Abstract

This paper presents a successful combination of ultra-high speed (120,000 depth scans/s), ultra-high resolution optical coherence tomography with adaptive optics and an achromatizing lens for compensation of monochromatic and longitudinal chromatic ocular aberrations, respectively, allowing for non-invasive volumetric imaging in normal and pathologic human retinas at cellular resolution. The capability of this imaging system is demonstrated here through preliminary studies by probing cellular intraretinal structures that have not been accessible so far with in vivo, non-invasive, label-free imaging techniques, including pigment epithelial cells, micro-vasculature of the choriocapillaris, single nerve fibre bundles and collagenous plates of the lamina cribrosa in the optic nerve head. In addition, the volumetric extent of cone loss in two colour-blinds could be quantified for the first time. This novel technique provides opportunities to enhance the understanding of retinal pathogenesis and early diagnosis of retinal diseases.

© 2009 OSA

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2009 (4)

2008 (7)

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

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

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

W. Drexler and J. G. Fujimoto, “State-of-the-art retinal optical coherence tomography,” Prog. Retin. Eye Res. 27(1), 45–88 (2008).
[CrossRef]

E. J. Fernández, B. Hermann, B. Považay, A. Unterhuber, H. Sattmann, B. Hofer, P. K. Anelt, and W. Drexler, “Ultrahigh resolution optical coherence tomography and pancorrection for cellular imaging of the living human retina,” Opt. Express 16, 11,083–11,094 (2008).
[CrossRef]

J. I. W. 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]

V. J. Srinivasan, D. C. Adler, Y. Chen, I. Gorczynska, R. Huber, J. S. Duker, J. S. Schuman, and J. G. Fujimoto, “Ultrahigh-speed optical coherence tomography for three-dimensional and en face imaging of the retina and optic nerve head,” Invest. Ophthalmol. Vis. Sci. 49(11), 5103–5110 (2008).
[CrossRef] [PubMed]

2007 (8)

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]

J. Carroll, R. C. Baraas, J. I. W. Morgan, D. R. Williams, D. H. Foster, and M. Neitz, “Expression of C203R mutant cone pigment results in cone degeneration,” Invest. Ophthalmol. Vis. Sci. 48(Suppl.), 3814 (2007).

F. C. Delori, R. H. Webb, and D. H. Sliney, “Maximum permissible exposures for ocular safety (ANSI 2000), with emphasis on ophthalmic devices,” J. Opt. Soc. Am. A 24(5), 1250–1265 (2007).
[CrossRef]

D. C. Chen, S. M. Jones, D. A. Silva, and S. S. Olivier, “High-resolution adaptive optics scanning laser ophthalmoscope with dual deformable mirrors,” J. Opt. Soc. Am. A 24(5), 1305–1312 (2007).
[CrossRef]

C. E. Bigelow, N. V. Iftimia, R. D. Ferguson, T. E. Ustun, B. Bloom, and D. X. Hammer, “Compact multimodal adaptive-optics spectral-domain optical coherence tomography instrument for retinal imaging,” J. Opt. Soc. Am. A 24(5), 1327–1336 (2007).
[CrossRef]

R. J. Zawadzki, S. S. Choi, S. M. Jones, S. S. Oliver, and J. S. Werner, “Adaptive optics-optical coherence tomography: optimizing visualization of microscopic retinal structures in three dimensions,” J. Opt. Soc. Am. A 24(5), 1373–1383 (2007).
[CrossRef]

A. S. Vilupuru, N. V. Rangaswamy, L. J. Frishman, E. L. Smith, R. S. Harwerth, and A. Roorda, “Adaptive optics scanning laser ophthalmoscopy for in vivo imaging of lamina cribrosa,” J. Opt. Soc. Am. A 24(5), 1417–1425 (2007).
[CrossRef]

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. A 24(5), 1438–1447 (2007).
[CrossRef]

2006 (6)

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

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

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

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. Express 14(16), 7144–7158 (2006).
[CrossRef] [PubMed]

E. J. Fernández, L. Vabre, B. Hermann, A. Unterhuber, B. Považay, and W. Drexler, “Adaptive optics with a magnetic deformable mirror: applications in the human eye,” Opt. Express 14(20), 8900–8917 (2006).
[CrossRef] [PubMed]

A. Kotecha, S. Izadi, and G. Jeffery, “Age-related changes in the thickness of the human lamina cribrosa,” Br. J. Ophthalmol. 90(12), 1531–1534 (2006).
[CrossRef] [PubMed]

2005 (6)

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

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

E. J. Fernández, A. Unterhuber, P. M. Prieto, B. Hermann, W. Drexler, and P. Artal, “Ocular aberrations as a function of wavelength in the near infrared measured with a femtosecond laser,” Opt. Express 13(2), 400–409 (2005).
[CrossRef] [PubMed]

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

E. J. Fernández and W. Drexler, “Influence of ocular chromatic aberration and pupil size on transverse resolution in ophthalmic adaptive optics optical coherence tomography,” Opt. Express 13(20), 8184–8197 (2005).
[CrossRef] [PubMed]

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

2004 (6)

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(11), 2404–2422 (2004).
[CrossRef] [PubMed]

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

B. Hermann, E. J. Fernández, 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(18), 2142–2144 (2004).
[CrossRef] [PubMed]

W. Drexler, “Ultrahigh-resolution optical coherence tomography,” J. Biomed. Opt. 9(1), 47–74 (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(22), 8461–8466 (2004).
[CrossRef] [PubMed]

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(36), 13352–13356 (2004).
[CrossRef] [PubMed]

2003 (2)

2002 (5)

A. Roorda, F. Romero-Borja, W. Donnelly III, H. Queener, T. J. Hebert, and M. Campbell, “Adaptive optics scanning laser ophthalmoscopy,” Opt. Express 10(9), 405–412 (2002).
[PubMed]

L. N. Thibos, X. Hong, A. Bradley, and X. Cheng, “Statistical variation of aberration structure and image quality in a normal population of healthy eyes,” J. Opt. Soc. Am. A 19(12), 2329–2348 (2002).
[CrossRef]

Q. V. Hoang, R. A. Linsenmeier, C. K. Chung, and C. A. Curcio, “Photoreceptor inner segments in monkey and human retina: mitochondrial density, optics, and regional variation,” Vis. Neurosci. 19(4), 395–407 (2002).
[CrossRef]

J. F. Castejón-Mochón, N. López-Gil, A. Benito, and P. Artal, “Ocular wave-front aberration statistics in a normal young population,” Vision Res. 42(13), 1611–1617 (2002).
[CrossRef] [PubMed]

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

2001 (3)

1998 (2)

P. Thevenaz, U. E. Ruttimann, and M. Unser, “A pyramid approach to subpixel registration based on intensity,” IEEE Trans. Image Process. 7(1), 27–41 (1998).
[CrossRef]

P. K. Ahnelt, “The photoreceptor mosaic,” Eye 12(Pt 3b), 531–540 (1998).
[CrossRef] [PubMed]

1997 (2)

A. M. Harman, P. A. Fleming, R. V. Hoskins, and S. R. Moore, “Development and aging of cell topography in the human retinal pigment epithelium,” Invest. Ophthalmol. Vis. Sci. 38(10), 2016–2026 (1997).
[PubMed]

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

1994 (1)

D. S. McLeod and G. A. Lutty, “High-resolution histologic analysis of the human choroidal vasculature,” Invest. Ophthalmol. Vis. Sci. 35(11), 3799–3811 (1994).
[PubMed]

1993 (2)

A. F. Fercher, C. K. Hitzenberger, W. Drexler, G. Kamp, and H. Sattmann, “In vivo optical coherence tomography,” Am. J. Ophthalmol. 116(1), 113–114 (1993).
[PubMed]

E. A. Swanson, J. A. Izatt, M. R. Hee, D. Huang, C. P. Lin, J. S. Schuman, C. A. Puliafito, and J. G. Fujimoto, “In vivo retinal imaging by optical coherence tomography,” Opt. Lett. 18(21), 1864–1866 (1993).
[CrossRef] [PubMed]

1992 (2)

M. Shensa, “The discrete wavelet transform: wedding the a trous and Mallat algorithms,” IEEE Trans. Signal Process. 40(10), 2464–2482 (1992).
[CrossRef]

H. Gao and J. G. Hollyfield, “Aging of the human retina. Differential loss of neurons and retinal pigment epithelial cells,” Invest. Ophthalmol. Vis. Sci. 33(1), 1–17 (1992).
[PubMed]

1991 (1)

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, and C. A. Puliafito, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
[CrossRef] [PubMed]

1990 (1)

C. A. Curcio, K. R. Sloan, R. E. Kalina, and A. E. Hendrickson, “Human photoreceptor topography,” J. Comp. Neurol. 292(4), 497–523 (1990).
[CrossRef] [PubMed]

1987 (1)

1982 (1)

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

1980 (1)

H. A. Quigley, R. W. Flower, E. M. Addicks, and D. S. McLeod, “The mechanism of optic nerve damage in experimental acute intraocular pressure elevation,” Invest. Ophthalmol. Vis. Sci. 19(5), 505–517 (1980).
[PubMed]

1971 (1)

S. J. Fricker, “Dynamic measurements of horizontal eye motion. I. Acceleration and velocity matrices,” Invest. Ophthalmol. 10(9), 724–732 (1971).
[PubMed]

1947 (1)

Addicks, E. M.

H. A. Quigley, R. W. Flower, E. M. Addicks, and D. S. McLeod, “The mechanism of optic nerve damage in experimental acute intraocular pressure elevation,” Invest. Ophthalmol. Vis. Sci. 19(5), 505–517 (1980).
[PubMed]

Adler, D. C.

V. J. Srinivasan, D. C. Adler, Y. Chen, I. Gorczynska, R. Huber, J. S. Duker, J. S. Schuman, and J. G. Fujimoto, “Ultrahigh-speed optical coherence tomography for three-dimensional and en face imaging of the retina and optic nerve head,” Invest. Ophthalmol. Vis. Sci. 49(11), 5103–5110 (2008).
[CrossRef] [PubMed]

Ahamd, K.

Ahnelt, P.

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

Ahnelt, P. K.

Anelt, P. K.

E. J. Fernández, B. Hermann, B. Považay, A. Unterhuber, H. Sattmann, B. Hofer, P. K. Anelt, and W. Drexler, “Ultrahigh resolution optical coherence tomography and pancorrection for cellular imaging of the living human retina,” Opt. Express 16, 11,083–11,094 (2008).
[CrossRef]

Anger, E. M.

Artal, P.

Bajraszewski, T.

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

Baraas, R. C.

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. A 24(5), 1438–1447 (2007).
[CrossRef]

J. Carroll, R. C. Baraas, J. I. W. Morgan, D. R. Williams, D. H. Foster, and M. Neitz, “Expression of C203R mutant cone pigment results in cone degeneration,” Invest. Ophthalmol. Vis. Sci. 48(Suppl.), 3814 (2007).

Benito, A.

J. F. Castejón-Mochón, N. López-Gil, A. Benito, and P. Artal, “Ocular wave-front aberration statistics in a normal young population,” Vision Res. 42(13), 1611–1617 (2002).
[CrossRef] [PubMed]

Bigelow, C. E.

Bird, A. C.

Bloom, B.

Bouma, B. E.

Bower, B. A.

Bradley, A.

Bradu, A.

Brown, J. M.

Cable, A.

Campbell, M.

Carroll, J.

J. Carroll, R. C. Baraas, J. I. W. Morgan, D. R. Williams, D. H. Foster, and M. Neitz, “Expression of C203R mutant cone pigment results in cone degeneration,” Invest. Ophthalmol. Vis. Sci. 48(Suppl.), 3814 (2007).

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. A 24(5), 1438–1447 (2007).
[CrossRef]

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

Castejón-Mochón, J. F.

J. F. Castejón-Mochón, N. López-Gil, A. Benito, and P. Artal, “Ocular wave-front aberration statistics in a normal young population,” Vision Res. 42(13), 1611–1617 (2002).
[CrossRef] [PubMed]

Cense, B.

Chang, W.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, and C. A. Puliafito, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
[CrossRef] [PubMed]

Chen, D. C.

Chen, L.

Chen, T. C.

Chen, Y.

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

V. J. Srinivasan, D. C. Adler, Y. Chen, I. Gorczynska, R. Huber, J. S. Duker, J. S. Schuman, and J. G. Fujimoto, “Ultrahigh-speed optical coherence tomography for three-dimensional and en face imaging of the retina and optic nerve head,” Invest. Ophthalmol. Vis. Sci. 49(11), 5103–5110 (2008).
[CrossRef] [PubMed]

Cheng, X.

Choi, S.

Choi, S. S.

Chung, C. K.

Q. V. Hoang, R. A. Linsenmeier, C. K. Chung, and C. A. Curcio, “Photoreceptor inner segments in monkey and human retina: mitochondrial density, optics, and regional variation,” Vis. Neurosci. 19(4), 395–407 (2002).
[CrossRef]

Chung, M.

Coletta, N. J.

Cordeiro, M. F.

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(36), 13352–13356 (2004).
[CrossRef] [PubMed]

Cowey, A.

Cox, I. G.

Curcio, C. A.

Q. V. Hoang, R. A. Linsenmeier, C. K. Chung, and C. A. Curcio, “Photoreceptor inner segments in monkey and human retina: mitochondrial density, optics, and regional variation,” Vis. Neurosci. 19(4), 395–407 (2002).
[CrossRef]

C. A. Curcio, K. R. Sloan, R. E. Kalina, and A. E. Hendrickson, “Human photoreceptor topography,” J. Comp. Neurol. 292(4), 497–523 (1990).
[CrossRef] [PubMed]

Dainty, C.

de Boer, J. F.

Delori, F. C.

Diaz-Santana, L.

Donnelly III, W.

Drexler, W.

B. Považay, B. Hofer, C. Torti, B. Hermann, A. R. Tumlinson, M. Esmaeelpour, C. A. Egan, A. C. Bird, and W. Drexler, “Impact of enhanced resolution, speed and penetration on three-dimensional retinal optical coherence tomography,” Opt. Express 17(5), 4134–4150 (2009).
[CrossRef] [PubMed]

B. Hofer, B. Považay, B. Hermann, A. Unterhuber, G. Matz, and W. Drexler, “Dispersion encoded full range frequency domain optical coherence tomography,” Opt. Express 17(1), 7–24 (2009).
[CrossRef] [PubMed]

E. J. Fernández, B. Hermann, B. Považay, A. Unterhuber, H. Sattmann, B. Hofer, P. K. Anelt, and W. Drexler, “Ultrahigh resolution optical coherence tomography and pancorrection for cellular imaging of the living human retina,” Opt. Express 16, 11,083–11,094 (2008).
[CrossRef]

W. Drexler and J. G. Fujimoto, “State-of-the-art retinal optical coherence tomography,” Prog. Retin. Eye Res. 27(1), 45–88 (2008).
[CrossRef]

E. J. Fernández, L. Vabre, B. Hermann, A. Unterhuber, B. Považay, and W. Drexler, “Adaptive optics with a magnetic deformable mirror: applications in the human eye,” Opt. Express 14(20), 8900–8917 (2006).
[CrossRef] [PubMed]

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

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

E. J. Fernández and W. Drexler, “Influence of ocular chromatic aberration and pupil size on transverse resolution in ophthalmic adaptive optics optical coherence tomography,” Opt. Express 13(20), 8184–8197 (2005).
[CrossRef] [PubMed]

E. J. Fernández, A. Unterhuber, P. M. Prieto, B. Hermann, W. Drexler, and P. Artal, “Ocular aberrations as a function of wavelength in the near infrared measured with a femtosecond laser,” Opt. Express 13(2), 400–409 (2005).
[CrossRef] [PubMed]

W. Drexler, “Ultrahigh-resolution optical coherence tomography,” J. Biomed. Opt. 9(1), 47–74 (2004).
[CrossRef] [PubMed]

B. Hermann, E. J. Fernández, 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(18), 2142–2144 (2004).
[CrossRef] [PubMed]

A. Unterhuber, B. Považay, B. Hermann, H. Sattmann, W. Drexler, V. Yakovlev, G. Tempea, C. Schubert, E. M. Anger, P. K. Ahnelt, M. Stur, J. E. Morgan, A. Cowey, G. Jung, T. Le, and A. Stingl, “Compact, low-cost Ti:Al2O3 laser for in vivo ultrahigh-resolution optical coherence tomography,” Opt. Lett. 28(11), 905–907 (2003).
[CrossRef] [PubMed]

W. Drexler, U. Morgner, R. K. Ghanta, F. X. Kärtner, J. S. Schuman, and J. G. Fujimoto, “Ultrahigh resolution ophthalmic optical coherence tomography,” Nat. Med. 24(7), 502–507 (2001).
[CrossRef]

A. F. Fercher, C. K. Hitzenberger, W. Drexler, G. Kamp, and H. Sattmann, “In vivo optical coherence tomography,” Am. J. Ophthalmol. 116(1), 113–114 (1993).
[PubMed]

Dubra, A.

J. I. W. 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. Express 14(16), 7144–7158 (2006).
[CrossRef] [PubMed]

Duker, J. S.

V. J. Srinivasan, D. C. Adler, Y. Chen, I. Gorczynska, R. Huber, J. S. Duker, J. S. Schuman, and J. G. Fujimoto, “Ultrahigh-speed optical coherence tomography for three-dimensional and en face imaging of the retina and optic nerve head,” Invest. Ophthalmol. Vis. Sci. 49(11), 5103–5110 (2008).
[CrossRef] [PubMed]

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

M. Wojtkowski, 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(11), 2404–2422 (2004).
[CrossRef] [PubMed]

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).
[CrossRef] [PubMed]

Egan, C. A.

Esmaeelpour, M.

Evans, J. W.

Fercher, A. F.

B. Hermann, E. J. Fernández, 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(18), 2142–2144 (2004).
[CrossRef] [PubMed]

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

A. F. Fercher, C. K. Hitzenberger, W. Drexler, G. Kamp, and H. Sattmann, “In vivo optical coherence tomography,” Am. J. Ophthalmol. 116(1), 113–114 (1993).
[PubMed]

Ferguson, R. D.

Fernández, E. J.

E. J. Fernández, B. Hermann, B. Považay, A. Unterhuber, H. Sattmann, B. Hofer, P. K. Anelt, and W. Drexler, “Ultrahigh resolution optical coherence tomography and pancorrection for cellular imaging of the living human retina,” Opt. Express 16, 11,083–11,094 (2008).
[CrossRef]

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

E. J. Fernández, L. Vabre, B. Hermann, A. Unterhuber, B. Považay, and W. Drexler, “Adaptive optics with a magnetic deformable mirror: applications in the human eye,” Opt. Express 14(20), 8900–8917 (2006).
[CrossRef] [PubMed]

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

E. J. Fernández and W. Drexler, “Influence of ocular chromatic aberration and pupil size on transverse resolution in ophthalmic adaptive optics optical coherence tomography,” Opt. Express 13(20), 8184–8197 (2005).
[CrossRef] [PubMed]

E. J. Fernández, A. Unterhuber, P. M. Prieto, B. Hermann, W. Drexler, and P. Artal, “Ocular aberrations as a function of wavelength in the near infrared measured with a femtosecond laser,” Opt. Express 13(2), 400–409 (2005).
[CrossRef] [PubMed]

B. Hermann, E. J. Fernández, 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(18), 2142–2144 (2004).
[CrossRef] [PubMed]

Fitzke, F. 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(36), 13352–13356 (2004).
[CrossRef] [PubMed]

Fleming, P. A.

A. M. Harman, P. A. Fleming, R. V. Hoskins, and S. R. Moore, “Development and aging of cell topography in the human retinal pigment epithelium,” Invest. Ophthalmol. Vis. Sci. 38(10), 2016–2026 (1997).
[PubMed]

Flotte, T.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, and C. A. Puliafito, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
[CrossRef] [PubMed]

Flower, R. W.

H. A. Quigley, R. W. Flower, E. M. Addicks, and D. S. McLeod, “The mechanism of optic nerve damage in experimental acute intraocular pressure elevation,” Invest. Ophthalmol. Vis. Sci. 19(5), 505–517 (1980).
[PubMed]

Foster, D. H.

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. A 24(5), 1438–1447 (2007).
[CrossRef]

J. Carroll, R. C. Baraas, J. I. W. Morgan, D. R. Williams, D. H. Foster, and M. Neitz, “Expression of C203R mutant cone pigment results in cone degeneration,” Invest. Ophthalmol. Vis. Sci. 48(Suppl.), 3814 (2007).

Fricker, S. J.

S. J. Fricker, “Dynamic measurements of horizontal eye motion. I. Acceleration and velocity matrices,” Invest. Ophthalmol. 10(9), 724–732 (1971).
[PubMed]

Frishman, L. J.

Fujimoto, J. G.

V. J. Srinivasan, D. C. Adler, Y. Chen, I. Gorczynska, R. Huber, J. S. Duker, J. S. Schuman, and J. G. Fujimoto, “Ultrahigh-speed optical coherence tomography for three-dimensional and en face imaging of the retina and optic nerve head,” Invest. Ophthalmol. Vis. Sci. 49(11), 5103–5110 (2008).
[CrossRef] [PubMed]

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

W. Drexler and J. G. Fujimoto, “State-of-the-art retinal optical coherence tomography,” Prog. Retin. Eye Res. 27(1), 45–88 (2008).
[CrossRef]

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

M. Wojtkowski, 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(11), 2404–2422 (2004).
[CrossRef] [PubMed]

W. Drexler, U. Morgner, R. K. Ghanta, F. X. Kärtner, J. S. Schuman, and J. G. Fujimoto, “Ultrahigh resolution ophthalmic optical coherence tomography,” Nat. Med. 24(7), 502–507 (2001).
[CrossRef]

E. A. Swanson, J. A. Izatt, M. R. Hee, D. Huang, C. P. Lin, J. S. Schuman, C. A. Puliafito, and J. G. Fujimoto, “In vivo retinal imaging by optical coherence tomography,” Opt. Lett. 18(21), 1864–1866 (1993).
[CrossRef] [PubMed]

Fuller, A. R.

Gao, H.

H. Gao and J. G. Hollyfield, “Aging of the human retina. Differential loss of neurons and retinal pigment epithelial cells,” Invest. Ophthalmol. Vis. Sci. 33(1), 1–17 (1992).
[PubMed]

Gao, W.

Gasson, P.

Gee, B. P.

Ghanta, R. K.

W. Drexler, U. Morgner, R. K. Ghanta, F. X. Kärtner, J. S. Schuman, and J. G. Fujimoto, “Ultrahigh resolution ophthalmic optical coherence tomography,” Nat. Med. 24(7), 502–507 (2001).
[CrossRef]

Gorczynska, I.

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

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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(36), 13352–13356 (2004).
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Vision Res. (3)

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

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

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[CrossRef] [PubMed]

Other (5)

G. S. Hagerman, and L. V. Johnson, “The photoreceptor-retinal pigmented epithelium interface,” in Principles and Practice of Clinical Electrophysiology of Vision, J.R. Heckenlively and G.B. Arden eds. (Mosby Year Book, St. Louis, 1991).

“Safe Use of Lasers” by American National Standard Institute (New York, 2000).

O. Marchal, and J. Mutterer, A trous filter plug-in for ImageJ, IBMP-CNRS Strasbourg France, http://rsbweb.nih.gov/ij/plugins/download/A_trous_filter.java , 2005.

P. Thevenaz, StackReg plug-in for ImageJ, EPFL/STI/IOA/LIB, Bldg. BM-Ecublens 4.137, Station 17, CH-1015 Lausanne VD, Switzerland, http://bigwww.epfl.ch/thevenaz/stackreg , 2005.

The Find maxima feature is a built-in tool of ImageJ and can be found in the Binary category of options in the Process tab.

Supplementary Material (4)

» Media 1: MOV (3925 KB)     
» Media 2: MOV (4092 KB)     
» Media 3: MOV (4048 KB)     
» Media 4: MOV (4048 KB)     

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Figures (7)

Fig. 1
Fig. 1

Optical set-up. AL: achromatizing lens, BS: beam-splitter, DG: diffraction grating, DM: deformable mirror, L: lens, PM: plane mirror, PP: polarization control paddles, RR: retro-reflector, SM: spherical mirror, WFS: wavefront sensor.

Fig. 2
Fig. 2

Cellular phenotyping in a normal and red/green colour-blind subject at 2.9° and 5.8° temporal. a h : En face images at the I/OS and OS tips after averaging of 15–22 slices filtered with BPF2–500 (a–b, e–f) or BPF3–500 (c–d, g–h). Photoreceptor densities per mm2 are indicated at the top-right corner of each panel. i m : Comparison of photoreceptor distributions in a normal ( i j ) and colour-blind ( l m ) subject at 5.8° temporal. Tomograms obtained by averaging 5 cross-sections filtered with ATF are shown in i and m, while in j and l, portions of integrations obtained from 200 fast-scan-axis tomograms filtered with AFT are shown to emphasize transversal cell densities (stack of 424 x 240 μm2 cross-sectional images filtered with ATF from a normal and colour-blind subject at 5.8° temporal, presented in Media 1 and Media 2). Layer thicknesses for the IS, OS and RPE are depicted in k . n : 2D power spectrum of the cone mosaic shown in c. ELM: external limiting membrane, IS: inner segments, OS: outer segments, RPE: retinal pigment epithelium, CC: choriocapillaris, BM: Bruch’s membrane. Scale bars: 50 μm.

Fig. 3
Fig. 3

Visualization of foveal stratification centred at 1°. a : Depth-dependent colour-coded composition of a grayscale image of retinal nerve fibre bundles (integration of 22 en face sections filtered with BPF2–500) and a red pseudo-coloured image of blood vessels (integration of 60 en face sections and filtered with BPF2–500). The white cross denotes the foveal centre and black graduations denote intervals of 1°. b: Average of 30 slow-scan-axis tomograms filtered with AFT within the blue region in a, piercing through a microvessel. Locations of intersecting vessels are denoted by blue arrows. NFL: Nerve fibre layer; GCL: ganglion cell layer; IPL: inner plexiform layer; INL: inner nuclear layer; OPL: outer plexiform layer. c : Average of 3 slow-axis-scan tomograms filtered with ATF within the yellow region in a, possibly showing a microvessel extending from the GCL (top yellow arrow) to the IPL, where it appears to branch out near the IPL/INL boundary (bottom yellow arrow). d : Average of 30 fast-axis-scan tomograms filtered with ATF and without slow-axis scanning centred at ~1° temporal exposing a zone of dark circular shaped structures likely corresponding to ganglion cell bodies, highlighted in e (magnification of d) by red arrows. Scale bars: 100 μm for a, b, d; 20 μm for c, e.

Fig. 4
Fig. 4

(previous page): Visualization of foveal retinal pigment epithelium (RPE) cells and choriocapillaris. a : 3D rendered OCT volume of a 28 year old normal male caucasian retina at the fovea after filtering with ATF. b : Schematic of RPE cell. OS: outer segments, MV: microvilli, SO: inner portion of RPE soma, NU: nuclear (basal) portion of RPE soma, BM: Bruch’s membrane, CC: choriocapillaris. Also indicated are the levels corresponding to panels c–d, f–g and j–k. c : 2D power spectrum of the RPE cell mosaic obtained by averaging of 15 en face slices followed by filtering of the resulting power spectrum with BPF4–500. d : Sectioned image at the level of the RPE soma (average of 15 en face sections filtered with ATF). At this depth, signal-producing elements are mainly melanin granules inferior to the inner portion of the RPE cell, also magnified in e. f : Histological section from a normal human fovea (selected portion of Fig. 1(a) from Harman et al. [55]) for comparison. g : Basal RPE exposing structure of the RPE cell mosaic at the level of the cell nuclei (average of 14 en face sections the filtered with BPF4–500). h : Enlarged portion of g with yellow circles enclosing 7 hexagonally arranged clusters of RPE cells. i–j : Light micrographs of tangentially sectioned tissue showing an en face view of human RPE cells from an 18 and 42 year old caucasian male, respectively (Fig. 3(i)–(j) reproduced from Gao et al. [56]). k : Sectioned image at the level of the choriocapillaris (averaging of 5 en face sections filtered with ATF). The emerging, structure possibly corresponds to microvessels. l : Inverted and enlarged selected portion of k. m : Histology of a human choriocapillaris in alkaline phosphatase preparation (selected portion of Fig. 1(a) from McLeod et al. [57]). Scale bars: 100 μm for a, d, g, k; 20 μm for e–f, h–j, l–m, 10 μm for b. White cross-hairs in d, g and k denote the foveal centre.

Fig. 6
Fig. 6

Visualization of RPE cell structure with and without filtering for speckle noise reduction. a: A 100x 100 μm2 patch of RPE mosaic obtained by averaging 15 (unfiltered) en face slices. b: Power spectrum of a. c: Obtained by averaging power spectrums from each of 15 (unfiltered) en face slices. d: Result of filtering the power spectrum in c with BPF4-500. e: A 100 x 100 μm2 patch of RPE mosaic obtained by averaging 15 en face slices filtered with BPF4-500. f: Power spectrum of e. g: Obtained by averaging power spectrums from each of 15 en face slices filtered with BPF4-500. h: Result of filtering the power spectrum in g with BPF4-500. i: A 100x100 μm2 patch of RPE mosaic obtained by averaging 15 en face slices filtered with ATF. j: Power spectrum of i. k: Obtained by averaging power spectrums from each of 15 en face slices filtered with ATF. l: Result of filtering of the power spectrum in k with BPF4-500.

Fig. 5
Fig. 5

Pores and collagenous fibres of the lamina cribrosa (LC). a : 3D rendered volume of the LC (filtered with ATF). b d : Single en face sections (filtered with ATF) denoted by yellow rectangles in a (Media 3 presents a 418 x 101 μm2 stack). e : Lateral section of the LC (left) as seen by histology of a human LC (selected portion of Fig. 1 from Kotecha et al. [58]) for comparison with OCT (right), obtained after averaging 5 fast-scan-axis tomograms filtered with ATF (Media 4 presents a 418 x 1234 μm2 stack). Collagen fibre bundles oriented orthogonal to the probing beam appear bright.

Fig. 7
Fig. 7

Depth-dependent peak cross-correlation between the central most en face section piercing through the RPE cell nuclei and sections at other depths.

Tables (1)

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Table 1 Summary of pixel number (N) and raster scanning densities (η) along the x and y direction for the data presented in Section 3.

Equations (1)

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s=(23D)12.

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