Abstract

Wavefront sensor noise and fidelity place a fundamental limit on achievable image quality in current adaptive optics ophthalmoscopes. Additionally, the wavefront sensor ‘beacon’ can interfere with visual experiments. We demonstrate real-time (25 Hz), wavefront sensorless adaptive optics imaging in the living human eye with image quality rivaling that of wavefront sensor based control in the same system. A stochastic parallel gradient descent algorithm directly optimized the mean intensity in retinal image frames acquired with a confocal adaptive optics scanning laser ophthalmoscope (AOSLO). When imaging through natural, undilated pupils, both control methods resulted in comparable mean image intensities. However, when imaging through dilated pupils, image intensity was generally higher following wavefront sensor-based control. Despite the typically reduced intensity, image contrast was higher, on average, with sensorless control. Wavefront sensorless control is a viable option for imaging the living human eye and future refinements of this technique may result in even greater optical gains.

© 2011 OSA

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2011 (4)

J. J. Hunter, B. Masella, A. Dubra, R. Sharma, L. Yin, W. H. Merigan, G. Palczewska, K. Palczewski, and D. R. Williams, “Images of photoreceptors in living primate eyes using adaptive optics two-photon ophthalmoscopy,” Biomed. Opt. Express 2(1), 139–148 (2011).
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[CrossRef]

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

W. Zou, X. Qi, and S. A. Burns, “Woofer-tweeter adaptive optics scanning laser ophthalmoscopic imaging based on Lagrange-multiplier damped least-squares algorithm,” Biomed. Opt. Express 2(7), 1986–2004 (2011).
[CrossRef] [PubMed]

2010 (4)

C. Li, N. Sredar, K. M. Ivers, H. Queener, and J. Porter, “A correction algorithm to simultaneously control dual deformable mirrors in a woofer-tweeter adaptive optics system,” Opt. Express 18(16), 16671–16684 (2010).
[CrossRef] [PubMed]

S. Ooto, M. Hangai, A. Sakamoto, A. Tsujikawa, K. Yamashiro, Y. Ojima, Y. Yamada, H. Mukai, S. Oshima, T. Inoue, and N. Yoshimura, “High-resolution imaging of resolved central serous chorioretinopathy using adaptive optics scanning laser ophthalmoscopy,” Ophthalmology 117(9), 1800.e1–1809.e2 (2010).
[CrossRef] [PubMed]

E. A. Rossi and A. Roorda, “The relationship between visual resolution and cone spacing in the human fovea,” Nat. Neurosci. 13(2), 156–157 (2010).
[CrossRef] [PubMed]

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

2009 (2)

L. C. Sincich, Y. Zhang, P. Tiruveedhula, J. C. Horton, and A. Roorda, “Resolving single cone inputs to visual receptive fields,” Nat. Neurosci. 12(8), 967–969 (2009).
[CrossRef] [PubMed]

D. Débarre, E. J. Botcherby, T. Watanabe, S. Srinivas, M. J. Booth, and T. Wilson, “Image-based adaptive optics for two-photon microscopy,” Opt. Lett. 34(16), 2495–2497 (2009).
[CrossRef] [PubMed]

2007 (3)

N. Doble, D. T. Miller, G. Yoon, and D. R. Williams, “Requirements for discrete actuator and segmented wavefront correctors for aberration compensation in two large populations of human eyes,” Appl. Opt. 46(20), 4501–4514 (2007).
[CrossRef] [PubMed]

M. J. Booth, “Adaptive optics in microscopy,” Philos. Transact. A Math. Phys. Eng. Sci. 365(1861), 2829–2843 (2007).
[CrossRef] [PubMed]

D. P. Biss, R. H. Webb, Z. Yaopeng, T. G. Bifano, P. Zamiri, and C. P. Lin, “An adaptive optics biomicroscope for mouse retinal imaging,” Proc. SPIE 6467, 646703, 646708 (2007).
[CrossRef]

2006 (5)

2005 (3)

N. Doble, “High-resolution, in vivo retinal imaging using adaptive optics and its future role in ophthalmology,” Expert Rev. Med. Devices 2(2), 205–216 (2005).
[CrossRef] [PubMed]

H. Hofer, B. Singer, and D. R. Williams, “Different sensations from cones with the same photopigment,” J. Vis. 5(5), 444–454 (2005).
[CrossRef] [PubMed]

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]

2004 (2)

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]

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]

2003 (1)

2002 (2)

2001 (1)

1999 (1)

A. Roorda and D. R. Williams, “The arrangement of the three cone classes in the living human eye,” Nature 397(6719), 520–522 (1999).
[CrossRef] [PubMed]

1997 (1)

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]

Adler, J.

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.

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]

Aragón, J. L.

Artal, P.

Besecker, J. R.

Bifano, T. G.

D. P. Biss, R. H. Webb, Z. Yaopeng, T. G. Bifano, P. Zamiri, and C. P. Lin, “An adaptive optics biomicroscope for mouse retinal imaging,” Proc. SPIE 6467, 646703, 646708 (2007).
[CrossRef]

Biss, D. P.

D. P. Biss, R. H. Webb, Z. Yaopeng, T. G. Bifano, P. Zamiri, and C. P. Lin, “An adaptive optics biomicroscope for mouse retinal imaging,” Proc. SPIE 6467, 646703, 646708 (2007).
[CrossRef]

Booth, M. J.

Botcherby, E. J.

Burns, S. A.

Campbell, M.

Carroll, J.

W. Makous, J. Carroll, J. I. Wolfing, J. Lin, N. Christie, and D. R. Williams, “Retinal microscotomas revealed with adaptive-optics microflashes,” Invest. Ophthalmol. Vis. Sci. 47(9), 4160–4167 (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(6), 1014–1019 (2006).
[CrossRef] [PubMed]

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

Cense, B.

Christie, N.

W. Makous, J. Carroll, J. I. Wolfing, J. Lin, N. Christie, and D. R. Williams, “Retinal microscotomas revealed with adaptive-optics microflashes,” Invest. Ophthalmol. Vis. Sci. 47(9), 4160–4167 (2006).
[CrossRef] [PubMed]

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(6), 1014–1019 (2006).
[CrossRef] [PubMed]

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]

Débarre, D.

Derby, J. C.

Doble, N.

Donnelly Iii, W.

Drexler, W.

Dubra, A.

Duncan, J. L.

K. E. Talcott, K. Ratnam, S. M. Sunquist, A. S. Lucero, B. J. Lujan, W. Tao, T. C. Porco, A. Roorda, and J. L. Duncan, “Longitudinal study of cone photoreceptors during retinal degeneration and in response to ciliary neurotrophic growth factor,” Invest. Ophthalmol. Vis. Sci. 52(5), 2219–2226 (2011).
[CrossRef]

Fercher, A. F.

Fernández, E. J.

Fienup, J. R.

Fujikado, T.

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

Gao, W.

Gee, B. P.

Gray, D. C.

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]

Hangai, M.

S. Ooto, M. Hangai, A. Sakamoto, A. Tsujikawa, K. Yamashiro, Y. Ojima, Y. Yamada, H. Mukai, S. Oshima, T. Inoue, and N. Yoshimura, “High-resolution imaging of resolved central serous chorioretinopathy using adaptive optics scanning laser ophthalmoscopy,” Ophthalmology 117(9), 1800.e1–1809.e2 (2010).
[CrossRef] [PubMed]

Hebert, T.

Hermann, B.

Hofer, H.

H. Hofer, B. Singer, and D. R. Williams, “Different sensations from cones with the same photopigment,” J. Vis. 5(5), 444–454 (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(22), 8461–8466 (2004).
[CrossRef] [PubMed]

H. Hofer, P. Artal, B. Singer, J. L. Aragón, and D. R. Williams, “Dynamics of the eye’s wave aberration,” J. Opt. Soc. Am. A 18(3), 497–506 (2001).
[CrossRef] [PubMed]

Horton, J. C.

L. C. Sincich, Y. Zhang, P. Tiruveedhula, J. C. Horton, and A. Roorda, “Resolving single cone inputs to visual receptive fields,” Nat. Neurosci. 12(8), 967–969 (2009).
[CrossRef] [PubMed]

Hunter, J. J.

Inoue, T.

S. Ooto, M. Hangai, A. Sakamoto, A. Tsujikawa, K. Yamashiro, Y. Ojima, Y. Yamada, H. Mukai, S. Oshima, T. Inoue, and N. Yoshimura, “High-resolution imaging of resolved central serous chorioretinopathy using adaptive optics scanning laser ophthalmoscopy,” Ophthalmology 117(9), 1800.e1–1809.e2 (2010).
[CrossRef] [PubMed]

Ivers, K. M.

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]

Jones, S.

Jonnal, R. S.

Kitaguchi, Y.

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

Kocaoglu, O. P.

Kusaka, S.

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

Li, C.

Liang, J.

Lin, C. P.

D. P. Biss, R. H. Webb, Z. Yaopeng, T. G. Bifano, P. Zamiri, and C. P. Lin, “An adaptive optics biomicroscope for mouse retinal imaging,” Proc. SPIE 6467, 646703, 646708 (2007).
[CrossRef]

Lin, J.

W. Makous, J. Carroll, J. I. Wolfing, J. Lin, N. Christie, and D. R. Williams, “Retinal microscotomas revealed with adaptive-optics microflashes,” Invest. Ophthalmol. Vis. Sci. 47(9), 4160–4167 (2006).
[CrossRef] [PubMed]

Lipson, S. G.

Lucero, A. S.

K. E. Talcott, K. Ratnam, S. M. Sunquist, A. S. Lucero, B. J. Lujan, W. Tao, T. C. Porco, A. Roorda, and J. L. Duncan, “Longitudinal study of cone photoreceptors during retinal degeneration and in response to ciliary neurotrophic growth factor,” Invest. Ophthalmol. Vis. Sci. 52(5), 2219–2226 (2011).
[CrossRef]

Lujan, B. J.

K. E. Talcott, K. Ratnam, S. M. Sunquist, A. S. Lucero, B. J. Lujan, W. Tao, T. C. Porco, A. Roorda, and J. L. Duncan, “Longitudinal study of cone photoreceptors during retinal degeneration and in response to ciliary neurotrophic growth factor,” Invest. Ophthalmol. Vis. Sci. 52(5), 2219–2226 (2011).
[CrossRef]

Makous, W.

W. Makous, J. Carroll, J. I. Wolfing, J. Lin, N. Christie, and D. R. Williams, “Retinal microscotomas revealed with adaptive-optics microflashes,” Invest. Ophthalmol. Vis. Sci. 47(9), 4160–4167 (2006).
[CrossRef] [PubMed]

Masella, B.

Merigan, W.

Merigan, W. H.

Mihashi, T.

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

Miller, D. T.

Miller, J. J.

Mukai, H.

S. Ooto, M. Hangai, A. Sakamoto, A. Tsujikawa, K. Yamashiro, Y. Ojima, Y. Yamada, H. Mukai, S. Oshima, T. Inoue, and N. Yoshimura, “High-resolution imaging of resolved central serous chorioretinopathy using adaptive optics scanning laser ophthalmoscopy,” Ophthalmology 117(9), 1800.e1–1809.e2 (2010).
[CrossRef] [PubMed]

Neitz, J.

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

Neitz, M.

J. Carroll, 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]

Ojima, Y.

S. Ooto, M. Hangai, A. Sakamoto, A. Tsujikawa, K. Yamashiro, Y. Ojima, Y. Yamada, H. Mukai, S. Oshima, T. Inoue, and N. Yoshimura, “High-resolution imaging of resolved central serous chorioretinopathy using adaptive optics scanning laser ophthalmoscopy,” Ophthalmology 117(9), 1800.e1–1809.e2 (2010).
[CrossRef] [PubMed]

Olivier, S.

Ooto, S.

S. Ooto, M. Hangai, A. Sakamoto, A. Tsujikawa, K. Yamashiro, Y. Ojima, Y. Yamada, H. Mukai, S. Oshima, T. Inoue, and N. Yoshimura, “High-resolution imaging of resolved central serous chorioretinopathy using adaptive optics scanning laser ophthalmoscopy,” Ophthalmology 117(9), 1800.e1–1809.e2 (2010).
[CrossRef] [PubMed]

Oshima, S.

S. Ooto, M. Hangai, A. Sakamoto, A. Tsujikawa, K. Yamashiro, Y. Ojima, Y. Yamada, H. Mukai, S. Oshima, T. Inoue, and N. Yoshimura, “High-resolution imaging of resolved central serous chorioretinopathy using adaptive optics scanning laser ophthalmoscopy,” Ophthalmology 117(9), 1800.e1–1809.e2 (2010).
[CrossRef] [PubMed]

Palczewska, G.

Palczewski, K.

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]

Porco, T. C.

K. E. Talcott, K. Ratnam, S. M. Sunquist, A. S. Lucero, B. J. Lujan, W. Tao, T. C. Porco, A. Roorda, and J. L. Duncan, “Longitudinal study of cone photoreceptors during retinal degeneration and in response to ciliary neurotrophic growth factor,” Invest. Ophthalmol. Vis. Sci. 52(5), 2219–2226 (2011).
[CrossRef]

Porter, J.

Prieto, P. M.

Qi, X.

Queener, H.

Ratnam, K.

K. E. Talcott, K. Ratnam, S. M. Sunquist, A. S. Lucero, B. J. Lujan, W. Tao, T. C. Porco, A. Roorda, and J. L. Duncan, “Longitudinal study of cone photoreceptors during retinal degeneration and in response to ciliary neurotrophic growth factor,” Invest. Ophthalmol. Vis. Sci. 52(5), 2219–2226 (2011).
[CrossRef]

Reinholz, F.

Rha, J.

Ribak, E. N.

Romero-Borja, F.

Roorda, A.

K. E. Talcott, K. Ratnam, S. M. Sunquist, A. S. Lucero, B. J. Lujan, W. Tao, T. C. Porco, A. Roorda, and J. L. Duncan, “Longitudinal study of cone photoreceptors during retinal degeneration and in response to ciliary neurotrophic growth factor,” Invest. Ophthalmol. Vis. Sci. 52(5), 2219–2226 (2011).
[CrossRef]

E. A. Rossi and A. Roorda, “The relationship between visual resolution and cone spacing in the human fovea,” Nat. Neurosci. 13(2), 156–157 (2010).
[CrossRef] [PubMed]

L. C. Sincich, Y. Zhang, P. Tiruveedhula, J. C. Horton, and A. Roorda, “Resolving single cone inputs to visual receptive fields,” Nat. Neurosci. 12(8), 967–969 (2009).
[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(6), 1014–1019 (2006).
[CrossRef] [PubMed]

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

A. Roorda and D. R. Williams, “The arrangement of the three cone classes in the living human eye,” Nature 397(6719), 520–522 (1999).
[CrossRef] [PubMed]

Rossi, E. A.

E. A. Rossi and A. Roorda, “The relationship between visual resolution and cone spacing in the human fovea,” Nat. Neurosci. 13(2), 156–157 (2010).
[CrossRef] [PubMed]

Sakamoto, A.

S. Ooto, M. Hangai, A. Sakamoto, A. Tsujikawa, K. Yamashiro, Y. Ojima, Y. Yamada, H. Mukai, S. Oshima, T. Inoue, and N. Yoshimura, “High-resolution imaging of resolved central serous chorioretinopathy using adaptive optics scanning laser ophthalmoscopy,” Ophthalmology 117(9), 1800.e1–1809.e2 (2010).
[CrossRef] [PubMed]

Sattmann, H.

Sharma, R.

Sincich, L. C.

L. C. Sincich, Y. Zhang, P. Tiruveedhula, J. C. Horton, and A. Roorda, “Resolving single cone inputs to visual receptive fields,” Nat. Neurosci. 12(8), 967–969 (2009).
[CrossRef] [PubMed]

Singer, B.

H. Hofer, B. Singer, and D. R. Williams, “Different sensations from cones with the same photopigment,” J. Vis. 5(5), 444–454 (2005).
[CrossRef] [PubMed]

H. Hofer, P. Artal, B. Singer, J. L. Aragón, and D. R. Williams, “Dynamics of the eye’s wave aberration,” J. Opt. Soc. Am. A 18(3), 497–506 (2001).
[CrossRef] [PubMed]

Sredar, N.

Srinivas, S.

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]

Sunquist, S. M.

K. E. Talcott, K. Ratnam, S. M. Sunquist, A. S. Lucero, B. J. Lujan, W. Tao, T. C. Porco, A. Roorda, and J. L. Duncan, “Longitudinal study of cone photoreceptors during retinal degeneration and in response to ciliary neurotrophic growth factor,” Invest. Ophthalmol. Vis. Sci. 52(5), 2219–2226 (2011).
[CrossRef]

Talcott, K. E.

K. E. Talcott, K. Ratnam, S. M. Sunquist, A. S. Lucero, B. J. Lujan, W. Tao, T. C. Porco, A. Roorda, and J. L. Duncan, “Longitudinal study of cone photoreceptors during retinal degeneration and in response to ciliary neurotrophic growth factor,” Invest. Ophthalmol. Vis. Sci. 52(5), 2219–2226 (2011).
[CrossRef]

Tao, W.

K. E. Talcott, K. Ratnam, S. M. Sunquist, A. S. Lucero, B. J. Lujan, W. Tao, T. C. Porco, A. Roorda, and J. L. Duncan, “Longitudinal study of cone photoreceptors during retinal degeneration and in response to ciliary neurotrophic growth factor,” Invest. Ophthalmol. Vis. Sci. 52(5), 2219–2226 (2011).
[CrossRef]

Tiruveedhula, P.

L. C. Sincich, Y. Zhang, P. Tiruveedhula, J. C. Horton, and A. Roorda, “Resolving single cone inputs to visual receptive fields,” Nat. Neurosci. 12(8), 967–969 (2009).
[CrossRef] [PubMed]

Tsujikawa, A.

S. Ooto, M. Hangai, A. Sakamoto, A. Tsujikawa, K. Yamashiro, Y. Ojima, Y. Yamada, H. Mukai, S. Oshima, T. Inoue, and N. Yoshimura, “High-resolution imaging of resolved central serous chorioretinopathy using adaptive optics scanning laser ophthalmoscopy,” Ophthalmology 117(9), 1800.e1–1809.e2 (2010).
[CrossRef] [PubMed]

Tumbar, R.

Twietmeyer, T. H.

Unterhuber, A.

Vorontsov, M. A.

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Watanabe, T.

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D. P. Biss, R. H. Webb, Z. Yaopeng, T. G. Bifano, P. Zamiri, and C. P. Lin, “An adaptive optics biomicroscope for mouse retinal imaging,” Proc. SPIE 6467, 646703, 646708 (2007).
[CrossRef]

Werner, J. S.

Williams, D. R.

J. J. Hunter, B. Masella, A. Dubra, R. Sharma, L. Yin, W. H. Merigan, G. Palczewska, K. Palczewski, and D. R. Williams, “Images of photoreceptors in living primate eyes using adaptive optics two-photon ophthalmoscopy,” Biomed. Opt. Express 2(1), 139–148 (2011).
[CrossRef] [PubMed]

N. Doble, D. T. Miller, G. Yoon, and D. R. Williams, “Requirements for discrete actuator and segmented wavefront correctors for aberration compensation in two large populations of human eyes,” Appl. Opt. 46(20), 4501–4514 (2007).
[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(6), 1014–1019 (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]

W. Makous, J. Carroll, J. I. Wolfing, J. Lin, N. Christie, and D. R. Williams, “Retinal microscotomas revealed with adaptive-optics microflashes,” Invest. Ophthalmol. Vis. Sci. 47(9), 4160–4167 (2006).
[CrossRef] [PubMed]

H. Hofer, B. Singer, and D. R. Williams, “Different sensations from cones with the same photopigment,” J. Vis. 5(5), 444–454 (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(22), 8461–8466 (2004).
[CrossRef] [PubMed]

H. Hofer, P. Artal, B. Singer, J. L. Aragón, and D. R. Williams, “Dynamics of the eye’s wave aberration,” J. Opt. Soc. Am. A 18(3), 497–506 (2001).
[CrossRef] [PubMed]

A. Roorda and D. R. Williams, “The arrangement of the three cone classes in the living human eye,” Nature 397(6719), 520–522 (1999).
[CrossRef] [PubMed]

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

Wilson, T.

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(6), 1014–1019 (2006).
[CrossRef] [PubMed]

W. Makous, J. Carroll, J. I. Wolfing, J. Lin, N. Christie, and D. R. Williams, “Retinal microscotomas revealed with adaptive-optics microflashes,” Invest. Ophthalmol. Vis. Sci. 47(9), 4160–4167 (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]

Yamada, Y.

S. Ooto, M. Hangai, A. Sakamoto, A. Tsujikawa, K. Yamashiro, Y. Ojima, Y. Yamada, H. Mukai, S. Oshima, T. Inoue, and N. Yoshimura, “High-resolution imaging of resolved central serous chorioretinopathy using adaptive optics scanning laser ophthalmoscopy,” Ophthalmology 117(9), 1800.e1–1809.e2 (2010).
[CrossRef] [PubMed]

Yamaguchi, T.

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

Yamashiro, K.

S. Ooto, M. Hangai, A. Sakamoto, A. Tsujikawa, K. Yamashiro, Y. Ojima, Y. Yamada, H. Mukai, S. Oshima, T. Inoue, and N. Yoshimura, “High-resolution imaging of resolved central serous chorioretinopathy using adaptive optics scanning laser ophthalmoscopy,” Ophthalmology 117(9), 1800.e1–1809.e2 (2010).
[CrossRef] [PubMed]

Yaopeng, Z.

D. P. Biss, R. H. Webb, Z. Yaopeng, T. G. Bifano, P. Zamiri, and C. P. Lin, “An adaptive optics biomicroscope for mouse retinal imaging,” Proc. SPIE 6467, 646703, 646708 (2007).
[CrossRef]

Yin, L.

Yoon, G.

Yoshimura, N.

S. Ooto, M. Hangai, A. Sakamoto, A. Tsujikawa, K. Yamashiro, Y. Ojima, Y. Yamada, H. Mukai, S. Oshima, T. Inoue, and N. Yoshimura, “High-resolution imaging of resolved central serous chorioretinopathy using adaptive optics scanning laser ophthalmoscopy,” Ophthalmology 117(9), 1800.e1–1809.e2 (2010).
[CrossRef] [PubMed]

Zamiri, P.

D. P. Biss, R. H. Webb, Z. Yaopeng, T. G. Bifano, P. Zamiri, and C. P. Lin, “An adaptive optics biomicroscope for mouse retinal imaging,” Proc. SPIE 6467, 646703, 646708 (2007).
[CrossRef]

Zawadzki, R. J.

Zhang, Y.

Zommer, S.

Zou, W.

Appl. Opt. (1)

Biomed. Opt. Express (2)

Clin. Ophthalmol. (1)

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

Expert Rev. Med. Devices (1)

N. Doble, “High-resolution, in vivo retinal imaging using adaptive optics and its future role in ophthalmology,” Expert Rev. Med. Devices 2(2), 205–216 (2005).
[CrossRef] [PubMed]

Invest. Ophthalmol. Vis. Sci. (2)

W. Makous, J. Carroll, J. I. Wolfing, J. Lin, N. Christie, and D. R. Williams, “Retinal microscotomas revealed with adaptive-optics microflashes,” Invest. Ophthalmol. Vis. Sci. 47(9), 4160–4167 (2006).
[CrossRef] [PubMed]

K. E. Talcott, K. Ratnam, S. M. Sunquist, A. S. Lucero, B. J. Lujan, W. Tao, T. C. Porco, A. Roorda, and J. L. Duncan, “Longitudinal study of cone photoreceptors during retinal degeneration and in response to ciliary neurotrophic growth factor,” Invest. Ophthalmol. Vis. Sci. 52(5), 2219–2226 (2011).
[CrossRef]

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

J. Vis. (1)

H. Hofer, B. Singer, and D. R. Williams, “Different sensations from cones with the same photopigment,” J. Vis. 5(5), 444–454 (2005).
[CrossRef] [PubMed]

Nat. Neurosci. (2)

L. C. Sincich, Y. Zhang, P. Tiruveedhula, J. C. Horton, and A. Roorda, “Resolving single cone inputs to visual receptive fields,” Nat. Neurosci. 12(8), 967–969 (2009).
[CrossRef] [PubMed]

E. A. Rossi and A. Roorda, “The relationship between visual resolution and cone spacing in the human fovea,” Nat. Neurosci. 13(2), 156–157 (2010).
[CrossRef] [PubMed]

Nature (1)

A. Roorda and D. R. Williams, “The arrangement of the three cone classes in the living human eye,” Nature 397(6719), 520–522 (1999).
[CrossRef] [PubMed]

Ophthalmology (2)

J. I. Wolfing, M. Chung, J. Carroll, A. Roorda, and D. R. Williams, “High-resolution retinal imaging of cone-rod dystrophy,” Ophthalmology 113(6), 1014–1019 (2006).
[CrossRef] [PubMed]

S. Ooto, M. Hangai, A. Sakamoto, A. Tsujikawa, K. Yamashiro, Y. Ojima, Y. Yamada, H. Mukai, S. Oshima, T. Inoue, and N. Yoshimura, “High-resolution imaging of resolved central serous chorioretinopathy using adaptive optics scanning laser ophthalmoscopy,” Ophthalmology 117(9), 1800.e1–1809.e2 (2010).
[CrossRef] [PubMed]

Opt. Express (5)

Opt. Lett. (3)

Philos. Transact. A Math. Phys. Eng. Sci. (1)

M. J. Booth, “Adaptive optics in microscopy,” Philos. Transact. A Math. Phys. Eng. Sci. 365(1861), 2829–2843 (2007).
[CrossRef] [PubMed]

Proc. Natl. Acad. Sci. U.S.A. (2)

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]

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]

Proc. SPIE (1)

D. P. Biss, R. H. Webb, Z. Yaopeng, T. G. Bifano, P. Zamiri, and C. P. Lin, “An adaptive optics biomicroscope for mouse retinal imaging,” Proc. SPIE 6467, 646703, 646708 (2007).
[CrossRef]

Other (3)

J. Porter, H. Queener, J. Lin, K. Thorne, and A. Awwal, eds., Adaptive Optics for Vision Science: Principles, Practices, Design, and Applications Ch. 5 (John Wiley and Sons, Inc., New Jersey, 2006).

T. Wilson, “The role of the pinhole in confocal imaging systems,” in Handbook of Biological Confocal Microscopy. Pawley, J. B., ed. (Plenum Press, New York, 1995).

W. Jiang and H. Li, “Hartmann-Shack Wavefront Sensing and Control Algorithm,” in Adaptive Optics and Optical Structures. Proceedings of the SPIE, Schulte-in-den-Baeumen, J.J., Tyson, R. K., eds. (SPIE 1990) 1271: 82–93.

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Figures (7)

Fig. 1
Fig. 1

Schematic diagram of the AOSLO [25] that consists of a Shack-Hartmann wavefront sensor (SHWFS), a 52-actuator woofer mirror (Mirao 52-e, Imagine Eyes, Inc., France), and a 140-actuator tweeter mirror (Multi-DM MEMS mirror, Boston Micromachines Inc., Cambridge, MA), all in pupil conjugate planes. 840 nm light (superluminescent diode (SLD); Superlum, Ireland) enters the eye’s pupil through a maximum diameter of 8 mm and is scanned (vertical scanner, VS; horizontal scanner, HS) over a 1.5 X 1.5 deg patch of retina. The reflected light is descanned as it propagates back through the system and ~20% is diverted to the SHWFS while the remaining light is focused through a 75 micron confocal pinhole (1.4’, ~1.6 X the width of the Airy disk with an 8 mm pupil) to a photomultiplier tube (PMT) for retinal imaging. One PC performs wavefront sensing and mirror control (AO PC), a second PC acquires and records retinal image sequences (SLO PC). The PCs operate independently during wavefront sensor based control but must communicate during sensorless control (SAO). An open loop correction of lower order aberrations (primarily defocus) is placed on the woofer mirror with the SHWFS prior to initiating closed loop correction with both control methods.

Fig. 2
Fig. 2

Wavefront sensorless control algorithm details. a. Correction timeline for one iteration of sensorless control. AOSLO frames are acquired after adding, and then subtracting, a set of random perturbations (δu) to the voltage signals (u) of the 140 MEMS mirror actuators. The voltage signals (u) for the next iteration are updated by adding the perturbation (δu) in proportion to the difference in the mean intensity of the two image frames (ΔJ). Exposure of the AOSLO image frames occur over 35 msec centered within each 40 msec interval (leaving a buffer for repositioning and settling of the vertical scanner between frames) and all required calculations and mirror control occur within the first 3 msec at the start of each interval. b. Optimal sensorless adaptive optics performance requires careful pairing of the SPGD control parameters. Mean image intensity after convergence for a model eye is displayed as a function of the gain (Γ) and perturbation (σ) amplitudes. Warmer colors denote higher intensities and cooler colors denote lower intensities. Similar behavior was observed in human eyes for low perturbation amplitudes, with Γ = 40-60 and σ = 0.02-0.03 generally providing the best correction with reasonable convergence times.

Fig. 3
Fig. 3

Sensorless adaptive optics control performance and non-common path error correction for wavefront sensor based adaptive optics in a model eye. Image intensities were 50% higher with sensorless control (SAO) than with traditional wavefront sensor based control (WFS AO pre-calibration). After using sensorless adaptive correction to calibrate for non-common path errors between the PMT and SHWFS (total rms wavefront error ~0.05 microns over the system pupil), the performance of wavefront sensor based control (WFS AO post-calibration) improved to the level of sensorless control. Error bars are ±1 standard deviation of the mean image frame intensity after convergence. Note that absolute intensity cannot be compared with that in Fig. 2b. due to different adjustments of the PMT gain between the two data sets.

Fig. 4
Fig. 4

Comparison of sensorless and wavefront sensor based control for AOSLO imaging though dilated (8 mm) pupils in 3 representative subjects. Images after sensorless adaptive optics (SAO, 1st column) and wavefront sensor based adaptive optics (WFS AO, 2nd column) were similar in all subjects. Images were acquired at ~1 deg eccentricity and are shown at the same scale. Scale bar is 10’. The center of the fovea is approximately located in the bottom left corner. Despite typically lower image intensities and somewhat slower convergence (3rd column), normalized image power spectra after sensorless control (red) were equal to or greater than those obtained with wavefront sensor based control (blue) (4th column). (The sharp dips in the mean intensity traces are due to blinks or partial blinks. The gradual drop in intensity after recovering from blinks with WFS AO, such as in S.74, likely reflects instability or break-up of tear film.) Note that the PMT gain was adjusted separately for each subject and pupil size, precluding direct comparison of absolute intensity values across subjects or between undilated and dilated pupils. Gain and perturbation amplitudes (Γ, σ) were as follows: S.30, (55, 0.02); S.31, (40, 0.03); S.74, (60, 0.02).

Fig. 5
Fig. 5

Comparison of sensorless and wavefront sensor based control for AOSLO imaging through natural, undilated pupils (S.30, 6 mm; S.31, 4 mm; S.74, 6 mm) in the same 3 representative subjects. Images after sensorless adaptive optics (SAO, 1st column) and wavefront sensor based adaptive optics (WFS AO, 2nd column) were subjectively similar for all subjects. Images were acquired at ~1 deg eccentricity and are shown at the same scale. Scale bar is 10’. The center of the fovea is approximately located in the bottom left corner. Both image intensity (3rd column), and relative spectral power density (4th column) after sensorless control (red) compare favorably with wavefront sensor based control (blue). The irregularity of the mean intensity traces with wavefront sensor based control likely reflects 1. difficulties in obtaining an accurate wavefront sensor based control signal with smaller, fluctuating, pupils, and 2. tear film instabilities or break-up. (The sharp dips in the mean intensity traces are due to blinks or partial blinks.) Note that the PMT gain was adjusted separately for each subject and pupil size, precluding direct comparison of absolute intensity values across subjects or between undilated and dilated pupils. Gain and perturbation amplitudes (Γ, σ) for each subject were as follows: S.30, (60, 0.02); S.31, (50, 0.02); S.74, (60, 0.02).

Fig. 6
Fig. 6

Sensorless adaptive optics allowed clear images of individual photoreceptors to be acquired in one subject (S.62) when the pupil was sufficiently small (3 mm) as to prevent wavefront sensor based correction. Location and image details are the same as for Figs. 4 & 5. Scale bar is 10’.

Fig. 7
Fig. 7

Ratio of the image contrast for averaged retinal images acquired with the sensorless control method to those acquired with traditional wavefront sensor based control in 5 subjects when imaging through a. natural and b. dilated pupils. Dilated pupil size was 8 mm, undilated pupil size was approximately: S.30, 6 mm; S.31, 4 mm; S.49, 6 mm; S.62, 4 mm; S.74, 6 mm. Contrast ratios were calculated by taking the square root of the ratio of the normalized image power spectra. With natural pupils the contrast ratio averaged across subjects (black line) is not significantly different from 1, indicating that sensorless control yielded images of comparable contrast to those obtained with wavefront sensor based control. However when imaging through dilated pupils the contrast ratio averaged across subjects was greater than 1 at most spatial frequencies, indicating higher contrast with sensorless control. The average contrast improvement with sensorless control approached 25% at the highest spatial frequencies.

Equations (1)

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u i k + 1 = u i k + Γ ( Δ J k ) ( δ u i k )

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