Abstract

Imaging of the retinal vascular structure and perfusion was explored by confocal illumination and nonconfocal detection in an adaptive optics scanning light ophthalmoscope (AOSLO), as an extension of the work by Chui et al. [Biomed. Opt. Express 3, 2537 (2012)]. Five different detection schemes were evaluated at multiple retinal locations: circular mask, annular mask, circular mask with filament, knife-edge, and split-detector. Given the superior image contrast in the reflectance and perfusion maps, the split-detection method was further tested using pupil apodization, polarized detection, and four different wavelengths. None of these variations provided noticeable contrast improvement. The noninvasive visualization of capillary flow and structure provided by AOSLO split-detection shows great promise for studying ocular and systemic conditions that affect the retinal vasculature.

© 2014 Optical Society of America

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2013 (3)

2012 (7)

2011 (2)

2010 (1)

J. Tam, J. A. Martin, and A. Roorda, “Non-invasive visualization and analysis of parafoveal capillaries in humans,” Investig. Ophthamol. Vis. Sci. 51, 1691–1698 (2010).

2009 (3)

2007 (1)

2005 (4)

D. A. Nelson, S. Krupsky, A. Pollack, E. Aloni, M. Belkin, I. Vanzetta, M. Rosner, and A. Grinvald, “Special report: noninvasive multi-parameter functional optical imaging of the eye,” Ophthalmic Surg. Lasers Imaging 36, 57–66 (2005).

A. V. Cideciyan, S. G. Jacobson, T. S. Aleman, D. Gu, S. E. Pearce-Kelling, A. Sumaroka, G. M. Acland, and G. D. Aguirre, “In vivo dynamics of retinal injury and repair in the rhodopsin mutant dog model of human retinitis pigmentosa,” Proc. Natl. Acad. Sci. USA 102, 5233–5238 (2005).

N. Patton, T. Aslam, T. MacGillivray, A. Pattie, I. J. Deary, and B. Dhillon, “Retinal vascular image analysis as a potential screening tool for cerebrovascular disease: a rationale based on homology between cerebral and retinal microvasculatures,” J. Anat. 206, 319–348 (2005).

A. D. Kulkarni and B. D. Kuppermann, “Wet age-related macular degeneration,” Adv. Drug Deliv. Rev. 57, 1994–2009 (2005).

2003 (3)

P. E. Stanga, J. I. Lim, and P. Hamilton, “Indocyanine green angiography in chorioretinal diseases: indications and interpretation: an evidence-based update,” Ophthalmology 110, 15–21 (2003).
[CrossRef]

J. M. Bueno and M. C. W. Campbell, “Polarization properties of the in vitro old human crystalline lens,” Ophthalmic Physiolog. Opt. 23, 109–118 (2003).

W. B. Amos, S. Reichelt, D. M. Cattermole, and J. Laufer, “Re-evaluation of differential phase contrast (DPC) in a scanning laser microscope using a split-detector as an alternative to differential interference contrast (DIC) optics,” J. Microsc. 210, 166–175 (2003).
[CrossRef]

2002 (2)

2000 (2)

S. Yazdanfar, A. M. Rollins, and J. A. Izatt, “Imaging and velocimetry of the human retinal circulation with color Doppler optical coherence tomography,” Opt. Lett. 25, 1448–1450 (2000).
[CrossRef]

D. S. Greenfield, R. W. Knighton, and X. R. Huang, “Effect of corneal polarization axis on assessment of retinal nerve fiber layer thickness by scanning laser polarimetry,” Am. J. Ophthalmol. 129, 715–722 (2000).

1997 (1)

Y. Tamaki, M. Araie, K. Tomita, M. Nagahara, A. Tomidokoro, and H. Fujii, “Real-time measurement of human optic nerve head and choroid circulation, using the laser speckle phenomenon,” Jpn. J. Ophthalmol. 41, 49–54 (1997).

1996 (1)

1995 (1)

G. Michelson and B. Schmauss, “Two dimensional mapping of the perfusion of the retina and optic nerve head,” Br. J. Ophthalmol. 79, 1126–1132 (1995).

1993 (1)

S. Wolf, O. Arend, W. E. Sponsel, K. Schulte, L. B. Cantor, and M. Reim, “Retinal hemodynamics using scanning laser ophthalmoscopy and hemorheology in chronic open-angle glaucoma,” Ophthalmology 100, 1561–1566 (1993).
[CrossRef]

1991 (1)

S. Wolf, O. Arend, H. Toonen, B. Bertram, F. Jung, and M. Reim, “Retinal capillary blood flow measurement with a scanning laser ophthalmoscope. Preliminary results,” Ophthalmology 98, 996–1000 (1991).
[CrossRef]

1987 (1)

1985 (1)

C. E. Riva, J. E. Grunwald, S. H. Sinclair, and B. L. Petrig, “Blood velocity and volumetric flow rate in human retinal vessels,” Investig. Ophthalmol. Vis. Sci. 26, 1124–1132 (1985).

1984 (1)

D. K. Hamilton and C. J. R. Sheppard, “Differential phase-contrast in scanning optical microscopy,” J. Microsc. 133, 27–39 (1984).
[CrossRef]

1983 (1)

T. Wilson and D. K. Hamilton, “Differential amplitude contrast imaging in the scanning optical microscope,” Appl. Phys. B 32, 187–191 (1983).
[CrossRef]

1982 (1)

J. D. Gass and R. T. Oyakawa, “Idiopathic juxtafoveolar retinal telangiectasis,” Arch. Ophthalmol. 100, 769–780 (1982).

1981 (1)

W. H. Stern and D. B. Archer, “Retinal vascular occlusion,” Annu. Rev. Med. 32, 101–106 (1981).

1980 (1)

T. J. Ffytche, J. S. Shilling, I. H. Chisholm, and J. L. Federman, “Indications for fluorescein angiography in disease of the ocular fundus: a review,” J. R. Soc. Med. 73, 362–365 (1980).

1975 (1)

E. M. Kohner, A. M. Hamilton, S. J. Saunders, B. A. Sutcliffe, and C. J. Bulpitt, “The retinal blood flow in diabetes,” Diabetologia 11, 27–33 (1975).
[CrossRef]

1974 (1)

T. Tanaka, C. Riva, and I. Ben-Sira, “Blood velocity measurements in human retinal vessels,” Science 186, 830–831 (1974).
[CrossRef]

1971 (1)

B. I. Chazan, M. C. Balodimos, and L. Koncz, “Untoward effects of fluorescein retinal angiography in diabetic patients,” Ann. Ophthalmol. 3, 42 (1971).

1955 (1)

G. J. Nomarski, “Microintérferomtrè différentiel à ondes polarisées,” J. Physiol. Paris 16, S9–S13 (1955).

1953 (1)

E. H. Linfoot and E. Wolf, “Diffraction images in systems with an annular aperture,” Proc. Phys. Soc. B 66, 145 (1953).

Acland, G. M.

A. V. Cideciyan, S. G. Jacobson, T. S. Aleman, D. Gu, S. E. Pearce-Kelling, A. Sumaroka, G. M. Acland, and G. D. Aguirre, “In vivo dynamics of retinal injury and repair in the rhodopsin mutant dog model of human retinitis pigmentosa,” Proc. Natl. Acad. Sci. USA 102, 5233–5238 (2005).

Aguirre, G. D.

A. V. Cideciyan, S. G. Jacobson, T. S. Aleman, D. Gu, S. E. Pearce-Kelling, A. Sumaroka, G. M. Acland, and G. D. Aguirre, “In vivo dynamics of retinal injury and repair in the rhodopsin mutant dog model of human retinitis pigmentosa,” Proc. Natl. Acad. Sci. USA 102, 5233–5238 (2005).

Aleman, T. S.

A. V. Cideciyan, S. G. Jacobson, T. S. Aleman, D. Gu, S. E. Pearce-Kelling, A. Sumaroka, G. M. Acland, and G. D. Aguirre, “In vivo dynamics of retinal injury and repair in the rhodopsin mutant dog model of human retinitis pigmentosa,” Proc. Natl. Acad. Sci. USA 102, 5233–5238 (2005).

Aloni, E.

D. A. Nelson, S. Krupsky, A. Pollack, E. Aloni, M. Belkin, I. Vanzetta, M. Rosner, and A. Grinvald, “Special report: noninvasive multi-parameter functional optical imaging of the eye,” Ophthalmic Surg. Lasers Imaging 36, 57–66 (2005).

Amos, W. B.

W. B. Amos, S. Reichelt, D. M. Cattermole, and J. Laufer, “Re-evaluation of differential phase contrast (DPC) in a scanning laser microscope using a split-detector as an alternative to differential interference contrast (DIC) optics,” J. Microsc. 210, 166–175 (2003).
[CrossRef]

Araie, M.

Y. Tamaki, M. Araie, K. Tomita, M. Nagahara, A. Tomidokoro, and H. Fujii, “Real-time measurement of human optic nerve head and choroid circulation, using the laser speckle phenomenon,” Jpn. J. Ophthalmol. 41, 49–54 (1997).

Archer, D. B.

W. H. Stern and D. B. Archer, “Retinal vascular occlusion,” Annu. Rev. Med. 32, 101–106 (1981).

Arend, O.

S. Wolf, O. Arend, W. E. Sponsel, K. Schulte, L. B. Cantor, and M. Reim, “Retinal hemodynamics using scanning laser ophthalmoscopy and hemorheology in chronic open-angle glaucoma,” Ophthalmology 100, 1561–1566 (1993).
[CrossRef]

S. Wolf, O. Arend, H. Toonen, B. Bertram, F. Jung, and M. Reim, “Retinal capillary blood flow measurement with a scanning laser ophthalmoscope. Preliminary results,” Ophthalmology 98, 996–1000 (1991).
[CrossRef]

Aslam, T.

N. Patton, T. Aslam, T. MacGillivray, A. Pattie, I. J. Deary, and B. Dhillon, “Retinal vascular image analysis as a potential screening tool for cerebrovascular disease: a rationale based on homology between cerebral and retinal microvasculatures,” J. Anat. 206, 319–348 (2005).

Balodimos, M. C.

B. I. Chazan, M. C. Balodimos, and L. Koncz, “Untoward effects of fluorescein retinal angiography in diabetic patients,” Ann. Ophthalmol. 3, 42 (1971).

Bedggood, P.

Belkin, M.

D. A. Nelson, S. Krupsky, A. Pollack, E. Aloni, M. Belkin, I. Vanzetta, M. Rosner, and A. Grinvald, “Special report: noninvasive multi-parameter functional optical imaging of the eye,” Ophthalmic Surg. Lasers Imaging 36, 57–66 (2005).

Ben-Sira, I.

T. Tanaka, C. Riva, and I. Ben-Sira, “Blood velocity measurements in human retinal vessels,” Science 186, 830–831 (1974).
[CrossRef]

Beringer, J.

A. M. Dubis, B. R. Hansen, R. F. Cooper, J. Beringer, A. Dubra, and J. Carroll, “Relationship between the foveal avascular zone and foveal pit morphology,” Investig. Ophthamol. Vis. Sci. 53, 1628–1636 (2012).

Bertram, B.

S. Wolf, O. Arend, H. Toonen, B. Bertram, F. Jung, and M. Reim, “Retinal capillary blood flow measurement with a scanning laser ophthalmoscope. Preliminary results,” Ophthalmology 98, 996–1000 (1991).
[CrossRef]

Born, M.

M. Born and E. Wolf, Principles of Optics, 6th (corrected) ed. (Pergamon, 1980).

Bour, L. J.

L. J. Bour, “Polarized light and the eye,” in Vision and Visual Dysfunction, J. R. Cronly-Dillon, ed. (MacMillan, 1991), pp. 310–325.

Brown, J. M.

Bueno, J. M.

J. M. Bueno and M. C. W. Campbell, “Polarization properties of the in vitro old human crystalline lens,” Ophthalmic Physiolog. Opt. 23, 109–118 (2003).

Bulpitt, C. J.

E. M. Kohner, A. M. Hamilton, S. J. Saunders, B. A. Sutcliffe, and C. J. Bulpitt, “The retinal blood flow in diabetes,” Diabetologia 11, 27–33 (1975).
[CrossRef]

Burns, S. A.

T. Y. P. Chui, T. J. Gast, and S. A. Burns, “Imaging of vascular wall fine structure in the human retina using adaptive optics scanning laser ophthalmoscopy,” Investig. Ophthamol. Vis. Sci. 54, 7115–7124 (2013).

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, 602–661 (2012).

T. Y. P. Chui, D. A. VanNasdale, and S. A. Burns, “The use of forward scatter to improve retinal vascular imaging with an adaptive optics scanning laser ophthalmoscope,” Biomed. Opt. Express 3, 2537–2549 (2012).
[CrossRef]

Campbell, M. C. W.

J. M. Bueno and M. C. W. Campbell, “Polarization properties of the in vitro old human crystalline lens,” Ophthalmic Physiolog. Opt. 23, 109–118 (2003).

Cantor, L. B.

S. Wolf, O. Arend, W. E. Sponsel, K. Schulte, L. B. Cantor, and M. Reim, “Retinal hemodynamics using scanning laser ophthalmoscopy and hemorheology in chronic open-angle glaucoma,” Ophthalmology 100, 1561–1566 (1993).
[CrossRef]

Carroll, J.

A. Pinhas, M. Dubow, N. Shah, T. Y. P. Chui, D. H. Scoles, Y. N. Sulai, R. Weitz, J. B. Walsh, J. Carroll, A. Dubra, and R. B. Rosen, “In vivo imaging of human retinal microvasculature using adaptive optics scanning light ophthalmoscope fluorescein angiography,” Biomed. Opt. Express 4, 1305–1317 (2013).
[CrossRef]

A. M. Dubis, B. R. Hansen, R. F. Cooper, J. Beringer, A. Dubra, and J. Carroll, “Relationship between the foveal avascular zone and foveal pit morphology,” Investig. Ophthamol. Vis. Sci. 53, 1628–1636 (2012).

Cattermole, D. M.

W. B. Amos, S. Reichelt, D. M. Cattermole, and J. Laufer, “Re-evaluation of differential phase contrast (DPC) in a scanning laser microscope using a split-detector as an alternative to differential interference contrast (DIC) optics,” J. Microsc. 210, 166–175 (2003).
[CrossRef]

Cense, B.

Chazan, B. I.

B. I. Chazan, M. C. Balodimos, and L. Koncz, “Untoward effects of fluorescein retinal angiography in diabetic patients,” Ann. Ophthalmol. 3, 42 (1971).

Chen, T. C.

Chisholm, I. H.

T. J. Ffytche, J. S. Shilling, I. H. Chisholm, and J. L. Federman, “Indications for fluorescein angiography in disease of the ocular fundus: a review,” J. R. Soc. Med. 73, 362–365 (1980).

Chu, K. K.

T. N. Ford, K. K. Chu, and J. Mertz, “Phase-gradient microscopy in thick tissue with oblique back-illumination,” Nat. Methods 9, 1195–1197 (2012).
[CrossRef]

Chui, T. Y. P.

A. Pinhas, M. Dubow, N. Shah, T. Y. P. Chui, D. H. Scoles, Y. N. Sulai, R. Weitz, J. B. Walsh, J. Carroll, A. Dubra, and R. B. Rosen, “In vivo imaging of human retinal microvasculature using adaptive optics scanning light ophthalmoscope fluorescein angiography,” Biomed. Opt. Express 4, 1305–1317 (2013).
[CrossRef]

T. Y. P. Chui, T. J. Gast, and S. A. Burns, “Imaging of vascular wall fine structure in the human retina using adaptive optics scanning laser ophthalmoscopy,” Investig. Ophthamol. Vis. Sci. 54, 7115–7124 (2013).

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, 602–661 (2012).

T. Y. P. Chui, D. A. VanNasdale, and S. A. Burns, “The use of forward scatter to improve retinal vascular imaging with an adaptive optics scanning laser ophthalmoscope,” Biomed. Opt. Express 3, 2537–2549 (2012).
[CrossRef]

Cideciyan, A. V.

A. V. Cideciyan, S. G. Jacobson, T. S. Aleman, D. Gu, S. E. Pearce-Kelling, A. Sumaroka, G. M. Acland, and G. D. Aguirre, “In vivo dynamics of retinal injury and repair in the rhodopsin mutant dog model of human retinitis pigmentosa,” Proc. Natl. Acad. Sci. USA 102, 5233–5238 (2005).

Cooper, R. F.

A. M. Dubis, B. R. Hansen, R. F. Cooper, J. Beringer, A. Dubra, and J. Carroll, “Relationship between the foveal avascular zone and foveal pit morphology,” Investig. Ophthamol. Vis. Sci. 53, 1628–1636 (2012).

de Boer, J. F.

Deary, I. J.

N. Patton, T. Aslam, T. MacGillivray, A. Pattie, I. J. Deary, and B. Dhillon, “Retinal vascular image analysis as a potential screening tool for cerebrovascular disease: a rationale based on homology between cerebral and retinal microvasculatures,” J. Anat. 206, 319–348 (2005).

Delori, F. C.

Dhillon, B.

N. Patton, T. Aslam, T. MacGillivray, A. Pattie, I. J. Deary, and B. Dhillon, “Retinal vascular image analysis as a potential screening tool for cerebrovascular disease: a rationale based on homology between cerebral and retinal microvasculatures,” J. Anat. 206, 319–348 (2005).

Dubis, A. M.

A. M. Dubis, B. R. Hansen, R. F. Cooper, J. Beringer, A. Dubra, and J. Carroll, “Relationship between the foveal avascular zone and foveal pit morphology,” Investig. Ophthamol. Vis. Sci. 53, 1628–1636 (2012).

Dubow, M.

Dubra, A.

Federman, J. L.

T. J. Ffytche, J. S. Shilling, I. H. Chisholm, and J. L. Federman, “Indications for fluorescein angiography in disease of the ocular fundus: a review,” J. R. Soc. Med. 73, 362–365 (1980).

Ffytche, T. J.

T. J. Ffytche, J. S. Shilling, I. H. Chisholm, and J. L. Federman, “Indications for fluorescein angiography in disease of the ocular fundus: a review,” J. R. Soc. Med. 73, 362–365 (1980).

Fingler, J.

Ford, T. N.

T. N. Ford, K. K. Chu, and J. Mertz, “Phase-gradient microscopy in thick tissue with oblique back-illumination,” Nat. Methods 9, 1195–1197 (2012).
[CrossRef]

Fraser, S. E.

Fujii, H.

Y. Tamaki, M. Araie, K. Tomita, M. Nagahara, A. Tomidokoro, and H. Fujii, “Real-time measurement of human optic nerve head and choroid circulation, using the laser speckle phenomenon,” Jpn. J. Ophthalmol. 41, 49–54 (1997).

Gao, W.

Gass, J. D.

J. D. Gass and R. T. Oyakawa, “Idiopathic juxtafoveolar retinal telangiectasis,” Arch. Ophthalmol. 100, 769–780 (1982).

Gast, T. J.

T. Y. P. Chui, T. J. Gast, and S. A. Burns, “Imaging of vascular wall fine structure in the human retina using adaptive optics scanning laser ophthalmoscopy,” Investig. Ophthamol. Vis. Sci. 54, 7115–7124 (2013).

Gee, B. P.

D. Scoles, D. C. Gray, J. J. Hunter, R. Wolfe, B. P. Gee, Y. Geng, B. D. Masella, R. T. Libby, S. Russell, D. R. Williams, and W. H. Merigan, “In-vivo imaging of retinal nerve fiber layer vasculature: imaging histology comparison,” BMC Ophthalmol. 9, 9 (2009).

Geng, Y.

D. Scoles, D. C. Gray, J. J. Hunter, R. Wolfe, B. P. Gee, Y. Geng, B. D. Masella, R. T. Libby, S. Russell, D. R. Williams, and W. H. Merigan, “In-vivo imaging of retinal nerve fiber layer vasculature: imaging histology comparison,” BMC Ophthalmol. 9, 9 (2009).

Gray, D. C.

D. Scoles, D. C. Gray, J. J. Hunter, R. Wolfe, B. P. Gee, Y. Geng, B. D. Masella, R. T. Libby, S. Russell, D. R. Williams, and W. H. Merigan, “In-vivo imaging of retinal nerve fiber layer vasculature: imaging histology comparison,” BMC Ophthalmol. 9, 9 (2009).

Greenfield, D. S.

D. S. Greenfield, R. W. Knighton, and X. R. Huang, “Effect of corneal polarization axis on assessment of retinal nerve fiber layer thickness by scanning laser polarimetry,” Am. J. Ophthalmol. 129, 715–722 (2000).

Grinvald, A.

D. A. Nelson, S. Krupsky, A. Pollack, E. Aloni, M. Belkin, I. Vanzetta, M. Rosner, and A. Grinvald, “Special report: noninvasive multi-parameter functional optical imaging of the eye,” Ophthalmic Surg. Lasers Imaging 36, 57–66 (2005).

Grunwald, J. E.

C. E. Riva, J. E. Grunwald, S. H. Sinclair, and B. L. Petrig, “Blood velocity and volumetric flow rate in human retinal vessels,” Investig. Ophthalmol. Vis. Sci. 26, 1124–1132 (1985).

Gu, D.

A. V. Cideciyan, S. G. Jacobson, T. S. Aleman, D. Gu, S. E. Pearce-Kelling, A. Sumaroka, G. M. Acland, and G. D. Aguirre, “In vivo dynamics of retinal injury and repair in the rhodopsin mutant dog model of human retinitis pigmentosa,” Proc. Natl. Acad. Sci. USA 102, 5233–5238 (2005).

Hamilton, A. M.

E. M. Kohner, A. M. Hamilton, S. J. Saunders, B. A. Sutcliffe, and C. J. Bulpitt, “The retinal blood flow in diabetes,” Diabetologia 11, 27–33 (1975).
[CrossRef]

Hamilton, D. K.

D. K. Hamilton and C. J. R. Sheppard, “Differential phase-contrast in scanning optical microscopy,” J. Microsc. 133, 27–39 (1984).
[CrossRef]

T. Wilson and D. K. Hamilton, “Differential amplitude contrast imaging in the scanning optical microscope,” Appl. Phys. B 32, 187–191 (1983).
[CrossRef]

Hamilton, P.

P. E. Stanga, J. I. Lim, and P. Hamilton, “Indocyanine green angiography in chorioretinal diseases: indications and interpretation: an evidence-based update,” Ophthalmology 110, 15–21 (2003).
[CrossRef]

Hansen, B. R.

A. M. Dubis, B. R. Hansen, R. F. Cooper, J. Beringer, A. Dubra, and J. Carroll, “Relationship between the foveal avascular zone and foveal pit morphology,” Investig. Ophthamol. Vis. Sci. 53, 1628–1636 (2012).

Harvey, Z.

A. Dubra and Z. Harvey, “Registration of 2D images from fast scanning ophthalmic instruments,” in The 4th International Workshop on Biomedical Image Registration, Lübeck, Germany (2010), pp. 60–71.

Hong, Y. J.

Huang, X. R.

R. W. Knighton and X. R. Huang, “Linear birefringence of the central human cornea,” Investig. Ophthamol. Vis. Sci. 43, 82–86 (2002).

D. S. Greenfield, R. W. Knighton, and X. R. Huang, “Effect of corneal polarization axis on assessment of retinal nerve fiber layer thickness by scanning laser polarimetry,” Am. J. Ophthalmol. 129, 715–722 (2000).

Hughes, G. W.

Hunter, J. J.

D. Scoles, D. C. Gray, J. J. Hunter, R. Wolfe, B. P. Gee, Y. Geng, B. D. Masella, R. T. Libby, S. Russell, D. R. Williams, and W. H. Merigan, “In-vivo imaging of retinal nerve fiber layer vasculature: imaging histology comparison,” BMC Ophthalmol. 9, 9 (2009).

Izatt, J. A.

Jacobson, S. G.

A. V. Cideciyan, S. G. Jacobson, T. S. Aleman, D. Gu, S. E. Pearce-Kelling, A. Sumaroka, G. M. Acland, and G. D. Aguirre, “In vivo dynamics of retinal injury and repair in the rhodopsin mutant dog model of human retinitis pigmentosa,” Proc. Natl. Acad. Sci. USA 102, 5233–5238 (2005).

Jones, S. M.

Jonnal, R. S.

Jung, F.

S. Wolf, O. Arend, H. Toonen, B. Bertram, F. Jung, and M. Reim, “Retinal capillary blood flow measurement with a scanning laser ophthalmoscope. Preliminary results,” Ophthalmology 98, 996–1000 (1991).
[CrossRef]

Juškaitis, R.

Kawata, S.

Kawata, Y.

Knighton, R. W.

R. W. Knighton and X. R. Huang, “Linear birefringence of the central human cornea,” Investig. Ophthamol. Vis. Sci. 43, 82–86 (2002).

D. S. Greenfield, R. W. Knighton, and X. R. Huang, “Effect of corneal polarization axis on assessment of retinal nerve fiber layer thickness by scanning laser polarimetry,” Am. J. Ophthalmol. 129, 715–722 (2000).

Kohner, E. M.

E. M. Kohner, A. M. Hamilton, S. J. Saunders, B. A. Sutcliffe, and C. J. Bulpitt, “The retinal blood flow in diabetes,” Diabetologia 11, 27–33 (1975).
[CrossRef]

Koncz, L.

B. I. Chazan, M. C. Balodimos, and L. Koncz, “Untoward effects of fluorescein retinal angiography in diabetic patients,” Ann. Ophthalmol. 3, 42 (1971).

Krupsky, S.

D. A. Nelson, S. Krupsky, A. Pollack, E. Aloni, M. Belkin, I. Vanzetta, M. Rosner, and A. Grinvald, “Special report: noninvasive multi-parameter functional optical imaging of the eye,” Ophthalmic Surg. Lasers Imaging 36, 57–66 (2005).

Kulkarni, A. D.

A. D. Kulkarni and B. D. Kuppermann, “Wet age-related macular degeneration,” Adv. Drug Deliv. Rev. 57, 1994–2009 (2005).

Kuppermann, B. D.

A. D. Kulkarni and B. D. Kuppermann, “Wet age-related macular degeneration,” Adv. Drug Deliv. Rev. 57, 1994–2009 (2005).

Kurokawa, K.

Laufer, J.

W. B. Amos, S. Reichelt, D. M. Cattermole, and J. Laufer, “Re-evaluation of differential phase contrast (DPC) in a scanning laser microscope using a split-detector as an alternative to differential interference contrast (DIC) optics,” J. Microsc. 210, 166–175 (2003).
[CrossRef]

Libby, R. T.

D. Scoles, D. C. Gray, J. J. Hunter, R. Wolfe, B. P. Gee, Y. Geng, B. D. Masella, R. T. Libby, S. Russell, D. R. Williams, and W. H. Merigan, “In-vivo imaging of retinal nerve fiber layer vasculature: imaging histology comparison,” BMC Ophthalmol. 9, 9 (2009).

Lim, J. I.

P. E. Stanga, J. I. Lim, and P. Hamilton, “Indocyanine green angiography in chorioretinal diseases: indications and interpretation: an evidence-based update,” Ophthalmology 110, 15–21 (2003).
[CrossRef]

Linfoot, E. H.

E. H. Linfoot and E. Wolf, “Diffraction images in systems with an annular aperture,” Proc. Phys. Soc. B 66, 145 (1953).

MacGillivray, T.

N. Patton, T. Aslam, T. MacGillivray, A. Pattie, I. J. Deary, and B. Dhillon, “Retinal vascular image analysis as a potential screening tool for cerebrovascular disease: a rationale based on homology between cerebral and retinal microvasculatures,” J. Anat. 206, 319–348 (2005).

Makita, S.

Martin, J. A.

J. Tam, J. A. Martin, and A. Roorda, “Non-invasive visualization and analysis of parafoveal capillaries in humans,” Investig. Ophthamol. Vis. Sci. 51, 1691–1698 (2010).

Masella, B. D.

D. Scoles, D. C. Gray, J. J. Hunter, R. Wolfe, B. P. Gee, Y. Geng, B. D. Masella, R. T. Libby, S. Russell, D. R. Williams, and W. H. Merigan, “In-vivo imaging of retinal nerve fiber layer vasculature: imaging histology comparison,” BMC Ophthalmol. 9, 9 (2009).

Merigan, W. H.

D. Scoles, D. C. Gray, J. J. Hunter, R. Wolfe, B. P. Gee, Y. Geng, B. D. Masella, R. T. Libby, S. Russell, D. R. Williams, and W. H. Merigan, “In-vivo imaging of retinal nerve fiber layer vasculature: imaging histology comparison,” BMC Ophthalmol. 9, 9 (2009).

Mertz, J.

T. N. Ford, K. K. Chu, and J. Mertz, “Phase-gradient microscopy in thick tissue with oblique back-illumination,” Nat. Methods 9, 1195–1197 (2012).
[CrossRef]

Metha, A.

Michelson, G.

G. Michelson and B. Schmauss, “Two dimensional mapping of the perfusion of the retina and optic nerve head,” Br. J. Ophthalmol. 79, 1126–1132 (1995).

Miller, D. T.

Mujat, M.

Nagahara, M.

Y. Tamaki, M. Araie, K. Tomita, M. Nagahara, A. Tomidokoro, and H. Fujii, “Real-time measurement of human optic nerve head and choroid circulation, using the laser speckle phenomenon,” Jpn. J. Ophthalmol. 41, 49–54 (1997).

Nelson, D. A.

D. A. Nelson, S. Krupsky, A. Pollack, E. Aloni, M. Belkin, I. Vanzetta, M. Rosner, and A. Grinvald, “Special report: noninvasive multi-parameter functional optical imaging of the eye,” Ophthalmic Surg. Lasers Imaging 36, 57–66 (2005).

Nomarski, G. J.

G. J. Nomarski, “Microintérferomtrè différentiel à ondes polarisées,” J. Physiol. Paris 16, S9–S13 (1955).

Oyakawa, R. T.

J. D. Gass and R. T. Oyakawa, “Idiopathic juxtafoveolar retinal telangiectasis,” Arch. Ophthalmol. 100, 769–780 (1982).

Park, B. H.

Pattie, A.

N. Patton, T. Aslam, T. MacGillivray, A. Pattie, I. J. Deary, and B. Dhillon, “Retinal vascular image analysis as a potential screening tool for cerebrovascular disease: a rationale based on homology between cerebral and retinal microvasculatures,” J. Anat. 206, 319–348 (2005).

Patton, N.

N. Patton, T. Aslam, T. MacGillivray, A. Pattie, I. J. Deary, and B. Dhillon, “Retinal vascular image analysis as a potential screening tool for cerebrovascular disease: a rationale based on homology between cerebral and retinal microvasculatures,” J. Anat. 206, 319–348 (2005).

Pearce-Kelling, S. E.

A. V. Cideciyan, S. G. Jacobson, T. S. Aleman, D. Gu, S. E. Pearce-Kelling, A. Sumaroka, G. M. Acland, and G. D. Aguirre, “In vivo dynamics of retinal injury and repair in the rhodopsin mutant dog model of human retinitis pigmentosa,” Proc. Natl. Acad. Sci. USA 102, 5233–5238 (2005).

Petrig, B. L.

C. E. Riva, J. E. Grunwald, S. H. Sinclair, and B. L. Petrig, “Blood velocity and volumetric flow rate in human retinal vessels,” Investig. Ophthalmol. Vis. Sci. 26, 1124–1132 (1985).

Pierce, M. C.

Pinhas, A.

Pollack, A.

D. A. Nelson, S. Krupsky, A. Pollack, E. Aloni, M. Belkin, I. Vanzetta, M. Rosner, and A. Grinvald, “Special report: noninvasive multi-parameter functional optical imaging of the eye,” Ophthalmic Surg. Lasers Imaging 36, 57–66 (2005).

Reichelt, S.

W. B. Amos, S. Reichelt, D. M. Cattermole, and J. Laufer, “Re-evaluation of differential phase contrast (DPC) in a scanning laser microscope using a split-detector as an alternative to differential interference contrast (DIC) optics,” J. Microsc. 210, 166–175 (2003).
[CrossRef]

Reim, M.

S. Wolf, O. Arend, W. E. Sponsel, K. Schulte, L. B. Cantor, and M. Reim, “Retinal hemodynamics using scanning laser ophthalmoscopy and hemorheology in chronic open-angle glaucoma,” Ophthalmology 100, 1561–1566 (1993).
[CrossRef]

S. Wolf, O. Arend, H. Toonen, B. Bertram, F. Jung, and M. Reim, “Retinal capillary blood flow measurement with a scanning laser ophthalmoscope. Preliminary results,” Ophthalmology 98, 996–1000 (1991).
[CrossRef]

Riva, C.

T. Tanaka, C. Riva, and I. Ben-Sira, “Blood velocity measurements in human retinal vessels,” Science 186, 830–831 (1974).
[CrossRef]

Riva, C. E.

C. E. Riva, J. E. Grunwald, S. H. Sinclair, and B. L. Petrig, “Blood velocity and volumetric flow rate in human retinal vessels,” Investig. Ophthalmol. Vis. Sci. 26, 1124–1132 (1985).

Rollins, A. M.

Roorda, A.

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]

J. Tam, J. A. Martin, and A. Roorda, “Non-invasive visualization and analysis of parafoveal capillaries in humans,” Investig. Ophthamol. Vis. Sci. 51, 1691–1698 (2010).

Rosen, R. B.

Rosner, M.

D. A. Nelson, S. Krupsky, A. Pollack, E. Aloni, M. Belkin, I. Vanzetta, M. Rosner, and A. Grinvald, “Special report: noninvasive multi-parameter functional optical imaging of the eye,” Ophthalmic Surg. Lasers Imaging 36, 57–66 (2005).

Russell, S.

D. Scoles, D. C. Gray, J. J. Hunter, R. Wolfe, B. P. Gee, Y. Geng, B. D. Masella, R. T. Libby, S. Russell, D. R. Williams, and W. H. Merigan, “In-vivo imaging of retinal nerve fiber layer vasculature: imaging histology comparison,” BMC Ophthalmol. 9, 9 (2009).

Sasaki, K.

Saunders, S. J.

E. M. Kohner, A. M. Hamilton, S. J. Saunders, B. A. Sutcliffe, and C. J. Bulpitt, “The retinal blood flow in diabetes,” Diabetologia 11, 27–33 (1975).
[CrossRef]

Schmauss, B.

G. Michelson and B. Schmauss, “Two dimensional mapping of the perfusion of the retina and optic nerve head,” Br. J. Ophthalmol. 79, 1126–1132 (1995).

Schulte, K.

S. Wolf, O. Arend, W. E. Sponsel, K. Schulte, L. B. Cantor, and M. Reim, “Retinal hemodynamics using scanning laser ophthalmoscopy and hemorheology in chronic open-angle glaucoma,” Ophthalmology 100, 1561–1566 (1993).
[CrossRef]

Schwartz, D.

Scoles, D.

D. Scoles, Y. N. Sulai, and A. Dubra, “In vivo dark-field imaging of the retinal pigment epithelium cellmosaic,” Biomed. Opt. Express 4, 1710–1723 (2013).
[CrossRef]

D. Scoles, D. C. Gray, J. J. Hunter, R. Wolfe, B. P. Gee, Y. Geng, B. D. Masella, R. T. Libby, S. Russell, D. R. Williams, and W. H. Merigan, “In-vivo imaging of retinal nerve fiber layer vasculature: imaging histology comparison,” BMC Ophthalmol. 9, 9 (2009).

Scoles, D. H.

Shah, N.

Sheppard, C. J. R.

D. K. Hamilton and C. J. R. Sheppard, “Differential phase-contrast in scanning optical microscopy,” J. Microsc. 133, 27–39 (1984).
[CrossRef]

Shilling, J. S.

T. J. Ffytche, J. S. Shilling, I. H. Chisholm, and J. L. Federman, “Indications for fluorescein angiography in disease of the ocular fundus: a review,” J. R. Soc. Med. 73, 362–365 (1980).

Sinclair, S. H.

C. E. Riva, J. E. Grunwald, S. H. Sinclair, and B. L. Petrig, “Blood velocity and volumetric flow rate in human retinal vessels,” Investig. Ophthalmol. Vis. Sci. 26, 1124–1132 (1985).

Sliney, D. H.

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, 602–661 (2012).

Sponsel, W. E.

S. Wolf, O. Arend, W. E. Sponsel, K. Schulte, L. B. Cantor, and M. Reim, “Retinal hemodynamics using scanning laser ophthalmoscopy and hemorheology in chronic open-angle glaucoma,” Ophthalmology 100, 1561–1566 (1993).
[CrossRef]

Stanga, P. E.

P. E. Stanga, J. I. Lim, and P. Hamilton, “Indocyanine green angiography in chorioretinal diseases: indications and interpretation: an evidence-based update,” Ophthalmology 110, 15–21 (2003).
[CrossRef]

Stern, W. H.

W. H. Stern and D. B. Archer, “Retinal vascular occlusion,” Annu. Rev. Med. 32, 101–106 (1981).

Sulai, Y.

Sulai, Y. N.

Sumaroka, A.

A. V. Cideciyan, S. G. Jacobson, T. S. Aleman, D. Gu, S. E. Pearce-Kelling, A. Sumaroka, G. M. Acland, and G. D. Aguirre, “In vivo dynamics of retinal injury and repair in the rhodopsin mutant dog model of human retinitis pigmentosa,” Proc. Natl. Acad. Sci. USA 102, 5233–5238 (2005).

Sutcliffe, B. A.

E. M. Kohner, A. M. Hamilton, S. J. Saunders, B. A. Sutcliffe, and C. J. Bulpitt, “The retinal blood flow in diabetes,” Diabetologia 11, 27–33 (1975).
[CrossRef]

Tam, J.

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]

J. Tam, J. A. Martin, and A. Roorda, “Non-invasive visualization and analysis of parafoveal capillaries in humans,” Investig. Ophthamol. Vis. Sci. 51, 1691–1698 (2010).

Tamaki, Y.

Y. Tamaki, M. Araie, K. Tomita, M. Nagahara, A. Tomidokoro, and H. Fujii, “Real-time measurement of human optic nerve head and choroid circulation, using the laser speckle phenomenon,” Jpn. J. Ophthalmol. 41, 49–54 (1997).

Tanaka, T.

Tiruveedhula, P.

Tomidokoro, A.

Y. Tamaki, M. Araie, K. Tomita, M. Nagahara, A. Tomidokoro, and H. Fujii, “Real-time measurement of human optic nerve head and choroid circulation, using the laser speckle phenomenon,” Jpn. J. Ophthalmol. 41, 49–54 (1997).

Tomita, K.

Y. Tamaki, M. Araie, K. Tomita, M. Nagahara, A. Tomidokoro, and H. Fujii, “Real-time measurement of human optic nerve head and choroid circulation, using the laser speckle phenomenon,” Jpn. J. Ophthalmol. 41, 49–54 (1997).

Toonen, H.

S. Wolf, O. Arend, H. Toonen, B. Bertram, F. Jung, and M. Reim, “Retinal capillary blood flow measurement with a scanning laser ophthalmoscope. Preliminary results,” Ophthalmology 98, 996–1000 (1991).
[CrossRef]

VanNasdale, D. A.

Vanzetta, I.

D. A. Nelson, S. Krupsky, A. Pollack, E. Aloni, M. Belkin, I. Vanzetta, M. Rosner, and A. Grinvald, “Special report: noninvasive multi-parameter functional optical imaging of the eye,” Ophthalmic Surg. Lasers Imaging 36, 57–66 (2005).

Walsh, J. B.

Webb, R. H.

Weitz, R.

Werner, J. S.

Williams, D. R.

D. Scoles, D. C. Gray, J. J. Hunter, R. Wolfe, B. P. Gee, Y. Geng, B. D. Masella, R. T. Libby, S. Russell, D. R. Williams, and W. H. Merigan, “In-vivo imaging of retinal nerve fiber layer vasculature: imaging histology comparison,” BMC Ophthalmol. 9, 9 (2009).

Wilson, T.

Wolf, E.

E. H. Linfoot and E. Wolf, “Diffraction images in systems with an annular aperture,” Proc. Phys. Soc. B 66, 145 (1953).

M. Born and E. Wolf, Principles of Optics, 6th (corrected) ed. (Pergamon, 1980).

Wolf, S.

S. Wolf, O. Arend, W. E. Sponsel, K. Schulte, L. B. Cantor, and M. Reim, “Retinal hemodynamics using scanning laser ophthalmoscopy and hemorheology in chronic open-angle glaucoma,” Ophthalmology 100, 1561–1566 (1993).
[CrossRef]

S. Wolf, O. Arend, H. Toonen, B. Bertram, F. Jung, and M. Reim, “Retinal capillary blood flow measurement with a scanning laser ophthalmoscope. Preliminary results,” Ophthalmology 98, 996–1000 (1991).
[CrossRef]

Wolfe, R.

D. Scoles, D. C. Gray, J. J. Hunter, R. Wolfe, B. P. Gee, Y. Geng, B. D. Masella, R. T. Libby, S. Russell, D. R. Williams, and W. H. Merigan, “In-vivo imaging of retinal nerve fiber layer vasculature: imaging histology comparison,” BMC Ophthalmol. 9, 9 (2009).

Yasuno, Y.

Yazdanfar, S.

Zawadzki, R. J.

Zhong, Z.

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, 602–661 (2012).

Adv. Drug Deliv. Rev. (1)

A. D. Kulkarni and B. D. Kuppermann, “Wet age-related macular degeneration,” Adv. Drug Deliv. Rev. 57, 1994–2009 (2005).

Am. J. Ophthalmol. (1)

D. S. Greenfield, R. W. Knighton, and X. R. Huang, “Effect of corneal polarization axis on assessment of retinal nerve fiber layer thickness by scanning laser polarimetry,” Am. J. Ophthalmol. 129, 715–722 (2000).

Ann. Ophthalmol. (1)

B. I. Chazan, M. C. Balodimos, and L. Koncz, “Untoward effects of fluorescein retinal angiography in diabetic patients,” Ann. Ophthalmol. 3, 42 (1971).

Annu. Rev. Med. (1)

W. H. Stern and D. B. Archer, “Retinal vascular occlusion,” Annu. Rev. Med. 32, 101–106 (1981).

Appl. Opt. (2)

Appl. Phys. B (1)

T. Wilson and D. K. Hamilton, “Differential amplitude contrast imaging in the scanning optical microscope,” Appl. Phys. B 32, 187–191 (1983).
[CrossRef]

Arch. Ophthalmol. (1)

J. D. Gass and R. T. Oyakawa, “Idiopathic juxtafoveolar retinal telangiectasis,” Arch. Ophthalmol. 100, 769–780 (1982).

Biomed. Opt. Express (7)

BMC Ophthalmol. (1)

D. Scoles, D. C. Gray, J. J. Hunter, R. Wolfe, B. P. Gee, Y. Geng, B. D. Masella, R. T. Libby, S. Russell, D. R. Williams, and W. H. Merigan, “In-vivo imaging of retinal nerve fiber layer vasculature: imaging histology comparison,” BMC Ophthalmol. 9, 9 (2009).

Br. J. Ophthalmol. (1)

G. Michelson and B. Schmauss, “Two dimensional mapping of the perfusion of the retina and optic nerve head,” Br. J. Ophthalmol. 79, 1126–1132 (1995).

Diabetologia (1)

E. M. Kohner, A. M. Hamilton, S. J. Saunders, B. A. Sutcliffe, and C. J. Bulpitt, “The retinal blood flow in diabetes,” Diabetologia 11, 27–33 (1975).
[CrossRef]

Investig. Ophthalmol. Vis. Sci. (1)

C. E. Riva, J. E. Grunwald, S. H. Sinclair, and B. L. Petrig, “Blood velocity and volumetric flow rate in human retinal vessels,” Investig. Ophthalmol. Vis. Sci. 26, 1124–1132 (1985).

Investig. Ophthamol. Vis. Sci. (4)

J. Tam, J. A. Martin, and A. Roorda, “Non-invasive visualization and analysis of parafoveal capillaries in humans,” Investig. Ophthamol. Vis. Sci. 51, 1691–1698 (2010).

A. M. Dubis, B. R. Hansen, R. F. Cooper, J. Beringer, A. Dubra, and J. Carroll, “Relationship between the foveal avascular zone and foveal pit morphology,” Investig. Ophthamol. Vis. Sci. 53, 1628–1636 (2012).

T. Y. P. Chui, T. J. Gast, and S. A. Burns, “Imaging of vascular wall fine structure in the human retina using adaptive optics scanning laser ophthalmoscopy,” Investig. Ophthamol. Vis. Sci. 54, 7115–7124 (2013).

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Supplementary Material (1)

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Figures (10)

Fig. 1.
Fig. 1.

Masks placed in the retinal conjugate plane in front of the AOSLO point detector(s), with black denoting opaque regions. The arrows indicate the sizes referenced in the text. Split-detection is the only detection scheme with two detectors (Ch. 1 and 2).

Fig. 2.
Fig. 2.

Reflectance AOSLO images of the inferior-temporal corner of the FAZ (0.6° temporal and inferior from fixation) collected in subject JC_0200 using the following detection apertures: circular, annulus, circular with an opaque filament, knife-edge, and split-detector. The red boxes indicate the vessel segment from which the intensity profiles in Fig. 4 are plotted. Scale bar is 50 μm across.

Fig. 3.
Fig. 3.

Perfusion maps corresponding to the image sequences averaged to create Fig. 2. The red boxes indicate the vessel segment from which the intensity profiles in Fig. 4 are plotted. Scale bar is 50 μm.

Fig. 4.
Fig. 4.

Intensity profiles of the vessel boxed in the reflectance images of Fig. 2 (blue, solid) and the perfusion maps of Fig. 3 (red, dashed). Each curve is normalized to its background (nonvessel values) and the shaded regions correspond to ±1 standard deviation away from the mean. The vertical axes refer to gray levels in arbitrary units. Scale bar is 20 μm across.

Fig. 5.
Fig. 5.

Reflectance AOSLO images at 5° nasal and inferior from fixation collected in subject JC_0200 using the following detection apertures: circular, annulus, circular with an opaque filament, knife-edge, and split-detector. Scale bar is 50 μm across.

Fig. 6.
Fig. 6.

Perfusion maps corresponding to the image sequences averaged to create Fig. 5. Scale bar is 50 μm.

Fig. 7.
Fig. 7.

Split-detection AOSLO reflectance (first and third columns) and perfusion (second and fourth columns) images collected in subject AD_1025 with and without an apodized illumination pupil at the edge of the FAZ (0.6° temporal and inferior from fixation) and at 5° nasal and inferior from fixation (5N5I). Scale bar is 50 μm across.

Fig. 8.
Fig. 8.

Split-detection AOSLO reflectance (first and third columns) and perfusion (second and fourth columns) from subject AD_1025 collected with linearly polarized illumination and a linear polarizer in different orientations in the exit pupil. The orientations indicated on the left are relative to the orientation for maximum transmission. Scale bar is 50 μm across.

Fig. 9.
Fig. 9.

Split-detection AOSLO reflectance and perfusion images collected in subject JC_1246 using different wavelengths. Each retinal eccentricity imaged with 560 or 600 nm was re-imaged with 680 nm for comparison. The locations are as follows: 560 nm—12° nasal, 4° inferior (1 ADD) and 7° nasal, 4° inferior (4 ADD). 600 nm—13° nasal, 5° superior (1 ADD) and 7° nasal, 5° superior (4 ADD). All locations listed in degrees of visual angle relative to fixation. Scale bar is 50 μm across.

Fig. 10.
Fig. 10.

Split-detection motion contrast (perfusion) artifacts due to the asymmetric intensity profile of blood cells (bright on the left, dark on the right; Media 1). Top row: Split-detector reflectance and perfusion images collected in subject JC_0200 at 3° nasal to fixation. Bottom row: Cross sections through a single capillary at the points along its path boxed in the top row images. The vertical axis refers to gray levels in arbitrary units. Scale bars are 20 μm across.

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