Abstract

Here we demonstrate a new imaging system that addresses several major problems limiting the clinical utility of conventional adaptive optics scanning light ophthalmoscopy (AOSLO), including its small field of view (FOV), reliance on patient fixation for targeting imaging, and substantial post-processing time. We previously showed an efficient image based eye tracking method for real-time optical stabilization and image registration in AOSLO. However, in patients with poor fixation, eye motion causes the FOV to drift substantially, causing this approach to fail. We solve that problem here by tracking eye motion at multiple spatial scales simultaneously by optically and electronically integrating a wide FOV SLO (WFSLO) with an AOSLO. This multi-scale approach, implemented with fast tip/tilt mirrors, has a large stabilization range of ± 5.6°. Our method consists of three stages implemented in parallel: 1) coarse optical stabilization driven by a WFSLO image, 2) fine optical stabilization driven by an AOSLO image, and 3) sub-pixel digital registration of the AOSLO image. We evaluated system performance in normal eyes and diseased eyes with poor fixation. Residual image motion with incremental compensation after each stage was: 1) ~2–3 arc minutes, (arcmin) 2) ~0.5–0.8 arcmin and, 3) ~0.05–0.07 arcmin, for normal eyes. Performance in eyes with poor fixation was: 1) ~3–5 arcmin, 2) ~0.7–1.1 arcmin and 3) ~0.07–0.14 arcmin. We demonstrate that this system is capable of reducing image motion by a factor of ~400, on average. This new optical design provides additional benefits for clinical imaging, including a steering subsystem for AOSLO that can be guided by the WFSLO to target specific regions of interest such as retinal pathology and real-time averaging of registered images to eliminate image post-processing.

© 2015 Optical Society of America

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Corrections

Jie Zhang, Qiang Yang, Kenichi Saito, Koji Nozato, Austin Roorda, David R. Williams, and Ethan A. Rossi, "An adaptive optics imaging system designed for clinical use: publisher’s note," Biomed. Opt. Express 6, 2864-2864 (2015)
https://www.osapublishing.org/boe/abstract.cfm?uri=boe-6-8-2864

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References

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2014 (5)

D. Scoles, Y. N. Sulai, C. S. Langlo, G. A. Fishman, C. A. Curcio, J. Carroll, and A. Dubra, “In vivo imaging of human cone photoreceptor inner segments,” Invest. Ophthalmol. Vis. Sci. 55(7), 4244–4251 (2014).
[Crossref] [PubMed]

M. Dubow, A. Pinhas, N. Shah, R. F. Cooper, A. Gan, R. C. Gentile, V. Hendrix, Y. N. Sulai, J. Carroll, T. Y. P. Chui, J. B. Walsh, R. Weitz, A. Dubra, and R. B. Rosen, “Classification of human retinal microaneurysms using adaptive optics scanning light ophthalmoscope fluorescein angiography,” Invest. Ophthalmol. Vis. Sci. 55(3), 1299–1309 (2014).
[Crossref] [PubMed]

Y. Zhang, X. Wang, E. B. Rivero, M. E. Clark, C. D. Witherspoon, R. F. Spaide, C. A. Girkin, C. Owsley, and C. A. Curcio, “Photoreceptor Perturbation Around Subretinal Drusenoid Deposits as Revealed by Adaptive Optics Scanning Laser Ophthalmoscopy,” Am. J. Ophthalmol. 158(3), 584–596 (2014).
[Crossref] [PubMed]

D. Scoles, B. P. Higgins, R. F. Cooper, A. M. Dubis, P. Summerfelt, D. V. Weinberg, J. E. Kim, K. E. Stepien, J. Carroll, and A. Dubra, “Microscopic Inner Retinal Hyper-Reflective Phenotypes in Retinal and Neurologic Disease,” Invest. Ophthalmol. Vis. Sci. 55(7), 4015–4029 (2014).
[Crossref] [PubMed]

Q. Yang, J. Zhang, K. Nozato, K. Saito, D. R. Williams, A. Roorda, and E. A. Rossi, “Closed-loop optical stabilization and digital image registration in adaptive optics scanning light ophthalmoscopy,” Biomed. Opt. Express 5(9), 3174–3191 (2014).
[Crossref] [PubMed]

2013 (1)

2011 (5)

A. Dubra and Y. Sulai, “Reflective afocal broadband adaptive optics scanning ophthalmoscope,” Biomed. Opt. Express 2(6), 1757–1768 (2011).
[Crossref] [PubMed]

A. Dubra, Y. Sulai, J. L. Norris, R. F. Cooper, A. M. Dubis, D. R. Williams, and J. Carroll, “Noninvasive imaging of the human rod photoreceptor mosaic using a confocal adaptive optics scanning ophthalmoscope,” Biomed. Opt. Express 2(7), 1864–1876 (2011).
[Crossref] [PubMed]

K. E. Talcott, K. Ratnam, S. M. Sundquist, 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 Factor Treatment,” Invest. Ophthalmol. Vis. Sci. 52(5), 2219–2226 (2011).
[Crossref] [PubMed]

E. A. Rossi, M. Chung, A. Dubra, J. J. Hunter, W. H. Merigan, and D. R. Williams, “Imaging retinal mosaics in the living eye,” Eye (Lond.) 25(3), 301–308 (2011).
[Crossref] [PubMed]

D. R. Williams, “Imaging single cells in the living retina,” Vision Res. 51(13), 1379–1396 (2011).
[Crossref] [PubMed]

2010 (1)

2008 (1)

2007 (3)

2006 (1)

2004 (1)

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]

2002 (1)

Bigelow, C. E.

Burns, S. A.

Campbell, M.

Carroll, J.

D. Scoles, B. P. Higgins, R. F. Cooper, A. M. Dubis, P. Summerfelt, D. V. Weinberg, J. E. Kim, K. E. Stepien, J. Carroll, and A. Dubra, “Microscopic Inner Retinal Hyper-Reflective Phenotypes in Retinal and Neurologic Disease,” Invest. Ophthalmol. Vis. Sci. 55(7), 4015–4029 (2014).
[Crossref] [PubMed]

D. Scoles, Y. N. Sulai, C. S. Langlo, G. A. Fishman, C. A. Curcio, J. Carroll, and A. Dubra, “In vivo imaging of human cone photoreceptor inner segments,” Invest. Ophthalmol. Vis. Sci. 55(7), 4244–4251 (2014).
[Crossref] [PubMed]

M. Dubow, A. Pinhas, N. Shah, R. F. Cooper, A. Gan, R. C. Gentile, V. Hendrix, Y. N. Sulai, J. Carroll, T. Y. P. Chui, J. B. Walsh, R. Weitz, A. Dubra, and R. B. Rosen, “Classification of human retinal microaneurysms using adaptive optics scanning light ophthalmoscope fluorescein angiography,” Invest. Ophthalmol. Vis. Sci. 55(3), 1299–1309 (2014).
[Crossref] [PubMed]

A. Dubra, Y. Sulai, J. L. Norris, R. F. Cooper, A. M. Dubis, D. R. Williams, and J. Carroll, “Noninvasive imaging of the human rod photoreceptor mosaic using a confocal adaptive optics scanning ophthalmoscope,” Biomed. Opt. Express 2(7), 1864–1876 (2011).
[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.

Choi, S. S.

Chui, T. Y. P.

M. Dubow, A. Pinhas, N. Shah, R. F. Cooper, A. Gan, R. C. Gentile, V. Hendrix, Y. N. Sulai, J. Carroll, T. Y. P. Chui, J. B. Walsh, R. Weitz, A. Dubra, and R. B. Rosen, “Classification of human retinal microaneurysms using adaptive optics scanning light ophthalmoscope fluorescein angiography,” Invest. Ophthalmol. Vis. Sci. 55(3), 1299–1309 (2014).
[Crossref] [PubMed]

Chung, M.

E. A. Rossi, M. Chung, A. Dubra, J. J. Hunter, W. H. Merigan, and D. R. Williams, “Imaging retinal mosaics in the living eye,” Eye (Lond.) 25(3), 301–308 (2011).
[Crossref] [PubMed]

Chung, M. M.

Clark, M. E.

Y. Zhang, X. Wang, E. B. Rivero, M. E. Clark, C. D. Witherspoon, R. F. Spaide, C. A. Girkin, C. Owsley, and C. A. Curcio, “Photoreceptor Perturbation Around Subretinal Drusenoid Deposits as Revealed by Adaptive Optics Scanning Laser Ophthalmoscopy,” Am. J. Ophthalmol. 158(3), 584–596 (2014).
[Crossref] [PubMed]

Cooper, R. F.

D. Scoles, B. P. Higgins, R. F. Cooper, A. M. Dubis, P. Summerfelt, D. V. Weinberg, J. E. Kim, K. E. Stepien, J. Carroll, and A. Dubra, “Microscopic Inner Retinal Hyper-Reflective Phenotypes in Retinal and Neurologic Disease,” Invest. Ophthalmol. Vis. Sci. 55(7), 4015–4029 (2014).
[Crossref] [PubMed]

M. Dubow, A. Pinhas, N. Shah, R. F. Cooper, A. Gan, R. C. Gentile, V. Hendrix, Y. N. Sulai, J. Carroll, T. Y. P. Chui, J. B. Walsh, R. Weitz, A. Dubra, and R. B. Rosen, “Classification of human retinal microaneurysms using adaptive optics scanning light ophthalmoscope fluorescein angiography,” Invest. Ophthalmol. Vis. Sci. 55(3), 1299–1309 (2014).
[Crossref] [PubMed]

A. Dubra, Y. Sulai, J. L. Norris, R. F. Cooper, A. M. Dubis, D. R. Williams, and J. Carroll, “Noninvasive imaging of the human rod photoreceptor mosaic using a confocal adaptive optics scanning ophthalmoscope,” Biomed. Opt. Express 2(7), 1864–1876 (2011).
[Crossref] [PubMed]

Curcio, C. A.

D. Scoles, Y. N. Sulai, C. S. Langlo, G. A. Fishman, C. A. Curcio, J. Carroll, and A. Dubra, “In vivo imaging of human cone photoreceptor inner segments,” Invest. Ophthalmol. Vis. Sci. 55(7), 4244–4251 (2014).
[Crossref] [PubMed]

Y. Zhang, X. Wang, E. B. Rivero, M. E. Clark, C. D. Witherspoon, R. F. Spaide, C. A. Girkin, C. Owsley, and C. A. Curcio, “Photoreceptor Perturbation Around Subretinal Drusenoid Deposits as Revealed by Adaptive Optics Scanning Laser Ophthalmoscopy,” Am. J. Ophthalmol. 158(3), 584–596 (2014).
[Crossref] [PubMed]

Delori, F. C.

Deng, C.

Donnelly, W.

Dubis, A. M.

D. Scoles, B. P. Higgins, R. F. Cooper, A. M. Dubis, P. Summerfelt, D. V. Weinberg, J. E. Kim, K. E. Stepien, J. Carroll, and A. Dubra, “Microscopic Inner Retinal Hyper-Reflective Phenotypes in Retinal and Neurologic Disease,” Invest. Ophthalmol. Vis. Sci. 55(7), 4015–4029 (2014).
[Crossref] [PubMed]

A. Dubra, Y. Sulai, J. L. Norris, R. F. Cooper, A. M. Dubis, D. R. Williams, and J. Carroll, “Noninvasive imaging of the human rod photoreceptor mosaic using a confocal adaptive optics scanning ophthalmoscope,” Biomed. Opt. Express 2(7), 1864–1876 (2011).
[Crossref] [PubMed]

Dubow, M.

M. Dubow, A. Pinhas, N. Shah, R. F. Cooper, A. Gan, R. C. Gentile, V. Hendrix, Y. N. Sulai, J. Carroll, T. Y. P. Chui, J. B. Walsh, R. Weitz, A. Dubra, and R. B. Rosen, “Classification of human retinal microaneurysms using adaptive optics scanning light ophthalmoscope fluorescein angiography,” Invest. Ophthalmol. Vis. Sci. 55(3), 1299–1309 (2014).
[Crossref] [PubMed]

Dubra, A.

D. Scoles, Y. N. Sulai, C. S. Langlo, G. A. Fishman, C. A. Curcio, J. Carroll, and A. Dubra, “In vivo imaging of human cone photoreceptor inner segments,” Invest. Ophthalmol. Vis. Sci. 55(7), 4244–4251 (2014).
[Crossref] [PubMed]

M. Dubow, A. Pinhas, N. Shah, R. F. Cooper, A. Gan, R. C. Gentile, V. Hendrix, Y. N. Sulai, J. Carroll, T. Y. P. Chui, J. B. Walsh, R. Weitz, A. Dubra, and R. B. Rosen, “Classification of human retinal microaneurysms using adaptive optics scanning light ophthalmoscope fluorescein angiography,” Invest. Ophthalmol. Vis. Sci. 55(3), 1299–1309 (2014).
[Crossref] [PubMed]

D. Scoles, B. P. Higgins, R. F. Cooper, A. M. Dubis, P. Summerfelt, D. V. Weinberg, J. E. Kim, K. E. Stepien, J. Carroll, and A. Dubra, “Microscopic Inner Retinal Hyper-Reflective Phenotypes in Retinal and Neurologic Disease,” Invest. Ophthalmol. Vis. Sci. 55(7), 4015–4029 (2014).
[Crossref] [PubMed]

E. A. Rossi, P. Rangel-Fonseca, K. Parkins, W. Fischer, L. R. Latchney, M. A. Folwell, D. R. Williams, A. Dubra, and M. M. Chung, “In vivo imaging of retinal pigment epithelium cells in age related macular degeneration,” Biomed. Opt. Express 4(11), 2527–2539 (2013).
[Crossref] [PubMed]

A. Dubra, Y. Sulai, J. L. Norris, R. F. Cooper, A. M. Dubis, D. R. Williams, and J. Carroll, “Noninvasive imaging of the human rod photoreceptor mosaic using a confocal adaptive optics scanning ophthalmoscope,” Biomed. Opt. Express 2(7), 1864–1876 (2011).
[Crossref] [PubMed]

A. Dubra and Y. Sulai, “Reflective afocal broadband adaptive optics scanning ophthalmoscope,” Biomed. Opt. Express 2(6), 1757–1768 (2011).
[Crossref] [PubMed]

E. A. Rossi, M. Chung, A. Dubra, J. J. Hunter, W. H. Merigan, and D. R. Williams, “Imaging retinal mosaics in the living eye,” Eye (Lond.) 25(3), 301–308 (2011).
[Crossref] [PubMed]

Duncan, J. L.

K. E. Talcott, K. Ratnam, S. M. Sundquist, 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 Factor Treatment,” Invest. Ophthalmol. Vis. Sci. 52(5), 2219–2226 (2011).
[Crossref] [PubMed]

Elsner, A. E.

Ferguson, D.

Ferguson, R. D.

Fischer, W.

Fishman, G. A.

D. Scoles, Y. N. Sulai, C. S. Langlo, G. A. Fishman, C. A. Curcio, J. Carroll, and A. Dubra, “In vivo imaging of human cone photoreceptor inner segments,” Invest. Ophthalmol. Vis. Sci. 55(7), 4244–4251 (2014).
[Crossref] [PubMed]

Folwell, M. A.

Gan, A.

M. Dubow, A. Pinhas, N. Shah, R. F. Cooper, A. Gan, R. C. Gentile, V. Hendrix, Y. N. Sulai, J. Carroll, T. Y. P. Chui, J. B. Walsh, R. Weitz, A. Dubra, and R. B. Rosen, “Classification of human retinal microaneurysms using adaptive optics scanning light ophthalmoscope fluorescein angiography,” Invest. Ophthalmol. Vis. Sci. 55(3), 1299–1309 (2014).
[Crossref] [PubMed]

Gao, W.

Gentile, R. C.

M. Dubow, A. Pinhas, N. Shah, R. F. Cooper, A. Gan, R. C. Gentile, V. Hendrix, Y. N. Sulai, J. Carroll, T. Y. P. Chui, J. B. Walsh, R. Weitz, A. Dubra, and R. B. Rosen, “Classification of human retinal microaneurysms using adaptive optics scanning light ophthalmoscope fluorescein angiography,” Invest. Ophthalmol. Vis. Sci. 55(3), 1299–1309 (2014).
[Crossref] [PubMed]

Girkin, C. A.

Y. Zhang, X. Wang, E. B. Rivero, M. E. Clark, C. D. Witherspoon, R. F. Spaide, C. A. Girkin, C. Owsley, and C. A. Curcio, “Photoreceptor Perturbation Around Subretinal Drusenoid Deposits as Revealed by Adaptive Optics Scanning Laser Ophthalmoscopy,” Am. J. Ophthalmol. 158(3), 584–596 (2014).
[Crossref] [PubMed]

Hammer, D. X.

Hebert, T.

Hendrix, V.

M. Dubow, A. Pinhas, N. Shah, R. F. Cooper, A. Gan, R. C. Gentile, V. Hendrix, Y. N. Sulai, J. Carroll, T. Y. P. Chui, J. B. Walsh, R. Weitz, A. Dubra, and R. B. Rosen, “Classification of human retinal microaneurysms using adaptive optics scanning light ophthalmoscope fluorescein angiography,” Invest. Ophthalmol. Vis. Sci. 55(3), 1299–1309 (2014).
[Crossref] [PubMed]

Higgins, B. P.

D. Scoles, B. P. Higgins, R. F. Cooper, A. M. Dubis, P. Summerfelt, D. V. Weinberg, J. E. Kim, K. E. Stepien, J. Carroll, and A. Dubra, “Microscopic Inner Retinal Hyper-Reflective Phenotypes in Retinal and Neurologic Disease,” Invest. Ophthalmol. Vis. Sci. 55(7), 4015–4029 (2014).
[Crossref] [PubMed]

Hofer, H.

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]

Hunter, J. J.

E. A. Rossi, M. Chung, A. Dubra, J. J. Hunter, W. H. Merigan, and D. R. Williams, “Imaging retinal mosaics in the living eye,” Eye (Lond.) 25(3), 301–308 (2011).
[Crossref] [PubMed]

Iftimia, N. V.

Jonnal, R. S.

Kim, J. E.

D. Scoles, B. P. Higgins, R. F. Cooper, A. M. Dubis, P. Summerfelt, D. V. Weinberg, J. E. Kim, K. E. Stepien, J. Carroll, and A. Dubra, “Microscopic Inner Retinal Hyper-Reflective Phenotypes in Retinal and Neurologic Disease,” Invest. Ophthalmol. Vis. Sci. 55(7), 4015–4029 (2014).
[Crossref] [PubMed]

Langlo, C. S.

D. Scoles, Y. N. Sulai, C. S. Langlo, G. A. Fishman, C. A. Curcio, J. Carroll, and A. Dubra, “In vivo imaging of human cone photoreceptor inner segments,” Invest. Ophthalmol. Vis. Sci. 55(7), 4244–4251 (2014).
[Crossref] [PubMed]

Latchney, L. R.

Lucero, A. S.

K. E. Talcott, K. Ratnam, S. M. Sundquist, 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 Factor Treatment,” Invest. Ophthalmol. Vis. Sci. 52(5), 2219–2226 (2011).
[Crossref] [PubMed]

Lujan, B. J.

K. E. Talcott, K. Ratnam, S. M. Sundquist, 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 Factor Treatment,” Invest. Ophthalmol. Vis. Sci. 52(5), 2219–2226 (2011).
[Crossref] [PubMed]

Merigan, W. H.

E. A. Rossi, M. Chung, A. Dubra, J. J. Hunter, W. H. Merigan, and D. R. Williams, “Imaging retinal mosaics in the living eye,” Eye (Lond.) 25(3), 301–308 (2011).
[Crossref] [PubMed]

Miller, D. T.

Mujat, M.

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]

Norris, J. L.

Nozato, K.

Owsley, C.

Y. Zhang, X. Wang, E. B. Rivero, M. E. Clark, C. D. Witherspoon, R. F. Spaide, C. A. Girkin, C. Owsley, and C. A. Curcio, “Photoreceptor Perturbation Around Subretinal Drusenoid Deposits as Revealed by Adaptive Optics Scanning Laser Ophthalmoscopy,” Am. J. Ophthalmol. 158(3), 584–596 (2014).
[Crossref] [PubMed]

Parkins, K.

Patel, A. H.

Pinhas, A.

M. Dubow, A. Pinhas, N. Shah, R. F. Cooper, A. Gan, R. C. Gentile, V. Hendrix, Y. N. Sulai, J. Carroll, T. Y. P. Chui, J. B. Walsh, R. Weitz, A. Dubra, and R. B. Rosen, “Classification of human retinal microaneurysms using adaptive optics scanning light ophthalmoscope fluorescein angiography,” Invest. Ophthalmol. Vis. Sci. 55(3), 1299–1309 (2014).
[Crossref] [PubMed]

Porco, T. C.

K. E. Talcott, K. Ratnam, S. M. Sundquist, 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 Factor Treatment,” Invest. Ophthalmol. Vis. Sci. 52(5), 2219–2226 (2011).
[Crossref] [PubMed]

Queener, H.

Rangel-Fonseca, P.

Ratnam, K.

K. E. Talcott, K. Ratnam, S. M. Sundquist, 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 Factor Treatment,” Invest. Ophthalmol. Vis. Sci. 52(5), 2219–2226 (2011).
[Crossref] [PubMed]

Rha, J.

Rivero, E. B.

Y. Zhang, X. Wang, E. B. Rivero, M. E. Clark, C. D. Witherspoon, R. F. Spaide, C. A. Girkin, C. Owsley, and C. A. Curcio, “Photoreceptor Perturbation Around Subretinal Drusenoid Deposits as Revealed by Adaptive Optics Scanning Laser Ophthalmoscopy,” Am. J. Ophthalmol. 158(3), 584–596 (2014).
[Crossref] [PubMed]

Romero-Borja, F.

Roorda, A.

Rosen, R. B.

M. Dubow, A. Pinhas, N. Shah, R. F. Cooper, A. Gan, R. C. Gentile, V. Hendrix, Y. N. Sulai, J. Carroll, T. Y. P. Chui, J. B. Walsh, R. Weitz, A. Dubra, and R. B. Rosen, “Classification of human retinal microaneurysms using adaptive optics scanning light ophthalmoscope fluorescein angiography,” Invest. Ophthalmol. Vis. Sci. 55(3), 1299–1309 (2014).
[Crossref] [PubMed]

Rossi, E. A.

Saito, K.

Scoles, D.

D. Scoles, Y. N. Sulai, C. S. Langlo, G. A. Fishman, C. A. Curcio, J. Carroll, and A. Dubra, “In vivo imaging of human cone photoreceptor inner segments,” Invest. Ophthalmol. Vis. Sci. 55(7), 4244–4251 (2014).
[Crossref] [PubMed]

D. Scoles, B. P. Higgins, R. F. Cooper, A. M. Dubis, P. Summerfelt, D. V. Weinberg, J. E. Kim, K. E. Stepien, J. Carroll, and A. Dubra, “Microscopic Inner Retinal Hyper-Reflective Phenotypes in Retinal and Neurologic Disease,” Invest. Ophthalmol. Vis. Sci. 55(7), 4015–4029 (2014).
[Crossref] [PubMed]

Shah, N.

M. Dubow, A. Pinhas, N. Shah, R. F. Cooper, A. Gan, R. C. Gentile, V. Hendrix, Y. N. Sulai, J. Carroll, T. Y. P. Chui, J. B. Walsh, R. Weitz, A. Dubra, and R. B. Rosen, “Classification of human retinal microaneurysms using adaptive optics scanning light ophthalmoscope fluorescein angiography,” Invest. Ophthalmol. Vis. Sci. 55(3), 1299–1309 (2014).
[Crossref] [PubMed]

Sliney, D. H.

Spaide, R. F.

Y. Zhang, X. Wang, E. B. Rivero, M. E. Clark, C. D. Witherspoon, R. F. Spaide, C. A. Girkin, C. Owsley, and C. A. Curcio, “Photoreceptor Perturbation Around Subretinal Drusenoid Deposits as Revealed by Adaptive Optics Scanning Laser Ophthalmoscopy,” Am. J. Ophthalmol. 158(3), 584–596 (2014).
[Crossref] [PubMed]

Stepien, K. E.

D. Scoles, B. P. Higgins, R. F. Cooper, A. M. Dubis, P. Summerfelt, D. V. Weinberg, J. E. Kim, K. E. Stepien, J. Carroll, and A. Dubra, “Microscopic Inner Retinal Hyper-Reflective Phenotypes in Retinal and Neurologic Disease,” Invest. Ophthalmol. Vis. Sci. 55(7), 4015–4029 (2014).
[Crossref] [PubMed]

Sulai, Y.

Sulai, Y. N.

D. Scoles, Y. N. Sulai, C. S. Langlo, G. A. Fishman, C. A. Curcio, J. Carroll, and A. Dubra, “In vivo imaging of human cone photoreceptor inner segments,” Invest. Ophthalmol. Vis. Sci. 55(7), 4244–4251 (2014).
[Crossref] [PubMed]

M. Dubow, A. Pinhas, N. Shah, R. F. Cooper, A. Gan, R. C. Gentile, V. Hendrix, Y. N. Sulai, J. Carroll, T. Y. P. Chui, J. B. Walsh, R. Weitz, A. Dubra, and R. B. Rosen, “Classification of human retinal microaneurysms using adaptive optics scanning light ophthalmoscope fluorescein angiography,” Invest. Ophthalmol. Vis. Sci. 55(3), 1299–1309 (2014).
[Crossref] [PubMed]

Summerfelt, P.

D. Scoles, B. P. Higgins, R. F. Cooper, A. M. Dubis, P. Summerfelt, D. V. Weinberg, J. E. Kim, K. E. Stepien, J. Carroll, and A. Dubra, “Microscopic Inner Retinal Hyper-Reflective Phenotypes in Retinal and Neurologic Disease,” Invest. Ophthalmol. Vis. Sci. 55(7), 4015–4029 (2014).
[Crossref] [PubMed]

Sundquist, S. M.

K. E. Talcott, K. Ratnam, S. M. Sundquist, 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 Factor Treatment,” Invest. Ophthalmol. Vis. Sci. 52(5), 2219–2226 (2011).
[Crossref] [PubMed]

Talcott, K. E.

K. E. Talcott, K. Ratnam, S. M. Sundquist, 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 Factor Treatment,” Invest. Ophthalmol. Vis. Sci. 52(5), 2219–2226 (2011).
[Crossref] [PubMed]

Tao, W.

K. E. Talcott, K. Ratnam, S. M. Sundquist, 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 Factor Treatment,” Invest. Ophthalmol. Vis. Sci. 52(5), 2219–2226 (2011).
[Crossref] [PubMed]

Tumbar, R.

Ustun, T. E.

Walsh, J. B.

M. Dubow, A. Pinhas, N. Shah, R. F. Cooper, A. Gan, R. C. Gentile, V. Hendrix, Y. N. Sulai, J. Carroll, T. Y. P. Chui, J. B. Walsh, R. Weitz, A. Dubra, and R. B. Rosen, “Classification of human retinal microaneurysms using adaptive optics scanning light ophthalmoscope fluorescein angiography,” Invest. Ophthalmol. Vis. Sci. 55(3), 1299–1309 (2014).
[Crossref] [PubMed]

Wang, X.

Y. Zhang, X. Wang, E. B. Rivero, M. E. Clark, C. D. Witherspoon, R. F. Spaide, C. A. Girkin, C. Owsley, and C. A. Curcio, “Photoreceptor Perturbation Around Subretinal Drusenoid Deposits as Revealed by Adaptive Optics Scanning Laser Ophthalmoscopy,” Am. J. Ophthalmol. 158(3), 584–596 (2014).
[Crossref] [PubMed]

Webb, R. H.

Weinberg, D. V.

D. Scoles, B. P. Higgins, R. F. Cooper, A. M. Dubis, P. Summerfelt, D. V. Weinberg, J. E. Kim, K. E. Stepien, J. Carroll, and A. Dubra, “Microscopic Inner Retinal Hyper-Reflective Phenotypes in Retinal and Neurologic Disease,” Invest. Ophthalmol. Vis. Sci. 55(7), 4015–4029 (2014).
[Crossref] [PubMed]

Weitz, R.

M. Dubow, A. Pinhas, N. Shah, R. F. Cooper, A. Gan, R. C. Gentile, V. Hendrix, Y. N. Sulai, J. Carroll, T. Y. P. Chui, J. B. Walsh, R. Weitz, A. Dubra, and R. B. Rosen, “Classification of human retinal microaneurysms using adaptive optics scanning light ophthalmoscope fluorescein angiography,” Invest. Ophthalmol. Vis. Sci. 55(3), 1299–1309 (2014).
[Crossref] [PubMed]

Werner, J. S.

Williams, D. R.

Witherspoon, C. D.

Y. Zhang, X. Wang, E. B. Rivero, M. E. Clark, C. D. Witherspoon, R. F. Spaide, C. A. Girkin, C. Owsley, and C. A. Curcio, “Photoreceptor Perturbation Around Subretinal Drusenoid Deposits as Revealed by Adaptive Optics Scanning Laser Ophthalmoscopy,” Am. J. Ophthalmol. 158(3), 584–596 (2014).
[Crossref] [PubMed]

Yang, Q.

Zawadzki, R. J.

Zhang, J.

Zhang, Y.

Zhong, Z.

Zou, W.

Am. J. Ophthalmol. (1)

Y. Zhang, X. Wang, E. B. Rivero, M. E. Clark, C. D. Witherspoon, R. F. Spaide, C. A. Girkin, C. Owsley, and C. A. Curcio, “Photoreceptor Perturbation Around Subretinal Drusenoid Deposits as Revealed by Adaptive Optics Scanning Laser Ophthalmoscopy,” Am. J. Ophthalmol. 158(3), 584–596 (2014).
[Crossref] [PubMed]

Biomed. Opt. Express (4)

Eye (Lond.) (1)

E. A. Rossi, M. Chung, A. Dubra, J. J. Hunter, W. H. Merigan, and D. R. Williams, “Imaging retinal mosaics in the living eye,” Eye (Lond.) 25(3), 301–308 (2011).
[Crossref] [PubMed]

Invest. Ophthalmol. Vis. Sci. (4)

D. Scoles, Y. N. Sulai, C. S. Langlo, G. A. Fishman, C. A. Curcio, J. Carroll, and A. Dubra, “In vivo imaging of human cone photoreceptor inner segments,” Invest. Ophthalmol. Vis. Sci. 55(7), 4244–4251 (2014).
[Crossref] [PubMed]

K. E. Talcott, K. Ratnam, S. M. Sundquist, 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 Factor Treatment,” Invest. Ophthalmol. Vis. Sci. 52(5), 2219–2226 (2011).
[Crossref] [PubMed]

D. Scoles, B. P. Higgins, R. F. Cooper, A. M. Dubis, P. Summerfelt, D. V. Weinberg, J. E. Kim, K. E. Stepien, J. Carroll, and A. Dubra, “Microscopic Inner Retinal Hyper-Reflective Phenotypes in Retinal and Neurologic Disease,” Invest. Ophthalmol. Vis. Sci. 55(7), 4015–4029 (2014).
[Crossref] [PubMed]

M. Dubow, A. Pinhas, N. Shah, R. F. Cooper, A. Gan, R. C. Gentile, V. Hendrix, Y. N. Sulai, J. Carroll, T. Y. P. Chui, J. B. Walsh, R. Weitz, A. Dubra, and R. B. Rosen, “Classification of human retinal microaneurysms using adaptive optics scanning light ophthalmoscope fluorescein angiography,” Invest. Ophthalmol. Vis. Sci. 55(3), 1299–1309 (2014).
[Crossref] [PubMed]

J. Opt. Soc. Am. A (3)

Opt. Express (4)

Proc. Natl. Acad. Sci. U.S.A. (1)

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]

Vision Res. (1)

D. R. Williams, “Imaging single cells in the living retina,” Vision Res. 51(13), 1379–1396 (2011).
[Crossref] [PubMed]

Other (4)

Q. Wang, W. S. Tuten, B. Lujan, J. Holland, P. S. Bernstein, S. Schwartz, J. L. Duncan, and A. Roorda, “Adaptive optics microperimetry and OCT images in macular telangiectasia type 2 retinal lesions show preserved function and recovery of cone visibility,” IOVS IOVS–14–15576 (2015).

E. A. Rossi and J. J. Hunter, Rochester Exposure Limit (REL) Calculator (Version 1.2) [Computer Software] (University of Rochester, 2013).

American National Standards Institute, American National Standard for Safe Use of Lasers (ANSI, 2007).

S. B. Stevenson and A. Roorda, “Correcting for miniature eye movements in high resolution scanning laser ophthalmoscopy,” in Ophthalmic Technologies XV,Proceedings of SPIE, F. Manns, P. G. Söderberg, A. Ho, B. E. Stuck, and M. Belkin, eds. (SPIE, Bellingham, WA, 2005), Vol. 5688, pp. 145–151.
[Crossref]

Supplementary Material (4)

» Media 1: MPG (1496 KB)     
» Media 2: MPG (1120 KB)     
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Figures (14)

Fig. 1
Fig. 1

Schematic diagram of the control blocks of the multi-scale stabilization engine. Solid red line denotes AOSLO signal path. Dashed dark red line is WFSLO signal path, thin blue line shows fixation path and thick gray line denotes pupil camera signal path. As can be seen here, WFSLO driven stabilization runs in open loop with the action of TTM2 not being ‘seen’ by the WFSLO system while TTM1 runs in closed loop where the AOSLO image captures the action of both TTMs.

Fig. 2
Fig. 2

Simplified schematic diagram of the flattened layout of the integrated dual FOV optical system. Shaded areas represent regions where the optics are folded in 3D. The WFSLO and the AOSLO steering and stabilization sub-system are in a two-layer structure; the optical beams are combined using a joint mirror and a dichroic mirror (not shown here, see Fig. 4). All pupil conjugates are labelled in bold fonts. Abbreviations are as follows: 90/10, beam splitter; DM, deformable mirror; FM, flat mirror; PMT, photo-multiplier tube; RS, resonant scanner; SHWS, Shack-Hartmann wavefront sensor; SM, steering mirror; SPH, spherical mirror; TTM, tip-tilt mirror.

Fig. 3
Fig. 3

Detailed view of the complex layout of the steering and WFSLO driven sub-system (upper right shaded portion of Fig. 2). Abbreviations are as follows: dm, dichroic mirror; FM, flat mirror; GM, galvo mirror; JM, joint mirror; L, lens; RS, resonant scanner; SM, steering mirror; SPH, spherical mirror; TTM, tip-tilt mirror.

Fig. 4
Fig. 4

A large FOV image is used as the reference frame for a narrow target image (brighter narrow image in foreground) for WFSLO eye tracking. A narrow target image increases the frame rate to ~51 fps during WFSLO driven optical stabilization. The narrow target image can be placed anywhere in the large reference image FOV, allowing target images to be optimized for cross-correlation by selecting an area with high contrast retinal features. Scale bar is 500μm.

Fig. 5
Fig. 5

Motion artifacts (a) appear in some stabilized images due to unsuccessful cross-correlation between the reference (b) and target (c) images. Yellow outline in (c) denotes area shown in (a). After a second round of cross-correlation, motion artifacts are cropped out, and the final image (d) is used for real-time averaging. Scale bars are 50 µm.

Fig. 6
Fig. 6

Integrated steering and stabilization allows a target area (dashed rectangle) in the WFSLO image (right) to be imaged with AOSLO (left) with minimal overlap between adjacent fields (e.g. areas as 1, 2, 3). Scale bar for AOSLO is 50 um and scale bar for WFSLO image is 500 um.

Fig. 7
Fig. 7

The resolution of the AOSLO was not compromised with the additional features we have added, as we maintained the visibility of not only the foveal cones (left) but also rods in the periphery (right). Scale bars are 20 µm (left) and 10 µm (right).

Fig. 8
Fig. 8

Simulations of the AOSLO raster at the most extreme steering angles demonstrate the field distortion and raster rotation induced by steering. These simulations were in line with empirical results.

Fig. 9
Fig. 9

Each stage of motion compensation reduces the amplitude of residual motion. Note that each stage is shown running consecutively here for illustrative purposes but in practice all three stages run simultaneously. White squares in left image and center images denote areas of images shown to the right. Scale bars for the images are (from left to right): 25 µm, 5 µm, and 1 µm.

Fig. 10
Fig. 10

Performance for each successive stage of eye motion compensation. Diamonds: raw motion; squares: WFSLO driven optical stabilization only; triangles: WFSLO & AOSLO driven optical stabilization combined; circles: WFSLO & AOSLO driven optical stabilization combined with digital registration. The error bars denote standard deviation.

Fig. 11
Fig. 11

A stitched 8° × 4° montage (cropped from an imaging area of 8° × 6°) from an AMD patient imaged with the protocol described in section 2.8 (see Fig. 6).

Fig. 12
Fig. 12

Simplified schematic diagrams for two steering optical solutions: a finite pupil conjugate design (A) and an infinite pupil conjugate design (B).

Fig. 13
Fig. 13

Block diagram of a completely closed-loop multi-scale optical stabilization system. Solid arrows are optical paths and dashed arrows are electronic paths. ( + ) denotes a simple digital or analog signal addition.

Fig. 14
Fig. 14

A large latency is involved in the existing open-loop WFSLO driven optical stabilization system when attempting to compensate for a microsaccade.

Tables (1)

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Table 1 Functionality and Specifications of Imaging Sub-systems

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