Abstract

Adaptive optics scanning laser ophthalmoscopy (AOSLO) has enabled in vivo visualization and enhanced understanding of retinal structure and function. Current generation AOSLOs have a large footprint and are mainly limited to imaging cooperative adult subjects. To extend the application of AOSLO to new patient populations, we have designed, to the best of our knowledge, the first portable handheld AOSLO (HAOSLO) system. By incorporating a novel computational wavefront sensorless AO algorithm and custom optics, we have miniaturized our HAOSLO to weigh less than 200 g. HAOSLO imaged the cones closest to the fovea with a handheld probe in adults and captured, to the best of our knowledge, the first AO-enhanced image of cones in infants.

© 2018 Optical Society of America under the terms of the OSA Open Access Publishing Agreement

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2017 (5)

S. Marcos, J. S. Werner, S. A. Burns, W. H. Merigan, P. Artal, D. A. Atchison, K. M. Hampson, R. Legras, L. Lundstrom, G. Yoon, J. Carroll, S. S. Choi, N. Doble, A. M. Dubis, A. Dubra, A. Elsner, R. Jonnal, D. T. Miller, M. Paques, H. E. Smithson, L. K. Young, Y. Zhang, M. Campbell, J. Hunter, A. Metha, G. Palczewska, J. Schallek, and L. C. Sincich, “Vision science and adaptive optics, the state of the field,” Vis. Res. 132, 3–33 (2017).
[Crossref]

E. A. Rossi, C. E. Granger, R. Sharma, Q. Yang, K. Saito, C. Schwarz, S. Walters, K. Nozato, J. Zhang, T. Kawakami, W. Fischer, L. R. Latchney, J. J. Hunter, M. M. Chung, and D. R. Williams, “Imaging individual neurons in the retinal ganglion cell layer of the living eye,” Proc. Natl. Acad. Sci. USA 114, 586–591 (2017).
[Crossref]

Z. Liu, K. Kurokawa, F. Zhang, J. J. Lee, and D. T. Miller, “Imaging and quantifying ganglion cells and other transparent neurons in the living human retina,” Proc. Natl. Acad. Sci. USA 114, 12803–12808 (2017).
[Crossref]

J. Polans, B. Keller, O. M. Carrasco-Zevallos, F. LaRocca, E. Cole, H. E. Whitson, E. M. Lad, S. Farsiu, and J. A. Izatt, “Wide-field retinal optical coherence tomography with wavefront sensorless adaptive optics for enhanced imaging of targeted regions,” Biomed. Opt. Express 8, 16–37 (2017).
[Crossref]

J. Polans, D. Cunefare, E. Cole, B. Keller, P. S. Mettu, S. W. Cousins, M. J. Allingham, J. A. Izatt, and S. Farsiu, “Enhanced visualization of peripheral retinal vasculature with wavefront sensorless adaptive optics optical coherence tomography angiography in diabetic patients,” Opt. Lett. 42, 17–20 (2017).
[Crossref]

2016 (2)

H. P. N. Scholl, R. W. Strauss, M. S. Singh, D. Dalkara, B. Roska, S. Picaud, and J.-A. Sahel, “Emerging therapies for inherited retinal degeneration,” Sci. Trans. Med. 8, 368rv6 (2016).
[Crossref]

F. LaRocca, D. Nankivil, T. DuBose, C. A. Toth, S. Farsiu, and J. A. Izatt, “In vivo cellular-resolution retinal imaging in infants and children using an ultracompact handheld probe,” Nat. Photonics 10, 580–584 (2016).
[Crossref]

2015 (4)

H. Song, E. A. Rossi, L. Latchney, A. Bessette, E. Stone, J. J. Hunter, D. R. Williams, and M. M. Chung, “Cone and rod loss in Stargardt disease revealed by adaptive optics scanning light ophthalmoscopy,” JAMA Ophthalmol. 133, 1198–1203 (2015).
[Crossref]

M. Skorsetz, P. Artal, and J. M. Bueno, “Performance evaluation of a sensorless adaptive optics multiphoton microscope,” J. Microsc. 261, 249–258 (2015).
[Crossref]

K. S. K. Wong, Y. Jian, M. Cua, S. Bonora, R. J. Zawadzki, and M. V. Sarunic, “In vivo imaging of human photoreceptor mosaic with wavefront sensorless adaptive optics optical coherence tomography,” Biomed. Opt. Express 6, 580–590 (2015).
[Crossref]

X. Zhou, P. Bedggood, B. Bui, C. T. O. Nguyen, Z. He, and A. Metha, “Contrast-based sensorless adaptive optics for retinal imaging,” Biomed. Opt. Express 6, 3577–3595 (2015).
[Crossref]

2014 (3)

Y. N. Sulai and A. Dubra, “Non-common path aberration correction in an adaptive optics scanning ophthalmoscope,” Biomed. Opt. Express 5, 3059–3073 (2014).
[Crossref]

F. LaRocca, D. Nankivil, S. Farsiu, and J. A. Izatt, “True color scanning laser ophthalmoscopy and optical coherence tomography handheld probe,” Biomed. Opt. Express 5, 3204–3216 (2014).
[Crossref]

W. A. Beltran, A. V. Cideciyan, K. E. Guziewicz, S. Iwabe, M. Swider, E. M. Scott, S. V. Savina, G. Ruthel, F. Stefano, L. Zhang, R. Zorger, A. Sumaroka, S. G. Jacobson, and G. D. Aguirre, “Canine retina has a primate fovea-like bouquet of cone photoreceptors which is affected by inherited macular degenerations,” PLoS ONE 9, e90390 (2014).
[Crossref]

2013 (4)

2012 (3)

J. Tam, K. P. Dhamdhere, P. Tiruveedhula, B. J. Lujan, R. N. Johnson, M. A. Bearse, A. J. Adams, and A. Roorda, “Subclinical capillary changes in non proliferative diabetic retinopathy,” Optom. Vis. Sci. 89, E692–E703 (2012).
[Crossref]

A. Boretsky, F. Khan, G. Burnett, D. X. Hammer, R. D. Ferguson, F. van Kuijk, and M. Motamedi, “In vivo imaging of photoreceptor disruption associated with age-related macular degeneration: a pilot study,” Lasers Surg. Med. 44, 603–610 (2012).
[Crossref]

W. A. Beltran, A. V. Cideciyan, A. S. Lewin, S. Iwabe, H. Khanna, A. Sumaroka, V. A. Chiodo, D. S. Fajardo, A. J. Román, W.-T. Deng, M. Swider, T. S. Alemán, S. L. Boye, S. Genini, A. Swaroop, W. W. Hauswirth, S. G. Jacobson, and G. D. Aguirre, “Gene therapy rescues photoreceptor blindness in dogs and paves the way for treating human X-linked retinitis pigmentosa,” Proc. Natl. Acad. Sci. USA 109, 2132–2137 (2012).
[Crossref]

2011 (6)

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. Visual Sci. 52, 2219–2226 (2011).
[Crossref]

M. A. Genead, G. A. Fishman, J. Rha, A. M. Dubis, D. M. O. Bonci, A. Dubra, E. M. Stone, M. Neitz, and J. Carroll, “Photoreceptor structure and function in patients with congenital achromatopsia,” Invest. Ophthalmol. Visual Sci. 52, 7298–7308 (2011).
[Crossref]

J. Tam, K. P. Dhamdhere, P. Tiruveedhula, S. Manzanera, S. Barez, M. A. Bearse, A. J. Adams, and A. Roorda, “Disruption of the retinal parafoveal capillary network in type 2 diabetes before the onset of diabetic retinopathy,” Invest. Ophthalmol. Visual Sci. 52, 9257–9266 (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]

H. Hofer, N. Sredar, H. Queener, C. Li, and J. Porter, “Wavefront sensorless adaptive optics ophthalmoscopy in the human eye,” Opt. Express 19, 14160–14171 (2011).
[Crossref]

D. E. Milkie, E. Betzig, and N. Ji, “Pupil-segmentation-based adaptive optical microscopy with full-pupil illumination,” Opt. Lett. 36, 4206–4208 (2011).
[Crossref]

2010 (2)

P. Bedggood and A. Metha, “System design considerations to improve isoplanatism for adaptive optics retinal imaging,” J. Opt. Soc. Am. A 27, A37–A47 (2010).
[Crossref]

N. Ji, D. E. Milkie, and E. Betzig, “Adaptive optics via pupil segmentation for high-resolution imaging in biological tissues,” Nat. Methods 7, 141–147 (2010).
[Crossref]

2009 (1)

2008 (3)

D. Débarre, E. J. Botcherby, M. J. Booth, and T. Wilson, “Adaptive optics for structured illumination microscopy,” Opt. Express 16, 9290–9305 (2008).
[Crossref]

U. Erdem, O. Muftuoglu, F. C. Gundogan, G. Sobaci, and A. Bayer, “Pupil center shift relative to the coaxially sighted corneal light reflex under natural and pharmacologically dilated conditions,” J. Refractive Surg. 24, 530–538 (2008).

P. Bedggood, M. Daaboul, R. A. Ashman, G. G. Smith, and A. Metha, “Characteristics of the human isoplanatic patch and implications for adaptive optics retinal imaging,” J. Biomed. Opt. 13, 024008 (2008).
[Crossref]

2007 (4)

2006 (2)

2005 (2)

D. A. Atchison and G. Smith, “Chromatic dispersions of the ocular media of human eyes,” J. Opt. Soc. Am. A 22, 29–37 (2005).
[Crossref]

A. J. Wright, D. Burns, B. A. Patterson, S. P. Poland, G. J. Valentine, and J. M. Girkin, “Exploration of the optimisation algorithms used in the implementation of adaptive optics in confocal and multiphoton microscopy,” Microsc. Res. Tech. 67, 36–44 (2005).
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2004 (3)

E. Theofanidou, L. Wilson, W. J. Hossack, and J. Arlt, “Spherical aberration correction for optical tweezers,” Opt. Commun. 236, 145–150 (2004).
[Crossref]

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

P. Villoresi, S. Bonora, M. Pascolini, L. Poletto, G. Tondello, C. Vozzi, M. Nisoli, G. Sansone, S. Stagira, and S. De Silvestri, “Optimization of high-order harmonic generation by adaptive control of a sub-10-fs pulse wave front,” Opt. Lett. 29, 207–209 (2004).
[Crossref]

2003 (3)

2002 (6)

F. Gonte, A. Courteville, and R. Dandliker, “Optimization of single-mode fiber coupling efficiency with an adaptive membrane mirror,” Opt. Eng. 41, 1073–1076 (2002).
[Crossref]

L. Sherman, J. Ye, O. Albert, and T. Norris, “Adaptive correction of depth-induced aberrations in multiphoton scanning microscopy using a deformable mirror,” J. Microsc. 206, 65–71 (2002).
[Crossref]

C. MacLachlan and H. C. Howland, “Normal values and standard deviations for pupil diameter and interpupillary distance in subjects aged 1 month to 19 years,” Ophthalmic Physiol. Opt. 22, 175–182 (2002).
[Crossref]

Y. Yang, K. Thompson, and S. A. Burns, “Pupil location under mesopic, photopic, and pharmacologically dilated conditions,” Invest. Ophthalmol. Visual Sci. 43, 2508–2512 (2002).

A. Roorda, F. Romero-Borja, W. J. Donnelly, H. Queener, T. J. Hebert, and M. C. W. Campbell, “Adaptive optics scanning laser ophthalmoscopy,” Opt. Express 10, 405–412 (2002).
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W. Lubeigt, G. Valentine, J. Girkin, E. Bente, and D. Burns, “Active transverse mode control and optimisation of an all-solid-state laser using an intracavity adaptive-optic mirror,” Opt. Express 10, 550–555 (2002).
[Crossref]

2000 (1)

1999 (1)

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

1998 (1)

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

1997 (3)

1996 (1)

1990 (1)

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

1977 (1)

1974 (1)

Adams, A. J.

J. Tam, K. P. Dhamdhere, P. Tiruveedhula, B. J. Lujan, R. N. Johnson, M. A. Bearse, A. J. Adams, and A. Roorda, “Subclinical capillary changes in non proliferative diabetic retinopathy,” Optom. Vis. Sci. 89, E692–E703 (2012).
[Crossref]

J. Tam, K. P. Dhamdhere, P. Tiruveedhula, S. Manzanera, S. Barez, M. A. Bearse, A. J. Adams, and A. Roorda, “Disruption of the retinal parafoveal capillary network in type 2 diabetes before the onset of diabetic retinopathy,” Invest. Ophthalmol. Visual Sci. 52, 9257–9266 (2011).
[Crossref]

Adler, J.

Aguirre, G. D.

W. A. Beltran, A. V. Cideciyan, K. E. Guziewicz, S. Iwabe, M. Swider, E. M. Scott, S. V. Savina, G. Ruthel, F. Stefano, L. Zhang, R. Zorger, A. Sumaroka, S. G. Jacobson, and G. D. Aguirre, “Canine retina has a primate fovea-like bouquet of cone photoreceptors which is affected by inherited macular degenerations,” PLoS ONE 9, e90390 (2014).
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W. A. Beltran, A. V. Cideciyan, A. S. Lewin, S. Iwabe, H. Khanna, A. Sumaroka, V. A. Chiodo, D. S. Fajardo, A. J. Román, W.-T. Deng, M. Swider, T. S. Alemán, S. L. Boye, S. Genini, A. Swaroop, W. W. Hauswirth, S. G. Jacobson, and G. D. Aguirre, “Gene therapy rescues photoreceptor blindness in dogs and paves the way for treating human X-linked retinitis pigmentosa,” Proc. Natl. Acad. Sci. USA 109, 2132–2137 (2012).
[Crossref]

Albert, O.

L. Sherman, J. Ye, O. Albert, and T. Norris, “Adaptive correction of depth-induced aberrations in multiphoton scanning microscopy using a deformable mirror,” J. Microsc. 206, 65–71 (2002).
[Crossref]

O. Albert, L. Sherman, G. Mourou, T. Norris, and G. Vdovin, “Smart microscope: an adaptive optics learning system for aberration correction in multiphoton confocal microscopy,” Opt. Lett. 25, 52–54 (2000).
[Crossref]

Alcelik, T.

O. Elibol, T. Alcelik, N. Yuksel, and Y. Caglar, “The influence of drop size of cyclopentolate, phenylephrine and tropicamide on pupil dilatation and systemic side effects in infants,” Acta Ophthalmol. Scand. 75, 178–180 (1997).

Alemán, T. S.

W. A. Beltran, A. V. Cideciyan, A. S. Lewin, S. Iwabe, H. Khanna, A. Sumaroka, V. A. Chiodo, D. S. Fajardo, A. J. Román, W.-T. Deng, M. Swider, T. S. Alemán, S. L. Boye, S. Genini, A. Swaroop, W. W. Hauswirth, S. G. Jacobson, and G. D. Aguirre, “Gene therapy rescues photoreceptor blindness in dogs and paves the way for treating human X-linked retinitis pigmentosa,” Proc. Natl. Acad. Sci. USA 109, 2132–2137 (2012).
[Crossref]

Allingham, M. J.

Arlt, J.

E. Theofanidou, L. Wilson, W. J. Hossack, and J. Arlt, “Spherical aberration correction for optical tweezers,” Opt. Commun. 236, 145–150 (2004).
[Crossref]

Artal, P.

S. Marcos, J. S. Werner, S. A. Burns, W. H. Merigan, P. Artal, D. A. Atchison, K. M. Hampson, R. Legras, L. Lundstrom, G. Yoon, J. Carroll, S. S. Choi, N. Doble, A. M. Dubis, A. Dubra, A. Elsner, R. Jonnal, D. T. Miller, M. Paques, H. E. Smithson, L. K. Young, Y. Zhang, M. Campbell, J. Hunter, A. Metha, G. Palczewska, J. Schallek, and L. C. Sincich, “Vision science and adaptive optics, the state of the field,” Vis. Res. 132, 3–33 (2017).
[Crossref]

M. Skorsetz, P. Artal, and J. M. Bueno, “Performance evaluation of a sensorless adaptive optics multiphoton microscope,” J. Microsc. 261, 249–258 (2015).
[Crossref]

Ashman, R. A.

P. Bedggood, M. Daaboul, R. A. Ashman, G. G. Smith, and A. Metha, “Characteristics of the human isoplanatic patch and implications for adaptive optics retinal imaging,” J. Biomed. Opt. 13, 024008 (2008).
[Crossref]

Atchison, D. A.

S. Marcos, J. S. Werner, S. A. Burns, W. H. Merigan, P. Artal, D. A. Atchison, K. M. Hampson, R. Legras, L. Lundstrom, G. Yoon, J. Carroll, S. S. Choi, N. Doble, A. M. Dubis, A. Dubra, A. Elsner, R. Jonnal, D. T. Miller, M. Paques, H. E. Smithson, L. K. Young, Y. Zhang, M. Campbell, J. Hunter, A. Metha, G. Palczewska, J. Schallek, and L. C. Sincich, “Vision science and adaptive optics, the state of the field,” Vis. Res. 132, 3–33 (2017).
[Crossref]

D. A. Atchison and G. Smith, “Chromatic dispersions of the ocular media of human eyes,” J. Opt. Soc. Am. A 22, 29–37 (2005).
[Crossref]

Barez, S.

J. Tam, K. P. Dhamdhere, P. Tiruveedhula, S. Manzanera, S. Barez, M. A. Bearse, A. J. Adams, and A. Roorda, “Disruption of the retinal parafoveal capillary network in type 2 diabetes before the onset of diabetic retinopathy,” Invest. Ophthalmol. Visual Sci. 52, 9257–9266 (2011).
[Crossref]

Bayer, A.

U. Erdem, O. Muftuoglu, F. C. Gundogan, G. Sobaci, and A. Bayer, “Pupil center shift relative to the coaxially sighted corneal light reflex under natural and pharmacologically dilated conditions,” J. Refractive Surg. 24, 530–538 (2008).

Bearse, M. A.

J. Tam, K. P. Dhamdhere, P. Tiruveedhula, B. J. Lujan, R. N. Johnson, M. A. Bearse, A. J. Adams, and A. Roorda, “Subclinical capillary changes in non proliferative diabetic retinopathy,” Optom. Vis. Sci. 89, E692–E703 (2012).
[Crossref]

J. Tam, K. P. Dhamdhere, P. Tiruveedhula, S. Manzanera, S. Barez, M. A. Bearse, A. J. Adams, and A. Roorda, “Disruption of the retinal parafoveal capillary network in type 2 diabetes before the onset of diabetic retinopathy,” Invest. Ophthalmol. Visual Sci. 52, 9257–9266 (2011).
[Crossref]

Bedggood, P.

Beltran, W. A.

W. A. Beltran, A. V. Cideciyan, K. E. Guziewicz, S. Iwabe, M. Swider, E. M. Scott, S. V. Savina, G. Ruthel, F. Stefano, L. Zhang, R. Zorger, A. Sumaroka, S. G. Jacobson, and G. D. Aguirre, “Canine retina has a primate fovea-like bouquet of cone photoreceptors which is affected by inherited macular degenerations,” PLoS ONE 9, e90390 (2014).
[Crossref]

W. A. Beltran, A. V. Cideciyan, A. S. Lewin, S. Iwabe, H. Khanna, A. Sumaroka, V. A. Chiodo, D. S. Fajardo, A. J. Román, W.-T. Deng, M. Swider, T. S. Alemán, S. L. Boye, S. Genini, A. Swaroop, W. W. Hauswirth, S. G. Jacobson, and G. D. Aguirre, “Gene therapy rescues photoreceptor blindness in dogs and paves the way for treating human X-linked retinitis pigmentosa,” Proc. Natl. Acad. Sci. USA 109, 2132–2137 (2012).
[Crossref]

Bente, E.

Bessette, A.

H. Song, E. A. Rossi, L. Latchney, A. Bessette, E. Stone, J. J. Hunter, D. R. Williams, and M. M. Chung, “Cone and rod loss in Stargardt disease revealed by adaptive optics scanning light ophthalmoscopy,” JAMA Ophthalmol. 133, 1198–1203 (2015).
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Betzig, E.

D. E. Milkie, E. Betzig, and N. Ji, “Pupil-segmentation-based adaptive optical microscopy with full-pupil illumination,” Opt. Lett. 36, 4206–4208 (2011).
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N. Ji, D. E. Milkie, and E. Betzig, “Adaptive optics via pupil segmentation for high-resolution imaging in biological tissues,” Nat. Methods 7, 141–147 (2010).
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Bonci, D. M. O.

M. A. Genead, G. A. Fishman, J. Rha, A. M. Dubis, D. M. O. Bonci, A. Dubra, E. M. Stone, M. Neitz, and J. Carroll, “Photoreceptor structure and function in patients with congenital achromatopsia,” Invest. Ophthalmol. Visual Sci. 52, 7298–7308 (2011).
[Crossref]

Bonora, S.

Booth, M.

Booth, M. J.

Boretsky, A.

A. Boretsky, F. Khan, G. Burnett, D. X. Hammer, R. D. Ferguson, F. van Kuijk, and M. Motamedi, “In vivo imaging of photoreceptor disruption associated with age-related macular degeneration: a pilot study,” Lasers Surg. Med. 44, 603–610 (2012).
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Botcherby, E. J.

Boye, S. L.

W. A. Beltran, A. V. Cideciyan, A. S. Lewin, S. Iwabe, H. Khanna, A. Sumaroka, V. A. Chiodo, D. S. Fajardo, A. J. Román, W.-T. Deng, M. Swider, T. S. Alemán, S. L. Boye, S. Genini, A. Swaroop, W. W. Hauswirth, S. G. Jacobson, and G. D. Aguirre, “Gene therapy rescues photoreceptor blindness in dogs and paves the way for treating human X-linked retinitis pigmentosa,” Proc. Natl. Acad. Sci. USA 109, 2132–2137 (2012).
[Crossref]

Bueno, J. M.

M. Skorsetz, P. Artal, and J. M. Bueno, “Performance evaluation of a sensorless adaptive optics multiphoton microscope,” J. Microsc. 261, 249–258 (2015).
[Crossref]

Buffington, A.

Bui, B.

Burnett, G.

A. Boretsky, F. Khan, G. Burnett, D. X. Hammer, R. D. Ferguson, F. van Kuijk, and M. Motamedi, “In vivo imaging of photoreceptor disruption associated with age-related macular degeneration: a pilot study,” Lasers Surg. Med. 44, 603–610 (2012).
[Crossref]

Burns, D.

Burns, S. A.

S. Marcos, J. S. Werner, S. A. Burns, W. H. Merigan, P. Artal, D. A. Atchison, K. M. Hampson, R. Legras, L. Lundstrom, G. Yoon, J. Carroll, S. S. Choi, N. Doble, A. M. Dubis, A. Dubra, A. Elsner, R. Jonnal, D. T. Miller, M. Paques, H. E. Smithson, L. K. Young, Y. Zhang, M. Campbell, J. Hunter, A. Metha, G. Palczewska, J. Schallek, and L. C. Sincich, “Vision science and adaptive optics, the state of the field,” Vis. Res. 132, 3–33 (2017).
[Crossref]

Y. Yang, K. Thompson, and S. A. Burns, “Pupil location under mesopic, photopic, and pharmacologically dilated conditions,” Invest. Ophthalmol. Visual Sci. 43, 2508–2512 (2002).

Caglar, Y.

O. Elibol, T. Alcelik, N. Yuksel, and Y. Caglar, “The influence of drop size of cyclopentolate, phenylephrine and tropicamide on pupil dilatation and systemic side effects in infants,” Acta Ophthalmol. Scand. 75, 178–180 (1997).

Campbell, M.

S. Marcos, J. S. Werner, S. A. Burns, W. H. Merigan, P. Artal, D. A. Atchison, K. M. Hampson, R. Legras, L. Lundstrom, G. Yoon, J. Carroll, S. S. Choi, N. Doble, A. M. Dubis, A. Dubra, A. Elsner, R. Jonnal, D. T. Miller, M. Paques, H. E. Smithson, L. K. Young, Y. Zhang, M. Campbell, J. Hunter, A. Metha, G. Palczewska, J. Schallek, and L. C. Sincich, “Vision science and adaptive optics, the state of the field,” Vis. Res. 132, 3–33 (2017).
[Crossref]

Campbell, M. C. W.

Carhart, G.

Carrasco-Zevallos, O. M.

Carroll, J.

S. Marcos, J. S. Werner, S. A. Burns, W. H. Merigan, P. Artal, D. A. Atchison, K. M. Hampson, R. Legras, L. Lundstrom, G. Yoon, J. Carroll, S. S. Choi, N. Doble, A. M. Dubis, A. Dubra, A. Elsner, R. Jonnal, D. T. Miller, M. Paques, H. E. Smithson, L. K. Young, Y. Zhang, M. Campbell, J. Hunter, A. Metha, G. Palczewska, J. Schallek, and L. C. Sincich, “Vision science and adaptive optics, the state of the field,” Vis. Res. 132, 3–33 (2017).
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S. O. Hansen, R. F. Cooper, A. Dubra, J. Carroll, and D. V. Weinberg, “Selective cone photoreceptor injury in acute macular neuroretinopathy,” Retina 33, 1650–1658 (2013).
[Crossref]

M. A. Genead, G. A. Fishman, J. Rha, A. M. Dubis, D. M. O. Bonci, A. Dubra, E. M. Stone, M. Neitz, and J. Carroll, “Photoreceptor structure and function in patients with congenital achromatopsia,” Invest. Ophthalmol. Visual Sci. 52, 7298–7308 (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]

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. USA 101, 8461–8466 (2004).
[Crossref]

Chiodo, V. A.

W. A. Beltran, A. V. Cideciyan, A. S. Lewin, S. Iwabe, H. Khanna, A. Sumaroka, V. A. Chiodo, D. S. Fajardo, A. J. Román, W.-T. Deng, M. Swider, T. S. Alemán, S. L. Boye, S. Genini, A. Swaroop, W. W. Hauswirth, S. G. Jacobson, and G. D. Aguirre, “Gene therapy rescues photoreceptor blindness in dogs and paves the way for treating human X-linked retinitis pigmentosa,” Proc. Natl. Acad. Sci. USA 109, 2132–2137 (2012).
[Crossref]

Choi, S. S.

S. Marcos, J. S. Werner, S. A. Burns, W. H. Merigan, P. Artal, D. A. Atchison, K. M. Hampson, R. Legras, L. Lundstrom, G. Yoon, J. Carroll, S. S. Choi, N. Doble, A. M. Dubis, A. Dubra, A. Elsner, R. Jonnal, D. T. Miller, M. Paques, H. E. Smithson, L. K. Young, Y. Zhang, M. Campbell, J. Hunter, A. Metha, G. Palczewska, J. Schallek, and L. C. Sincich, “Vision science and adaptive optics, the state of the field,” Vis. Res. 132, 3–33 (2017).
[Crossref]

Chung, M. M.

E. A. Rossi, C. E. Granger, R. Sharma, Q. Yang, K. Saito, C. Schwarz, S. Walters, K. Nozato, J. Zhang, T. Kawakami, W. Fischer, L. R. Latchney, J. J. Hunter, M. M. Chung, and D. R. Williams, “Imaging individual neurons in the retinal ganglion cell layer of the living eye,” Proc. Natl. Acad. Sci. USA 114, 586–591 (2017).
[Crossref]

H. Song, E. A. Rossi, L. Latchney, A. Bessette, E. Stone, J. J. Hunter, D. R. Williams, and M. M. Chung, “Cone and rod loss in Stargardt disease revealed by adaptive optics scanning light ophthalmoscopy,” JAMA Ophthalmol. 133, 1198–1203 (2015).
[Crossref]

Cideciyan, A. V.

W. A. Beltran, A. V. Cideciyan, K. E. Guziewicz, S. Iwabe, M. Swider, E. M. Scott, S. V. Savina, G. Ruthel, F. Stefano, L. Zhang, R. Zorger, A. Sumaroka, S. G. Jacobson, and G. D. Aguirre, “Canine retina has a primate fovea-like bouquet of cone photoreceptors which is affected by inherited macular degenerations,” PLoS ONE 9, e90390 (2014).
[Crossref]

W. A. Beltran, A. V. Cideciyan, A. S. Lewin, S. Iwabe, H. Khanna, A. Sumaroka, V. A. Chiodo, D. S. Fajardo, A. J. Román, W.-T. Deng, M. Swider, T. S. Alemán, S. L. Boye, S. Genini, A. Swaroop, W. W. Hauswirth, S. G. Jacobson, and G. D. Aguirre, “Gene therapy rescues photoreceptor blindness in dogs and paves the way for treating human X-linked retinitis pigmentosa,” Proc. Natl. Acad. Sci. USA 109, 2132–2137 (2012).
[Crossref]

Cole, E.

Cooper, R. F.

Courteville, A.

F. Gonte, A. Courteville, and R. Dandliker, “Optimization of single-mode fiber coupling efficiency with an adaptive membrane mirror,” Opt. Eng. 41, 1073–1076 (2002).
[Crossref]

Cousins, S. W.

Crawford, F.

Cua, M.

Cunefare, D.

Curcio, C. A.

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

Da Deppo, V.

Daaboul, M.

P. Bedggood, M. Daaboul, R. A. Ashman, G. G. Smith, and A. Metha, “Characteristics of the human isoplanatic patch and implications for adaptive optics retinal imaging,” J. Biomed. Opt. 13, 024008 (2008).
[Crossref]

Dainty, C.

Dalkara, D.

H. P. N. Scholl, R. W. Strauss, M. S. Singh, D. Dalkara, B. Roska, S. Picaud, and J.-A. Sahel, “Emerging therapies for inherited retinal degeneration,” Sci. Trans. Med. 8, 368rv6 (2016).
[Crossref]

Dandliker, R.

F. Gonte, A. Courteville, and R. Dandliker, “Optimization of single-mode fiber coupling efficiency with an adaptive membrane mirror,” Opt. Eng. 41, 1073–1076 (2002).
[Crossref]

De Silvestri, S.

Débarre, D.

Deng, W.-T.

W. A. Beltran, A. V. Cideciyan, A. S. Lewin, S. Iwabe, H. Khanna, A. Sumaroka, V. A. Chiodo, D. S. Fajardo, A. J. Román, W.-T. Deng, M. Swider, T. S. Alemán, S. L. Boye, S. Genini, A. Swaroop, W. W. Hauswirth, S. G. Jacobson, and G. D. Aguirre, “Gene therapy rescues photoreceptor blindness in dogs and paves the way for treating human X-linked retinitis pigmentosa,” Proc. Natl. Acad. Sci. USA 109, 2132–2137 (2012).
[Crossref]

Dhamdhere, K. P.

J. Tam, K. P. Dhamdhere, P. Tiruveedhula, B. J. Lujan, R. N. Johnson, M. A. Bearse, A. J. Adams, and A. Roorda, “Subclinical capillary changes in non proliferative diabetic retinopathy,” Optom. Vis. Sci. 89, E692–E703 (2012).
[Crossref]

J. Tam, K. P. Dhamdhere, P. Tiruveedhula, S. Manzanera, S. Barez, M. A. Bearse, A. J. Adams, and A. Roorda, “Disruption of the retinal parafoveal capillary network in type 2 diabetes before the onset of diabetic retinopathy,” Invest. Ophthalmol. Visual Sci. 52, 9257–9266 (2011).
[Crossref]

Doble, N.

S. Marcos, J. S. Werner, S. A. Burns, W. H. Merigan, P. Artal, D. A. Atchison, K. M. Hampson, R. Legras, L. Lundstrom, G. Yoon, J. Carroll, S. S. Choi, N. Doble, A. M. Dubis, A. Dubra, A. Elsner, R. Jonnal, D. T. Miller, M. Paques, H. E. Smithson, L. K. Young, Y. Zhang, M. Campbell, J. Hunter, A. Metha, G. Palczewska, J. Schallek, and L. C. Sincich, “Vision science and adaptive optics, the state of the field,” Vis. Res. 132, 3–33 (2017).
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Donnelly, W. J.

Dreher, A. W.

J. P. Kelly, A. H. Weiss, S. Schmode, and A. W. Dreher, “Imaging a child’s fundus without dilation using a handheld confocal scanning laser ophthalmoscope,” Arch. Ophthalmol. 121, 391–396 (2003).
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Dubis, A. M.

S. Marcos, J. S. Werner, S. A. Burns, W. H. Merigan, P. Artal, D. A. Atchison, K. M. Hampson, R. Legras, L. Lundstrom, G. Yoon, J. Carroll, S. S. Choi, N. Doble, A. M. Dubis, A. Dubra, A. Elsner, R. Jonnal, D. T. Miller, M. Paques, H. E. Smithson, L. K. Young, Y. Zhang, M. Campbell, J. Hunter, A. Metha, G. Palczewska, J. Schallek, and L. C. Sincich, “Vision science and adaptive optics, the state of the field,” Vis. Res. 132, 3–33 (2017).
[Crossref]

M. A. Genead, G. A. Fishman, J. Rha, A. M. Dubis, D. M. O. Bonci, A. Dubra, E. M. Stone, M. Neitz, and J. Carroll, “Photoreceptor structure and function in patients with congenital achromatopsia,” Invest. Ophthalmol. Visual Sci. 52, 7298–7308 (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]

DuBose, T.

F. LaRocca, D. Nankivil, T. DuBose, C. A. Toth, S. Farsiu, and J. A. Izatt, “In vivo cellular-resolution retinal imaging in infants and children using an ultracompact handheld probe,” Nat. Photonics 10, 580–584 (2016).
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Dubra, A.

S. Marcos, J. S. Werner, S. A. Burns, W. H. Merigan, P. Artal, D. A. Atchison, K. M. Hampson, R. Legras, L. Lundstrom, G. Yoon, J. Carroll, S. S. Choi, N. Doble, A. M. Dubis, A. Dubra, A. Elsner, R. Jonnal, D. T. Miller, M. Paques, H. E. Smithson, L. K. Young, Y. Zhang, M. Campbell, J. Hunter, A. Metha, G. Palczewska, J. Schallek, and L. C. Sincich, “Vision science and adaptive optics, the state of the field,” Vis. Res. 132, 3–33 (2017).
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J. Tam, K. P. Dhamdhere, P. Tiruveedhula, B. J. Lujan, R. N. Johnson, M. A. Bearse, A. J. Adams, and A. Roorda, “Subclinical capillary changes in non proliferative diabetic retinopathy,” Optom. Vis. Sci. 89, E692–E703 (2012).
[Crossref]

J. Tam, K. P. Dhamdhere, P. Tiruveedhula, S. Manzanera, S. Barez, M. A. Bearse, A. J. Adams, and A. Roorda, “Disruption of the retinal parafoveal capillary network in type 2 diabetes before the onset of diabetic retinopathy,” Invest. Ophthalmol. Visual Sci. 52, 9257–9266 (2011).
[Crossref]

Tondello, G.

Toth, C. A.

F. LaRocca, D. Nankivil, T. DuBose, C. A. Toth, S. Farsiu, and J. A. Izatt, “In vivo cellular-resolution retinal imaging in infants and children using an ultracompact handheld probe,” Nat. Photonics 10, 580–584 (2016).
[Crossref]

Unser, M.

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

Valentine, G.

Valentine, G. J.

A. J. Wright, D. Burns, B. A. Patterson, S. P. Poland, G. J. Valentine, and J. M. Girkin, “Exploration of the optimisation algorithms used in the implementation of adaptive optics in confocal and multiphoton microscopy,” Microsc. Res. Tech. 67, 36–44 (2005).
[Crossref]

Vallone, G.

van Kuijk, F.

A. Boretsky, F. Khan, G. Burnett, D. X. Hammer, R. D. Ferguson, F. van Kuijk, and M. Motamedi, “In vivo imaging of photoreceptor disruption associated with age-related macular degeneration: a pilot study,” Lasers Surg. Med. 44, 603–610 (2012).
[Crossref]

Vdovin, G.

Villoresi, P.

Voelz, D.

Vorontsov, M.

Vozzi, C.

Walters, S.

E. A. Rossi, C. E. Granger, R. Sharma, Q. Yang, K. Saito, C. Schwarz, S. Walters, K. Nozato, J. Zhang, T. Kawakami, W. Fischer, L. R. Latchney, J. J. Hunter, M. M. Chung, and D. R. Williams, “Imaging individual neurons in the retinal ganglion cell layer of the living eye,” Proc. Natl. Acad. Sci. USA 114, 586–591 (2017).
[Crossref]

Weale, R. A.

R. A. Weale, A Biography of the Eye: Development, Growth, Age (HK Lewis, 1982).

Weinberg, D. V.

S. O. Hansen, R. F. Cooper, A. Dubra, J. Carroll, and D. V. Weinberg, “Selective cone photoreceptor injury in acute macular neuroretinopathy,” Retina 33, 1650–1658 (2013).
[Crossref]

Weiss, A. H.

J. P. Kelly, A. H. Weiss, S. Schmode, and A. W. Dreher, “Imaging a child’s fundus without dilation using a handheld confocal scanning laser ophthalmoscope,” Arch. Ophthalmol. 121, 391–396 (2003).
[Crossref]

Werner, J. S.

S. Marcos, J. S. Werner, S. A. Burns, W. H. Merigan, P. Artal, D. A. Atchison, K. M. Hampson, R. Legras, L. Lundstrom, G. Yoon, J. Carroll, S. S. Choi, N. Doble, A. M. Dubis, A. Dubra, A. Elsner, R. Jonnal, D. T. Miller, M. Paques, H. E. Smithson, L. K. Young, Y. Zhang, M. Campbell, J. Hunter, A. Metha, G. Palczewska, J. Schallek, and L. C. Sincich, “Vision science and adaptive optics, the state of the field,” Vis. Res. 132, 3–33 (2017).
[Crossref]

Whitson, H. E.

Williams, D. R.

E. A. Rossi, C. E. Granger, R. Sharma, Q. Yang, K. Saito, C. Schwarz, S. Walters, K. Nozato, J. Zhang, T. Kawakami, W. Fischer, L. R. Latchney, J. J. Hunter, M. M. Chung, and D. R. Williams, “Imaging individual neurons in the retinal ganglion cell layer of the living eye,” Proc. Natl. Acad. Sci. USA 114, 586–591 (2017).
[Crossref]

H. Song, E. A. Rossi, L. Latchney, A. Bessette, E. Stone, J. J. Hunter, D. R. Williams, and M. M. Chung, “Cone and rod loss in Stargardt disease revealed by adaptive optics scanning light ophthalmoscopy,” JAMA Ophthalmol. 133, 1198–1203 (2015).
[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]

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. USA 101, 8461–8466 (2004).
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A. Roorda and D. R. Williams, “The arrangement of the three cone classes in the living human eye,” Nature 397, 520–522 (1999).
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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, 2884–2892 (1997).
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Wilson, L.

E. Theofanidou, L. Wilson, W. J. Hossack, and J. Arlt, “Spherical aberration correction for optical tweezers,” Opt. Commun. 236, 145–150 (2004).
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Wilson, T.

Wong, K. S. K.

Wright, A. J.

A. J. Wright, D. Burns, B. A. Patterson, S. P. Poland, G. J. Valentine, and J. M. Girkin, “Exploration of the optimisation algorithms used in the implementation of adaptive optics in confocal and multiphoton microscopy,” Microsc. Res. Tech. 67, 36–44 (2005).
[Crossref]

Yang, Q.

E. A. Rossi, C. E. Granger, R. Sharma, Q. Yang, K. Saito, C. Schwarz, S. Walters, K. Nozato, J. Zhang, T. Kawakami, W. Fischer, L. R. Latchney, J. J. Hunter, M. M. Chung, and D. R. Williams, “Imaging individual neurons in the retinal ganglion cell layer of the living eye,” Proc. Natl. Acad. Sci. USA 114, 586–591 (2017).
[Crossref]

Yang, Y.

Y. Yang, K. Thompson, and S. A. Burns, “Pupil location under mesopic, photopic, and pharmacologically dilated conditions,” Invest. Ophthalmol. Visual Sci. 43, 2508–2512 (2002).

Ye, J.

L. Sherman, J. Ye, O. Albert, and T. Norris, “Adaptive correction of depth-induced aberrations in multiphoton scanning microscopy using a deformable mirror,” J. Microsc. 206, 65–71 (2002).
[Crossref]

Yoon, G.

S. Marcos, J. S. Werner, S. A. Burns, W. H. Merigan, P. Artal, D. A. Atchison, K. M. Hampson, R. Legras, L. Lundstrom, G. Yoon, J. Carroll, S. S. Choi, N. Doble, A. M. Dubis, A. Dubra, A. Elsner, R. Jonnal, D. T. Miller, M. Paques, H. E. Smithson, L. K. Young, Y. Zhang, M. Campbell, J. Hunter, A. Metha, G. Palczewska, J. Schallek, and L. C. Sincich, “Vision science and adaptive optics, the state of the field,” Vis. Res. 132, 3–33 (2017).
[Crossref]

Young, L. K.

S. Marcos, J. S. Werner, S. A. Burns, W. H. Merigan, P. Artal, D. A. Atchison, K. M. Hampson, R. Legras, L. Lundstrom, G. Yoon, J. Carroll, S. S. Choi, N. Doble, A. M. Dubis, A. Dubra, A. Elsner, R. Jonnal, D. T. Miller, M. Paques, H. E. Smithson, L. K. Young, Y. Zhang, M. Campbell, J. Hunter, A. Metha, G. Palczewska, J. Schallek, and L. C. Sincich, “Vision science and adaptive optics, the state of the field,” Vis. Res. 132, 3–33 (2017).
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Yuksel, N.

O. Elibol, T. Alcelik, N. Yuksel, and Y. Caglar, “The influence of drop size of cyclopentolate, phenylephrine and tropicamide on pupil dilatation and systemic side effects in infants,” Acta Ophthalmol. Scand. 75, 178–180 (1997).

Zawadzki, R. J.

Zhang, F.

Z. Liu, K. Kurokawa, F. Zhang, J. J. Lee, and D. T. Miller, “Imaging and quantifying ganglion cells and other transparent neurons in the living human retina,” Proc. Natl. Acad. Sci. USA 114, 12803–12808 (2017).
[Crossref]

Zhang, J.

E. A. Rossi, C. E. Granger, R. Sharma, Q. Yang, K. Saito, C. Schwarz, S. Walters, K. Nozato, J. Zhang, T. Kawakami, W. Fischer, L. R. Latchney, J. J. Hunter, M. M. Chung, and D. R. Williams, “Imaging individual neurons in the retinal ganglion cell layer of the living eye,” Proc. Natl. Acad. Sci. USA 114, 586–591 (2017).
[Crossref]

Zhang, L.

W. A. Beltran, A. V. Cideciyan, K. E. Guziewicz, S. Iwabe, M. Swider, E. M. Scott, S. V. Savina, G. Ruthel, F. Stefano, L. Zhang, R. Zorger, A. Sumaroka, S. G. Jacobson, and G. D. Aguirre, “Canine retina has a primate fovea-like bouquet of cone photoreceptors which is affected by inherited macular degenerations,” PLoS ONE 9, e90390 (2014).
[Crossref]

Zhang, Y.

S. Marcos, J. S. Werner, S. A. Burns, W. H. Merigan, P. Artal, D. A. Atchison, K. M. Hampson, R. Legras, L. Lundstrom, G. Yoon, J. Carroll, S. S. Choi, N. Doble, A. M. Dubis, A. Dubra, A. Elsner, R. Jonnal, D. T. Miller, M. Paques, H. E. Smithson, L. K. Young, Y. Zhang, M. Campbell, J. Hunter, A. Metha, G. Palczewska, J. Schallek, and L. C. Sincich, “Vision science and adaptive optics, the state of the field,” Vis. Res. 132, 3–33 (2017).
[Crossref]

Zhou, X.

Zommer, S.

Zorger, R.

W. A. Beltran, A. V. Cideciyan, K. E. Guziewicz, S. Iwabe, M. Swider, E. M. Scott, S. V. Savina, G. Ruthel, F. Stefano, L. Zhang, R. Zorger, A. Sumaroka, S. G. Jacobson, and G. D. Aguirre, “Canine retina has a primate fovea-like bouquet of cone photoreceptors which is affected by inherited macular degenerations,” PLoS ONE 9, e90390 (2014).
[Crossref]

Acta Ophthalmol. Scand. (1)

O. Elibol, T. Alcelik, N. Yuksel, and Y. Caglar, “The influence of drop size of cyclopentolate, phenylephrine and tropicamide on pupil dilatation and systemic side effects in infants,” Acta Ophthalmol. Scand. 75, 178–180 (1997).

Appl. Opt. (1)

Arch. Ophthalmol. (1)

J. P. Kelly, A. H. Weiss, S. Schmode, and A. W. Dreher, “Imaging a child’s fundus without dilation using a handheld confocal scanning laser ophthalmoscope,” Arch. Ophthalmol. 121, 391–396 (2003).
[Crossref]

Biomed. Opt. Express (7)

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. N. Sulai and A. Dubra, “Non-common path aberration correction in an adaptive optics scanning ophthalmoscope,” Biomed. Opt. Express 5, 3059–3073 (2014).
[Crossref]

F. LaRocca, D. Nankivil, S. Farsiu, and J. A. Izatt, “True color scanning laser ophthalmoscopy and optical coherence tomography handheld probe,” Biomed. Opt. Express 5, 3204–3216 (2014).
[Crossref]

K. S. K. Wong, Y. Jian, M. Cua, S. Bonora, R. J. Zawadzki, and M. V. Sarunic, “In vivo imaging of human photoreceptor mosaic with wavefront sensorless adaptive optics optical coherence tomography,” Biomed. Opt. Express 6, 580–590 (2015).
[Crossref]

X. Zhou, P. Bedggood, B. Bui, C. T. O. Nguyen, Z. He, and A. Metha, “Contrast-based sensorless adaptive optics for retinal imaging,” Biomed. Opt. Express 6, 3577–3595 (2015).
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J. Polans, B. Keller, O. M. Carrasco-Zevallos, F. LaRocca, E. Cole, H. E. Whitson, E. M. Lad, S. Farsiu, and J. A. Izatt, “Wide-field retinal optical coherence tomography with wavefront sensorless adaptive optics for enhanced imaging of targeted regions,” Biomed. Opt. Express 8, 16–37 (2017).
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F. LaRocca, D. Nankivil, S. Farsiu, and J. A. Izatt, “Handheld simultaneous scanning laser ophthalmoscopy and optical coherence tomography system,” Biomed. Opt. Express 4, 2307–2321 (2013).
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IEEE Trans. Image Process. (1)

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

Invest. Ophthalmol. Visual Sci. (4)

Y. Yang, K. Thompson, and S. A. Burns, “Pupil location under mesopic, photopic, and pharmacologically dilated conditions,” Invest. Ophthalmol. Visual Sci. 43, 2508–2512 (2002).

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. Visual Sci. 52, 2219–2226 (2011).
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M. A. Genead, G. A. Fishman, J. Rha, A. M. Dubis, D. M. O. Bonci, A. Dubra, E. M. Stone, M. Neitz, and J. Carroll, “Photoreceptor structure and function in patients with congenital achromatopsia,” Invest. Ophthalmol. Visual Sci. 52, 7298–7308 (2011).
[Crossref]

J. Tam, K. P. Dhamdhere, P. Tiruveedhula, S. Manzanera, S. Barez, M. A. Bearse, A. J. Adams, and A. Roorda, “Disruption of the retinal parafoveal capillary network in type 2 diabetes before the onset of diabetic retinopathy,” Invest. Ophthalmol. Visual Sci. 52, 9257–9266 (2011).
[Crossref]

J. Biomed. Opt. (1)

P. Bedggood, M. Daaboul, R. A. Ashman, G. G. Smith, and A. Metha, “Characteristics of the human isoplanatic patch and implications for adaptive optics retinal imaging,” J. Biomed. Opt. 13, 024008 (2008).
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J. Comp. Neurol. (1)

C. A. Curcio, K. R. Sloan, R. E. Kalina, and A. E. Hendrickson, “Human photoreceptor topography,” J. Comp. Neurol. 292, 497–523 (1990).
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J. Microsc. (2)

L. Sherman, J. Ye, O. Albert, and T. Norris, “Adaptive correction of depth-induced aberrations in multiphoton scanning microscopy using a deformable mirror,” J. Microsc. 206, 65–71 (2002).
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M. Skorsetz, P. Artal, and J. M. Bueno, “Performance evaluation of a sensorless adaptive optics multiphoton microscope,” J. Microsc. 261, 249–258 (2015).
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J. Opt. Soc. Am. (2)

J. Opt. Soc. Am. A (6)

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JAMA Ophthalmol. (1)

H. Song, E. A. Rossi, L. Latchney, A. Bessette, E. Stone, J. J. Hunter, D. R. Williams, and M. M. Chung, “Cone and rod loss in Stargardt disease revealed by adaptive optics scanning light ophthalmoscopy,” JAMA Ophthalmol. 133, 1198–1203 (2015).
[Crossref]

Lasers Surg. Med. (1)

A. Boretsky, F. Khan, G. Burnett, D. X. Hammer, R. D. Ferguson, F. van Kuijk, and M. Motamedi, “In vivo imaging of photoreceptor disruption associated with age-related macular degeneration: a pilot study,” Lasers Surg. Med. 44, 603–610 (2012).
[Crossref]

Microsc. Res. Tech. (1)

A. J. Wright, D. Burns, B. A. Patterson, S. P. Poland, G. J. Valentine, and J. M. Girkin, “Exploration of the optimisation algorithms used in the implementation of adaptive optics in confocal and multiphoton microscopy,” Microsc. Res. Tech. 67, 36–44 (2005).
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Nat. Methods (1)

N. Ji, D. E. Milkie, and E. Betzig, “Adaptive optics via pupil segmentation for high-resolution imaging in biological tissues,” Nat. Methods 7, 141–147 (2010).
[Crossref]

Nat. Photonics (1)

F. LaRocca, D. Nankivil, T. DuBose, C. A. Toth, S. Farsiu, and J. A. Izatt, “In vivo cellular-resolution retinal imaging in infants and children using an ultracompact handheld probe,” Nat. Photonics 10, 580–584 (2016).
[Crossref]

Nature (1)

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

Ophthalmic Physiol. Opt. (1)

C. MacLachlan and H. C. Howland, “Normal values and standard deviations for pupil diameter and interpupillary distance in subjects aged 1 month to 19 years,” Ophthalmic Physiol. Opt. 22, 175–182 (2002).
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Opt. Commun. (1)

E. Theofanidou, L. Wilson, W. J. Hossack, and J. Arlt, “Spherical aberration correction for optical tweezers,” Opt. Commun. 236, 145–150 (2004).
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Opt. Eng. (1)

F. Gonte, A. Courteville, and R. Dandliker, “Optimization of single-mode fiber coupling efficiency with an adaptive membrane mirror,” Opt. Eng. 41, 1073–1076 (2002).
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Opt. Express (7)

Opt. Lett. (9)

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M. Minozzi, S. Bonora, A. Sergienko, G. Vallone, and P. Villoresi, “Optimization of two-photon wave function in parametric down conversion by adaptive optics control of the pump radiation,” Opt. Lett. 38, 489–491 (2013).
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J. Polans, D. Cunefare, E. Cole, B. Keller, P. S. Mettu, S. W. Cousins, M. J. Allingham, J. A. Izatt, and S. Farsiu, “Enhanced visualization of peripheral retinal vasculature with wavefront sensorless adaptive optics optical coherence tomography angiography in diabetic patients,” Opt. Lett. 42, 17–20 (2017).
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S. Bonora and R. J. Zawadzki, “Wavefront sensorless modal deformable mirror correction in adaptive optics: optical coherence tomography,” Opt. Lett. 38, 4801–4804 (2013).
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P. Villoresi, S. Bonora, M. Pascolini, L. Poletto, G. Tondello, C. Vozzi, M. Nisoli, G. Sansone, S. Stagira, and S. De Silvestri, “Optimization of high-order harmonic generation by adaptive control of a sub-10-fs pulse wave front,” Opt. Lett. 29, 207–209 (2004).
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M. Vorontsov, G. Carhart, and J. Ricklin, “Adaptive phase-distortion correction based on parallel gradient-descent optimization,” Opt. Lett. 22, 907–909 (1997).
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S. Zommer, E. Ribak, S. Lipson, and J. Adler, “Simulated annealing in ocular adaptive optics,” Opt. Lett. 31, 939–941 (2006).
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Optom. Vis. Sci. (1)

J. Tam, K. P. Dhamdhere, P. Tiruveedhula, B. J. Lujan, R. N. Johnson, M. A. Bearse, A. J. Adams, and A. Roorda, “Subclinical capillary changes in non proliferative diabetic retinopathy,” Optom. Vis. Sci. 89, E692–E703 (2012).
[Crossref]

Optometry (1)

T. Hug and S. Olitsky, “Dilation efficacy: is 1% cyclopentolate enough?” Optometry 78, 119–121 (2007).
[Crossref]

PLoS ONE (1)

W. A. Beltran, A. V. Cideciyan, K. E. Guziewicz, S. Iwabe, M. Swider, E. M. Scott, S. V. Savina, G. Ruthel, F. Stefano, L. Zhang, R. Zorger, A. Sumaroka, S. G. Jacobson, and G. D. Aguirre, “Canine retina has a primate fovea-like bouquet of cone photoreceptors which is affected by inherited macular degenerations,” PLoS ONE 9, e90390 (2014).
[Crossref]

Proc. Natl. Acad. Sci. USA (4)

W. A. Beltran, A. V. Cideciyan, A. S. Lewin, S. Iwabe, H. Khanna, A. Sumaroka, V. A. Chiodo, D. S. Fajardo, A. J. Román, W.-T. Deng, M. Swider, T. S. Alemán, S. L. Boye, S. Genini, A. Swaroop, W. W. Hauswirth, S. G. Jacobson, and G. D. Aguirre, “Gene therapy rescues photoreceptor blindness in dogs and paves the way for treating human X-linked retinitis pigmentosa,” Proc. Natl. Acad. Sci. USA 109, 2132–2137 (2012).
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E. A. Rossi, C. E. Granger, R. Sharma, Q. Yang, K. Saito, C. Schwarz, S. Walters, K. Nozato, J. Zhang, T. Kawakami, W. Fischer, L. R. Latchney, J. J. Hunter, M. M. Chung, and D. R. Williams, “Imaging individual neurons in the retinal ganglion cell layer of the living eye,” Proc. Natl. Acad. Sci. USA 114, 586–591 (2017).
[Crossref]

Z. Liu, K. Kurokawa, F. Zhang, J. J. Lee, and D. T. Miller, “Imaging and quantifying ganglion cells and other transparent neurons in the living human retina,” Proc. Natl. Acad. Sci. USA 114, 12803–12808 (2017).
[Crossref]

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

Retina (1)

S. O. Hansen, R. F. Cooper, A. Dubra, J. Carroll, and D. V. Weinberg, “Selective cone photoreceptor injury in acute macular neuroretinopathy,” Retina 33, 1650–1658 (2013).
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Sci. Trans. Med. (1)

H. P. N. Scholl, R. W. Strauss, M. S. Singh, D. Dalkara, B. Roska, S. Picaud, and J.-A. Sahel, “Emerging therapies for inherited retinal degeneration,” Sci. Trans. Med. 8, 368rv6 (2016).
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Vis. Res. (1)

S. Marcos, J. S. Werner, S. A. Burns, W. H. Merigan, P. Artal, D. A. Atchison, K. M. Hampson, R. Legras, L. Lundstrom, G. Yoon, J. Carroll, S. S. Choi, N. Doble, A. M. Dubis, A. Dubra, A. Elsner, R. Jonnal, D. T. Miller, M. Paques, H. E. Smithson, L. K. Young, Y. Zhang, M. Campbell, J. Hunter, A. Metha, G. Palczewska, J. Schallek, and L. C. Sincich, “Vision science and adaptive optics, the state of the field,” Vis. Res. 132, 3–33 (2017).
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Z. Popovic, J. Thaung, P. Knutsson, and M. Owner-Petersen, “Dual conjugate adaptive optics prototype for wide field high resolution retinal imaging,” in Adaptive Optics Progress (InTech, 2012).

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Figures (8)

Fig. 1.
Fig. 1. (a) Photograph of an adult subject being imaged by a typical large-footprint AOSLO imaging system. (b) Photograph of an infant patient being imaged by our HAOSLO probe prior to retinal surgery.
Fig. 2.
Fig. 2. HAOSLO probe system schematic and optical design: red and blue rays depict the illumination and collection paths, respectively. APD, avalanche photodiode; DM, deformable mirror; FM, fold mirror; L1–L10, lenses; LP, linear polarizer; MMF, multimode fiber; PBS, polarizing beam splitter; PM, polarization-maintaining; QWP, quarter wave plate; SLD, superluminescent diode; SMF, single-mode fiber; VOA, variable optical attenuator.
Fig. 3.
Fig. 3. Spot diagrams for the HAOSLO probe on the retina spanning a 1.6 ° × 1.6 ° FOV. HAOSLO is diffraction-limited at 2.3 μm (spot FWHM). Spot diagrams are color coded by wavelength across the source bandwidth. Airy disks are shown by black circles. Scale bar, 2 μm.
Fig. 4.
Fig. 4. (a), (b) Renderings of the handheld probe’s optomechanical design. Dimensions: 10.3    cm × 5.3    cm × 14.4    cm . (a) Left cross-section of the probe’s internal skeleton. (b) Isometric view of the probe’s internal skeleton. (c) Photograph of the fabricated probe in hand.
Fig. 5.
Fig. 5. Flow diagram of the SZGD algorithm. First, images are 5 × subsampled to increase the algorithm’s iteration speed. Next, the perturbing shape δ is determined by randomly selecting one of eight Zernike modes or a uniformly random shape in the actuator basis. All subsequent steps follow the SPGD technique laid out previously in Ref. [43]. Prior to ending the optimization, the subsampling is removed and the image acquisition speed is restored to its pre-optimization state.
Fig. 6.
Fig. 6. Quantitative comparison of WS-AO algorithms’ speed and correction quality on a model eye. (a) Time course of WS-AO optimization. Mean intensity across the central 1.4 ° × 1.4 ° FOV is shown as a function of iteration number when optimizing in three different optimization modes. (b) Results from imaging a USAF 1951 test target in a model eye with the HAOSLO probe. (c)–(e) Images obtained after inserting trial lenses and optimizing for 5 min using defocus only correction, SPGD, and SZGD, respectively. (f)–(i) Insets from (b)–(e) on Group 5 Elements 2–6. (j)–(m) Insets from (b)–(e) on the Group 3 Square with sections of the horizontal and vertical edges indicated. (n)–(q) and (r)–(u) Plots of edge-derived PSFs with Gaussian fit and calculated FWHMs indicated for horizontal and vertical directions, respectively. Error bars indicate standard deviation in intensity across the edge.
Fig. 7.
Fig. 7. HAOSLO images acquired in handheld operation on three adult volunteers after natural dark adaptation using SZGD correction. (a) Retinal mosaic from subject 1 centered at a location slightly superior to the fovea. Inset (red) is located 2° from the fovea. (b) Retinal mosaic from subject 2 centered at a location slightly inferior to the fovea. Inset (green) is located 2.1° from the fovea. (c) Retinal mosaic from subject 3 centered at a location slightly inferior to the fovea. Inset (blue) is located 1.9° from the fovea. All insets have a 0.75° FOV. Scale bar, 0.25°. (d)–(f) 0.75° FOV excerpts from the three subjects encoded by the bounding box color. (g)–(l) Radial power spectra of 0.25° FOV excerpts and comparison to the average histological cone spacing predicted for the corresponding eccentricities in Ref. [58]. (g) S1 at 1.75°. (h) S1 at 2.1°. (i) S2 at 1.8°. (j) S2 at 2.5°. (k) S3 at 1.4°. (l) S3 at 1.7°.
Fig. 8.
Fig. 8. HAOSLO images acquired in handheld operation on dilated, supine subjects. Scale bars, 0.25°. (a) Single cropped frame from subject S2 (emmetropic adult) at 2.1° eccentricity. (b) Single cropped frame from fellow eye of SI1 (31-month-old) during examination under anesthesia. (c) Cropped composite of five frames from fellow eye of SI2 (22-month-old) during examination under anesthesia.

Tables (2)

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Table 1. Diameter and Effective Focal Length (EFL) of All Custom Lenses in the HAOSLO Probe

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Table 2. Modal Perturbation Frequencies (MPFs) of the SZGD Algorithm for 4.8 mm and 6.0 mm Input Beam Sizes in Percent

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