Abstract

The adaptive optics scanning light ophthalmoscope (AOSLO) allows visualization of microscopic structures of the human retina in vivo. In this work, we demonstrate its application in combination with oral and intravenous (IV) fluorescein angiography (FA) to the in vivo visualization of the human retinal microvasculature. Ten healthy subjects ages 20 to 38 years were imaged using oral (7 and/or 20 mg/kg) and/or IV (500 mg) fluorescein. In agreement with current literature, there were no adverse effects among the patients receiving oral fluorescein while one patient receiving IV fluorescein experienced some nausea and heaving. We determined that all retinal capillary beds can be imaged using clinically accepted fluorescein dosages and safe light levels according to the ANSI Z136.1-2000 maximum permissible exposure. As expected, the 20 mg/kg oral dose showed higher image intensity for a longer period of time than did the 7 mg/kg oral and the 500 mg IV doses. The increased resolution of AOSLO FA, compared to conventional FA, offers great opportunity for studying physiological and pathological vascular processes.

©2013 Optical Society of America

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2013 (2)

M. K. Ikram, Y. T. Ong, C. Y. Cheung, and T. Y. Wong, “Retinal vascular caliber measurements: clinical significance, current knowledge and future perspectives,” Ophthalmologica 229(3), 125–136 (2013).
[Crossref] [PubMed]

J. Flammer, K. Konieczka, R. M. Bruno, A. Virdis, A. J. Flammer, and S. Taddei, “The eye and the heart,” Eur. Heart J. 34(17), 1270–1278 (2013).
[Crossref] [PubMed]

2012 (5)

T. Y. 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(10), 2537–2549 (2012).
[Crossref] [PubMed]

Z. Zhi, X. Yin, S. Dziennis, T. Wietecha, K. L. Hudkins, C. E. Alpers, and R. K. Wang, “Optical microangiography of retina and choroid and measurement of total retinal blood flow in mice,” Biomed. Opt. Express 3(11), 2976–2986 (2012).
[Crossref] [PubMed]

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

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] [PubMed]

D. Y. Kim, J. Fingler, R. J. Zawadzki, S. S. Park, L. S. Morse, D. M. Schwartz, S. E. Fraser, and J. S. Werner, “Noninvasive imaging of the foveal avascular zone with high-speed, phase-variance optical coherence tomography,” Invest. Ophthalmol. Vis. Sci. 53(1), 85–92 (2012).
[Crossref] [PubMed]

2011 (10)

Q. Wang, O. P. Kocaoglu, B. Cense, J. Bruestle, R. S. Jonnal, W. Gao, and D. T. Miller, “Imaging retinal capillaries using ultrahigh-resolution optical coherence tomography and adaptive optics,” Invest. Ophthalmol. Vis. Sci. 52(9), 6292–6299 (2011).
[Crossref] [PubMed]

D. A. Nelson, Z. Burgansky-Eliash, H. Barash, A. Loewenstein, A. Barak, E. Bartov, T. Rock, and A. Grinvald, “High-resolution wide-field imaging of perfused capillaries without the use of contrast agent,” Clin Opthalmol 5, 1095–1106 (2011).
[PubMed]

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. Vis. Sci. 52(12), 9257–9266 (2011).
[Crossref] [PubMed]

O. P. Kocaoglu, B. Cense, R. S. Jonnal, Q. Wang, S. Lee, W. Gao, and D. T. Miller, “Imaging retinal nerve fiber bundles using optical coherence tomography with adaptive optics,” Vision Res. 51(16), 1835–1844 (2011).
[Crossref] [PubMed]

D. C. Kalogeromitros, M. P. Makris, X. S. Aggelides, A. I. Mellios, F. C. Giannoula, K. A. Sideri, A. A. Rouvas, and P. G. Theodossiadis, “Allergy skin testing in predicting adverse reactions to fluorescein: a prospective clinical study,” Acta Ophthalmol. (Copenh.) 89(5), 480–483 (2011).
[Crossref] [PubMed]

E. Zudaire, L. Gambardella, C. Kurcz, and S. Vermeren, “A computational tool for quantitative analysis of vascular networks,” PLoS ONE 6(11), e27385 (2011).
[Crossref] [PubMed]

S. Zotter, M. Pircher, T. Torzicky, M. Bonesi, E. Götzinger, R. A. Leitgeb, and C. K. Hitzenberger, “Visualization of microvasculature by dual-beam phase-resolved Doppler optical coherence tomography,” Opt. Express 19(2), 1217–1227 (2011).
[Crossref] [PubMed]

T. Schmoll, A. S. G. Singh, C. Blatter, S. Schriefl, C. Ahlers, U. Schmidt-Erfurth, and R. A. Leitgeb, “Imaging of the parafoveal capillary network and its integrity analysis using fractal dimension,” Biomed. Opt. Express 2(5), 1159–1168 (2011).
[Crossref] [PubMed]

D. Y. Kim, J. Fingler, J. S. Werner, D. M. Schwartz, S. E. Fraser, and R. J. Zawadzki, “In vivo volumetric imaging of human retinal circulation with phase-variance optical coherence tomography,” Biomed. Opt. Express 2(6), 1504–1513 (2011).
[Crossref] [PubMed]

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

2010 (4)

G. Dougherty, M. J. Johnson, and M. D. Wiers, “Measurement of retinal vascular tortuosity and its application to retinal pathologies,” Med. Biol. Eng. Comput. 48(1), 87–95 (2010).
[Crossref] [PubMed]

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] [PubMed]

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

K. R. Mendis, C. Balaratnasingam, P. Yu, C. J. Barry, I. L. McAllister, S. J. Cringle, and D. Y. Yu, “Correlation of histologic and clinical images to determine the diagnostic value of fluorescein angiography for studying retinal capillary detail,” Invest. Ophthalmol. Vis. Sci. 51(11), 5864–5869 (2010).
[Crossref] [PubMed]

2009 (2)

M. B. Vickerman, P. A. Keith, T. L. McKay, D. J. Gedeon, M. Watanabe, M. Montano, G. Karunamuni, P. K. Kaiser, J. E. Sears, Q. Ebrahem, D. Ribita, A. G. Hylton, and P. Parsons-Wingerter, “VESGEN 2D: automated, user-interactive software for quantification and mapping of angiogenic and lymphangiogenic trees and networks,” Anat. Rec. (Hoboken) 292(3), 320–332 (2009).
[Crossref] [PubMed]

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(1), 9 (2009).
[Crossref] [PubMed]

2008 (3)

J. Carroll, S. S. Choi, and D. R. Williams, “In vivo imaging of the photoreceptor mosaic of a rod monochromat,” Vision Res. 48(26), 2564–2568 (2008).
[Crossref] [PubMed]

V. J. Srinivasan, D. C. Adler, Y. Chen, I. Gorczynska, R. Huber, J. S. Duker, J. S. Schuman, and J. G. Fujimoto, “Ultrahigh-speed optical coherence tomography for three-dimensional and en face imaging of the retina and optic nerve head,” Invest. Ophthalmol. Vis. Sci. 49(11), 5103–5110 (2008).
[Crossref] [PubMed]

J. I. W. Morgan, A. Dubra, R. Wolfe, W. H. Merigan, and D. R. Williams, “In vivo autofluorescence imaging of the human and macaque retinal pigment epithelial cell mosaic,” Invest. Ophthalmol. Vis. Sci. 50(3), 1350–1359 (2008).
[Crossref] [PubMed]

2007 (3)

2006 (4)

J. Rha, R. S. Jonnal, K. E. Thorn, J. Qu, Y. Zhang, and D. T. Miller, “Adaptive optics flood-illumination camera for high speed retinal imaging,” Opt. Express 14(10), 4552–4569 (2006).
[Crossref] [PubMed]

D. C. Gray, W. Merigan, J. I. Wolfing, B. P. Gee, J. Porter, A. Dubra, T. H. Twietmeyer, K. Ahamd, R. Tumbar, F. Reinholz, and D. R. Williams, “In vivo fluorescence imaging of primate retinal ganglion cells and retinal pigment epithelial cells,” Opt. Express 14(16), 7144–7158 (2006).
[Crossref] [PubMed]

A. S. Kwan, C. Barry, I. L. McAllister, and I. Constable, “Fluorescein angiography and adverse drug reactions revisited: the Lions Eye experience,” Clin. Experiment. Ophthalmol. 34(1), 33–38 (2006).
[Crossref] [PubMed]

R. V. Azad, B. Baishya, N. Pal, Y. R. Sharma, A. Kumar, and R. Vohra, “Comparative evaluation of oral fluorescein angiography using the confocal scanning laser ophthalmoscope and digital fundus camera with intravenous fluorescein angiography using the digital fundus camera,” Clin. Experiment. Ophthalmol. 34(5), 425–429 (2006).
[Crossref] [PubMed]

2005 (2)

D. Squirrell, S. Dinakaran, S. Dhingra, C. Mody, C. Brand, and J. Talbot, “Oral fluorescein angiography with the scanning laser ophthalmoscope in diabetic retinopathy: a case controlled comparison with intravenous fluorescein angiography,” Eye (Lond.) 19(4), 411–417 (2005).
[Crossref] [PubMed]

E. Bullitt, K. E. Muller, I. Jung, W. Lin, and S. Aylward, “Analyzing attributes of vessel populations,” Med. Image Anal. 9(1), 39–49 (2005).
[Crossref] [PubMed]

2004 (1)

T. Y. Wong and P. Mitchell, “Hypertensive retinopathy,” N. Engl. J. Med. 351(22), 2310–2317 (2004).
[Crossref] [PubMed]

2003 (1)

E. Nucera, D. Schiavino, E. Merendino, A. Buonomo, C. Roncallo, E. Pollastrini, C. Lombardo, T. De Pasquale, and G. Patriarca, “Successful fluorescein desensitization,” Allergy 58(5), 458 (2003).
[Crossref] [PubMed]

2001 (1)

F. M. Razvi, E. E. Kritzinger, M. D. Tsaloumas, and R. E. Ryder, “Use of oral fluorescein angiography in the diagnosis of macular oedema within a diabetic retinopathy screening programme,” Diabet. Med. 18(12), 1003–1006 (2001).
[Crossref] [PubMed]

2000 (1)

R. Newsom, B. Moate, and T. Casswell, “Screening for diabetic retinopathy using digital colour photography and oral fluorescein angiography,” Eye (Lond.) 14(4), 579–582 (2000).
[Crossref] [PubMed]

1999 (3)

C. R. Garcia, M. E. Rivero, D. U. Bartsch, S. Ishiko, A. Takamiya, K. Fukui, H. Hirokawa, T. Clark, A. Yoshida, and W. R. Freeman, “Oral fluorescein angiography with the confocal scanning laser ophthalmoscope,” Ophthalmology 106(6), 1114–1118 (1999).
[Crossref] [PubMed]

V. Fineschi, G. Monasterolo, R. Rosi, and E. Turillazzi, “Fatal anaphylactic shock during a fluorescein angiography,” Forensic Sci. Int. 100(1-2), 137–142 (1999).
[Crossref] [PubMed]

A. Roorda and D. R. Williams, “The arrangement of the three cone classes in the living human eye,” Nature 397(6719), 520–522 (1999).
[Crossref] [PubMed]

1998 (2)

A. Bradley, H. Zhang, R. A. Applegate, L. N. Thibos, and A. E. Elsner, “Entoptic image quality of the retinal vasculature,” Vision Res. 38(17), 2685–2696 (1998).
[Crossref] [PubMed]

T. Hara, M. Inami, and T. Hara, “Efficacy and safety of fluorescein angiography with orally administered sodium fluorescein,” Am. J. Ophthalmol. 126(4), 560–564 (1998).
[Crossref] [PubMed]

1993 (1)

F. J. Ascaso, M. T. Tiestos, J. Navales, F. Iturbe, A. Palomar, and J. I. Ayala, ““Fatal acute myocardial infarction after intravenous fluorescein angiography,” Retina - J,” Ret. Vit. Dis 13, 238–239 (1993).

1992 (1)

F. Gómez-Ulla, A. Malvar, M. Parafita, P. Polo, and I. Seoane, “Oral fluorescein angiography and fluoroscopy: determination of plasma fluorescein levels and clinical application,” Optom. Vis. Sci. 69(12), 986–990 (1992).
[Crossref] [PubMed]

1991 (1)

F. Gómez-Ulla, C. Gutiérrez, and I. Seoane, “Severe anaphylactic reaction to orally administered fluorescein,” Am. J. Ophthalmol. 112(1), 94 (1991).
[PubMed]

1990 (1)

A. P. Watson and E. S. Rosen, “Oral fluorescein angiography: reassessment of its relative safety and evaluation of optimum conditions with use of capsules,” Br. J. Ophthalmol. 74(8), 458–461 (1990).
[Crossref] [PubMed]

1988 (1)

F. P. Kinsella and D. J. Mooney, “Anaphylaxis following oral fluorescein angiography,” Am. J. Ophthalmol. 106(6), 745–746 (1988).
[PubMed]

1987 (3)

S. Ghose and B. K. Nayak, “Role of oral fluorescein in the diagnosis of early papilloedema in children,” Br. J. Ophthalmol. 71(12), 910–915 (1987).
[Crossref] [PubMed]

M. Yap, J. Gilchrist, and J. Weatherill, “Psychophysical measurement of the foveal avascular zone,” Ophthalmic Physiol. Opt. 7(4), 405–410 (1987).
[Crossref] [PubMed]

T. Wilson and A. R. Carlini, “Size of the detector in confocal imaging systems,” Opt. Lett. 12(4), 227–229 (1987).
[Crossref] [PubMed]

1986 (1)

L. A. Yannuzzi, K. T. Rohrer, L. J. Tindel, R. S. Sobel, M. A. Costanza, W. Shields, and E. Zang, “Fluorescein angiography complication survey,” Ophthalmology 93(5), 611–617 (1986).
[PubMed]

1985 (1)

R. E. Barry and W. A. Behrendt, “Studies on the pharmacokinetics of fluorescein and its dilaurate ester under the conditions of the fluorescein dilaurate test,” Arzneimittelforschung 35(3), 644–648 (1985).
[PubMed]

1984 (3)

K. S. Morgan and R. M. Franklin, ““Oral fluorescein angioscopy in aphakic children,” J Pediat. Ophth,” Strab. 21, 33–36 (1984).

M. J. Noble, H. Cheng, and P. M. Jacobs, “Oral fluorescein and cystoid macular oedema: detection in aphakic and pseudophakic eyes,” Br. J. Ophthalmol. 68(4), 221–224 (1984).
[Crossref] [PubMed]

R. Azad, B. K. Nayak, H. K. Tewari, and P. K. Khosla, “Oral fluorescein angiography,” Indian J. Ophthalmol. 32(5), 415–417 (1984).
[PubMed]

1979 (1)

J. S. Kelley and M. Kincaid, “Retinal fluorography using oral fluorescein,” Arch. Ophthalmol. 97(12), 2331–2332 (1979).
[Crossref] [PubMed]

1974 (1)

A. C. Bird and R. A. Weale, “On the retinal vasculature of the human fovea,” Exp. Eye Res. 19(5), 409–417 (1974).
[Crossref] [PubMed]

1961 (1)

H. R. Novotny and D. L. Alvis, “A method of photographing fluorescence in circulating blood in the human retina,” Circulation 24(1), 82–86 (1961).
[Crossref] [PubMed]

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. Vis. Sci. 52(12), 9257–9266 (2011).
[Crossref] [PubMed]

Adler, D. C.

V. J. Srinivasan, D. C. Adler, Y. Chen, I. Gorczynska, R. Huber, J. S. Duker, J. S. Schuman, and J. G. Fujimoto, “Ultrahigh-speed optical coherence tomography for three-dimensional and en face imaging of the retina and optic nerve head,” Invest. Ophthalmol. Vis. Sci. 49(11), 5103–5110 (2008).
[Crossref] [PubMed]

Aggelides, X. S.

D. C. Kalogeromitros, M. P. Makris, X. S. Aggelides, A. I. Mellios, F. C. Giannoula, K. A. Sideri, A. A. Rouvas, and P. G. Theodossiadis, “Allergy skin testing in predicting adverse reactions to fluorescein: a prospective clinical study,” Acta Ophthalmol. (Copenh.) 89(5), 480–483 (2011).
[Crossref] [PubMed]

Ahamd, K.

Ahlers, C.

Alpers, C. E.

Alvis, D. L.

H. R. Novotny and D. L. Alvis, “A method of photographing fluorescence in circulating blood in the human retina,” Circulation 24(1), 82–86 (1961).
[Crossref] [PubMed]

Applegate, R. A.

A. Bradley, H. Zhang, R. A. Applegate, L. N. Thibos, and A. E. Elsner, “Entoptic image quality of the retinal vasculature,” Vision Res. 38(17), 2685–2696 (1998).
[Crossref] [PubMed]

Ascaso, F. J.

F. J. Ascaso, M. T. Tiestos, J. Navales, F. Iturbe, A. Palomar, and J. I. Ayala, ““Fatal acute myocardial infarction after intravenous fluorescein angiography,” Retina - J,” Ret. Vit. Dis 13, 238–239 (1993).

Ayala, J. I.

F. J. Ascaso, M. T. Tiestos, J. Navales, F. Iturbe, A. Palomar, and J. I. Ayala, ““Fatal acute myocardial infarction after intravenous fluorescein angiography,” Retina - J,” Ret. Vit. Dis 13, 238–239 (1993).

Aylward, S.

E. Bullitt, K. E. Muller, I. Jung, W. Lin, and S. Aylward, “Analyzing attributes of vessel populations,” Med. Image Anal. 9(1), 39–49 (2005).
[Crossref] [PubMed]

Azad, R.

R. Azad, B. K. Nayak, H. K. Tewari, and P. K. Khosla, “Oral fluorescein angiography,” Indian J. Ophthalmol. 32(5), 415–417 (1984).
[PubMed]

Azad, R. V.

R. V. Azad, B. Baishya, N. Pal, Y. R. Sharma, A. Kumar, and R. Vohra, “Comparative evaluation of oral fluorescein angiography using the confocal scanning laser ophthalmoscope and digital fundus camera with intravenous fluorescein angiography using the digital fundus camera,” Clin. Experiment. Ophthalmol. 34(5), 425–429 (2006).
[Crossref] [PubMed]

Baishya, B.

R. V. Azad, B. Baishya, N. Pal, Y. R. Sharma, A. Kumar, and R. Vohra, “Comparative evaluation of oral fluorescein angiography using the confocal scanning laser ophthalmoscope and digital fundus camera with intravenous fluorescein angiography using the digital fundus camera,” Clin. Experiment. Ophthalmol. 34(5), 425–429 (2006).
[Crossref] [PubMed]

Balaratnasingam, C.

K. R. Mendis, C. Balaratnasingam, P. Yu, C. J. Barry, I. L. McAllister, S. J. Cringle, and D. Y. Yu, “Correlation of histologic and clinical images to determine the diagnostic value of fluorescein angiography for studying retinal capillary detail,” Invest. Ophthalmol. Vis. Sci. 51(11), 5864–5869 (2010).
[Crossref] [PubMed]

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] [PubMed]

D. A. Nelson, Z. Burgansky-Eliash, H. Barash, A. Loewenstein, A. Barak, E. Bartov, T. Rock, and A. Grinvald, “High-resolution wide-field imaging of perfused capillaries without the use of contrast agent,” Clin Opthalmol 5, 1095–1106 (2011).
[PubMed]

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] [PubMed]

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] [PubMed]

D. A. Nelson, Z. Burgansky-Eliash, H. Barash, A. Loewenstein, A. Barak, E. Bartov, T. Rock, and A. Grinvald, “High-resolution wide-field imaging of perfused capillaries without the use of contrast agent,” Clin Opthalmol 5, 1095–1106 (2011).
[PubMed]

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. Vis. Sci. 52(12), 9257–9266 (2011).
[Crossref] [PubMed]

Barry, C.

A. S. Kwan, C. Barry, I. L. McAllister, and I. Constable, “Fluorescein angiography and adverse drug reactions revisited: the Lions Eye experience,” Clin. Experiment. Ophthalmol. 34(1), 33–38 (2006).
[Crossref] [PubMed]

Barry, C. J.

K. R. Mendis, C. Balaratnasingam, P. Yu, C. J. Barry, I. L. McAllister, S. J. Cringle, and D. Y. Yu, “Correlation of histologic and clinical images to determine the diagnostic value of fluorescein angiography for studying retinal capillary detail,” Invest. Ophthalmol. Vis. Sci. 51(11), 5864–5869 (2010).
[Crossref] [PubMed]

Barry, R. E.

R. E. Barry and W. A. Behrendt, “Studies on the pharmacokinetics of fluorescein and its dilaurate ester under the conditions of the fluorescein dilaurate test,” Arzneimittelforschung 35(3), 644–648 (1985).
[PubMed]

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] [PubMed]

Bartov, E.

D. A. Nelson, Z. Burgansky-Eliash, H. Barash, A. Loewenstein, A. Barak, E. Bartov, T. Rock, and A. Grinvald, “High-resolution wide-field imaging of perfused capillaries without the use of contrast agent,” Clin Opthalmol 5, 1095–1106 (2011).
[PubMed]

Bartsch, D. U.

C. R. Garcia, M. E. Rivero, D. U. Bartsch, S. Ishiko, A. Takamiya, K. Fukui, H. Hirokawa, T. Clark, A. Yoshida, and W. R. Freeman, “Oral fluorescein angiography with the confocal scanning laser ophthalmoscope,” Ophthalmology 106(6), 1114–1118 (1999).
[Crossref] [PubMed]

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. Vis. Sci. 52(12), 9257–9266 (2011).
[Crossref] [PubMed]

Behrendt, W. A.

R. E. Barry and W. A. Behrendt, “Studies on the pharmacokinetics of fluorescein and its dilaurate ester under the conditions of the fluorescein dilaurate test,” Arzneimittelforschung 35(3), 644–648 (1985).
[PubMed]

Bifano, T. G.

Bird, A. C.

A. C. Bird and R. A. Weale, “On the retinal vasculature of the human fovea,” Exp. Eye Res. 19(5), 409–417 (1974).
[Crossref] [PubMed]

Biss, D. P.

Blatter, C.

Bonesi, M.

Bradley, A.

A. Bradley, H. Zhang, R. A. Applegate, L. N. Thibos, and A. E. Elsner, “Entoptic image quality of the retinal vasculature,” Vision Res. 38(17), 2685–2696 (1998).
[Crossref] [PubMed]

Brand, C.

D. Squirrell, S. Dinakaran, S. Dhingra, C. Mody, C. Brand, and J. Talbot, “Oral fluorescein angiography with the scanning laser ophthalmoscope in diabetic retinopathy: a case controlled comparison with intravenous fluorescein angiography,” Eye (Lond.) 19(4), 411–417 (2005).
[Crossref] [PubMed]

Bruestle, J.

Q. Wang, O. P. Kocaoglu, B. Cense, J. Bruestle, R. S. Jonnal, W. Gao, and D. T. Miller, “Imaging retinal capillaries using ultrahigh-resolution optical coherence tomography and adaptive optics,” Invest. Ophthalmol. Vis. Sci. 52(9), 6292–6299 (2011).
[Crossref] [PubMed]

Bruno, R. M.

J. Flammer, K. Konieczka, R. M. Bruno, A. Virdis, A. J. Flammer, and S. Taddei, “The eye and the heart,” Eur. Heart J. 34(17), 1270–1278 (2013).
[Crossref] [PubMed]

Bullitt, E.

E. Bullitt, K. E. Muller, I. Jung, W. Lin, and S. Aylward, “Analyzing attributes of vessel populations,” Med. Image Anal. 9(1), 39–49 (2005).
[Crossref] [PubMed]

Buonomo, A.

E. Nucera, D. Schiavino, E. Merendino, A. Buonomo, C. Roncallo, E. Pollastrini, C. Lombardo, T. De Pasquale, and G. Patriarca, “Successful fluorescein desensitization,” Allergy 58(5), 458 (2003).
[Crossref] [PubMed]

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] [PubMed]

D. A. Nelson, Z. Burgansky-Eliash, H. Barash, A. Loewenstein, A. Barak, E. Bartov, T. Rock, and A. Grinvald, “High-resolution wide-field imaging of perfused capillaries without the use of contrast agent,” Clin Opthalmol 5, 1095–1106 (2011).
[PubMed]

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] [PubMed]

Burns, S. A.

Carlini, A. R.

Carroll, J.

J. Carroll, S. S. Choi, and D. R. Williams, “In vivo imaging of the photoreceptor mosaic of a rod monochromat,” Vision Res. 48(26), 2564–2568 (2008).
[Crossref] [PubMed]

Casswell, T.

R. Newsom, B. Moate, and T. Casswell, “Screening for diabetic retinopathy using digital colour photography and oral fluorescein angiography,” Eye (Lond.) 14(4), 579–582 (2000).
[Crossref] [PubMed]

Cense, B.

Q. Wang, O. P. Kocaoglu, B. Cense, J. Bruestle, R. S. Jonnal, W. Gao, and D. T. Miller, “Imaging retinal capillaries using ultrahigh-resolution optical coherence tomography and adaptive optics,” Invest. Ophthalmol. Vis. Sci. 52(9), 6292–6299 (2011).
[Crossref] [PubMed]

O. P. Kocaoglu, B. Cense, R. S. Jonnal, Q. Wang, S. Lee, W. Gao, and D. T. Miller, “Imaging retinal nerve fiber bundles using optical coherence tomography with adaptive optics,” Vision Res. 51(16), 1835–1844 (2011).
[Crossref] [PubMed]

Chen, Y.

V. J. Srinivasan, D. C. Adler, Y. Chen, I. Gorczynska, R. Huber, J. S. Duker, J. S. Schuman, and J. G. Fujimoto, “Ultrahigh-speed optical coherence tomography for three-dimensional and en face imaging of the retina and optic nerve head,” Invest. Ophthalmol. Vis. Sci. 49(11), 5103–5110 (2008).
[Crossref] [PubMed]

Cheng, H.

M. J. Noble, H. Cheng, and P. M. Jacobs, “Oral fluorescein and cystoid macular oedema: detection in aphakic and pseudophakic eyes,” Br. J. Ophthalmol. 68(4), 221–224 (1984).
[Crossref] [PubMed]

Cheung, C. Y.

M. K. Ikram, Y. T. Ong, C. Y. Cheung, and T. Y. Wong, “Retinal vascular caliber measurements: clinical significance, current knowledge and future perspectives,” Ophthalmologica 229(3), 125–136 (2013).
[Crossref] [PubMed]

Choi, S. S.

J. Carroll, S. S. Choi, and D. R. Williams, “In vivo imaging of the photoreceptor mosaic of a rod monochromat,” Vision Res. 48(26), 2564–2568 (2008).
[Crossref] [PubMed]

Chui, T. Y.

Clark, T.

C. R. Garcia, M. E. Rivero, D. U. Bartsch, S. Ishiko, A. Takamiya, K. Fukui, H. Hirokawa, T. Clark, A. Yoshida, and W. R. Freeman, “Oral fluorescein angiography with the confocal scanning laser ophthalmoscope,” Ophthalmology 106(6), 1114–1118 (1999).
[Crossref] [PubMed]

Constable, I.

A. S. Kwan, C. Barry, I. L. McAllister, and I. Constable, “Fluorescein angiography and adverse drug reactions revisited: the Lions Eye experience,” Clin. Experiment. Ophthalmol. 34(1), 33–38 (2006).
[Crossref] [PubMed]

Costanza, M. A.

L. A. Yannuzzi, K. T. Rohrer, L. J. Tindel, R. S. Sobel, M. A. Costanza, W. Shields, and E. Zang, “Fluorescein angiography complication survey,” Ophthalmology 93(5), 611–617 (1986).
[PubMed]

Côté, D.

Cringle, S. J.

K. R. Mendis, C. Balaratnasingam, P. Yu, C. J. Barry, I. L. McAllister, S. J. Cringle, and D. Y. Yu, “Correlation of histologic and clinical images to determine the diagnostic value of fluorescein angiography for studying retinal capillary detail,” Invest. Ophthalmol. Vis. Sci. 51(11), 5864–5869 (2010).
[Crossref] [PubMed]

De Pasquale, T.

E. Nucera, D. Schiavino, E. Merendino, A. Buonomo, C. Roncallo, E. Pollastrini, C. Lombardo, T. De Pasquale, and G. Patriarca, “Successful fluorescein desensitization,” Allergy 58(5), 458 (2003).
[Crossref] [PubMed]

Delori, F. C.

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. Vis. Sci. 52(12), 9257–9266 (2011).
[Crossref] [PubMed]

Dhingra, S.

D. Squirrell, S. Dinakaran, S. Dhingra, C. Mody, C. Brand, and J. Talbot, “Oral fluorescein angiography with the scanning laser ophthalmoscope in diabetic retinopathy: a case controlled comparison with intravenous fluorescein angiography,” Eye (Lond.) 19(4), 411–417 (2005).
[Crossref] [PubMed]

Dinakaran, S.

D. Squirrell, S. Dinakaran, S. Dhingra, C. Mody, C. Brand, and J. Talbot, “Oral fluorescein angiography with the scanning laser ophthalmoscope in diabetic retinopathy: a case controlled comparison with intravenous fluorescein angiography,” Eye (Lond.) 19(4), 411–417 (2005).
[Crossref] [PubMed]

Dougherty, G.

G. Dougherty, M. J. Johnson, and M. D. Wiers, “Measurement of retinal vascular tortuosity and its application to retinal pathologies,” Med. Biol. Eng. Comput. 48(1), 87–95 (2010).
[Crossref] [PubMed]

Dubra, A.

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 (to be published).
[PubMed]

Duker, J. S.

V. J. Srinivasan, D. C. Adler, Y. Chen, I. Gorczynska, R. Huber, J. S. Duker, J. S. Schuman, and J. G. Fujimoto, “Ultrahigh-speed optical coherence tomography for three-dimensional and en face imaging of the retina and optic nerve head,” Invest. Ophthalmol. Vis. Sci. 49(11), 5103–5110 (2008).
[Crossref] [PubMed]

Dziennis, S.

Ebrahem, Q.

M. B. Vickerman, P. A. Keith, T. L. McKay, D. J. Gedeon, M. Watanabe, M. Montano, G. Karunamuni, P. K. Kaiser, J. E. Sears, Q. Ebrahem, D. Ribita, A. G. Hylton, and P. Parsons-Wingerter, “VESGEN 2D: automated, user-interactive software for quantification and mapping of angiogenic and lymphangiogenic trees and networks,” Anat. Rec. (Hoboken) 292(3), 320–332 (2009).
[Crossref] [PubMed]

Elsner, A. E.

A. Bradley, H. Zhang, R. A. Applegate, L. N. Thibos, and A. E. Elsner, “Entoptic image quality of the retinal vasculature,” Vision Res. 38(17), 2685–2696 (1998).
[Crossref] [PubMed]

Fineschi, V.

V. Fineschi, G. Monasterolo, R. Rosi, and E. Turillazzi, “Fatal anaphylactic shock during a fluorescein angiography,” Forensic Sci. Int. 100(1-2), 137–142 (1999).
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Fingler, J.

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Lin, W.

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D. Squirrell, S. Dinakaran, S. Dhingra, C. Mody, C. Brand, and J. Talbot, “Oral fluorescein angiography with the scanning laser ophthalmoscope in diabetic retinopathy: a case controlled comparison with intravenous fluorescein angiography,” Eye (Lond.) 19(4), 411–417 (2005).
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R. Azad, B. K. Nayak, H. K. Tewari, and P. K. Khosla, “Oral fluorescein angiography,” Indian J. Ophthalmol. 32(5), 415–417 (1984).
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L. A. Yannuzzi, K. T. Rohrer, L. J. Tindel, R. S. Sobel, M. A. Costanza, W. Shields, and E. Zang, “Fluorescein angiography complication survey,” Ophthalmology 93(5), 611–617 (1986).
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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. Vis. Sci. 52(12), 9257–9266 (2011).
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F. M. Razvi, E. E. Kritzinger, M. D. Tsaloumas, and R. E. Ryder, “Use of oral fluorescein angiography in the diagnosis of macular oedema within a diabetic retinopathy screening programme,” Diabet. Med. 18(12), 1003–1006 (2001).
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V. Fineschi, G. Monasterolo, R. Rosi, and E. Turillazzi, “Fatal anaphylactic shock during a fluorescein angiography,” Forensic Sci. Int. 100(1-2), 137–142 (1999).
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M. B. Vickerman, P. A. Keith, T. L. McKay, D. J. Gedeon, M. Watanabe, M. Montano, G. Karunamuni, P. K. Kaiser, J. E. Sears, Q. Ebrahem, D. Ribita, A. G. Hylton, and P. Parsons-Wingerter, “VESGEN 2D: automated, user-interactive software for quantification and mapping of angiogenic and lymphangiogenic trees and networks,” Anat. Rec. (Hoboken) 292(3), 320–332 (2009).
[Crossref] [PubMed]

Virdis, A.

J. Flammer, K. Konieczka, R. M. Bruno, A. Virdis, A. J. Flammer, and S. Taddei, “The eye and the heart,” Eur. Heart J. 34(17), 1270–1278 (2013).
[Crossref] [PubMed]

Vohra, R.

R. V. Azad, B. Baishya, N. Pal, Y. R. Sharma, A. Kumar, and R. Vohra, “Comparative evaluation of oral fluorescein angiography using the confocal scanning laser ophthalmoscope and digital fundus camera with intravenous fluorescein angiography using the digital fundus camera,” Clin. Experiment. Ophthalmol. 34(5), 425–429 (2006).
[Crossref] [PubMed]

Wang, Q.

Q. Wang, O. P. Kocaoglu, B. Cense, J. Bruestle, R. S. Jonnal, W. Gao, and D. T. Miller, “Imaging retinal capillaries using ultrahigh-resolution optical coherence tomography and adaptive optics,” Invest. Ophthalmol. Vis. Sci. 52(9), 6292–6299 (2011).
[Crossref] [PubMed]

O. P. Kocaoglu, B. Cense, R. S. Jonnal, Q. Wang, S. Lee, W. Gao, and D. T. Miller, “Imaging retinal nerve fiber bundles using optical coherence tomography with adaptive optics,” Vision Res. 51(16), 1835–1844 (2011).
[Crossref] [PubMed]

Wang, R. K.

Watanabe, M.

M. B. Vickerman, P. A. Keith, T. L. McKay, D. J. Gedeon, M. Watanabe, M. Montano, G. Karunamuni, P. K. Kaiser, J. E. Sears, Q. Ebrahem, D. Ribita, A. G. Hylton, and P. Parsons-Wingerter, “VESGEN 2D: automated, user-interactive software for quantification and mapping of angiogenic and lymphangiogenic trees and networks,” Anat. Rec. (Hoboken) 292(3), 320–332 (2009).
[Crossref] [PubMed]

Watson, A. P.

A. P. Watson and E. S. Rosen, “Oral fluorescein angiography: reassessment of its relative safety and evaluation of optimum conditions with use of capsules,” Br. J. Ophthalmol. 74(8), 458–461 (1990).
[Crossref] [PubMed]

Weale, R. A.

A. C. Bird and R. A. Weale, “On the retinal vasculature of the human fovea,” Exp. Eye Res. 19(5), 409–417 (1974).
[Crossref] [PubMed]

Weatherill, J.

M. Yap, J. Gilchrist, and J. Weatherill, “Psychophysical measurement of the foveal avascular zone,” Ophthalmic Physiol. Opt. 7(4), 405–410 (1987).
[Crossref] [PubMed]

Webb, R. H.

Werner, J. S.

D. Y. Kim, J. Fingler, R. J. Zawadzki, S. S. Park, L. S. Morse, D. M. Schwartz, S. E. Fraser, and J. S. Werner, “Noninvasive imaging of the foveal avascular zone with high-speed, phase-variance optical coherence tomography,” Invest. Ophthalmol. Vis. Sci. 53(1), 85–92 (2012).
[Crossref] [PubMed]

D. Y. Kim, J. Fingler, J. S. Werner, D. M. Schwartz, S. E. Fraser, and R. J. Zawadzki, “In vivo volumetric imaging of human retinal circulation with phase-variance optical coherence tomography,” Biomed. Opt. Express 2(6), 1504–1513 (2011).
[Crossref] [PubMed]

Wiers, M. D.

G. Dougherty, M. J. Johnson, and M. D. Wiers, “Measurement of retinal vascular tortuosity and its application to retinal pathologies,” Med. Biol. Eng. Comput. 48(1), 87–95 (2010).
[Crossref] [PubMed]

Wietecha, T.

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(1), 9 (2009).
[Crossref] [PubMed]

J. I. W. Morgan, A. Dubra, R. Wolfe, W. H. Merigan, and D. R. Williams, “In vivo autofluorescence imaging of the human and macaque retinal pigment epithelial cell mosaic,” Invest. Ophthalmol. Vis. Sci. 50(3), 1350–1359 (2008).
[Crossref] [PubMed]

J. Carroll, S. S. Choi, and D. R. Williams, “In vivo imaging of the photoreceptor mosaic of a rod monochromat,” Vision Res. 48(26), 2564–2568 (2008).
[Crossref] [PubMed]

D. C. Gray, W. Merigan, J. I. Wolfing, B. P. Gee, J. Porter, A. Dubra, T. H. Twietmeyer, K. Ahamd, R. Tumbar, F. Reinholz, and D. R. Williams, “In vivo fluorescence imaging of primate retinal ganglion cells and retinal pigment epithelial cells,” Opt. Express 14(16), 7144–7158 (2006).
[Crossref] [PubMed]

A. Roorda and D. R. Williams, “The arrangement of the three cone classes in the living human eye,” Nature 397(6719), 520–522 (1999).
[Crossref] [PubMed]

Wilson, T.

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(1), 9 (2009).
[Crossref] [PubMed]

J. I. W. Morgan, A. Dubra, R. Wolfe, W. H. Merigan, and D. R. Williams, “In vivo autofluorescence imaging of the human and macaque retinal pigment epithelial cell mosaic,” Invest. Ophthalmol. Vis. Sci. 50(3), 1350–1359 (2008).
[Crossref] [PubMed]

Wolfing, J. I.

Wong, T. Y.

M. K. Ikram, Y. T. Ong, C. Y. Cheung, and T. Y. Wong, “Retinal vascular caliber measurements: clinical significance, current knowledge and future perspectives,” Ophthalmologica 229(3), 125–136 (2013).
[Crossref] [PubMed]

T. Y. Wong and P. Mitchell, “Hypertensive retinopathy,” N. Engl. J. Med. 351(22), 2310–2317 (2004).
[Crossref] [PubMed]

Yannuzzi, L. A.

L. A. Yannuzzi, K. T. Rohrer, L. J. Tindel, R. S. Sobel, M. A. Costanza, W. Shields, and E. Zang, “Fluorescein angiography complication survey,” Ophthalmology 93(5), 611–617 (1986).
[PubMed]

Yap, M.

M. Yap, J. Gilchrist, and J. Weatherill, “Psychophysical measurement of the foveal avascular zone,” Ophthalmic Physiol. Opt. 7(4), 405–410 (1987).
[Crossref] [PubMed]

Yin, X.

Yoshida, A.

C. R. Garcia, M. E. Rivero, D. U. Bartsch, S. Ishiko, A. Takamiya, K. Fukui, H. Hirokawa, T. Clark, A. Yoshida, and W. R. Freeman, “Oral fluorescein angiography with the confocal scanning laser ophthalmoscope,” Ophthalmology 106(6), 1114–1118 (1999).
[Crossref] [PubMed]

Yu, D. Y.

K. R. Mendis, C. Balaratnasingam, P. Yu, C. J. Barry, I. L. McAllister, S. J. Cringle, and D. Y. Yu, “Correlation of histologic and clinical images to determine the diagnostic value of fluorescein angiography for studying retinal capillary detail,” Invest. Ophthalmol. Vis. Sci. 51(11), 5864–5869 (2010).
[Crossref] [PubMed]

Yu, P.

K. R. Mendis, C. Balaratnasingam, P. Yu, C. J. Barry, I. L. McAllister, S. J. Cringle, and D. Y. Yu, “Correlation of histologic and clinical images to determine the diagnostic value of fluorescein angiography for studying retinal capillary detail,” Invest. Ophthalmol. Vis. Sci. 51(11), 5864–5869 (2010).
[Crossref] [PubMed]

Zamiri, P.

Zang, E.

L. A. Yannuzzi, K. T. Rohrer, L. J. Tindel, R. S. Sobel, M. A. Costanza, W. Shields, and E. Zang, “Fluorescein angiography complication survey,” Ophthalmology 93(5), 611–617 (1986).
[PubMed]

Zawadzki, R. J.

D. Y. Kim, J. Fingler, R. J. Zawadzki, S. S. Park, L. S. Morse, D. M. Schwartz, S. E. Fraser, and J. S. Werner, “Noninvasive imaging of the foveal avascular zone with high-speed, phase-variance optical coherence tomography,” Invest. Ophthalmol. Vis. Sci. 53(1), 85–92 (2012).
[Crossref] [PubMed]

D. Y. Kim, J. Fingler, J. S. Werner, D. M. Schwartz, S. E. Fraser, and R. J. Zawadzki, “In vivo volumetric imaging of human retinal circulation with phase-variance optical coherence tomography,” Biomed. Opt. Express 2(6), 1504–1513 (2011).
[Crossref] [PubMed]

Zhang, H.

A. Bradley, H. Zhang, R. A. Applegate, L. N. Thibos, and A. E. Elsner, “Entoptic image quality of the retinal vasculature,” Vision Res. 38(17), 2685–2696 (1998).
[Crossref] [PubMed]

Zhang, Y.

Zhi, Z.

Zhong, Z.

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

Zhou, Y.

Zotter, S.

Zudaire, E.

E. Zudaire, L. Gambardella, C. Kurcz, and S. Vermeren, “A computational tool for quantitative analysis of vascular networks,” PLoS ONE 6(11), e27385 (2011).
[Crossref] [PubMed]

Acta Ophthalmol. (Copenh.) (1)

D. C. Kalogeromitros, M. P. Makris, X. S. Aggelides, A. I. Mellios, F. C. Giannoula, K. A. Sideri, A. A. Rouvas, and P. G. Theodossiadis, “Allergy skin testing in predicting adverse reactions to fluorescein: a prospective clinical study,” Acta Ophthalmol. (Copenh.) 89(5), 480–483 (2011).
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Allergy (1)

E. Nucera, D. Schiavino, E. Merendino, A. Buonomo, C. Roncallo, E. Pollastrini, C. Lombardo, T. De Pasquale, and G. Patriarca, “Successful fluorescein desensitization,” Allergy 58(5), 458 (2003).
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T. Hara, M. Inami, and T. Hara, “Efficacy and safety of fluorescein angiography with orally administered sodium fluorescein,” Am. J. Ophthalmol. 126(4), 560–564 (1998).
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M. B. Vickerman, P. A. Keith, T. L. McKay, D. J. Gedeon, M. Watanabe, M. Montano, G. Karunamuni, P. K. Kaiser, J. E. Sears, Q. Ebrahem, D. Ribita, A. G. Hylton, and P. Parsons-Wingerter, “VESGEN 2D: automated, user-interactive software for quantification and mapping of angiogenic and lymphangiogenic trees and networks,” Anat. Rec. (Hoboken) 292(3), 320–332 (2009).
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Arch. Ophthalmol. (1)

J. S. Kelley and M. Kincaid, “Retinal fluorography using oral fluorescein,” Arch. Ophthalmol. 97(12), 2331–2332 (1979).
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Arzneimittelforschung (1)

R. E. Barry and W. A. Behrendt, “Studies on the pharmacokinetics of fluorescein and its dilaurate ester under the conditions of the fluorescein dilaurate test,” Arzneimittelforschung 35(3), 644–648 (1985).
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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(1), 9 (2009).
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Br. J. Ophthalmol. (3)

S. Ghose and B. K. Nayak, “Role of oral fluorescein in the diagnosis of early papilloedema in children,” Br. J. Ophthalmol. 71(12), 910–915 (1987).
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Circulation (1)

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Clin Opthalmol (1)

D. A. Nelson, Z. Burgansky-Eliash, H. Barash, A. Loewenstein, A. Barak, E. Bartov, T. Rock, and A. Grinvald, “High-resolution wide-field imaging of perfused capillaries without the use of contrast agent,” Clin Opthalmol 5, 1095–1106 (2011).
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R. V. Azad, B. Baishya, N. Pal, Y. R. Sharma, A. Kumar, and R. Vohra, “Comparative evaluation of oral fluorescein angiography using the confocal scanning laser ophthalmoscope and digital fundus camera with intravenous fluorescein angiography using the digital fundus camera,” Clin. Experiment. Ophthalmol. 34(5), 425–429 (2006).
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A. S. Kwan, C. Barry, I. L. McAllister, and I. Constable, “Fluorescein angiography and adverse drug reactions revisited: the Lions Eye experience,” Clin. Experiment. Ophthalmol. 34(1), 33–38 (2006).
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Diabet. Med. (1)

F. M. Razvi, E. E. Kritzinger, M. D. Tsaloumas, and R. E. Ryder, “Use of oral fluorescein angiography in the diagnosis of macular oedema within a diabetic retinopathy screening programme,” Diabet. Med. 18(12), 1003–1006 (2001).
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Eur. Heart J. (1)

J. Flammer, K. Konieczka, R. M. Bruno, A. Virdis, A. J. Flammer, and S. Taddei, “The eye and the heart,” Eur. Heart J. 34(17), 1270–1278 (2013).
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Exp. Eye Res. (1)

A. C. Bird and R. A. Weale, “On the retinal vasculature of the human fovea,” Exp. Eye Res. 19(5), 409–417 (1974).
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Eye (Lond.) (2)

D. Squirrell, S. Dinakaran, S. Dhingra, C. Mody, C. Brand, and J. Talbot, “Oral fluorescein angiography with the scanning laser ophthalmoscope in diabetic retinopathy: a case controlled comparison with intravenous fluorescein angiography,” Eye (Lond.) 19(4), 411–417 (2005).
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Forensic Sci. Int. (1)

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K. R. Mendis, C. Balaratnasingam, P. Yu, C. J. Barry, I. L. McAllister, S. J. Cringle, and D. Y. Yu, “Correlation of histologic and clinical images to determine the diagnostic value of fluorescein angiography for studying retinal capillary detail,” Invest. Ophthalmol. Vis. Sci. 51(11), 5864–5869 (2010).
[Crossref] [PubMed]

J. I. W. Morgan, A. Dubra, R. Wolfe, W. H. Merigan, and D. R. Williams, “In vivo autofluorescence imaging of the human and macaque retinal pigment epithelial cell mosaic,” Invest. Ophthalmol. Vis. Sci. 50(3), 1350–1359 (2008).
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V. J. Srinivasan, D. C. Adler, Y. Chen, I. Gorczynska, R. Huber, J. S. Duker, J. S. Schuman, and J. G. Fujimoto, “Ultrahigh-speed optical coherence tomography for three-dimensional and en face imaging of the retina and optic nerve head,” Invest. Ophthalmol. Vis. Sci. 49(11), 5103–5110 (2008).
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D. Y. Kim, J. Fingler, R. J. Zawadzki, S. S. Park, L. S. Morse, D. M. Schwartz, S. E. Fraser, and J. S. Werner, “Noninvasive imaging of the foveal avascular zone with high-speed, phase-variance optical coherence tomography,” Invest. Ophthalmol. Vis. Sci. 53(1), 85–92 (2012).
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J. Tam, J. A. Martin, and A. Roorda, “Noninvasive visualization and analysis of parafoveal capillaries in humans,” Invest. Ophthalmol. Vis. Sci. 51(3), 1691–1698 (2010).
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Q. Wang, O. P. Kocaoglu, B. Cense, J. Bruestle, R. S. Jonnal, W. Gao, and D. T. Miller, “Imaging retinal capillaries using ultrahigh-resolution optical coherence tomography and adaptive optics,” Invest. Ophthalmol. Vis. Sci. 52(9), 6292–6299 (2011).
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J. Opt. Soc. Am. A (1)

Med. Biol. Eng. Comput. (1)

G. Dougherty, M. J. Johnson, and M. D. Wiers, “Measurement of retinal vascular tortuosity and its application to retinal pathologies,” Med. Biol. Eng. Comput. 48(1), 87–95 (2010).
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N. Engl. J. Med. (1)

T. Y. Wong and P. Mitchell, “Hypertensive retinopathy,” N. Engl. J. Med. 351(22), 2310–2317 (2004).
[Crossref] [PubMed]

Nature (1)

A. Roorda and D. R. Williams, “The arrangement of the three cone classes in the living human eye,” Nature 397(6719), 520–522 (1999).
[Crossref] [PubMed]

Ophthalmic Physiol. Opt. (1)

M. Yap, J. Gilchrist, and J. Weatherill, “Psychophysical measurement of the foveal avascular zone,” Ophthalmic Physiol. Opt. 7(4), 405–410 (1987).
[Crossref] [PubMed]

Ophthalmologica (1)

M. K. Ikram, Y. T. Ong, C. Y. Cheung, and T. Y. Wong, “Retinal vascular caliber measurements: clinical significance, current knowledge and future perspectives,” Ophthalmologica 229(3), 125–136 (2013).
[Crossref] [PubMed]

Ophthalmology (2)

C. R. Garcia, M. E. Rivero, D. U. Bartsch, S. Ishiko, A. Takamiya, K. Fukui, H. Hirokawa, T. Clark, A. Yoshida, and W. R. Freeman, “Oral fluorescein angiography with the confocal scanning laser ophthalmoscope,” Ophthalmology 106(6), 1114–1118 (1999).
[Crossref] [PubMed]

L. A. Yannuzzi, K. T. Rohrer, L. J. Tindel, R. S. Sobel, M. A. Costanza, W. Shields, and E. Zang, “Fluorescein angiography complication survey,” Ophthalmology 93(5), 611–617 (1986).
[PubMed]

Opt. Express (3)

Opt. Lett. (2)

Optom. Vis. Sci. (2)

T. Y. Chui, Z. Zhong, H. Song, and S. A. Burns, “Foveal avascular zone and its relationship to foveal pit shape,” Optom. Vis. Sci. 89(5), 602–610 (2012).
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F. Gómez-Ulla, A. Malvar, M. Parafita, P. Polo, and I. Seoane, “Oral fluorescein angiography and fluoroscopy: determination of plasma fluorescein levels and clinical application,” Optom. Vis. Sci. 69(12), 986–990 (1992).
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PLoS ONE (1)

E. Zudaire, L. Gambardella, C. Kurcz, and S. Vermeren, “A computational tool for quantitative analysis of vascular networks,” PLoS ONE 6(11), e27385 (2011).
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Proc. SPIE (1)

D. P. Biss, R. H. Webb, Y. Zhou, T. G. Bifano, P. Zamiri, and C. P. Lin, “An adaptive optics biomicroscope for mouse retinal imaging,” Proc. SPIE 6467, 646703 (2007).
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F. J. Ascaso, M. T. Tiestos, J. Navales, F. Iturbe, A. Palomar, and J. I. Ayala, ““Fatal acute myocardial infarction after intravenous fluorescein angiography,” Retina - J,” Ret. Vit. Dis 13, 238–239 (1993).

Retina (3)

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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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 (to be published).
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K. S. Morgan and R. M. Franklin, ““Oral fluorescein angioscopy in aphakic children,” J Pediat. Ophth,” Strab. 21, 33–36 (1984).

Vision Res. (3)

O. P. Kocaoglu, B. Cense, R. S. Jonnal, Q. Wang, S. Lee, W. Gao, and D. T. Miller, “Imaging retinal nerve fiber bundles using optical coherence tomography with adaptive optics,” Vision Res. 51(16), 1835–1844 (2011).
[Crossref] [PubMed]

J. Carroll, S. S. Choi, and D. R. Williams, “In vivo imaging of the photoreceptor mosaic of a rod monochromat,” Vision Res. 48(26), 2564–2568 (2008).
[Crossref] [PubMed]

A. Bradley, H. Zhang, R. A. Applegate, L. N. Thibos, and A. E. Elsner, “Entoptic image quality of the retinal vasculature,” Vision Res. 38(17), 2685–2696 (1998).
[Crossref] [PubMed]

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A. Dubra and Z. Harvey, “Registration of 2D Images from Fast Scanning Ophthalmic Instruments ” in The 4th International Workshop on Biomedical Image Registration, B. Fischer, B. M. Dawant, and C. Lorenz, ed. (Springer Berlin Heidelberg, Germany, 2010), pp. 60–71.

G. Smith and D. A. Atchison, The Eye and Visual Optical Instruments, 1st ed. (Cambridge University Press, Cambridge, 1997).

A. Perez-Rovira, T. MacGillivray, E. Trucco, K. S. Chin, K. Zutis, C. Lupascu, D. Tegolo, A. Giachetti, P. J. Wilson, A. Doney, and B. Dhillon, “VAMPIRE: Vessel assessment and measurement platform for images of the retina,” in Proceedings of IEEE Conference on Engineering in Medicine and Biology Society (Institute of Electrical and Electronics Engineers, Boston, 2011), pp. 3391–3394.
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Figures (5)

Fig. 1
Fig. 1 Conventional SLO FA image (A) taken 20 minutes after oral administration of 20 mg/kg fluorescein, with two areas of interest (A insets B and C) approximately 5° from the fovea. These same areas were magnified and contrast stretched (B1 and C1) for comparison with AOSLO FA images of the corresponding areas (B2 and C2), collected 30 minutes after oral fluorescein administration. The scale bar represents 100 µm and applies to all images other than image A.

Download Full Size | PPT Slide | PDF

Fig. 2
Fig. 2 Conventional IV FA image of the FAZ was magnified and contrast stretched (A) for comparison with an AOSLO FA image montage of the same region (B). The AOSLO scale bar represents 500 µm.

Download Full Size | PPT Slide | PDF

Fig. 3
Fig. 3 Comparison of AOSLO FA image sequences after oral or IV fluorescein administration, showing a retinal area approximately 5° inferotemporal from the fovea. Fluorescein was administered at time zero. Mean pixel value was calculated for each image and then normalized to the maximum value of the oral and IV image series to generate the intensity percentages, presented on the top right corner of each image. All images were then contrast stretched to make optimal use of the gray scale while avoiding saturation. The contrast-stretched images are presented in this figure. The scale bar represents 100 µm.

Download Full Size | PPT Slide | PDF

Fig. 4
Fig. 4 Comparison of AOSLO FA image sequences between 20 mg/kg and 7 mg/kg oral administration of fluorescein, showing a retinal area approximately 5° superior-nasal from the fovea. Mean pixel values were calculated for each image and then normalized to the maximum value of the oral and IV image series to generate the intensity percentages, presented on the top right corner of each image. All images were then contrast stretched to make optimal use of the gray scale while avoiding saturation. The contrast-stretched images are presented in this figure. The scale bar represents 100 µm.

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Fig. 5
Fig. 5 Conventional SLO FA image acquired approximately 30 minutes after oral fluorescein administration (A) showing four peripapillary locations chosen for AOSLO imaging (A insets B, C, D and E). The reflectance AOSLO images of these small areas, focused on the nerve fiber layer (B1, C1, D1 and E1), show large blood vessels, capillaries and nerve fiber bundles. The corresponding AOSLO FA images recorded at the same focus (B2, C2, D2 and E2) approximately 15 minutes after oral fluorescein administration show only vasculature, revealing the radial peripapillary capillary bed with high contrast and detail. Peripapillary capillaries (B2, C2, D2 and E2) can be seen radiating parallel to the nerve fibers (B1, C1, D1 and E1). Capillary free zones can be seen surrounding arteries (B2, C2 and lower E2) and not veins (D2 and upper E2). AOSLO FA images focused closer to the outer retina (B3, C3, D3 and E3) show additional non-radial capillaries (arrow heads). These retinal capillaries can be seen deriving from the same retinal arteries (arrows) that supply the peripapillary capillaries. The scale bar represents 100 µm and applies to all images other than image A.

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Table 1 AOSLO FA Experiments

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