Optical Coherence Tomography Updates on Clinical and Technical Developments. Age-Related Macular Degeneration: Drusen and Geographic Atrophy

  • Monika Fleckenstein
  • Steffen Schmitz-Valckenberg
  • Frank G. Holz
Part of the Biological and Medical Physics, Biomedical Engineering book series (BIOMEDICAL)


Age-related macular degeneration (AMD) is a complex disease with both genetic and environmental factors influencing its development. With the advent of high-resolution OCT imaging, the characterization of drusen in AMD has become possible. The in vivo morphologic characteristics imaged with SD-OCT may represent distinct subclasses of drusen variants, may relate closely to ultrastructural drusen elements identified in donor eyes, and may be useful imaging biomarkers for disease severity or risk of progression [Khanifar et al. Ophthalmology 115(11):1883–1890, 2008].


Retinal Pigment Epithelium Retinal Pigment Epithelium Cell Retinal Thickness External Limit Membrane Outer Retinal Layer 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    J. Ambati, B.K. Ambati, S.H. Yoo, S. Ianchulev, A.P. Adamis, Age-related macular degeneration: etiology, pathogenesis, and therapeutic strategies. Surv. Ophthalmol. 48(3), 257–293 (2003)CrossRefGoogle Scholar
  2. 2.
    U. Chakravarthy, C. Augood, G.C. Bentham, P.T. de Jong, M. Rahu, J. Seland, G. Soubrane, L. Tomazzoli, F. Topouzis, J.R. Vingerling, J. Vioque, I.S. Young, A.E. Fletcher, Cigarette smoking and age-related macular degeneration in the EUREYE Study. Ophthalmology 114(6), 1157–1163 (2007)CrossRefGoogle Scholar
  3. 3.
    C.C. Klaver, R.C. Wolfs, J.R. Vingerling, A. Hofman, P.T. de Jong, Age-specific prevalence and causes of blindness and visual impairment in an older population: the Rotterdam Study. Arch. Ophthalmol. 116(5), 653–658 (1998)Google Scholar
  4. 4.
    R. Klein, B.E. Klein, M.D. Knudtson, S.M. Meuer, M. Swift, R.E. Gangnon, Fifteen-year cumulative incidence of age-related macular degeneration: the Beaver Dam Eye Study. Ophthalmology 114(2), 253–262 (2007)CrossRefGoogle Scholar
  5. 5.
    S. Schmitz-Valckenberg, M. Fleckenstein, H.P. Scholl, F.G. Holz, Fundus autofluorescence and progression of age-related macular degeneration. Surv. Ophthalmol 54(1), 96–117 (2009)CrossRefGoogle Scholar
  6. 6.
    S.C. Tomany, J.J. Wang, R. Van Leeuwen, R. Klein, P. Mitchell, J.R. Vingerling, B.E. Klein, W. Smith, P.T. De Jong, Risk factors for incident age-related macular degeneration: pooled findings from 3 continents. Ophthalmology 111(7), 1280–1287 (2004)CrossRefGoogle Scholar
  7. 7.
    R. van Leeuwen, C.C. Klaver, J.R. Vingerling, A. Hofman, P.T. de Jong, Epidemiology of age-related maculopathy: a review. Eur. J. Epidemiol. 18(9), 845–854 (2003)CrossRefGoogle Scholar
  8. 8.
    J.J. Wang, E. Rochtchina, A.J. Lee, E.M. Chia, W. Smith, R.G. Cumming, P. Mitchell, Ten-year incidence and progression of age-related maculopathy: the blue Mountains Eye Study. Ophthalmology. 114(1), 92–98 (2007)CrossRefGoogle Scholar
  9. 9.
    D.S. Friedman, B.J. O’Colmain, B. Muñoz, S.C. Tomany, C. McCarty, P.T. de Jong, B. Nemesure, P. Mitchell, J. Kempen, Eye Diseases Prevalence Research Group, Prevalence of age-related macular degeneration in the United States. Arch. Ophthalmol. 122(4), 564–572 (2004)Google Scholar
  10. 10.
    R. Klein, B.E. Klein, S.C. Tomany, S.M. Meuer, G.H. Huang, Ten-year incidence and progression of age-related maculopathy: the Beaver Dam eye study. Ophthalmology 109(10), 1767–1779 (2002)CrossRefGoogle Scholar
  11. 11.
    P. Mitchell, W. Smith, K. Attebo, J.J. Wang, Prevalence of age-related maculopathy in Australia. The Blue Mountains Eye Study. Ophthalmology 102(10), 1450–1460 (1995)Google Scholar
  12. 12.
    J.S. Sunness, J. Gonzalez-Baron, C.A. Applegate, N.M. Bressler, Y. Tian, B. Hawkins, Y. Barron, A. Bergman, Enlargement of atrophy and visual acuity loss in the geographic atrophy form of age-related macular degeneration. Ophthalmology 106(9), 1768–1779 (1999)CrossRefGoogle Scholar
  13. 13.
    S. Wolf, U. Wolf-Schnurrbusch, Spectral-domain optical coherence tomography use in macular diseases: a review. Ophthalmologica 224(6), 333–340 (2010)CrossRefGoogle Scholar
  14. 14.
    A.A. Khanifar, A.F. Koreishi, J.A. Izatt, C.A. Toth, Drusen ultrastructure imaging with spectral domain optical coherence tomography in age-related macular degeneration. Ophthalmology 115(11), 1883–1890 (2008)CrossRefGoogle Scholar
  15. 15.
    S.G. Schuman, A.F. Koreishi, S. Farsiu, S.H. Jung, J.A. Izatt, C.A. Toth, Photoreceptor layer thinning over drusen in eyes with age-related macular degeneration imaged in vivo with spectral-domain optical coherence tomography. Ophthalmology 116(3), 488.e2–496.e2 (2009)Google Scholar
  16. 16.
    M. Fleckenstein, P. Charbel Issa, H.M. Helb, S. Schmitz-Valckenberg, R.P. Finger, H.P. Scholl, K.U. Loeffler, F.G. Holz, High-resolution spectral domain-OCT imaging in geographic atrophy associated with age-related macular degeneration. Invest. Ophthalmol. Vis. Sci. 49(9), 4137–4144 (2008)CrossRefGoogle Scholar
  17. 17.
    C.G. Pieroni, A.J. Witkin, T.H. Ko, J.G. Fujimoto, A. Chan, J.S. Schuman, H. Ishikawa, E. Reichel, J.S. Duker, Ultrahigh resolution optical coherence tomography in non-exudative age related macular degeneration. Br. J. Ophthalmol. 90(2), 191–197 (2006)CrossRefGoogle Scholar
  18. 18.
    J. Ho, A.J. Witkin, J. Liu, Y. Chen, J.G. Fujimoto, J.S. Schuman, J.S. Duker, Documentation of intraretinal retinal pigment epithelium migration via high-speed ultrahigh-resolution optical coherence tomography. Ophthalmology 118(4), 687–693 (2011)CrossRefGoogle Scholar
  19. 19.
    B.L. Sikorski, D. Bukowska, J.J. Kaluzny, M. Szkulmowski, A. Kowalczyk, M. Wojtkowski, Drusen with accompanying fluid underneath the sensory retina. Ophthalmology 118(1), 82–92 (2011)CrossRefGoogle Scholar
  20. 20.
    G. Mimoun, G. Soubrane, G. Coscas, [Macular drusen]. J. Fr. Ophtalmol. 13(10), 511–530 (1990)Google Scholar
  21. 21.
    S. Schmitz-Valckenberg, J.S. Steinberg, M. Fleckenstein, S. Visvalingam, C.K. Brinkmann, F.G. Holz, Combined confocal scanning laser ophthalmoscopy and spectral-domain optical coherence tomography imaging of reticular drusen associated with age-related macular degeneration. Ophthalmology 117(6), 1169–1176 (2010)CrossRefGoogle Scholar
  22. 22.
    R.F. Spaide, C.A. Curcio, Drusen characterization with multimodal imaging. Retina 30(9), 1441–1454 (2010)Google Scholar
  23. 23.
    S.A. Zweifel, R.F. Spaide, C.A. Curcio, G. Malek, Y. Imamura, Reticular pseudodrusen are subretinal drusenoid deposits. Ophthalmology 117(2), 303.e1–312.e1 (2010)Google Scholar
  24. 24.
    M. Rudolf, G. Malek, J.D. Messinger, M.E. Clark, L. Wang, C.A. Curcio, Sub-retinal drusenoid deposits in human retina: organization and composition. Exp. Eye Res. 87(5), 402–408 (2008)CrossRefGoogle Scholar
  25. 25.
    S.R. Freeman, I. Kozak, L. Cheng, D.U. Bartsch, F. Mojana, N. Nigam, M. Brar, R. Yuson, W.R. Freeman, Optical coherence tomography-raster scanning and manual segmentation in determining drusen volume in age-related macular degeneration. Retina 30(3), 431–435 (2010)CrossRefGoogle Scholar
  26. 26.
    N. Jain, S. Farsiu, A.A. Khanifar, S. Bearelly, R.T. Smith, J.A. Izatt, C.A. Toth, Quantitative comparison of drusen segmented on SD OCT versus drusen delineated on color fundus photographs. Invest. Ophthalmol. Vis. Sci. 51(10), 4875–4883 (2010)CrossRefGoogle Scholar
  27. 27.
    M. Wojtkowski, B.L. Sikorski, I. Gorczynska, M. Gora, M. Szkulmowski, D. Bukowska, J. Kaluzny, J.G. Fujimoto, A. Kowalczyk, Comparison of reflectivity maps and outer retinal topography in retinal disease by 3-D Fourier domain optical coherence tomography. Opt. Express. 17(5), 4189–4207 (2009)ADSCrossRefGoogle Scholar
  28. 28.
    K. Yi, M. Mujat, B.H. Park, W. Sun, J.W. Miller, J.M. Seddon, L.H. Young, J.F. de Boer, T.C. Chen, Spectral domain optical coherence tomography for quantitative evaluation of drusen and associated structural changes in non-neovascular age-related macular degeneration. Br. J. Ophthalmol. 93(2), 176–181 (2009)CrossRefGoogle Scholar
  29. 29.
    F.G. Schlanitz, C. Ahlers, S. Sacu, C. Schütze, M. Rodriguez, S. Schriefl, I. Golbaz, T. Spalek, G. Stock, U. Schmidt-Erfurth, Performance of drusen detection by spectral-domain optical coherence tomography. Invest. Ophthalmol. Vis. Sci. 51(12), 6715–6721 (2010)CrossRefGoogle Scholar
  30. 30.
    S. Bearelly, F.Y. Chau, A. Koreishi, S.S. Stinnett, J.A. Izatt, C.A. Toth, Spectral domain optical coherence tomography imaging of geographic atrophy margins. Ophthalmology 116(9), 1762–1769 (2009)CrossRefGoogle Scholar
  31. 31.
    M. Brar, I. Kozak, L. Cheng, D.U. Bartsch, R. Yuson, N. Nigam, S.F. Oster, F. Mojana, W.R. Freeman, Correlation between spectral-domain optical coherence tomography and fundus autofluorescence at the margins of geographic atrophy. Am. J. Ophthalmol. 148(3), 439–444 (2009)CrossRefGoogle Scholar
  32. 32.
    S.Y. Cohen, L. Dubois, S. Nghiem-Buffet, S. Ayrault, F. Fajnkuchen, B. Guiberteau, C. Delahaye-Mazza, G. Quentel, R. Tadayoni, Retinal pseudocysts in age-related geographic atrophy. Am. J. Ophthalmol. 150(2), 211.e1–217.e1 (2010)Google Scholar
  33. 33.
    M. Fleckenstein, S. Schmitz-Valckenberg, C. Adrion, I. Krämer, N. Eter, H.M. Helb, C.K. Brinkmann, P. Charbel Issa, U. Mansmann, F.G. Holz, Tracking progression with spectral-domain optical coherence tomography in geographic atrophy caused by age-related macular degeneration. Invest. Ophthalmol. Vis. Sci. 51(8), 3846–3852 (2010)CrossRefGoogle Scholar
  34. 34.
    H.M. Helb, P. Charbel Issa, M. Fleckenstein, S. Schmitz-Valckenberg, H.P. Scholl, C.H. Meyer, N. Eter, F.G. Holz, Clinical evaluation of simultaneous confocal scanning laser ophthalmoscopy imaging combined with high-resolution, spectral-domain optical coherence tomography. Acta Ophthalmol. 88(8), 842–849 (2010)CrossRefGoogle Scholar
  35. 35.
    B.J. Lujan, P.J. Rosenfeld, G. Gregori, F. Wang, R.W. Knighton, W.J. Feuer, C.A. Puliafito, Spectral domain optical coherence tomographic imaging of geographic atrophy. Ophthalmic Surg. Lasers Imaging 40(2), 96–101 (2009)CrossRefGoogle Scholar
  36. 36.
    S. Schmitz-Valckenberg, M. Fleckenstein, H.M. Helb, P. Charbel Issa, H.P. Scholl, F.G. Holz, In vivo imaging of foveal sparing in geographic atrophy secondary to age-related macular degeneration. Invest. Ophthalmol. Vis. Sci. 50(8), 3915–3921 (2009)CrossRefGoogle Scholar
  37. 37.
    U.E. Wolf-Schnurrbusch, V. Enzmann, C.K. Brinkmann, S. Wolf, Morphologic changes in patients with geographic atrophy assessed with a novel spectral OCT-SLO combination. Invest. Ophthalmol. Vis. Sci. 49(7), 3095–3099 (2008)CrossRefGoogle Scholar
  38. 38.
    Z. Yehoshua, P.J. Rosenfeld, G. Gregori, W.J. Feuer, M. Falcão, B.J. Lujan, C. Puliafito, Progression of geographic atrophy in age-related macular degeneration imaged with spectral domain optical coherence tomography. Ophthalmology 118(4), 679–686 (2011)CrossRefGoogle Scholar
  39. 39.
    M. Fleckenstein, U. Wolf-Schnurrbusch, S. Wolf, C. von Strachwitz, F.G. Holz, S. Schmitz-Valckenberg, [Imaging diagnostics of geographic atrophy]. Ophthalmologe 107(11), 1007–1015 (2010)CrossRefGoogle Scholar
  40. 40.
    M. Fleckenstein, S. Schmitz-Valckenberg, C. Martens, S. Kosanetzky, C.K. Brinkmann, G.S. Hageman, F.G. Holz, Fundus autofluorescence and spectral domain optical coherence tomography characteristics in a rapidly progressing form of geographic atrophy. Invest. Ophthalmol. Vis. Sci. 52(6):3761–3766 (2011)CrossRefGoogle Scholar
  41. 41.
    S. Schmitz-Valckenberg, M. Fleckenstein, A.P. Göbel, T.C. Hohman, F.G. Holz, Optical coherence tomography and autofluorescence findings in areas with geographic atrophy due to age-related macular degeneration. Invest. Ophthalmol. Vis. Sci. 52(1), 1–6 (2011)CrossRefGoogle Scholar
  42. 42.
    M. Boulton, P. Dayhaw-Barker, The role of the retinal pigment epithelium: topographical variation and ageing changes. Eye (Lond.) 15(Pt 3), 384–389 (2001)Google Scholar
  43. 43.
    F. Schütt, S. Davies, J. Kopitz, F.G. Holz, M.E. Boulton, Photodamage to human RPE cells by A2-E, a retinoid component of lipofuscin. Invest. Ophthalmol. Vis. Sci. 41(8), 2303–2308 (2000)Google Scholar
  44. 44.
    F.C. Delori, C.K. Dorey, G. Staurenghi, O. Arend, D.G. Goger, J.J. Weiter, In vivo fluorescence of the ocular fundus exhibits retinal pigment epithelium lipofuscin characteristics. Invest. Ophthalmol. Vis. Sci. 36(3), 718–729 (1995)Google Scholar
  45. 45.
    C. Bellmann, F.G. Holz, O. Schapp, H.E. Völcker, T.P. Otto, [Topography of fundus autofluorescence with a new confocal scanning laser ophthalmoscope] Ophthalmologe 94(6), 385–391 (1997)Google Scholar
  46. 46.
    U. Solbach, C. Keilhauer, H. Knabben, S. Wolf, Imaging of retinal autofluorescence in patients with age-related macular degeneration. Retina 17(5), 385–389 (1997)CrossRefGoogle Scholar
  47. 47.
    A. von Rückmann, F.W. Fitzke, A.C. Bird, Distribution of fundus autofluorescence with a scanning laser ophthalmoscope. Br. J. Ophthalmol. 79(5), 407–412 (1995)CrossRefGoogle Scholar
  48. 48.
    A. von Rückmann, F.W. Fitzke, A.C. Bird, Fundus autofluorescence in age-related macular disease imaged with a laser scanning ophthalmoscope. Invest. Ophthalmol. Vis. Sci. 38(2), 478–486 (1997)Google Scholar
  49. 49.
    A. Deckert, S. Schmitz-Valckenberg, J. Jorzik, A. Bindewald, F.G. Holz, U. Mansmann, Automated analysis of digital fundus autofluorescence images of geographic atrophy in advanced age-related macular degeneration using confocal scanning laser ophthalmoscopy (cSLO). BMC Ophthalmol. 5, 8 (2005)CrossRefGoogle Scholar
  50. 50.
    S. Schmitz-Valckenberg, J. Jorzik, K. Unnebrink, F.G. Holz, FAM Study Group, Analysis of digital scanning laser ophthalmoscopy fundus autofluorescence images of geographic atrophy in advanced age-related macular degeneration. Graefes Arch. Clin. Exp. Ophthalmol. 240(2), 73–78 (2002)Google Scholar
  51. 51.
    F.G. Holz, C. Bellman, S. Staudt, F. Schütt, H.E. Völcker, Fundus autofluorescence and development of geographic atrophy in age-related macular degeneration. Invest. Ophthalmol. Vis. Sci. 42(5), 1051–1056 (2001)Google Scholar
  52. 52.
    S. Schmitz-Valckenberg, A. Bindewald-Wittich, J. Dolar-Szczasny, J. Dreyhaupt, S. Wolf, H.P. Scholl, F.G. Holz, Fundus Autofluorescence in Age-Related Macular Degeneration Study Group, Correlation between the area of increased autofluorescence surrounding geographic atrophy and disease progression in patients with AMD. Invest. Ophthalmol. Vis. Sci. 47(6), 2648–2654 (2006)Google Scholar
  53. 53.
    F.G. Holz, A. Bindewald-Wittich, M. Fleckenstein, J. Dreyhaupt, H.P. Scholl, S. Schmitz-Valckenberg, FAM-Study Group, Progression of geographic atrophy and impact of fundus autofluorescence patterns in age-related macular degeneration. Am. J. Ophthalmol. 143(3), 463–472 (2007)Google Scholar
  54. 54.
    S. Schmitz-Valckenberg, G.J. Jaffe, M. Fleckenstein, P. Kozma, T. Hohman, F.G. Holz, GAP-Study Group. Lesion Characteristics and Progression in the Natural History of Geographic Atrophy (GAP)-Study. ARVO Meeting Abstracts April 11 2009; 50:3914Google Scholar
  55. 55.
    F.G. Holz, S. Schmitz-Valckenberg, M. Fleckenstein, G.J. Jaffe, T. Hohman. Lesion Characteristics and Progression in the Natural History of Geographic Atrophy (GAP)-Study. ARVO Meeting Abstracts April 11 2010; 51:94Google Scholar
  56. 56.
    B. Baumann, E. Gotzinger, M. Pircher, H. Sattmann, C. Schuutze, F. Schlanitz, C. Ahlers, U. Schmidt-Erfurth, C.K. Hitzenberger, Segmentation and quantification of retinal lesions in age-related macular degeneration using polarization-sensitive optical coherence tomography. J. Biomed. Opt. 15(6), 061704 (2010)Google Scholar
  57. 57.
    C. Schütze, C. Ahlers, S. Sacu, G. Mylonas, R. Sayegh, I. Golbaz, G. Matt, G. Stock, U. Schmidt-Erfurth, Performance of OCT segmentation procedures to assess morphology and extension in geographic atrophy. Acta Ophthalmol. 89(3), 235–240 (2011)CrossRefGoogle Scholar
  58. 58.
    E. Götzinger, M. Pircher, W. Geitzenauer, C. Ahlers, B. Baumann, S. Michels, U. Schmidt-Erfurth, C.K. Hitzenberger, Retinal pigment epithelium segmentation by polarization sensitive optical coherence tomography. Opt. Express. 16(21), 16410–16422 (2008)ADSCrossRefGoogle Scholar
  59. 59.
    C. Ahlers, E. Götzinger, M. Pircher, I. Golbaz, F. Prager, C. Schütze, B. Baumann, C.K. Hitzenberger, U. Schmidt-Erfurth, Imaging of the retinal pigment epithelium in age-related macular degeneration using polarization-sensitive optical coherence tomography. Invest. Ophthalmol. Vis. Sci. 51(4), 2149–2157 (2010)CrossRefGoogle Scholar
  60. 60.
    S. Michels, M. Pircher, W. Geitzenauer, C. Simader, E. Götzinger, O. Findl, U. Schmidt-Erfurth, C.K. Hitzenberger, Value of polarisation-sensitive optical coherence tomography in diseases affecting the retinal pigment epithelium. Br. J. Ophthalmol. 92(2), 204–209 (2008)CrossRefGoogle Scholar
  61. 61.
    E. Ergun, B. Hermann, M. Wirtitsch, A. Unterhuber, T.H. Ko, H. Sattmann, C. Scholda, J.G. Fujimoto, M. Stur, W. Drexler, Assessment of central visual function in Stargardt’s disease/fundus flavimaculatus with ultrahigh-resolution optical coherence tomography. Invest. Ophthalmol. Vis. Sci. 46(1), 310–316 (2005)CrossRefGoogle Scholar
  62. 62.
    P. Charbel Issa, E. Troeger, R. Finger, F.G. Holz, R. Wilke, H.P. Scholl, Structure-function correlation of the human central retina. PLoS One 5(9), e12864 (2010)Google Scholar
  63. 63.
    D. Iwama, A. Tsujikawa, Y. Ojima, H. Nakanishi, K. Yamashiro, H. Tamura, S. Ooto, N. Yoshimura, Relationship between retinal sensitivity and morphologic changes in eyes with confluent soft drusen. Clin. Exp. Ophthalmol. 38(5), 483–488 (2010)CrossRefGoogle Scholar
  64. 64.
    P. Godara, C. Siebe, J. Rha, M. Michaelides, J. Carroll, Assessing the photoreceptor mosaic over drusen using adaptive optics and SD-OCT. Ophthalmic Surg. Lasers Imaging 41(Suppl), S104–S108 (2010)CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  • Monika Fleckenstein
    • 1
  • Steffen Schmitz-Valckenberg
    • 1
  • Frank G. Holz
    • 2
  1. 1.Department of OphthalmologyUniversity of BonnBonnGermany
  2. 2.Department of OphthalmologyUniversity of BonnBonnGermany

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