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The Role of Drusen in Macular Degeneration and New Methods of Quantification

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Retinal Degenerations

Part of the book series: Ophthalmology Research ((OPHRES))

Abstract

Drusen are yellowish-white subretinal deposits that vary in size and composition. Often easily visible during slit lamp biomicroscopy, they tend to present in multiple morphologies that may vary throughout the lifetime of an eye. The mystery surrounding their relevance has been at the center of attempts to understand age-related macular degeneration (AMD) over the past several decades (1).

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References

  1. Smiddy WE, Fine SL. Prognosis of patients with bilateral macular drusen. Ophthalmology 1984;91:271–277.

    CAS  PubMed  Google Scholar 

  2. Sarks JP, Sarks SH, Killingsworth MC. Evolution of soft drusen in age-related macular degeneration. Eye 1994;8:269–283.

    PubMed  Google Scholar 

  3. Klein R, Davis MD, Magli YL, Segal P, Klein BE, Hubbard L. The Wisconsin age-related maculopathy grading system. Ophthalmology 1991;98:1128–1134.

    CAS  PubMed  Google Scholar 

  4. Gass J, Jallow S, Davis B. Adult Vitelliform macular detachment occuring in patients with basal laminar drusen. Am J Ophthalmol 1985;99:445–459.

    CAS  PubMed  Google Scholar 

  5. Russell S, Mullins R, Schnieder B, Hageman G. Location, substructure, and composition of basal laminar drusen compared with aging and aging associated with age-related macular degeneration. Am J Ophthalmol 2000;129:205–214.

    Article  CAS  PubMed  Google Scholar 

  6. Wang JJ, Foran S, Smith W, Mitchell P. Risk of age-related macular degeneration in eyes with macular drusen or hyperpigmentation: the Blue Mountain Eye Study cohort. Arch Ophthalmol 2003;121:658–663.

    Article  PubMed  Google Scholar 

  7. Klein R, Klein BE, Linton KL. Prevalence of age-related maculopathy: The Beaver Dam Eye Study. Ophthalmology 1992;99:933–943.

    CAS  PubMed  Google Scholar 

  8. Bressler SB, Maguire MG, Bressler NM, Fine SL. Relationship of drusen and abnormalities of the retinal pigment epithelium to the prognosis of neovascular macular degeneration. The Macular Photocoagulation Study group. Arch Ophthalmol 1990;108:1442–1447.

    CAS  PubMed  Google Scholar 

  9. Hageman GS, Luthert PJ, Victor Chong NH, Johnson LV, Anderson DH, Mullins RF. An integrated hypothesis that considers drusen as biomarkers of immune-mediated processes at the RPE-Bruch’s membrane interface in aging and age-related macular degeneration. Prog Retin Eye Res 2001;20:705–732.

    Article  CAS  PubMed  Google Scholar 

  10. Crabb J, Miyagi M, Gu X, et al. Drusen Proteome Analysis: an approach to the etiology of age-related macular degeneration. Proc Natl Acad Sci USA 2002;23:14,682–14,687.

    Article  CAS  Google Scholar 

  11. Evans K, Gregory C, Wijesuriya S, et al. Assessment of the phenotypic range seen in Doyne honeycomb retinal dystrophy. Arch Ophthalmol 1997;115:904–910.

    CAS  PubMed  Google Scholar 

  12. Narendran N, Guymer RH, Cain M, Baird PN. Analysis of the EFEMP1 gene in individuals and families with early onset drusen. Eye 2005;19:11–15.

    Article  CAS  PubMed  Google Scholar 

  13. D’Souza Y, Duvall-Young J, Mcleod D, Short C, Roberts I, Bonshek R. Ten year review of drusen like lesions in mesangiocapillary glomerulonephritis. Invest Ophthalmol Vis Sci 2000;4:S164.

    Google Scholar 

  14. Fishman G, Apple D, Goldberg M. Retinal and pigment epithelial alterations over choroidal malignant melanomas. Ann Ophthalmol 1975;7:487–489.

    CAS  PubMed  Google Scholar 

  15. Muller H. Anatomische beitrage zur ophthalmologie. Graefe Arch Ophthalmol 1856;2:1–69.

    Google Scholar 

  16. Donders F. Beitrage, zur pathologischen Anatomie des auges. Graefe’s Arch Clin Exp Ophthalmol 1854;1:106–118.

    Google Scholar 

  17. Ambati J, Anand A, Fernandez S, et al. An animal model of age-related macular degeneration in senescent Ccl-2-or Ccr-2-deficient mice. Nature Med 2003;9:1390–1397.

    Article  CAS  PubMed  Google Scholar 

  18. Wilson HL, Schwartz DM, Bhatt HRF, McCulloch CE, Duncan JL. Statin and aspirin therapy are associated with decreased rates of choroidal neovascularization among patients with age-related macular degeneration. Am J Ophthalmol 2004;137:615–624.

    Article  CAS  PubMed  Google Scholar 

  19. Friedman E. Update of the vascular model of AMD. Br J Ophthalmol 2004;88:161–163.

    Article  CAS  PubMed  Google Scholar 

  20. Ibrahim M, Chain B, Katz D. The injured cell: the role of the dendritic cell system as a sentinel receptor pathway. Immunol Today 1995;16:181–186.

    Article  CAS  PubMed  Google Scholar 

  21. Berger JW, Fine SL, Maguire MG. Age related macular degeneration, first ed. St. Louis: Mosby, 1999;263-264.

    Google Scholar 

  22. Gass JD. Drusen and disciform macular detachment and degeneration. Arch Ophthalmol 1973;90:206–217.

    CAS  PubMed  Google Scholar 

  23. Gass J. Photocoagulation of macular lesions. Trans Am Acad Ophthalmol Otolaryngol 1971;75:580–608.

    CAS  PubMed  Google Scholar 

  24. Group MPS. Argon laser photocoagulation for neovascular maculopathy: five year results from randomized clinical trials. Arch Ophthalmol 1991;109:1109–1114.

    Google Scholar 

  25. Wetzig P. Photocoagulation of drusen-related aging macular degeneration by photocoagulation: a long term outcome. Trans Am Ophthalmol Soc 1994;136:276–290.

    Google Scholar 

  26. Figueroa MS, Regueras A, Bertrand J. Laser photocoagulation to treat macular soft drusen in age-related macular degeneration. Retina 1994;14:391–396.

    Article  CAS  PubMed  Google Scholar 

  27. Choroidal Neovascularization Prevention Trial Study Group. Choroidal neovascularization in the Choroidal Neovascularization Prevention Trial. Ophthalmology 1998;105:1364–1372.

    Article  Google Scholar 

  28. Owens SL, Bunce C, Brannon AJ, Xing W, et al. Prophylactic laser treatment hastens choroidal neovascularization in unilateral age-related maculopathy: Final results of the drusen laser study. Am J Ophthalmol 2006;141:276–281.

    Article  PubMed  Google Scholar 

  29. Age-Related Eye Disease Study Research Group. A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E, beta carotene, and zinc for age-related macular degeneration and vision loss: AREDS report no. 8. Arch Ophthalmol 2001;119:1417–1436.

    Google Scholar 

  30. Bressler NM, Bressler SB, Seddon JM, Gragoudas ES, Jacobson LP. Drusen characteristics in patients with exudative versus non-exudative age-related macular degeneration. Retina 1998;8:109–114.

    Article  Google Scholar 

  31. Holz FG, Wolfensberger TJ, Piguet B, et al. Bilateral macular drusen in age-related macular degeneration. Prognosis and risk factors. Ophthalmology 1994;101:1522–1528.

    CAS  PubMed  Google Scholar 

  32. Zarbin MA. Current concepts in the pathogenesis of age-related macular degeneration. Arch Ophthalmol 2004;122:598–614.

    Article  PubMed  Google Scholar 

  33. Little HL, Showman JM, Brown BW. A pilot randomized controlled study on the effect of laser photocoagulation of confluent soft macular drusen [see comments]. Ophthalmology 1997;104:623–631.

    CAS  PubMed  Google Scholar 

  34. Frennesson IC, Nilsson SE. Effects of argon (green) laser treatment of soft drusen in early age-related maculopathy: a 6 month prospective studs Br J Ophthalmol 1995; 79: 905–909

    Article  CAS  PubMed  Google Scholar 

  35. Bressler NM, Munoz B, Maguire MG, et al. Five-year incidence and disappearance of drusen and retinal pigment epithelial abnormalities. Waterman study. Arch Ophthalmol 1995;113:301–308.

    CAS  PubMed  Google Scholar 

  36. Bird AC, Bressler NM, Bressler SB, et al. An international classification and grading system for age-related maculopathy and age-related macular degeneration. The International ARM Epidemiological Study Group. Surv Ophthalmol 1995;39:367–374.

    Article  CAS  PubMed  Google Scholar 

  37. Bressler SB, Bressler NM, Seddon JM, Gragoudas ES, Jacobson LP. Interobserver and intraobserver reliability in the clinical classification of drusen. Retina 1988;8:102–108.

    CAS  PubMed  Google Scholar 

  38. Sparrow JR, Parish CA, Nashimoto M, Nakanishi K. A2E, a lipofuscin fluorophore, in human retinal pigmented epithelial cells in culture. Invest Ophthalmol Vis Sci 1999;40:2988–2995.

    CAS  PubMed  Google Scholar 

  39. Sparrow J, Fishkin N, Zhou J, et al. A2E, a byproduct of the visual cycle. Vision Res 2003;43:2983–2990.

    Article  CAS  PubMed  Google Scholar 

  40. Lois N, Owens SL, Coco R, Hopkins J, Fitzke FW, Bird AC. Fundus autofluorescence in patients with age-related macular degeneration and high risk of visual loss. Am J Ophthalmol 2002;133:341–349.

    Article  PubMed  Google Scholar 

  41. von Ruckmann A, Fitzke FW, Bird AC. Fundus autofluorescence in age-related macular disease imaged with a laser scanning ophthalmoscope. Invest Ophthalmol Vis Sci 1997; 38:478–486.

    Google Scholar 

  42. Busuioc M, Smith RT, Chan JK, Sparow J, Koniarek J, Nagasaki T. Drusen and autofluorescence co-localization in early and late age related macular degeneration. Invest Ophthalmol Vis Sci 2004;45:E–2961.

    Google Scholar 

  43. Kirkpatrick JN, Spencer T, Manivannan A, Sharp PF, Forrester JV. Quantitative image analysis of macular drusen from fundus photographs and scanning laser ophthalmoscope images. Eye 1995;9:48–55.

    PubMed  Google Scholar 

  44. Elsner AE, Burns SA, Weiter JJ, Delori FC. Infrared imaging of sub-retinal structures in the human ocular fundus. Vision Res 1996;36:191–205.

    Article  CAS  PubMed  Google Scholar 

  45. Beausencourt E, Remky A, Elsner AE, Hartnett ME, Trempe CL. Infrared scanning laser tomography of macular cysts. Ophthalmology 2000;107:375–385.

    Article  CAS  PubMed  Google Scholar 

  46. Kunze C, Elsner AE, Beausencourt E, Moraes L, Hartnett ME, Trempe CL. Spatial extent of pigment epithelial detachments in age-related macular degeneration. Ophthalmology 1999;106:1830–1840.

    Article  CAS  PubMed  Google Scholar 

  47. Miura M, Elsner AE, Beausencourt E, et al. Grading of infrared confocal scanning laser tomography and video displays of digitized color slides in exudative age-related macular degeneration. Retina 2002;22:300–308.

    Article  PubMed  Google Scholar 

  48. Zhang X, Hargitai J, Tammur J. Macular pigment and visual acuity in Stargardt macular dystrophy. Graefes Arch Clin Exp Ophthalmol 2002;240:802–809.

    PubMed  Google Scholar 

  49. Goldbaum MH, Kouznetsova V, Cote BL, Hart WE, Nelson M. Automated registration of digital ocular fundus images for comparison of lesions. Proc SPIE 1993;187:94–99.

    Article  Google Scholar 

  50. Hart WE, Goldbaum MH. Registering retinal images using automatically selected control point pairs. Image Processing, Proceedings. ICIP-94., IEEE International Conference. Nov. 1994;3:576–580.

    Article  Google Scholar 

  51. Brown LG. A survey of image registration techniques. ACM Computing Surveys 1992; 24:326–376.

    Article  Google Scholar 

  52. Can A, Shen H, Turner JN, Tanenbaum HL, Roysam B. Rapid automated tracing and feature extraction from retinal fundus images using direct exploratory algorithms. IEEE Trans Inf Technol Biomed 1999;3:125–138.

    Article  CAS  PubMed  Google Scholar 

  53. Can A, Stewart CV, Roysam B. Robust hierarchical algorithm for constructing a mosaic from images of the curved human retina. IEEE Computer Society Conference on Computer Vision and Pattern Recognition. Vol. 2, 23–25 June, 1999.

    Google Scholar 

  54. Can A, Stewart CV, Roysam B, Tanenbaum HL. A feature-based technique for joint, linear estimation of high-order image-to-mosaic transformations: application to mosaicing the curved human retina. IEEE Conference on Computer Vision and Pattern Recognition. June 2000; vol. 2:585–591.

    Google Scholar 

  55. Rivero ME, Bartsch DU, Otto T, Freeman WR. Automated scanning laser ophthalmoscope image montages of retinal diseases. Ophthalmology 1999;106:2296–2300.

    Article  CAS  PubMed  Google Scholar 

  56. Bogoni L. Extending dynamic range of monochrome and color images through fusion. 15th International Conference on Pattern Recognition. Sept. 2000; vol. 3:7–12.

    Google Scholar 

  57. Bogoni L, Hansen M, Burt P. Image enhancement using pattern-selective color image fusion. International Conference on Image Analysis and Processing. 27-29 Sept. 1999; pp. 44–49.

    Google Scholar 

  58. Burt PJ, Kolczynski RJ. Enhanced image capture through fusion. Fourth International Conference on Computer Vision. 11-14 May 1993; pp. 173–182.

    Google Scholar 

  59. Berger JW. Quantitative, spatio-temporal image analysis of fundus features in age-related macular degeneration. Proc SPIE (Ophthalmic Technologies) 1998;3246:48–53.

    Article  Google Scholar 

  60. Sunness JS, Bressler NM, Tian Y, Alexander J, Applegate CA. Measuring geographic atrophy in advanced age-related macular degeneration. Invest Ophthalmol Vis Sci 1999;40:1761–1769.

    CAS  PubMed  Google Scholar 

  61. Shin DS, Javornik NB, Berger JW. Computer-assisted, interactive fundus image processing for macular drusen quantitation [see comments]. Ophthalmology 1999;106:1119–1125.

    Article  CAS  PubMed  Google Scholar 

  62. Sebag M, Peli E, Lahav M. Image analysis of changes in drusen area. Acta Ophthalmologica 1991;69:603–610.

    CAS  PubMed  Google Scholar 

  63. Morgan WH, Cooper RL, Constable IJ, Eikelboom RH. Automated extraction and quantification of macular drusen from fundal photographs. Aust New Zealand J Ophthalmol 1994;22:7–12.

    CAS  Google Scholar 

  64. Peli E, Lahav M. Drusen measurement from fundus photographs using computer image analysis. Ophthalmology 1986;93:1575–1580.

    CAS  PubMed  Google Scholar 

  65. Rapantzikos K, Zervakis M, Balas K. Detection and segmentation of drusen deposits on human retina: Potential in the diagnosis of age-related macular degeneration. Med Image Anal 2003;7:95–108.

    Article  CAS  PubMed  Google Scholar 

  66. Sbeh B, Cohen LD, Mimoun G, Coscas G. A new approach of geodesic reconstruction for drusen segmentation in eye fundus images. IEEE Trans Med Imaging 2001;20(12):1321–1333.

    Article  PubMed  Google Scholar 

  67. Goldbaum MH, Katz NP, Nelson MR, Haff LR. The discrimination of similarly colored objects in computer images of the ocular fundus. Invest Ophthalmol Vis Sci 1990; 31:617–623.

    CAS  PubMed  Google Scholar 

  68. Sivagnanavel V, Smith RT, Chong NHV. Digital drusen quantification in high-risk patients with age related maculopathy. Invest Ophthalmol Vis Sci 2003;44:E–5002.

    Google Scholar 

  69. Smith RT, Chan JK, Nagasaki T, et al. Automated detection of macular drusen using geometric background leveling and threshold selection. Arch Ophthalmol 2005;123:200–207.

    Article  PubMed  Google Scholar 

  70. Lee MS, Shin DS, Berger JW. Grading, image analysis, and stereopsis of digitally compressed fundus images. Retina 2000;20:275–281.

    Article  CAS  PubMed  Google Scholar 

  71. Scholl HPN, Dandekar SS, Peto T, et al. What is lost by digitizing stereoscopic fundus color slides for macular grading in age-related maculopathy and degeneration? Ophthalmology 2004;111:125–132.

    Article  PubMed  Google Scholar 

  72. Sajda P, Spence C, Pearson J. Learning contextual relationships in mammograms using a hierarchical pyramid neural network. IEEE Trans Med Imaging 2002;21:239–250.

    Article  PubMed  Google Scholar 

  73. Sajda P, Du S, Parra L, Stoyanova R, Brown T. Recovery of constituent spectra in 3D chemical shift imaging using non-negative matrix factorization. Proc. 4th International Symposium on Independent Component Analysis and Blind Signal Separation. April, 2003, Nara, Japan, pp. 71–76.

    Google Scholar 

  74. Sajda P, Du S, Brown TR, et al. (2004). Non-negative matrix factorization for rapid recovery of constituent spectra in magnetic resonance chemical shift imaging of the brain. IEEE Trans Med Imaging 2004;23(12):1453–1465.

    Article  Google Scholar 

  75. Smith RT, Nagasaki T, Sparrow JR, Barbazetto I, Klaver CCW, Chan JK. A method of drusen measurement based on the geometry of fundus reflectance. BioMed Eng Online 2003;2:10.

    Article  CAS  PubMed  Google Scholar 

  76. Smith RT, Nagasaki T, Sparrow JR, Barbazetto I, Koniarek JP, Bickmann LJ. Patterns of reflectance in macular images: representation by a mathematical model. J Biomed Optics 2004;9:162–172.

    Article  Google Scholar 

  77. Smith RT, Koniarek JP, Chan JK, Nagasaki T, Sparow J, Langton K. Autofluorescence characteristics of normal foveas and reconstruction of foveal autofluorescence from limited data subsets. Invest Ophthalmol Vis Sci 2005;46(8):2940–2946.

    Article  PubMed  Google Scholar 

  78. Smith RT, Chan JK, Nagasaki T, Sparrow JR, Barbazetto I. A method of drusen measurement based on reconstruction of fundus reflectance. B J Opthalmol 2005;89:87–91.

    Article  CAS  Google Scholar 

  79. Otsu N. A threshold selection method from gray-level histograms. IEEE Trans Syst Man Cybern 1979;9:62–66.

    Article  Google Scholar 

  80. Schweitzer D, Hammer M, Schweitzer F, et al. In-vivo measurement of time-resolved autofluorescence at the human fundus. J Biomed Optics 2004;9:1214–1222.

    Article  Google Scholar 

  81. Carano R, Lynch JA, Redei J, et al. Multispectral analysis of bone lesions in the hands of patients with rheumatoid arthritis. Magn Reson Imaging 2004;22:505–514.

    Article  PubMed  Google Scholar 

  82. Ward J, Magnotta V, Andreason NC, Ooteman W, Nopoulos P, Pierson R. Color enhancement of multispectral MR images: improving the visualization of subcortical structures. J Comput Assist Tomogr 2001;25:942–949.

    Article  CAS  PubMed  Google Scholar 

  83. Akita K, Kuga H. A computer method of understanding ocular fundus images. Pattern Recognit 1992;15:431–433.

    Article  Google Scholar 

  84. Undrill P. Towards the automatic interpretation of retinal images. Br J Opthalmol 1996; 80:937–938.

    Article  CAS  Google Scholar 

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Smith, R.T., Ahmad, U.F. (2007). The Role of Drusen in Macular Degeneration and New Methods of Quantification. In: Tombran-Tink, J., Barnstable, C.J. (eds) Retinal Degenerations. Ophthalmology Research. Humana Press. https://doi.org/10.1007/978-1-59745-186-4_11

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