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Age-Related Macular Degeneration

Epidemiology and Optimal Treatment

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Abstract

Age-related macular degeneration (AMD) is a common macular disease affecting elderly people in the Western world. It is characterised by the appearance of drusen in the macula, accompanied by choroidal neovascularisation (CNV) or geographic atrophy. The disease is more common in Caucasian individuals than in pigmented races. In predominantly Caucasian populations, the age-standardised prevalence of AMD in at least one eye is 7760 cases per million. The age-standardised cumulated 1-year incidence of AMD in at least one eye is 1051 cases per million individuals. AMD is the most important single cause of blindness among Caucasian individuals in developed countries. Blindness resulting from AMD rarely occurs before age 70, and most cases occur after age 80. The age-standardised 1-year incidence of legal blindness resulting from AMD is 212 cases per million. Two-thirds of AMD cases have CNV (exudative cases); the remainder has only geographic atrophy. In cross-sectional population-based studies about 45% of eyes with AMD have visual acuity reduced to 20/200 or worse. This is true both for exudative AMD and pure geographic atrophy. Age and genetic predisposition are known risk factors for AMD. Smoking is probably also a risk factor.

Preventive strategies using macular laser photocoagulation are under investigation, but their efficacy in preventing visual loss is as yet unproven. There is no treatment with proven efficacy for geographic atrophy. Optimal treatment for exudative AMD requires a fluorescein angiographic study and a physician capable of interpreting it. For CNV not involving the foveal centre, the only evidence-based treatment is laser photocoagulation. For AMD cases with subfoveal CNV, good visual acuity, and predominantly classic fluorescence pattern on fluorescein angiography, photodynamic therapy with verteporfin is the treatment of choice. Photodynamic therapy is also effective in eyes with pure occult CNV and evidence of recent disease progression. For new subfoveal CNV with poor vision and recurrent CNV, laser photocoagulation can be considered.

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References

  1. Treatment of Age-related Macular Degeneration with Photodynamic Therapy (TAP) Study Group. Photodynamic therapy of subfoveal choroidal neovascularization in age-related macular degeneration with verteporfin: two-year results of 2 randomized clinical trials-TAP report 2. Arch Ophthalmol 2001; 119(2): 198–207

    Google Scholar 

  2. Verteporfin in Photodynamic Therapy Study Group. Verteporfin therapy of subfoveal choroidal neovascularization in age-related macular degeneration: two-year results of a randomized clinical trial including lesions with occult with no classic choroidal neovascularization-verteporfin in photodynamic therapy report 2. Am J Ophthalmol 2001; 131(5): 541–60

    Google Scholar 

  3. Hyman L. Epidemiology of AMD. In: Hampton GR, Nelsen PT, editors. Age related macular degeneration. Principles and practice. New York: Raven Press, 1992: 1–36

    Google Scholar 

  4. Leibowitz HM, Krueger DE, Maunder LR, et al. The Framingham Eye Study monograph: an ophthalmological and epidemiological study of cataract, glaucoma, diabetic retinopathy, macular degeneration, and visual acuity in a general population of 2631 adults, 1973–1975. Surv Ophthalmol 1980; 24 Suppl.: 335–610

    PubMed  CAS  Google Scholar 

  5. Vinding T. Age-related macular degeneration. An epidemiological study of 1000 elderly individuals. With reference to prevalence, funduscopic findings, visual impairment and risk factors. Acta Ophthalmol Scand Suppl 1995; (217): 1–32

    Google Scholar 

  6. 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(5): 367–74

    PubMed  CAS  Google Scholar 

  7. Klein R, Davis MD, Magli YL, et al. The Wisconsin age-related maculopathy grading system. Ophthalmology 1991; 98(7): 1128–34

    PubMed  CAS  Google Scholar 

  8. Mitchell P, Smith W, Attebo K, et al. Prevalence of age-related maculopathy in Australia. The Blue Mountains Eye Study. Ophthalmology 1995; 102(10): 1450–60

    PubMed  CAS  Google Scholar 

  9. Wang JJ, Mitchell P, Smith W, et al. Bilateral involvement by age related maculopathy lesions in a population. Br J Ophthalmol 1998; 82(7): 743–7

    PubMed  CAS  Google Scholar 

  10. Klein R, Klein BE, Linton KL. Prevalence of age-related maculopathy. The Beaver Dam Eye Study. Ophthalmology 1992; 99(6): 933–43

    PubMed  CAS  Google Scholar 

  11. Vingerling JR, Dielemans I, Hofman A, et al. The prevalence of age-related maculopathy in the Rotterdam Study. Ophthalmology 1995; 102(2): 205–10

    PubMed  CAS  Google Scholar 

  12. Pieramici DJ, Bressler SB. Fluorescein angiography. In: Berger JW, Fine SL, Maguire MG, editors. Age-related macular degeneration. St. Louis (MO): Mosby, 1999: 219–36

    Google Scholar 

  13. Bressler NM, Silva JC, Bressler SB, et al. Clinicopathologic correlation of drusen and retinal pigment epithelial abnormalities in age-related macular degeneration. Retina 1994; 14(2): 130–42

    PubMed  CAS  Google Scholar 

  14. Sarks JP, Sarks SH, Killingsworth MC. Evolution of soft drusen in age-related macular degeneration. Eye 1994; 8(Pt 3): 269–83

    PubMed  Google Scholar 

  15. Wang JJ, Mitchell P, Smith W. Refractive error and age-related maculopathy: the Blue Mountains Eye Study. Invest Ophthalmol Vis Sci 1998; 39(11): 2167–71

    PubMed  CAS  Google Scholar 

  16. Green WR, Harlan Jr JB. Histopathologic features. In: Berger JW, Fine SL, Maguire MG, editors. Age-related macular degeneration. St. Louis (MO): Mosby, 1999: 81–154

    Google Scholar 

  17. Sarks JP, Sarks SH, Killingsworth MC. Evolution of geographic atrophy of the retinal pigment epithelium. Eye 1988; 2(Pt 5): 552–77

    PubMed  Google Scholar 

  18. Macular Photocoagulation Study Group. Subfoveal neovascular lesions in age-related macular degeneration. Guidelines for evaluation and treatment in the macular photocoagulation study. Arch Ophthalmol 1991; 109(9): 1242–57

    Google Scholar 

  19. Freund KB, Yannuzzi LA, Sorenson JA. Age-related macular degeneration and choroidal neovascularization. Am J Ophthalmol 1993; 115(6): 786–91

    PubMed  CAS  Google Scholar 

  20. Moisseiev J, Alhalel A, Masuri R, et al. The impact of the macular photocoagulation study results on the treatment of exudative age-related macular degeneration. Arch Ophthalmol 1995; 113(2): 185–9

    PubMed  CAS  Google Scholar 

  21. Margherio RR, Margherio AR, DeSantis ME. Laser treatments with verteporfin therapy and its potential impact on retinal practices. Retina 2000; 20(4): 325–30

    PubMed  CAS  Google Scholar 

  22. Lafaut BA, Bartz-Schmidt KU, Vanden Broecke C, et al. Clinicopathological correlation in exudative age related macular degeneration: histological differentiation between classic and occult choroidal neovascularisation. Br J Ophthalmol 2000; 84(3): 239–43

    PubMed  CAS  Google Scholar 

  23. Grossniklaus HE, Gass JD. Clinicopathologic correlations of surgically excised type 1 and type 2 submacular choroidal neovascular membranes. Am J Ophthalmol 1998; 126(1): 59–69

    PubMed  CAS  Google Scholar 

  24. la Cour M, Nielsen NV, Larsen M, et al. Aldersrelateret makuladegeneration en folkesygdom. Ugeskr Laeger 2001; 163(43): 6396–400

    PubMed  Google Scholar 

  25. Kwun RC, Guyer DR. Indocyanine green angiography. In: Berger JW, Fine SL, Maguire MG, editors. Age-related macular degeneration. St. Louis (MO): Mosby, 1999: 237–47

    Google Scholar 

  26. Yannuzzi LA, Hope-Ross M, Slakter JS, et al. Analysis of vascularized pigment epithelial detachments using indocyanine green videoangiography. Retina 1994; 14(2): 99–113

    PubMed  CAS  Google Scholar 

  27. Chang TS, Freund KB, de la Cruz Z, et al. Clinicopathologic correlation of choroidal neovascularization demonstrated by indocyanine green angiography in a patient with retention of good vision for almost four years. Retina 1994; 14(2): 114–24

    PubMed  CAS  Google Scholar 

  28. Kuhn D, Meunier I, Soubrane G, et al. Imaging of chorioretinal anastomoses in vascularized retinal pigment epithelium detachments. Arch Ophthalmol 1995; 113(11): 1392–8

    PubMed  CAS  Google Scholar 

  29. Slakter JS, Yannuzzi LA, Schneider U, et al. Retinal choroidal anastomoses and occult choroidal neovascularization in age-related macular degeneration. Ophthalmology 2000; 107(4): 742–53

    PubMed  CAS  Google Scholar 

  30. Yannuzzi LA, Ciardella A, Spaide RF, et al. The expanding clinical spectrum of idiopathic polypoidal choroidal vasculopathy. Arch Ophthalmol 1997; 115(4): 478–85

    PubMed  CAS  Google Scholar 

  31. Ahuja RM, Stanga PE, Vingerling JR, et al. Polypoidal choroidal vasculopathy in exudative and haemorrhagic pigment epithelial detachments. Br J Ophthalmol 2000; 84(5): 479–84

    PubMed  CAS  Google Scholar 

  32. Yannuzzi LA, Wong DW, Sforzolini BS, et al. Polypoidal choroidal vasculopathy and neovascularized age-related macular degeneration. Arch Ophthalmol 1999; 117(11): 1503–10

    PubMed  CAS  Google Scholar 

  33. Wang Q, Chappell RJ, Klein R, et al. Pattern of age-related maculopathy in the macular area. The Beaver Dam Eye Study. Invest Ophthalmol Vis Sci 1996; 37(11): 2234–42

    PubMed  CAS  Google Scholar 

  34. Klein R, Clegg L, Cooper LS, et al. Prevalence of age-related maculopathy in the Atherosclerosis Risk in Communities Study. Arch Ophthalmol 1999; 117(9): 1203–10

    PubMed  CAS  Google Scholar 

  35. Klein R, Klein BE, Jensen SC, et al. Age-related maculopathy in a multiracial United States population: the National Health and Nutrition Examination Survey III. Ophthalmology 1999; 106(6): 1056–65

    PubMed  CAS  Google Scholar 

  36. Cruickshanks KJ, Hamman RF, Klein R, et al. The prevalence of age-related maculopathy by geographic region and ethnicity. The Colorado-Wisconsin Study of Age-Related Maculopathy. Arch Ophthalmol 1997; 115(2): 242–50

    PubMed  CAS  Google Scholar 

  37. Uyama M, Takahashi K, Ida N, et al. The second eye of Japanese patients with unilateral exudative age related macular degeneration. Br J Ophthalmol 2000; 84(9): 1018–23

    PubMed  CAS  Google Scholar 

  38. Yuzawa M, Tamakoshi A, Kawamura T, et al. Report on the nationwide epidemiological survey of exudative age-related macular degeneration in Japan. Int Ophthalmol 1997; 21(1): 1–3

    PubMed  CAS  Google Scholar 

  39. Schachat AP, Hyman L, Leske MC, et al. Features of age-related macular degeneration in a black population. The Barbados Eye Study Group. Arch Ophthalmol 1995; 113(6): 728–35

    PubMed  CAS  Google Scholar 

  40. Friedman DS, Katz J, Bressler NM, et al. Racial differences in the prevalence of age-related macular degeneration: the Baltimore Eye Survey. Ophthalmology 1999; 106(6): 1049–55

    PubMed  CAS  Google Scholar 

  41. Rosenberg T. Prevalence and causes of blindness in Greenland. Arctic Med Res 1987; 46(1): 13–7

    PubMed  CAS  Google Scholar 

  42. Rosenberg T. Prevalence of blindness caused by senile macular degeneration in Greenland. Arctic Med Res 1987; 46(2): 64–70

    PubMed  CAS  Google Scholar 

  43. Ostenfeld-Akerblom A. Age-related macular degeneration in Inuit. Acta Ophthalmol Scand 1999; 77(1): 76–8

    PubMed  CAS  Google Scholar 

  44. Bressler NM, Bressler SB, West SK, et al. The grading and prevalence of macular degeneration in Chesapeake Bay watermen. Arch Ophthalmol 1989; 107(6): 847–52

    PubMed  CAS  Google Scholar 

  45. VanNewkirk MR, Nanjan MB, Wang JJ, et al. The prevalence of age-related maculopathy: the visual impairment project. Ophthalmology 2000; 107(8): 1593–600

    PubMed  CAS  Google Scholar 

  46. Delcourt C, Diaz JL, Ponton-Sanchez A, et al. Smoking and age-related macular degeneration. The POLA Study. Pathologies Oculaires Liees a l’Age. Arch Ophthalmol 1998; 116(8): 1031–5

    PubMed  CAS  Google Scholar 

  47. EUROSTAT. Demographic statistics, 1960–99. Luxembourg: EUROSTAT, 1999

    Google Scholar 

  48. Danmarks Statistik. Statbank Denmark [online]. Available from URL: http://www.statistikbank.dk/ [Accessed 2001 Jan 24]

  49. Smith W, Assink J, Klein R, et al. Risk factors for age-related macular degeneration: Pooled findings from three continents. Ophthalmology 2001; 108(4): 697–704

    PubMed  CAS  Google Scholar 

  50. Laatikainen L, Hirvela H. Prevalence and visual consequences of macular changes in a population aged 70 years and older. Acta Ophthalmol Scand 1995; 73(2): 105–10

    PubMed  CAS  Google Scholar 

  51. 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(3): 301–8

    PubMed  CAS  Google Scholar 

  52. Klein R, Klein BE, Jensen SC, et al. The five-year incidence and progression of age-related maculopathy: the Beaver Dam Eye Study. Ophthalmology 1997; 104(1): 7–21

    PubMed  CAS  Google Scholar 

  53. Attebo K, Mitchell P, Smith W. Visual acuity and the causes of visual loss in Australia. The Blue Mountains Eye Study. Ophthalmology 1996; 103(3): 357–64

    PubMed  CAS  Google Scholar 

  54. Klein R, Wang Q, Klein BE, et al. The relationship of age-related maculopathy, cataract, and glaucoma to visual acuity. Invest Ophthalmol Vis Sci 1995; 36(1): 182–91

    PubMed  CAS  Google Scholar 

  55. Rahmani B, Tielsch JM, Katz J, et al. The cause-specific prevalence of visual impairment in an urban population. The Baltimore Eye Survey. Ophthalmology 1996; 103(11): 1721–6

    PubMed  CAS  Google Scholar 

  56. Munoz B, West SK, Rubin GS, et al. Causes of blindness and visual impairment in a population of older Americans: the Salisbury Eye Evaluation Study. Arch Ophthalmol 2000; 118(6): 819–25

    PubMed  CAS  Google Scholar 

  57. Vinding T. Visual impairment of age-related macular degeneration. An epidemiological study of 1000 aged individuals. Acta Ophthalmol (Copenh) 1990; 68(2): 162–7

    CAS  Google Scholar 

  58. Ferris III FL, Fine SL, Hyman L. Age-related macular degeneration and blindness due to neovascular maculopathy. Arch Ophthalmol 1984; 102(11): 1640–2

    PubMed  Google Scholar 

  59. Hyman LG, Lilienfeld AM, Ferris III FL, et al. Senile macular degeneration: a case-control study. Am J Epidemiol 1983; 118(2): 213–27

    PubMed  CAS  Google Scholar 

  60. Sunness JS, Rubin GS, Applegate CA, et al. Visual function abnormalities and prognosis in eyes with age-related geographic atrophy of the macula and good visual acuity. Ophthalmology 1997; 104(10): 1677–91

    PubMed  CAS  Google Scholar 

  61. Holz FG, Wolfensberger TJ, Piguet B, et al. Bilateral macular drusen in age-related macular degeneration. Prognosis and risk factors. Ophthalmology 1994; 101(9): 1522–8

    PubMed  CAS  Google Scholar 

  62. Macular Photocoagulation Study Group. Five-year follow-up of fellow eyes of patients with age-related macular degeneration and unilateral extrafoveal choroidal neovascularization. Arch Ophthalmol 1993; 111(9): 1189–99

    Google Scholar 

  63. Krumpaszky HG, Ludtke R, Mickler A, et al. Blindness incidence in Germany. A population-based study from Wurttemberg-Hohenzollern. Ophthalmologica 1999; 213(3): 176–82

    PubMed  CAS  Google Scholar 

  64. Rosenberg T, Klie F. The incidence of registered blindness caused by age-related macular degeneration. Acta Ophthalmol Scand 1996; 74(4): 399–402

    PubMed  CAS  Google Scholar 

  65. Sparrow JM, Dickinson AJ, Duke AM, et al. Seven year follow-up of age-related maculopathy in an elderly British population. Eye 1997; 11(Pt 3): 315–24

    PubMed  Google Scholar 

  66. Sarks SH, Arnold JJ, Killingsworth MC, et al. Early drusen formation in the normal and aging eye and their relation to age related maculopathy: a clinicopathological study. Br J Ophthalmol 1999; 83(3): 358–68

    PubMed  CAS  Google Scholar 

  67. Smiddy WE, Fine SL. Prognosis of patients with bilateral macular drusen. Ophthalmology 1984; 91(3): 271–7

    PubMed  CAS  Google Scholar 

  68. The Choroidal Neovascularization Prevention Trial Research Group. Laser treatment in eyes with large drusen. Short-term effects seen in a pilot randomized clinical trial. Ophthalmology 1998; 105(1): 11–23

    Google Scholar 

  69. The Choroidal Neovascularization Prevention Trial Research Group. Choroidal neovascularization in the Choroidal Neovascularization Prevention Trial. Ophthalmology 1998; 105(8): 1364–72

    Google Scholar 

  70. Macular Photocoagulation Study Group. Risk factors for choroidal neovascularization in the second eye of patients with juxtafoveal or subfoveal choroidal neovascularization secondary to age-related macular degeneration. Arch Ophthalmol 1997; 115(6): 741–7

    Google Scholar 

  71. Macular Photocoagulation Study Group. Argon laser photocoagulation for neovascular maculopathy. Five-year results from randomized clinical trials. Arch Ophthalmol 1991; 109(8): 1109–14

    Google Scholar 

  72. Ferris III FL, Kassoff A, Bailey I. New visual acuity charts for clinical research. Am J Ophthalmol 1982; 94: 91–6

    PubMed  Google Scholar 

  73. Macular Photocoagulation Study Group. Laser photocoagulation of subfoveal neovascular lesions of age-related macular degeneration. Updated findings from two clinical trials. Arch Ophthalmol 1993; 111(9): 1200–9

    Google Scholar 

  74. Treatment of Age-related Macular Degeneration with Photodynamic Therapy (TAP) Study Group. Photodynamic therapy of subfoveal choroidal neovascularization in age-related macular degeneration with verteporfin: one-year results of 2 randomized clinical trials-TAP report. Arch Ophthalmol 1999; 117(10): 1329–45

    Google Scholar 

  75. Macular Photocoagulation Study Group. Occult choroidal neovascularization. Influence on visual outcome in patients with age-related macular degeneration. Arch Ophthalmol 1996; 114(4): 400–12

    Google Scholar 

  76. Soubrane G, Coscas G, Francais C, et al. Occult subretinal new vessels in age-related macular degeneration. Natural history and early laser treatment. Ophthalmology 1990; 97(5): 649–57

    PubMed  CAS  Google Scholar 

  77. Maguire MG. Natural history. In: Berger JW, Fine SL, Maguire MG, editors. Age-related macular degeneration. St. Louis (MO): Mosby, 1999: 17–30

    Google Scholar 

  78. Gass JD. Pathogenesis of disciform detachment of the neuroepithelium. I general concepts and classifications. Am J Ophthalmol 1967; 63: 573–712

    Google Scholar 

  79. Sarks SH. Ageing and degeneration in the macular region: a clinico-pathological study. Br J Ophthalmol 1976; 60(5): 324–41

    PubMed  CAS  Google Scholar 

  80. Scupola A, Coscas G, Soubrane G, et al. Natural history of macular subretinal hemorrhage in age-related macular degeneration. Ophthalmologica 1999; 213(2): 97–102

    PubMed  CAS  Google Scholar 

  81. Berrocal MH, Lewis ML, Flynn Jr HW. Variations in the clinical course of submacular hemorrhage. Am J Ophthalmol 1996; 122(4): 486–93

    PubMed  CAS  Google Scholar 

  82. Sunness JS. Geographic atrophy. In: Berger JW, Fine SL, Maguire MG, editors. Age-related macular degeneration. St. Louis (MO): Mosby, 1999: 155–66

    Google Scholar 

  83. Sunness JS, Gonzalez-Baron J, Applegate CA, et al. Enlargement of atrophy and visual acuity loss in the geographic atrophy form of age-related macular degeneration. Ophthalmology 1999; 106(9): 1768–79

    PubMed  CAS  Google Scholar 

  84. Sunness JS, Gonzalez-Baron J, Bressler NM, et al. The development of choroidal neovascularization in eyes with the geographic atrophy form of age-related macular degeneration. Ophthalmology 1999; 106(5): 910–9

    PubMed  CAS  Google Scholar 

  85. Klein R. Epidemiology. In: Berger JW, Fine SL, Maguire MG, editors. Age-related macular degeneration. St. Louis (MO): Mosby, 1999: 31–55

    Google Scholar 

  86. Smith W, Mitchell P, Wang JJ. Gender, oestrogen, hormone replacement and age-related macular degeneration: results from the Blue Mountains Eye Study. Aust N Z J Ophthalmol 1997; 25Suppl. 1: S13–5

    PubMed  Google Scholar 

  87. Gorin MB, Breitner JC, de Jong PT, et al. The genetics of age-related macular degeneration. Mol Vis 1999; 5: 29

    PubMed  CAS  Google Scholar 

  88. Smith W, Mitchell P. Family history and age-related maculopathy: the Blue Mountains Eye Study. Aust N Z J Ophthalmol 1998; 26(3): 203–6

    PubMed  CAS  Google Scholar 

  89. Klaver CC, Wolfs RC, Assink JJ, et al. Genetic risk of age-related maculopathy. Population-based familial aggregation study. Arch Ophthalmol 1998; 116(12): 1646–51

    PubMed  CAS  Google Scholar 

  90. Seddon JM, Ajani UA, Mitchell BD. Familial aggregation of age-related maculopathy. Am J Ophthalmol 1997; 123(2): 199–206

    PubMed  CAS  Google Scholar 

  91. Silvestri G, Johnston PB, Hughes AE. Is genetic predisposition an important risk factor in age-related macular degeneration? Eye 1994; 8(Pt 5): 564–8

    PubMed  Google Scholar 

  92. Gottfredsdottir MS, Sverrisson T, Musch DC, et al. Age related macular degeneration in monozygotic twins and their spouses in Iceland. Acta Ophthalmol Scand 1999; 77(4): 422–5

    PubMed  CAS  Google Scholar 

  93. Klein ML, Mauldin WM, Stoumbos VD. Heredity and age-related macular degeneration. Observations in monozygotic twins. Arch Ophthalmol 1994; 112(7): 932–7

    PubMed  CAS  Google Scholar 

  94. Meyers SM, Greene T, Gutman FA. A twin study of age-related macular degeneration. Am J Ophthalmol 1995; 120(6): 757–66

    PubMed  CAS  Google Scholar 

  95. Klaver CC, Kliffen M, van Duijn CM, et al. Genetic association of apolipoprotein E with age-related macular degeneration. Am J Hum Genet 1998; 63(1): 200–6

    PubMed  CAS  Google Scholar 

  96. Souied EH, Benlian P, Amouyel P, et al. The epsilon4 allele of the apolipoprotein E gene as a potential protective factor for exudative age-related macular degeneration. Am J Ophthalmol 1998; 125(3): 353–9

    PubMed  CAS  Google Scholar 

  97. Allikmets R, Shroyer NF, Singh N, et al. Mutation of the Stargardt disease gene (ABCR) in age-related macular degeneration. Science 1997; 277(5333): 1805–7

    PubMed  CAS  Google Scholar 

  98. Allikmets R. Further evidence for an association of ABCR alleles with age-related macular degeneration. The International ABCR Screening Consortium. Am J Hum Genet 2000; 67(2): 487–91

    PubMed  CAS  Google Scholar 

  99. Stone EM, Webster AR, Vandenburgh K, et al. Allelic variation in ABCR associated with Stargardt disease but not age-related macular degeneration [letter]. Nat Genet 1998; 20(4): 328–9

    PubMed  CAS  Google Scholar 

  100. Souied EH, Ducroq D, Rozet JM, et al. ABCR gene analysis in familial exudative age-related macular degeneration. Invest Ophthalmol Vis Sci 2000; 41(1): 244–7

    PubMed  CAS  Google Scholar 

  101. Lotery AJ, Munier FL, Fishman GA, et al. Allelic variation in the VMD2 gene in best disease and age-related macular degeneration. Invest Ophthalmol Vis Sci 2000; 41(6): 1291–6

    PubMed  CAS  Google Scholar 

  102. Weeks DE, Conley YP, Mah TS, et al. A full genome scan for age-related maculopathy. Hum Mol Genet 2000; 9(9): 1329–49

    PubMed  CAS  Google Scholar 

  103. Delcourt C, Cristol JP, Leger CL, et al. Associations of antioxidant enzymes with cataract and age-related macular degeneration. The POLA Study. Pathologies Oculaires Liees a l’Age. Ophthalmology 1999; 106(2): 215–22

    PubMed  CAS  Google Scholar 

  104. Vinding T, Appleyard M, Nyboe J, et al. Risk factor analysis for atrophic and exudative age-related macular degeneration. An epidemiological study of 1000 aged individuals. Acta Ophthalmol(Copenh) 1992; 70(1): 66–72

    CAS  Google Scholar 

  105. The Eye Disease Case-Control Study Group. Risk factors for neovascular age-related macular degeneration. Arch Ophthalmol 1992; 110(12): 1701–8

    Google Scholar 

  106. Age-Related Eye Disease Study Research Group. Risk factors associated with age-related macular degeneration: a case-control study in the age-related eye disease study: age-related eye disease study report number 3. Ophthalmology 2000; 107(12): 2224–32

    Google Scholar 

  107. Klaver CC, Assink JJ, Vingerling JR, et al. Smoking is also associated with age-related macular degeneration in persons aged 85 years and older: the Rotterdam Study [letter]. Arch Ophthalmol 1997; 115(7): 945

    PubMed  CAS  Google Scholar 

  108. Klein R, Klein BE, Linton KL, et al. The Beaver Dam Eye Study: the relation of age-related maculopathy to smoking. Am J Epidemiol 1993; 137(2): 190–200

    PubMed  CAS  Google Scholar 

  109. Smith W, Mitchell P, Leeder SR. Smoking and age-related maculopathy. The Blue Mountains Eye Study. Arch Ophthalmol 1996; 114(12): 1518–23

    PubMed  CAS  Google Scholar 

  110. Vingerling JR, Hofman A, Grobbee DE, et al. Age-relatedmacular degeneration and smoking. The Rotterdam Study. Arch Ophthalmol 1996; 114(10): 1193–6

    PubMed  CAS  Google Scholar 

  111. Seddon JM, Willett WC, Speizer FE, et al. Aprospective study of cigarette smoking and age-related macular degeneration in women. JAMA 1996; 276(14): 1141–6

    PubMed  CAS  Google Scholar 

  112. Christen WG, Glynn RJ, Manson JE, et al. A prospective study of cigarette smoking and risk of age-related macular degeneration in men. JAMA1996; 276(14): 1147–51

    PubMed  CAS  Google Scholar 

  113. Chaine G, Hullo A, Sahel J, et al. Case-control study of the risk factors for age related macular degeneration. France-DMLA Study Group. Br J Ophthalmol 1998; 82(9): 996–1002

    PubMed  CAS  Google Scholar 

  114. Klein R, Klein BE, Franke T. The relationship of cardiovascular disease and its risk factors to age-related maculopathy. The Beaver Dam Eye Study. Ophthalmology 1993; 100(3): 406–14

    PubMed  CAS  Google Scholar 

  115. Klein BE, Klein R. Cataracts and macular degeneration in older Americans. Arch Ophthalmol 1982; 100(4): 571–3

    PubMed  CAS  Google Scholar 

  116. Goldberg J, Flowerdew G, Smith E, et al. Factors associated with age-related macular degeneration. An analysis of data from the first National Health and Nutrition Examination Survey. Am J Epidemiol 1988; 128(4): 700–10

    PubMed  CAS  Google Scholar 

  117. Sperduto RD, Hiller R. Systemic hypertension and age-related maculopathy in the Framingham Study. Arch Ophthalmol 1986; 104(2): 216–9

    PubMed  CAS  Google Scholar 

  118. Smith W, Mitchell P, Leeder SR, et al. Plasma fibrinogen levels, other cardiovascular risk factors, and age-related maculopathy: the Blue Mountains Eye Study. Arch Ophthalmol 1998; 116(5): 583–7

    PubMed  CAS  Google Scholar 

  119. Hirvela H, Luukinen H, Laara E, et al. Risk factors ofage-related maculopathy in a population 70 years of age or older. Ophthalmology 1996; 103(6): 871–7

    PubMed  CAS  Google Scholar 

  120. Vingerling JR, Dielemans I, Bots ML, et al. Age-related macular degeneration is associated with atherosclerosis. The Rotterdam Study. Am J Epidemiol 1995; 142(4): 404–9

    PubMed  CAS  Google Scholar 

  121. Hyman L, Schachat AP, He Q, et al. Hypertension, cardiovascular disease, and age-related macular degeneration. Age-Related Macular Degeneration Risk Factors Study Group. Arch Ophthalmol 2000; 118(3): 351–8

    PubMed  CAS  Google Scholar 

  122. Klein R, Klein BE, Jensen SC. The relation of cardiovascular disease and its risk factors to the 5-year incidence of age-related maculopathy: the Beaver Dam Eye Study. Ophthalmology 1997; 104(11): 1804–12

    PubMed  CAS  Google Scholar 

  123. Darzins P, Mitchell P, Heller RF. Sun exposure and age-related macular degeneration. An Australian case-control study. Ophthalmology 1997; 104(5): 770–6

    PubMed  CAS  Google Scholar 

  124. Smith W, Mitchell P, Leeder SR. Dietary fat and fish intake and age-related maculopathy. Arch Ophthalmol 2000; 118(3): 401–4

    PubMed  CAS  Google Scholar 

  125. Weiter JJ, Delori FC, Wing GL, et al. Relationship of senile macular degeneration to ocular pigmentation. Am J Ophthalmol 1985; 99(2): 185–7

    PubMed  CAS  Google Scholar 

  126. Holz FG, Piguet B, Minassian DC, et al. Decreasing stromal iris pigmentation as a risk factor for age-related macular degeneration. Am J Ophthalmol 1994; 117(1): 19–23

    PubMed  CAS  Google Scholar 

  127. Mitchell P, Smith W, Wang JJ. Iris color, skin sun sensitivity, and age-related maculopathy. The Blue Mountains Eye Study. Ophthalmology 1998; 105(8): 1359–63

    PubMed  CAS  Google Scholar 

  128. Klein R, Klein BE, Jensen SC, et al. The relationship of ocular factors to the incidence and progression of age-related maculopathy. Arch Ophthalmol 1998; 116(4): 506–13

    PubMed  CAS  Google Scholar 

  129. Vinding T. Pigmentation of the eye and hair in relation to age-related macular degeneration. An epidemiological study of 1000 aged individuals. Acta Ophthalmol (Copenh) 1990; 68(1): 53–8

    CAS  Google Scholar 

  130. Pollack A, Marcovich A, Bukelman A, et al. Age-related macular degeneration after extracapsular cataract extraction with intraocular lens implantation. Ophthalmology 1996; 103(10): 1546–54

    PubMed  CAS  Google Scholar 

  131. Cruickshanks KJ, Klein R, Klein BE. Sunlight and age-related macular degeneration. The Beaver Dam Eye Study. Arch Ophthalmol 1993; 111(4): 514–8

    PubMed  CAS  Google Scholar 

  132. West SK, Rosenthal FS, Bressler NM, et al. Exposure to sunlight and other risk factors for age-related macular degeneration. Arch Ophthalmol 1989; 107(6): 875–9

    PubMed  CAS  Google Scholar 

  133. Winkler BS, Boulton ME, Gottsch JD, et al. Oxidative damage and age-related macular degeneration. Mol Vis 1999; 5: 32

    PubMed  CAS  Google Scholar 

  134. Beatty S, Koh H, Phil M, et al. The role of oxidative stress in the pathogenesis of age-related macular degeneration. Surv Ophthalmol 2000; 45(2): 115–34

    PubMed  CAS  Google Scholar 

  135. Cai J, Nelson KC, Wu M, et al. Oxidative damage and protection of the RPE. Prog Retin Eye Res 2000; 19(2): 205–21

    PubMed  CAS  Google Scholar 

  136. Seddon JM, Ajani UA, Sperduto RD, et al. Dietary carotenoids, vitamins A, C, and E, and advanced age-related macular degeneration. Eye Disease Case-Control Study Group. JAMA 1994; 272(18): 1413–20

    PubMed  CAS  Google Scholar 

  137. Eye Disease Case-Control Study Group. Antioxidant status and neovascular age-related macular degeneration. Arch Ophthalmol 1993; 111(1): 104–9

    Google Scholar 

  138. West S, Vitale S, Hallfrisch J, et al. Are antioxidants or supplements protective for age-related macular degeneration? Arch Ophthalmol 1994; 112(2): 222–7

    PubMed  CAS  Google Scholar 

  139. Mares-Perlman JA, Brady WE, Klein R, et al. Serum antioxidants and age-related macular degeneration in a population-based case-control study. Arch Ophthalmol 1995; 113(12): 1518–23

    PubMed  CAS  Google Scholar 

  140. VandenLangenberg GM, Mares-Perlman JA, Klein R, et al. Associations between antioxidant and zinc intake and the 5-year incidence of early age-related maculopathy in the Beaver Dam Eye Study. Am J Epidemiol 1998; 148(2): 204–14

    PubMed  CAS  Google Scholar 

  141. Mares-Perlman JA, Klein R, Klein BE, et al. Association of zinc and antioxidant nutrients with age-related maculopathy. Arch Ophthalmol 1996; 114(8): 991–7

    PubMed  CAS  Google Scholar 

  142. Smith W, Mitchell P, Rochester C. Serum beta carotene, alpha tocopherol, and age-related maculopathy: the Blue Mountains Eye Study. Am J Ophthalmol 1997; 124(6): 838–40

    PubMed  CAS  Google Scholar 

  143. Smith W, Mitchell P, Webb K, et al. Dietary antioxidants and age-related maculopathy: the Blue Mountains Eye Study. Ophthalmology 1999; 106(4): 761–7

    PubMed  CAS  Google Scholar 

  144. Delcourt C, Cristol JP, Tessier F, et al. Age-related macular degeneration and antioxidant status in the POLA study. POLA Study Group. Pathologies Oculaires Liees a l’Age. Arch Ophthalmol 1999; 117(10): 1384–90

    PubMed  CAS  Google Scholar 

  145. Christen WG, Ajani UA, Glynn RJ, et al. Prospective cohort study of antioxidant vitamin supplement use and the risk of age-related maculopathy. Am J Epidemiol 1999; 149(5): 476–84

    PubMed  CAS  Google Scholar 

  146. Obisesan TO, Hirsch R, Kosoko O, et al. Moderate wine consumption is associated with decreased odds of developing age-related macular degeneration in NHANES-1. J Am Geriatr Soc 1998; 46(1): 1–7

    PubMed  CAS  Google Scholar 

  147. Ritter LL, Klein R, Klein BE, et al. Alcohol use and age-related maculopathy in the Beaver Dam Eye Study. Am J Ophthalmol 1995; 120(2): 190–6

    PubMed  CAS  Google Scholar 

  148. Smith W, Mitchell P. Alcohol intake and age-related maculopathy. Am J Ophthalmol 1996; 122(5): 743–5

    PubMed  CAS  Google Scholar 

  149. Ajani UA, Christen WG, Manson JE, et al. A prospective study of alcohol consumption and the risk of age-related macular degeneration. Ann Epidemiol 1999; 9(3): 172–7

    PubMed  CAS  Google Scholar 

  150. Cho E, Hankinson SE, Willett WC, et al. Prospective study of alcohol consumption and the risk of age-related macular degeneration. Arch Ophthalmol 2000; 118(5): 681–8

    PubMed  CAS  Google Scholar 

  151. Sarks JP, Sarks SH, Killingsworth MC. Evolution of geographic atrophy of the retinal pigment epithelium. Eye 1988; 2(Pt 5): 552–77

    PubMed  Google Scholar 

  152. Green WR, Enger C. Age-related macular degeneration histopathologic studies. The 1992 Lorenz E. Zimmerman Lecture. Ophthalmology 1993; 100(10): 1519–35

    PubMed  CAS  Google Scholar 

  153. Holz FG, Sheraidah G, Pauleikhoff D, et al. Analysis of lipid deposits extracted from human macular and peripheral Bruch’s membrane. Arch Ophthalmol 1994; 112(3): 402–6

    PubMed  CAS  Google Scholar 

  154. Feeney-Burns L, Hilderbrand ES, Eldridge S. Aging human RPE: morphometric analysis of macular, equatorial, and peripheral cells. Invest Ophthalmol Vis Sci 1984; 25(2): 195–200

    PubMed  CAS  Google Scholar 

  155. Feeney-Burns L, Eldred GE. The fate of the phagosome: conversion to ‘age pigment’ and impact in human retinal pigment epithelium. Trans Ophthalmol Soc UK 1983; 103(Pt 4): 416–21

    PubMed  Google Scholar 

  156. Feeney-Burns L, Ellersieck MR. Age-related changes in the ultrastructure of Bruch’s membrane. Am J Ophthalmol 1985; 100(5): 686–97

    PubMed  CAS  Google Scholar 

  157. Dorey CK, Wu G, Ebenstein D, et al. Cell loss in the aging retina. Relationship to lipofuscin accumulation and macular degeneration. Invest Ophthalmol Vis Sci 1989; 30(8): 1691–9

    PubMed  CAS  Google Scholar 

  158. Ishibashi T, Sorgente N, Patterson R, et al. Pathogenesis of drusen in the primate. Invest Ophthalmol Vis Sci 1986; 27(2): 184–93

    PubMed  CAS  Google Scholar 

  159. Duvall J, Tso MO. Cellular mechanisms of resolution of drusen after laser coagulation. An experimental study. Arch Ophthalmol 1985; 103(5): 694–703

    PubMed  CAS  Google Scholar 

  160. Penfold PL, Killingsworth MC, Sarks SH. Senile macular degeneration: the involvement of immunocompetent cells. Graefes Arch Clin Exp Ophthalmol 1985; 223(2): 69–76

    PubMed  CAS  Google Scholar 

  161. Ramrattan RS, van der Schaft TL, Mooy CM, et al. Morphometric analysis of Bruch’s membrane, the choriocapillaris, and the choroid in aging. Invest Ophthalmol Vis Sci 1994; 35(6): 2857–64

    PubMed  CAS  Google Scholar 

  162. Marshall J, Hussain AA, Starita C, et al. Aging and Bruch’s membrane. In: Marmor MF, Wolfensberger TJ, editors. The retinal pigment epithelium. New York: Oxford University Press, 1998: 669–92

    Google Scholar 

  163. Moore DJ, Hussain AA, Marshall J. Age-related variation in the hydraulic conductivity of Bruch’s membrane. Invest Ophthalmol Vis Sci 1995; 36(7): 1290–7

    PubMed  CAS  Google Scholar 

  164. Starita C, Hussain AA, Marshall J. Decreasing hydraulic conductivity of Bruch’s membrane: relevance to photoreceptor survival and lipofuscinoses. Am J Med Genet 1995; 57(2): 235–7

    PubMed  CAS  Google Scholar 

  165. Starita C, Hussain AA, Pagliarini S, et al. Hydrodynamics of ageing Bruch’s membrane: implications for macular disease. Exp Eye Res 1996; 62(5): 565–72

    PubMed  CAS  Google Scholar 

  166. Starita C, Hussain AA, Patmore A, et al. Localization of the site of major resistance to fluid transport in Bruch’s membrane. Invest Ophthalmol Vis Sci 1997; 38(3): 762–7

    PubMed  CAS  Google Scholar 

  167. Bird AC, Marshall J. Retinal pigment epithelial detachments in the elderly. Trans Ophthalmol Soc U K 1986; 105(Pt 6): 674–82

    PubMed  Google Scholar 

  168. Nicolini J, Kiilgaard JF, Wiencke AK, et al. The anterior lens capsule used as support material in RPE cell-transplantation. Acta Ophthalmol Scand 2000; 78(5): 527–31

    PubMed  CAS  Google Scholar 

  169. Song MK, Lui GM. Propagation of fetal human RPE cells: preservation of original culture morphology after serial passage. J Cell Physiol 1990; 143: 196–203

    PubMed  CAS  Google Scholar 

  170. Liang YG, Jorgensen AG, Kaestel CG, et al. Bcl-2, Bax, and c-Fos expression correlates to RPE cell apoptosis induced by UV-light and daunorubicin. Curr Eye Res 2000; 20(1): 25–34

    PubMed  CAS  Google Scholar 

  171. Castellarin AA, Sugino IK, Vargas JA, et al. In vitro transplantation of fetal human retinal pigment epithelial cells onto human cadaver Bruch’s membrane. Exp Eye Res 1998; 66(1): 49–67

    PubMed  CAS  Google Scholar 

  172. Del Priore LV, Tezel TH. Reattachment rate of human retinal pigment epithelium to layers of human Bruch’s membrane. Arch Ophthalmol 1998; 116(3): 335–41

    PubMed  Google Scholar 

  173. Tezel TH, Kaplan HJ, Del Priore LV. Fate of human retinal pigment epithelial cells seeded onto layers of human Bruch’s membrane. Invest Ophthalmol Vis Sci 1999; 40(2): 467–76

    PubMed  CAS  Google Scholar 

  174. Tezel TH, Del Priore LV. Repopulation of different layers of host human Bruch’s membrane by retinal pigment epithelial cell grafts. Invest Ophthalmol Vis Sci 1999; 40(3): 767–74

    PubMed  CAS  Google Scholar 

  175. Shiragami C, Matsuo T, Shiraga F, et al. Transplanted and repopulated retinal pigment epithelial cells on damaged Bruch’s membrane in rabbits. Br J Ophthalmol 1998; 82(9): 1056–62

    PubMed  CAS  Google Scholar 

  176. Wihlmark U, Wrigstad A, Roberg K, et al. Lipofuscin accumulation in cultured retinal pigment epithelial cells causes enhanced sensitivity to blue light irradiation. Free Radic Biol Med 1997; 22(7): 1229–34

    PubMed  CAS  Google Scholar 

  177. Schutt F, Davies S, Kopitz J, et al. Photodamage to human RPE cells by A2-E, a retinoid component of lipofuscin. Invest Ophthalmol Vis Sci 2000; 41(8): 2303–8

    PubMed  CAS  Google Scholar 

  178. 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

    PubMed  CAS  Google Scholar 

  179. Eldred GE. Lipofuscin and other lysosomal storage deposits in the retinal pigment epithelium. In: Marmor MF, Wolfensberger TJ, editors. The retinal pigment epithelium. New York: Oxford University Press, 1998: 651–68

    Google Scholar 

  180. Zarbin MA. Age-related macular degeneration: review of pathogenesis. Eur J Ophthalmol 1998; 8(4): 199–206

    PubMed  CAS  Google Scholar 

  181. Korte GE, Burns MS, Bellhorn RW. Epithelium-capillary interactions in the eye: the retinal pigment epithelium and the choriocapillaris. Int Rev Cytol 1989; 114: 221–48

    PubMed  CAS  Google Scholar 

  182. Korte GE, Reppucci V, Henkind P. RPE destruction causes choriocapillary atrophy. Invest Ophthalmol Vis Sci 1984; 25(10): 1135–45

    PubMed  CAS  Google Scholar 

  183. Allikmets R. A photoreceptor cell-specific ATP-binding transportergene(ABCR) is mutated in recessive Stargardt macular dystrophy. Nat Genet 1997; 17(1): 122

    PubMed  CAS  Google Scholar 

  184. Illing M, Molday LL, Molday RS. The 220-kDa rim protein of retinal rod outer segments is a member of the ABC transporter superfamily. J Biol Chem 1997; 272(15): 10303–10

    PubMed  CAS  Google Scholar 

  185. Sun H, Molday RS, Nathans J. Retinal stimulates ATP hydrolysis by purified and reconstituted ABCR, the photoreceptor-specific ATP-binding cassette transporter responsible for Stargardt disease. J Biol Chem 1999; 274(12): 8269–81

    PubMed  CAS  Google Scholar 

  186. Bok D. Photoreceptor ‘retinoid pumps’ in health and disease. Neuron 1999; 23(3): 412–4

    PubMed  CAS  Google Scholar 

  187. Mata NL, Weng J, Travis GH. Biosynthesis of a major lipofuscin fluorophore in mice and humans with ABCR-me-diated retinal and macular degeneration. Proc Natl Acad Sci U S A 2000; 97(13): 7154–9

    PubMed  CAS  Google Scholar 

  188. Weng J, Mata NL, Azarian SM, et al. Insights into the function of Rim protein in photoreceptors and etiology of Stargardt’s disease from the phenotype in abcr knockout mice. Cell 1999; 98(1): 13–23

    PubMed  CAS  Google Scholar 

  189. Curcio CA, Millican CL, Bailey T, et al. Accumulation of cholesterol with age in human Bruch’s membrane. Invest Ophthalmol Vis Sci 2001; 42(1): 265–74

    PubMed  CAS  Google Scholar 

  190. Killingsworth MC, Sarks JP, Sarks SH. Macrophages related to Bruch’s membrane in age-related macular degeneration. Eye 1990; 4(Pt 4): 613–21

    PubMed  Google Scholar 

  191. Dastgheib K, Green WR. Granulomatous reaction to Bruch’s membrane in age-related macular degeneration. Arch Ophthalmol 1994; 112(6): 813–8

    PubMed  CAS  Google Scholar 

  192. Johnson LV, Ozaki S, Staples MK, et al. A potential role for immune complex pathogenesis in drusen formation. Exp Eye Res 2000; 70(4): 441–9

    PubMed  CAS  Google Scholar 

  193. Ono M, Torisu H, Fukushi J, et al. Biological implications of macrophage infiltration in human tumor angiogenesis. Cancer Chemother Pharmacol 1999; 43 Suppl.: S69–71

    PubMed  CAS  Google Scholar 

  194. Talks KL, Harris AL. Current status of antiangiogenic factors. Br J Haematol 2000; 109(3): 477–89

    PubMed  CAS  Google Scholar 

  195. Torisu H, Ono M, Kiryu H, et al. Macrophage infiltration correlates with tumor stage and angiogenesis in human malignant melanoma: possible involvement of TNFalpha and IL-1alpha. Int J Cancer 2000; 85(2): 182–8

    PubMed  CAS  Google Scholar 

  196. Sarks JP, Sarks SH, Killingsworth MC. Morphology of early choroidal neovascularisation in age-related macular degeneration: correlation with activity. Eye 1997; 11(Pt 4): 515–22

    PubMed  Google Scholar 

  197. Jorgensen A, Wiencke AK, la Cour M, et al. Human retinal pigment epithelial cell-induced apoptosis in activated T cells. Invest Ophthalmol Vis Sci 1998; 39(9): 1590–9

    PubMed  CAS  Google Scholar 

  198. Dawson DW, Volpert OV, Gillis P, et al. Pigment epithelium-derived factor: a potent inhibitor of angiogenesis. Science 1999; 285(5425): 245–8

    PubMed  CAS  Google Scholar 

  199. Mori K, Duh E, Gehlbach P, et al. Pigment epithelium-derived factor inhibits retinal and choroidal neovascularization. J Cell Physiol 2001; 188(2): 253–63

    PubMed  CAS  Google Scholar 

  200. Kim I, Ryan AM, Rohan R, et al. Constitutive expression of VEGF, VEGFR-1, and VEGFR-2 in normal eyes. Invest Ophthalmol Vis Sci 1999; 40(9): 2115–21

    PubMed  CAS  Google Scholar 

  201. Blaauwgeers HG, Holtkamp GM, Rutten H, et al. Polarized vascular endothelial growth factor secretion by human retinal pigment epithelium and localization of vascular endothelial growth factor receptors on the inner choriocapillaris. Evidence for a trophic paracrine relation. Am J Pathol 1999; 155(2): 421–8

    PubMed  CAS  Google Scholar 

  202. Schwesinger C, Yee C, Rohan RM, et al. Intrachoroidal neovascularization in transgenic mice overexpressing vascular endothelial growth factor in the retinal pigment epithelium. Am J Pathol 2001; 158(3): 1161–72

    PubMed  CAS  Google Scholar 

  203. Ohno-Matsui K, Morita I, Tombran-Tink J, et al. A novel mechanism for age-related macular degeneration: an equilibrium shift between the angiogenesis factors, VEGF and PEDF [ARVO abstract]. Invest Ophthalmol Vis Sci 2001; 42(4): S227

    Google Scholar 

  204. Friedman E, Krupsky S, Lane AM, et al. Ocular blood flow velocity inage-related macular degeneration. Ophthalmology 1995; 102(4): 640–6

    PubMed  CAS  Google Scholar 

  205. Grunwald JE, Hariprasad SM, DuPont J, et al. Foveolar choroidal blood flow in age-related macular degeneration. Invest Ophthalmol Vis Sci 1998; 39(2): 385–90

    PubMed  CAS  Google Scholar 

  206. Ross RD, Barofsky JM, Cohen G, et al. Presumed macular choroidal watershed vascular filling, choroidal neovascularization, and systemic vascular disease in patients with age-related macular degeneration. Am J Ophthalmol 1998; 125(1): 71–80

    PubMed  CAS  Google Scholar 

  207. Friedman E. Ahemodynamic model of the pathogenesis of age-related macular degeneration [editorial]. Am J Ophthalmol 1997; 124(5): 677–82

    PubMed  CAS  Google Scholar 

  208. Friedman E, Ivry M, Ebert E, et al. Increased scleral rigidity and age-related macular degeneration. Ophthalmology 1989; 96(1): 104–8

    PubMed  CAS  Google Scholar 

  209. Bone RA, Landrum JT, Dixon Z, et al. Lutein and zeaxanthin in the eyes, serum and diet of human subjects. Exp Eye Res 2000; 71(3): 239–45

    PubMed  CAS  Google Scholar 

  210. Bone RA, Landrum JT, Mayne ST, et al. Macular pigment in donor eyes with and without AMD: a case-control study. Invest Ophthalmol Vis Sci 2001; 42(1): 235–40

    PubMed  CAS  Google Scholar 

  211. Landrum JT, Bone RA, Joa H, et al. A one year study of the macular pigment: the effect of 140 days of a lutein supplement. Exp Eye Res 1997; 65(1): 57–62

    PubMed  CAS  Google Scholar 

  212. Brown GC, Brown MM, Sharma S. Difference between ophthalmologists’ and patients’ perceptions of quality of life associated with age-related macular degeneration. Can J Ophthalmol 2000; 35(3): 127–33

    PubMed  CAS  Google Scholar 

  213. Hazel CA, Petre KL, Armstrong RA, et al. Visual function and subjective quality of life compared in subjects with acquired macular disease. Invest Ophthalmol Vis Sci 2000; 41(6): 1309–15

    PubMed  CAS  Google Scholar 

  214. Teikari JM, Laatikainen L, Virtamo J, et al. Six-year supplementation with alpha-tocopherol and beta-carotene and age-related maculopathy. Acta Ophthalmol Scand 1998; 76(2): 224–9

    PubMed  CAS  Google Scholar 

  215. Teikari JM, Virtamo J, Rautalahti M, et al. Long-term supplementation with alpha-tocopherol and beta-carotene and age-related cataract. Acta Ophthalmol Scand 1997; 75(6): 634–40

    PubMed  CAS  Google Scholar 

  216. Albanes D, Heinonen OP, Taylor PR, et al. Alpha-tocopherol and beta-carotene supplements and lung cancer incidence in the alpha-tocopherol, beta-carotene cancer prevention study: effects of base-line characteristics and study compliance. J Natl Cancer Inst 1996; 88(21): 1560–70

    PubMed  CAS  Google Scholar 

  217. Evans JR, Henshaw K. Antioxidant vitamin and mineral supplementation for preventing age-related macular degeneration. In: The Cochrane Database of Systematic Reviews. Available in The Cochrane Library [database on disk and CD ROM]. Updated quarterly. The Cochrane Collaboration; issue 2. Oxford: Oxford Update Software, 2000: CD000253

    Google Scholar 

  218. The Alpha-Tocopherol BCCPSG. The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers inmale smokers. N Engl J Med 1994; 330(15): 1029–35

    Google Scholar 

  219. Omenn GS, Goodman GE, Thornquist MD, et al. Effects of a combination of beta carotene and vitamin A on lung cancer and cardiovascular disease. N Engl J Med 1996; 334(18): 1150–5

    PubMed  CAS  Google Scholar 

  220. Omenn GS, Goodman GE, Thornquist MD, et al. Risk factors for lung cancer and for intervention effects in CARET, the Beta-Carotene and Retinol Efficacy Trial. J Natl Cancer Inst 1996; 88(21): 1550–9

    PubMed  CAS  Google Scholar 

  221. Hennekens CH, Buring JE, Manson JE, et al. Lack of effect of long-term supplementation with beta carotene on the incidence of malignant neoplasms and cardiovascular disease. N Engl J Med 1996; 334(18): 1145–9

    PubMed  CAS  Google Scholar 

  222. Robman LD, Tikellis G, Garrett SK, et al. Baseline ophthalmic findings in the vitamin E, cataract and age-related maculopathy (VECAT) study. Aust N Z J Ophthalmol 1999; 27(6): 410–6

    PubMed  CAS  Google Scholar 

  223. Tikellis G, Robman LD, Harper CA, et al. The VECAT study: methodology and statistical power for measurement of age-related macular features. Vitamin E, Cataract, and Age-related Maculopathy Study. Ophthalmic Epidemiol 1999; 6(3): 181–94

    PubMed  CAS  Google Scholar 

  224. Christen WG, Gaziano JM, Hennekens CH. Design of Physicians’ Health Study II-a randomized trial of beta-carotene, vitamins E and C, and multivitamins, in prevention of cancer, cardiovascular disease, and eye disease, and review of results of completed trials. Ann Epidemiol 2000; 10(2): 125–34

    PubMed  CAS  Google Scholar 

  225. Buring JE, Hennekens CH. Randomized trials of primary prevention of cardiovascular disease in women. An investigator’s view. Ann Epidemiol 1994; 4(2): 111–4

    PubMed  CAS  Google Scholar 

  226. Manson JE, Gaziano JM, Spelsberg A, et al. A secondary prevention trial of antioxidant vitamins and cardiovascular disease in women. Rationale, design, and methods. The WACS Research Group. Ann Epidemiol 1995; 5(4): 261–9

    PubMed  CAS  Google Scholar 

  227. Newsome DA, Swartz M, Leone NC, et al. Oral zinc in macular degeneration. Arch Ophthalmol 1988; 106(2): 192–8

    PubMed  CAS  Google Scholar 

  228. Stur M, Tittl M, Reitner A, et al. Oral zinc and the second eye in age-related macular degeneration. Invest Ophthalmol Vis Sci 1996; 37(7): 1225–35

    PubMed  CAS  Google Scholar 

  229. Kaiser HJ, Flammer J, Stumpfig D, et al. Visaline in the treatment of age-related macular degeneration: a pilot study. Ophthalmologica 1995; 209(6): 302–5

    PubMed  CAS  Google Scholar 

  230. Richer S. Multicenter ophthalmic and nutritional age-related macular degeneration study -part 1: design, subjects and procedures. J Am Optom Assoc 1996; 67(1): 12–29

    Google Scholar 

  231. Richer S. Multicenter ophthalmic and nutritional age-related macular degeneration study -part 2: antioxidant intervention and conclusions. J Am Optom Assoc 1996; 67(1): 30–49

    PubMed  CAS  Google Scholar 

  232. Evans JR. Antioxidant vitamin and mineral supplements for age-related macular degeneration. In: The Cochrane Database of Systematic Reviews. Available in The Cochrane Library [database on disk and CD ROM]. Updated quarterly. The Cochrane Collaboration; issue 2. Oxford: Oxford Update Software, 2000: CD000254

    Google Scholar 

  233. The Age-Related Eye Disease Study (AREDS): design implications AREDS report no. 1. The Age-Related Eye Disease Study Research Group. Control Clin Trials 1999; 20(6): 573–600

    Google Scholar 

  234. Ho AC, Maguire MG. Laser prophylaxis. In: Berger JW, Fine SL, Maguire MG, editors. Age-related macular degeneration. St. Louis (MO): Mosby, 1999: 263–77

    Google Scholar 

  235. Abdelsalam A, Del Priore L, Zarbin MA. Drusen in age-related macular degeneration: pathogenesis, natural course, and laser photocoagulation-induced regression. Surv Ophthalmol 1999; 44(1): 1–29

    PubMed  CAS  Google Scholar 

  236. Gass JD. Drusen and disciform macular detachment and degeneration. Arch Ophthalmol 1973; 90(3): 206–17

    PubMed  CAS  Google Scholar 

  237. Gass JD. Photocoagulation of macular lesions. Trans Am Acad Ophthalmol Otolaryngol 1971; 75(3): 580–608

    PubMed  CAS  Google Scholar 

  238. Frennesson C, Nilsson SE. Prophylactic laser treatment in early age related maculopathy reduced the incidence of exudative complications. Br J Ophthalmol 1998; 82(10): 1169–74

    PubMed  CAS  Google Scholar 

  239. Frennesson IC, Nilsson SE. Laser photocoagulation of soft drusen in early age-related maculopathy (ARM). The one-year results of a prospective, randomised trial. Eur J Ophthalmol 1996; 6(3): 307–14

    PubMed  CAS  Google Scholar 

  240. Little HL, Showman JM, Brown BW. A pilot randomized controlled tudy on the effect of laser photocoagulation of confluent soft macular drusen. Ophthalmology 1997; 104(4): 623–31

    PubMed  CAS  Google Scholar 

  241. Ho AC, Maguire MG, Yoken J, et al. Laser-induced drusen reduction improves visual function at 1 year. Choroidal Neovascularization Prevention Trial Research Group. Ophthalmology 1999; 106(7): 1367–73

    PubMed  CAS  Google Scholar 

  242. Fine SL, Maguire MG, Javornik NB, et al. The choroidal neovascularization prevention trial (CNVPT): 4-year results [ARVO abstract]. Invest Ophthalmol Vis Sci 2001; 42(4): S127

    Google Scholar 

  243. Olk RJ, Friberg TR, Stickney KL, et al. Therapeutic benefits of infrared (810-nm) diode laser macular grid photocoagulation in prophylactic treatment of nonexudative age-related macular degeneration: two-year results of arandomized pilot study. Ophthalmology 1999; 106(11): 2082–90

    PubMed  CAS  Google Scholar 

  244. Olk RJ, Akduman L, Wong KL, et al. Therapeutic benefits of diode laser grid photocoagulation in prophylactic treatment of age-related macular degeneration (AMD). Long term (4-5 years) results of a randomized pilot study [ARVO abstract]. Invest Ophthalmol Vis Sci 2000; 41(4): S319

    Google Scholar 

  245. Pharmacological Therapy for Macular Degeneration Study Group. Interferon alfa-2a is ineffective for patients with choroidal neovascularization secondary to age-related macular degeneration. Results of a prospective randomized placebo-controlled clinical trial. Arch Ophthalmol 1997; 115(7): 865–72

    Google Scholar 

  246. Maguire MG, Fine SL, Maguire AM, et al. Results of the age-related macular degeneration and thalidomide study (AMDATS) [ARVO abstract]. Invest Ophthalmol Vis Sci 2001; 42(4): S233

    Google Scholar 

  247. Ishibashi T, Miki K, Sorgente N, et al. Effects of intravitreal administration of steroids on experimental subretinal neovascularization in the subhuman primate. Arch Ophthalmol 1985; 103(5): 708–11

    PubMed  CAS  Google Scholar 

  248. Challa JK, Gillies MC, Penfold PL, et al. Exudative macular degeneration and intravitreal triamcinolone: 18 month follow up. Aust N Z J Ophthalmol 1998; 26(4): 277–81

    PubMed  CAS  Google Scholar 

  249. Danis RP, Ciulla TA, Pratt LM, et al. Intravitreal triamcinolone acetonide in exudative age-related macular degeneration. Retina 2000; 20(3): 244–50

    PubMed  CAS  Google Scholar 

  250. Luo W, Gillies M, Simpson J, et al. The safety of single intravitreal injection of triamcinolone among patients with age-related macular degeneration. One year results of a randomised clinicaltrial: IVTAS [ARVO abstract]. Invest Ophthalmol Vis Sci 2001; 42(4): S232

    Google Scholar 

  251. Gillies MC, Luo W, Chua W, et al. The efficacy of a single intravitreal injection of triamcinolone for neovascular age-related macular degeneration. One year results of a randomised clinical trial: IVTAS [ARVO abstract]. Invest Ophthalmol Vis Sci 2001; 42(4): S522

    Google Scholar 

  252. Singerman LJ, Yannuzzi LA, Russell S, et al. Sub-Tenon’s retrobulbar anecortave acetate with and without Visudyne™ photo-dynamic therapy (PDT) in patients with subfoveal choroidal neovascularization (CNV) in age-related macular degeneration (AMD) [ARVO abstract]. Invest Ophthalmol Vis Sci 2001; 42(4): S231

    Google Scholar 

  253. Penn JS, Rajaratnam VS, Collier RJ, et al. The effect of an angiostatic steroid on neovascularization in a rat model of retinopathy of prematurity. Invest Ophthalmol Vis Sci 2001; 42(1): 283–90

    PubMed  CAS  Google Scholar 

  254. D’Amico DJ, Adamis AP, Duker J, et al. Sub-Tenon’s retrobulbar anecortave acetate with and without Visudyne PDT in patients with subfoveal age-related macular degeneration (AMD)-a review of the emerging clinical safety profile of this new experimental treatment [ARVO abstract]. Invest Ophthalmol Vis Sci 2001; 42(4): S232

    Google Scholar 

  255. Guyer DR, Martin DM, Klein M, et al. Anti-VEGF Therapy in patients with exudative age-related macular degeneration [ARVO abstract]. Invest Ophthalmol Vis Sci 2001; 42(4): S522

    Google Scholar 

  256. Schwartz SD, Blumenkranz MS, Rosenfeld PJ, et al. Safety of rhuFab V2, an anti-VEGF antibody fragment, as a single intravitreal injection in subjects with neovascular age-related macular degeneration [ARVO abstract]. Invest Ophthalmol Vis Sci 2001; 42(4): S522

    Google Scholar 

  257. O’Neill CA, Miller P, Christian B, et al. Safety evaluation of differing schedules of intravitreal administration of rhuFab VEGF in cynomolgus monkeys for two months [ARVO abstract]. Invest Ophthalmol Vis Sci 2001; 42(4): S225

    Google Scholar 

  258. Seo MS, Kwak N, Ozaki H, et al. Dramatic inhibition of retinal and choroidal neovascularization by oral administration of a kinase inhibitor. Am J Pathol 1999; 154(6): 1743–53

    PubMed  CAS  Google Scholar 

  259. Chakravarthy U, Gardiner TA, Archer DB, et al. A light microscopic and autoradiographic study of non-irradiated and irradiated ocular wounds. Curr Eye Res 1989; 8(4): 337–48

    PubMed  CAS  Google Scholar 

  260. Chakravarthy U, Houston RF, Archer DB. Treatment of age-related subfoveal neovascular membranes by teletherapy: a pilot study. Br J Ophthalmol 1993; 77(5): 265–73

    PubMed  CAS  Google Scholar 

  261. Marcus DM, Sheils WC. Radiation therapy. In: Berger JW, Fine SL, Maguire MG, editors. Age-related macular degeneration. St. Louis (MO): Mosby, 1999: 309–34

    Google Scholar 

  262. Berson AM, Finger PT, Sherr DL, et al. Radiotherapy for age-related macular degeneration: preliminary results of a potentially new treatment. Int J Radiat Oncol Biol Phys 1996; 36(4): 861–5

    PubMed  CAS  Google Scholar 

  263. Bergink GJ, Deutman AF, van den Broek JF, et al. Radiation therapy for subfoveal choroidal neovascular membranes in age-related macular degeneration. Apilot study. Graefes Arch Clin Exp Ophthalmol 1994; 232(10): 591–8

    PubMed  CAS  Google Scholar 

  264. Bergink GJ, Deutman AF, van den Broek JE, et al. Radiation therapy for age-related subfoveal choroidal neovascular membranes. A pilot study. Doc Ophthalmol 1995; 90(1): 67–74

    PubMed  CAS  Google Scholar 

  265. Subasi M, Akmansu M, Or M. Treatment of age-related subfoveal neovascular membranes by teletherapy: results of a non-randomized study. Radiat Med 1999; 17(2): 169–73

    PubMed  CAS  Google Scholar 

  266. Hart PM, Chakravarthy U, MacKenzie G, et al. Teletherapy for subfoveal choroidal neovascularisation of age-related macular degeneration: results of follow up in a non-randomised study. Br J Ophthalmol 1996; 80(12): 1046–50

    PubMed  CAS  Google Scholar 

  267. Freire J, Longton WA, Miyamoto CT, et al. External radiotherapy in macular degeneration: technique and preliminary subjective response. Int J Radiat Oncol Biol Phys 1996; 36(4): 857–60

    PubMed  CAS  Google Scholar 

  268. Spaide RF, Guyer DR, McCormick B, et al. External beam radiation therapy for choroidal neovascularization. Ophthalmology 1998; 105(1): 24–30

    PubMed  CAS  Google Scholar 

  269. Stalmans P, Leys A, Van Limbergen E. External beam radiotherapy (20 Gy, 2 Gy fractions) fails to control the growth of choroidal neovascularization in age-related macular degeneration: a review of 111 cases. Retina 1997; 17(6): 481–92

    PubMed  CAS  Google Scholar 

  270. The Radiation Therapy for Age-related Macular Degeneration (RAD) Study Group. A prospective, randomized, double-masked trial on radiation therapy for neovascular age-related macular degeneration (RAD Study). Ophthalmology 1999; 106(12): 2239–47

    Google Scholar 

  271. Bergink GJ, Hoyng CB, van der Maazen RW, et al. A randomized controlled clinical trial on the efficacy of radiation therapy in the control of subfoveal choroidal neovascularization in age-related macular degeneration: radiation versus observation. Graefes Arch Clin Exp Ophthalmol 1998; 236(5): 321–5

    PubMed  CAS  Google Scholar 

  272. Char DH, Irvine AI, Posner MD, et al. Randomized trial of radiation for age-related macular degeneration. Am J Ophthalmol 1999; 127(5): 574–8

    PubMed  CAS  Google Scholar 

  273. Finger PT, Berson A, Ng T, et al. Ophthalmic plaque radiotherapy for age-related macular degeneration associated with sub-retinal neovascularization. Am J Ophthalmol 1999; 127(2): 170–7

    PubMed  CAS  Google Scholar 

  274. Moyers MF, Galindo RA, Yonemoto LT, et al. Treatment of macular degeneration with proton beams. Med Phys 1999; 26(5): 777–82

    PubMed  CAS  Google Scholar 

  275. Yonemoto LT, Slater JD, Friedrichsen EJ, et al. Phase I/II study of proton beam irradiation for the treatment of subfoveal choroidal neovascularization in age-related macular degeneration: treatment techniques and preliminary results. Int J Radiat Oncol Biol Phys 1996; 36(4): 867–71

    PubMed  CAS  Google Scholar 

  276. Flaxel CJ, Friedrichsen EJ, Smith JO, et al. Proton beam irradiation of subfoveal choroidal neovascularisation in age-related macular degeneration. Eye 2000; 14(Pt 2): 155–64

    PubMed  Google Scholar 

  277. Spaide RF, Leys A, Herrmann-Delemazure B, et al. Radiation-associated choroidal neovasculopathy. Ophthalmology 1999; 106(12): 2254–60

    PubMed  CAS  Google Scholar 

  278. Smiddy WE, Fine SL, Quigley HA, et al. Comparison of krypton and argon laser photocoagulation. Results of stimulated clinical treatment of primate retina. Arch Ophthalmol 1984; 102(7): 1086–92

    PubMed  CAS  Google Scholar 

  279. Green WR. Clinicopathologic studies of treated choroidal neovascular membranes. A review and report of two cases. Retina 1991; 11(3): 328–56

    PubMed  CAS  Google Scholar 

  280. Macular Photocoagulation Study Group. Persistent and recurrent neovascularization after krypton laser photocoagulation for neovascular lesions of age-related macular degeneration. Arch Ophthalmol 1990; 108(6): 825–31

    Google Scholar 

  281. Macular Photocoagulation Study Group. Laser photocoagulation of subfoveal recurrent neovascular lesions in age-related macular degeneration. Results of a randomized clinical trial. Arch Ophthalmol 1991; 109(9): 1232–41

    Google Scholar 

  282. Macular Photocoagulation Study Group. Argon laser photocoagulation for neovascular maculopathy. Five-year results from randomized clinical trials. Arch Ophthalmol 1991; 109(8): 1109–14

    Google Scholar 

  283. Macular Photocoagulation Study Group. Persistent and recurrent neovascularization after laser photocoagulation for subfoveal choroidal neovascularization of age-related macular degeneration. Arch Ophthalmol 1994; 112(4): 489–99

    Google Scholar 

  284. Macular Photocoagulation Study Group. Visual outcome after laser photocoagulation for subfoveal choroidal neovascularization secondary to age-related macular degeneration. The influence of initial lesion size and initial visual acuity. Arch Ophthalmol 1994; 112(4): 480–8

    Google Scholar 

  285. Macular Photocoagulation Study (MPS) Group. Evaluation of argon green vs krypton red laser for photocoagulation of subfoveal choroidal neovascularization in the macular photocoagulation study. Arch Ophthalmol 1994; 112(9): 1176–84

    Google Scholar 

  286. Macular Photocoagulation Study Group. Laser photocoagulation for juxtafoveal choroidal neovascularization. Five-year results from randomized clinical trials. Arch Ophthalmol 1994; 112(4): 500–9

    Google Scholar 

  287. Weisz JM, O’Connell SR, Bressler NM. Choroidal neovascularization. Treatment guidelines forage-related macular degeneration based upon results from the macular photocoagulation study. In: Quiroz-Mercado H, Alfaro DV, Liggett PE, et al., editors. Macular surgery. Philadelphia (PA): Lippincott, 2000: 201–12

    Google Scholar 

  288. Sykes SO, Bressler NM, Maguire MG, et al. Detecting recurrent choroidal neovascularization. Comparison of clinical examination with and without fluorescein angiography. Arch Ophthalmol 1994; 112(12): 1561–6

    PubMed  CAS  Google Scholar 

  289. Klein ML, Jorizzo PA, Watzke RC. Growth features of choroidal neovascular membranes in age-related macular degeneration. Ophthalmology 1989; 96(9): 1416–9

    PubMed  CAS  Google Scholar 

  290. Macular Photocoagulation Study Group. Argon laser photocoagulation for senile macular degeneration. Results of a randomized clinical trial. Arch Ophthalmol 1982; 100(6): 912–8

    Google Scholar 

  291. Macular Photocoagulation Study Group. Laser photocoagulation of subfoveal neovascular lesions in age-related macular degeneration. Results of arandomized clinical trial. Arch Ophthalmol 1991; 109(9): 1220–31

    Google Scholar 

  292. Macular Photocoagulation Study Group. Krypton laser photocoagulation for neovascular lesions of age-related macular degeneration. Results of arandomized clinical trial. Arch Ophthalmol 1990; 108(6): 816–24

    Google Scholar 

  293. Submacular Surgery Trials Pilot Study Investigators. Submacular surgery trials randomized pilot trial of laser photocoagulation versus surgery for recurrent choroidal neovascularization secondary to age-related macular degeneration: I. Ophthalmic outcomes. Submacular surgery trials pilot study report number1(2). Am J Ophthalmol 2000; 130(4): 387–407

    Google Scholar 

  294. Bressler NM, Maguire MG, Murphy PL, et al. Macular scatter (‘grid’) laser treatment of poorly demarcated subfoveal choroidal neovascularization in age-related macular degeneration. Results of a randomized pilot trial. Arch Ophthalmol 1996; 114(12): 1456–64

    PubMed  CAS  Google Scholar 

  295. Barondes MJ, Pagliarini S, Chisholm IH, et al. Controlled trial of laser photocoagulation of pigment epithelial detachments in the elderly: 4 year review. Br J Ophthalmol 1992; 76(1): 5–7

    PubMed  CAS  Google Scholar 

  296. Guyer DR, Yannuzzi LA, Ladas I, et al. Indocyanine greenguided laser photocoagulation of focal spots at the edge of plaques of choroidal neovascularization. Arch Ophthalmol 1996; 114(6): 693–7

    PubMed  CAS  Google Scholar 

  297. Slakter JS, Yannuzzi LA, Sorenson JA, et al. A pilot study of indocyanine green videoangiography-guided laser photocoagulation of occult choroidal neovascularization in age-related macular degeneration. Arch Ophthalmol 1994; 112(4): 465–72

    PubMed  CAS  Google Scholar 

  298. Bressler NM, Bressler SB. Indocyanine green angiography. Can it help preserve the vision of our patients? Arch Ophthalmol 1996; 114(6): 747–9

    PubMed  CAS  Google Scholar 

  299. Schmidt-Erfurth U, Hasan T. Mechanisms of action of photo-dynamic therapy with verteporfin for the treatment of age-related macular degeneration. Surv Ophthalmol 2000; 45(3): 195–214

    PubMed  CAS  Google Scholar 

  300. Mainster MA, Reichel E. Transpupillary thermotherapy for age-related macular degeneration: long-pulse photocoagulation, apoptosis, and heat shock proteins. Ophthalmic Surg Lasers 2000; 31(5): 359–73

    PubMed  CAS  Google Scholar 

  301. Miller JM, Gragoudas ES. Photodynamic therapy for choroidal neovascularization and age-related macular degeneration. In: Quiroz-Mercado H, Alfaro DV, Liggett PE, et al., editors. Macular surgery. Philadelphia (PA): Lippincott, 2000: 240–50

    Google Scholar 

  302. Husain D, Miller JW, Michaud N, et al. Intravenous infusion of liposomal benzoporphyrin derivative for photodynamic therapy of experimental choroidal neovascularization. Arch Ophthalmol 1996; 114(8): 978–85

    PubMed  CAS  Google Scholar 

  303. Husain D, Miller JW, Kenney AG, et al. Photodynamic therapy and digital angiography of experimental iris neovascularization using liposomal benzoporphyrin derivative. Ophthalmology 1997; 104(8): 1242–50

    PubMed  CAS  Google Scholar 

  304. Kramer M, Miller JW, Michaud N, et al. Liposomal benzoporphyrin derivative verteporfin photodynamic therapy. Selective treatment of choroidal neovascularization in monkeys. Ophthalmology 1996; 103(3): 427–38

    PubMed  CAS  Google Scholar 

  305. Miller JW, Walsh AW, Kramer M, et al. Photodynamic therapy of experimental choroidal neovascularization using lipoprotein-delivered benzoporphyrin. Arch Ophthalmol 1995; 113(6): 810–8

    PubMed  CAS  Google Scholar 

  306. Husain D, Kramer M, Kenny AG, et al. Effects of photodynamic therapy using verteporfin on experimental choroidal neovascularization and normal retina and choroid up to 7 weeks after treatment. Invest Ophthalmol Vis Sci 1999; 40(10): 2322–31

    PubMed  CAS  Google Scholar 

  307. Reinke MH, Canakis C, Husain D, et al. Verteporfin photodynamic therapy retreatment of normal retina and choroid in the cynomolgus monkey. Ophthalmology 1999; 106(10): 1915–23

    PubMed  CAS  Google Scholar 

  308. Miller JW, Schmidt-Erfurth U, Sickenberg M, 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

    PubMed  CAS  Google Scholar 

  309. CIBA Vision. Visudyne TM. Product monograph. 1st ed. Bülach: CIBA Vision AG, 2000

    Google Scholar 

  310. Novartis Ophthalmics. Visudyne international symposia. Online program for 2001. ARVO 2001 [online]. Available from URL: http://www.visudyne.wwwebposium.com/indexfs.html [Accessed 2001 Jan 24]

  311. Verteporfin in photodynamic therapy study group. Photodynamic therapy of subfoveal choroidal neovascularization in pathologic myopia with verteporfin. 1-year results of a randomized clinical trial-VIP report no. 1. Ophthalmology 2001; 108(5): 841–52

    Google Scholar 

  312. Stur M. Rationale for and design of the Visudyne in Early Retreatment (VER) Trial [ARVO abstract]. Invest Ophthalmol Vis Sci 2001; 42(4): S442

    Google Scholar 

  313. Sharma S. Update in retina: photodynamic therapy for the treatment of subfoveal choroidal neovascularization secondary to age-related macular degeneration. Can J Ophthalmol 2001; 36(1): 7–10

    PubMed  CAS  Google Scholar 

  314. Baudo TA, Velez G, Luu JK, et al. Incidence of predominantly classic choroidal neovascular membranes (CNV) in exudative age related macular degeneration (AMD): percentage of new patients eligible for photodynamic therapy with verteporfin [ARVO abstract]. Invest Ophthalmol Vis Sci 2001; 42(4): S438

    Google Scholar 

  315. Thomas EL, Murphy RP, Tressler CS, et al. Photodynamic therapy with tin ethyl etiopurpurin (SnET2) of subfoveal choroidal neovascularization (CNV) in age-related maculopathy: study design and baseline characteristics [ARVO abstract]. Invest Ophthalmol Vis Sci 2000; 42(4): S531

    Google Scholar 

  316. Blumenkranz MS, Miller JM, Guyer DR, et al. Preliminary results from a phase II dose-response study of photodynamic therapy with motexafin lutetium(Lu-Tex™) to treat subfoveal CNV [ARVO abstract]. Invest Ophthalmol Vis Sci 2000; 42(4): S531

    Google Scholar 

  317. Blumenkranz MS, Woodburn KW, Qing F, et al. Lutetium texaphyrin (Lu-Tex): a potential new agent for ocular fundus angiography and photodynamic therapy. Am J Ophthalmol 2000; 129(3): 353–62

    PubMed  CAS  Google Scholar 

  318. Branco A, Blumenkranz M, Miller J, et al. Photodynamic angiography: a new technique utilizing lutex [ARVO abstract]. Invest Ophthalmol Vis Sci 2000; 42(4): S512

    Google Scholar 

  319. National Eye Institute. Clinical studies supported by the National Eye Institute. Submacular Surgery Trials (SST) [online]. Available from URL: http://www.nei.nih.gov/neitrials_script/studydtl.asp?.ID=52 [Accessed 2000 Jan 28]

  320. Submacular Surgery Trials Pilot Study Investigators. Submacular surgery trials randomized pilot trial of laser photocoagulation versus surgery for recurrent choroidal neovascularization secondary to age-related macular degeneration: II Quality of life outcomes. Submacular surgery trials pilot study report number2. Am J Ophthalmol 2000; 130(4): 408–18

    Google Scholar 

  321. Holekamp NM, Thomas MA. Submacular surgery. In: QuirozMercado H, Alfaro DV, Liggert PE, et al., editors. Macular surgery. Philadelphia (PA): Lippincott, 2000: 212–20

    Google Scholar 

  322. Merrill PT, LoRusso FJ, Lomeo MD, et al. Surgical removal of subfoveal choroidal neovascularization in age-related macular degeneration. Ophthalmology 1999; 106(4): 782–9

    PubMed  CAS  Google Scholar 

  323. Scheider A, Gundisch O, Kampik A. Surgical extraction of subfoveal choroidal new vessels and submacular haemorrhage in age-related macular degeneration: results of a prospective study. Graefes Arch Clin Exp Ophthalmol 1999; 237(1): 10–5

    PubMed  CAS  Google Scholar 

  324. Ormerod LD, Puklin JE, Frank RN. Long-term outcomes after the surgical removal of advanced subfoveal neovascular membranes in age-related macular degeneration. Ophthalmology 1994; 101(7): 1201–10

    PubMed  CAS  Google Scholar 

  325. Nasir MA, Sugino I, Zarbin MA. Decreased choriocapillaris perfusion following surgical excision of choroidal neovascular membranes in age-related macular degeneration. Br J Ophthalmol 1997; 81(6): 481–9

    PubMed  CAS  Google Scholar 

  326. Horle S, Postgens H, Schmidt J, et al. Pigment epithelium defects after submacular surgery for choroidal neovascularization: first results. Ophthalmologica 2000; 214(2): 122–5

    PubMed  CAS  Google Scholar 

  327. Hsu JK, Thomas MA, Ibanez H, et al. Clinicopathologic studies of an eye after submacular membranectomy for choroidal neovascularization. Retina 1995; 15(1): 43–52

    PubMed  CAS  Google Scholar 

  328. Rosa Jr RH, Glaser BM, de la Cruz Z, et al. Clinicopathologic correlation of an untreated macular hole and a macular hole treated by vitrectomy, transforming growth factor-beta 2, and gas tamponade. Am J Ophthalmol 1996; 122(6): 853–63

    PubMed  Google Scholar 

  329. Algvere PV, Gouras P, Dafgard KE. Long-termoutcome of RPE allografts in non-immunosuppressed patients with AMD. Eur J Ophthalmol 1999; 9(3): 217–30

    PubMed  CAS  Google Scholar 

  330. Algvere PV, Berglin L, Gouras P, et al. Transplantation of RPE in age-related macular degeneration: observations in disciform lesions and dry RPE atrophy. Graefes Arch Clin Exp Ophthalmol 1997; 235(3): 149–58

    PubMed  CAS  Google Scholar 

  331. Lappas A, Weinberger AW, Foerster AM, et al. Iris pigment epithelial cell translocation in exudative age-related macular degeneration. A pilot study in patients. Graefes Arch Clin Exp Ophthalmol 2000; 238(8): 631–41

    PubMed  CAS  Google Scholar 

  332. Avery RL, Fekrat S, Hawkins BS, et al. Natural history of subfoveal subretinal hemorrhage in age-related macular degeneration. Retina 1996; 16(3): 183–9

    PubMed  CAS  Google Scholar 

  333. Bennett SR, Folk JC, Blodi CF, et al. Factors prognostic of visual outcome in patients with subretinal hemorrhage. Am J Ophthalmol 1990; 109(1): 33–7

    PubMed  CAS  Google Scholar 

  334. Toth CA, Morse LS, Hjelmeland LM, et al. Fibrin directs early retinal damage after experimental subretinal hemorrhage. Arch Ophthalmol 1991; 109(5): 723–9

    PubMed  CAS  Google Scholar 

  335. Ohji M, Saito Y, Hayashi A, et al. Pneumatic displacement of subretinal hemorrhage without tissue plasminogen activator. Arch Ophthalmol 1998; 116(10): 1326–32

    PubMed  CAS  Google Scholar 

  336. Hesse L, Schmidt J, Kroll P. Management of acute submacular hemorrhage using recombinant tissue plasminogen activator and gas. Graefes Arch Clin Exp Ophthalmol 1999; 237(4): 273–7

    PubMed  CAS  Google Scholar 

  337. Hassan AS, Johnson MW, Schneiderman TE, et al. Management of submacular hemorrhage with intravitreous tissue plasminogen activator injection and pneumatic displacement. Ophthalmology 1999; 106(10): 1900–6

    PubMed  CAS  Google Scholar 

  338. Kamei M, Misono K, Lewis H. A study of the ability of tissue plasminogen activator to diffuse into the subretinal space after intravitreal injection in rabbits. Am J Ophthalmol 1999; 128(6): 739–46

    PubMed  CAS  Google Scholar 

  339. Hrach CJ, Johnson MW, Hassan AS, et al. Retinal toxicity of commercial intravitreal tissue plasminogen activator solution in cat eyes. Arch Ophthalmol 2000; 118(5): 659–63

    PubMed  CAS  Google Scholar 

  340. Machemer R, Steinhorst UH. Retinal separation, retinotomy and macular relocation: II. A surgical approach for age-related macular degeneration? Graefes Arch Clin Exp Ophthalmol 1993; 231(11): 635–41

    PubMed  CAS  Google Scholar 

  341. Eckardt C, Eckardt U, Conrad HG. Macular rotation with and without counter-rotation of the globe in patients with age-related macular degeneration. Graefes Arch Clin Exp Ophthalmol 1999; 237(4): 313–25

    PubMed  CAS  Google Scholar 

  342. Wolf S, Lappas A, Weinberger AW, et al. Macular translocation for surgical management of subfoveal choroidal neovascularizations in patients with AMD: first results. Graefes Arch Clin Exp Ophthalmol 1999; 237(1): 51–7

    PubMed  CAS  Google Scholar 

  343. De Juan Jr E, Loewenstein A, Bressler NM, et al. Translocation of the retina for management of subfoveal choroidal neovascularization II: a preliminary report in humans. Am J Ophthalmol 1998; 125(5): 635–46

    PubMed  Google Scholar 

  344. Fujii GY, Pieramici DJ, Humayun MS, et al. Complications associated with limited macular translocation. Am J Ophthalmol 2000; 130(6): 751–62

    PubMed  CAS  Google Scholar 

  345. Pieramici DJ, de Juan E, Fujii GY, et al. Limited inferior macular translocation for the treatment of subfoveal choroidal neovascularization secondary to age-related macular degeneration. Am J Ophthalmol 2000; 130(4): 419–28

    PubMed  CAS  Google Scholar 

  346. Lewis H, Kaiser PK, Lewis S, et al. Macular translocation for subfoveal choroidal neovascularization in age-related macular degeneration: a prospective study. Am J Ophthalmol 1999; 128(2): 135–46

    PubMed  CAS  Google Scholar 

  347. American Academy of Ophthalmology. Macular translocation. Ophthalmology 2000; 107(5): 1015–8

    Google Scholar 

  348. Oosterhuis JA, Journee-de Korver HG, Kakebeeke-Kemme HM, et al. Transpupillary thermotherapy in choroidal melanomas. Arch Ophthalmol 1995; 113(3): 315–21

    PubMed  CAS  Google Scholar 

  349. Reichel E, Berrocal AM, Ip M, et al. Transpupillary therm otherapy of occult subfoveal choroidal neovascularization in patients with age-related macular degeneration. Ophthalmology 1999; 106(10): 1908–14

    PubMed  CAS  Google Scholar 

  350. Age-related eye disease study 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. Arch Ophthalmol 2001; 119(10): 1417–36

    Google Scholar 

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Acknowledgements

The work was supported by grants from the Hede-Nielsen Foundation and the DANDY Foundation. Dr Kamilla Rothe Nissen is thanked for useful discussions.

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  1. Eye Department 2061, National University Hospital (Rigshospitalet), Blegdamsvej 9, Copenhagen, Ø, DK 2100, Denmark

    Morten la Cour

  2. Eye Pathology Institute, University of Copenhagen, Copenhagen, Denmark

    Jens Folke Kiilgaard

  3. Department of Medical Anatomy, University of Copenhagen, Copenhagen, Denmark

    Mogens Holst Nissen

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  1. Morten la Cour
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Correspondence to Morten la Cour.

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la Cour, M., Kiilgaard, J.F. & Nissen, M.H. Age-Related Macular Degeneration. Drugs & Aging 19, 101–133 (2002). https://doi.org/10.2165/00002512-200219020-00003

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