Assessment of choroidal blood flow using laser speckle flowgraphy

Giacomo Calzetti, Klemens Fondi, Ahmed M Bata, Nikolaus Luft, Piotr A Wozniak, Katarzyna J Witkowska, Matthias Bolz, Alina Popa-Cherecheanu, René M Werkmeister, Doreen Schmidl, Gerhard Garhöfer, Leopold Schmetterer, Giacomo Calzetti, Klemens Fondi, Ahmed M Bata, Nikolaus Luft, Piotr A Wozniak, Katarzyna J Witkowska, Matthias Bolz, Alina Popa-Cherecheanu, René M Werkmeister, Doreen Schmidl, Gerhard Garhöfer, Leopold Schmetterer

Abstract

Background/aims: There is considerable interest in novel techniques to quantify choroidal blood flow (CBF) in humans. In the present study, we investigated a novel technique to measure CBF based on laser speckle flowgraphy (LSFG) in healthy subjects.

Methods: This study included 31 eyes of 31 healthy, non-smoking subjects aged between 19 and 74 years. A commercial LSFG instrument was used to measure choroidal vessel diameter (CVD) and relative flow volume (RFV) in choroidal vessels that were identified on fundus photos, an approach that was used previously only for retinal vessels. The reproducibility and the effect of isometric exercise on these parameters were investigated. The latter was compared with measurement of subfoveal CBF using laser Doppler flowmetry (LDF).

Results: Intraclass correlation coefficients for CVD and RFV were higher than 0.8 indicating excellent reproducibility. During isometric exercise, we observed an increase in ocular perfusion pressure of approximately 60% (P<0.001). The increase in RFV and CBF was lower, but also highly significant versus baseline (at minute 6 of isometric exercise: RFV 10.5%±4.2%, CBF 8.3%±3.6%; P<0.001 each) indicating choroidal autoregulation.

Conclusion: LSFG may be a novel approach to study blood flow in choroidal vessels. Data are reproducible and show good agreement with LDF data.

Trial registration number: NCT02102880, Results.

Keywords: choroid; imaging; physiology.

Conflict of interest statement

Competing interests: None declared.

© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Figures

Figure 1
Figure 1
Identification of choroidal blood vessels for Laser Speckle Flowgraphy (LSFG) analysis. (A) First a choroidal vessel is identified based on a fundus photograph. The choroidal vessel of interest is shown inside a white rectangular band that is manually placed. (B) The presence of the choroidal vessel is then confirmed at the LSFG intensity image. (C) In the perfusion map, a rectangular white band is traced across the vessel which appears red because of the high intravascular blood velocity.
Figure 2
Figure 2
Ocular perfusion pressure (OPP), relative flow volume (RFV) and choroidal vessel diameter (CVD) during isometric exercise. Data are expressed as per cent change from baseline. Data are presented as means±SD (n=10).
Figure 3
Figure 3
Ocular perfusion pressure (OPP) and choroidal blood flow (CBF) during isometric exercise. Data are expressed as per cent change from baseline. Data are presented as means±SD (n=10).

References

    1. Pemp B, Schmetterer L. Ocular blood flow in diabetes and age-related macular degeneration. Can J Ophthalmol 2008;43:295–301. 10.3129/i08-049
    1. Feigl B. Age-related maculopathy – linking aetiology and pathophysiological changes to the ischaemia hypothesis. Prog Retin Eye Res 2009;28:63–86. 10.1016/j.preteyeres.2008.11.004
    1. Kashani AH, Chen CL, Gahm JK, et al. . Optical coherence tomography angiography: a comprehensive review of current methods and clinical applications. Prog Retin Eye Res 2017;60:66–100. 10.1016/j.preteyeres.2017.07.002
    1. Riva CE, Geiser M, Petrig BL, et al. . Ocular blood flow assessment using continuous laser Doppler flowmetry. Acta Ophthalmol 2010;88:622–9. 10.1111/j.1755-3768.2009.01621.x
    1. Stalmans I, Vandewalle E, Anderson DR, et al. . Use of colour Doppler imaging in ocular blood flow research. Acta Ophthalmol 2011;89:e609–e630. 10.1111/j.1755-3768.2011.02178.x
    1. Polska E, Polak K, Luksch A, et al. . Twelve hour reproducibility of choroidal blood flow parameters in healthy subjects. Br J Ophthalmol 2004;88:533–7. 10.1136/bjo.2003.028480
    1. van Stokkum IH, Lambrou GN, van den Berg TJ. Hemodynamic parameter estimation from ocular fluorescein angiograms. Graefes Arch Clin Exp Ophthalmol 1995;233:123–30. 10.1007/BF00166603
    1. Leitgeb RA, Werkmeister RM, Blatter C, et al. . Doppler optical coherence tomography. Prog Retin Eye Res 2014;41:26–43. 10.1016/j.preteyeres.2014.03.004
    1. Wang J, Zhang M, Hwang TS, et al. . Reflectance-based projection-resolved optical coherence tomography angiography [Invited]. Biomed Opt Express 2017;8:1536–48. 10.1364/BOE.8.001536
    1. Miura M, Makita S, Iwasaki T, et al. . An approach to measure blood flow in single choroidal vessel using Doppler optical coherence tomography. Invest Ophthalmol Vis Sci 2012;53:7137–41. 10.1167/iovs.12-10666
    1. Metelitsina TI, Grunwald JE, DuPont JC, et al. . Foveolar choroidal circulation and choroidal neovascularization in age-related macular degeneration. Invest Ophthalmol Vis Sci 2008;49:358–63. 10.1167/iovs.07-0526
    1. Boltz A, Luksch A, Wimpissinger B, et al. . Choroidal blood flow and progression of age-related macular degeneration in the fellow eye in patients with unilateral choroidal neovascularization. Invest Ophthalmol Vis Sci 2010;51:4220–5. 10.1167/iovs.09-4968
    1. Zhou Q, Daniel E, Grunwald JE, et al. . Association between pseudodrusen and delayed patchy choroidal filling in the comparison of age-related macular degeneration treatments trials. Acta Ophthalmol 2017;95:e518–e520. 10.1111/aos.13398
    1. Choi W, Moult EM, Waheed NK, et al. . Ultrahigh-speed, swept-source optical coherence tomography angiography in nonexudative age-related macular degeneration with geographic atrophy. Ophthalmology 2015;122:2532–44. 10.1016/j.ophtha.2015.08.029
    1. Spaide RF. Choriocapillaris flow features follow a power law distribution: implications for characterization and mechanisms of disease progression. Am J Ophthalmol 2016;170:58–67. 10.1016/j.ajo.2016.07.023
    1. Moult EM, Waheed NK, Novais EA, et al. . Swept-source optical coherence tomography angiography reveals choriocapillaris alterations in eyes with nascent geographic atrophy and drusen-associated geographic atrophy. Retina 2016;36(Suppl 1):S2–S11. 10.1097/IAE.0000000000001287
    1. Nesper PL, Soetikno BT, Fawzi AA. Choriocapillaris nonperfusion is associated with poor visual acuity in eyes with reticular pseudodrusen. Am J Ophthalmol 2017;174:42–55. 10.1016/j.ajo.2016.10.005
    1. Sugiyama T, Araie M, Riva CE, et al. . Use of laser speckle flowgraphy in ocular blood flow research. Acta Ophthalmol 2010;88:723–9. 10.1111/j.1755-3768.2009.01586.x
    1. Wang L, Cull GA, Piper C, et al. . Anterior and posterior optic nerve head blood flow in nonhuman primate experimental glaucoma model measured by laser speckle imaging technique and microsphere method. Invest Ophthalmol Vis Sci 2012;53:8303–9. 10.1167/iovs.12-10911
    1. Shiga Y, Kunikata H, Aizawa N, et al. . Optic nerve head blood flow, as measured by laser speckle flowgraphy, is significantly reduced in preperimetric glaucoma. Curr Eye Res 2016;41:1447–53. 10.3109/02713683.2015.1127974
    1. Shiga Y, Asano T, Kunikata H, et al. . Relative flow volume, a novel blood flow index in the human retina derived from laser speckle flowgraphy. Invest Ophthalmol Vis Sci 2014;55:3899–904. 10.1167/iovs.14-14116
    1. Luft N, Wozniak PA, Aschinger GC, et al. . Ocular blood flow measurements in healthy white subjects using laser speckle flowgraphy. PLoS One 2016;11:e0168190 10.1371/journal.pone.0168190
    1. Witkowska KJ, Bata AM, Calzetti G, et al. . Optic nerve head and retinal blood flow regulation during isometric exercise as assessed with laser speckle flowgraphy. PLoS One 2017;12:e0184772 10.1371/journal.pone.0184772
    1. Fuchsjäger-Mayrl G, Luksch A, Malec M, et al. . Role of endothelin-1 in choroidal blood flow regulation during isometric exercise in healthy humans. Invest Ophthalmol Vis Sci 2003;44:728–33. 10.1167/iovs.02-0372
    1. Luksch A, Polska E, Imhof A, et al. . Role of NO in choroidal blood flow regulation during isometric exercise in healthy humans. Invest Ophthalmol Vis Sci 2003;44:734–9. 10.1167/iovs.02-0177
    1. Riva CE, Cranstoun SD, Grunwald JE, et al. . Choroidal blood flow in the foveal region of the human ocular fundus. Invest Ophthalmol Vis Sci 1994;35:4273–81.
    1. Geiser MH, Diermann U, Riva CE. Compact laser Doppler choroidal flowmeter. J Biomed Opt 1999;4:459–64. 10.1117/1.429960
    1. Cicchetti DV. Guidelines, criteria, and rules of thumb for evaluating normed and standardized assessment instruments in psychology. Psychol Assess 1994;6:284–90. 10.1037/1040-3590.6.4.284
    1. Luft N, Wozniak PA, Aschinger GC, et al. . Measurements of retinal perfusion using laser speckle flowgraphy and doppler optical coherence tomography. Invest Ophthalmol Vis Sci 2016;57:5417–25. 10.1167/iovs.16-19896
    1. Riva CE, Grunwald JE, Sinclair SH, et al. . Blood velocity and volumetric flow rate in human retinal vessels. Invest Ophthalmol Vis Sci 1985;26:1124–32.
    1. Doblhoff-Dier V, Schmetterer L, Vilser W, et al. . Measurement of the total retinal blood flow using dual beam Fourier-domain Doppler optical coherence tomography with orthogonal detection planes. Biomed Opt Express 2014;5:630–42. 10.1364/BOE.5.000630
    1. Silver DM, Farrell RA. Validity of pulsatile ocular blood flow measurements. Surv Ophthalmol 1994;38:S72–S80. 10.1016/0039-6257(94)90049-3
    1. Schmetterer L, Dallinger S, Findl O, et al. . A comparison between laser interferometric measurement of fundus pulsation and pneumotonometric measurement of pulsatile ocular blood flow. 1. Baseline considerations. Eye 2000;14(Pt 1):39–45. 10.1038/eye.2000.9
    1. Riva CE, Titze P, Hero M, et al. . Choroidal blood flow during isometric exercises. Invest Ophthalmol Vis Sci 1997;38:2338–43.
    1. Schmidl D, Boltz A, Kaya S, et al. . Comparison of choroidal and optic nerve head blood flow regulation during changes in ocular perfusion pressure. Invest Ophthalmol Vis Sci 2012;53:4337–46. 10.1167/iovs.11-9055
    1. Schmidl D, Schmetterer L, Witkowska KJ, et al. . Factors associated with choroidal blood flow regulation in healthy young subjects. Invest Ophthalmol Vis Sci 2016;57:5705–13. 10.1167/iovs.16-20225
    1. Kiel JW, Shepherd AP. Autoregulation of choroidal blood flow in the rabbit. Invest Ophthalmol Vis Sci 1992;33:2399–410.
    1. Kiel JW. Choroidal myogenic autoregulation and intraocular pressure. Exp Eye Res 1994;58:529–43. 10.1006/exer.1994.1047
    1. Kiel JW, van Heuven WA. Ocular perfusion pressure and choroidal blood flow in the rabbit. Invest Ophthalmol Vis Sci 1995;36:579–85.

Source: PubMed

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