We used optical coherence tomography (OCT) angiography with a high-speed swept-source OCT system to investigate retinal blood flow changes induced by visual stimulation with a reversing checkerboard pattern. The split-spectrum amplitude-decorrelation angiography (SSADA) algorithm was used to quantify blood flow as measured with parafoveal flow index (PFI), which is proportional to the density of blood vessels and the velocity of blood flow in the parafoveal region of the macula. PFI measurements were taken in 15 second intervals during a 4 minute period consisting of 1 minute of baseline, 2 minutes with an 8 Hz reversing checkerboard pattern stimulation, and 1 minute without stimulation. PFI measurements increased 6.1±4.7% (p = .001) during the first minute of stimulation, with the most significant increase in PFI occurring 30 seconds into stimulation (p<0.001). These results suggest that pattern stimulation induces a change to retinal blood flow that can be reliably measured with OCT angiography.
References
[1]
Roy CS, Sherrington CS (1890) On the Regulation of the Blood-supply of the Brain. J Physiol 11: : 85–158 117.
[2]
Villringer A, Dirnagl U (1995) Coupling of brain activity and cerebral blood flow: basis of functional neuroimaging. Cerebrovasc Brain Metab Rev 7: 240–276.
[3]
Riva CE, Harino S, Shonat RD, Petrig BL (1991) Flicker evoked increase in optic nerve head blood flow in anesthetized cats. Neurosci Lett 128: 291–296.
[4]
Kiryu J, Asrani S, Shahidi M, Mori M, Zeimer R (1995) Local response of the primate retinal microcirculation to increased metabolic demand induced by flicker. Invest Ophthalmol Vis Sci 36: 1240–1246.
[5]
Scheiner AJ, Riva CE, Kazahaya K, Petrig BL (1994) Effect of flicker on macular blood flow assessed by the blue field simulation technique. Invest Ophthalmol Vis Sci 35: 3436–3441.
Garhofer G, Zawinka C, Resch H, Huemer KH, Dorner GT, et al. (2004) Diffuse luminance flicker increases blood flow in major retinal arteries and veins. Vision Res 44: 833–838.
[8]
Wang Y, Fawzi AA, Tan O, Zhang X, Huang D (2011) Flicker-induced changes in retinal blood flow assessed by Doppler optical coherence tomography. Biomed Opt Express 2: 1852–1860.
[9]
Riva CE, Falsini B, Logean E (2001) Flicker-evoked responses of human optic nerve head blood flow: luminance versus chromatic modulation. Invest Ophthalmol Vis Sci 42: 756–762.
[10]
Falsini B, Riva CE, Logean E (2002) Flicker-evoked changes in human optic nerve blood flow: relationship with retinal neural activity. Invest Ophthalmol Vis Sci 43: 2309–2316.
[11]
Potsaid B, Baumann B, Huang D, Barry S, Cable AE, et al. (2010) Ultrahigh speed 1050 nm swept source/Fourier domain OCT retinal and anterior segment imaging at 100,000 to 400,000 axial scans per second. Opt Express 18: 20029–20048.
[12]
Jia Y, Tan O, Tokayer J, Potsaid B, Wang Y, et al. (2012) Split-spectrum amplitude-decorrelation angiography with optical coherence tomography. Opt Express 20: 4710–4725.
[13]
Strenn K, Menapace R, Rainer G, Findl O, Wolzt M, et al. (1997) Reproducibility and sensitivity of scanning laser Doppler flowmetry during graded changes in PO2. Br J Ophthalmol 81: 360–364.
[14]
Tam J, Tiruveedhula P, Roorda A (2011) Characterization of single-file flow through human retinal parafoveal capillaries using an adaptive optics scanning laser ophthalmoscope. Biomed Opt Express 2: 781–793.
[15]
Zhong Z, Petrig BL, Qi X, Burns SA (2008) In vivo measurement of erythrocyte velocity and retinal blood flow using adaptive optics scanning laser ophthalmoscopy. Opt Express 16: 12746–12756.
[16]
Chui TYP, VanNasdale DA, Burns SA (2012) The use of forward scatter to improve retinal vascular imaging with an adaptive optics scanning laser ophthalmoscope. Biomed Opt Express 3: 2537–2549.
[17]
Zou W, Qi X, Huang G, Burns SA (2011) Improving wavefront boundary condition for in vivo high resolution adaptive optics ophthalmic imaging. Biomed Opt Express 2: 3309–3320.
[18]
Pinhas A, Dubow M, Shah N, Chui TY, Scoles D, et al. (2013) In vivo imaging of human retinal microvasculature using adaptive optics scanning light ophthalmoscope fluorescein angiography. Biomed Opt Express 4: 1305–1317.
[19]
Zawadzki RJ, Jones SM, Pilli S, Balderas-Mata S, Kim DY, et al. (2011) Integrated adaptive optics optical coherence tomography and adaptive optics scanning laser ophthalmoscope system for simultaneous cellular resolution in vivo retinal imaging. Biomed Opt Express 2: 1674–1686.
[20]
Sato Y, Jian C, Zoroofi RA, Harada N, Tamura S, et al. (1997) Automatic extraction and measurement of leukocyte motion in microvessels using spatiotemporal image analysis. Biomedical Engineering, IEEE Transactions on 44: 225–236.
[21]
Nelson DA, Krupsky S, Pollack A, Aloni E, Belkin M, et al. (2005) Special report: Noninvasive multi-parameter functional optical imaging of the eye. Ophthalmic surgery, lasers & imaging: the official journal of the International Society for Imaging in the Eye 36: 57–66.
[22]
Bedggood P, Metha A (2012) Direct visualization and characterization of erythrocyte flow in human retinalcapillaries. Biomed Opt Express 3: 3264–3277.
[23]
American National Standard for Safe Use of Lasers, ANSI Z136, 1–22007 (American National Standards Institute, New York, 2007).
[24]
Holder GE (2001) Pattern electroretinography (PERG) and an integrated approach to visual pathway diagnosis. Prog Retin Eye Res 20: 531–561.
[25]
Polak K, Schmetterer L, Riva CE (2002) Influence of flicker frequency on flicker-induced changes of retinal vessel diameter. Invest Ophthalmol Vis Sci 43: 2721–2726.
[26]
Barton J, Stromski S (2005) Flow measurement without phase information in optical coherence tomography images. Opt Express 13: 5234–5239.
[27]
Tokayer J, Jia Y, Dhalla A-H, Huang D (2013) Blood flow velocity quantification using split-spectrum amplitude-decorrelation angiography with optical coherence tomography. Biomed Opt Express 4: 1909–1924.
[28]
Liu G, Lin AJ, Tromberg BJ, Chen Z (2012) A comparison of Doppler optical coherence tomography methods. Biomed Opt Express 3: 2669–2680.
[29]
Jia Y, Tan O, Tokayer J, Potsaid B, Wang Y, et al. (2012) Split-spectrum amplitude-decorrelation angiography with optical coherence tomography. Opt Express 20: 4710–4725.
[30]
Huang D, Swanson EA, Lin CP, Schuman JS, Stinson WG, et al. (1991) Optical coherence tomography. Science 254: 1178–1181.
[31]
Puliafito CA, Hee MR, Lin CP, Reichel E, Schuman JS, et al. (1995) Imaging of macular diseases with optical coherence tomography. Ophthalmology 102: 217–229.
[32]
Schuman JS, Hee MR, Puliafito CA, Wong C, Pedut-Kloizman T, et al. (1995) Quantification of nerve fiber layer thickness in normal and glaucomatous eyes using optical coherence tomography. Arch Ophthalmol 113: 586–596.
[33]
Flammer J (1994) The vascular concept of glaucoma. Surv Ophthalmol 38 Suppl: S3–6
[34]
Cogan DG, Toussaint D, Kuwabara T (1961) Retinal vascular patterns. IV. Diabetic retinopathy. Arch Ophthalmol 66: 366–378.
[35]
Garhofer G, Zawinka C, Resch H, Huemer KH, Schmetterer L, et al. (2004) Response of retinal vessel diameters to flicker stimulation in patients with early open angle glaucoma. J Glaucoma 13: 340–344.
[36]
Gugleta K, Kochkorov A, Waldmann N, Polunina A, Katamay R, et al. (2012) Dynamics of retinal vessel response to flicker light in glaucoma patients and ocular hypertensives. Graefes Arch Clin Exp Ophthalmol 250: 589–594.
[37]
Mandecka A, Dawczynski J, Blum M, Muller N, Kloos C, et al. (2007) Influence of flickering light on the retinal vessels in diabetic patients. Diabetes Care 30: 3048–3052.
[38]
Ritt M, Harazny JM, Ott C, Raff U, Bauernschubert P, et al. (2012) Impaired increase of retinal capillary blood flow to flicker light exposure in arterial hypertension. Hypertension 60: 871–876.
[39]
Kotliar KE, Lanzl IM, Schmidt-Trucksass A, Sitnikova D, Ali M, et al. (2011) Dynamic retinal vessel response to flicker in obesity: A methodological approach. Microvasc Res 81: 123–128.
[40]
Garhofer G, Resch H, Sacu S, Weigert G, Schmidl D, et al. (2011) Effect of regular smoking on flicker induced retinal vasodilatation in healthy subjects. Microvasc Res 82: 351–355.
[41]
Formaz F, Riva CE, Geiser M (1997) Diffuse luminance flicker increases retinal vessel diameter in humans. Curr Eye Res 16: 1252–1257.
[42]
Riva CE, Logean E, Falsini B (2005) Visually evoked hemodynamical response and assessment of neurovascular coupling in the optic nerve and retina. Prog Retin Eye Res 24: 183–215.
[43]
Baker HD (1949) The Course of Foveal Light Adaptation Measured by the Threshold Intensity Increment. J Opt Soc Am 39: 172–179.
[44]
PattanaikSN, TumblinJ, YeeH, GreenbergDP. Time-dependent visual adaptation for fast realistic image display; 2000; New York, NY, USA. ACM Press/Addison-Wesley Publishing Co. pp . 47–54.
[45]
Kimura I, Shinoda K, Tanino T, Ohtake Y, Mashima Y, et al. (2003) Scanning laser Doppler flowmeter study of retinal blood flow in macular area of healthy volunteers. Br J Ophthalmol 87: 1469–1473.
[46]
Wang Y, Fawzi AA, Varma R, Sadun AA, Zhang X, et al. (2011) Pilot study of optical coherence tomography measurement of retinal blood flow in retinal and optic nerve diseases. Invest Ophthalmol Vis Sci 52: 840–845.
[47]
Riva CE, Grunwald JE, Sinclair SH, Petrig BL (1985) Blood velocity and volumetric flow rate in human retinal vessels. Invest Ophthalmol Vis Sci 26: 1124–1132.
