Abstract

Capillary flow largely consists of alternating red cells and plasma whose speed oscillates predictably with the cardiac cycle. Superimposed on this regular background are sporadic events potentially disruptive to capillary exchange: the passage of white cells, aggregates of red cells, epochs of sparse haematocrit, or unusually slow flow. Such events are not readily differentiated with velocimetry or perfusion mapping. Here we propose a method to identify these phenomena in retinal capillaries imaged with high frame-rate adaptive optics, by calculating and representing pictorially the autocorrelation of intensity through time at each pixel during short epochs. The phenomena described above manifest as bright regions which transiently appear and propagate across an otherwise dark image. Drawing data from normal subjects and those with Type I diabetes, we demonstrate proof of concept and high sensitivity and specificity of this metric to variations in capillary contents and rate of flow in health and disease. The proposed metric offers a useful adjunct to velocimetry and perfusion mapping in the study of normal and abnormal capillary blood flow.

© 2019 Optical Society of America under the terms of the OSA Open Access Publishing Agreement

Full Article  |  PDF Article
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References

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    [Crossref]
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    [Crossref]
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    [Crossref]
  6. J. Tam and A. Roorda, “Speed quantification and tracking of moving objects in adaptive optics scanning laser ophthalmoscopy,” J. Biomed. Opt. 16(3), 036002 (2011).
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    [Crossref]
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    [Crossref]
  24. S. Arichika, A. Uji, T. Murakami, N. Unoki, S. Yoshitake, Y. Dodo, S. Ooto, K. Miyamoto, and N. Yoshimura, “Retinal hemorheologic characterization of early-stage diabetic retinopathy using adaptive optics scanning laser ophthalmoscopy,” Invest. Ophthalmol. Visual Sci. 55(12), 8513–8522 (2014).
    [Crossref]
  25. Z. Burgansky-Eliash, A. Barak, H. Barash, D. A. Nelson, O. Pupko, A. Lowenstein, A. Grinvald, and A. Rubinstein, “Increased retinal blood flow velocity in patients with early diabetes mellitus,” Retina 32(1), 112–119 (2012).
    [Crossref]
  26. Z. Burgansky-Eliash, D. A. Nelson, O. P. Bar-Tal, A. Lowenstein, A. Grinvald, and A. Barak, “Reduced retinal blood flow velocity in diabetic retinopathy,” Retina 30(5), 765–773 (2010).
    [Crossref]
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    [Crossref]
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    [Crossref]
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    [Crossref]
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    [Crossref]
  31. B. Gu, X. Wang, M. D. Twa, J. Tam, C. A. Girkin, and Y. Zhang, “Noninvasive in vivo characterization of erythrocyte motion in human retinal capillaries using high-speed adaptive optics near-confocal imaging,” Biomed. Opt. Express 9(8), 3653–3677 (2018).
    [Crossref]
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    [Crossref]
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    [Crossref]
  37. S. Reitsma, D. W. Slaaf, H. Vink, M. A. Van Zandvoort, and M. G. Oude Egbrink, “The endothelial glycocalyx: composition, functions, and visualization,” Pfluegers Arch. 454(3), 345–359 (2007).
    [Crossref]

2019 (3)

C. Berry, N. Sidik, A. C. Pereira, T. J. Ford, R. M. Touyz, J. C. Kaski, and A. H. Hainsworth, “Small-Vessel Disease in the Heart and Brain: Current Knowledge, Unmet Therapeutic Need, and Future Directions,” J. Am. Heart Assoc. 8(3), e011104 (2019).
[Crossref]

P. Bedggood and A. Metha, “Mapping flow velocity in the human retinal capillary network with pixel intensity cross correlation,” PLoS One 14(6), e0218918 (2019).
[Crossref]

A. Joseph, A. Guevara-Torres, and J. Schallek, “Imaging single-cell blood flow in the smallest to largest vessels in the living retina,” eLife 8, e45077 (2019).
[Crossref]

2018 (2)

B. Gu, X. Wang, M. D. Twa, J. Tam, C. A. Girkin, and Y. Zhang, “Noninvasive in vivo characterization of erythrocyte motion in human retinal capillaries using high-speed adaptive optics near-confocal imaging,” Biomed. Opt. Express 9(8), 3653–3677 (2018).
[Crossref]

J. Lammer, S. G. Karst, M. M. Lin, M. Cheney, P. S. Silva, S. A. Burns, L. P. Aiello, and J. K. Sun, “Association of Microaneurysms on Adaptive Optics Scanning Laser Ophthalmoscopy With Surrounding Neuroretinal Pathology and Visual Function in Diabetes,” Invest. Ophthalmol. Visual Sci. 59(13), 5633–5640 (2018).
[Crossref]

2017 (1)

T. Luo, T. J. Gast, T. J. Vermeer, and S. A. Burns, “Retinal vascular branching in healthy and diabetic subjects,” Invest. Ophthalmol. Visual Sci. 58(5), 2685–2694 (2017).
[Crossref]

2016 (9)

J. G. Hillard, T. J. Gast, T. Y. Chui, D. Sapir, and S. A. Burns, “Retinal arterioles in hypo-, normo-, and hypertensive subjects measured using adaptive optics,” Trans. Vis. Sci. Tech. 5(4), 16 (2016).
[Crossref]

T. Y. Chui, S. Mo, B. Krawitz, N. R. Menon, N. Choudhury, A. Gan, M. Razeen, N. Shah, A. Pinhas, and R. B. Rosen, “Human retinal microvascular imaging using adaptive optics scanning light ophthalmoscopy,” Int. J. Retin. Vitr. 2(1), 11 (2016).
[Crossref]

T. Y. P. Chui, A. Pinhas, A. Gan, M. Razeen, N. Shah, E. Cheang, C. L. Liu, A. Dubra, and R. B. Rosen, “Longitudinal imaging of microvascular remodelling in proliferative diabetic retinopathy using adaptive optics scanning light ophthalmoscopy,” Ophthalmic Physiol. Opt. 36(3), 290–302 (2016).
[Crossref]

F. Bosetti, Z. S. Galis, M. S. Bynoe, M. Charette, M. J. Cipolla, G. J. Del Zoppo, D. Gould, T. S. Hatsukami, T. L. Jones, and J. I. Koenig, ““Small Blood Vessels: Big Health Problems?”: Scientific Recommendations of the National Institutes of Health Workshop,” J. Am. Heart Assoc. 5(11), e004389 (2016).
[Crossref]

A. de Castro, G. Huang, L. Sawides, T. Luo, and S. A. Burns, “Rapid high resolution imaging with a dual-channel scanning technique,” Opt. Lett. 41(8), 1881–1884 (2016).
[Crossref]

A. Guevara-Torres, A. Joseph, and J. Schallek, “Label free measurement of retinal blood cell flux, velocity, hematocrit and capillary width in the living mouse eye,” Biomed. Opt. Express 7(10), 4228–4249 (2016).
[Crossref]

D. Rosenbaum, A. Mattina, E. Koch, F. Rossant, A. Gallo, N. Kachenoura, M. Paques, A. Redheuil, and X. Girerd, “Effects of age, blood pressure and antihypertensive treatments on retinal arterioles remodeling assessed by adaptive optics,” J. Hypertens. 34(6), 1115–1122 (2016).
[Crossref]

A. Duan, P. A. Bedggood, B. V. Bui, and A. B. Metha, “Evidence of flicker-induced functional hyperaemia in the smallest vessels of the human retinal blood supply,” PLoS One 11(9), e0162621 (2016).
[Crossref]

X. Fu, J. S. Gens, J. A. Glazier, S. A. Burns, and T. J. Gast, “Progression of diabetic capillary occlusion: a model,” PLoS Comput. Biol. 12(6), e1004932 (2016).
[Crossref]

2015 (1)

S. Arichika, A. Uji, S. Ooto, Y. Muraoka, and N. Yoshimura, “Effects of age and blood pressure on the retinal arterial wall, analyzed using adaptive optics scanning laser ophthalmoscopy,” Sci. Rep. 5(1), 12283 (2015).
[Crossref]

2014 (5)

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

P. Bedggood and A. Metha, “Analysis of contrast and motion signals generated by human blood constituents in capillary flow,” Opt. Lett. 39(3), 610–613 (2014).
[Crossref]

S. A. Burns, A. E. Elsner, T. Y. Chui, D. A. VanNasdale, C. A. Clark, T. J. Gast, V. E. Malinovsky, and A.-D. T. Phan, “In vivo adaptive optics microvascular imaging in diabetic patients without clinically severe diabetic retinopathy,” Biomed. Opt. Express 5(3), 961–974 (2014).
[Crossref]

A. Pinhas, M. Razeen, M. Dubow, A. Gan, T. Y. Chui, N. Shah, M. Mehta, R. C. Gentile, R. Weitz, and J. B. Walsh, “Assessment of perfused foveal microvascular density and identification of nonperfused capillaries in healthy and vasculopathic eyes,” Invest. Ophthalmol. Visual Sci. 55(12), 8056–8066 (2014).
[Crossref]

S. Arichika, A. Uji, T. Murakami, N. Unoki, S. Yoshitake, Y. Dodo, S. Ooto, K. Miyamoto, and N. Yoshimura, “Retinal hemorheologic characterization of early-stage diabetic retinopathy using adaptive optics scanning laser ophthalmoscopy,” Invest. Ophthalmol. Visual Sci. 55(12), 8513–8522 (2014).
[Crossref]

2013 (2)

M. Lombardo, M. Parravano, S. Serrao, P. Ducoli, M. Stirpe, and G. Lombardo, “Analysis of retinal capillaries in patients with type 1 diabetes and nonproliferative diabetic retinopathy using adaptive optics imaging,” Retina 33(8), 1630–1639 (2013).
[Crossref]

S. Arichika, A. Uji, M. Hangai, S. Ooto, and N. Yoshimura, “Noninvasive and direct monitoring of erythrocyte aggregates in human retinal microvasculature using adaptive optics scanning laser ophthalmoscopy,” Invest. Ophthalmol. Visual Sci. 54(6), 4394–4402 (2013).
[Crossref]

2012 (3)

T. Y. Chui, Z. Zhong, H. Song, and S. A. Burns, “Foveal avascular zone and its relationship to foveal pit shape,” Optometry Vision Sci. 89(5), 602–610 (2012).
[Crossref]

Z. Burgansky-Eliash, A. Barak, H. Barash, D. A. Nelson, O. Pupko, A. Lowenstein, A. Grinvald, and A. Rubinstein, “Increased retinal blood flow velocity in patients with early diabetes mellitus,” Retina 32(1), 112–119 (2012).
[Crossref]

P. Bedggood and A. Metha, “Direct visualization and characterization of erythrocyte flow in human retinal capillaries,” Biomed. Opt. Express 3(12), 3264–3277 (2012).
[Crossref]

2011 (3)

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(4), 781–793 (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(12), 9257–9266 (2011).
[Crossref]

J. Tam and A. Roorda, “Speed quantification and tracking of moving objects in adaptive optics scanning laser ophthalmoscopy,” J. Biomed. Opt. 16(3), 036002 (2011).
[Crossref]

2010 (3)

J. Tam, J. A. Martin, and A. Roorda, “Noninvasive visualization and analysis of parafoveal capillaries in humans,” Invest. Ophthalmol. Visual Sci. 51(3), 1691–1698 (2010).
[Crossref]

N. B. Hamilton, D. Attwell, and C. N. Hall, “Pericyte-mediated regulation of capillary diameter: a component of neurovascular coupling in health and disease,” Front. Neuroenerg. 2, 5 (2010).
[Crossref]

Z. Burgansky-Eliash, D. A. Nelson, O. P. Bar-Tal, A. Lowenstein, A. Grinvald, and A. Barak, “Reduced retinal blood flow velocity in diabetic retinopathy,” Retina 30(5), 765–773 (2010).
[Crossref]

2007 (1)

S. Reitsma, D. W. Slaaf, H. Vink, M. A. Van Zandvoort, and M. G. Oude Egbrink, “The endothelial glycocalyx: composition, functions, and visualization,” Pfluegers Arch. 454(3), 345–359 (2007).
[Crossref]

1996 (1)

H. Vink and B. R. Duling, “Identification of distinct luminal domains for macromolecules, erythrocytes, and leukocytes within mammalian capillaries,” Circ. Res. 79(3), 581–589 (1996).
[Crossref]

1992 (1)

L. G. Brown, “A survey of image registration techniques,” ACM Comput. Surv. 24(4), 325–376 (1992).
[Crossref]

1984 (1)

G. P. Rodgers, A. N. Schechter, C. T. Noguchi, H. G. Klein, A. W. Nienhuis, and R. F. Bonner, “Periodic microcirculatory flow in patients with sickle-cell disease,” N. Engl. J. Med. 311(24), 1534–1538 (1984).
[Crossref]

Adams, A. J.

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(12), 9257–9266 (2011).
[Crossref]

Aiello, L. P.

J. Lammer, S. G. Karst, M. M. Lin, M. Cheney, P. S. Silva, S. A. Burns, L. P. Aiello, and J. K. Sun, “Association of Microaneurysms on Adaptive Optics Scanning Laser Ophthalmoscopy With Surrounding Neuroretinal Pathology and Visual Function in Diabetes,” Invest. Ophthalmol. Visual Sci. 59(13), 5633–5640 (2018).
[Crossref]

Arichika, S.

S. Arichika, A. Uji, S. Ooto, Y. Muraoka, and N. Yoshimura, “Effects of age and blood pressure on the retinal arterial wall, analyzed using adaptive optics scanning laser ophthalmoscopy,” Sci. Rep. 5(1), 12283 (2015).
[Crossref]

S. Arichika, A. Uji, T. Murakami, N. Unoki, S. Yoshitake, Y. Dodo, S. Ooto, K. Miyamoto, and N. Yoshimura, “Retinal hemorheologic characterization of early-stage diabetic retinopathy using adaptive optics scanning laser ophthalmoscopy,” Invest. Ophthalmol. Visual Sci. 55(12), 8513–8522 (2014).
[Crossref]

S. Arichika, A. Uji, M. Hangai, S. Ooto, and N. Yoshimura, “Noninvasive and direct monitoring of erythrocyte aggregates in human retinal microvasculature using adaptive optics scanning laser ophthalmoscopy,” Invest. Ophthalmol. Visual Sci. 54(6), 4394–4402 (2013).
[Crossref]

Attwell, D.

N. B. Hamilton, D. Attwell, and C. N. Hall, “Pericyte-mediated regulation of capillary diameter: a component of neurovascular coupling in health and disease,” Front. Neuroenerg. 2, 5 (2010).
[Crossref]

Barak, A.

Z. Burgansky-Eliash, A. Barak, H. Barash, D. A. Nelson, O. Pupko, A. Lowenstein, A. Grinvald, and A. Rubinstein, “Increased retinal blood flow velocity in patients with early diabetes mellitus,” Retina 32(1), 112–119 (2012).
[Crossref]

Z. Burgansky-Eliash, D. A. Nelson, O. P. Bar-Tal, A. Lowenstein, A. Grinvald, and A. Barak, “Reduced retinal blood flow velocity in diabetic retinopathy,” Retina 30(5), 765–773 (2010).
[Crossref]

Barash, H.

Z. Burgansky-Eliash, A. Barak, H. Barash, D. A. Nelson, O. Pupko, A. Lowenstein, A. Grinvald, and A. Rubinstein, “Increased retinal blood flow velocity in patients with early diabetes mellitus,” Retina 32(1), 112–119 (2012).
[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(12), 9257–9266 (2011).
[Crossref]

Bar-Tal, O. P.

Z. Burgansky-Eliash, D. A. Nelson, O. P. Bar-Tal, A. Lowenstein, A. Grinvald, and A. Barak, “Reduced retinal blood flow velocity in diabetic retinopathy,” Retina 30(5), 765–773 (2010).
[Crossref]

Bearse, M. A.

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(12), 9257–9266 (2011).
[Crossref]

Bedggood, P.

Bedggood, P. A.

A. Duan, P. A. Bedggood, B. V. Bui, and A. B. Metha, “Evidence of flicker-induced functional hyperaemia in the smallest vessels of the human retinal blood supply,” PLoS One 11(9), e0162621 (2016).
[Crossref]

Berry, C.

C. Berry, N. Sidik, A. C. Pereira, T. J. Ford, R. M. Touyz, J. C. Kaski, and A. H. Hainsworth, “Small-Vessel Disease in the Heart and Brain: Current Knowledge, Unmet Therapeutic Need, and Future Directions,” J. Am. Heart Assoc. 8(3), e011104 (2019).
[Crossref]

Bonner, R. F.

G. P. Rodgers, A. N. Schechter, C. T. Noguchi, H. G. Klein, A. W. Nienhuis, and R. F. Bonner, “Periodic microcirculatory flow in patients with sickle-cell disease,” N. Engl. J. Med. 311(24), 1534–1538 (1984).
[Crossref]

Bosetti, F.

F. Bosetti, Z. S. Galis, M. S. Bynoe, M. Charette, M. J. Cipolla, G. J. Del Zoppo, D. Gould, T. S. Hatsukami, T. L. Jones, and J. I. Koenig, ““Small Blood Vessels: Big Health Problems?”: Scientific Recommendations of the National Institutes of Health Workshop,” J. Am. Heart Assoc. 5(11), e004389 (2016).
[Crossref]

Brown, L. G.

L. G. Brown, “A survey of image registration techniques,” ACM Comput. Surv. 24(4), 325–376 (1992).
[Crossref]

Bui, B. V.

A. Duan, P. A. Bedggood, B. V. Bui, and A. B. Metha, “Evidence of flicker-induced functional hyperaemia in the smallest vessels of the human retinal blood supply,” PLoS One 11(9), e0162621 (2016).
[Crossref]

Burgansky-Eliash, Z.

Z. Burgansky-Eliash, A. Barak, H. Barash, D. A. Nelson, O. Pupko, A. Lowenstein, A. Grinvald, and A. Rubinstein, “Increased retinal blood flow velocity in patients with early diabetes mellitus,” Retina 32(1), 112–119 (2012).
[Crossref]

Z. Burgansky-Eliash, D. A. Nelson, O. P. Bar-Tal, A. Lowenstein, A. Grinvald, and A. Barak, “Reduced retinal blood flow velocity in diabetic retinopathy,” Retina 30(5), 765–773 (2010).
[Crossref]

Burns, S. A.

J. Lammer, S. G. Karst, M. M. Lin, M. Cheney, P. S. Silva, S. A. Burns, L. P. Aiello, and J. K. Sun, “Association of Microaneurysms on Adaptive Optics Scanning Laser Ophthalmoscopy With Surrounding Neuroretinal Pathology and Visual Function in Diabetes,” Invest. Ophthalmol. Visual Sci. 59(13), 5633–5640 (2018).
[Crossref]

T. Luo, T. J. Gast, T. J. Vermeer, and S. A. Burns, “Retinal vascular branching in healthy and diabetic subjects,” Invest. Ophthalmol. Visual Sci. 58(5), 2685–2694 (2017).
[Crossref]

J. G. Hillard, T. J. Gast, T. Y. Chui, D. Sapir, and S. A. Burns, “Retinal arterioles in hypo-, normo-, and hypertensive subjects measured using adaptive optics,” Trans. Vis. Sci. Tech. 5(4), 16 (2016).
[Crossref]

X. Fu, J. S. Gens, J. A. Glazier, S. A. Burns, and T. J. Gast, “Progression of diabetic capillary occlusion: a model,” PLoS Comput. Biol. 12(6), e1004932 (2016).
[Crossref]

A. de Castro, G. Huang, L. Sawides, T. Luo, and S. A. Burns, “Rapid high resolution imaging with a dual-channel scanning technique,” Opt. Lett. 41(8), 1881–1884 (2016).
[Crossref]

S. A. Burns, A. E. Elsner, T. Y. Chui, D. A. VanNasdale, C. A. Clark, T. J. Gast, V. E. Malinovsky, and A.-D. T. Phan, “In vivo adaptive optics microvascular imaging in diabetic patients without clinically severe diabetic retinopathy,” Biomed. Opt. Express 5(3), 961–974 (2014).
[Crossref]

T. Y. Chui, Z. Zhong, H. Song, and S. A. Burns, “Foveal avascular zone and its relationship to foveal pit shape,” Optometry Vision Sci. 89(5), 602–610 (2012).
[Crossref]

Bynoe, M. S.

F. Bosetti, Z. S. Galis, M. S. Bynoe, M. Charette, M. J. Cipolla, G. J. Del Zoppo, D. Gould, T. S. Hatsukami, T. L. Jones, and J. I. Koenig, ““Small Blood Vessels: Big Health Problems?”: Scientific Recommendations of the National Institutes of Health Workshop,” J. Am. Heart Assoc. 5(11), e004389 (2016).
[Crossref]

Carroll, J.

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

Charette, M.

F. Bosetti, Z. S. Galis, M. S. Bynoe, M. Charette, M. J. Cipolla, G. J. Del Zoppo, D. Gould, T. S. Hatsukami, T. L. Jones, and J. I. Koenig, ““Small Blood Vessels: Big Health Problems?”: Scientific Recommendations of the National Institutes of Health Workshop,” J. Am. Heart Assoc. 5(11), e004389 (2016).
[Crossref]

Cheang, E.

T. Y. P. Chui, A. Pinhas, A. Gan, M. Razeen, N. Shah, E. Cheang, C. L. Liu, A. Dubra, and R. B. Rosen, “Longitudinal imaging of microvascular remodelling in proliferative diabetic retinopathy using adaptive optics scanning light ophthalmoscopy,” Ophthalmic Physiol. Opt. 36(3), 290–302 (2016).
[Crossref]

Cheney, M.

J. Lammer, S. G. Karst, M. M. Lin, M. Cheney, P. S. Silva, S. A. Burns, L. P. Aiello, and J. K. Sun, “Association of Microaneurysms on Adaptive Optics Scanning Laser Ophthalmoscopy With Surrounding Neuroretinal Pathology and Visual Function in Diabetes,” Invest. Ophthalmol. Visual Sci. 59(13), 5633–5640 (2018).
[Crossref]

Choudhury, N.

T. Y. Chui, S. Mo, B. Krawitz, N. R. Menon, N. Choudhury, A. Gan, M. Razeen, N. Shah, A. Pinhas, and R. B. Rosen, “Human retinal microvascular imaging using adaptive optics scanning light ophthalmoscopy,” Int. J. Retin. Vitr. 2(1), 11 (2016).
[Crossref]

Chui, T. Y.

T. Y. Chui, S. Mo, B. Krawitz, N. R. Menon, N. Choudhury, A. Gan, M. Razeen, N. Shah, A. Pinhas, and R. B. Rosen, “Human retinal microvascular imaging using adaptive optics scanning light ophthalmoscopy,” Int. J. Retin. Vitr. 2(1), 11 (2016).
[Crossref]

J. G. Hillard, T. J. Gast, T. Y. Chui, D. Sapir, and S. A. Burns, “Retinal arterioles in hypo-, normo-, and hypertensive subjects measured using adaptive optics,” Trans. Vis. Sci. Tech. 5(4), 16 (2016).
[Crossref]

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

A. Pinhas, M. Razeen, M. Dubow, A. Gan, T. Y. Chui, N. Shah, M. Mehta, R. C. Gentile, R. Weitz, and J. B. Walsh, “Assessment of perfused foveal microvascular density and identification of nonperfused capillaries in healthy and vasculopathic eyes,” Invest. Ophthalmol. Visual Sci. 55(12), 8056–8066 (2014).
[Crossref]

S. A. Burns, A. E. Elsner, T. Y. Chui, D. A. VanNasdale, C. A. Clark, T. J. Gast, V. E. Malinovsky, and A.-D. T. Phan, “In vivo adaptive optics microvascular imaging in diabetic patients without clinically severe diabetic retinopathy,” Biomed. Opt. Express 5(3), 961–974 (2014).
[Crossref]

T. Y. Chui, Z. Zhong, H. Song, and S. A. Burns, “Foveal avascular zone and its relationship to foveal pit shape,” Optometry Vision Sci. 89(5), 602–610 (2012).
[Crossref]

Chui, T. Y. P.

T. Y. P. Chui, A. Pinhas, A. Gan, M. Razeen, N. Shah, E. Cheang, C. L. Liu, A. Dubra, and R. B. Rosen, “Longitudinal imaging of microvascular remodelling in proliferative diabetic retinopathy using adaptive optics scanning light ophthalmoscopy,” Ophthalmic Physiol. Opt. 36(3), 290–302 (2016).
[Crossref]

Cipolla, M. J.

F. Bosetti, Z. S. Galis, M. S. Bynoe, M. Charette, M. J. Cipolla, G. J. Del Zoppo, D. Gould, T. S. Hatsukami, T. L. Jones, and J. I. Koenig, ““Small Blood Vessels: Big Health Problems?”: Scientific Recommendations of the National Institutes of Health Workshop,” J. Am. Heart Assoc. 5(11), e004389 (2016).
[Crossref]

Clark, C. A.

Cooper, R. F.

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

de Castro, A.

Del Zoppo, G. J.

F. Bosetti, Z. S. Galis, M. S. Bynoe, M. Charette, M. J. Cipolla, G. J. Del Zoppo, D. Gould, T. S. Hatsukami, T. L. Jones, and J. I. Koenig, ““Small Blood Vessels: Big Health Problems?”: Scientific Recommendations of the National Institutes of Health Workshop,” J. Am. Heart Assoc. 5(11), e004389 (2016).
[Crossref]

Dhamdhere, K. P.

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(12), 9257–9266 (2011).
[Crossref]

Dodo, Y.

S. Arichika, A. Uji, T. Murakami, N. Unoki, S. Yoshitake, Y. Dodo, S. Ooto, K. Miyamoto, and N. Yoshimura, “Retinal hemorheologic characterization of early-stage diabetic retinopathy using adaptive optics scanning laser ophthalmoscopy,” Invest. Ophthalmol. Visual Sci. 55(12), 8513–8522 (2014).
[Crossref]

Duan, A.

A. Duan, P. A. Bedggood, B. V. Bui, and A. B. Metha, “Evidence of flicker-induced functional hyperaemia in the smallest vessels of the human retinal blood supply,” PLoS One 11(9), e0162621 (2016).
[Crossref]

Dubow, M.

A. Pinhas, M. Razeen, M. Dubow, A. Gan, T. Y. Chui, N. Shah, M. Mehta, R. C. Gentile, R. Weitz, and J. B. Walsh, “Assessment of perfused foveal microvascular density and identification of nonperfused capillaries in healthy and vasculopathic eyes,” Invest. Ophthalmol. Visual Sci. 55(12), 8056–8066 (2014).
[Crossref]

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

Dubra, A.

T. Y. P. Chui, A. Pinhas, A. Gan, M. Razeen, N. Shah, E. Cheang, C. L. Liu, A. Dubra, and R. B. Rosen, “Longitudinal imaging of microvascular remodelling in proliferative diabetic retinopathy using adaptive optics scanning light ophthalmoscopy,” Ophthalmic Physiol. Opt. 36(3), 290–302 (2016).
[Crossref]

Ducoli, P.

M. Lombardo, M. Parravano, S. Serrao, P. Ducoli, M. Stirpe, and G. Lombardo, “Analysis of retinal capillaries in patients with type 1 diabetes and nonproliferative diabetic retinopathy using adaptive optics imaging,” Retina 33(8), 1630–1639 (2013).
[Crossref]

Duling, B. R.

H. Vink and B. R. Duling, “Identification of distinct luminal domains for macromolecules, erythrocytes, and leukocytes within mammalian capillaries,” Circ. Res. 79(3), 581–589 (1996).
[Crossref]

Elsner, A. E.

Ford, T. J.

C. Berry, N. Sidik, A. C. Pereira, T. J. Ford, R. M. Touyz, J. C. Kaski, and A. H. Hainsworth, “Small-Vessel Disease in the Heart and Brain: Current Knowledge, Unmet Therapeutic Need, and Future Directions,” J. Am. Heart Assoc. 8(3), e011104 (2019).
[Crossref]

Fu, X.

X. Fu, J. S. Gens, J. A. Glazier, S. A. Burns, and T. J. Gast, “Progression of diabetic capillary occlusion: a model,” PLoS Comput. Biol. 12(6), e1004932 (2016).
[Crossref]

Galis, Z. S.

F. Bosetti, Z. S. Galis, M. S. Bynoe, M. Charette, M. J. Cipolla, G. J. Del Zoppo, D. Gould, T. S. Hatsukami, T. L. Jones, and J. I. Koenig, ““Small Blood Vessels: Big Health Problems?”: Scientific Recommendations of the National Institutes of Health Workshop,” J. Am. Heart Assoc. 5(11), e004389 (2016).
[Crossref]

Gallo, A.

D. Rosenbaum, A. Mattina, E. Koch, F. Rossant, A. Gallo, N. Kachenoura, M. Paques, A. Redheuil, and X. Girerd, “Effects of age, blood pressure and antihypertensive treatments on retinal arterioles remodeling assessed by adaptive optics,” J. Hypertens. 34(6), 1115–1122 (2016).
[Crossref]

Gan, A.

T. Y. P. Chui, A. Pinhas, A. Gan, M. Razeen, N. Shah, E. Cheang, C. L. Liu, A. Dubra, and R. B. Rosen, “Longitudinal imaging of microvascular remodelling in proliferative diabetic retinopathy using adaptive optics scanning light ophthalmoscopy,” Ophthalmic Physiol. Opt. 36(3), 290–302 (2016).
[Crossref]

T. Y. Chui, S. Mo, B. Krawitz, N. R. Menon, N. Choudhury, A. Gan, M. Razeen, N. Shah, A. Pinhas, and R. B. Rosen, “Human retinal microvascular imaging using adaptive optics scanning light ophthalmoscopy,” Int. J. Retin. Vitr. 2(1), 11 (2016).
[Crossref]

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

A. Pinhas, M. Razeen, M. Dubow, A. Gan, T. Y. Chui, N. Shah, M. Mehta, R. C. Gentile, R. Weitz, and J. B. Walsh, “Assessment of perfused foveal microvascular density and identification of nonperfused capillaries in healthy and vasculopathic eyes,” Invest. Ophthalmol. Visual Sci. 55(12), 8056–8066 (2014).
[Crossref]

Gast, T. J.

T. Luo, T. J. Gast, T. J. Vermeer, and S. A. Burns, “Retinal vascular branching in healthy and diabetic subjects,” Invest. Ophthalmol. Visual Sci. 58(5), 2685–2694 (2017).
[Crossref]

J. G. Hillard, T. J. Gast, T. Y. Chui, D. Sapir, and S. A. Burns, “Retinal arterioles in hypo-, normo-, and hypertensive subjects measured using adaptive optics,” Trans. Vis. Sci. Tech. 5(4), 16 (2016).
[Crossref]

X. Fu, J. S. Gens, J. A. Glazier, S. A. Burns, and T. J. Gast, “Progression of diabetic capillary occlusion: a model,” PLoS Comput. Biol. 12(6), e1004932 (2016).
[Crossref]

S. A. Burns, A. E. Elsner, T. Y. Chui, D. A. VanNasdale, C. A. Clark, T. J. Gast, V. E. Malinovsky, and A.-D. T. Phan, “In vivo adaptive optics microvascular imaging in diabetic patients without clinically severe diabetic retinopathy,” Biomed. Opt. Express 5(3), 961–974 (2014).
[Crossref]

Gens, J. S.

X. Fu, J. S. Gens, J. A. Glazier, S. A. Burns, and T. J. Gast, “Progression of diabetic capillary occlusion: a model,” PLoS Comput. Biol. 12(6), e1004932 (2016).
[Crossref]

Gentile, R. C.

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

A. Pinhas, M. Razeen, M. Dubow, A. Gan, T. Y. Chui, N. Shah, M. Mehta, R. C. Gentile, R. Weitz, and J. B. Walsh, “Assessment of perfused foveal microvascular density and identification of nonperfused capillaries in healthy and vasculopathic eyes,” Invest. Ophthalmol. Visual Sci. 55(12), 8056–8066 (2014).
[Crossref]

Girerd, X.

D. Rosenbaum, A. Mattina, E. Koch, F. Rossant, A. Gallo, N. Kachenoura, M. Paques, A. Redheuil, and X. Girerd, “Effects of age, blood pressure and antihypertensive treatments on retinal arterioles remodeling assessed by adaptive optics,” J. Hypertens. 34(6), 1115–1122 (2016).
[Crossref]

Girkin, C. A.

Glazier, J. A.

X. Fu, J. S. Gens, J. A. Glazier, S. A. Burns, and T. J. Gast, “Progression of diabetic capillary occlusion: a model,” PLoS Comput. Biol. 12(6), e1004932 (2016).
[Crossref]

Gould, D.

F. Bosetti, Z. S. Galis, M. S. Bynoe, M. Charette, M. J. Cipolla, G. J. Del Zoppo, D. Gould, T. S. Hatsukami, T. L. Jones, and J. I. Koenig, ““Small Blood Vessels: Big Health Problems?”: Scientific Recommendations of the National Institutes of Health Workshop,” J. Am. Heart Assoc. 5(11), e004389 (2016).
[Crossref]

Grinvald, A.

Z. Burgansky-Eliash, A. Barak, H. Barash, D. A. Nelson, O. Pupko, A. Lowenstein, A. Grinvald, and A. Rubinstein, “Increased retinal blood flow velocity in patients with early diabetes mellitus,” Retina 32(1), 112–119 (2012).
[Crossref]

Z. Burgansky-Eliash, D. A. Nelson, O. P. Bar-Tal, A. Lowenstein, A. Grinvald, and A. Barak, “Reduced retinal blood flow velocity in diabetic retinopathy,” Retina 30(5), 765–773 (2010).
[Crossref]

Gu, B.

Guevara-Torres, A.

A. Joseph, A. Guevara-Torres, and J. Schallek, “Imaging single-cell blood flow in the smallest to largest vessels in the living retina,” eLife 8, e45077 (2019).
[Crossref]

A. Guevara-Torres, A. Joseph, and J. Schallek, “Label free measurement of retinal blood cell flux, velocity, hematocrit and capillary width in the living mouse eye,” Biomed. Opt. Express 7(10), 4228–4249 (2016).
[Crossref]

Hainsworth, A. H.

C. Berry, N. Sidik, A. C. Pereira, T. J. Ford, R. M. Touyz, J. C. Kaski, and A. H. Hainsworth, “Small-Vessel Disease in the Heart and Brain: Current Knowledge, Unmet Therapeutic Need, and Future Directions,” J. Am. Heart Assoc. 8(3), e011104 (2019).
[Crossref]

Hall, C. N.

N. B. Hamilton, D. Attwell, and C. N. Hall, “Pericyte-mediated regulation of capillary diameter: a component of neurovascular coupling in health and disease,” Front. Neuroenerg. 2, 5 (2010).
[Crossref]

Hamilton, N. B.

N. B. Hamilton, D. Attwell, and C. N. Hall, “Pericyte-mediated regulation of capillary diameter: a component of neurovascular coupling in health and disease,” Front. Neuroenerg. 2, 5 (2010).
[Crossref]

Hangai, M.

S. Arichika, A. Uji, M. Hangai, S. Ooto, and N. Yoshimura, “Noninvasive and direct monitoring of erythrocyte aggregates in human retinal microvasculature using adaptive optics scanning laser ophthalmoscopy,” Invest. Ophthalmol. Visual Sci. 54(6), 4394–4402 (2013).
[Crossref]

Hatsukami, T. S.

F. Bosetti, Z. S. Galis, M. S. Bynoe, M. Charette, M. J. Cipolla, G. J. Del Zoppo, D. Gould, T. S. Hatsukami, T. L. Jones, and J. I. Koenig, ““Small Blood Vessels: Big Health Problems?”: Scientific Recommendations of the National Institutes of Health Workshop,” J. Am. Heart Assoc. 5(11), e004389 (2016).
[Crossref]

Hendrix, V.

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

Hillard, J. G.

J. G. Hillard, T. J. Gast, T. Y. Chui, D. Sapir, and S. A. Burns, “Retinal arterioles in hypo-, normo-, and hypertensive subjects measured using adaptive optics,” Trans. Vis. Sci. Tech. 5(4), 16 (2016).
[Crossref]

Huang, G.

Jerman, T.

T. Jerman, F. Pernuš, B. Likar, and Ž. Špiclin, “Beyond Frangi: an improved multiscale vesselness filter,” in Medical Imaging 2015: Image Processing, (International Society for Optics and Photonics, 2015), 94132A.

Jones, T. L.

F. Bosetti, Z. S. Galis, M. S. Bynoe, M. Charette, M. J. Cipolla, G. J. Del Zoppo, D. Gould, T. S. Hatsukami, T. L. Jones, and J. I. Koenig, ““Small Blood Vessels: Big Health Problems?”: Scientific Recommendations of the National Institutes of Health Workshop,” J. Am. Heart Assoc. 5(11), e004389 (2016).
[Crossref]

Joseph, A.

A. Joseph, A. Guevara-Torres, and J. Schallek, “Imaging single-cell blood flow in the smallest to largest vessels in the living retina,” eLife 8, e45077 (2019).
[Crossref]

A. Guevara-Torres, A. Joseph, and J. Schallek, “Label free measurement of retinal blood cell flux, velocity, hematocrit and capillary width in the living mouse eye,” Biomed. Opt. Express 7(10), 4228–4249 (2016).
[Crossref]

Kachenoura, N.

D. Rosenbaum, A. Mattina, E. Koch, F. Rossant, A. Gallo, N. Kachenoura, M. Paques, A. Redheuil, and X. Girerd, “Effects of age, blood pressure and antihypertensive treatments on retinal arterioles remodeling assessed by adaptive optics,” J. Hypertens. 34(6), 1115–1122 (2016).
[Crossref]

Karst, S. G.

J. Lammer, S. G. Karst, M. M. Lin, M. Cheney, P. S. Silva, S. A. Burns, L. P. Aiello, and J. K. Sun, “Association of Microaneurysms on Adaptive Optics Scanning Laser Ophthalmoscopy With Surrounding Neuroretinal Pathology and Visual Function in Diabetes,” Invest. Ophthalmol. Visual Sci. 59(13), 5633–5640 (2018).
[Crossref]

Kaski, J. C.

C. Berry, N. Sidik, A. C. Pereira, T. J. Ford, R. M. Touyz, J. C. Kaski, and A. H. Hainsworth, “Small-Vessel Disease in the Heart and Brain: Current Knowledge, Unmet Therapeutic Need, and Future Directions,” J. Am. Heart Assoc. 8(3), e011104 (2019).
[Crossref]

Klein, H. G.

G. P. Rodgers, A. N. Schechter, C. T. Noguchi, H. G. Klein, A. W. Nienhuis, and R. F. Bonner, “Periodic microcirculatory flow in patients with sickle-cell disease,” N. Engl. J. Med. 311(24), 1534–1538 (1984).
[Crossref]

Koch, E.

D. Rosenbaum, A. Mattina, E. Koch, F. Rossant, A. Gallo, N. Kachenoura, M. Paques, A. Redheuil, and X. Girerd, “Effects of age, blood pressure and antihypertensive treatments on retinal arterioles remodeling assessed by adaptive optics,” J. Hypertens. 34(6), 1115–1122 (2016).
[Crossref]

Koenig, J. I.

F. Bosetti, Z. S. Galis, M. S. Bynoe, M. Charette, M. J. Cipolla, G. J. Del Zoppo, D. Gould, T. S. Hatsukami, T. L. Jones, and J. I. Koenig, ““Small Blood Vessels: Big Health Problems?”: Scientific Recommendations of the National Institutes of Health Workshop,” J. Am. Heart Assoc. 5(11), e004389 (2016).
[Crossref]

Krawitz, B.

T. Y. Chui, S. Mo, B. Krawitz, N. R. Menon, N. Choudhury, A. Gan, M. Razeen, N. Shah, A. Pinhas, and R. B. Rosen, “Human retinal microvascular imaging using adaptive optics scanning light ophthalmoscopy,” Int. J. Retin. Vitr. 2(1), 11 (2016).
[Crossref]

Lammer, J.

J. Lammer, S. G. Karst, M. M. Lin, M. Cheney, P. S. Silva, S. A. Burns, L. P. Aiello, and J. K. Sun, “Association of Microaneurysms on Adaptive Optics Scanning Laser Ophthalmoscopy With Surrounding Neuroretinal Pathology and Visual Function in Diabetes,” Invest. Ophthalmol. Visual Sci. 59(13), 5633–5640 (2018).
[Crossref]

Likar, B.

T. Jerman, F. Pernuš, B. Likar, and Ž. Špiclin, “Beyond Frangi: an improved multiscale vesselness filter,” in Medical Imaging 2015: Image Processing, (International Society for Optics and Photonics, 2015), 94132A.

Lin, M. M.

J. Lammer, S. G. Karst, M. M. Lin, M. Cheney, P. S. Silva, S. A. Burns, L. P. Aiello, and J. K. Sun, “Association of Microaneurysms on Adaptive Optics Scanning Laser Ophthalmoscopy With Surrounding Neuroretinal Pathology and Visual Function in Diabetes,” Invest. Ophthalmol. Visual Sci. 59(13), 5633–5640 (2018).
[Crossref]

Liu, C. L.

T. Y. P. Chui, A. Pinhas, A. Gan, M. Razeen, N. Shah, E. Cheang, C. L. Liu, A. Dubra, and R. B. Rosen, “Longitudinal imaging of microvascular remodelling in proliferative diabetic retinopathy using adaptive optics scanning light ophthalmoscopy,” Ophthalmic Physiol. Opt. 36(3), 290–302 (2016).
[Crossref]

Lombardo, G.

M. Lombardo, M. Parravano, S. Serrao, P. Ducoli, M. Stirpe, and G. Lombardo, “Analysis of retinal capillaries in patients with type 1 diabetes and nonproliferative diabetic retinopathy using adaptive optics imaging,” Retina 33(8), 1630–1639 (2013).
[Crossref]

Lombardo, M.

M. Lombardo, M. Parravano, S. Serrao, P. Ducoli, M. Stirpe, and G. Lombardo, “Analysis of retinal capillaries in patients with type 1 diabetes and nonproliferative diabetic retinopathy using adaptive optics imaging,” Retina 33(8), 1630–1639 (2013).
[Crossref]

Lowenstein, A.

Z. Burgansky-Eliash, A. Barak, H. Barash, D. A. Nelson, O. Pupko, A. Lowenstein, A. Grinvald, and A. Rubinstein, “Increased retinal blood flow velocity in patients with early diabetes mellitus,” Retina 32(1), 112–119 (2012).
[Crossref]

Z. Burgansky-Eliash, D. A. Nelson, O. P. Bar-Tal, A. Lowenstein, A. Grinvald, and A. Barak, “Reduced retinal blood flow velocity in diabetic retinopathy,” Retina 30(5), 765–773 (2010).
[Crossref]

Luo, T.

T. Luo, T. J. Gast, T. J. Vermeer, and S. A. Burns, “Retinal vascular branching in healthy and diabetic subjects,” Invest. Ophthalmol. Visual Sci. 58(5), 2685–2694 (2017).
[Crossref]

A. de Castro, G. Huang, L. Sawides, T. Luo, and S. A. Burns, “Rapid high resolution imaging with a dual-channel scanning technique,” Opt. Lett. 41(8), 1881–1884 (2016).
[Crossref]

Malinovsky, V. E.

Manzanera, 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(12), 9257–9266 (2011).
[Crossref]

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J. Tam, J. A. Martin, and A. Roorda, “Noninvasive visualization and analysis of parafoveal capillaries in humans,” Invest. Ophthalmol. Visual Sci. 51(3), 1691–1698 (2010).
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D. Rosenbaum, A. Mattina, E. Koch, F. Rossant, A. Gallo, N. Kachenoura, M. Paques, A. Redheuil, and X. Girerd, “Effects of age, blood pressure and antihypertensive treatments on retinal arterioles remodeling assessed by adaptive optics,” J. Hypertens. 34(6), 1115–1122 (2016).
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A. Pinhas, M. Razeen, M. Dubow, A. Gan, T. Y. Chui, N. Shah, M. Mehta, R. C. Gentile, R. Weitz, and J. B. Walsh, “Assessment of perfused foveal microvascular density and identification of nonperfused capillaries in healthy and vasculopathic eyes,” Invest. Ophthalmol. Visual Sci. 55(12), 8056–8066 (2014).
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T. Y. Chui, S. Mo, B. Krawitz, N. R. Menon, N. Choudhury, A. Gan, M. Razeen, N. Shah, A. Pinhas, and R. B. Rosen, “Human retinal microvascular imaging using adaptive optics scanning light ophthalmoscopy,” Int. J. Retin. Vitr. 2(1), 11 (2016).
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Metha, A. B.

A. Duan, P. A. Bedggood, B. V. Bui, and A. B. Metha, “Evidence of flicker-induced functional hyperaemia in the smallest vessels of the human retinal blood supply,” PLoS One 11(9), e0162621 (2016).
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S. Arichika, A. Uji, T. Murakami, N. Unoki, S. Yoshitake, Y. Dodo, S. Ooto, K. Miyamoto, and N. Yoshimura, “Retinal hemorheologic characterization of early-stage diabetic retinopathy using adaptive optics scanning laser ophthalmoscopy,” Invest. Ophthalmol. Visual Sci. 55(12), 8513–8522 (2014).
[Crossref]

Mo, S.

T. Y. Chui, S. Mo, B. Krawitz, N. R. Menon, N. Choudhury, A. Gan, M. Razeen, N. Shah, A. Pinhas, and R. B. Rosen, “Human retinal microvascular imaging using adaptive optics scanning light ophthalmoscopy,” Int. J. Retin. Vitr. 2(1), 11 (2016).
[Crossref]

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S. Arichika, A. Uji, T. Murakami, N. Unoki, S. Yoshitake, Y. Dodo, S. Ooto, K. Miyamoto, and N. Yoshimura, “Retinal hemorheologic characterization of early-stage diabetic retinopathy using adaptive optics scanning laser ophthalmoscopy,” Invest. Ophthalmol. Visual Sci. 55(12), 8513–8522 (2014).
[Crossref]

Muraoka, Y.

S. Arichika, A. Uji, S. Ooto, Y. Muraoka, and N. Yoshimura, “Effects of age and blood pressure on the retinal arterial wall, analyzed using adaptive optics scanning laser ophthalmoscopy,” Sci. Rep. 5(1), 12283 (2015).
[Crossref]

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Z. Burgansky-Eliash, A. Barak, H. Barash, D. A. Nelson, O. Pupko, A. Lowenstein, A. Grinvald, and A. Rubinstein, “Increased retinal blood flow velocity in patients with early diabetes mellitus,” Retina 32(1), 112–119 (2012).
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Z. Burgansky-Eliash, D. A. Nelson, O. P. Bar-Tal, A. Lowenstein, A. Grinvald, and A. Barak, “Reduced retinal blood flow velocity in diabetic retinopathy,” Retina 30(5), 765–773 (2010).
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G. P. Rodgers, A. N. Schechter, C. T. Noguchi, H. G. Klein, A. W. Nienhuis, and R. F. Bonner, “Periodic microcirculatory flow in patients with sickle-cell disease,” N. Engl. J. Med. 311(24), 1534–1538 (1984).
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G. P. Rodgers, A. N. Schechter, C. T. Noguchi, H. G. Klein, A. W. Nienhuis, and R. F. Bonner, “Periodic microcirculatory flow in patients with sickle-cell disease,” N. Engl. J. Med. 311(24), 1534–1538 (1984).
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S. Arichika, A. Uji, S. Ooto, Y. Muraoka, and N. Yoshimura, “Effects of age and blood pressure on the retinal arterial wall, analyzed using adaptive optics scanning laser ophthalmoscopy,” Sci. Rep. 5(1), 12283 (2015).
[Crossref]

S. Arichika, A. Uji, T. Murakami, N. Unoki, S. Yoshitake, Y. Dodo, S. Ooto, K. Miyamoto, and N. Yoshimura, “Retinal hemorheologic characterization of early-stage diabetic retinopathy using adaptive optics scanning laser ophthalmoscopy,” Invest. Ophthalmol. Visual Sci. 55(12), 8513–8522 (2014).
[Crossref]

S. Arichika, A. Uji, M. Hangai, S. Ooto, and N. Yoshimura, “Noninvasive and direct monitoring of erythrocyte aggregates in human retinal microvasculature using adaptive optics scanning laser ophthalmoscopy,” Invest. Ophthalmol. Visual Sci. 54(6), 4394–4402 (2013).
[Crossref]

Oude Egbrink, M. G.

S. Reitsma, D. W. Slaaf, H. Vink, M. A. Van Zandvoort, and M. G. Oude Egbrink, “The endothelial glycocalyx: composition, functions, and visualization,” Pfluegers Arch. 454(3), 345–359 (2007).
[Crossref]

Paques, M.

D. Rosenbaum, A. Mattina, E. Koch, F. Rossant, A. Gallo, N. Kachenoura, M. Paques, A. Redheuil, and X. Girerd, “Effects of age, blood pressure and antihypertensive treatments on retinal arterioles remodeling assessed by adaptive optics,” J. Hypertens. 34(6), 1115–1122 (2016).
[Crossref]

Parravano, M.

M. Lombardo, M. Parravano, S. Serrao, P. Ducoli, M. Stirpe, and G. Lombardo, “Analysis of retinal capillaries in patients with type 1 diabetes and nonproliferative diabetic retinopathy using adaptive optics imaging,” Retina 33(8), 1630–1639 (2013).
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Pereira, A. C.

C. Berry, N. Sidik, A. C. Pereira, T. J. Ford, R. M. Touyz, J. C. Kaski, and A. H. Hainsworth, “Small-Vessel Disease in the Heart and Brain: Current Knowledge, Unmet Therapeutic Need, and Future Directions,” J. Am. Heart Assoc. 8(3), e011104 (2019).
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Pernuš, F.

T. Jerman, F. Pernuš, B. Likar, and Ž. Špiclin, “Beyond Frangi: an improved multiscale vesselness filter,” in Medical Imaging 2015: Image Processing, (International Society for Optics and Photonics, 2015), 94132A.

Phan, A.-D. T.

Pinhas, A.

T. Y. P. Chui, A. Pinhas, A. Gan, M. Razeen, N. Shah, E. Cheang, C. L. Liu, A. Dubra, and R. B. Rosen, “Longitudinal imaging of microvascular remodelling in proliferative diabetic retinopathy using adaptive optics scanning light ophthalmoscopy,” Ophthalmic Physiol. Opt. 36(3), 290–302 (2016).
[Crossref]

T. Y. Chui, S. Mo, B. Krawitz, N. R. Menon, N. Choudhury, A. Gan, M. Razeen, N. Shah, A. Pinhas, and R. B. Rosen, “Human retinal microvascular imaging using adaptive optics scanning light ophthalmoscopy,” Int. J. Retin. Vitr. 2(1), 11 (2016).
[Crossref]

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

A. Pinhas, M. Razeen, M. Dubow, A. Gan, T. Y. Chui, N. Shah, M. Mehta, R. C. Gentile, R. Weitz, and J. B. Walsh, “Assessment of perfused foveal microvascular density and identification of nonperfused capillaries in healthy and vasculopathic eyes,” Invest. Ophthalmol. Visual Sci. 55(12), 8056–8066 (2014).
[Crossref]

Pupko, O.

Z. Burgansky-Eliash, A. Barak, H. Barash, D. A. Nelson, O. Pupko, A. Lowenstein, A. Grinvald, and A. Rubinstein, “Increased retinal blood flow velocity in patients with early diabetes mellitus,” Retina 32(1), 112–119 (2012).
[Crossref]

Razeen, M.

T. Y. P. Chui, A. Pinhas, A. Gan, M. Razeen, N. Shah, E. Cheang, C. L. Liu, A. Dubra, and R. B. Rosen, “Longitudinal imaging of microvascular remodelling in proliferative diabetic retinopathy using adaptive optics scanning light ophthalmoscopy,” Ophthalmic Physiol. Opt. 36(3), 290–302 (2016).
[Crossref]

T. Y. Chui, S. Mo, B. Krawitz, N. R. Menon, N. Choudhury, A. Gan, M. Razeen, N. Shah, A. Pinhas, and R. B. Rosen, “Human retinal microvascular imaging using adaptive optics scanning light ophthalmoscopy,” Int. J. Retin. Vitr. 2(1), 11 (2016).
[Crossref]

A. Pinhas, M. Razeen, M. Dubow, A. Gan, T. Y. Chui, N. Shah, M. Mehta, R. C. Gentile, R. Weitz, and J. B. Walsh, “Assessment of perfused foveal microvascular density and identification of nonperfused capillaries in healthy and vasculopathic eyes,” Invest. Ophthalmol. Visual Sci. 55(12), 8056–8066 (2014).
[Crossref]

Redheuil, A.

D. Rosenbaum, A. Mattina, E. Koch, F. Rossant, A. Gallo, N. Kachenoura, M. Paques, A. Redheuil, and X. Girerd, “Effects of age, blood pressure and antihypertensive treatments on retinal arterioles remodeling assessed by adaptive optics,” J. Hypertens. 34(6), 1115–1122 (2016).
[Crossref]

Reitsma, S.

S. Reitsma, D. W. Slaaf, H. Vink, M. A. Van Zandvoort, and M. G. Oude Egbrink, “The endothelial glycocalyx: composition, functions, and visualization,” Pfluegers Arch. 454(3), 345–359 (2007).
[Crossref]

Rodgers, G. P.

G. P. Rodgers, A. N. Schechter, C. T. Noguchi, H. G. Klein, A. W. Nienhuis, and R. F. Bonner, “Periodic microcirculatory flow in patients with sickle-cell disease,” N. Engl. J. Med. 311(24), 1534–1538 (1984).
[Crossref]

Roorda, A.

J. Tam and A. Roorda, “Speed quantification and tracking of moving objects in adaptive optics scanning laser ophthalmoscopy,” J. Biomed. Opt. 16(3), 036002 (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(12), 9257–9266 (2011).
[Crossref]

J. Tam, P. Tiruveedhula, and A. Roorda, “Characterization of single-file flow through human retinal parafoveal capillaries using an adaptive optics scanning laser ophthalmoscope,” Biomed. Opt. Express 2(4), 781–793 (2011).
[Crossref]

J. Tam, J. A. Martin, and A. Roorda, “Noninvasive visualization and analysis of parafoveal capillaries in humans,” Invest. Ophthalmol. Visual Sci. 51(3), 1691–1698 (2010).
[Crossref]

Rosen, R. B.

T. Y. Chui, S. Mo, B. Krawitz, N. R. Menon, N. Choudhury, A. Gan, M. Razeen, N. Shah, A. Pinhas, and R. B. Rosen, “Human retinal microvascular imaging using adaptive optics scanning light ophthalmoscopy,” Int. J. Retin. Vitr. 2(1), 11 (2016).
[Crossref]

T. Y. P. Chui, A. Pinhas, A. Gan, M. Razeen, N. Shah, E. Cheang, C. L. Liu, A. Dubra, and R. B. Rosen, “Longitudinal imaging of microvascular remodelling in proliferative diabetic retinopathy using adaptive optics scanning light ophthalmoscopy,” Ophthalmic Physiol. Opt. 36(3), 290–302 (2016).
[Crossref]

Rosenbaum, D.

D. Rosenbaum, A. Mattina, E. Koch, F. Rossant, A. Gallo, N. Kachenoura, M. Paques, A. Redheuil, and X. Girerd, “Effects of age, blood pressure and antihypertensive treatments on retinal arterioles remodeling assessed by adaptive optics,” J. Hypertens. 34(6), 1115–1122 (2016).
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D. Rosenbaum, A. Mattina, E. Koch, F. Rossant, A. Gallo, N. Kachenoura, M. Paques, A. Redheuil, and X. Girerd, “Effects of age, blood pressure and antihypertensive treatments on retinal arterioles remodeling assessed by adaptive optics,” J. Hypertens. 34(6), 1115–1122 (2016).
[Crossref]

Rubinstein, A.

Z. Burgansky-Eliash, A. Barak, H. Barash, D. A. Nelson, O. Pupko, A. Lowenstein, A. Grinvald, and A. Rubinstein, “Increased retinal blood flow velocity in patients with early diabetes mellitus,” Retina 32(1), 112–119 (2012).
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Sapir, D.

J. G. Hillard, T. J. Gast, T. Y. Chui, D. Sapir, and S. A. Burns, “Retinal arterioles in hypo-, normo-, and hypertensive subjects measured using adaptive optics,” Trans. Vis. Sci. Tech. 5(4), 16 (2016).
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Sawides, L.

Schallek, J.

A. Joseph, A. Guevara-Torres, and J. Schallek, “Imaging single-cell blood flow in the smallest to largest vessels in the living retina,” eLife 8, e45077 (2019).
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A. Guevara-Torres, A. Joseph, and J. Schallek, “Label free measurement of retinal blood cell flux, velocity, hematocrit and capillary width in the living mouse eye,” Biomed. Opt. Express 7(10), 4228–4249 (2016).
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Schechter, A. N.

G. P. Rodgers, A. N. Schechter, C. T. Noguchi, H. G. Klein, A. W. Nienhuis, and R. F. Bonner, “Periodic microcirculatory flow in patients with sickle-cell disease,” N. Engl. J. Med. 311(24), 1534–1538 (1984).
[Crossref]

Serrao, S.

M. Lombardo, M. Parravano, S. Serrao, P. Ducoli, M. Stirpe, and G. Lombardo, “Analysis of retinal capillaries in patients with type 1 diabetes and nonproliferative diabetic retinopathy using adaptive optics imaging,” Retina 33(8), 1630–1639 (2013).
[Crossref]

Shah, N.

T. Y. P. Chui, A. Pinhas, A. Gan, M. Razeen, N. Shah, E. Cheang, C. L. Liu, A. Dubra, and R. B. Rosen, “Longitudinal imaging of microvascular remodelling in proliferative diabetic retinopathy using adaptive optics scanning light ophthalmoscopy,” Ophthalmic Physiol. Opt. 36(3), 290–302 (2016).
[Crossref]

T. Y. Chui, S. Mo, B. Krawitz, N. R. Menon, N. Choudhury, A. Gan, M. Razeen, N. Shah, A. Pinhas, and R. B. Rosen, “Human retinal microvascular imaging using adaptive optics scanning light ophthalmoscopy,” Int. J. Retin. Vitr. 2(1), 11 (2016).
[Crossref]

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

A. Pinhas, M. Razeen, M. Dubow, A. Gan, T. Y. Chui, N. Shah, M. Mehta, R. C. Gentile, R. Weitz, and J. B. Walsh, “Assessment of perfused foveal microvascular density and identification of nonperfused capillaries in healthy and vasculopathic eyes,” Invest. Ophthalmol. Visual Sci. 55(12), 8056–8066 (2014).
[Crossref]

Sidik, N.

C. Berry, N. Sidik, A. C. Pereira, T. J. Ford, R. M. Touyz, J. C. Kaski, and A. H. Hainsworth, “Small-Vessel Disease in the Heart and Brain: Current Knowledge, Unmet Therapeutic Need, and Future Directions,” J. Am. Heart Assoc. 8(3), e011104 (2019).
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J. Lammer, S. G. Karst, M. M. Lin, M. Cheney, P. S. Silva, S. A. Burns, L. P. Aiello, and J. K. Sun, “Association of Microaneurysms on Adaptive Optics Scanning Laser Ophthalmoscopy With Surrounding Neuroretinal Pathology and Visual Function in Diabetes,” Invest. Ophthalmol. Visual Sci. 59(13), 5633–5640 (2018).
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Slaaf, D. W.

S. Reitsma, D. W. Slaaf, H. Vink, M. A. Van Zandvoort, and M. G. Oude Egbrink, “The endothelial glycocalyx: composition, functions, and visualization,” Pfluegers Arch. 454(3), 345–359 (2007).
[Crossref]

Song, H.

T. Y. Chui, Z. Zhong, H. Song, and S. A. Burns, “Foveal avascular zone and its relationship to foveal pit shape,” Optometry Vision Sci. 89(5), 602–610 (2012).
[Crossref]

Špiclin, Ž.

T. Jerman, F. Pernuš, B. Likar, and Ž. Špiclin, “Beyond Frangi: an improved multiscale vesselness filter,” in Medical Imaging 2015: Image Processing, (International Society for Optics and Photonics, 2015), 94132A.

Stirpe, M.

M. Lombardo, M. Parravano, S. Serrao, P. Ducoli, M. Stirpe, and G. Lombardo, “Analysis of retinal capillaries in patients with type 1 diabetes and nonproliferative diabetic retinopathy using adaptive optics imaging,” Retina 33(8), 1630–1639 (2013).
[Crossref]

Sulai, Y. N.

M. Dubow, A. Pinhas, N. Shah, R. F. Cooper, A. Gan, R. C. Gentile, V. Hendrix, Y. N. Sulai, J. Carroll, and T. Y. Chui, “Classification of human retinal microaneurysms using adaptive optics scanning light ophthalmoscope fluorescein angiography,” Invest. Ophthalmol. Visual Sci. 55(3), 1299–1309 (2014).
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Sun, J. K.

J. Lammer, S. G. Karst, M. M. Lin, M. Cheney, P. S. Silva, S. A. Burns, L. P. Aiello, and J. K. Sun, “Association of Microaneurysms on Adaptive Optics Scanning Laser Ophthalmoscopy With Surrounding Neuroretinal Pathology and Visual Function in Diabetes,” Invest. Ophthalmol. Visual Sci. 59(13), 5633–5640 (2018).
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Tam, J.

B. Gu, X. Wang, M. D. Twa, J. Tam, C. A. Girkin, and Y. Zhang, “Noninvasive in vivo characterization of erythrocyte motion in human retinal capillaries using high-speed adaptive optics near-confocal imaging,” Biomed. Opt. Express 9(8), 3653–3677 (2018).
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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(4), 781–793 (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(12), 9257–9266 (2011).
[Crossref]

J. Tam and A. Roorda, “Speed quantification and tracking of moving objects in adaptive optics scanning laser ophthalmoscopy,” J. Biomed. Opt. 16(3), 036002 (2011).
[Crossref]

J. Tam, J. A. Martin, and A. Roorda, “Noninvasive visualization and analysis of parafoveal capillaries in humans,” Invest. Ophthalmol. Visual Sci. 51(3), 1691–1698 (2010).
[Crossref]

Tiruveedhula, P.

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(4), 781–793 (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(12), 9257–9266 (2011).
[Crossref]

Touyz, R. M.

C. Berry, N. Sidik, A. C. Pereira, T. J. Ford, R. M. Touyz, J. C. Kaski, and A. H. Hainsworth, “Small-Vessel Disease in the Heart and Brain: Current Knowledge, Unmet Therapeutic Need, and Future Directions,” J. Am. Heart Assoc. 8(3), e011104 (2019).
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Twa, M. D.

Uji, A.

S. Arichika, A. Uji, S. Ooto, Y. Muraoka, and N. Yoshimura, “Effects of age and blood pressure on the retinal arterial wall, analyzed using adaptive optics scanning laser ophthalmoscopy,” Sci. Rep. 5(1), 12283 (2015).
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S. Arichika, A. Uji, T. Murakami, N. Unoki, S. Yoshitake, Y. Dodo, S. Ooto, K. Miyamoto, and N. Yoshimura, “Retinal hemorheologic characterization of early-stage diabetic retinopathy using adaptive optics scanning laser ophthalmoscopy,” Invest. Ophthalmol. Visual Sci. 55(12), 8513–8522 (2014).
[Crossref]

S. Arichika, A. Uji, M. Hangai, S. Ooto, and N. Yoshimura, “Noninvasive and direct monitoring of erythrocyte aggregates in human retinal microvasculature using adaptive optics scanning laser ophthalmoscopy,” Invest. Ophthalmol. Visual Sci. 54(6), 4394–4402 (2013).
[Crossref]

Unoki, N.

S. Arichika, A. Uji, T. Murakami, N. Unoki, S. Yoshitake, Y. Dodo, S. Ooto, K. Miyamoto, and N. Yoshimura, “Retinal hemorheologic characterization of early-stage diabetic retinopathy using adaptive optics scanning laser ophthalmoscopy,” Invest. Ophthalmol. Visual Sci. 55(12), 8513–8522 (2014).
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Van Zandvoort, M. A.

S. Reitsma, D. W. Slaaf, H. Vink, M. A. Van Zandvoort, and M. G. Oude Egbrink, “The endothelial glycocalyx: composition, functions, and visualization,” Pfluegers Arch. 454(3), 345–359 (2007).
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Vermeer, T. J.

T. Luo, T. J. Gast, T. J. Vermeer, and S. A. Burns, “Retinal vascular branching in healthy and diabetic subjects,” Invest. Ophthalmol. Visual Sci. 58(5), 2685–2694 (2017).
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H. Vink and B. R. Duling, “Identification of distinct luminal domains for macromolecules, erythrocytes, and leukocytes within mammalian capillaries,” Circ. Res. 79(3), 581–589 (1996).
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A. Pinhas, M. Razeen, M. Dubow, A. Gan, T. Y. Chui, N. Shah, M. Mehta, R. C. Gentile, R. Weitz, and J. B. Walsh, “Assessment of perfused foveal microvascular density and identification of nonperfused capillaries in healthy and vasculopathic eyes,” Invest. Ophthalmol. Visual Sci. 55(12), 8056–8066 (2014).
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Weitz, R.

A. Pinhas, M. Razeen, M. Dubow, A. Gan, T. Y. Chui, N. Shah, M. Mehta, R. C. Gentile, R. Weitz, and J. B. Walsh, “Assessment of perfused foveal microvascular density and identification of nonperfused capillaries in healthy and vasculopathic eyes,” Invest. Ophthalmol. Visual Sci. 55(12), 8056–8066 (2014).
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S. Arichika, A. Uji, S. Ooto, Y. Muraoka, and N. Yoshimura, “Effects of age and blood pressure on the retinal arterial wall, analyzed using adaptive optics scanning laser ophthalmoscopy,” Sci. Rep. 5(1), 12283 (2015).
[Crossref]

S. Arichika, A. Uji, T. Murakami, N. Unoki, S. Yoshitake, Y. Dodo, S. Ooto, K. Miyamoto, and N. Yoshimura, “Retinal hemorheologic characterization of early-stage diabetic retinopathy using adaptive optics scanning laser ophthalmoscopy,” Invest. Ophthalmol. Visual Sci. 55(12), 8513–8522 (2014).
[Crossref]

S. Arichika, A. Uji, M. Hangai, S. Ooto, and N. Yoshimura, “Noninvasive and direct monitoring of erythrocyte aggregates in human retinal microvasculature using adaptive optics scanning laser ophthalmoscopy,” Invest. Ophthalmol. Visual Sci. 54(6), 4394–4402 (2013).
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S. Arichika, A. Uji, T. Murakami, N. Unoki, S. Yoshitake, Y. Dodo, S. Ooto, K. Miyamoto, and N. Yoshimura, “Retinal hemorheologic characterization of early-stage diabetic retinopathy using adaptive optics scanning laser ophthalmoscopy,” Invest. Ophthalmol. Visual Sci. 55(12), 8513–8522 (2014).
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Zhong, Z.

T. Y. Chui, Z. Zhong, H. Song, and S. A. Burns, “Foveal avascular zone and its relationship to foveal pit shape,” Optometry Vision Sci. 89(5), 602–610 (2012).
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Supplementary Material (10)

NameDescription
» Visualization 1       Example sequence for calculation of the decay time metric. See Figure 1.
» Visualization 2       Relative stasis of retinal capillary flow in a young healthy subject. See Figure 2.
» Visualization 3       Relative stasis of retinal capillary flow in a young healthy subject. See Figure 2.
» Visualization 4       Relative stasis of retinal capillary flow in a young healthy subject. See Figure 3.
» Visualization 5       Relative stasis of retinal capillary flow in a young healthy subject. See Figure 3.
» Visualization 6       Relative stasis of retinal capillary flow in a young healthy subject. See Figure 4.
» Visualization 7       Relative stasis of retinal capillary flow in Type I diabetes. See Figure 6.
» Visualization 8       Relative stasis of retinal capillary flow in Type I diabetes. See Figure 6.
» Visualization 9       Relative stasis of retinal capillary flow in Type I diabetes. See Figure 6.
» Visualization 10       Relative stasis of retinal capillary flow in Type I diabetes. See Figure 6.

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Figures (6)

Fig. 1.
Fig. 1. Calculation of the decay time image, illustrated with data from a human subject with Type I diabetes. Image sequence acquired at 400 fps with 593 nm light ∼2° from fixation. Data is separated into 100 ms epochs for analysis and each pixel considered independently; the figure shows one such epoch. A) Average pixel intensity. Red and green squares indicate 2 example pixels, and white arrows indicate 3 example vessels. B) Plot of intensity for the example pixels. The green pixel varied rapidly while the red pixel changed more slowly. C) Motion contrast calculated by the “division” method. The example vessels (white arrows) appear either dim or not visible at all. D) Motion contrast calculated by the standard deviation method. All indicated vessels appear visible. E) Intensity data is used to compute the Fourier transform of the autocorrelation function (or equivalently, the power spectrum). Dashed vertical lines indicate the centre of gravity for each pixel; centroids in frequency space are inverted to the time domain and used to populate the decay time image, shown in F). Bright vessels in the decay time image result from sluggish flow and/or low haematocrit; especially of note are the indicated vessels (white arrows) which did not appear on the division image. The flow in these vessels during this epoch can be inspected directly in Visualization 1. Images are linearly stretched to fill an 8-bit colormap; decay time values shown range from 7 to 35 ms. Scale bar is 100 µm.
Fig. 2.
Fig. 2. Example of long, slowly moving capillary contents. Data acquired over 3.3 sec at 300 fps with 750 nm light, ∼1.5° from the foveal centre in a healthy subject. A) Motion contrast (division image) for this sequence, with two vessel segments of interest labelled (“g”, “h”) and highlighted in magenta. B) Average decay time metric for this sequence; neither example segment had elevated decay time on average. C) Single processed frame from an example epoch (at time t≈2.8s). Within the vessel segment of interest (magenta), a chain of red cells to the right creates a black appearance (with a white “shadow” underneath); a length of plasma creates the reverse appearance on the left. The flow characteristics are best appreciated in Visualization 2. D) Single processed frame from another example epoch (at t≈0.6s). Within the vessel of interest (magenta), an uninterrupted column of plasma can be seen (refer to Visualization 3). E) Decay time image for the epoch corresponding to C, showing marked elevation of decay time in the highlighted vessel. F) As for E, but for the epoch corresponding to D. G) Evolution of flow velocity (blue) and decay time (red) for vessel “g”. Expected velocity based on the field average is indicated (dashed blue). Black arrow corresponds to the epoch in C and E, and shows a pronounced drop in velocity associated with passage of the long cell aggregate. Outliers in decay time are indicated (circles). H) As for G, but data corresponds to segment “h”, and the black arrow corresponds to the epoch shown in D and F. The long chain of plasma was associated with a spike in decay time but minimal disruption to velocity. Scale bar is 100 µm.
Fig. 3.
Fig. 3. Examples of a shorter cell aggregate and of a vessel with consistently low haematocrit. Data acquired over 3.3 sec at 300 fps with 750 nm light, ∼2° from the foveal centre in a healthy subject. A) Motion contrast (division image) for this sequence, with two vessels of interest labelled (“g”, “h”) and highlighted in magenta. B) Average decay time metric for this sequence. Vessel h shows elevated decay time on average, whilst vessel g does not. C) Single processed frame from an example epoch (at t≈1.0s). Within the vessel of interest (magenta), a cell aggregate is seen exiting the left (venous) side of the segment. D) Single processed frame from another example epoch (at t≈2.5s). Within the vessel of interest (magenta), a long section of plasma is broken up by a single red blood cell, i.e. the local haematocrit is low. The flow characteristics for each example are best appreciated in Visualization 4 and Visualization 5 for segments g and h, respectively. E) Decay time image for the epoch corresponding to C. F) Decay time image for the epoch corresponding to D. G) Evolution of flow velocity (blue) and decay time (red) for vessel “g”. Expected velocity based on the field average is indicated (dashed blue). Black arrow corresponds to the epoch in C and E, and shows a pronounced drop in velocity. Outliers in decay time are indicated (circles). H) As for G, but data corresponds to segment “h”. The decay time metric varied inversely to the flow velocity. There are many outliers because decay time in this vessel is consistently elevated. Scale bar is 100 µm.
Fig. 4.
Fig. 4. Examples of the three categories of stasis captured during a single epoch. Data acquired over 3.3 sec at 300 fps with 750 nm light, 1.5° from the foveal centre in a healthy subject. A) Motion contrast (division image) for the sequence, with 3 vessels of interest labelled (“e”, “f”, “g”) and highlighted in magenta. B) Single processed frame from an example epoch (at t≈1.4s). In segment e, a cellular aggregate creates a dark appearance. In segment f, an uninterrupted column of plasma creates a bright appearance, which extends significantly along the segment above. In segment g the capillary shows typical single file alternating flow; these observations can be verified in Visualization 6. C) Decay time image for the same epoch corresponding to B, which shows elevated decay time within and, notably, around all 3 vessels of interest. D) Average decay time metric for this sequence. Segment e shows consistently elevated decay time; segments f and g do not. E) Evolution of flow velocity (blue) and decay time (red) for segment e. Expected velocity based on the field average is indicated (dashed blue). Black arrow corresponds to the example epoch; minimal change from expected velocity is noted here despite a spike in the decay time. Outliers in decay time are indicated (circles). F) Plot for segment f, as per panel E. The extended plasma length noted in the example epoch was associated with a significant drop in velocity (black arrow). G) Plot for segment g, as per panel E. Velocity is slowed significantly from the expected value despite normal capillary contents; inspection of Visualization 6 reveals this is associated with “traffic” due to passage of the cell aggregate in segment e (segments e and g feed into the same collecting segment). Scale bar is 100 µm.
Fig. 5.
Fig. 5. Distribution of decay time values. A) Histogram of decay time for background pixels (black) and segmented vessel pixels (blue). Vessels are generally darker than background, but encounter sporadic spikes (outliers-to-self shown in red, outliers-to-field in yellow). B) Decay time for each vessel-epoch, plotted as a function of instantaneous velocity (12,421 vessel-epochs, 266 unique vessel segments). The correlation between velocity and decay time disappeared, on average, beyond ∼2 mm/sec due to sampling limitations at 300 fps (red line).
Fig. 6.
Fig. 6. Epochs of relative capillary stasis associated with sub-clinical microvascular pathology in Type I diabetes. Data collected at 200 fps with 593 nm light from 3 subjects without clinically observed retinopathy based on colour fundus photography. Each row depicts a different imaged field. Columns from left to right show mean intensity, division motion contrast, and decay time during a 100 ms epoch. Red boxes indicate the most obvious pathology in each field based on the intensity image. Green boxes show areas of relative stasis, i.e. elevated decay time. A-C) A small cyst is surrounded by several static appearing vessels, which contain long, slowly moving cell aggregates as seen in Visualization 7. D-F) A highly tortuous “knot” structure shows little elevation in decay time, but a nearby, less severe malformation does show elevated decay time. In the accompanying sequence (Visualization 8), the latter structure appears to dissipate high flow from the right into much slower flow to the left, over a very short distance. G-I) A microaneurysm is neighboured by a tight loop. Decay time appears elevated in the loop only. Accompanying sequence shown in Visualization 9. J-L) Hyperreflective spots and microvascular abnormality are seen in the vicinity of two vessels showing elevated decay time. Inspection of the accompanying sequence (Visualization 10) shows passage of long cell aggregates accompanied by extreme apparent variations in the vessel width for the vessel indicated by the left-hand green box; the vessel in the right-hand green box shows long cell aggregates undergoing extremely slow flow. Scale bars = 100 µm.

Tables (1)

Tables Icon

Table 1. Decay time and associated metrics together with manual categorization of capillary contents for both “outlier” and “control” vessel-epochs.