Fundus Imaging of Age-Related Macular Degeneration

  • Allen Chiang
  • Andre J. Witkin
  • Carl D. Regillo
  • Allen C. Ho


Digital fundus cameras and confocal scanning laser ophthalmoscopes have increased the efficiency and resolution of fundus photography. Autofluorescent images yield information about the functional status of the outer retina and retinal pigment epithelium (RPE). Fluorescein angiography remains invaluable for studying retinal vascular anatomy and physiology in eyes with neovascular age-related macular degeneration (AMD). Optical coherence tomography (OCT) permits visualization of the vitreoretinal interface, retina, RPE, and choroid, though the implementation of enhanced-depth imaging, in exquisite detail. Indocyanine green (ICG) angiography is useful for differentiating neovascular AMD from masquerading conditions.


Optical Coherence Tomography Retinal Pigment Epithelium Fluorescein Angiography Polypoidal Choroidal Vasculopathy Central Serous Chorioretinopathy 
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.
    Spaide R. Fluorescein angiography. Philadelphia: W.B. Saunders Co.; 1999.Google Scholar
  2. 2.
    Tittl M, Slakter J, Spaide R, Sorenson J, Guyer DR. Indocyanine green videoangiography. Philadelphia: W.B. Saunders Co.; 1999.Google Scholar
  3. 3.
    Holz FG, Schmitz-Valckenberg S, Spaide R, Bird AC. Atlas of fundus autofluorescence imaging. Dordrecht: Springer; 2007.CrossRefGoogle Scholar
  4. 4.
    Cohen SY, Dubois L, Tadayoni R, Delahaye-Mazza C, Debibie C, Quentel G. Prevalence of reticular pseudodrusen in age-related macular degeneration with newly diagnosed choroidal neovascularisation. Br J Ophthalmol. 2007;91(3):354–9.PubMedCrossRefGoogle Scholar
  5. 5.
    Delori FC, Dorey CK, Staurenghi G, Arend O, Goger DG, Weiter JJ. In vivo fluorescence of the ocular fundus exhibits retinal pigment epithelium lipofuscin characteristics. Invest Ophthalmol Vis Sci. 1995;36(3):718–29.PubMedGoogle Scholar
  6. 6.
    von Ruckmann A, Fitzke FW, Bird AC. Distribution of fundus autofluorescence with a scanning laser ophthalmoscope. Br J Ophthalmol. 1995;79(5):407–12.CrossRefGoogle Scholar
  7. 7.
    Eldred GE, Katz ML. Fluorophores of the human retinal pigment epithelium: separation and spectral characterization. Exp Eye Res. 1988;47(1):71–86.PubMedCrossRefGoogle Scholar
  8. 8.
    Webb RH, Hughes GW, Delori FC. Confocal scanning laser ophthalmoscope. Appl Opt. 1987;26(8):1492–9.PubMedCrossRefGoogle Scholar
  9. 9.
    Liu J, Itagaki Y, Ben-Shabat S, Nakanishi K, Sparrow JR. The biosynthesis of A2E, a fluorophore of aging retina, involves the formation of the precursor, A2-PE, in the photoreceptor outer segment membrane. J Biol Chem. 2000;275(38):29354–60.PubMedCrossRefGoogle Scholar
  10. 10.
    Fishkin N, Jang YP, Itagaki Y, Sparrow JR, Nakanishi K. A2-rhodopsin: a new fluorophore isolated from photoreceptor outer segments. Org Biomol Chem. 2003;1(7):1101–5.PubMedCrossRefGoogle Scholar
  11. 11.
    Eldred GE. Lipofuscin fluorophore inhibits lysosomal protein degradation and may cause early stages of macular degeneration. Gerontology. 1995;41 Suppl 2:15–28.PubMedCrossRefGoogle Scholar
  12. 12.
    Gaillard ER, Atherton SJ, Eldred G, Dillon J. Photophysical studies on human retinal lipofuscin. Photochem Photobiol. 1995;61(5):448–53.PubMedCrossRefGoogle Scholar
  13. 13.
    Suter M, Reme C, Grimm C, Wenzel A, Jaattela M, Esser P, et al. Age-related macular degeneration. The lipofusion component N-retinyl-N-retinylidene ethanolamine detaches proapoptotic proteins from mitochondria and induces apoptosis in mammalian retinal pigment epithelial cells. J Biol Chem. 2000;275(50):39625–30.PubMedCrossRefGoogle Scholar
  14. 14.
    Sparrow JR, Nakanishi K, Parish CA. The lipofuscin fluorophore A2E mediates blue light-induced damage to retinal pigmented epithelial cells. Invest Ophthalmol Vis Sci. 2000;41(7):1981–9.PubMedGoogle Scholar
  15. 15.
    Dillon J, Wang Z, Avalle LB, Gaillard ER. The photochemical oxidation of A2E results in the formation of a 5,8,5′,8′-bis-furanoid oxide. Exp Eye Res. 2004;79(4):537–42.PubMedCrossRefGoogle Scholar
  16. 16.
    Avalle LB, Wang Z, Dillon JP, Gaillard ER. Observation of A2E oxidation products in human retinal lipofuscin. Exp Eye Res. 2004;78(4):895–8.PubMedCrossRefGoogle Scholar
  17. 17.
    Sparrow JR, Zhou J, Ben-Shabat S, Vollmer H, Itagaki Y, Nakanishi K. Involvement of oxidative mech­anisms in blue-light-induced damage to A2E-laden RPE. Invest Ophthalmol Vis Sci. 2002;43(4):1222–7.PubMedGoogle Scholar
  18. 18.
    Dorey CK, Wu G, Ebenstein D, Garsd A, Weiter JJ. Cell loss in the aging retina. Relationship to lipofuscin accumulation and macular degeneration. Invest Ophthalmol Vis Sci. 1989;30(8):1691–9.PubMedGoogle Scholar
  19. 19.
    Holz FG, Bellman C, Staudt S, Schutt F, Volcker HE. Fundus autofluorescence and development of geographic atrophy in age-related macular degeneration. Invest Ophthalmol Vis Sci. 2001;42(5):1051–6.PubMedGoogle Scholar
  20. 20.
    Wing GL, Blanchard GC, Weiter JJ. The topography and age relationship of lipofuscin concentration in the retinal pigment epithelium. Invest Ophthalmol Vis Sci. 1978;17(7):601–7.PubMedGoogle Scholar
  21. 21.
    Hee MR, Izatt JA, Swanson EA, Huang D, Schuman JS, Lin CP, et al. Optical coherence tomography of the human retina. Arch Ophthalmol. 1995;113(3):325–32.PubMedGoogle Scholar
  22. 22.
    Huang D, Swanson EA, Lin CP, Schuman JS, Stinson WG, Chang W, et al. Optical coherence tomography. Science. 1991;254(5035):1178–81.PubMedCrossRefGoogle Scholar
  23. 23.
    Drexler W, Sattmann H, Hermann B, Ko TH, Stur M, Unterhuber A, et al. Enhanced visualization of macular pathology with the use of ultrahigh-resolution optical coherence tomography. Arch Ophthalmol. 2003;121(5):695–706.PubMedCrossRefGoogle Scholar
  24. 24.
    Drexler W, Morgner U, Ghanta RK, Kartner FX, Schuman JS, Fujimoto JG. Ultrahigh-resolution ophthalmic optical coherence tomography. Nat Med. 2001;7(4):502–7.PubMedCrossRefGoogle Scholar
  25. 25.
    Wojtkowski M, Bajraszewski T, Gorczynska I, Targowski P, Kowalczyk A, Wasilewski W, et al. Ophthalmic imaging by spectral optical coherence tomography. Am J Ophthalmol. 2004;138(3):412–9.PubMedCrossRefGoogle Scholar
  26. 26.
    Anger EM, Unterhuber A, Hermann B, Sattmann H, Schubert C, Morgan JE, et al. Ultrahigh resolution optical coherence tomography of the monkey fovea. Identification of retinal sublayers by correlation with semi-thin histology sections. Exp Eye Res. 2004;78(6):1117–25.PubMedCrossRefGoogle Scholar
  27. 27.
    Gloesmann M, Hermann B, Schubert C, Sattmann H, Ahnelt PK, Drexler W. Histologic correlation of pig retina radial stratification with ultrahigh-resolution optical coherence tomography. Invest Ophthalmol Vis Sci. 2003;44(4):1696–703.PubMedCrossRefGoogle Scholar
  28. 28.
    Srinivasan VJ, Monson BK, Wojtkowski M, Bilonick RA, Gorczynska I, Chen R, et al. Charac­terization of outer retinal morphology with high-speed, ultrahigh-resolution optical coherence tomog­raphy. Invest Ophthalmol Vis Sci. 2008;49(4):1571–9.PubMedCrossRefGoogle Scholar
  29. 29.
    Spaide RF, Koizumi H, Pozzoni MC. Enhanced depth imaging spectral-domain optical coherence tomography. Am J Ophthalmol. 2008;146(4):496–500.PubMedCrossRefGoogle Scholar
  30. 30.
    Guyer DR, Yannuzzi LA, Slakter JS, Sorenson JA, Hanutsaha P, Spaide RF, et al. Classification of choroidal neovascularization by digital indocyanine green ­videoangiography. Ophthalmology. 1996;103(12):2054–60.PubMedGoogle Scholar
  31. 31.
    Pawley JB, editor. Handbook of biological confocal microscopy. Berlin: Springer; 2006.Google Scholar
  32. 32.
    Desatnik H, Treister G, Alhalel A, Krupsky S, Moisseiev J. ICGA-guided laser photocoagulation of feeder vessels of choroidal neovascular membranes in age-related macular degeneration. Indocyanine green angiography. Retina. 2000;20(2):143–50.PubMedCrossRefGoogle Scholar
  33. 33.
    Fox IJ, Wood EH. Applications of dilution curves recorded from the right side of the heart or venous circulation with the aid of a new indicator dye. Proc Staff Meet Mayo Clin. 1957;32(19):541–50.PubMedGoogle Scholar
  34. 34.
    Kwiterovich KA, Maguire MG, Murphy RP, Schachat AP, Bressler NM, Bressler SB, et al. Frequency of adverse systemic reactions after fluorescein angiography. Results of a prospective study. Ophthalmology. 1991;98(7):1139–42.PubMedGoogle Scholar
  35. 35.
    Yannuzzi LA, Rohrer KT, Tindel LJ, Sobel RS, Costanza MA, Shields W, et al. Fluorescein angiography complication survey. Ophthalmology. 1986;93(5):611–7.PubMedGoogle Scholar
  36. 36.
    Hope-Ross M, Yannuzzi LA, Gragoudas ES, Guyer DR, Slakter JS, Sorenson JA, et al. Adverse reactions due to indocyanine green. Ophthalmology. 1994;101(3):529–33.PubMedGoogle Scholar
  37. 37.
    Obana A, Miki T, Hayashi K, Takeda M, Kawamura A, Mutoh T, et al. Survey of complications of indocyanine green angiography in Japan. Am J Ophthalmol. 1994;118(6):749–53.PubMedGoogle Scholar
  38. 38.
    Fineman MS, Maguire JI, Fineman SW, Benson WE. Safety of indocyanine green angiography during pregnancy: a survey of the retina, macula, and vitreous societies. Arch Ophthalmol. 2001;119(3):353–5.PubMedGoogle Scholar
  39. 39.
    Costa DL, Huang SJ, Orlock DA, Freund KB, Yannuzzi LA, Spaide RF, et al. Retinal-choroidal indocyanine green dye clearance and liver dysfunction. Retina. 2003;23(4):557–61.PubMedCrossRefGoogle Scholar
  40. 40.
    Zweifel SA, Spaide RF, Curcio CA, Malek G, Imamura Y. Reticular pseudodrusen are subretinal drusenoid deposits. Ophthalmology. 2010;117(2):303–12.e1.PubMedCrossRefGoogle Scholar
  41. 41.
    Pauleikhoff D, Zuels S, Sheraidah GS, Marshall J, Wessing A, Bird AC. Correlation between biochemical composition and fluorescein binding of deposits in Bruch’s membrane. Ophthalmology. 1992;99(10):1548–53.PubMedGoogle Scholar
  42. 42.
    Arnold JJ, Quaranta M, Soubrane G, Sarks SH, Coscas G. Indocyanine green angiography of drusen. Am J Ophthalmol. 1997;124(3):344–56.PubMedGoogle Scholar
  43. 43.
    Spaide RF, Curcio CA. Drusen characterization with multimodal imaging. Retina. 2010;30(9):1441–54.PubMedCrossRefGoogle Scholar
  44. 44.
    Spaide RF. Fundus autofluorescence and age-related macular degeneration. Ophthalmology. 2003;110(2):392–9.PubMedCrossRefGoogle Scholar
  45. 45.
    Ho J, Witkin AJ, Liu J, Chen Y, Fujimoto JG, Schuman JS, et al. Documentation of intraretinal retinal pigment epithelium migration via high-speed ultrahigh-resolution optical coherence tomography. Ophthalmology. 2011;118(4):687–93. Epub 2010 Nov 20.PubMedCrossRefGoogle Scholar
  46. 46.
    Holz FG, Bellmann C, Margaritidis M, Schutt F, Otto TP, Volcker HE. Patterns of increased in vivo fundus autofluorescence in the junctional zone of geographic atrophy of the retinal pigment epithelium associated with age-related macular degeneration. Graefes Arch Clin Exp Ophthalmol. 1999;237(2):145–52.PubMedCrossRefGoogle Scholar
  47. 47.
    Holz FG, Bellman C, Staudt S, et al. Fundus autofluorescence and development of geographic atrophy in age-related macular degeneration. Invest Ophthalmol Vis Sci. 2001;42:1051–6.PubMedGoogle Scholar
  48. 48.
    Bearelly S, Chau FY, Koreishi A, Stinnett SS, Izatt JA, Toth CA. Spectral domain optical coherence tomography imaging of geographic atrophy margins. Ophthalmology. 2009;116(9):1762–9.PubMedCrossRefGoogle Scholar
  49. 49.
    Cohen SY, Dubois L, Nghiem-Buffet S, et al. Retinal pseudocysts in age-related geographic atrophy. Am J Ophthalmol. 2010;150(2):211–7. e1.PubMedCrossRefGoogle Scholar
  50. 50.
    Klein ML, Wilson DJ. Clinicopathologic correlation of choroidal and retinal neovascular lesions in age-related macular degeneration. Am J Ophthalmol. 2011;151(1):161–9.PubMedCrossRefGoogle Scholar
  51. 51.
    Subfoveal neovascular lesions in age-related macular degeneration. Guidelines for evaluation and treatment in the macular photocoagulation study. Macular Photocoagulation Study Group. Arch Ophthalmol. 1991 Sep;109(9):1242–57.Google Scholar
  52. 52.
    Solomon SD, Bressler SB, Hawkins BS, Marsh MJ, Bressler NM. Guidelines for interpreting retinal photographs and coding findings in the Submacular Surgery Trials (SST): SST report no. 8. Retina. 2005;25(3):253–68.PubMedCrossRefGoogle Scholar
  53. 53.
    Barbazetto I, Burdan A, Bressler NM, Bressler SB, Haynes L, Kapetanios AD, et al. Photodynamic therapy of subfoveal choroidal neovascularization with verteporfin: fluorescein angiographic guidelines for evaluation and treatment – TAP and VIP report No. 2. Arch Ophthalmol. 2003;121(9):1253–68.PubMedCrossRefGoogle Scholar
  54. 54.
    Coscas F, Coscas G, Souied E, Tick S, Soubrane G. Optical coherence tomography identification of occult choroidal neovascularization in age-related macular degeneration. Am J Ophthalmol. 2007;144(4):592–9.PubMedCrossRefGoogle Scholar
  55. 55.
    Yannuzzi LA, Negrao S, Iida T, Carvalho C, Rodriguez-Coleman H, Slakter J, et al. Retinal angiomatous proliferation in age-related macular degeneration. Retina. 2001;21(5):416–34.PubMedCrossRefGoogle Scholar
  56. 56.
    Massacesi AL, Sacchi L, Bergamini F, Bottoni F. The prevalence of retinal angiomatous proliferation in age-related macular degeneration with occult choroidal neovascularization. Graefes Arch Clin Exp Ophthalmol. 2008;246(1):89–92.PubMedCrossRefGoogle Scholar
  57. 57.
    Hemeida TS, Keane PA, Dustin L, Sadda SR, Fawzi AA. Long-term visual and anatomical outcomes following anti-VEGF monotherapy for retinal angiomatous proliferation. Br J Ophthalmol. 2010;94(6):701–5.PubMedCrossRefGoogle Scholar
  58. 58.
    Bearelly S, Espinosa-Heidmann DG, Cousins SW. The role of dynamic indocyanine green angiography in the diagnosis and treatment of retinal angiomatous proliferation. Br J Ophthalmol. 2008;92(2):191–6.PubMedCrossRefGoogle Scholar
  59. 59.
    Imamura Y, Engelbert M, Iida T, Freund KB, Yannuzzi LA. Polypoidal choroidal vasculopathy: a review. Surv Ophthalmol. 2010;55(6):501–15.PubMedCrossRefGoogle Scholar
  60. 60.
    Sho K, Takahashi K, Yamada H, Wada M, Nagai Y, Otsuji T, et al. Polypoidal choroidal vasculopathy: incidence, demographic features, and clinical characteristics. Arch Ophthalmol. 2003;121(10):1392–6.PubMedCrossRefGoogle Scholar
  61. 61.
    Okubo A, Ito M, Sameshima M, Uemura A, Sakamoto T. Pulsatile blood flow in the polypoidal choroidal vasculopathy. Ophthalmology. 2005;112(8):1436–41.PubMedCrossRefGoogle Scholar
  62. 62.
    Casswell AG, Kohen D, Bird AC. Retinal pigment epithelial detachments in the elderly: classification and outcome. Br J Ophthalmol. 1985;69(6):397–403.PubMedCrossRefGoogle Scholar
  63. 63.
    Spaide RF. Enhanced depth imaging optical coherence tomography of retinal pigment epithelial detachment in age-related macular degeneration. Am J Ophthalmol. 2009;147(4):644–52.PubMedCrossRefGoogle Scholar
  64. 64.
    Hoskin A, Bird AC, Sehmi K. Tears of detached retinal pigment epithelium. Br J Ophthalmol. 1981;65(6):417–22.PubMedCrossRefGoogle Scholar
  65. 65.
    Gass JD. Pathogenesis of tears of the retinal pigment epithelium. Br J Ophthalmol. 1984;68(8):513–9.PubMedCrossRefGoogle Scholar
  66. 66.
    Chiang A, Chang LK, Yu F, Sarraf D. Predictors of anti-VEGF-associated retinal pigment epithelial tear using FA and OCT analysis. Retina. 2008;28(9):1265–9.PubMedCrossRefGoogle Scholar
  67. 67.
    Chan CK, Meyer CH, Gross JG, Abraham P, Nuthi AS, Kokame GT, et al. Retinal pigment epithelial tears after intravitreal bevacizumab injection for neovascular age-related macular degeneration. Retina. 2007;27(5):541–51.PubMedCrossRefGoogle Scholar
  68. 68.
    Sarraf D, Reddy S, Chiang A, Yu F, Jain A. A new grading system for retinal pigment epithelial tears. Retina. 2010;30(7):1039–45.PubMedCrossRefGoogle Scholar
  69. 69.
    Peiretti E, Iranmanesh R, Lee JJ, Klancnik Jr JM, Sorenson JA, Yannuzzi LA. Repopulation of the retinal pigment epithelium after pigment epithelial rip. Retina. 2006;26(9):1097–9.PubMedCrossRefGoogle Scholar
  70. 70.
    Hartnett ME, Weiter JJ, Staurenghi G, Elsner AE. Deep retinal vascular anomalous complexes in advanced age-related macular degeneration. Ophthalmology. 1996;103(12):2042–53.PubMedGoogle Scholar
  71. 71.
    Gass JD, Agarwal A, Lavina AM, Tawansy KA. Focal inner retinal hemorrhages in patients with drusen: an early sign of occult choroidal neovascularization and chorioretinal anastomosis. Retina. 2003;23(6):741–51.PubMedCrossRefGoogle Scholar
  72. 72.
    Krypton laser photocoagulation for neovascular lesions of age-related macular degeneration. Results of a randomized clinical trial. Macular Photocoagulation Study Group. Arch Ophthalmol. 1990 Jun;108(6):816–24.Google Scholar
  73. 73.
    Laser photocoagulation of subfoveal neovascular lesions in age-related macular degeneration. Results of a randomized clinical trial. Macular Photocoagulation Study Group. Arch Ophthalmol. 1991 Sep;109(9):1220–31.Google Scholar
  74. 74.
    Schmidt-Erfurth U, Michels S, Barbazetto I, Laqua H. Photodynamic effects on choroidal neovascularization and physiological choroid. Invest Ophthalmol Vis Sci. 2002;43(3):830–41.PubMedGoogle Scholar
  75. 75.
    Schmidt-Erfurth U, Miller JW, Sickenberg M, Laqua H, Barbazetto I, Gragoudas ES, et al. Photodynamic therapy with verteporfin for choroidal neovascularization caused by age-related macular degeneration: results of retreatments in a phase 1 and 2 study. Arch Ophthalmol. 1999;117(9):1177–87.PubMedGoogle Scholar
  76. 76.
    Miller JW, Schmidt-Erfurth U, Sickenberg M, Pournaras CJ, Laqua H, Barbazetto I, et al. Photodynamic therapy with verteporfin for choroidal neovascularization caused by age-related macular degeneration: results of a single treatment in a phase 1 and 2 study. Arch Ophthalmol. 1999;117(9):1161–73.PubMedGoogle Scholar
  77. 77.
    Photodynamic therapy of subfoveal choroidal neovascularization in age-related macular degeneration with verteporfin: one-year results of 2 randomized clinical trials—TAP report. Treatment of age-related macular degeneration with photodynamic therapy (TAP) Study Group. Arch Ophthalmol. 1999 Oct;117(10):1329–45.Google Scholar
  78. 78.
    Sadda SR, Stoller G, Boyer DS, Blodi BA, Shapiro H, Ianchulev T. Anatomical benefit from ranibizumab treatment of predominantly classic neovascular age-related macular degeneration in the 2-year anchor study. Retina. 2010;30(9):1390–9.PubMedCrossRefGoogle Scholar
  79. 79.
    Spaide R. Ranibizumab according to need: a treatment for age-related macular degeneration. Am J Ophthalmol. 2007;143(4):679–80.PubMedCrossRefGoogle Scholar
  80. 80.
    Fung AE, Lalwani GA, Rosenfeld PJ, Dubovy SR, Michels S, Feuer WJ, et al. An optical coherence tomography-guided, variable dosing regimen with intravitreal ranibizumab (Lucentis) for neovascular age-related macular degeneration. Am J Ophthalmol. 2007;143(4):566–83.PubMedCrossRefGoogle Scholar
  81. 81.
    Boyer DS, Heier JS, Brown DM, Francom SF, Ianchulev T, Rubio RG. A Phase IIIb study to evaluate the safety of ranibizumab in subjects with neovascular age-related macular degeneration. Ophthalmology. 2009;116(9):1731–9.PubMedCrossRefGoogle Scholar
  82. 82.
    Brown DM, Regillo CD. Anti-VEGF agents in the treatment of neovascular age-related macular degeneration: applying clinical trial results to the treatment of everyday patients. Am J Ophthalmol. 2007;144(4):627–37.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Allen Chiang
    • 1
  • Andre J. Witkin
    • 2
  • Carl D. Regillo
    • 2
  • Allen C. Ho
    • 2
  1. 1.Retina Service, Wills Eye Institute/Mid-Atlantic RetinaPhiladelphiaUSA
  2. 2.Retina Service, Wills Eye Institute/Mid-Atlantic RetinaPhiladelphiaUSA

Personalised recommendations