■Qualitative D-OCT methods yield vascular contrast similar to fluorescent angiography, but with the important difference that only blood in motion can be visualized.

■Novel D-OCT instruments with enhanced penetration promise assessing both inner retinal and choroidal perfusion dynamics with high contrast and sensitivity.

■Quantitative D-OCT gives insight into vascular dynamics and mechanics. The assessment of vascular stiffness is an important factor for determining vascular-disease predisposition.

■Patient studies are currently underway with the hope to exploit the full potential of modern D-OCT concepts for early diagnosis of perfusion disorders, such as precursors of retinal disease (AMD, diabetic retinopathy, glaucoma) as well as for pharmacological research.

Acknowledgements  The authors acknowledge all the members of the Biomedical Imaging Group at the School of Optometry and Vision Sciences, Cardiff University, Alan C. Bird and Catherine A. Egan, Medical Retina Service, Moorfields, London, United Kingdom; B. Baumann, E. Götzinger, M. Pircher, T. Schmoll, C. Kolbitsch, L. Schmetterer and H. Sattmann, Center for Biomedical Engineering and Physics, Medical University of Vienna; C. Ahlers, W. Geitzenauer, S. Michels,andU.Schmidt-Erfurth,DepartmentofOphthalmology, Medical University of Vienna, T. Lasser, A. Bachmann, R. Michaely, and M. Villiger, Ecole Polytechnique Federale de Lausanne, Switzerland. Financial and equipment support by the following institutions is also acknowledged: Cardiff University, FP6-IST-NMP-2 STREPT (017128), Action Medical Research (AP1110), DTI (1544C), European Union project FUN OCT (FP7 HEALTH, contract no. 201880); FEMTOLASERS GmbH, Carl Zeiss Meditec Inc., Exalos Inc, Maxon Computer GmbH, Multiwave Photonics and The Lowy Foundation, Sydney, Australia; Austrian Science Fund (P19624).

References

 1. Huang D, Swanson EA, Lin CP, Schuman JS, Stinson WG, Chang W, Hee MR, Flotte T, Gregory K, Puliafito CA, Fujimoto JG (1991) Optical coherence tomography. Science 254:1178–1181

 2. Drexler W, Fujimoto JG (2008) Optical coherence tomography: technology and applications. Springer, Verlag

 3. Drexler W, Fujimoto JG (2008) State-of-the-art retinal optical coherence tomography. Prog Retin Eye Res 27:45–88

 4. Fercher AF, Hitzenberger CK, Kamp G, El-Zaiat SY (1995) Measurement of intraocular distances by backscattering spectral interferometry. Opt Commun 117:43–48

References 213

 5. Leitgeb R, Hitzenberger CK, Fercher AF (2003) Perfor­ mance of fourier domain vs. time domain optical coherence tomography. Opt Express 11:889–894

 6. Unterhuber A, Považay B, Hermann B, Sattmann H, Chavez-Pirson A, Drexler W (2005) In vivo retinal optical coherence tomography at 1040 nm-enhanced penetration into the choroid. Opt Express 13:3252–3258

 7. Považay B, Bizheva K, Hermann B, Unterhuber A, Sattmann H, Fercher AF, Drexler W, Schubert C, Ahnelt PK, Mei M, Holzwarth R, Wadsworth WJ, Knight JC, Russel PS (2003) Enhanced visualization of choroidal vessels using ultrahigh resolution ophthalmic OCT at 1050 nm. Opt Express 11:1980–1986

 8. Považay B, Hermann B, Unterhuber A, Hofer B, Sattmann H, Zeiler F, Morgan JE, Falkner-Radler C, Glittenberg C, Binder S, Drexler W (2007) Three-dimensional optical coherence tomography at 1050 nm versus 800 nm in retinal pathologies: enhanced performance and choroidal penetration in cataract patients. J Biomed Opt 12:041211

 9. Makita S, Hong Y, Yamanari M, Yatagai T, Yasuno Y (2006) Optical coherence angiography. Opt Express 14: 7821–7840

10.Lee EC, de Boer JF, Mujat M, Lim H, Yun SH (2006) In vivo optical frequency domain imaging of human retina and choroid. Opt Express 14:4403–4411

11.Yasuno Y, Hong YJ, Makita S, Yamanari M, Akiba M, Miura M, Yatagai T (2007) In vivo high-contrast imaging of deep posterior eye by 1-µm swept source optical coherence tomography and scattering optical coherence angiography. Opt Express 15:6121–6139

12.Hong Y, Makita S, Yamanari M, Miura M, Kim S, Yatagai T, Yasuno Y (2007) Three-dimensional visualization of choroidal vessels by using standard and ultra-high resolution scattering optical coherence angiography. Opt Express 15: 7538–7550

13.Makita S, Fabritius T, Yasuno Y (2008) Full-range, highspeed, high-resolution 1-µm spectral-domain optical coherence tomography using BM-scan for volumetric imaging of the human posterior eye. Opt Express 16: 8406–8420

14.Huber R, Adler DC, Srinivasan VJ, Fujimoto JG (2007) Fourier domain mode locking at 1050 nm for ultra-high- speed optical coherence tomography of the human retina at 236,000 axial scans per second. Opt Lett 32:2049–2051

15.Srinivasan VJ, Adler DC, Chen Y, Gorczynska I, Huber R, Duker J, Schuman JS, Fujimoto JG (2008) Ultrahigh-speed optical coherence tomography for three-dimensional and en face imaging of the retina and optic nerve head. Invest Ophthalmol Vis Sci iovs.08–2127%U http://www.iovs.org/ cgi/content/abstract/iovs.2108–2127v2121

16.Povazay B, Hermann B, Hofer B, Kajic V, Simpson E, Bridgford T, Drexler W (2009) Wide field optical coherence­

tomography of the choroid in vivo. Invest Ophthalmol Vis Sci 50:1856–1863

17.Považay B, Hofer B, Torti C, Hermann B, Tumlinson AR, Esmaeelpour M, Egan CA, Bird AC, Drexler W (2009)

Opt Express 17:4134–4150

18.Howland HC, Howland B (1977) A subjective method for the measurement of monochromatic aberrations of the eye. J Opt Soc Am 67:1508–1518

19.Liang JZ, Williams DR, Miller DT (1997) Supernormal vision and high-resolution retinal imaging through adaptive optics. J Opt Soc Am A Opt Image Sci Vis 14:2884–2892

20.Roorda A, Williams DR (1999) The arrangement of the three cone classes in the living human eye. Nature 397:520–522

21.Roorda A, Romero-Borja F, Donnelly WJ, Queener H, Hebert TJ, Campbell MCW (2002) Adaptive optics scanning laser ophthalmoscopy. Opt Express 10:405–412

22.Gray DC, Merigan W, Wolfing JI, Gee BP, Porter J, Dubra A, Twietmeyer TH, Ahmad K, Tumbar R, Reinholz F, Williams DR (2006) In vivo fluorescence imaging of primate retinal ganglion cells and retinal pigment epithelial cells. Opt Express 14:7144–7158

23.Hermann B, Fernandez EJ, Unterhuber A, Sattmann H, Fercher AF, Drexler W, Prieto PM, Artal P (2004) Adaptiveoptics ultrahigh-resolution optical coherence tomography. Opt Lett 29:2142–2144

24.Zhang Y, Rha JT, Jonnal RS, Miller DT (2005) Adaptive optics parallel spectral domain optical coherence tomography for imaging the living retina. Opt Express 13:4792–4811

25.Zhang Y, Cense B, Rha J, Jonnal RS, Gao W, Zawadzki RJ, Werner JS, Jones S, Olivier S, Miller DT (2006) High-speed volumetric imaging of cone photoreceptors with adaptive optics spectral-domain optical coherence tomography. Opt Express 14:4380–4394

26.Zawadzki RJ, Jones SM, Olivier SS, Zhao MT, Bower BA, Izatt JA, Choi S, Laut S, Werner JS (2005) Adaptive-optics optical coherence tomography for high-resolution and high-speed 3D retinal in vivo imaging. Opt Express 13: 8532–8546

27.Fernandez EJ, Hermann B, Povazay B, Unterhuber A, Sattmann H, Hofer B, Ahnelt PK, Drexler W (2008) Ultrahigh resolution optical coherence tomography and pancorrection for cellular imaging of the living human retina. Opt Express 16:11083–11094

28.Fernandez EJ, Vabre L, Hermann B, Unterhuber A, Povazay B, Drexler W (2006) Adaptive optics with a magnetic deformable mirror: applications in the human eye. Opt Express 14:8900–8917

29.Hee MR, Huang D, Swanson EA, Fujimoto JG (1992) Polarization-sensitive low-coherence reflectometer for birefringence characterization and ranging. J Opt Soc Am B Opt Phys 9:903–908

30.deBoer JF, Milner TE, vanGemert MJC, Nelson JS (1997) Two-dimensional birefringence imaging in biological tissue by polarization-sensitive optical coherence tomography. Opt Lett 22:934–936

31.Götzinger E, Pircher M, Hitzenberger CK (2005) High speed spectral domain polarization sensitive optical coherence tomography of the human retina. Opt Express 13: 10217–10229

32.Cense B, Mujat M, Chen TC, Park BH, de Boer JF (2007) Polarization-sensitive spectral-domain optical coherence tomography using a single line scan camera. Opt Express 15:2421–2431

33.Yamanari M, Miura M, Makita S, Yatagai T, Yasuno Y (2008) Phase retardation measurement of retinal nerve fiber layer by polarization-sensitive spectral-domain optical coherence tomography and scanning laser polarimetry. J Biomed Opt 13:10

34.Cense B, Chen TC, Park BH, Pierce MC, de Boer JF (2004) Thickness and birefringence of healthy retinal nerve fiber layer tissue measured with polarization-sensitive optical coherence tomography. Invest Ophthalmol Vis Sci 45:2606–2612

35.Pircher M, Götzinger E, Leitgeb R, Sattmann H, Findl O, Hitzenberger CK (2004) Imaging of polarization properties of human retina in vivo with phase resolved transversal PS-OCT. Opt Express 12:5940–5951

36.Pircher M, Götzinger E, Findl O, Michels S, Geitzenauer W, Leydolt C, Schmidt-Erfurth U, Hitzenberger CK (2006) Human macula investigated in vivo with polarization-­ sensitive optical coherence tomography. Invest Ophthalmol Vis Sci 47:5487–5494

37.Michels S, Pircher M, Geitzenauer W, Simader C, Gotzinger E, Findl O, Schmidt-Erfurth U, Hitzenberger CK (2008) Value of polarisation-sensitive optical coherence tomography­ in diseases affecting the retinal pigment epithelium. Br J Ophthalmol 92:204–209

38.Götzinger E, Pircher M, Baumann B, Ahlers C, Geitzenauer W, Schmidt-Erfurt U, Hitzenberger CK (2009) Three-dimensional polarization sensitive OCT imaging and interactive display of the human retina. Opt Express 17: 4151–4165

39.Götzinger E, Pircher M, Baumann B, Hirn C, Vass C, Hitzenberger CK (2008) Analysis of the origin of atypical scanning laser polarimetry patterns by polarization sensitive optical coherence tomography. Invest Ophthalmol Vis Sci 49:5366–5372

40.Fortune B, Cull GA, Burgoyne CF (2008) Relative course of retinal nerve fiber layer birefringence and thickness and

retinal function changes after optic nerve transection. Invest Ophthalmol Vis Sci 49:4444–4452

41.Mujat M, Park BH, Cense B, Chen TC, de Boer JF (2007) Autocalibration of spectral-domain optical coherence tomography spectrometers for in vivo quantitative retinal nerve fiber layer birefringence determination. J Biomed Opt 12:6

42.Miura M, Yamanari M, Iwasaki T, Elsner AE, Makita S, Yatagai T, Yasuno Y (2008) Imaging polarimetry in agerelated macular degeneration. Invest Ophthalmol Vis Sci 49:2661–2667

43.Götzinger E, Pircher M, Geitzenauer W, Ahlers C, Baumann B, Michels S, Schmidt-Erfurt U, Hitzenberger CK (2008) Retinal pigment epithelium segmentation by polarization sensitive optical coherence tomography. Opt Express 16: 16410–16422

44.Logean E, Schmetterer LF, Riva CE (2000) Optical doppler velocimetry at various retinal vessel depths by variation of the source coherence length. Appl Opt 39:2858–2862

45.Flammer J, Orgul S, Costa VP, Orzalesi N, Krieglstein GK, Serra LM, Renard VX, Stefansson E (2002) The impact of ocular blood flow in glaucoma. Prog Retin Eye Res 21:359–393

46.Friedman E (1997) A hemodynamic model of the pathogenesis of age-related macular degeneration. Am J Ophthalmol 124:677–682

47.Schmetterer L, Wolzt M (1999) Ocular blood flow and associated functional deviations in diabetic retinopathy. Diabetologia 42:387–405

48.Wang XJ, Milner TE, Nelson JS (1995) Characterization of fluid flow velocity by optical Doppler tomography. Opt Lett 20:1337–1339

49.Izatt JA, Kulkarni MD, Yazdanfar S, Barton JK, Welch AJ (1997) In vivo bidirectional color Doppler flow imaging of picoliter blood volumes using optical coherence tomography. Opt Lett 22:1439–1441

50.Chen Z, Milner TE, Dave D, Nelson JS (1997) Optical Doppler tomographic imaging of fluid flow velocity in highly scattering media. Opt Lett 22:64–66

51.Yazdanfar S, Rollins AM, Izatt JA (2000) Imaging and velocimetry of the human retinal circulation with color Doppler optical coherence tomography. Opt Lett 25: 1448–1450

52.Yazdanfar S, Rollins AM, Izatt J (2003) In vivo imaging of human retinal flow dynamics by color Doppler optical coherence tomography. Arch Ophthalmol 121:235–239

53.Schmidt-Erfurth U, Leitgeb RA, Michels S, Povazay B, Sacu S, Hermann B, Ahlers C, Sattmann H, Scholda C, Fercher AF, Drexler W (2005) Three-dimensional ultra- high-resolution optical coherence tomography of macular diseases. Invest Ophthalmol Vis Sci 46:3393–3402

54.Nassif N, Cense B, Park BH, Yun SH, Chen TC, Bouma BE, Tearney GJ, de Boer JF (2004) In vivo human retinal imag-

ing by ultrahigh-speed spectral domain optical coherence tomography. Opt Lett 29:480–482

55.Fercher AF, Hitzenberger CK, Kamp G, Elzaiat SY (1995) Measurement of intraocular distances by backscattering spectral interferometry. Opt Commun 117:43–48

56.de Boer JF, Cense B, Park BH, Pierce MC, Tearney GJ, Bouma BE (2003) Improved signal-to-noise ratio in spec- tral-domain compared with time-domain optical coherence tomography. Opt Lett 28:2067–2069

57.Choma MA, Sarunic MV, Yang C, Izatt J (2003) Sensitivity advantage of swept source and Fourier domain optical coherence tomography. Opt Express 11:2183–2189

58.Wojtkowski M, Leitgeb R, Kowalczyk A, Bajraszewski T, Fercher AF (2002) In vivo human retinal imaging by Fourier domain optical coherence tomography. J Biomed Opt 7:457–463

59.Wojtkowski M, Srinivasan V, Fujimoto JG, Ko T, Schuman JS, Kowalczyk A, Duker JS (2005) Threedimensional retinal imaging with high-speed ultrahighresolution optical coherence tomography. Ophthalmology 112:1734–1746

60.Leitgeb RA, Schmetterer L, Drexler W, Fercher AF, Zawadzki RJ, Bajraszewski T (2003) Real-time assessment of retinal blood flow with ultrafast acquisition by color Doppler Fourier domain optical coherence tomography. Optics Express 11:3116–3121

61.Leitgeb RA, Schmetterer L, Hitzenberger CK, Fercher AF, Berisha F, Wojtkowski M, Bajraszewski T (2004) Real-time measurement of in vitro flow by Fourier-domain color Doppler optical coherence tomography. Opt Lett 29:171–173

62.White BR, Pierce MC, Nassif N, Cense B, Park BH, Tearney GJ, Bouma BE, Chen TC, de Boer JF (2003) In vivo dynamic human retinal blood flow imaging using ultra-high-speed spectral domain optical Doppler tomography. Opt Express 11:3490–3497

63.Schmoll T, Kolbitsch C, Leitgeb RA (2009) Ultra-high- speed volumetric tomography of human retinal blood flow. Opt Express 17:4166–4176

64.Bachmann AH, Villiger ML, Blatter C, Lasser T, Leitgeb RA (2007) Resonant Doppler flow imaging and optical vivisection of retinal blood vessels. Opt Express 15:408–422

65.An L, Wang RK (2008) In vivo volumetric imaging of vascular perfusion within human retina and choroids with optical micro-angiography. Opt Express 16:11438–11452

66.Szkulmowski M, Szkulmowska A, Bajraszewski T, Kowalczyk A, Wojtkowski M (2008) Flow velocity estimation using joint spectral and time domain optical coherence tomography. Opt Express 16:6008–6025

67.Tao YK, Davis AM, Izatt JA (2008) Single-pass volumetric bidirectional blood flow imaging spectral domain optical coherence tomography using a modified Hilbert transform. Optics Express 16:12350–12361

70.Hong Y, Makita S, Yamanari M, Miura M, Kim S, Yatagai T, Yasuno Y (2007) Three-dimensional visualization of choroidal vessels by using standard and ultra-high resolution scattering optical coherence angiography. Opt Express 15: 7538–7550

71.Unterhuber A, Pova?ay B, Hermann B, Sattmann H, Chavez-Pirson A, Drexler W (2005) In vivo retinal optical coherence tomography at 1040 nm - enhanced penetration into the choroid. Opt Express 13:3252–3258

72.Yasuno Y, Hong Y, Makita S, Yamanari M, Akiba M, Miura M, Yatagai T (2007) In vivo high-contrast imaging of deep posterior eye by 1-um swept source optical coherence tomography andscattering optical coherence angiography. Opt Express 15:6121–6139

73.Michaely R, Bachmann AH, Villiger ML, Blatter C, Lasser T, Leitgeb RA (2007) Vectorial reconstruction of retinal blood flow in three dimensions measured with high resolution resonant Doppler Fourier domain optical coherence tomography. J Biomed Opt 12:041213–041217

74.Makita S, Fabritius T, Yasuno Y (2008) Quantitative reti- nal-blood flow measurement with three-dimensional ves-

sel geometry determination using ultrahigh-resolution Doppler optical coherence angiography. Opt Lett 33: 836–838

75.Werkmeister RM, Dragostinoff N, Pircher M, Gˆtzinger E, Hitzenberger CK, Leitgeb RA, Schmetterer L (2008) Bidirectional Doppler Fourier-domain optical coherence tomography for measurement of absolute flow velocities in human retinal vessels. Opt Lett 33:2967–2969

76.Wang YM, Bower BA, Izatt JA, Tan O, Huang D (2008) Retinal blood flow measurement by circumpapillary Fourier domain Doppler optical coherence tomography. J Biomed Opt 13:064003

77.van Leeuwen TG, Kulkarni MD, Yazdanfar S, Rollins AM, Izatt JA (1999) High-flow-velocity and shear-rate imaging by use of color Doppler optical coherence tomography. Opt Lett 24:1584–1586

78.Davies PF, Tripathi SC (1993) Mechanical stress mechanisms and the cell. An endothelial paradigm. Circ Res 72:239–245

79.Vilser W, Nagel E, Lanzl I (2002) Retinal vessel analysisnew possibilities. Biomed Tech 47(Suppl 1):682–685

80.Wang Y, Fawzi A, Tan O, Gil-Flamer J, Huang D (2009) Retinal blood flow detection in diabetic patients by Doppler Fourier domain optical coherence tomography. Opt Express 17:4061–4073