C. Glazer and T. P. Dryja, "Understanding the etiology of Stargardt's disease," Ophthalmol. Clin. North. Am.15, 93-100 (2002).

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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]

H. Tanna, A. M. Dubis, N. Ayub, D. M. Tait, J. Rha, K. E. Stepien, and J. Carroll, “Retinal imaging using commercial broadband optical coherence tomography,” Br. J. Ophthalmol.94(3), 372–376 (2010).
[CrossRef] [PubMed]

Dubra, A.

R. F. Cooper, C. S. Langlo, A. Dubra, and J. Carroll, “Automatic detection of modal spacing (Yellott’s ring) in adaptive optics scanning light ophthalmoscope images,” Ophthalmic Physiol. Opt.33(4), 540–549 (2013).
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Y. N. Sulai and A. Dubra, “Adaptive optics scanning ophthalmoscopy with annular pupils,” Biomed. Opt. Express3(7), 1647–1661 (2012).
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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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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]

J. I. Morgan, A. Dubra, R. Wolfe, W. H. Merigan, and D. R. Williams, “In vivo autofluorescence imaging of the human and macaque retinal pigment epithelial cell mosaic,” Invest. Ophthalmol. Vis. Sci.50(3), 1350–1359 (2008).
[CrossRef] [PubMed]

D. C. Gray, W. Merigan, J. I. Wolfing, B. P. Gee, J. Porter, A. Dubra, T. H. Twietmeyer, K. Ahamd, R. Tumbar, F. Reinholz, and D. R. Williams, “In vivo fluorescence imaging of primate retinal ganglion cells and retinal pigment epithelial cells,” Opt. Express14(16), 7144–7158 (2006).
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Duncan, J. L.

A. Roorda, Y. Zhang, and J. L. Duncan, “High-resolution in vivo imaging of the RPE mosaic in eyes with retinal disease,” Invest. Ophthalmol. Vis. Sci.48(5), 2297–2303 (2007).
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Duncker, T.

V. C. Greenstein, T. Duncker, K. Holopigian, R. E. Carr, J. P. Greenberg, S. H. Tsang, and D. C. Hood, “Structural and functional changes associated with normal and abnormal fundus autofluorescence in patients with retinitis pigmentosa,” Retina32(2), 349–357 (2012).
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Ebenstein, D.

C. K. Dorey, G. Wu, D. Ebenstein, A. Garsd, and J. J. Weiter, “Cell loss in the aging retina. Relationship to lipofuscin accumulation and macular degeneration,” Invest. Ophthalmol. Vis. Sci.30(8), 1691–1699 (1989).
[PubMed]

Eliaou, C.

F. Marlhens, C. Bareil, J. M. Griffoin, E. Zrenner, P. Amalric, C. Eliaou, S. Y. Liu, E. Harris, T. M. Redmond, B. Arnaud, M. Claustres, and C. P. Hamel, “Mutations in RPE65 cause Leber’s congenital amaurosis,” Nat. Genet.17(2), 139–141 (1997).
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Elsner, A. E.

A. E. Elsner, S. A. Burns, J. J. Weiter, and F. C. Delori, “Infrared imaging of sub-retinal structures in the human ocular fundus,” Vision Res.36(1), 191–205 (1996).
[CrossRef] [PubMed]

Fiebig, B.

U. Kellner, S. Kellner, B. H. Weber, B. Fiebig, S. Weinitz, and K. Ruether, “Lipofuscin- and melanin-related fundus autofluorescence visualize different retinal pigment epithelial alterations in patients with retinitis pigmentosa,” Eye (Lond.)23(6), 1349–1359 (2009).
[CrossRef] [PubMed]

Finger, R. P.

M. Fleckenstein, P. Charbel Issa, H. M. Helb, S. Schmitz-Valckenberg, R. P. Finger, H. P. Scholl, K. U. Loeffler, and F. G. Holz, “High-resolution spectral domain-OCT imaging in geographic atrophy associated with age-related macular degeneration,” Invest. Ophthalmol. Vis. Sci.49(9), 4137–4144 (2008).
[CrossRef] [PubMed]

Fleckenstein, M.

M. Fleckenstein, P. Charbel Issa, H. M. Helb, S. Schmitz-Valckenberg, R. P. Finger, H. P. Scholl, K. U. Loeffler, and F. G. Holz, “High-resolution spectral domain-OCT imaging in geographic atrophy associated with age-related macular degeneration,” Invest. Ophthalmol. Vis. Sci.49(9), 4137–4144 (2008).
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Fowler, B. J.

J. Ambati and B. J. Fowler, “Mechanisms of age-related macular degeneration,” Neuron75(1), 26–39 (2012).
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R. Simó, M. Villarroel, L. Corraliza, C. Hernández, and M. Garcia-Ramírez, “The retinal pigment epithelium: something more than a constituent of the blood-retinal barrier--implications for the pathogenesis of diabetic retinopathy,” J. Biomed. Biotechnol.2010, 190724 (2010).
[CrossRef] [PubMed]

Garsd, A.

C. K. Dorey, G. Wu, D. Ebenstein, A. Garsd, and J. J. Weiter, “Cell loss in the aging retina. Relationship to lipofuscin accumulation and macular degeneration,” Invest. Ophthalmol. Vis. Sci.30(8), 1691–1699 (1989).
[PubMed]

Gee, B. P.

Glazer, L. C.

L. C. Glazer and T. P. Dryja, "Understanding the etiology of Stargardt's disease," Ophthalmol. Clin. North. Am.15, 93-100 (2002).

Gray, D. C.

J. I. W. Morgan, J. J. Hunter, B. Masella, R. Wolfe, D. C. Gray, W. H. Merigan, F. C. Delori, and D. R. Williams, “Light-induced retinal changes observed with high-resolution autofluorescence imaging of the retinal pigment epithelium,” Invest. Ophthalmol. Vis. Sci.49(8), 3715–3729 (2008).
[CrossRef] [PubMed]

D. C. Gray, W. Merigan, J. I. Wolfing, B. P. Gee, J. Porter, A. Dubra, T. H. Twietmeyer, K. Ahamd, R. Tumbar, F. Reinholz, and D. R. Williams, “In vivo fluorescence imaging of primate retinal ganglion cells and retinal pigment epithelial cells,” Opt. Express14(16), 7144–7158 (2006).
[CrossRef] [PubMed]

Greenberg, J. P.

V. C. Greenstein, T. Duncker, K. Holopigian, R. E. Carr, J. P. Greenberg, S. H. Tsang, and D. C. Hood, “Structural and functional changes associated with normal and abnormal fundus autofluorescence in patients with retinitis pigmentosa,” Retina32(2), 349–357 (2012).
[CrossRef] [PubMed]

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V. C. Greenstein, T. Duncker, K. Holopigian, R. E. Carr, J. P. Greenberg, S. H. Tsang, and D. C. Hood, “Structural and functional changes associated with normal and abnormal fundus autofluorescence in patients with retinitis pigmentosa,” Retina32(2), 349–357 (2012).
[CrossRef] [PubMed]

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F. Marlhens, C. Bareil, J. M. Griffoin, E. Zrenner, P. Amalric, C. Eliaou, S. Y. Liu, E. Harris, T. M. Redmond, B. Arnaud, M. Claustres, and C. P. Hamel, “Mutations in RPE65 cause Leber’s congenital amaurosis,” Nat. Genet.17(2), 139–141 (1997).
[CrossRef] [PubMed]

Gu, D.

A. V. Cideciyan, S. G. Jacobson, T. S. Aleman, D. Gu, S. E. Pearce-Kelling, A. Sumaroka, G. M. Acland, and G. D. Aguirre, “In vivo dynamics of retinal injury and repair in the rhodopsin mutant dog model of human retinitis pigmentosa,” Proc. Natl. Acad. Sci. U.S.A.102(14), 5233–5238 (2005).
[CrossRef] [PubMed]

Gunther, K. L.

Hamel, C. P.

F. Marlhens, C. Bareil, J. M. Griffoin, E. Zrenner, P. Amalric, C. Eliaou, S. Y. Liu, E. Harris, T. M. Redmond, B. Arnaud, M. Claustres, and C. P. Hamel, “Mutations in RPE65 cause Leber’s congenital amaurosis,” Nat. Genet.17(2), 139–141 (1997).
[CrossRef] [PubMed]

Harris, E.

F. Marlhens, C. Bareil, J. M. Griffoin, E. Zrenner, P. Amalric, C. Eliaou, S. Y. Liu, E. Harris, T. M. Redmond, B. Arnaud, M. Claustres, and C. P. Hamel, “Mutations in RPE65 cause Leber’s congenital amaurosis,” Nat. Genet.17(2), 139–141 (1997).
[CrossRef] [PubMed]

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M. Fleckenstein, P. Charbel Issa, H. M. Helb, S. Schmitz-Valckenberg, R. P. Finger, H. P. Scholl, K. U. Loeffler, and F. G. Holz, “High-resolution spectral domain-OCT imaging in geographic atrophy associated with age-related macular degeneration,” Invest. Ophthalmol. Vis. Sci.49(9), 4137–4144 (2008).
[CrossRef] [PubMed]

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R. Simó, M. Villarroel, L. Corraliza, C. Hernández, and M. Garcia-Ramírez, “The retinal pigment epithelium: something more than a constituent of the blood-retinal barrier--implications for the pathogenesis of diabetic retinopathy,” J. Biomed. Biotechnol.2010, 190724 (2010).
[CrossRef] [PubMed]

Hogan, M. J.

M. Spitznas and M. J. Hogan, “Outer segments of photoreceptors and the retinal pigment epithelium. Interrelationship in the human eye,” Arch. Ophthalmol.84(6), 810–819 (1970).
[CrossRef] [PubMed]

Holopigian, K.

V. C. Greenstein, T. Duncker, K. Holopigian, R. E. Carr, J. P. Greenberg, S. H. Tsang, and D. C. Hood, “Structural and functional changes associated with normal and abnormal fundus autofluorescence in patients with retinitis pigmentosa,” Retina32(2), 349–357 (2012).
[CrossRef] [PubMed]

Holz, F. G.

M. Fleckenstein, P. Charbel Issa, H. M. Helb, S. Schmitz-Valckenberg, R. P. Finger, H. P. Scholl, K. U. Loeffler, and F. G. Holz, “High-resolution spectral domain-OCT imaging in geographic atrophy associated with age-related macular degeneration,” Invest. Ophthalmol. Vis. Sci.49(9), 4137–4144 (2008).
[CrossRef] [PubMed]

S. Schmitz-Valckenberg, F. G. Holz, A. C. Bird, and R. F. Spaide, “Fundus autofluorescence imaging: review and perspectives,” Retina28(3), 385–409 (2008).
[CrossRef] [PubMed]

Hood, D. C.

V. C. Greenstein, T. Duncker, K. Holopigian, R. E. Carr, J. P. Greenberg, S. H. Tsang, and D. C. Hood, “Structural and functional changes associated with normal and abnormal fundus autofluorescence in patients with retinitis pigmentosa,” Retina32(2), 349–357 (2012).
[CrossRef] [PubMed]

Hughes, G. W.

Hunter, J. J.

J. I. W. Morgan, J. J. Hunter, B. Masella, R. Wolfe, D. C. Gray, W. H. Merigan, F. C. Delori, and D. R. Williams, “Light-induced retinal changes observed with high-resolution autofluorescence imaging of the retinal pigment epithelium,” Invest. Ophthalmol. Vis. Sci.49(8), 3715–3729 (2008).
[CrossRef] [PubMed]

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A. Yoshida, S. Ishiko, J. Akiba, N. Kitaya, and T. Nagaoka, “Radiating retinal folds detected by scanning laser ophthalmoscopy using a diode laser in a dark-field mode in idiopathic macular holes,” Graefes Arch. Clin. Exp. Ophthalmol.236(6), 445–450 (1998).
[CrossRef] [PubMed]

Jacobson, S. G.

A. V. Cideciyan, S. G. Jacobson, T. S. Aleman, D. Gu, S. E. Pearce-Kelling, A. Sumaroka, G. M. Acland, and G. D. Aguirre, “In vivo dynamics of retinal injury and repair in the rhodopsin mutant dog model of human retinitis pigmentosa,” Proc. Natl. Acad. Sci. U.S.A.102(14), 5233–5238 (2005).
[CrossRef] [PubMed]

Kellner, S.

U. Kellner, S. Kellner, and S. Weinitz, “Fundus autofluorescence (488 NM) and near-infrared autofluorescence (787 NM) visualize different retinal pigment epithelium alterations in patients with age-related macular degeneration,” Retina30(1), 6–15 (2010).
[CrossRef] [PubMed]

U. Kellner, S. Kellner, B. H. Weber, B. Fiebig, S. Weinitz, and K. Ruether, “Lipofuscin- and melanin-related fundus autofluorescence visualize different retinal pigment epithelial alterations in patients with retinitis pigmentosa,” Eye (Lond.)23(6), 1349–1359 (2009).
[CrossRef] [PubMed]

Kellner, U.

U. Kellner, S. Kellner, and S. Weinitz, “Fundus autofluorescence (488 NM) and near-infrared autofluorescence (787 NM) visualize different retinal pigment epithelium alterations in patients with age-related macular degeneration,” Retina30(1), 6–15 (2010).
[CrossRef] [PubMed]

U. Kellner, S. Kellner, B. H. Weber, B. Fiebig, S. Weinitz, and K. Ruether, “Lipofuscin- and melanin-related fundus autofluorescence visualize different retinal pigment epithelial alterations in patients with retinitis pigmentosa,” Eye (Lond.)23(6), 1349–1359 (2009).
[CrossRef] [PubMed]

Kitaya, N.

A. Yoshida, S. Ishiko, J. Akiba, N. Kitaya, and T. Nagaoka, “Radiating retinal folds detected by scanning laser ophthalmoscopy using a diode laser in a dark-field mode in idiopathic macular holes,” Graefes Arch. Clin. Exp. Ophthalmol.236(6), 445–450 (1998).
[CrossRef] [PubMed]

Langlo, C. S.

R. F. Cooper, C. S. Langlo, A. Dubra, and J. Carroll, “Automatic detection of modal spacing (Yellott’s ring) in adaptive optics scanning light ophthalmoscope images,” Ophthalmic Physiol. Opt.33(4), 540–549 (2013).
[CrossRef] [PubMed]

Lee, B. R.

Y. U. Shin and B. R. Lee, “Retro-mode Imaging for retinal pigment epithelium alterations in central serous chorioretinopathy,” Am. J. Ophthalmol154, 155–163 (2012).

Li, K. Y.

Liu, S. Y.

F. Marlhens, C. Bareil, J. M. Griffoin, E. Zrenner, P. Amalric, C. Eliaou, S. Y. Liu, E. Harris, T. M. Redmond, B. Arnaud, M. Claustres, and C. P. Hamel, “Mutations in RPE65 cause Leber’s congenital amaurosis,” Nat. Genet.17(2), 139–141 (1997).
[CrossRef] [PubMed]

Loeffler, K. U.

M. Fleckenstein, P. Charbel Issa, H. M. Helb, S. Schmitz-Valckenberg, R. P. Finger, H. P. Scholl, K. U. Loeffler, and F. G. Holz, “High-resolution spectral domain-OCT imaging in geographic atrophy associated with age-related macular degeneration,” Invest. Ophthalmol. Vis. Sci.49(9), 4137–4144 (2008).
[CrossRef] [PubMed]

Marlhens, F.

F. Marlhens, C. Bareil, J. M. Griffoin, E. Zrenner, P. Amalric, C. Eliaou, S. Y. Liu, E. Harris, T. M. Redmond, B. Arnaud, M. Claustres, and C. P. Hamel, “Mutations in RPE65 cause Leber’s congenital amaurosis,” Nat. Genet.17(2), 139–141 (1997).
[CrossRef] [PubMed]

Masella, B.

J. I. W. Morgan, J. J. Hunter, B. Masella, R. Wolfe, D. C. Gray, W. H. Merigan, F. C. Delori, and D. R. Williams, “Light-induced retinal changes observed with high-resolution autofluorescence imaging of the retinal pigment epithelium,” Invest. Ophthalmol. Vis. Sci.49(8), 3715–3729 (2008).
[CrossRef] [PubMed]

Merigan, W.

Merigan, W. H.

J. I. W. Morgan, J. J. Hunter, B. Masella, R. Wolfe, D. C. Gray, W. H. Merigan, F. C. Delori, and D. R. Williams, “Light-induced retinal changes observed with high-resolution autofluorescence imaging of the retinal pigment epithelium,” Invest. Ophthalmol. Vis. Sci.49(8), 3715–3729 (2008).
[CrossRef] [PubMed]

J. I. Morgan, A. Dubra, R. Wolfe, W. H. Merigan, and D. R. Williams, “In vivo autofluorescence imaging of the human and macaque retinal pigment epithelial cell mosaic,” Invest. Ophthalmol. Vis. Sci.50(3), 1350–1359 (2008).
[CrossRef] [PubMed]

Morgan, J. I.

J. I. Morgan, A. Dubra, R. Wolfe, W. H. Merigan, and D. R. Williams, “In vivo autofluorescence imaging of the human and macaque retinal pigment epithelial cell mosaic,” Invest. Ophthalmol. Vis. Sci.50(3), 1350–1359 (2008).
[CrossRef] [PubMed]

Morgan, J. I. W.

J. I. W. Morgan, J. J. Hunter, B. Masella, R. Wolfe, D. C. Gray, W. H. Merigan, F. C. Delori, and D. R. Williams, “Light-induced retinal changes observed with high-resolution autofluorescence imaging of the retinal pigment epithelium,” Invest. Ophthalmol. Vis. Sci.49(8), 3715–3729 (2008).
[CrossRef] [PubMed]

Nagaoka, T.

A. Yoshida, S. Ishiko, J. Akiba, N. Kitaya, and T. Nagaoka, “Radiating retinal folds detected by scanning laser ophthalmoscopy using a diode laser in a dark-field mode in idiopathic macular holes,” Graefes Arch. Clin. Exp. Ophthalmol.236(6), 445–450 (1998).
[CrossRef] [PubMed]

Neitz, M.

Norris, J. L.

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]

Pearce-Kelling, S. E.

A. V. Cideciyan, S. G. Jacobson, T. S. Aleman, D. Gu, S. E. Pearce-Kelling, A. Sumaroka, G. M. Acland, and G. D. Aguirre, “In vivo dynamics of retinal injury and repair in the rhodopsin mutant dog model of human retinitis pigmentosa,” Proc. Natl. Acad. Sci. U.S.A.102(14), 5233–5238 (2005).
[CrossRef] [PubMed]

Porter, J.

Redmond, T. M.

F. Marlhens, C. Bareil, J. M. Griffoin, E. Zrenner, P. Amalric, C. Eliaou, S. Y. Liu, E. Harris, T. M. Redmond, B. Arnaud, M. Claustres, and C. P. Hamel, “Mutations in RPE65 cause Leber’s congenital amaurosis,” Nat. Genet.17(2), 139–141 (1997).
[CrossRef] [PubMed]

Reinholz, F.

Rha, J.

H. Tanna, A. M. Dubis, N. Ayub, D. M. Tait, J. Rha, K. E. Stepien, and J. Carroll, “Retinal imaging using commercial broadband optical coherence tomography,” Br. J. Ophthalmol.94(3), 372–376 (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).
[CrossRef] [PubMed]

A. Roorda, Y. Zhang, and J. L. Duncan, “High-resolution in vivo imaging of the RPE mosaic in eyes with retinal disease,” Invest. Ophthalmol. Vis. Sci.48(5), 2297–2303 (2007).
[CrossRef] [PubMed]

Ruether, K.

U. Kellner, S. Kellner, B. H. Weber, B. Fiebig, S. Weinitz, and K. Ruether, “Lipofuscin- and melanin-related fundus autofluorescence visualize different retinal pigment epithelial alterations in patients with retinitis pigmentosa,” Eye (Lond.)23(6), 1349–1359 (2009).
[CrossRef] [PubMed]

Schmitz-Valckenberg, S.

M. Fleckenstein, P. Charbel Issa, H. M. Helb, S. Schmitz-Valckenberg, R. P. Finger, H. P. Scholl, K. U. Loeffler, and F. G. Holz, “High-resolution spectral domain-OCT imaging in geographic atrophy associated with age-related macular degeneration,” Invest. Ophthalmol. Vis. Sci.49(9), 4137–4144 (2008).
[CrossRef] [PubMed]

S. Schmitz-Valckenberg, F. G. Holz, A. C. Bird, and R. F. Spaide, “Fundus autofluorescence imaging: review and perspectives,” Retina28(3), 385–409 (2008).
[CrossRef] [PubMed]

Scholl, H. P.

M. Fleckenstein, P. Charbel Issa, H. M. Helb, S. Schmitz-Valckenberg, R. P. Finger, H. P. Scholl, K. U. Loeffler, and F. G. Holz, “High-resolution spectral domain-OCT imaging in geographic atrophy associated with age-related macular degeneration,” Invest. Ophthalmol. Vis. Sci.49(9), 4137–4144 (2008).
[CrossRef] [PubMed]

Shin, Y. U.

Y. U. Shin and B. R. Lee, “Retro-mode Imaging for retinal pigment epithelium alterations in central serous chorioretinopathy,” Am. J. Ophthalmol154, 155–163 (2012).

Simó, R.

R. Simó, M. Villarroel, L. Corraliza, C. Hernández, and M. Garcia-Ramírez, “The retinal pigment epithelium: something more than a constituent of the blood-retinal barrier--implications for the pathogenesis of diabetic retinopathy,” J. Biomed. Biotechnol.2010, 190724 (2010).
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Spaide, R. F.

R. F. Spaide and C. A. Curcio, “Anatomical correlates to the bands seen in the outer retina by optical coherence tomography: literature review and model,” Retina31(8), 1609–1619 (2011).
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S. Schmitz-Valckenberg, F. G. Holz, A. C. Bird, and R. F. Spaide, “Fundus autofluorescence imaging: review and perspectives,” Retina28(3), 385–409 (2008).
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M. Spitznas and M. J. Hogan, “Outer segments of photoreceptors and the retinal pigment epithelium. Interrelationship in the human eye,” Arch. Ophthalmol.84(6), 810–819 (1970).
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R. H. Steinberg, “Interactions between the retinal pigment epithelium and the neural retina,” Doc. Ophthalmol.60(4), 327–346 (1985).
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H. Tanna, A. M. Dubis, N. Ayub, D. M. Tait, J. Rha, K. E. Stepien, and J. Carroll, “Retinal imaging using commercial broadband optical coherence tomography,” Br. J. Ophthalmol.94(3), 372–376 (2010).
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W. Stiles and B. Crawford, “The luminous efficiency of rays entering the eye pupil at different points,” Proc. R. Soc. Lond. B Biol. Sci.112(778), 428–450 (1933).
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C. F. Blodi and E. M. Stone, “Best’s vitelliform dystrophy,” Ophthalmic Paediatr. Genet.11(1), 49–59 (1990).
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Sulai, Y.

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]

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

Sulai, Y. N.

Sumaroka, A.

A. V. Cideciyan, S. G. Jacobson, T. S. Aleman, D. Gu, S. E. Pearce-Kelling, A. Sumaroka, G. M. Acland, and G. D. Aguirre, “In vivo dynamics of retinal injury and repair in the rhodopsin mutant dog model of human retinitis pigmentosa,” Proc. Natl. Acad. Sci. U.S.A.102(14), 5233–5238 (2005).
[CrossRef] [PubMed]

Tait, D. M.

H. Tanna, A. M. Dubis, N. Ayub, D. M. Tait, J. Rha, K. E. Stepien, and J. Carroll, “Retinal imaging using commercial broadband optical coherence tomography,” Br. J. Ophthalmol.94(3), 372–376 (2010).
[CrossRef] [PubMed]

Tanna, H.

H. Tanna, A. M. Dubis, N. Ayub, D. M. Tait, J. Rha, K. E. Stepien, and J. Carroll, “Retinal imaging using commercial broadband optical coherence tomography,” Br. J. Ophthalmol.94(3), 372–376 (2010).
[CrossRef] [PubMed]

Tsang, S. H.

V. C. Greenstein, T. Duncker, K. Holopigian, R. E. Carr, J. P. Greenberg, S. H. Tsang, and D. C. Hood, “Structural and functional changes associated with normal and abnormal fundus autofluorescence in patients with retinitis pigmentosa,” Retina32(2), 349–357 (2012).
[CrossRef] [PubMed]

Tumbar, R.

Twietmeyer, T. H.

Vannasdale, D. A.

Villarroel, M.

R. Simó, M. Villarroel, L. Corraliza, C. Hernández, and M. Garcia-Ramírez, “The retinal pigment epithelium: something more than a constituent of the blood-retinal barrier--implications for the pathogenesis of diabetic retinopathy,” J. Biomed. Biotechnol.2010, 190724 (2010).
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H. Tanna, A. M. Dubis, N. Ayub, D. M. Tait, J. Rha, K. E. Stepien, and J. Carroll, “Retinal imaging using commercial broadband optical coherence tomography,” Br. J. Ophthalmol.94(3), 372–376 (2010).
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[CrossRef] [PubMed]

Graefes Arch. Clin. Exp. Ophthalmol.

A. Yoshida, S. Ishiko, J. Akiba, N. Kitaya, and T. Nagaoka, “Radiating retinal folds detected by scanning laser ophthalmoscopy using a diode laser in a dark-field mode in idiopathic macular holes,” Graefes Arch. Clin. Exp. Ophthalmol.236(6), 445–450 (1998).
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Invest. Ophthalmol. Vis. Sci.

M. Fleckenstein, P. Charbel Issa, H. M. Helb, S. Schmitz-Valckenberg, R. P. Finger, H. P. Scholl, K. U. Loeffler, and F. G. Holz, “High-resolution spectral domain-OCT imaging in geographic atrophy associated with age-related macular degeneration,” Invest. Ophthalmol. Vis. Sci.49(9), 4137–4144 (2008).
[CrossRef] [PubMed]

J. I. W. Morgan, J. J. Hunter, B. Masella, R. Wolfe, D. C. Gray, W. H. Merigan, F. C. Delori, and D. R. Williams, “Light-induced retinal changes observed with high-resolution autofluorescence imaging of the retinal pigment epithelium,” Invest. Ophthalmol. Vis. Sci.49(8), 3715–3729 (2008).
[CrossRef] [PubMed]

Invest. Ophthalmol. Vis. Sci.

C. K. Dorey, G. Wu, D. Ebenstein, A. Garsd, and J. J. Weiter, “Cell loss in the aging retina. Relationship to lipofuscin accumulation and macular degeneration,” Invest. Ophthalmol. Vis. Sci.30(8), 1691–1699 (1989).
[PubMed]

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[CrossRef] [PubMed]

Invest. Ophthalmol. Vis. Sci.

A. Roorda, Y. Zhang, and J. L. Duncan, “High-resolution in vivo imaging of the RPE mosaic in eyes with retinal disease,” Invest. Ophthalmol. Vis. Sci.48(5), 2297–2303 (2007).
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Figures (13)

Fig. 1
Fig. 1

AOSLO image plane apertures in front of the detector: a) traditional confocal pinhole, approximately one Airy disk diameter (ADD), and b) large pinhole with centered filament.

Fig. 2
Fig. 2

AOSLO confocal (left) and dark-field (right) retinal images in four different subjects, all collected at the foveal center (center of fixation). The confocal images show the cone photoreceptor mosaic, while the dark-field images show the characteristic hexagonal RPE cell mosaic. The scale bar is 100 μm across.

Fig. 3
Fig. 3

AOSLO confocal (left) and dark-field (right) retinal images in four different subjects, all collected at 10° temporal to fixation. The confocal images show the cone and rod photoreceptor mosaic, while the dark-field images show the hexagonal RPE cell mosaic with significant cross-talk from the photoreceptor mosaic. The scale bar is 100 μm across.

Fig. 4
Fig. 4

Comparison of SD-OCT data and an AOSLO dark-field image (subject AD_1025). The en face view shown in B was created by coarsely segmenting the SD-OCT signal from the choroid over the area highlighted in panel A over the depth range indicated by the blue band. Panel D, shows the same retinal area as B as seen using AOSLO dark-field imaging. Scale bars are: A) 500 μm; C) 500 μm horizontal and 100 μm vertical; B) & D) 100 μm.

Fig. 5
Fig. 5

Confocal (photoreceptor) and dark-field (RPE) images collected simultaneously (subject JC_0616) at approximately 0.8° from fixation. Panels A-B and C-F show cones recorded with 1 ADD pinhole and dark-field recorded with a 16 ADD pinhole and 1 ADD filament, respectively. Panels B and E show the cone and RPE cell centers marked with crosses and circles superimposed to the images in A and D, respectively. Panel C shows the dark-field image with cone centers and RPE centers superimposed, while panel F adds the cell borders, determined as Voronoi cells derived from the estimated cell centers. The scale bar is 10 μm across.

Fig. 6
Fig. 6

Dark-field AOSLO images of the RPE mosaic at the center of fixation in volunteer JC_0616 collected using a 1 ADD thick filament and different pinhole diameters: A) 16, B) 12, C) 8 and D) 4 ADDs. The scale bar is 100 μm across.

Fig. 7
Fig. 7

Dark-field AOSLO images of the RPE mosaic at the center of fixation of volunteer JC_0616 collected using a 16 ADD diameter pinhole and either 1 (A) or 3 ADD thick filament (B). The scale bar is 100 μm across.

Fig. 8
Fig. 8

Time-averaged retinal point-spread function (PSF) recorded from research volunteer JC_0616 (left), focused on the photoreceptor layer (logarithmic color scale). The central and right panels show the radial average and integral, respectively, compared to that of a single retinal layer theoretical PSF (red solid lines).

Fig. 9
Fig. 9

Dark-field AOSLO images of the RPE mosaic at the center of fixation of volunteer JC_0616, using a 16 ADD diameter pinhole, 1 ADD thick filament and 790 nm (A) and 680nm (B) light. The scale bar is 100 μm across.

Fig. 10
Fig. 10

Effect of pupil apodization on image quality and contrast at 10° temporal to fixation in volunteer JC_0616 using 790 nm illumination, 16 ADD pinhole, 1 ADD filament (A) and with a centered 3 mm diameter circular block in the imaging (B) or the illumination paths (C). The scale bar is 100 μm across.

Fig. 11
Fig. 11

Comparison of autofluorescence to dark-field RPE imaging in AD_1025 at 3° superior and 9° temporal from fixation. A) dark-field image, B) autofluorescence images collected using 565 nm excitation and 625±45 nm emission. The scale bar is 100 μm across.

Fig. 12
Fig. 12

RPE images collected in a patient DW_1188 with central serous retinopathy. The SD-OCT image in panel A shows the 187 µm thick fluid collection that separates the retina from the RPE (below). En face AOSLO images of the area between the white arrows in A show RPE morphology in confocal mode (B), as well as in dark-field mode (C) at this location approximately 6° superior to fixation. The scale bar is 100 μm across.

Fig. 13
Fig. 13

AOSLO dark-field view from the fovea of volunteer JC_0616, with ‘*’ denoting the point of maximum cone density. The scale bar is 100 μm across.

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