Abstract

Optical coherence tomography (OCT) and scanning laser ophthalmoscopy (SLO) are complementary imaging modalities, the combination of which can provide clinicians with a wealth of information to detect retinal diseases, monitor disease progression, or assess new therapies. Adaptive optics (AO) is a tool that enables correction of wavefront distortions from ocular aberrations. We have developed a multimodal adaptive optics system (MAOS) for high-resolution multifunctional use in a variety of research and clinical applications. The system integrates both OCT and SLO imaging channels into an AO beam path. The optics and hardware were designed with specific features for simultaneous SLO/OCT output, for high-fidelity AO correction, for use in humans, primates, and small animals, and for efficient location and orientation of retinal regions of interest. The MAOS system was tested on human subjects and rodents. The design, performance characterization, and initial representative results from the human and animal studies are presented and discussed.

© 2012 Optical Society of America

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2012

T. Y. P. Chui, Z. Zhong, H. Song, and S. A. Burns, “Foveal avascular zone and its relationship to foveal pit shape,” Optom. Vis. Sci. 89, 602–610 (2012).
[CrossRef]

C. Alt and C. P. Lin, “In vivo quantification of microglia dynamics with a scanning laser ophthalmoscope in a mouse model of focal laser injury,” Proc. SPIE 8209, 820907 (2012).
[CrossRef]

Y. Geng, A. Dubra, L. Yin, W. H. Merigan, R. Sharma, R. T. Libby, and D. R. Williams, “Adaptive optics retinal imaging in the living mouse eye,” Biomed. Opt. Express 3, 715–734 (2012).
[CrossRef]

M. F. Kraus, B. Potsaid, M. A. Mayer, R. Bock, B. Baumann, J. J. Liu, J. Hornegger, and J. G. Fujimoto, “Motion correction in optical coherence tomography volumes on a per A-scan basis using orthogonal scan patterns,” Biomed. Opt. Express 3, 1182–1199 (2012).
[CrossRef]

2011

D. X. Hammer, R. D. Ferguson, M. Mujat, D. P. Biss, N. V. Iftimia, A. H. Patel, E. Plumb, M. Campbell, J. L Norris, A. Dubra, T. Y. P. Chui, J. D. Akula, and A. B. Fulton, “Advanced capabilities of the multimodal adaptive optics imager,” Proc. SPIE 7885, 78850A (2011).
[CrossRef]

J. Won, L. Y. Shi, W. Hicks, J. Wang, R. Hurd, J. K. Naggert, B. Chang, and P. M. Nishina, “Mouse model resources for vision research,” J. Ophthalmol. 2011, 391384 (2011).
[CrossRef]

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[CrossRef]

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[CrossRef]

O. P. Kocaoglu, S. Lee, R. S. Jonnal, Q. Wang, A. E. Herde, J. C. Derby, W. Gao, and D. T. Miller, “Imaging cone photoreceptors in three dimensions and in time using ultrahigh resolution optical coherence tomography with adaptive optics,” Biomed. Opt. Express 2, 748–763 (2011).
[CrossRef]

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[CrossRef]

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[CrossRef]

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. Express 2, 1864–1876 (2011).
[CrossRef]

2010

2009

2008

T. E. Ustun, N. V. Iftimia, R. D. Ferguson, and D. X. Hammer, “Real-time processing for Fourier domain optical coherence tomography using a field programmable gate array,” Rev. Sci. Instrum. 79, 114301 (2008).
[CrossRef]

U. E. Wolf-Schnurrbusch, V. Enzmann, C. K. Brinkmann, and S. Wolf, “Morphologic changes in patients with geographic atrophy assessed with a novel spectral OCT-SLO combination,” Invest. Ophthalmol. Visual Sci. 49, 3095–3099 (2008).
[CrossRef]

T. P. Chui, H. Song, and S. A. Burns, “Adaptive-optics imaging of human cone photoreceptor distribution,” J. Opt. Soc. Am. A 25, 3021–3029 (2008).
[CrossRef]

2007

2006

2005

2004

2002

2000

G. Li, H. Zwick, B. Stuck, and D. J. Lund, “On the use of schematic eye models to estimate retinal image quality,” J. Biomed. Opt. 5, 307–314 (2000).
[CrossRef]

1997

1994

1991

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

1987

Ahamd, K.

Ahnelt, P. K.

Akula, J. D.

D. X. Hammer, R. D. Ferguson, M. Mujat, D. P. Biss, N. V. Iftimia, A. H. Patel, E. Plumb, M. Campbell, J. L Norris, A. Dubra, T. Y. P. Chui, J. D. Akula, and A. B. Fulton, “Advanced capabilities of the multimodal adaptive optics imager,” Proc. SPIE 7885, 78850A (2011).
[CrossRef]

Ali Rahman, I. S.

E. P. Rakoczy, I. S. Ali Rahman, N. Binz, C. R. Li, N. N. Vagaja, M. de Pinho, and C. M. Lai, “Characterization of a mouse model of hyperglycemia and retinal neovascularization,” Am. J. Pathol. 177, 2659–2670 (2010).
[CrossRef]

Alt, C.

C. Alt and C. P. Lin, “In vivo quantification of microglia dynamics with a scanning laser ophthalmoscope in a mouse model of focal laser injury,” Proc. SPIE 8209, 820907 (2012).
[CrossRef]

Artal, P.

Balderas-Mata, S.

Baumann, B.

Besecker, J. R.

Bifano, T. G.

Bigelow, C. E.

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

D. X. Hammer, R. D. Ferguson, T. E. Ustun, C. E. Bigelow, N. V. Iftimia, and R. H. Webb, “Line-scanning laser ophthalmoscope,” J. Biomed. Opt. 11, 041126 (2006).
[CrossRef]

Binz, N.

E. P. Rakoczy, I. S. Ali Rahman, N. Binz, C. R. Li, N. N. Vagaja, M. de Pinho, and C. M. Lai, “Characterization of a mouse model of hyperglycemia and retinal neovascularization,” Am. J. Pathol. 177, 2659–2670 (2010).
[CrossRef]

Biss, D. P.

D. X. Hammer, R. D. Ferguson, M. Mujat, D. P. Biss, N. V. Iftimia, A. H. Patel, E. Plumb, M. Campbell, J. L Norris, A. Dubra, T. Y. P. Chui, J. D. Akula, and A. B. Fulton, “Advanced capabilities of the multimodal adaptive optics imager,” Proc. SPIE 7885, 78850A (2011).
[CrossRef]

D. P. Biss, D. Sumorok, S. A. Burns, R. H. Webb, Y. Zhou, T. G. Bifano, D. Côté, I. Veilleux, P. Zamiri, and C. P. Lin, “In vivo fluorescent imaging of the mouse retina using adaptive optics,” Opt. Lett. 32, 659–661 (2007).
[CrossRef]

Bock, R.

Bower, B. A.

Brinkmann, C. K.

U. E. Wolf-Schnurrbusch, V. Enzmann, C. K. Brinkmann, and S. Wolf, “Morphologic changes in patients with geographic atrophy assessed with a novel spectral OCT-SLO combination,” Invest. Ophthalmol. Visual Sci. 49, 3095–3099 (2008).
[CrossRef]

Burns, S. A.

Campbell, M.

D. X. Hammer, R. D. Ferguson, M. Mujat, D. P. Biss, N. V. Iftimia, A. H. Patel, E. Plumb, M. Campbell, J. L Norris, A. Dubra, T. Y. P. Chui, J. D. Akula, and A. B. Fulton, “Advanced capabilities of the multimodal adaptive optics imager,” Proc. SPIE 7885, 78850A (2011).
[CrossRef]

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

Carroll, J.

Cashman, S. M.

D. L. Greenwald, S. M. Cashman, and R. Kumar-Singh, “Mutation-independent rescue of a novel mouse model of retinitis pigmentosa,” Gene Ther. (2012). .
[CrossRef]

Cense, B.

Chang, B.

J. Won, L. Y. Shi, W. Hicks, J. Wang, R. Hurd, J. K. Naggert, B. Chang, and P. M. Nishina, “Mouse model resources for vision research,” J. Ophthalmol. 2011, 391384 (2011).
[CrossRef]

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, C. A. Puliafito, and J. G. Fujimoto, “Optical coherence tomography,” Science 254, 1178–1181 (1991).
[CrossRef]

Choi, S.

Chui, T. P.

Chui, T. Y. P.

T. Y. P. Chui, Z. Zhong, H. Song, and S. A. Burns, “Foveal avascular zone and its relationship to foveal pit shape,” Optom. Vis. Sci. 89, 602–610 (2012).
[CrossRef]

D. X. Hammer, R. D. Ferguson, M. Mujat, D. P. Biss, N. V. Iftimia, A. H. Patel, E. Plumb, M. Campbell, J. L Norris, A. Dubra, T. Y. P. Chui, J. D. Akula, and A. B. Fulton, “Advanced capabilities of the multimodal adaptive optics imager,” Proc. SPIE 7885, 78850A (2011).
[CrossRef]

Cooper, R. F.

Côté, D.

Cucu, R. G.

R. B. Rosen, M. E. J. van Velthoven, P. M. T. Garcia, R. G. Cucu, M. D. de Smet, T. O. Muldoon, and A. Gh. Podoleanu, “Ultrahigh-resolution combined coronal optical coherence tomography confocal scanning ophthalmoscope (OCT/SLO): a pilot study,” Spektrum Augeheilkd 21, 17–28 (2007).
[CrossRef]

de Pinho, M.

E. P. Rakoczy, I. S. Ali Rahman, N. Binz, C. R. Li, N. N. Vagaja, M. de Pinho, and C. M. Lai, “Characterization of a mouse model of hyperglycemia and retinal neovascularization,” Am. J. Pathol. 177, 2659–2670 (2010).
[CrossRef]

de Smet, M. D.

R. B. Rosen, M. E. J. van Velthoven, P. M. T. Garcia, R. G. Cucu, M. D. de Smet, T. O. Muldoon, and A. Gh. Podoleanu, “Ultrahigh-resolution combined coronal optical coherence tomography confocal scanning ophthalmoscope (OCT/SLO): a pilot study,” Spektrum Augeheilkd 21, 17–28 (2007).
[CrossRef]

Delori, F. C.

Deng, C.

Derby, J. C.

Donnelly, W. I.

Drexler, W.

Dubis, A. M.

Dubra, A.

Elsner, A. E.

Enzmann, V.

U. E. Wolf-Schnurrbusch, V. Enzmann, C. K. Brinkmann, and S. Wolf, “Morphologic changes in patients with geographic atrophy assessed with a novel spectral OCT-SLO combination,” Invest. Ophthalmol. Visual Sci. 49, 3095–3099 (2008).
[CrossRef]

Felberer, F.

Fercher, A. F.

Ferguson, R. D.

D. X. Hammer, R. D. Ferguson, M. Mujat, D. P. Biss, N. V. Iftimia, A. H. Patel, E. Plumb, M. Campbell, J. L Norris, A. Dubra, T. Y. P. Chui, J. D. Akula, and A. B. Fulton, “Advanced capabilities of the multimodal adaptive optics imager,” Proc. SPIE 7885, 78850A (2011).
[CrossRef]

R. D. Ferguson, Z. Zhong, D. X. Hammer, M. Mujat, A. H. Patel, C. Deng, W. Zou, and S. A. Burns, “Adaptive optics SLO with integrated wide-field retinal imaging and tracking,” J. Opt. Soc. Am. A 27, A265–A277 (2010).
[CrossRef]

M. Mujat, R. D. Ferguson, A. H. Patel, N. Iftimia, N. Lue, and D. X. Hammer, “High resolution multimodal clinical ophthalmic imaging system,” Opt. Express 18, 11607–11621 (2010).
[CrossRef]

T. E. Ustun, N. V. Iftimia, R. D. Ferguson, and D. X. Hammer, “Real-time processing for Fourier domain optical coherence tomography using a field programmable gate array,” Rev. Sci. Instrum. 79, 114301 (2008).
[CrossRef]

S. A. Burns, R. Tumbar, A. E. Elsner, R. D. Ferguson, and D. X. Hammer, “Large field of view, modular, stabilized, adaptive-optics-based scanning laser ophthalmoscope,” J. Opt. Soc. Am. A 24, 1313–1326 (2007).
[CrossRef]

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

D. X. Hammer, R. D. Ferguson, T. E. Ustun, C. E. Bigelow, N. V. Iftimia, and R. H. Webb, “Line-scanning laser ophthalmoscope,” J. Biomed. Opt. 11, 041126 (2006).
[CrossRef]

Z. Nadler, G. Wollstein, J. E. Nevins, H. Ishikawa, L. Kagemann, I. A. Sigal, R. D. Ferguson, D. X. Hammer, and J. S. Schuman, “Three-dimensional morphological evaluation of Lamina Cribrosa,” Ophthalmology (to be published).

Fernández, E. J.

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, C. A. Puliafito, and J. G. Fujimoto, “Optical coherence tomography,” Science 254, 1178–1181 (1991).
[CrossRef]

Fujimoto, J. G.

M. F. Kraus, B. Potsaid, M. A. Mayer, R. Bock, B. Baumann, J. J. Liu, J. Hornegger, and J. G. Fujimoto, “Motion correction in optical coherence tomography volumes on a per A-scan basis using orthogonal scan patterns,” Biomed. Opt. Express 3, 1182–1199 (2012).
[CrossRef]

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

Fulton, A. B.

D. X. Hammer, R. D. Ferguson, M. Mujat, D. P. Biss, N. V. Iftimia, A. H. Patel, E. Plumb, M. Campbell, J. L Norris, A. Dubra, T. Y. P. Chui, J. D. Akula, and A. B. Fulton, “Advanced capabilities of the multimodal adaptive optics imager,” Proc. SPIE 7885, 78850A (2011).
[CrossRef]

Gao, W.

Garcia, P. M. T.

R. B. Rosen, M. E. J. van Velthoven, P. M. T. Garcia, R. G. Cucu, M. D. de Smet, T. O. Muldoon, and A. Gh. Podoleanu, “Ultrahigh-resolution combined coronal optical coherence tomography confocal scanning ophthalmoscope (OCT/SLO): a pilot study,” Spektrum Augeheilkd 21, 17–28 (2007).
[CrossRef]

García de la Cera, E.

E. García de la Cera, G. Rodríquez, L. Llorente, F. Schaeffel, and S. Marcos, “Optical aberrations in the mouse eye,” Vis. Res. 46, 2546–2553 (2006).
[CrossRef]

Gee, B. P.

Geng, Y.

Götzinger, E.

Gray, D. C.

Greenwald, D. L.

D. L. Greenwald, S. M. Cashman, and R. Kumar-Singh, “Mutation-independent rescue of a novel mouse model of retinitis pigmentosa,” Gene Ther. (2012). .
[CrossRef]

Gregory, K.

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

Hammer, D. X.

D. X. Hammer, R. D. Ferguson, M. Mujat, D. P. Biss, N. V. Iftimia, A. H. Patel, E. Plumb, M. Campbell, J. L Norris, A. Dubra, T. Y. P. Chui, J. D. Akula, and A. B. Fulton, “Advanced capabilities of the multimodal adaptive optics imager,” Proc. SPIE 7885, 78850A (2011).
[CrossRef]

R. D. Ferguson, Z. Zhong, D. X. Hammer, M. Mujat, A. H. Patel, C. Deng, W. Zou, and S. A. Burns, “Adaptive optics SLO with integrated wide-field retinal imaging and tracking,” J. Opt. Soc. Am. A 27, A265–A277 (2010).
[CrossRef]

M. Mujat, R. D. Ferguson, A. H. Patel, N. Iftimia, N. Lue, and D. X. Hammer, “High resolution multimodal clinical ophthalmic imaging system,” Opt. Express 18, 11607–11621 (2010).
[CrossRef]

T. E. Ustun, N. V. Iftimia, R. D. Ferguson, and D. X. Hammer, “Real-time processing for Fourier domain optical coherence tomography using a field programmable gate array,” Rev. Sci. Instrum. 79, 114301 (2008).
[CrossRef]

S. A. Burns, R. Tumbar, A. E. Elsner, R. D. Ferguson, and D. X. Hammer, “Large field of view, modular, stabilized, adaptive-optics-based scanning laser ophthalmoscope,” J. Opt. Soc. Am. A 24, 1313–1326 (2007).
[CrossRef]

D. X. Hammer, R. D. Ferguson, T. E. Ustun, C. E. Bigelow, N. V. Iftimia, and R. H. Webb, “Line-scanning laser ophthalmoscope,” J. Biomed. Opt. 11, 041126 (2006).
[CrossRef]

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

Z. Nadler, G. Wollstein, J. E. Nevins, H. Ishikawa, L. Kagemann, I. A. Sigal, R. D. Ferguson, D. X. Hammer, and J. S. Schuman, “Three-dimensional morphological evaluation of Lamina Cribrosa,” Ophthalmology (to be published).

Hebert, T.

Hee, M. R.

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

Herde, A. E.

Hermann, B.

Hicks, W.

J. Won, L. Y. Shi, W. Hicks, J. Wang, R. Hurd, J. K. Naggert, B. Chang, and P. M. Nishina, “Mouse model resources for vision research,” J. Ophthalmol. 2011, 391384 (2011).
[CrossRef]

Hitzenberger, C. K.

Hofer, B.

Hornegger, J.

Huang, D.

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

Hughes, G. W.

Hunter, J. J.

Hurd, R.

J. Won, L. Y. Shi, W. Hicks, J. Wang, R. Hurd, J. K. Naggert, B. Chang, and P. M. Nishina, “Mouse model resources for vision research,” J. Ophthalmol. 2011, 391384 (2011).
[CrossRef]

Iftimia, N.

Iftimia, N. V.

D. X. Hammer, R. D. Ferguson, M. Mujat, D. P. Biss, N. V. Iftimia, A. H. Patel, E. Plumb, M. Campbell, J. L Norris, A. Dubra, T. Y. P. Chui, J. D. Akula, and A. B. Fulton, “Advanced capabilities of the multimodal adaptive optics imager,” Proc. SPIE 7885, 78850A (2011).
[CrossRef]

T. E. Ustun, N. V. Iftimia, R. D. Ferguson, and D. X. Hammer, “Real-time processing for Fourier domain optical coherence tomography using a field programmable gate array,” Rev. Sci. Instrum. 79, 114301 (2008).
[CrossRef]

D. X. Hammer, R. D. Ferguson, T. E. Ustun, C. E. Bigelow, N. V. Iftimia, and R. H. Webb, “Line-scanning laser ophthalmoscope,” J. Biomed. Opt. 11, 041126 (2006).
[CrossRef]

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

Ishikawa, H.

Z. Nadler, G. Wollstein, J. E. Nevins, H. Ishikawa, L. Kagemann, I. A. Sigal, R. D. Ferguson, D. X. Hammer, and J. S. Schuman, “Three-dimensional morphological evaluation of Lamina Cribrosa,” Ophthalmology (to be published).

Izatt, J. A.

Jones, S. M.

Jonnal, R. S.

Kagemann, L.

Z. Nadler, G. Wollstein, J. E. Nevins, H. Ishikawa, L. Kagemann, I. A. Sigal, R. D. Ferguson, D. X. Hammer, and J. S. Schuman, “Three-dimensional morphological evaluation of Lamina Cribrosa,” Ophthalmology (to be published).

Kim, D. Y.

Kocaoglu, O. P.

Kraus, M. F.

Kroisamer, J. S.

Kumar-Singh, R.

D. L. Greenwald, S. M. Cashman, and R. Kumar-Singh, “Mutation-independent rescue of a novel mouse model of retinitis pigmentosa,” Gene Ther. (2012). .
[CrossRef]

Lai, C. M.

E. P. Rakoczy, I. S. Ali Rahman, N. Binz, C. R. Li, N. N. Vagaja, M. de Pinho, and C. M. Lai, “Characterization of a mouse model of hyperglycemia and retinal neovascularization,” Am. J. Pathol. 177, 2659–2670 (2010).
[CrossRef]

Laut, S.

Lee, S.

Li, C. R.

E. P. Rakoczy, I. S. Ali Rahman, N. Binz, C. R. Li, N. N. Vagaja, M. de Pinho, and C. M. Lai, “Characterization of a mouse model of hyperglycemia and retinal neovascularization,” Am. J. Pathol. 177, 2659–2670 (2010).
[CrossRef]

Li, G.

G. Li, H. Zwick, B. Stuck, and D. J. Lund, “On the use of schematic eye models to estimate retinal image quality,” J. Biomed. Opt. 5, 307–314 (2000).
[CrossRef]

Liang, J.

Libby, R. T.

Lin, C. P.

C. Alt and C. P. Lin, “In vivo quantification of microglia dynamics with a scanning laser ophthalmoscope in a mouse model of focal laser injury,” Proc. SPIE 8209, 820907 (2012).
[CrossRef]

D. P. Biss, D. Sumorok, S. A. Burns, R. H. Webb, Y. Zhou, T. G. Bifano, D. Côté, I. Veilleux, P. Zamiri, and C. P. Lin, “In vivo fluorescent imaging of the mouse retina using adaptive optics,” Opt. Lett. 32, 659–661 (2007).
[CrossRef]

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

Liu, J. J.

Llorente, L.

E. García de la Cera, G. Rodríquez, L. Llorente, F. Schaeffel, and S. Marcos, “Optical aberrations in the mouse eye,” Vis. Res. 46, 2546–2553 (2006).
[CrossRef]

Lue, N.

Lund, D. J.

G. Li, H. Zwick, B. Stuck, and D. J. Lund, “On the use of schematic eye models to estimate retinal image quality,” J. Biomed. Opt. 5, 307–314 (2000).
[CrossRef]

Marcos, S.

E. García de la Cera, G. Rodríquez, L. Llorente, F. Schaeffel, and S. Marcos, “Optical aberrations in the mouse eye,” Vis. Res. 46, 2546–2553 (2006).
[CrossRef]

Masella, B.

Mayer, M. A.

McKinnon, S. J.

S. J. McKinnon, C. L. Schlamp, and R. W. Nickells, “Mouse models of retinal ganglion cell death and glaucoma,” Exp. Eye Res. 88, 816–824 (2009).
[CrossRef]

Merigan, W.

Merigan, W. H.

Miller, D. T.

Mujat, M.

Muldoon, T. O.

R. B. Rosen, M. E. J. van Velthoven, P. M. T. Garcia, R. G. Cucu, M. D. de Smet, T. O. Muldoon, and A. Gh. Podoleanu, “Ultrahigh-resolution combined coronal optical coherence tomography confocal scanning ophthalmoscope (OCT/SLO): a pilot study,” Spektrum Augeheilkd 21, 17–28 (2007).
[CrossRef]

Nadler, Z.

Z. Nadler, G. Wollstein, J. E. Nevins, H. Ishikawa, L. Kagemann, I. A. Sigal, R. D. Ferguson, D. X. Hammer, and J. S. Schuman, “Three-dimensional morphological evaluation of Lamina Cribrosa,” Ophthalmology (to be published).

Naggert, J. K.

J. Won, L. Y. Shi, W. Hicks, J. Wang, R. Hurd, J. K. Naggert, B. Chang, and P. M. Nishina, “Mouse model resources for vision research,” J. Ophthalmol. 2011, 391384 (2011).
[CrossRef]

Nevins, J. E.

Z. Nadler, G. Wollstein, J. E. Nevins, H. Ishikawa, L. Kagemann, I. A. Sigal, R. D. Ferguson, D. X. Hammer, and J. S. Schuman, “Three-dimensional morphological evaluation of Lamina Cribrosa,” Ophthalmology (to be published).

Nickells, R. W.

S. J. McKinnon, C. L. Schlamp, and R. W. Nickells, “Mouse models of retinal ganglion cell death and glaucoma,” Exp. Eye Res. 88, 816–824 (2009).
[CrossRef]

Nishina, P. M.

J. Won, L. Y. Shi, W. Hicks, J. Wang, R. Hurd, J. K. Naggert, B. Chang, and P. M. Nishina, “Mouse model resources for vision research,” J. Ophthalmol. 2011, 391384 (2011).
[CrossRef]

Norris, J. L

D. X. Hammer, R. D. Ferguson, M. Mujat, D. P. Biss, N. V. Iftimia, A. H. Patel, E. Plumb, M. Campbell, J. L Norris, A. Dubra, T. Y. P. Chui, J. D. Akula, and A. B. Fulton, “Advanced capabilities of the multimodal adaptive optics imager,” Proc. SPIE 7885, 78850A (2011).
[CrossRef]

Norris, J. L.

Olivier, S. S.

Palczewska, G.

Palczewski, K.

Patel, A. H.

Pilli, S.

Pircher, M.

Plumb, E.

D. X. Hammer, R. D. Ferguson, M. Mujat, D. P. Biss, N. V. Iftimia, A. H. Patel, E. Plumb, M. Campbell, J. L Norris, A. Dubra, T. Y. P. Chui, J. D. Akula, and A. B. Fulton, “Advanced capabilities of the multimodal adaptive optics imager,” Proc. SPIE 7885, 78850A (2011).
[CrossRef]

Podoleanu, A. G.

Podoleanu, A. Gh.

R. B. Rosen, M. E. J. van Velthoven, P. M. T. Garcia, R. G. Cucu, M. D. de Smet, T. O. Muldoon, and A. Gh. Podoleanu, “Ultrahigh-resolution combined coronal optical coherence tomography confocal scanning ophthalmoscope (OCT/SLO): a pilot study,” Spektrum Augeheilkd 21, 17–28 (2007).
[CrossRef]

Porter, J.

Potsaid, B.

Povazay, B.

Prieto, P. M.

Puliafito, C. A.

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

Queener, H.

Rakoczy, E. P.

E. P. Rakoczy, I. S. Ali Rahman, N. Binz, C. R. Li, N. N. Vagaja, M. de Pinho, and C. M. Lai, “Characterization of a mouse model of hyperglycemia and retinal neovascularization,” Am. J. Pathol. 177, 2659–2670 (2010).
[CrossRef]

Reinholz, F.

Rodríquez, G.

E. García de la Cera, G. Rodríquez, L. Llorente, F. Schaeffel, and S. Marcos, “Optical aberrations in the mouse eye,” Vis. Res. 46, 2546–2553 (2006).
[CrossRef]

Romero-Borja, F.

Roorda, A.

Rosen, R. B.

R. B. Rosen, M. E. J. van Velthoven, P. M. T. Garcia, R. G. Cucu, M. D. de Smet, T. O. Muldoon, and A. Gh. Podoleanu, “Ultrahigh-resolution combined coronal optical coherence tomography confocal scanning ophthalmoscope (OCT/SLO): a pilot study,” Spektrum Augeheilkd 21, 17–28 (2007).
[CrossRef]

Sattmann, H.

Schaeffel, F.

E. García de la Cera, G. Rodríquez, L. Llorente, F. Schaeffel, and S. Marcos, “Optical aberrations in the mouse eye,” Vis. Res. 46, 2546–2553 (2006).
[CrossRef]

Schlamp, C. L.

S. J. McKinnon, C. L. Schlamp, and R. W. Nickells, “Mouse models of retinal ganglion cell death and glaucoma,” Exp. Eye Res. 88, 816–824 (2009).
[CrossRef]

Schuman, J. S.

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

Z. Nadler, G. Wollstein, J. E. Nevins, H. Ishikawa, L. Kagemann, I. A. Sigal, R. D. Ferguson, D. X. Hammer, and J. S. Schuman, “Three-dimensional morphological evaluation of Lamina Cribrosa,” Ophthalmology (to be published).

Sharma, R.

Shi, L. Y.

J. Won, L. Y. Shi, W. Hicks, J. Wang, R. Hurd, J. K. Naggert, B. Chang, and P. M. Nishina, “Mouse model resources for vision research,” J. Ophthalmol. 2011, 391384 (2011).
[CrossRef]

Sigal, I. A.

Z. Nadler, G. Wollstein, J. E. Nevins, H. Ishikawa, L. Kagemann, I. A. Sigal, R. D. Ferguson, D. X. Hammer, and J. S. Schuman, “Three-dimensional morphological evaluation of Lamina Cribrosa,” Ophthalmology (to be published).

Song, H.

T. Y. P. Chui, Z. Zhong, H. Song, and S. A. Burns, “Foveal avascular zone and its relationship to foveal pit shape,” Optom. Vis. Sci. 89, 602–610 (2012).
[CrossRef]

T. P. Chui, H. Song, and S. A. Burns, “Adaptive-optics imaging of human cone photoreceptor distribution,” J. Opt. Soc. Am. A 25, 3021–3029 (2008).
[CrossRef]

Stinson, W. G.

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

Stuck, B.

G. Li, H. Zwick, B. Stuck, and D. J. Lund, “On the use of schematic eye models to estimate retinal image quality,” J. Biomed. Opt. 5, 307–314 (2000).
[CrossRef]

Sulai, Y.

Sumorok, D.

Swanson, E. A.

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

Tam, J.

Tiruveedhula, P.

Torti, C.

Tumbar, R.

Tuohy, S.

Twietmeyer, T. H.

Unterhuber, A.

Ustun, T. E.

T. E. Ustun, N. V. Iftimia, R. D. Ferguson, and D. X. Hammer, “Real-time processing for Fourier domain optical coherence tomography using a field programmable gate array,” Rev. Sci. Instrum. 79, 114301 (2008).
[CrossRef]

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

D. X. Hammer, R. D. Ferguson, T. E. Ustun, C. E. Bigelow, N. V. Iftimia, and R. H. Webb, “Line-scanning laser ophthalmoscope,” J. Biomed. Opt. 11, 041126 (2006).
[CrossRef]

Vagaja, N. N.

E. P. Rakoczy, I. S. Ali Rahman, N. Binz, C. R. Li, N. N. Vagaja, M. de Pinho, and C. M. Lai, “Characterization of a mouse model of hyperglycemia and retinal neovascularization,” Am. J. Pathol. 177, 2659–2670 (2010).
[CrossRef]

van Velthoven, M. E. J.

R. B. Rosen, M. E. J. van Velthoven, P. M. T. Garcia, R. G. Cucu, M. D. de Smet, T. O. Muldoon, and A. Gh. Podoleanu, “Ultrahigh-resolution combined coronal optical coherence tomography confocal scanning ophthalmoscope (OCT/SLO): a pilot study,” Spektrum Augeheilkd 21, 17–28 (2007).
[CrossRef]

Veilleux, I.

Wang, J.

J. Won, L. Y. Shi, W. Hicks, J. Wang, R. Hurd, J. K. Naggert, B. Chang, and P. M. Nishina, “Mouse model resources for vision research,” J. Ophthalmol. 2011, 391384 (2011).
[CrossRef]

Wang, Q.

Webb, R. H.

Werner, J. S.

Williams, D. R.

Wolf, S.

U. E. Wolf-Schnurrbusch, V. Enzmann, C. K. Brinkmann, and S. Wolf, “Morphologic changes in patients with geographic atrophy assessed with a novel spectral OCT-SLO combination,” Invest. Ophthalmol. Visual Sci. 49, 3095–3099 (2008).
[CrossRef]

Wolfing, J. I.

Wolf-Schnurrbusch, U. E.

U. E. Wolf-Schnurrbusch, V. Enzmann, C. K. Brinkmann, and S. Wolf, “Morphologic changes in patients with geographic atrophy assessed with a novel spectral OCT-SLO combination,” Invest. Ophthalmol. Visual Sci. 49, 3095–3099 (2008).
[CrossRef]

Wollstein, G.

Z. Nadler, G. Wollstein, J. E. Nevins, H. Ishikawa, L. Kagemann, I. A. Sigal, R. D. Ferguson, D. X. Hammer, and J. S. Schuman, “Three-dimensional morphological evaluation of Lamina Cribrosa,” Ophthalmology (to be published).

Won, J.

J. Won, L. Y. Shi, W. Hicks, J. Wang, R. Hurd, J. K. Naggert, B. Chang, and P. M. Nishina, “Mouse model resources for vision research,” J. Ophthalmol. 2011, 391384 (2011).
[CrossRef]

Yin, L.

Zamiri, P.

Zawadzki, R. J.

Zhao, M.

Zhong, Z.

Zhou, Y.

Zou, W.

Zwick, H.

G. Li, H. Zwick, B. Stuck, and D. J. Lund, “On the use of schematic eye models to estimate retinal image quality,” J. Biomed. Opt. 5, 307–314 (2000).
[CrossRef]

Am. J. Pathol.

E. P. Rakoczy, I. S. Ali Rahman, N. Binz, C. R. Li, N. N. Vagaja, M. de Pinho, and C. M. Lai, “Characterization of a mouse model of hyperglycemia and retinal neovascularization,” Am. J. Pathol. 177, 2659–2670 (2010).
[CrossRef]

Appl. Opt.

Biomed. Opt. Express

M. Pircher, J. S. Kroisamer, F. Felberer, H. Sattmann, E. Götzinger, and C. K. Hitzenberger, “Temporal changes of human cone photoreceptors observed in vivo with SLO/OCT,” Biomed. Opt. Express 2, 100–112 (2011).
[CrossRef]

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, 139–148 (2011).
[CrossRef]

O. P. Kocaoglu, S. Lee, R. S. Jonnal, Q. Wang, A. E. Herde, J. C. Derby, W. Gao, and D. T. Miller, “Imaging cone photoreceptors in three dimensions and in time using ultrahigh resolution optical coherence tomography with adaptive optics,” Biomed. Opt. Express 2, 748–763 (2011).
[CrossRef]

J. Tam, P. Tiruveedhula, and A. Roorda, “Characterization of single-file flow through human retinal parafoveal capillaries using an adaptive optics scanning laser ophthalmoscope,” Biomed. Opt. Express 2, 781–793 (2011).
[CrossRef]

R. J. Zawadzki, S. M. Jones, S. Pilli, S. Balderas-Mata, D. Y. Kim, S. S. Olivier, and J. S. Werner, “Integrated adaptive optics optical coherence tomography and adaptive optics scanning laser ophthalmoscope system for simultaneous cellular resolution in vivo retinal imaging,” Biomed. Opt. Express 2, 1674–1686 (2011).
[CrossRef]

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. Express 2, 1864–1876 (2011).
[CrossRef]

Y. Geng, A. Dubra, L. Yin, W. H. Merigan, R. Sharma, R. T. Libby, and D. R. Williams, “Adaptive optics retinal imaging in the living mouse eye,” Biomed. Opt. Express 3, 715–734 (2012).
[CrossRef]

M. F. Kraus, B. Potsaid, M. A. Mayer, R. Bock, B. Baumann, J. J. Liu, J. Hornegger, and J. G. Fujimoto, “Motion correction in optical coherence tomography volumes on a per A-scan basis using orthogonal scan patterns,” Biomed. Opt. Express 3, 1182–1199 (2012).
[CrossRef]

Exp. Eye Res.

S. J. McKinnon, C. L. Schlamp, and R. W. Nickells, “Mouse models of retinal ganglion cell death and glaucoma,” Exp. Eye Res. 88, 816–824 (2009).
[CrossRef]

Invest. Ophthalmol. Visual Sci.

U. E. Wolf-Schnurrbusch, V. Enzmann, C. K. Brinkmann, and S. Wolf, “Morphologic changes in patients with geographic atrophy assessed with a novel spectral OCT-SLO combination,” Invest. Ophthalmol. Visual Sci. 49, 3095–3099 (2008).
[CrossRef]

J. Biomed. Opt.

G. Li, H. Zwick, B. Stuck, and D. J. Lund, “On the use of schematic eye models to estimate retinal image quality,” J. Biomed. Opt. 5, 307–314 (2000).
[CrossRef]

D. X. Hammer, R. D. Ferguson, T. E. Ustun, C. E. Bigelow, N. V. Iftimia, and R. H. Webb, “Line-scanning laser ophthalmoscope,” J. Biomed. Opt. 11, 041126 (2006).
[CrossRef]

J. Ophthalmol.

J. Won, L. Y. Shi, W. Hicks, J. Wang, R. Hurd, J. K. Naggert, B. Chang, and P. M. Nishina, “Mouse model resources for vision research,” J. Ophthalmol. 2011, 391384 (2011).
[CrossRef]

J. Opt. Soc. Am. A

Opt. Express

C. Torti, B. Povazay, B. Hofer, A. Unterhuber, J. Carroll, P. K. Ahnelt, and W. Drexler, “Adaptive optics optical coherence tomography at 120,000 depth scans/s for non-invasive cellular phenotyping of the living human retina,” Opt. Express 17, 19382–19400 (2009).
[CrossRef]

S. Tuohy and A. G. Podoleanu, “Depth-resolved wavefront aberrations using a coherence-gated Shack-Hartmann wavefront sensor,” Opt. Express 18, 3458–3476 (2010).
[CrossRef]

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, 5257–5270 (2010).
[CrossRef]

M. Mujat, R. D. Ferguson, A. H. Patel, N. Iftimia, N. Lue, and D. X. Hammer, “High resolution multimodal clinical ophthalmic imaging system,” Opt. Express 18, 11607–11621 (2010).
[CrossRef]

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, 8532–8546 (2005).
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Supplementary Material (4)

» Media 1: MOV (15362 KB)     
» Media 2: MOV (14384 KB)     
» Media 3: MOV (23449 KB)     
» Media 4: MOV (6634 KB)     

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Figures (12)

Fig. 1.
Fig. 1.

Photograph of the multimodal adaptive optics system (MAOS).

Fig. 2.
Fig. 2.

MAOS retinal imager functional block diagram. LCD FT, simulus/fixation target; FM, flip mount; D, dichroic beamsplitter; FG, framegrabber; DM, deformable mirror; HS-WS, Hartmann–Shack wavefront sensor; P, pellicle beamsplitter; PMT, photomultiplier tube; Amp, pre-amp; BF, barrier filter; exc/ems, excitation/emission light; FC, fiber coupler; ODL, optical delay line; SLD, superluminescent diode. Standard wavelength set is shown; other versions with alternate wavelength sets have been built.

Fig. 3.
Fig. 3.

Unfolded optical schematic for the MAOS imager.

Fig. 4.
Fig. 4.

Integrated SolidWorks-Zemax opto-mechanical model of MAOS. (a) Isometric view. (b) Top view. Small platforms mounted above the main optical table for the OCT optical delay line and spectrometer are not shown. Fluorescence detection channel is not included in this version.

Fig. 5.
Fig. 5.

Zemax optical model illustrating (a) large and (b) small beam diameter configurations. SM7 is affixed to a flip mount and removed from the beam path to access the alternate TM2a/SM7a path.

Fig. 6.
Fig. 6.

Simultaneous SLO/OCT scanning arrangement. The fast SLO scanner 1 is a resonant scanner (RS). Scanners 2 and 3 are galvanometers. The SLO raster and OCT line are created simultaneously with scanner 2, as are the OCT raster and SLO montage with scanner 3.

Fig. 7.
Fig. 7.

MAOS instrumentation diagram. See text or Figs. 2 and 3 for abbreviations.

Fig. 8.
Fig. 8.

High-resolution AOSLO retinal images from the multimodal AO retinal imager. (a) 1 deg fovea scan (note the dense cone packing in the fovea, lower left), (b) 2 deg macular scan at 5deg eccentricity, (c) 1 deg macular scan at 5deg eccentricity, (d) 1 deg scan at 10deg eccentricity showing a mixture of cones and rods, and (e) 2 deg scan of nerve fibers and bundles (focus pulled to inner retina).

Fig. 9.
Fig. 9.

Demonstration of simultaneous output of the multimodal AO retinal imager using larger field for a 38-year-old emmetropic subject without retinal disease. (a) AOSLO, (b) AO-SDOCT, and (c) wide-field LSO images. The OCT scan length is 10 deg, the SLO field size is 2×10deg, and the LSO image is 30deg. Scale bar is 100 μm for SLO and OCT and 1 mm for LSO. (Media 1)

Fig. 10.
Fig. 10.

Stitched montage from 2×10deg scan shown in Fig. 9. Montage size is 10×10deg.

Fig. 11.
Fig. 11.

Demonstration of simultaneous output of the multimodal AO retinal imager (for the primary AO imaging channels) for small field. (a) AOSLO, (b) AO-SDOCT. OCT scan length is 2 deg, and SLO field size is 2×2deg. Scale bar is 100 μm. (Media 2)

Fig. 12.
Fig. 12.

Multimodal output in albino rats. (a) System focus set to the PR/RPE complex. (Media 3) (b) System focus set to the NFL. (Media 4) Shown from left to right are the SLO, OCT, and LSO images acquired simultaneously. Scale bar is 100 μm for SLO and OCT and 1 mm for LSO. NFL, nerve fiber layer; GCL, ganglion cell layer; IPL, inner plexiform layer; INL, inner nuclear layer; OPL, outer plexiform layer; ONL, outer nuclear layer; ELM, external limiting membrane; IS/OS, inner/outer segment junction; OS, outer segments; RPE, retinal pigment epithelium; C, choroid; S, sclera; and M, muscle. Inset of (a) shows 2× zoomed region of PR/RPE complex.

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