Abstract

Fluorescence lifetime imaging ophthalmoscopy (FLIO) is a new technique to detect changes in the human retina. The autofluorescence decay over time, generated by endogenous fluorophores, is measured in vivo. The strong autofluorescence of the crystalline lens, however, superimposes the intensity decay of the retina fluorescence, as the confocal principle is not able to suppress it sufficiently. Thus, the crystalline lens autofluorescence causes artifacts in the retinal fluorescence lifetimes determined from the intensity decays. Here, we present a new technique to suppress the autofluorescence of the crystalline lens by introducing an annular stop into the detection light path, which we call Schweitzer’s principle. The efficacy of annular stops with an outer diameter of 7 mm and inner diameters of 1 to 5 mm are analyzed in an experimental setup using a model eye based on fluorescent dyes. Compared to the confocal principle, Schweitzer’s principle with an inner diameter of 3 mm is able to reduce the simulated crystalline lens fluorescence to 4%, while 42% of the simulated retina fluorescence is preserved. Thus, we recommend the implementation of Schweitzer’s principle in scanning laser ophthalmoscopes used for fundus autofluorescence measurements, especially the FLIO device, for improved image quality.

© 2016 Optical Society of America

Full Article  |  PDF Article
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  1. M. Hammer, E. Königsdörffer, C. Liebermann, C. Framme, G. Schuch, D. Schweitzer, and J. Strobel, “Ocular fundus auto-fluorescence observations at different wavelengths in patients with age-related macular degeneration and diabetic retinopathy,” Graefes Arch. Clin. Exp. Ophthalmol. 246(1), 105–114 (2007).
    [Crossref] [PubMed]
  2. S. Schmitz-Valckenberg, F. G. Holz, A. C. Bird, and R. F. Spaide, “Fundus autofluorescence imaging: Review and perspectives,” Retina 28(3), 385–409 (2008).
    [Crossref] [PubMed]
  3. D. Schweitzer, S. Schenke, M. Hammer, F. Schweitzer, S. Jentsch, E. Birckner, W. Becker, and A. Bergmann, “Towards metabolic mapping of the human retina,” Microsc. Res. Tech. 70(5), 410–419 (2007).
    [Crossref] [PubMed]
  4. D. Schweitzer, M. Hammer, F. Schweitzer, R. Anders, T. Doebbecke, S. Schenke, E. R. Gaillard, and E. R. Gaillard, “In vivo measurement of time-resolved autofluorescence at the human fundus,” J. Biomed. Opt. 9(6), 1214–1222 (2004).
    [Crossref] [PubMed]
  5. J. R. Lakowicz, Principles of Fluorescence Spectroscopy, 3rd ed. (Springer, New York, 2006), p. 954.
  6. W. Becker, “Fluorescence lifetime imaging--techniques and applications,” J. Microsc. 247(2), 119–136 (2012).
    [Crossref] [PubMed]
  7. L. Marcu, “Fluorescence Lifetime Techniques in Medical Applications,” Ann. Biomed. Eng. 40(2), 304–331 (2012).
    [Crossref] [PubMed]
  8. D. Schweitzer, E. R. Gaillard, J. Dillon, R. F. Mullins, S. Russell, B. Hoffmann, S. Peters, M. Hammer, and C. Biskup, “Time-Resolved Autofluorescence Imaging of Human Donor Retina Tissue from Donors with Significant Extramacular Drusen,” Invest. Ophthalmol. Vis. Sci. 53(7), 3376–3386 (2012).
    [Crossref] [PubMed]
  9. L. Sauer, D. Schweitzer, L. Ramm, R. Augsten, M. Hammer, and S. Peters, “Impact of macular pigment on fundus autofluorescence lifetimes,” Invest. Ophthalmol. Vis. Sci. 56(8), 4668–4679 (2015).
    [Crossref] [PubMed]
  10. L. Ramm, S. Jentsch, R. Augsten, and M. Hammer, “Fluorescence lifetime imaging ophthalmoscopy in glaucoma,” Graefes Arch. Clin. Exp. Ophthalmol. 252(12), 2025–2026 (2014).
    [Crossref] [PubMed]
  11. D. Schweitzer, S. Quick, M. Klemm, M. Hammer, S. Jentsch, and J. Dawczynski, “[Time-resolved autofluorescence in retinal vascular occlusions],” Ophthalmologe 107(12), 1145–1152 (2010).
    [Crossref] [PubMed]
  12. C. Dysli, S. Wolf, and M. S. Zinkernagel, “Fluorescence Lifetime Imaging in Retinal Artery Occlusion,” Invest. Ophthalmol. Vis. Sci. 56(5), 3329–3336 (2015).
    [Crossref] [PubMed]
  13. S. Jentsch, D. Schweitzer, K. U. Schmidtke, S. Peters, J. Dawczynski, K. J. Bar, and M. Hammer, “Retinal fluorescence lifetime imaging ophthalmoscopy measures depend on the severity of Alzheimer’s disease,” Acta Ophthalmologica 93, e241–e247 (2014).
    [PubMed]
  14. C. Dysli, S. Wolf, K. Hatz, and M. S. Zinkernagel, “Fluorescence lifetime imaging in stargardt disease: potential marker for disease progression,” Invest. Ophthalmol. Vis. Sci. 57(3), 832–841 (2016).
    [Crossref] [PubMed]
  15. H. Pau, J. Degen, and H. H. Schmidtke, “Different Regional Changes of Fluorescence Spectra of Clear Human Lenses and Nuclear Cataracts,” Graefes Arch. Clin. Exp. Ophthalmol. 231(11), 656–661 (1993).
    [Crossref] [PubMed]
  16. D. Schweitzer, L. Deutsch, M. Klemm, S. Jentsch, M. Hammer, S. Peters, J. Haueisen, U. A. Müller, and J. Dawczynski, “Fluorescence lifetime imaging ophthalmoscopy in type 2 diabetic patients who have no signs of diabetic retinopathy,” J. Biomed. Opt. 20(6), 061106 (2015).
    [Crossref] [PubMed]
  17. M. Klemm, D. Schweitzer, S. Peters, L. Sauer, M. Hammer, and J. Haueisen, “FLIMX: A Software Package to Determine and Analyze the Fluorescence Lifetime in Time-Resolved Fluorescence Data from the Human Eye,” PLoS One 10(7), e0131640 (2015).
    [Crossref] [PubMed]
  18. D. Schweitzer, M. Hammer, and F. Schweitzer, “Limits of the confocal laser-scanning technique in measurements of time-resolved autofluorescence of the ocular fundus,” Biomed. Tech. (Berl.) 50(9), 263–267 (2005).
    [Crossref] [PubMed]
  19. P. F. Sharp and A. Manivannan, “The scanning laser ophthalmoscope,” Phys. Med. Biol. 42(5), 951–966 (1997).
    [Crossref] [PubMed]
  20. A. A. Michelson, Studies in Optics, The University of Chicago science series (The University of Chicago Press, Chicago, Ill., 1927), pp. ix, 176.
  21. C. N. Keilhauer and F. C. Delori, “Near-infrared autofluorescence imaging of the fundus: Visualization of ocular melanin,” Invest. Ophthalmol. Vis. Sci. 47(8), 3556–3564 (2006).
    [Crossref] [PubMed]
  22. A. V. Cideciyan, M. Swider, T. S. Aleman, M. I. Roman, A. Sumaroka, S. B. Schwartz, E. M. Stone, and S. G. Jacobson, “Reduced-illuminance autofluorescence imaging in ABCA4-associated retinal degenerations,” J. Opt. Soc. Am. A 24(5), 1457–1467 (2007).
    [Crossref] [PubMed]
  23. A. W. A. Weinberger, A. Lappas, T. Kirschkamp, B. A. E. Mazinani, J. K. Huth, B. Mohammadi, and P. Walter, “Fundus near infrared fluorescence correlates with fundus near infrared reflectance,” Invest. Ophthalmol. Vis. Sci. 47(7), 3098–3108 (2006).
    [Crossref] [PubMed]
  24. G. E. Eldred and M. L. Katz, “Fluorophores of the Human Retinal Pigment Epithelium: Separation and Spectral Characterization,” Exp. Eye Res. 47(1), 71–86 (1988).
    [Crossref] [PubMed]
  25. S. Schmitz-Valckenberg, D. Lara, S. Nizari, E. M. Normando, L. Guo, A. R. Wegener, A. Tufail, F. W. Fitzke, F. G. Holz, and M. F. Cordeiro, “Localisation and significance of in vivo near-infrared autofluorescent signal in retinal imaging,” Br. J. Ophthalmol. 95(8), 1134–1139 (2011).
    [Crossref] [PubMed]
  26. T. Duncker, M. R. Tabacaru, W. Lee, S. H. Tsang, J. R. Sparrow, and V. C. Greenstein, “Comparison of Near-Infrared and Short-Wavelength Autofluorescence in Retinitis Pigmentosa,” Invest. Ophthalmol. Vis. Sci. 54(1), 585–591 (2013).
    [Crossref] [PubMed]

2016 (1)

C. Dysli, S. Wolf, K. Hatz, and M. S. Zinkernagel, “Fluorescence lifetime imaging in stargardt disease: potential marker for disease progression,” Invest. Ophthalmol. Vis. Sci. 57(3), 832–841 (2016).
[Crossref] [PubMed]

2015 (4)

D. Schweitzer, L. Deutsch, M. Klemm, S. Jentsch, M. Hammer, S. Peters, J. Haueisen, U. A. Müller, and J. Dawczynski, “Fluorescence lifetime imaging ophthalmoscopy in type 2 diabetic patients who have no signs of diabetic retinopathy,” J. Biomed. Opt. 20(6), 061106 (2015).
[Crossref] [PubMed]

M. Klemm, D. Schweitzer, S. Peters, L. Sauer, M. Hammer, and J. Haueisen, “FLIMX: A Software Package to Determine and Analyze the Fluorescence Lifetime in Time-Resolved Fluorescence Data from the Human Eye,” PLoS One 10(7), e0131640 (2015).
[Crossref] [PubMed]

L. Sauer, D. Schweitzer, L. Ramm, R. Augsten, M. Hammer, and S. Peters, “Impact of macular pigment on fundus autofluorescence lifetimes,” Invest. Ophthalmol. Vis. Sci. 56(8), 4668–4679 (2015).
[Crossref] [PubMed]

C. Dysli, S. Wolf, and M. S. Zinkernagel, “Fluorescence Lifetime Imaging in Retinal Artery Occlusion,” Invest. Ophthalmol. Vis. Sci. 56(5), 3329–3336 (2015).
[Crossref] [PubMed]

2014 (2)

S. Jentsch, D. Schweitzer, K. U. Schmidtke, S. Peters, J. Dawczynski, K. J. Bar, and M. Hammer, “Retinal fluorescence lifetime imaging ophthalmoscopy measures depend on the severity of Alzheimer’s disease,” Acta Ophthalmologica 93, e241–e247 (2014).
[PubMed]

L. Ramm, S. Jentsch, R. Augsten, and M. Hammer, “Fluorescence lifetime imaging ophthalmoscopy in glaucoma,” Graefes Arch. Clin. Exp. Ophthalmol. 252(12), 2025–2026 (2014).
[Crossref] [PubMed]

2013 (1)

T. Duncker, M. R. Tabacaru, W. Lee, S. H. Tsang, J. R. Sparrow, and V. C. Greenstein, “Comparison of Near-Infrared and Short-Wavelength Autofluorescence in Retinitis Pigmentosa,” Invest. Ophthalmol. Vis. Sci. 54(1), 585–591 (2013).
[Crossref] [PubMed]

2012 (3)

W. Becker, “Fluorescence lifetime imaging--techniques and applications,” J. Microsc. 247(2), 119–136 (2012).
[Crossref] [PubMed]

L. Marcu, “Fluorescence Lifetime Techniques in Medical Applications,” Ann. Biomed. Eng. 40(2), 304–331 (2012).
[Crossref] [PubMed]

D. Schweitzer, E. R. Gaillard, J. Dillon, R. F. Mullins, S. Russell, B. Hoffmann, S. Peters, M. Hammer, and C. Biskup, “Time-Resolved Autofluorescence Imaging of Human Donor Retina Tissue from Donors with Significant Extramacular Drusen,” Invest. Ophthalmol. Vis. Sci. 53(7), 3376–3386 (2012).
[Crossref] [PubMed]

2011 (1)

S. Schmitz-Valckenberg, D. Lara, S. Nizari, E. M. Normando, L. Guo, A. R. Wegener, A. Tufail, F. W. Fitzke, F. G. Holz, and M. F. Cordeiro, “Localisation and significance of in vivo near-infrared autofluorescent signal in retinal imaging,” Br. J. Ophthalmol. 95(8), 1134–1139 (2011).
[Crossref] [PubMed]

2010 (1)

D. Schweitzer, S. Quick, M. Klemm, M. Hammer, S. Jentsch, and J. Dawczynski, “[Time-resolved autofluorescence in retinal vascular occlusions],” Ophthalmologe 107(12), 1145–1152 (2010).
[Crossref] [PubMed]

2008 (1)

S. Schmitz-Valckenberg, F. G. Holz, A. C. Bird, and R. F. Spaide, “Fundus autofluorescence imaging: Review and perspectives,” Retina 28(3), 385–409 (2008).
[Crossref] [PubMed]

2007 (3)

D. Schweitzer, S. Schenke, M. Hammer, F. Schweitzer, S. Jentsch, E. Birckner, W. Becker, and A. Bergmann, “Towards metabolic mapping of the human retina,” Microsc. Res. Tech. 70(5), 410–419 (2007).
[Crossref] [PubMed]

M. Hammer, E. Königsdörffer, C. Liebermann, C. Framme, G. Schuch, D. Schweitzer, and J. Strobel, “Ocular fundus auto-fluorescence observations at different wavelengths in patients with age-related macular degeneration and diabetic retinopathy,” Graefes Arch. Clin. Exp. Ophthalmol. 246(1), 105–114 (2007).
[Crossref] [PubMed]

A. V. Cideciyan, M. Swider, T. S. Aleman, M. I. Roman, A. Sumaroka, S. B. Schwartz, E. M. Stone, and S. G. Jacobson, “Reduced-illuminance autofluorescence imaging in ABCA4-associated retinal degenerations,” J. Opt. Soc. Am. A 24(5), 1457–1467 (2007).
[Crossref] [PubMed]

2006 (2)

A. W. A. Weinberger, A. Lappas, T. Kirschkamp, B. A. E. Mazinani, J. K. Huth, B. Mohammadi, and P. Walter, “Fundus near infrared fluorescence correlates with fundus near infrared reflectance,” Invest. Ophthalmol. Vis. Sci. 47(7), 3098–3108 (2006).
[Crossref] [PubMed]

C. N. Keilhauer and F. C. Delori, “Near-infrared autofluorescence imaging of the fundus: Visualization of ocular melanin,” Invest. Ophthalmol. Vis. Sci. 47(8), 3556–3564 (2006).
[Crossref] [PubMed]

2005 (1)

D. Schweitzer, M. Hammer, and F. Schweitzer, “Limits of the confocal laser-scanning technique in measurements of time-resolved autofluorescence of the ocular fundus,” Biomed. Tech. (Berl.) 50(9), 263–267 (2005).
[Crossref] [PubMed]

2004 (1)

D. Schweitzer, M. Hammer, F. Schweitzer, R. Anders, T. Doebbecke, S. Schenke, E. R. Gaillard, and E. R. Gaillard, “In vivo measurement of time-resolved autofluorescence at the human fundus,” J. Biomed. Opt. 9(6), 1214–1222 (2004).
[Crossref] [PubMed]

1997 (1)

P. F. Sharp and A. Manivannan, “The scanning laser ophthalmoscope,” Phys. Med. Biol. 42(5), 951–966 (1997).
[Crossref] [PubMed]

1993 (1)

H. Pau, J. Degen, and H. H. Schmidtke, “Different Regional Changes of Fluorescence Spectra of Clear Human Lenses and Nuclear Cataracts,” Graefes Arch. Clin. Exp. Ophthalmol. 231(11), 656–661 (1993).
[Crossref] [PubMed]

1988 (1)

G. E. Eldred and M. L. Katz, “Fluorophores of the Human Retinal Pigment Epithelium: Separation and Spectral Characterization,” Exp. Eye Res. 47(1), 71–86 (1988).
[Crossref] [PubMed]

Aleman, T. S.

Anders, R.

D. Schweitzer, M. Hammer, F. Schweitzer, R. Anders, T. Doebbecke, S. Schenke, E. R. Gaillard, and E. R. Gaillard, “In vivo measurement of time-resolved autofluorescence at the human fundus,” J. Biomed. Opt. 9(6), 1214–1222 (2004).
[Crossref] [PubMed]

Augsten, R.

L. Sauer, D. Schweitzer, L. Ramm, R. Augsten, M. Hammer, and S. Peters, “Impact of macular pigment on fundus autofluorescence lifetimes,” Invest. Ophthalmol. Vis. Sci. 56(8), 4668–4679 (2015).
[Crossref] [PubMed]

L. Ramm, S. Jentsch, R. Augsten, and M. Hammer, “Fluorescence lifetime imaging ophthalmoscopy in glaucoma,” Graefes Arch. Clin. Exp. Ophthalmol. 252(12), 2025–2026 (2014).
[Crossref] [PubMed]

Bar, K. J.

S. Jentsch, D. Schweitzer, K. U. Schmidtke, S. Peters, J. Dawczynski, K. J. Bar, and M. Hammer, “Retinal fluorescence lifetime imaging ophthalmoscopy measures depend on the severity of Alzheimer’s disease,” Acta Ophthalmologica 93, e241–e247 (2014).
[PubMed]

Becker, W.

W. Becker, “Fluorescence lifetime imaging--techniques and applications,” J. Microsc. 247(2), 119–136 (2012).
[Crossref] [PubMed]

D. Schweitzer, S. Schenke, M. Hammer, F. Schweitzer, S. Jentsch, E. Birckner, W. Becker, and A. Bergmann, “Towards metabolic mapping of the human retina,” Microsc. Res. Tech. 70(5), 410–419 (2007).
[Crossref] [PubMed]

Bergmann, A.

D. Schweitzer, S. Schenke, M. Hammer, F. Schweitzer, S. Jentsch, E. Birckner, W. Becker, and A. Bergmann, “Towards metabolic mapping of the human retina,” Microsc. Res. Tech. 70(5), 410–419 (2007).
[Crossref] [PubMed]

Birckner, E.

D. Schweitzer, S. Schenke, M. Hammer, F. Schweitzer, S. Jentsch, E. Birckner, W. Becker, and A. Bergmann, “Towards metabolic mapping of the human retina,” Microsc. Res. Tech. 70(5), 410–419 (2007).
[Crossref] [PubMed]

Bird, A. C.

S. Schmitz-Valckenberg, F. G. Holz, A. C. Bird, and R. F. Spaide, “Fundus autofluorescence imaging: Review and perspectives,” Retina 28(3), 385–409 (2008).
[Crossref] [PubMed]

Biskup, C.

D. Schweitzer, E. R. Gaillard, J. Dillon, R. F. Mullins, S. Russell, B. Hoffmann, S. Peters, M. Hammer, and C. Biskup, “Time-Resolved Autofluorescence Imaging of Human Donor Retina Tissue from Donors with Significant Extramacular Drusen,” Invest. Ophthalmol. Vis. Sci. 53(7), 3376–3386 (2012).
[Crossref] [PubMed]

Cideciyan, A. V.

Cordeiro, M. F.

S. Schmitz-Valckenberg, D. Lara, S. Nizari, E. M. Normando, L. Guo, A. R. Wegener, A. Tufail, F. W. Fitzke, F. G. Holz, and M. F. Cordeiro, “Localisation and significance of in vivo near-infrared autofluorescent signal in retinal imaging,” Br. J. Ophthalmol. 95(8), 1134–1139 (2011).
[Crossref] [PubMed]

Dawczynski, J.

D. Schweitzer, L. Deutsch, M. Klemm, S. Jentsch, M. Hammer, S. Peters, J. Haueisen, U. A. Müller, and J. Dawczynski, “Fluorescence lifetime imaging ophthalmoscopy in type 2 diabetic patients who have no signs of diabetic retinopathy,” J. Biomed. Opt. 20(6), 061106 (2015).
[Crossref] [PubMed]

S. Jentsch, D. Schweitzer, K. U. Schmidtke, S. Peters, J. Dawczynski, K. J. Bar, and M. Hammer, “Retinal fluorescence lifetime imaging ophthalmoscopy measures depend on the severity of Alzheimer’s disease,” Acta Ophthalmologica 93, e241–e247 (2014).
[PubMed]

D. Schweitzer, S. Quick, M. Klemm, M. Hammer, S. Jentsch, and J. Dawczynski, “[Time-resolved autofluorescence in retinal vascular occlusions],” Ophthalmologe 107(12), 1145–1152 (2010).
[Crossref] [PubMed]

Degen, J.

H. Pau, J. Degen, and H. H. Schmidtke, “Different Regional Changes of Fluorescence Spectra of Clear Human Lenses and Nuclear Cataracts,” Graefes Arch. Clin. Exp. Ophthalmol. 231(11), 656–661 (1993).
[Crossref] [PubMed]

Delori, F. C.

C. N. Keilhauer and F. C. Delori, “Near-infrared autofluorescence imaging of the fundus: Visualization of ocular melanin,” Invest. Ophthalmol. Vis. Sci. 47(8), 3556–3564 (2006).
[Crossref] [PubMed]

Deutsch, L.

D. Schweitzer, L. Deutsch, M. Klemm, S. Jentsch, M. Hammer, S. Peters, J. Haueisen, U. A. Müller, and J. Dawczynski, “Fluorescence lifetime imaging ophthalmoscopy in type 2 diabetic patients who have no signs of diabetic retinopathy,” J. Biomed. Opt. 20(6), 061106 (2015).
[Crossref] [PubMed]

Dillon, J.

D. Schweitzer, E. R. Gaillard, J. Dillon, R. F. Mullins, S. Russell, B. Hoffmann, S. Peters, M. Hammer, and C. Biskup, “Time-Resolved Autofluorescence Imaging of Human Donor Retina Tissue from Donors with Significant Extramacular Drusen,” Invest. Ophthalmol. Vis. Sci. 53(7), 3376–3386 (2012).
[Crossref] [PubMed]

Doebbecke, T.

D. Schweitzer, M. Hammer, F. Schweitzer, R. Anders, T. Doebbecke, S. Schenke, E. R. Gaillard, and E. R. Gaillard, “In vivo measurement of time-resolved autofluorescence at the human fundus,” J. Biomed. Opt. 9(6), 1214–1222 (2004).
[Crossref] [PubMed]

Duncker, T.

T. Duncker, M. R. Tabacaru, W. Lee, S. H. Tsang, J. R. Sparrow, and V. C. Greenstein, “Comparison of Near-Infrared and Short-Wavelength Autofluorescence in Retinitis Pigmentosa,” Invest. Ophthalmol. Vis. Sci. 54(1), 585–591 (2013).
[Crossref] [PubMed]

Dysli, C.

C. Dysli, S. Wolf, K. Hatz, and M. S. Zinkernagel, “Fluorescence lifetime imaging in stargardt disease: potential marker for disease progression,” Invest. Ophthalmol. Vis. Sci. 57(3), 832–841 (2016).
[Crossref] [PubMed]

C. Dysli, S. Wolf, and M. S. Zinkernagel, “Fluorescence Lifetime Imaging in Retinal Artery Occlusion,” Invest. Ophthalmol. Vis. Sci. 56(5), 3329–3336 (2015).
[Crossref] [PubMed]

Eldred, G. E.

G. E. Eldred and M. L. Katz, “Fluorophores of the Human Retinal Pigment Epithelium: Separation and Spectral Characterization,” Exp. Eye Res. 47(1), 71–86 (1988).
[Crossref] [PubMed]

Fitzke, F. W.

S. Schmitz-Valckenberg, D. Lara, S. Nizari, E. M. Normando, L. Guo, A. R. Wegener, A. Tufail, F. W. Fitzke, F. G. Holz, and M. F. Cordeiro, “Localisation and significance of in vivo near-infrared autofluorescent signal in retinal imaging,” Br. J. Ophthalmol. 95(8), 1134–1139 (2011).
[Crossref] [PubMed]

Framme, C.

M. Hammer, E. Königsdörffer, C. Liebermann, C. Framme, G. Schuch, D. Schweitzer, and J. Strobel, “Ocular fundus auto-fluorescence observations at different wavelengths in patients with age-related macular degeneration and diabetic retinopathy,” Graefes Arch. Clin. Exp. Ophthalmol. 246(1), 105–114 (2007).
[Crossref] [PubMed]

Gaillard, E. R.

D. Schweitzer, E. R. Gaillard, J. Dillon, R. F. Mullins, S. Russell, B. Hoffmann, S. Peters, M. Hammer, and C. Biskup, “Time-Resolved Autofluorescence Imaging of Human Donor Retina Tissue from Donors with Significant Extramacular Drusen,” Invest. Ophthalmol. Vis. Sci. 53(7), 3376–3386 (2012).
[Crossref] [PubMed]

D. Schweitzer, M. Hammer, F. Schweitzer, R. Anders, T. Doebbecke, S. Schenke, E. R. Gaillard, and E. R. Gaillard, “In vivo measurement of time-resolved autofluorescence at the human fundus,” J. Biomed. Opt. 9(6), 1214–1222 (2004).
[Crossref] [PubMed]

D. Schweitzer, M. Hammer, F. Schweitzer, R. Anders, T. Doebbecke, S. Schenke, E. R. Gaillard, and E. R. Gaillard, “In vivo measurement of time-resolved autofluorescence at the human fundus,” J. Biomed. Opt. 9(6), 1214–1222 (2004).
[Crossref] [PubMed]

Greenstein, V. C.

T. Duncker, M. R. Tabacaru, W. Lee, S. H. Tsang, J. R. Sparrow, and V. C. Greenstein, “Comparison of Near-Infrared and Short-Wavelength Autofluorescence in Retinitis Pigmentosa,” Invest. Ophthalmol. Vis. Sci. 54(1), 585–591 (2013).
[Crossref] [PubMed]

Guo, L.

S. Schmitz-Valckenberg, D. Lara, S. Nizari, E. M. Normando, L. Guo, A. R. Wegener, A. Tufail, F. W. Fitzke, F. G. Holz, and M. F. Cordeiro, “Localisation and significance of in vivo near-infrared autofluorescent signal in retinal imaging,” Br. J. Ophthalmol. 95(8), 1134–1139 (2011).
[Crossref] [PubMed]

Hammer, M.

D. Schweitzer, L. Deutsch, M. Klemm, S. Jentsch, M. Hammer, S. Peters, J. Haueisen, U. A. Müller, and J. Dawczynski, “Fluorescence lifetime imaging ophthalmoscopy in type 2 diabetic patients who have no signs of diabetic retinopathy,” J. Biomed. Opt. 20(6), 061106 (2015).
[Crossref] [PubMed]

M. Klemm, D. Schweitzer, S. Peters, L. Sauer, M. Hammer, and J. Haueisen, “FLIMX: A Software Package to Determine and Analyze the Fluorescence Lifetime in Time-Resolved Fluorescence Data from the Human Eye,” PLoS One 10(7), e0131640 (2015).
[Crossref] [PubMed]

L. Sauer, D. Schweitzer, L. Ramm, R. Augsten, M. Hammer, and S. Peters, “Impact of macular pigment on fundus autofluorescence lifetimes,” Invest. Ophthalmol. Vis. Sci. 56(8), 4668–4679 (2015).
[Crossref] [PubMed]

L. Ramm, S. Jentsch, R. Augsten, and M. Hammer, “Fluorescence lifetime imaging ophthalmoscopy in glaucoma,” Graefes Arch. Clin. Exp. Ophthalmol. 252(12), 2025–2026 (2014).
[Crossref] [PubMed]

S. Jentsch, D. Schweitzer, K. U. Schmidtke, S. Peters, J. Dawczynski, K. J. Bar, and M. Hammer, “Retinal fluorescence lifetime imaging ophthalmoscopy measures depend on the severity of Alzheimer’s disease,” Acta Ophthalmologica 93, e241–e247 (2014).
[PubMed]

D. Schweitzer, E. R. Gaillard, J. Dillon, R. F. Mullins, S. Russell, B. Hoffmann, S. Peters, M. Hammer, and C. Biskup, “Time-Resolved Autofluorescence Imaging of Human Donor Retina Tissue from Donors with Significant Extramacular Drusen,” Invest. Ophthalmol. Vis. Sci. 53(7), 3376–3386 (2012).
[Crossref] [PubMed]

D. Schweitzer, S. Quick, M. Klemm, M. Hammer, S. Jentsch, and J. Dawczynski, “[Time-resolved autofluorescence in retinal vascular occlusions],” Ophthalmologe 107(12), 1145–1152 (2010).
[Crossref] [PubMed]

M. Hammer, E. Königsdörffer, C. Liebermann, C. Framme, G. Schuch, D. Schweitzer, and J. Strobel, “Ocular fundus auto-fluorescence observations at different wavelengths in patients with age-related macular degeneration and diabetic retinopathy,” Graefes Arch. Clin. Exp. Ophthalmol. 246(1), 105–114 (2007).
[Crossref] [PubMed]

D. Schweitzer, S. Schenke, M. Hammer, F. Schweitzer, S. Jentsch, E. Birckner, W. Becker, and A. Bergmann, “Towards metabolic mapping of the human retina,” Microsc. Res. Tech. 70(5), 410–419 (2007).
[Crossref] [PubMed]

D. Schweitzer, M. Hammer, and F. Schweitzer, “Limits of the confocal laser-scanning technique in measurements of time-resolved autofluorescence of the ocular fundus,” Biomed. Tech. (Berl.) 50(9), 263–267 (2005).
[Crossref] [PubMed]

D. Schweitzer, M. Hammer, F. Schweitzer, R. Anders, T. Doebbecke, S. Schenke, E. R. Gaillard, and E. R. Gaillard, “In vivo measurement of time-resolved autofluorescence at the human fundus,” J. Biomed. Opt. 9(6), 1214–1222 (2004).
[Crossref] [PubMed]

Hatz, K.

C. Dysli, S. Wolf, K. Hatz, and M. S. Zinkernagel, “Fluorescence lifetime imaging in stargardt disease: potential marker for disease progression,” Invest. Ophthalmol. Vis. Sci. 57(3), 832–841 (2016).
[Crossref] [PubMed]

Haueisen, J.

M. Klemm, D. Schweitzer, S. Peters, L. Sauer, M. Hammer, and J. Haueisen, “FLIMX: A Software Package to Determine and Analyze the Fluorescence Lifetime in Time-Resolved Fluorescence Data from the Human Eye,” PLoS One 10(7), e0131640 (2015).
[Crossref] [PubMed]

D. Schweitzer, L. Deutsch, M. Klemm, S. Jentsch, M. Hammer, S. Peters, J. Haueisen, U. A. Müller, and J. Dawczynski, “Fluorescence lifetime imaging ophthalmoscopy in type 2 diabetic patients who have no signs of diabetic retinopathy,” J. Biomed. Opt. 20(6), 061106 (2015).
[Crossref] [PubMed]

Hoffmann, B.

D. Schweitzer, E. R. Gaillard, J. Dillon, R. F. Mullins, S. Russell, B. Hoffmann, S. Peters, M. Hammer, and C. Biskup, “Time-Resolved Autofluorescence Imaging of Human Donor Retina Tissue from Donors with Significant Extramacular Drusen,” Invest. Ophthalmol. Vis. Sci. 53(7), 3376–3386 (2012).
[Crossref] [PubMed]

Holz, F. G.

S. Schmitz-Valckenberg, D. Lara, S. Nizari, E. M. Normando, L. Guo, A. R. Wegener, A. Tufail, F. W. Fitzke, F. G. Holz, and M. F. Cordeiro, “Localisation and significance of in vivo near-infrared autofluorescent signal in retinal imaging,” Br. J. Ophthalmol. 95(8), 1134–1139 (2011).
[Crossref] [PubMed]

S. Schmitz-Valckenberg, F. G. Holz, A. C. Bird, and R. F. Spaide, “Fundus autofluorescence imaging: Review and perspectives,” Retina 28(3), 385–409 (2008).
[Crossref] [PubMed]

Huth, J. K.

A. W. A. Weinberger, A. Lappas, T. Kirschkamp, B. A. E. Mazinani, J. K. Huth, B. Mohammadi, and P. Walter, “Fundus near infrared fluorescence correlates with fundus near infrared reflectance,” Invest. Ophthalmol. Vis. Sci. 47(7), 3098–3108 (2006).
[Crossref] [PubMed]

Jacobson, S. G.

Jentsch, S.

D. Schweitzer, L. Deutsch, M. Klemm, S. Jentsch, M. Hammer, S. Peters, J. Haueisen, U. A. Müller, and J. Dawczynski, “Fluorescence lifetime imaging ophthalmoscopy in type 2 diabetic patients who have no signs of diabetic retinopathy,” J. Biomed. Opt. 20(6), 061106 (2015).
[Crossref] [PubMed]

S. Jentsch, D. Schweitzer, K. U. Schmidtke, S. Peters, J. Dawczynski, K. J. Bar, and M. Hammer, “Retinal fluorescence lifetime imaging ophthalmoscopy measures depend on the severity of Alzheimer’s disease,” Acta Ophthalmologica 93, e241–e247 (2014).
[PubMed]

L. Ramm, S. Jentsch, R. Augsten, and M. Hammer, “Fluorescence lifetime imaging ophthalmoscopy in glaucoma,” Graefes Arch. Clin. Exp. Ophthalmol. 252(12), 2025–2026 (2014).
[Crossref] [PubMed]

D. Schweitzer, S. Quick, M. Klemm, M. Hammer, S. Jentsch, and J. Dawczynski, “[Time-resolved autofluorescence in retinal vascular occlusions],” Ophthalmologe 107(12), 1145–1152 (2010).
[Crossref] [PubMed]

D. Schweitzer, S. Schenke, M. Hammer, F. Schweitzer, S. Jentsch, E. Birckner, W. Becker, and A. Bergmann, “Towards metabolic mapping of the human retina,” Microsc. Res. Tech. 70(5), 410–419 (2007).
[Crossref] [PubMed]

Katz, M. L.

G. E. Eldred and M. L. Katz, “Fluorophores of the Human Retinal Pigment Epithelium: Separation and Spectral Characterization,” Exp. Eye Res. 47(1), 71–86 (1988).
[Crossref] [PubMed]

Keilhauer, C. N.

C. N. Keilhauer and F. C. Delori, “Near-infrared autofluorescence imaging of the fundus: Visualization of ocular melanin,” Invest. Ophthalmol. Vis. Sci. 47(8), 3556–3564 (2006).
[Crossref] [PubMed]

Kirschkamp, T.

A. W. A. Weinberger, A. Lappas, T. Kirschkamp, B. A. E. Mazinani, J. K. Huth, B. Mohammadi, and P. Walter, “Fundus near infrared fluorescence correlates with fundus near infrared reflectance,” Invest. Ophthalmol. Vis. Sci. 47(7), 3098–3108 (2006).
[Crossref] [PubMed]

Klemm, M.

M. Klemm, D. Schweitzer, S. Peters, L. Sauer, M. Hammer, and J. Haueisen, “FLIMX: A Software Package to Determine and Analyze the Fluorescence Lifetime in Time-Resolved Fluorescence Data from the Human Eye,” PLoS One 10(7), e0131640 (2015).
[Crossref] [PubMed]

D. Schweitzer, L. Deutsch, M. Klemm, S. Jentsch, M. Hammer, S. Peters, J. Haueisen, U. A. Müller, and J. Dawczynski, “Fluorescence lifetime imaging ophthalmoscopy in type 2 diabetic patients who have no signs of diabetic retinopathy,” J. Biomed. Opt. 20(6), 061106 (2015).
[Crossref] [PubMed]

D. Schweitzer, S. Quick, M. Klemm, M. Hammer, S. Jentsch, and J. Dawczynski, “[Time-resolved autofluorescence in retinal vascular occlusions],” Ophthalmologe 107(12), 1145–1152 (2010).
[Crossref] [PubMed]

Königsdörffer, E.

M. Hammer, E. Königsdörffer, C. Liebermann, C. Framme, G. Schuch, D. Schweitzer, and J. Strobel, “Ocular fundus auto-fluorescence observations at different wavelengths in patients with age-related macular degeneration and diabetic retinopathy,” Graefes Arch. Clin. Exp. Ophthalmol. 246(1), 105–114 (2007).
[Crossref] [PubMed]

Lappas, A.

A. W. A. Weinberger, A. Lappas, T. Kirschkamp, B. A. E. Mazinani, J. K. Huth, B. Mohammadi, and P. Walter, “Fundus near infrared fluorescence correlates with fundus near infrared reflectance,” Invest. Ophthalmol. Vis. Sci. 47(7), 3098–3108 (2006).
[Crossref] [PubMed]

Lara, D.

S. Schmitz-Valckenberg, D. Lara, S. Nizari, E. M. Normando, L. Guo, A. R. Wegener, A. Tufail, F. W. Fitzke, F. G. Holz, and M. F. Cordeiro, “Localisation and significance of in vivo near-infrared autofluorescent signal in retinal imaging,” Br. J. Ophthalmol. 95(8), 1134–1139 (2011).
[Crossref] [PubMed]

Lee, W.

T. Duncker, M. R. Tabacaru, W. Lee, S. H. Tsang, J. R. Sparrow, and V. C. Greenstein, “Comparison of Near-Infrared and Short-Wavelength Autofluorescence in Retinitis Pigmentosa,” Invest. Ophthalmol. Vis. Sci. 54(1), 585–591 (2013).
[Crossref] [PubMed]

Liebermann, C.

M. Hammer, E. Königsdörffer, C. Liebermann, C. Framme, G. Schuch, D. Schweitzer, and J. Strobel, “Ocular fundus auto-fluorescence observations at different wavelengths in patients with age-related macular degeneration and diabetic retinopathy,” Graefes Arch. Clin. Exp. Ophthalmol. 246(1), 105–114 (2007).
[Crossref] [PubMed]

Manivannan, A.

P. F. Sharp and A. Manivannan, “The scanning laser ophthalmoscope,” Phys. Med. Biol. 42(5), 951–966 (1997).
[Crossref] [PubMed]

Marcu, L.

L. Marcu, “Fluorescence Lifetime Techniques in Medical Applications,” Ann. Biomed. Eng. 40(2), 304–331 (2012).
[Crossref] [PubMed]

Mazinani, B. A. E.

A. W. A. Weinberger, A. Lappas, T. Kirschkamp, B. A. E. Mazinani, J. K. Huth, B. Mohammadi, and P. Walter, “Fundus near infrared fluorescence correlates with fundus near infrared reflectance,” Invest. Ophthalmol. Vis. Sci. 47(7), 3098–3108 (2006).
[Crossref] [PubMed]

Mohammadi, B.

A. W. A. Weinberger, A. Lappas, T. Kirschkamp, B. A. E. Mazinani, J. K. Huth, B. Mohammadi, and P. Walter, “Fundus near infrared fluorescence correlates with fundus near infrared reflectance,” Invest. Ophthalmol. Vis. Sci. 47(7), 3098–3108 (2006).
[Crossref] [PubMed]

Müller, U. A.

D. Schweitzer, L. Deutsch, M. Klemm, S. Jentsch, M. Hammer, S. Peters, J. Haueisen, U. A. Müller, and J. Dawczynski, “Fluorescence lifetime imaging ophthalmoscopy in type 2 diabetic patients who have no signs of diabetic retinopathy,” J. Biomed. Opt. 20(6), 061106 (2015).
[Crossref] [PubMed]

Mullins, R. F.

D. Schweitzer, E. R. Gaillard, J. Dillon, R. F. Mullins, S. Russell, B. Hoffmann, S. Peters, M. Hammer, and C. Biskup, “Time-Resolved Autofluorescence Imaging of Human Donor Retina Tissue from Donors with Significant Extramacular Drusen,” Invest. Ophthalmol. Vis. Sci. 53(7), 3376–3386 (2012).
[Crossref] [PubMed]

Nizari, S.

S. Schmitz-Valckenberg, D. Lara, S. Nizari, E. M. Normando, L. Guo, A. R. Wegener, A. Tufail, F. W. Fitzke, F. G. Holz, and M. F. Cordeiro, “Localisation and significance of in vivo near-infrared autofluorescent signal in retinal imaging,” Br. J. Ophthalmol. 95(8), 1134–1139 (2011).
[Crossref] [PubMed]

Normando, E. M.

S. Schmitz-Valckenberg, D. Lara, S. Nizari, E. M. Normando, L. Guo, A. R. Wegener, A. Tufail, F. W. Fitzke, F. G. Holz, and M. F. Cordeiro, “Localisation and significance of in vivo near-infrared autofluorescent signal in retinal imaging,” Br. J. Ophthalmol. 95(8), 1134–1139 (2011).
[Crossref] [PubMed]

Pau, H.

H. Pau, J. Degen, and H. H. Schmidtke, “Different Regional Changes of Fluorescence Spectra of Clear Human Lenses and Nuclear Cataracts,” Graefes Arch. Clin. Exp. Ophthalmol. 231(11), 656–661 (1993).
[Crossref] [PubMed]

Peters, S.

L. Sauer, D. Schweitzer, L. Ramm, R. Augsten, M. Hammer, and S. Peters, “Impact of macular pigment on fundus autofluorescence lifetimes,” Invest. Ophthalmol. Vis. Sci. 56(8), 4668–4679 (2015).
[Crossref] [PubMed]

D. Schweitzer, L. Deutsch, M. Klemm, S. Jentsch, M. Hammer, S. Peters, J. Haueisen, U. A. Müller, and J. Dawczynski, “Fluorescence lifetime imaging ophthalmoscopy in type 2 diabetic patients who have no signs of diabetic retinopathy,” J. Biomed. Opt. 20(6), 061106 (2015).
[Crossref] [PubMed]

M. Klemm, D. Schweitzer, S. Peters, L. Sauer, M. Hammer, and J. Haueisen, “FLIMX: A Software Package to Determine and Analyze the Fluorescence Lifetime in Time-Resolved Fluorescence Data from the Human Eye,” PLoS One 10(7), e0131640 (2015).
[Crossref] [PubMed]

S. Jentsch, D. Schweitzer, K. U. Schmidtke, S. Peters, J. Dawczynski, K. J. Bar, and M. Hammer, “Retinal fluorescence lifetime imaging ophthalmoscopy measures depend on the severity of Alzheimer’s disease,” Acta Ophthalmologica 93, e241–e247 (2014).
[PubMed]

D. Schweitzer, E. R. Gaillard, J. Dillon, R. F. Mullins, S. Russell, B. Hoffmann, S. Peters, M. Hammer, and C. Biskup, “Time-Resolved Autofluorescence Imaging of Human Donor Retina Tissue from Donors with Significant Extramacular Drusen,” Invest. Ophthalmol. Vis. Sci. 53(7), 3376–3386 (2012).
[Crossref] [PubMed]

Quick, S.

D. Schweitzer, S. Quick, M. Klemm, M. Hammer, S. Jentsch, and J. Dawczynski, “[Time-resolved autofluorescence in retinal vascular occlusions],” Ophthalmologe 107(12), 1145–1152 (2010).
[Crossref] [PubMed]

Ramm, L.

L. Sauer, D. Schweitzer, L. Ramm, R. Augsten, M. Hammer, and S. Peters, “Impact of macular pigment on fundus autofluorescence lifetimes,” Invest. Ophthalmol. Vis. Sci. 56(8), 4668–4679 (2015).
[Crossref] [PubMed]

L. Ramm, S. Jentsch, R. Augsten, and M. Hammer, “Fluorescence lifetime imaging ophthalmoscopy in glaucoma,” Graefes Arch. Clin. Exp. Ophthalmol. 252(12), 2025–2026 (2014).
[Crossref] [PubMed]

Roman, M. I.

Russell, S.

D. Schweitzer, E. R. Gaillard, J. Dillon, R. F. Mullins, S. Russell, B. Hoffmann, S. Peters, M. Hammer, and C. Biskup, “Time-Resolved Autofluorescence Imaging of Human Donor Retina Tissue from Donors with Significant Extramacular Drusen,” Invest. Ophthalmol. Vis. Sci. 53(7), 3376–3386 (2012).
[Crossref] [PubMed]

Sauer, L.

L. Sauer, D. Schweitzer, L. Ramm, R. Augsten, M. Hammer, and S. Peters, “Impact of macular pigment on fundus autofluorescence lifetimes,” Invest. Ophthalmol. Vis. Sci. 56(8), 4668–4679 (2015).
[Crossref] [PubMed]

M. Klemm, D. Schweitzer, S. Peters, L. Sauer, M. Hammer, and J. Haueisen, “FLIMX: A Software Package to Determine and Analyze the Fluorescence Lifetime in Time-Resolved Fluorescence Data from the Human Eye,” PLoS One 10(7), e0131640 (2015).
[Crossref] [PubMed]

Schenke, S.

D. Schweitzer, S. Schenke, M. Hammer, F. Schweitzer, S. Jentsch, E. Birckner, W. Becker, and A. Bergmann, “Towards metabolic mapping of the human retina,” Microsc. Res. Tech. 70(5), 410–419 (2007).
[Crossref] [PubMed]

D. Schweitzer, M. Hammer, F. Schweitzer, R. Anders, T. Doebbecke, S. Schenke, E. R. Gaillard, and E. R. Gaillard, “In vivo measurement of time-resolved autofluorescence at the human fundus,” J. Biomed. Opt. 9(6), 1214–1222 (2004).
[Crossref] [PubMed]

Schmidtke, H. H.

H. Pau, J. Degen, and H. H. Schmidtke, “Different Regional Changes of Fluorescence Spectra of Clear Human Lenses and Nuclear Cataracts,” Graefes Arch. Clin. Exp. Ophthalmol. 231(11), 656–661 (1993).
[Crossref] [PubMed]

Schmidtke, K. U.

S. Jentsch, D. Schweitzer, K. U. Schmidtke, S. Peters, J. Dawczynski, K. J. Bar, and M. Hammer, “Retinal fluorescence lifetime imaging ophthalmoscopy measures depend on the severity of Alzheimer’s disease,” Acta Ophthalmologica 93, e241–e247 (2014).
[PubMed]

Schmitz-Valckenberg, S.

S. Schmitz-Valckenberg, D. Lara, S. Nizari, E. M. Normando, L. Guo, A. R. Wegener, A. Tufail, F. W. Fitzke, F. G. Holz, and M. F. Cordeiro, “Localisation and significance of in vivo near-infrared autofluorescent signal in retinal imaging,” Br. J. Ophthalmol. 95(8), 1134–1139 (2011).
[Crossref] [PubMed]

S. Schmitz-Valckenberg, F. G. Holz, A. C. Bird, and R. F. Spaide, “Fundus autofluorescence imaging: Review and perspectives,” Retina 28(3), 385–409 (2008).
[Crossref] [PubMed]

Schuch, G.

M. Hammer, E. Königsdörffer, C. Liebermann, C. Framme, G. Schuch, D. Schweitzer, and J. Strobel, “Ocular fundus auto-fluorescence observations at different wavelengths in patients with age-related macular degeneration and diabetic retinopathy,” Graefes Arch. Clin. Exp. Ophthalmol. 246(1), 105–114 (2007).
[Crossref] [PubMed]

Schwartz, S. B.

Schweitzer, D.

M. Klemm, D. Schweitzer, S. Peters, L. Sauer, M. Hammer, and J. Haueisen, “FLIMX: A Software Package to Determine and Analyze the Fluorescence Lifetime in Time-Resolved Fluorescence Data from the Human Eye,” PLoS One 10(7), e0131640 (2015).
[Crossref] [PubMed]

D. Schweitzer, L. Deutsch, M. Klemm, S. Jentsch, M. Hammer, S. Peters, J. Haueisen, U. A. Müller, and J. Dawczynski, “Fluorescence lifetime imaging ophthalmoscopy in type 2 diabetic patients who have no signs of diabetic retinopathy,” J. Biomed. Opt. 20(6), 061106 (2015).
[Crossref] [PubMed]

L. Sauer, D. Schweitzer, L. Ramm, R. Augsten, M. Hammer, and S. Peters, “Impact of macular pigment on fundus autofluorescence lifetimes,” Invest. Ophthalmol. Vis. Sci. 56(8), 4668–4679 (2015).
[Crossref] [PubMed]

S. Jentsch, D. Schweitzer, K. U. Schmidtke, S. Peters, J. Dawczynski, K. J. Bar, and M. Hammer, “Retinal fluorescence lifetime imaging ophthalmoscopy measures depend on the severity of Alzheimer’s disease,” Acta Ophthalmologica 93, e241–e247 (2014).
[PubMed]

D. Schweitzer, E. R. Gaillard, J. Dillon, R. F. Mullins, S. Russell, B. Hoffmann, S. Peters, M. Hammer, and C. Biskup, “Time-Resolved Autofluorescence Imaging of Human Donor Retina Tissue from Donors with Significant Extramacular Drusen,” Invest. Ophthalmol. Vis. Sci. 53(7), 3376–3386 (2012).
[Crossref] [PubMed]

D. Schweitzer, S. Quick, M. Klemm, M. Hammer, S. Jentsch, and J. Dawczynski, “[Time-resolved autofluorescence in retinal vascular occlusions],” Ophthalmologe 107(12), 1145–1152 (2010).
[Crossref] [PubMed]

M. Hammer, E. Königsdörffer, C. Liebermann, C. Framme, G. Schuch, D. Schweitzer, and J. Strobel, “Ocular fundus auto-fluorescence observations at different wavelengths in patients with age-related macular degeneration and diabetic retinopathy,” Graefes Arch. Clin. Exp. Ophthalmol. 246(1), 105–114 (2007).
[Crossref] [PubMed]

D. Schweitzer, S. Schenke, M. Hammer, F. Schweitzer, S. Jentsch, E. Birckner, W. Becker, and A. Bergmann, “Towards metabolic mapping of the human retina,” Microsc. Res. Tech. 70(5), 410–419 (2007).
[Crossref] [PubMed]

D. Schweitzer, M. Hammer, and F. Schweitzer, “Limits of the confocal laser-scanning technique in measurements of time-resolved autofluorescence of the ocular fundus,” Biomed. Tech. (Berl.) 50(9), 263–267 (2005).
[Crossref] [PubMed]

D. Schweitzer, M. Hammer, F. Schweitzer, R. Anders, T. Doebbecke, S. Schenke, E. R. Gaillard, and E. R. Gaillard, “In vivo measurement of time-resolved autofluorescence at the human fundus,” J. Biomed. Opt. 9(6), 1214–1222 (2004).
[Crossref] [PubMed]

Schweitzer, F.

D. Schweitzer, S. Schenke, M. Hammer, F. Schweitzer, S. Jentsch, E. Birckner, W. Becker, and A. Bergmann, “Towards metabolic mapping of the human retina,” Microsc. Res. Tech. 70(5), 410–419 (2007).
[Crossref] [PubMed]

D. Schweitzer, M. Hammer, and F. Schweitzer, “Limits of the confocal laser-scanning technique in measurements of time-resolved autofluorescence of the ocular fundus,” Biomed. Tech. (Berl.) 50(9), 263–267 (2005).
[Crossref] [PubMed]

D. Schweitzer, M. Hammer, F. Schweitzer, R. Anders, T. Doebbecke, S. Schenke, E. R. Gaillard, and E. R. Gaillard, “In vivo measurement of time-resolved autofluorescence at the human fundus,” J. Biomed. Opt. 9(6), 1214–1222 (2004).
[Crossref] [PubMed]

Sharp, P. F.

P. F. Sharp and A. Manivannan, “The scanning laser ophthalmoscope,” Phys. Med. Biol. 42(5), 951–966 (1997).
[Crossref] [PubMed]

Spaide, R. F.

S. Schmitz-Valckenberg, F. G. Holz, A. C. Bird, and R. F. Spaide, “Fundus autofluorescence imaging: Review and perspectives,” Retina 28(3), 385–409 (2008).
[Crossref] [PubMed]

Sparrow, J. R.

T. Duncker, M. R. Tabacaru, W. Lee, S. H. Tsang, J. R. Sparrow, and V. C. Greenstein, “Comparison of Near-Infrared and Short-Wavelength Autofluorescence in Retinitis Pigmentosa,” Invest. Ophthalmol. Vis. Sci. 54(1), 585–591 (2013).
[Crossref] [PubMed]

Stone, E. M.

Strobel, J.

M. Hammer, E. Königsdörffer, C. Liebermann, C. Framme, G. Schuch, D. Schweitzer, and J. Strobel, “Ocular fundus auto-fluorescence observations at different wavelengths in patients with age-related macular degeneration and diabetic retinopathy,” Graefes Arch. Clin. Exp. Ophthalmol. 246(1), 105–114 (2007).
[Crossref] [PubMed]

Sumaroka, A.

Swider, M.

Tabacaru, M. R.

T. Duncker, M. R. Tabacaru, W. Lee, S. H. Tsang, J. R. Sparrow, and V. C. Greenstein, “Comparison of Near-Infrared and Short-Wavelength Autofluorescence in Retinitis Pigmentosa,” Invest. Ophthalmol. Vis. Sci. 54(1), 585–591 (2013).
[Crossref] [PubMed]

Tsang, S. H.

T. Duncker, M. R. Tabacaru, W. Lee, S. H. Tsang, J. R. Sparrow, and V. C. Greenstein, “Comparison of Near-Infrared and Short-Wavelength Autofluorescence in Retinitis Pigmentosa,” Invest. Ophthalmol. Vis. Sci. 54(1), 585–591 (2013).
[Crossref] [PubMed]

Tufail, A.

S. Schmitz-Valckenberg, D. Lara, S. Nizari, E. M. Normando, L. Guo, A. R. Wegener, A. Tufail, F. W. Fitzke, F. G. Holz, and M. F. Cordeiro, “Localisation and significance of in vivo near-infrared autofluorescent signal in retinal imaging,” Br. J. Ophthalmol. 95(8), 1134–1139 (2011).
[Crossref] [PubMed]

Walter, P.

A. W. A. Weinberger, A. Lappas, T. Kirschkamp, B. A. E. Mazinani, J. K. Huth, B. Mohammadi, and P. Walter, “Fundus near infrared fluorescence correlates with fundus near infrared reflectance,” Invest. Ophthalmol. Vis. Sci. 47(7), 3098–3108 (2006).
[Crossref] [PubMed]

Wegener, A. R.

S. Schmitz-Valckenberg, D. Lara, S. Nizari, E. M. Normando, L. Guo, A. R. Wegener, A. Tufail, F. W. Fitzke, F. G. Holz, and M. F. Cordeiro, “Localisation and significance of in vivo near-infrared autofluorescent signal in retinal imaging,” Br. J. Ophthalmol. 95(8), 1134–1139 (2011).
[Crossref] [PubMed]

Weinberger, A. W. A.

A. W. A. Weinberger, A. Lappas, T. Kirschkamp, B. A. E. Mazinani, J. K. Huth, B. Mohammadi, and P. Walter, “Fundus near infrared fluorescence correlates with fundus near infrared reflectance,” Invest. Ophthalmol. Vis. Sci. 47(7), 3098–3108 (2006).
[Crossref] [PubMed]

Wolf, S.

C. Dysli, S. Wolf, K. Hatz, and M. S. Zinkernagel, “Fluorescence lifetime imaging in stargardt disease: potential marker for disease progression,” Invest. Ophthalmol. Vis. Sci. 57(3), 832–841 (2016).
[Crossref] [PubMed]

C. Dysli, S. Wolf, and M. S. Zinkernagel, “Fluorescence Lifetime Imaging in Retinal Artery Occlusion,” Invest. Ophthalmol. Vis. Sci. 56(5), 3329–3336 (2015).
[Crossref] [PubMed]

Zinkernagel, M. S.

C. Dysli, S. Wolf, K. Hatz, and M. S. Zinkernagel, “Fluorescence lifetime imaging in stargardt disease: potential marker for disease progression,” Invest. Ophthalmol. Vis. Sci. 57(3), 832–841 (2016).
[Crossref] [PubMed]

C. Dysli, S. Wolf, and M. S. Zinkernagel, “Fluorescence Lifetime Imaging in Retinal Artery Occlusion,” Invest. Ophthalmol. Vis. Sci. 56(5), 3329–3336 (2015).
[Crossref] [PubMed]

Acta Ophthalmologica (1)

S. Jentsch, D. Schweitzer, K. U. Schmidtke, S. Peters, J. Dawczynski, K. J. Bar, and M. Hammer, “Retinal fluorescence lifetime imaging ophthalmoscopy measures depend on the severity of Alzheimer’s disease,” Acta Ophthalmologica 93, e241–e247 (2014).
[PubMed]

Ann. Biomed. Eng. (1)

L. Marcu, “Fluorescence Lifetime Techniques in Medical Applications,” Ann. Biomed. Eng. 40(2), 304–331 (2012).
[Crossref] [PubMed]

Biomed. Tech. (Berl.) (1)

D. Schweitzer, M. Hammer, and F. Schweitzer, “Limits of the confocal laser-scanning technique in measurements of time-resolved autofluorescence of the ocular fundus,” Biomed. Tech. (Berl.) 50(9), 263–267 (2005).
[Crossref] [PubMed]

Br. J. Ophthalmol. (1)

S. Schmitz-Valckenberg, D. Lara, S. Nizari, E. M. Normando, L. Guo, A. R. Wegener, A. Tufail, F. W. Fitzke, F. G. Holz, and M. F. Cordeiro, “Localisation and significance of in vivo near-infrared autofluorescent signal in retinal imaging,” Br. J. Ophthalmol. 95(8), 1134–1139 (2011).
[Crossref] [PubMed]

Exp. Eye Res. (1)

G. E. Eldred and M. L. Katz, “Fluorophores of the Human Retinal Pigment Epithelium: Separation and Spectral Characterization,” Exp. Eye Res. 47(1), 71–86 (1988).
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Graefes Arch. Clin. Exp. Ophthalmol. (3)

H. Pau, J. Degen, and H. H. Schmidtke, “Different Regional Changes of Fluorescence Spectra of Clear Human Lenses and Nuclear Cataracts,” Graefes Arch. Clin. Exp. Ophthalmol. 231(11), 656–661 (1993).
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L. Ramm, S. Jentsch, R. Augsten, and M. Hammer, “Fluorescence lifetime imaging ophthalmoscopy in glaucoma,” Graefes Arch. Clin. Exp. Ophthalmol. 252(12), 2025–2026 (2014).
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M. Hammer, E. Königsdörffer, C. Liebermann, C. Framme, G. Schuch, D. Schweitzer, and J. Strobel, “Ocular fundus auto-fluorescence observations at different wavelengths in patients with age-related macular degeneration and diabetic retinopathy,” Graefes Arch. Clin. Exp. Ophthalmol. 246(1), 105–114 (2007).
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Invest. Ophthalmol. Vis. Sci. (7)

D. Schweitzer, E. R. Gaillard, J. Dillon, R. F. Mullins, S. Russell, B. Hoffmann, S. Peters, M. Hammer, and C. Biskup, “Time-Resolved Autofluorescence Imaging of Human Donor Retina Tissue from Donors with Significant Extramacular Drusen,” Invest. Ophthalmol. Vis. Sci. 53(7), 3376–3386 (2012).
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L. Sauer, D. Schweitzer, L. Ramm, R. Augsten, M. Hammer, and S. Peters, “Impact of macular pigment on fundus autofluorescence lifetimes,” Invest. Ophthalmol. Vis. Sci. 56(8), 4668–4679 (2015).
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C. Dysli, S. Wolf, K. Hatz, and M. S. Zinkernagel, “Fluorescence lifetime imaging in stargardt disease: potential marker for disease progression,” Invest. Ophthalmol. Vis. Sci. 57(3), 832–841 (2016).
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C. Dysli, S. Wolf, and M. S. Zinkernagel, “Fluorescence Lifetime Imaging in Retinal Artery Occlusion,” Invest. Ophthalmol. Vis. Sci. 56(5), 3329–3336 (2015).
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C. N. Keilhauer and F. C. Delori, “Near-infrared autofluorescence imaging of the fundus: Visualization of ocular melanin,” Invest. Ophthalmol. Vis. Sci. 47(8), 3556–3564 (2006).
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A. W. A. Weinberger, A. Lappas, T. Kirschkamp, B. A. E. Mazinani, J. K. Huth, B. Mohammadi, and P. Walter, “Fundus near infrared fluorescence correlates with fundus near infrared reflectance,” Invest. Ophthalmol. Vis. Sci. 47(7), 3098–3108 (2006).
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T. Duncker, M. R. Tabacaru, W. Lee, S. H. Tsang, J. R. Sparrow, and V. C. Greenstein, “Comparison of Near-Infrared and Short-Wavelength Autofluorescence in Retinitis Pigmentosa,” Invest. Ophthalmol. Vis. Sci. 54(1), 585–591 (2013).
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J. Biomed. Opt. (2)

D. Schweitzer, L. Deutsch, M. Klemm, S. Jentsch, M. Hammer, S. Peters, J. Haueisen, U. A. Müller, and J. Dawczynski, “Fluorescence lifetime imaging ophthalmoscopy in type 2 diabetic patients who have no signs of diabetic retinopathy,” J. Biomed. Opt. 20(6), 061106 (2015).
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D. Schweitzer, M. Hammer, F. Schweitzer, R. Anders, T. Doebbecke, S. Schenke, E. R. Gaillard, and E. R. Gaillard, “In vivo measurement of time-resolved autofluorescence at the human fundus,” J. Biomed. Opt. 9(6), 1214–1222 (2004).
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J. Microsc. (1)

W. Becker, “Fluorescence lifetime imaging--techniques and applications,” J. Microsc. 247(2), 119–136 (2012).
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J. Opt. Soc. Am. A (1)

Microsc. Res. Tech. (1)

D. Schweitzer, S. Schenke, M. Hammer, F. Schweitzer, S. Jentsch, E. Birckner, W. Becker, and A. Bergmann, “Towards metabolic mapping of the human retina,” Microsc. Res. Tech. 70(5), 410–419 (2007).
[Crossref] [PubMed]

Ophthalmologe (1)

D. Schweitzer, S. Quick, M. Klemm, M. Hammer, S. Jentsch, and J. Dawczynski, “[Time-resolved autofluorescence in retinal vascular occlusions],” Ophthalmologe 107(12), 1145–1152 (2010).
[Crossref] [PubMed]

Phys. Med. Biol. (1)

P. F. Sharp and A. Manivannan, “The scanning laser ophthalmoscope,” Phys. Med. Biol. 42(5), 951–966 (1997).
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PLoS One (1)

M. Klemm, D. Schweitzer, S. Peters, L. Sauer, M. Hammer, and J. Haueisen, “FLIMX: A Software Package to Determine and Analyze the Fluorescence Lifetime in Time-Resolved Fluorescence Data from the Human Eye,” PLoS One 10(7), e0131640 (2015).
[Crossref] [PubMed]

Retina (1)

S. Schmitz-Valckenberg, F. G. Holz, A. C. Bird, and R. F. Spaide, “Fundus autofluorescence imaging: Review and perspectives,” Retina 28(3), 385–409 (2008).
[Crossref] [PubMed]

Other (2)

J. R. Lakowicz, Principles of Fluorescence Spectroscopy, 3rd ed. (Springer, New York, 2006), p. 954.

A. A. Michelson, Studies in Optics, The University of Chicago science series (The University of Chicago Press, Chicago, Ill., 1927), pp. ix, 176.

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Figures (7)

Fig. 1
Fig. 1 FLIO data of the short spectral channel (498 nm – 560 nm) before (left) and after (right) cataract surgery in the left eye of a 74 years old male volunteer. The improved contrast in the fluorescence intensity image after cataract surgery (B) is clearly visible. The mean fluorescence lifetime τm after cataract surgery (D) is much shorter than before the surgery (C). The color scaling of the fluorescence lifetimes is identical in both images for better comparison.
Fig. 2
Fig. 2 Schema of the aperture stop separation in a fundus camera (A), the confocal principle of a scanning laser ophthalmoscope (C) and Schweitzer’s principle (E). The fundus autofluorescence in a 30° field of a patient with AMD measured by a fundus camera (B; FF450, Carl Zeiss Meditec AG, Jena, Germany) using the aperture stop separation approach and by a scanning laser ophthalmoscope (D) using the confocal principle. Both approaches are able to image the fundus autofluorescence while the scanning laser ophthalmoscope delivers better contrast.
Fig. 3
Fig. 3 Schema of the optical setup used for the experiments.
Fig. 4
Fig. 4 CAD-model of an annular aperture stop with an inner diameter of 3 mm. The length of the scale bar is 2 mm.
Fig. 5
Fig. 5 Spectra of simulated crystalline lens fluorescence (peak at 514 nm) and simulated retina fluorescence (peak at 576 nm / 594 nm) with (B) and without confocal principle (A) for different annular aperture stops after filtering and normalization. The gray line marks the emission maxima of both fluorophores.
Fig. 6
Fig. 6 Extracted fluorescence intensities for simulated crystalline lens and simulated retina for all measurements, normalized to the confocal principle. This normalization allows for a direct quantification of the benefits and costs of Schweitzer’s principle. For example, the best compromise we propose is Schweitzer’s principle with an inner diameter of 3 mm, which reduces the simulated crystalline lens fluorescence to 4% while preserving 42% of the simulated retina fluorescence. The suppressions of simulated crystalline lens fluorescence and simulated retina fluorescence are given in dark green and red. The plots are on a logarithmic scale, values are rounded.
Fig. 7
Fig. 7 Ratio between suppression of simulated crystalline lens fluorescence and suppression of simulated retina fluorescence (ratio of suppressions, black) and Michelson contrast between fluorescence intensities of the simulated crystalline lens and simulated retina (blue). The highest ratio and the highest Michelson contrast are achieved for Schweitzer’s principle with an inner diameter of 4 mm.

Tables (2)

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Table 1 Properties of the annular aperture stops and the required corrections of the focal point.

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Table 2 Ratios between the suppression of the simulated crystalline lens fluorescence and the suppression of the simulated retina multiplied by the fluorescence intensity of the simulated retina for confocal principle and Schweitzer’s principle. The largest value is the best compromise between suppressing the simulated crystalline lens fluorescence and the remaining simulated retina fluorescence.

Equations (2)

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I corrected = I measured π d o,ideal 2 π d i,ideal 2 π d o,real 2 ( d o,real d i,real ) d s,real 4π d i,real 2
mc= I retina I lens I retina + I lens

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