Clinical Strategies for Diagnosis and Treatment of AMD: Implications from Research

  • Scott W. Cousins
  • Karl G. Csaky
  • Diego G. Espinosa-Heidmann


Retinal Pigment Epithelial Choroidal Neovascularization Macular Photocoagulation Study Basal Laminar Deposit Macular Photocoagulation Study Group 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Abdelsalam A, Del Priore L, Zarbin MA (1999) Drusen in age-related macular degeneration: pathogenesis, natural course, and laser photocoagulation-induced regression. Surv Ophthalmol 44: 1–29PubMedGoogle Scholar
  2. Abedi H, Zachary I (1995) Signalling mechanisms in the regulation of vascular cell migration. Cardiovasc Res 30: 544–556CrossRefPubMedGoogle Scholar
  3. Aiello LP, Pierce EA, Foley ED, Takagi H, Chen H, Riddle L, Ferrara N, King GL, Smith LE (1995) Suppression of retinal neovascularization in vivo by inhibition of vascular endothelial growth factor (VEGF) using soluble VEGF-receptor chimeric proteins. Proc Natl Acad Sci USA 92: 10457–10461PubMedGoogle Scholar
  4. Aisenbrey S, Lafaut BA, Szurman P, Grisanti S, Luke C, Krott R, Thumann G, Fricke J, Neugebauer A, Hilgers RD, Esser P, Walter P, Bartz-Schmidt KU (2002) Macular translocation with 360 degrees retinotomy for exudative age-related macular degeneration. Arch Ophthalmol 120: 451–459PubMedGoogle Scholar
  5. Ambati J, Ambati BK, Yoo SH, Ianchulev S, Adamis AP (2003) Age-related macular degeneration: etiology, pathogenesis, and therapeutic strategies. Surv Ophthalmol 48: 257–293PubMedGoogle Scholar
  6. Andersen MS, Sorensen CB, Bolund L, Jensen TG (2002) Mechanisms underlying targeted gene correction using chimeric RNA/DNA and single-stranded DNA oligonucleotides. J Mol Med 80: 770–781CrossRefPubMedGoogle Scholar
  7. Anderson DH, Mullins RF, Hageman GS, Johnson LV (2002) A role for local inflammation in the formation of drusen in the aging eye. Am J Ophthalmol 134: 411–43CrossRefPubMedGoogle Scholar
  8. Archer DB, Gardiner TA (1980) Experimental subretinal neovascularization. Trans Ophthalmol Soc UK 100: 363–368PubMedGoogle Scholar
  9. Archer DB, Gardiner TA (1994) Ionizing radiation and the retina. Curr Opin Ophthalmol 5: 59–65PubMedGoogle Scholar
  10. AREDS (2001) A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E and beta carotene for age-related cataract and vision loss: AREDS report no. 9. Arch Ophthalmol 119: 1417–1436Google Scholar
  11. Asahara T, Murohara T, Sullivan A, Silver M, van der Zee R, Li T, Witzenbichler B, Schatteman G, Isner JM (1997) Isolation of putative progenitor endothelial cells for angiogenesis. Science 275: 964–967CrossRefPubMedGoogle Scholar
  12. Asahara T, Takahashi T, Masuda H, Kalka C, Chen D, Iwaguro H, Inai Y, Silver M, Isner JM (1999) VEGF contributes to postnatal neovascularization by mobilizing bone marrow-derived endothelial progenitor cells. EMBO J 18: 3964–3972CrossRefPubMedGoogle Scholar
  13. Au Eong KG, Pieramici DJ, Fujii GY, Ng EW, Humayun MS, Maia M, Harlan JB Jr, Schachat AP, Beatty S, Toth CA, Thomas MA, Lewis H, Eckardt C, Tano Y, de Juan E (2001) Macular translocation: unifying concepts, terminology, and classification. Am J Ophthalmol 131: 244–253Google Scholar
  14. Aumailley M, Gayraud B (1998) Structure and biological activity of the extracellular matrix. J Mol Med 76: 253–265CrossRefPubMedGoogle Scholar
  15. Azevedo LC, Pedro MA, Souza LC, Souza HP de, Janiszewski M, Luz PL da, Laurindo FR (2000) Oxidative stress as a signaling mechanism of the vascular response to injury: the redox hypothesis of restenosis. Cardiovasc Res 47: 436–445CrossRefPubMedGoogle Scholar
  16. Bailey AS, Fleming WH (2003) Converging roads: evidence for an adult hemangioblast. Exp Hematol 31: 987–993CrossRefPubMedGoogle Scholar
  17. Bartlett H, Eperjesi F (2003) Age-related macular degeneration and nutritional supplementation: a review of randomised controlled trials. Ophthalmic Physiol Opt 23: 383–399CrossRefPubMedGoogle Scholar
  18. Beatty S, Koh H, Phil M, Henson D, Boulton M (2000) The role of oxidative stress in the pathogenesis of age-related macular degeneration. Surv Ophthalmol 45: 115–134PubMedGoogle Scholar
  19. Belkhiri A, Richards C, Whaley M, McQueen SA, Orr FW (1997) Increased expression of activated matrix metalloproteinase-2 by human endothelial cells after sublethal H2O2 exposure. Laboratory Invest 77: 533–539Google Scholar
  20. Bellmann C, Unnebrink K, Rubin GS, Miller D, Holz FG (2003) Visual acuity and contrast sensitivity in patients with neovascular age-related macular degeneration. Results from the Radiation Therapy for Age-Related Macular Degeneration (RAD-) Study. Graefes Arch Clin Exp Ophthalmol 241: 968–974CrossRefPubMedGoogle Scholar
  21. BenEzra D, Griffin BW, Maftzir G, Sharif NA, Clark AF (1997) Topical formulations of novel angiostatic steroids inhibit rabbit corneal neovascularization. Invest Ophthalmol Vis Sci 38: 1954–1962PubMedGoogle Scholar
  22. Berglin L, Algvere P, Olivestedt G, Crafoord S, Stenkula S, Hansson LJ, Tomic Z, Kvanta A, Seregard S (2001) The Swedish national survey of surgical excision for submacular choroidal neovascularization (CNV). Acta Ophthalmol Scand 79: 580–584CrossRefPubMedGoogle Scholar
  23. Bird AC, Bressler NM, Bressler SB, Chisholm IH, Coscas G, Davis MD, Jong PT de, Klaver CC, Klein BE, Klein R (1995) An international classification and grading system for age-related maculopathy and age-related macular degeneration. The International ARM Epidemiological Study Group. Surv Ophthalmol 39: 367–374PubMedGoogle Scholar
  24. Blei F, Wilson EL, Mignatti P, Rifkin DB (1993) Mechanism of action of angiostatic steroids: suppression of plasminogen activator activity via stimulation of plasminogen activator inhibitor synthesis. J Cell Physiol 155: 568–578CrossRefPubMedGoogle Scholar
  25. Blumenkranz MS, Woodburn KW, Qing F, Verdooner S, Kessel D, Miller R (2000) Lutetium texaphyrin (Lu-Tex): a potential new agent for ocular fundus angiography and photodynamic therapy. Am J Ophthalmol 129: 353–362CrossRefPubMedGoogle Scholar
  26. Bressler NM (2001) 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 119: 198–207PubMedGoogle Scholar
  27. Bressler NM, Bressler SB, Fine SL (1988) Age-related macular degeneration. Surv Ophthalmol 32: 375–413PubMedGoogle Scholar
  28. Bundy RE, Marczin N, Birks EF, Chester AH, Yacoub MH (2000) Transplant atherosclerosis: role of phenotypic modulation of vascular smooth muscle by nitric oxide. Gen Pharmacol 34: 73–84CrossRefPubMedGoogle Scholar
  29. Burton EA, Fink DJ, Glorioso JC (2002) Gene delivery using herpes simplex virus vectors. DNA Cell Biol 21: 915–936CrossRefPubMedGoogle Scholar
  30. Caicedo A (2003) Photoreceptor synapses are disrupted after experimental choroidal neovascularization. Soc Neurosci 816: 3 (abstract)Google Scholar
  31. Caicedo A, Espinosa-Heidmann DG, Cousins SW (2003) Glutamate transporters at photoreceptor synapses are downregulated after experimental choroidal neovascularization. Invest Ophthalmol Vis Sci E (Abstract 3935)Google Scholar
  32. Castellarin AA, Nasir MA, Sugino IK, Zarbin MA (1998) Clinicopathological correlation of primary and recurrent choroidal neovascularisation following surgical excision in age related macular degeneration. Br J Ophthalmol 82: 480–487PubMedGoogle Scholar
  33. Chang AA, Tan W, Beaumont PE, Zeldovich A (2003) Limited macular translocation for subfoveal choroidal neovascularization in age-related macular degeneration. Clin Exp Ophthalmol 31: 103–109Google Scholar
  34. Choroidal Neovascularization Prevention Trial Research Group (1998) Choroidal neovascularization in the Choroidal Neovascularization Prevention Trial. Ophthalmology 105: 1364–1372Google Scholar
  35. Choroidal Neovascularization Prevention Trial Research Group (2003) Laser treatment in fellow eyes with large drusen: updated findings from a pilot randomized clinical trial. Ophthalmology 110: 971–978Google Scholar
  36. Chung M, Lotery AJ (2002) Genetics update of macular diseases. Ophthalmol Clin North Am 15: 459–465CrossRefPubMedGoogle Scholar
  37. Ciardella AP, Donsoff IM, Guyer DR, Adamis A, Yannuzzi LA (2002) Antiangiogenesis agents. Ophthalmol Clin North Am 15: 453–458PubMedGoogle Scholar
  38. Ciulla TA, Criswell MH, Danis RP, Fronheiser M, Yuan P, Cox TA, Csaky KG, Robinson MR (2003) Choroidal neovascular membrane inhibition in a laser treated rat model with intraocular sustained release triamcinolone acetonide microimplants. Br J Ophthalmol 87: 1032–1037CrossRefPubMedGoogle Scholar
  39. Clark AF, Mellon J, Li XY, Ma D, Leher H, Apte R, Alizadeh H, Hegde S, McLenaghan A, Mayhew E, D’Orazio TJ, Niederkorn JY (1999) Inhibition of intraocular tumor growth by topical application of the angiostatic steroid anecortave acetate. Invest Ophthalmol Vis Sci 40: 2158–2162PubMedGoogle Scholar
  40. Cornacchia F, Fornoni A, Plati AR, Thomas A, Wang Y, Inverardi L, Striker LJ, Striker GE (2001) Glomerulosclerosis is transmitted by bone marrow-derived mesangial cell progenitors. J Clin Invest 108: 1649–1656CrossRefPubMedGoogle Scholar
  41. Cour M la, Kiilgaard JF, Nissen MH (2002) Age-related macular degeneration: epidemiology and optimal treatment. Drugs Aging 19: 101–133PubMedGoogle Scholar
  42. Cousins SW, Csaky KG (2002) Immunology of age-related macular degeneration. In: Lim JI (ed.) Age-related macular degeneration. Marcel Decker, New York, pp 27–65Google Scholar
  43. Cousins SW, Espinosa-Heidmann DG, Alexandridou A, Sall J, Dubovy S, Csaky K (2002) The role of aging, high fat diet and blue light exposure in an experimental mouse model for basal laminar deposit formation. Exp Eye Res 75: 543–553CrossRefPubMedGoogle Scholar
  44. Cousins SW, Espinosa-Heidmann DG, Marin-Castano ME (2003a) Smoking-related oxidants and RPE injury in vitro and in vivo. Invest Ophthalmol Vis Sci E (Abstract 1619)Google Scholar
  45. Cousins SW, Marin-Castano ME, Espinosa-Heidmann DG, Alexandridou A, Striker L, Elliot S (2003b) Female gender, estrogen loss, and Sub-RPE deposit formation in aged mice. Invest Ophthalmol Vis Sci 44: 1221–1229CrossRefPubMedGoogle Scholar
  46. Cousins SW, Espinosa-Heidmann DG, Csaky KG (2004) Macrophage function in patients with age-related macular degeneration (AMD): A biomarker for progression? Arch Ophthalmol 22: 1013–1018Google Scholar
  47. Csaky K (2003) Anti-vascular endothelial growth factor therapy for neovascular age-related macular degeneration: promises and pitfalls. Ophthalmology 110: 879–881CrossRefPubMedGoogle Scholar
  48. Curcio CA, Millican CL (1999) Basal linear deposit and large drusen are specific for early age-related maculopathy. Arch Ophthalmol 117: 329–339PubMedGoogle Scholar
  49. Curcio CA, Medeiros NE, Millican CL (1996) Photoreceptor loss in age-related macular degeneration. Invest Ophthalmol Vis Sci 37: 1236–1249PubMedGoogle Scholar
  50. Curcio CA, Owsley C, Jackson GR (2000) Spare the rods, save the cones in aging and age-related maculopathy. Invest Ophthalmol Vis Sci 41: 2015–2018PubMedGoogle Scholar
  51. Curcio CA, Bradley K, Guidry C, et al. (2002) A local source for esterified cholesterol (EC) in human Bruch’s membrane (BrM). Invest Ophthalmol Vis Sci E (Abstract 862)Google Scholar
  52. D’Amico DJ, Goldberg MF, Hudson H, Jerdan JA, Krueger S, Luna S, Robertson SM, Russell S, Singerman L, Slakter JS, Sullivan EK, Yannuzzi L, Zilliox P (2003) Anecortave acetate as monotherapy for the treatment of subfoveal lesions in patients with exudative age-related macular degeneration (AMD): interim (month 6) analysis of clinical safety and efficacy. Retina 23: 14–23PubMedGoogle Scholar
  53. Davies KJ (1995) Oxidative stress: the paradox of aerobic life. Biochem Soc Symp 61: 1–31PubMedGoogle Scholar
  54. DeFaller JM, Clark AF (2000) A new pharmacological treatment for angiogenesis. In: Taylor HR (ed.) Pterygium. Kugler, The Hague, The Netherlands,pp 159–181Google Scholar
  55. Desatnik H, Treister G, Alhalel A, Krupsky S, Moisseiev J (2000) ICGA-guided laser photocoagulation of feeder vessels of choroidal neovascular membranes in age-related macular degeneration. Indocyanine green angiography. Retina 20: 143–150PubMedGoogle Scholar
  56. Deviere J (2002) Do selective cyclo-oxygenase inhibitors eliminate the adverse events associated with nonsteroidal anti-inflammatory drug therapy? Eur J Gastroenterol Hepatol 14(Suppl 1): S29–33PubMedGoogle Scholar
  57. Diaz-Flores L, Gutierrez R, Varela H (1994) Angiogenesis: an update. Histol Histopathol 9: 807–843PubMedGoogle Scholar
  58. Distler JH, Hirth A, Kurowska-Stolarska M, Gay RE, Gay S, Distler O (2003) Angiogenic and angiostatic factors in the molecular control of angiogenesis. Q J Nucl Med 47: 149–161PubMedGoogle Scholar
  59. Donati G, Kapetanios AD, Pournaras CJ (1999) Principles of treatment of choroidal neovascularization with photodynamic therapy in age-related macular degeneration. Semin Ophthalmol 14: 2–10PubMedGoogle Scholar
  60. Dorey CK, Wu G, Ebenstein D, Garsd A, Weiter JJ (1989) Cell loss in the aging retina. Relationship to lipofuscin accumulation and macular degeneration. Invest Ophthalmol Vis Sci 30: 1691–1699PubMedGoogle Scholar
  61. Drew MJ (2002) Plasmapheresis in the dysproteinemias. Ther Apher 6: 45–52PubMedGoogle Scholar
  62. Drolet DW, Nelson J, Tucker CE, Zack PM, Nixon K, Bolin R, Judkins MB, Farmer JA, Wolf JL, Gill SC, Bendele RA (2000) Pharmacokinetics and safety of an anti-vascular endothelial growth factor aptamer (NX1838) following injection into the vitreous humor of rhesus monkeys. Pharm Res 17: 1503–1510CrossRefPubMedGoogle Scholar
  63. Espinosa-Heidmann DG, Caicedo A, Cousins SW (2003a) Adult bone marrow derived progenitor cells contribute to choroidal neovascularization and modulate the severity. Invest Ophthalmol Vis Sci E (Abstract 3936)Google Scholar
  64. Espinosa-Heidmann DG, Caicedo A, Hernandez EP, Csaky KG, Cousins SW (2003b) Bone marrow-derived progenitor cells contribute to experimental choroidal neovascularization. Invest Ophthalmol Vis Sci 44: 4914–4919PubMedGoogle Scholar
  65. Espinosa-Heidmann DG, Suner IJ, Hernandez EP, Monroy D, Csaky KG, Cousins SW (2003c) Macrophage depletion diminishes lesion size and severity in experimental choroidal neovascularization. Invest Ophthalmol Vis Sci 44: 3586–3592PubMedGoogle Scholar
  66. Espinosa-Heidmann DG, Sall J, Hernandez EP, Cousins SW (2004) Basal laminar deposit formation in APO B100 transgenic mice: complex interactions between dietary fat, blue light, and vitamin E. Invest Ophthalmol Vis Sci 45: 260–266CrossRefPubMedGoogle Scholar
  67. Evans JR (2001) Risk factors for age-related macular degeneration. Prog Retin Eye Res 20: 227–253CrossRefPubMedGoogle Scholar
  68. Eyetech Study Group (2002) Preclinical and phase 1A clinical evaluation of an anti-VEGF pegylated aptamer (EYE001) for the treatment of exudative agerelated macular degeneration. Retina 22: 143–152Google Scholar
  69. Eyetech Study Group (2003) Anti-vascular endothelial growth factor therapy for subfoveal choroidal neovascularization secondary to age-related macular degeneration: phase II study results. Ophthalmology 110: 979–986Google Scholar
  70. Felbor U, Benkwitz C, Klein ML, Greenberg J, Gregory CY, Weber BH (1997) Sorsby fundus dystrophy: reevaluation of variable expressivity in patients carrying a TIMP3 founder mutation. Arch Ophthalmol 115: 1569–1571PubMedGoogle Scholar
  71. Flower RW (2002) Optimizing treatment of choroidal neovascularization feeder vessels associated with age-related macular degeneration. Am J Ophthalmol 134: 228–239CrossRefPubMedGoogle Scholar
  72. Folkman J (2003) Fundamental concepts of the angiogenic process. Curr Mol Med 3: 643–651CrossRefPubMedGoogle Scholar
  73. Folkman J, Shing Y (1992) Angiogenesis. J Biol Chem 267: 10931–10934PubMedGoogle Scholar
  74. Friberg TR (1999) Laser photocoagulation of eyes with drusen: will It help? Semin Ophthalmol 14: 45–50PubMedGoogle Scholar
  75. Friberg TR, Musch D (2002) Prophylactic treatment of age-related macular degeneration (PTAMD): update on the clinical trial. Invest Ophthalmol Vis Sci E (Abstract 2904)Google Scholar
  76. Fujii GY, Juan E Jrde, Au Eong KG, Harlan JB Jr (2001a) Effective nasal limited macular translocation. Am J Ophthalmol 132: 124–126CrossRefPubMedGoogle Scholar
  77. Fujii GY, Juan E de, Thomas MA, Pieramici DJ, Humayun MS, Au Eong KG (2001b) Limited macular translocation for the management of subfoveal retinal pigment epithelial loss after submacular surgery. Am J Ophthalmol 131: 272–275PubMedGoogle Scholar
  78. Fujii GY, Au Eong KG, Humayun MS, Juan E Jr de (2002) Limited macular translocation: current concepts. Ophthalmol Clin North Am 15: 425–436CrossRefPubMedGoogle Scholar
  79. Fujiyama S, Amano K, Uehira K, Yoshida M, Nishiwaki Y, Nozawa Y, Jin D, Takai S, Miyazaki M, Egashira K, Imada T, Iwasaka T, Matsubara H (2003) Bone marrow monocyte lineage cells adhere on injured endothelium in a monocyte chemoattractant protein-1-dependent manner and accelerate reendothelialization as endothelial progenitor cells. Circ Res 93: 980–989CrossRefPubMedGoogle Scholar
  80. Gandorfer A, Scheider A, Gundisch O, Kampik A (1998) [Recurrent choroid neovascularization in age-related macular degeneration. Fluorescein angiographic morphology after surgical membranectomy]. Ophthalmologe 95: 408–412CrossRefPubMedGoogle Scholar
  81. Gass JD (1987) Stereoscopic atlas of macular diseases. Mosby, St. LouisGoogle Scholar
  82. Gebicke-Haerter PJ, Van Calker D, Norenberg W, Illes P (1996) Molecular mechanisms of microglial activation. A. Implications for regeneration and neurodegenerative diseases. Neurochem Int 29: 1–12CrossRefPubMedGoogle Scholar
  83. Gehlbach P, Demetriades AM, Yamamoto S, Deering T, Duh EJ, Yang HS, Cingolani C, Lai H, Wei L, Campochiaro PA (2003) Periocular injection of an adenoviral vector encoding pigment epithelium-derived factor inhibits choroidal neovascularization. Gene Ther 10: 637–646CrossRefPubMedGoogle Scholar
  84. Genaidy M, Kazi AA, Peyman GA, Passos-Machado E, Farahat HG, Williams JI, Holroyd KJ, Blake DA (2002) Effect of squalamine on iris neovascularization in monkeys. Retina 22: 772–778PubMedGoogle Scholar
  85. Goncalves AR, Fujihara CK, Mattar AL, Malheiros DM, Noronha Ide L, de Nucci G, Zatz R (2004) Renal expression of COX-2, ANG II, and AT1 receptor in remnant kidney: strong renoprotection by therapy with losartan and a nonsteroidal anti-inflammatory. Am J Physiol Renal Physiol 286: F945–954 (Epub 2003 Dec 16)CrossRefPubMedGoogle Scholar
  86. Gorin MB, Breitner JC, Jong PT de, Hageman GS, Klaver CC, Kuehn MH, Seddon JM (1999) The genetics of age-related macular degeneration. Mol Vis 5: 29PubMedGoogle Scholar
  87. Grant MB, May WS, Caballero S, Brown GA, Guthrie SM, Mames RN, Byrne BJ, Vaught T, Spoerri PE, Peck AB, Scott EW (2002) Adult hematopoietic stem cells provide functional hemangioblast activity during retinal neovascularization. Nat Med 8: 607–612CrossRefPubMedGoogle Scholar
  88. Green WR (1999) Histopathology of age-related macular degeneration. Mol Vis 5: 27PubMedGoogle Scholar
  89. Green WR, Harlan JB (1999) Histopathologic Features. In: Berger JW, Fine SL, Maguire MG (eds) Age-related macular degeneration. Mosby, St. Louis, pp 81–154Google Scholar
  90. Griggs J, Hesketh R, Smith GA, Brindle KM, Metcalfe JC, Thomas GA, Williams ED (2001a) Combretastatin-A4 disrupts neovascular development in non-neoplastic tissue. Br J Cancer 84: 832–835CrossRefPubMedGoogle Scholar
  91. Griggs J, Metcalfe JC, Hesketh R (2001b) Targeting tumour vasculature: the development of combretastatin A4. Lancet Oncol 2: 82–87CrossRefPubMedGoogle Scholar
  92. Griggs J, Skepper JN, Smith GA, Brindle KM, Metcalfe JC, Hesketh R (2002) Inhibition of proliferative retinopathy by the anti-vascular agent combretastatin-A4. Am J Pathol 160: 1097–1103PubMedGoogle Scholar
  93. Grossniklaus HE, Cingle KA, Yoon YD, Ketkar N, L’Hernault N, Brown S (2000) Correlation of histologic 2-dimensional reconstruction and confocal scanning laser microscopic imaging of choroidal neovascularization in eyes with age-related maculopathy. Arch Ophthalmol 118: 625–629PubMedGoogle Scholar
  94. Grossniklaus HE, Ling JX, Wallace TM, Dithmar S, Lawson DH, Cohen C, Elner VM, Elner SG, Sternberg P Jr (2002) Macrophage and retinal pigment epithelium expression of angiogenic cytokines in choroidal neovascularization. Mol Vis 8: 119–126PubMedGoogle Scholar
  95. Grunwald JE (1999) Choroidal blood flow. In: Berger JW, Fine SL, Maguire MG (eds) Age-related macular degeneration. Mosby, St. Louis, pp 167–172Google Scholar
  96. Gupta A, Pansari K (2003) Inflammation and Alzheimer’s disease. Int J Clin Pract 57: 36–39PubMedGoogle Scholar
  97. Guyer DR, Yannuzzi LA, Slakter JS, Sorenson JA, Hanutsaha P, Spaide RF, Schwartz SG, Hirschfeld JM, Orlock DA (1996) Classification of choroidal neovascularization by digital indocyanine green videoangiography. Ophthalmology 103: 2054–2060PubMedGoogle Scholar
  98. Hageman GS, Mullins RF (1999) Molecular composition of drusen as related to substructural phenotype. Mol Vis 5: 28PubMedGoogle Scholar
  99. Hageman GS, Luthert PJ, Victor Chong NH, Johnson LV, Anderson DH, Mullins RF (2001) 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 20: 705–732CrossRefPubMedGoogle Scholar
  100. Hamdi HK, Kenney C (2003) Age-related macular degeneration: a new viewpoint. Front Biosci 8: e305–e314PubMedGoogle Scholar
  101. Hanutsaha P, Guyer DR, Yannuzzi LA, Naing A, Slakter JS, Sorenson JS, Spaide RF, Freund KB, Feinsod M, Orlock DA (1998) Indocyanine-green videoangiography of drusen as a possible predictive indicator of exudative maculopathy. Ophthalmology 105: 1632–1636CrossRefPubMedGoogle Scholar
  102. Harding S (2001) Photodynamic therapy in the treatment of subfoveal choroidal neovascularisation. Eye 15: 407–412PubMedGoogle Scholar
  103. Harjai KJ, Chowdhury P, Grines CL (2002) Therapeutic angiogenesis: a fantastic new adventure. J Interv Cardiol 15: 223–229PubMedGoogle Scholar
  104. Harraz M, Jiao C, Hanlon HD, Hartley RS, Schatteman GC (2001) CD34 — blood-derived human endothelial cell progenitors. Stem Cells 19: 304–312CrossRefPubMedGoogle Scholar
  105. Hart PM, Chakravarthy U, Mackenzie G, Chisholm IH, Bird AC, Stevenson MR, Owens SL, Hall V, Houston RF, McCulloch DW, Plowman N (2002) Visual outcomes in the subfoveal radiotherapy study: a randomized controlled trial of teletherapy for age-related macular degeneration. Arch Ophthalmol 120: 1029–1038PubMedGoogle Scholar
  106. Hawkins BS, Bird A, Klein R, West SK (1999) Epidemiology of age-related macular degeneration. Mol Vis 5: 26PubMedGoogle Scholar
  107. Hee MR, Baumal CR, Puliafito CA, Duker JS, Reichel E, Wilkins JR, Coker JG, Schuman JS, Swanson EA, Fujimoto JG (1996) Optical coherence tomography of age-related macular degeneration and choroidal neovascularization. Ophthalmology 103: 1260–1270PubMedGoogle Scholar
  108. Hermans P, Lommatzsch A, Bomfeld N, Pauleikhoff D (2003) [Angiographic-histological correlation of late exudative age-related macular degeneration]. Ophthalmologe 100: 378–383CrossRefPubMedGoogle Scholar
  109. Higgins RD, Sanders RJ, Yan Y, Zasloff M, Williams JI (2000) Squalamine improves retinal neovascularization. Invest Ophthalmol Vis Sci 41: 1507–1512PubMedGoogle Scholar
  110. Ho AC (1999) Laser treatment in eyes with drusen. Curr Opin Ophthalmol 10: 204–208CrossRefPubMedGoogle Scholar
  111. Ho CL (2000) Macular translocation — an innovative treatment for macular degenerative diseases. Changgeng Yi Xue Za Zhi 23: 672–680PubMedGoogle Scholar
  112. Hoffmann S, Friedrichs U, Eichler W, Rosenthal A, Wiedemann P (2002) Advanced glycation end products induce choroidal endothelial cell proliferation, matrix metalloproteinase-2 and VEGF upregulation in vitro. Graefes Arch Clin Exp Ophthalmol 240: 996–1002PubMedGoogle Scholar
  113. Holz FG, Miller DW (2003) [Pharmacological therapy for age-related macular degeneration. Current developments and perspectives]. Ophthalmologe 100: 97–103PubMedGoogle Scholar
  114. Hunt DW, Margaron P (2003) Status of therapies in development for the treatment of age-related macular degeneration. IDrugs 6: 464–469PubMedGoogle Scholar
  115. Hyman L, Neborsky R (2002) Risk factors for age-related macular degeneration: an update. Curr Opin Ophthalmol 13: 171–175CrossRefPubMedGoogle Scholar
  116. Hyman L, Schachat AP, He Q, Leske MC (2000) Hypertension, cardiovascular disease, and age-related macular degeneration. Age-Related Macular Degeneration Risk Factors Study Group. Arch Ophthalmol 118: 351–358PubMedGoogle Scholar
  117. Ianus A, Holz GG, Theise ND, Hussain MA (2003) In vivo derivation of glucose-competent pancreatic endocrine cells from bone marrow without evidence of cell fusion. J Clin Invest 111: 843–850CrossRefPubMedGoogle Scholar
  118. Ishiko S, Akiba J, Horikawa Y, Yoshida A (2002) Detection of drusen in the fellow eye of Japanese patients with age-related macular degeneration using scanning laser ophthalmoscopy. Ophthalmology 109: 2165–2169CrossRefPubMedGoogle Scholar
  119. Isner JM, Asahara T (1999) Angiogenesis and vasculogenesis as therapeutic strategies for postnatal neovascularization. J Clin Invest 103: 1231–1236PubMedCrossRefGoogle Scholar
  120. Ito T, Ikeda U (2003) Inflammatory cytokines and cardiovascular disease. Curr Drug Targets Inflamm Allergy 2: 257–265PubMedGoogle Scholar
  121. Jacot TA, Striker GE, Stetler-Stevenson M, Striker LJ (1996) Mesangial cells from transgenic mice with progressive glomerulosclerosis exhibit stable, phenotypic changes including undetectable MMP-9 and increased type IV collagen. Laboratory Invest 75: 791–799Google Scholar
  122. Johnson LV, Leitner WP, Staples MK, Anderson DH (2001a) Complement activation and inflammatory processes in Drusen formation and age related macular degeneration. Exp Eye Res 73: 887–896CrossRefPubMedGoogle Scholar
  123. Johnson LV, Ozaki, S, Staples MK, Erikson, PA and Anderson, DH (2001b) A potential role for immune complex pathogenesis in drusen formation. Exp Eye Res 70: 441–449Google Scholar
  124. Juan E Jr de, Fujii GY (2001) Limited macular translocation. Eye 15: 413–423PubMedGoogle Scholar
  125. Juan E Jr de, Machemer R (1988) Vitreous surgery for hemorrhagic and fibrous complications of age-related macular degeneration. Am J Ophthalmol 105: 25–29PubMedGoogle Scholar
  126. Juan E Jr de, Vander JF (1999) Effective macular translocation without scleral imbrication. Am J Ophthalmol 128: 380–382PubMedGoogle Scholar
  127. Juan E Jr de, Loewenstein A, Bressler NM, Alexander J (1998) Translocation of the retina for management of subfoveal choroidal neovascularization II: a preliminary report in humans. Am J Ophthalmol 125: 635–646PubMedGoogle Scholar
  128. Kaiser HJ, Flammer J, Stumpfig D, Hendrickson P (1995) Visaline in the treatment of age-related macular degeneration: a pilot study. Ophthalmologica 209: 302–305PubMedCrossRefGoogle Scholar
  129. Kampik A, Gandorfer A (2000) Silicone oil removal strategies. Semin Ophthalmol 15: 88–91PubMedCrossRefGoogle Scholar
  130. Kieran MW, Billett A (2001) Antiangiogenesis therapy. Current and future agents. Hematol Oncol Clin North Am 15: 835–851, viiiCrossRefPubMedGoogle Scholar
  131. Killingsworth MC, Sarks JP, Sarks SH (1990) Macrophages related to Bruch’s membrane in age-related macular degeneration. Eye 4: 613–621PubMedGoogle Scholar
  132. Klaver CC, Allikmets R (2003) Genetics of macular dystrophies and implications for age-related macular degeneration. Dev Ophthalmol 37: 155–169PubMedGoogle Scholar
  133. Klaver CC, Kliffen M, Duijn CM van, Hofman A, Cruts M, Grobbee DE, Broeckhoven C van, Jong PT de (1998) Genetic association of apolipoprotein E with age-related macular degeneration. Am J Hum Genet 63: 200–206CrossRefPubMedGoogle Scholar
  134. Klein EA (1999) Epidemiology. In: Berger JW, Fine SL, Maguire MG (eds) Age-related macular disease. Mosby, St. Louis, pp 31–55Google Scholar
  135. Kliffen M, Schaft TL van der, Mooy CM, Jong PT de (1997) Morphologic changes in age-related maculopathy. Microsc Res Tech 36: 106–122CrossRefPubMedGoogle Scholar
  136. Klingel R, Fassbender C, Fischer I, Hattenbach L, Gumbel H, Pulido J, Koch F (2002) Rheopheresis for agerelated macular degeneration: a novel indication for therapeutic apheresis in ophthalmology. Ther Apher 6: 271–281PubMedGoogle Scholar
  137. Kramer I, Wibulswas A, Croft D, Genot E (2003) Rheumatoid arthritis: targeting the proliferative fibroblasts. Prog Cell Cycle Res 5: 59–70PubMedGoogle Scholar
  138. Krzystolik MG, Afshari MA, Adamis AP, Gaudreault J, Gragoudas ES, Michaud NA, Li W, Connolly E, O’-Neill CA, Miller JW (2002) Prevention of experimental choroidal neovascularization with intravitreal anti-vascular endothelial growth factor antibody fragment. Arch Ophthalmol 120: 338–346PubMedGoogle Scholar
  139. Labarge MA, Blau HM (2002) Biological progression from adult bone marrow to mononucleate muscle stem cell to multinucleate muscle fiber in response to injury. Cell 111: 589–601CrossRefPubMedGoogle Scholar
  140. Lai CM, Lai YK, Rakoczy PE (2002) Adenovirus and adeno-associated virus vectors. DNA Cell Biol 21: 895–913CrossRefPubMedGoogle Scholar
  141. Lambert V, Munaut C, Jost M, Noel A, Werb Z, Foidart JM, Rakic JM (2002) Matrix metalloproteinase-9 contributes to choroidal neovascularization. Am J Pathol 161: 1247–1253PubMedGoogle Scholar
  142. Li G, Gao R (1995) [Vitrectomy for treatment of vitreous hemorrhage associated with age-related macular degeneration]. Zhonghua Yan Ke Za Zhi 31: 262–263PubMedGoogle Scholar
  143. Lim JI (2002) Photodynamic therapy for choroidal neovascular disease: photosensitizers and clinical trials. Ophthalmol Clin North Am 15: 473–478, viiCrossRefPubMedGoogle Scholar
  144. Lopez PF, Sippy BD, Lambert HM, Thach AB, Hinton DR (1996) Transdifferentiated retinal pigment epithelial cells are immunoreactive for vascular endothelial growth factor in surgically excised age-related macular degeneration-related choroidal neovascular membranes. Invest Ophthalmol Vis Sci 37: 855–868PubMedGoogle Scholar
  145. Lowe GD (2001) The relationship between infection, inflammation, and cardiovascular disease: an overview. Ann Periodontol 6: 1–8CrossRefPubMedGoogle Scholar
  146. Lutty G, Grunwald J, Majji AB, Uyama M, Yoneya S (1999) Changes in choriocapillaris and retinal pigment epithelium in age-related macular degeneration. Mol Vis 5: 35PubMedGoogle Scholar
  147. Macular Photocoagulation Study Group (1991a) Laser photocoagulation of subfoveal neovascular lesions in age-related macular degeneration. Results of a randomized clinical trial. Macular Photocoagulation Study Group. Arch Ophthalmol 109: 1220–1231Google Scholar
  148. Macular Photocoagulation Study Group (1991b) Laser photocoagulation of subfoveal recurrent neovascular lesions in age-related macular degeneration. Results of a randomized clinical trial. Macular Photocoagulation Study Group. Arch Ophthalmol 109: 1232–1241Google Scholar
  149. Macular Photocoagulation Study Group (1991c) Subfoveal neovascular lesions in age-related macular degeneration. Guidelines for evaluation and treatment in the macular photocoagulation study. Arch Ophthalmol 109: 1242–1257Google Scholar
  150. Macular Photocoagulation Study Group (1994) Laser photocoagulation for juxtafoveal choroidal neovascularization. Five-year results from randomized clinical trials. Macular Photocoagulation Study Group. Arch Ophthalmol 112: 500–509Google Scholar
  151. Macular Photocoagulation Study Group (1996) Occult choroidal neovascularization. Influence on visual outcome in patients with age-related macular degeneration. Arch Ophthalmol 114: 400–412Google Scholar
  152. Maguire MG (2004) Natural history. In: Berger JW, Fine SL, Maguire MG (eds) Age-related macular degeneration. Mosby, St. Louis, pp 16–30Google Scholar
  153. Malorni W, Donelli G (1992) Cell death. General features and morphological aspects. Ann NY Acad Sci 663: 218–233PubMedGoogle Scholar
  154. Malorni W, Iosi F, Mirabelli F, Bellomo G (1991) Cytoskeleton as a target in menadione-induced oxidative stress in cultured mammalian cells: alterations underlying surface bleb formation. Chem Biol Interact 80: 217–236PubMedGoogle Scholar
  155. Mandelcorn MS, Menezes AV (1993) Surgical removal of subretinal hemorrhage and choroidal neovascular membranes in acute hemorrhagic age-related macular degeneration. Can J Ophthalmol 28: 19–23PubMedGoogle Scholar
  156. Marcus DM, Sheils W, Johnson MH, McIntosh SB, Leibach DB, Maguire A, Alexander J, Samy CN (2001) External beam irradiation of subfoveal choroidal neovascularization complicating age-related macular degeneration: one-year results of a prospective, double-masked, randomized clinical trial. Arch Ophthalmol 119: 171–180PubMedGoogle Scholar
  157. McCarty CA, Mukesh BN, Fu CL, Mitchell P, Wang JJ, Taylor HR (2001) Risk factors for age-related maculopathy: the Visual Impairment Project. Arch Ophthalmol 119: 1455–1462PubMedGoogle Scholar
  158. McGeer EG, McGeer PL (2003) Inflammatory processes in Alzheimer’s disease. Prog Neuropsychopharmacol Biol Psychiatry 27: 741–749CrossRefPubMedGoogle Scholar
  159. McNatt LG, Weimer L, Yanni J, Clark AF (1999) Angiostatic activity of steroids in the chick embryo CAM and rabbit cornea models of neovascularization. J Ocul Pharmacol Ther 15: 413–423PubMedGoogle Scholar
  160. Michalowski AS (1994) On radiation damage to normal tissues and its treatment. II. Anti-inflammatory drugs. Acta Oncol 33: 139–157PubMedCrossRefGoogle Scholar
  161. Mittra RA, Singerman LJ (2002) Recent advances in the management of age-related macular degeneration. Optom Vis Sci 79: 218–224PubMedGoogle Scholar
  162. Moisseiev J, Alhalel A, Masuri R, Treister G (1995) The impact of the macular photocoagulation study results on the treatment of exudative age-related macular degeneration. Arch Ophthalmol 113: 185–189PubMedGoogle Scholar
  163. Monroy D, Marin-Castano ME, Striker LJ, et al. (2001) RPE expression of matrix metalloproteinase (MMP-2) and MCP-1 after different kinds of injury. Invest Ophthalmol Vis Sci 42(4): 4060Google Scholar
  164. Moore DJ, Hussain AA, Marshall J (1995) Age-related variation in the hydraulic conductivity of Bruch’s membrane. Invest Ophthalmol Vis Sci 36: 1290–1297PubMedGoogle Scholar
  165. Moore KS, Wehrli S, Roder H, Rogers M, Forrest JN Jr, McCrimmon D, Zasloff M (1993) Squalamine: an aminosterol antibiotic from the shark. Proc Natl Acad Sci USA 90: 1354–1358PubMedGoogle Scholar
  166. Mordenti J, Cuthbertson RA, Ferrara N, Thomsen K, Berleau L, Licko V, Allen PC, Valverde CR, Meng YG, Fei DT, Fourre KM, Ryan AM (1999) Comparisons of the intraocular tissue distribution, pharmacokinetics, and safety of 125I-labeled full-length and Fab antibodies in rhesus monkeys following intravitreal administration. Toxicol Pathol 27: 536–544PubMedGoogle Scholar
  167. Mori K, Yoneya S, Anzail K, Kabasawa S, Sodeyama T, Peyman GA, Moshfeghi DM (2001) Photodynamic therapy of experimental choroidal neovascularization with a hydrophilic photosensitizer: mono-Laspartyl chlorine6. Retina 21: 499–508PubMedGoogle Scholar
  168. Mori K, Gehlbach P, Ando A, McVey D, Wei L, Campochiaro PA (2002) Regression of ocular neovascularization in response to increased expression of pigment epithelium-derived factor. Invest Ophthalmol Vis Sci 43: 2428–2434PubMedGoogle Scholar
  169. Moshfeghi DM, Peyman GA, Moshfeghi AA, Khoobehi B, Primbs GB, Crean DH (1998) Ocular vascular thrombosis following tin ethyl etiopurpurin (SnET2) photodynamic therapy: time dependencies. Ophthalmic Surg Lasers 29: 663–668PubMedGoogle Scholar
  170. Mullins RF, Russell SR, Anderson DH, Hageman GS (2000) Drusen associated with aging and age-related macular degeneration contain proteins common to extracellular deposits associated with atherosclerosis, elastosis, amyloidosis, and dense deposit disease. FASEB J 14: 835–846PubMedGoogle Scholar
  171. Murohara T (2003) Angiogenesis and vasculogenesis for therapeutic neovascularization. Nagoya J Med Sci 66: 1–7PubMedGoogle Scholar
  172. Nakashizuka T, Mori K, Hayashi N, Anzail K, Kanail K, Yoneya S, Moshfeghi DM, Peyman GA (2001) Retreatment effect of NPe6 photodynamic therapy on the normal primate macula. Retina 21: 493–498PubMedGoogle Scholar
  173. Nambu H, Nambu R, Melia M, Campochiaro PA (2003) Combretastatin A-4 phosphate suppresses development and induces regression of choroidal neovascularization. Invest Ophthalmol Vis Sci 44: 3650–3655CrossRefPubMedGoogle Scholar
  174. Navajas EV, Costa RA, Farah ME, Cardillo JA, Bonomo PP (2003) Indocyanine green-mediated photothrombosis combined with intravitreal triamcinolone for the treatment of choroidal neovascularization in serpiginous choroiditis. Eye 17: 563–566CrossRefPubMedGoogle Scholar
  175. Newsom RS, McAlister JC, Saeed M, McHugh JD (2001) Transpupillary thermotherapy (TTT) for the treatment of choroidal neovascularisation. Br J Ophthalmol 85: 173–178PubMedGoogle Scholar
  176. Newsome DA, Swartz M, Leone NC, Elston RC, Miller E (1988) Oral zinc in macular degeneration. Arch Ophthalmol 106: 192–198PubMedGoogle Scholar
  177. Oh H, Takagi H, Takagi C, Suzuma K, Otani A, Ishida K, Matsumura M, Ogura Y, Honda Y (1999) The potential angiogenic role of macrophages in the formation of choroidal neovascular membranes. Invest Ophthalmol Vis Sci 40: 1891–1898PubMedGoogle Scholar
  178. Ohji M, Fujikado T, Kusaka S, Hayashi A, Hosohata J, Ikuno Y, Sawa M, Kubota A, Hashida N, Tano Y (2001) Comparison of three techniques of foveal translocation in patients with subfoveal choroidal neovascularization resulting from age-related macular degeneration. Am J Ophthalmol 132: 888–896CrossRefPubMedGoogle Scholar
  179. Olk RJ, Friberg TR, Stickney KL, Akduman L, Wong KL, Chen MC, Levy MH, Garcia CA, Morse LS (1999) Therapeutic benefits of infrared (810-nm) diode laser macular grid photocoagulation in prophylactic treatment of nonexudative age-related macular degeneration: two-year results of a randomized pilot study. Ophthalmology 106: 2082–2090CrossRefPubMedGoogle Scholar
  180. Pauleikhoff D, Koch JM (1995) Prevalence of age-related macular degeneration. Curr Opin Ophthalmol 6: 51–56PubMedGoogle Scholar
  181. Penfold PL, Killingsworth MC, Sarks SH (1985) Senile macular degeneration: the involvement of immuno-competent cells. Graefes Arch Clin Exp Ophthalmol 223: 69–76CrossRefPubMedGoogle Scholar
  182. Penfold PL, Provis JM, Billson FA (1987) Age-related macular degeneration: ultrastructural studies of the relationship of leucocytes to angiogenesis. Graefes Arch Clin Exp Ophthalmol 225: 70–76PubMedGoogle Scholar
  183. Penfold PL, Madigan MC, Gillies MC, Provis JM (2001) Immunological and aetiological aspects of macular degeneration. Prog Retin Eye Res 20: 385–414CrossRefPubMedGoogle Scholar
  184. Penn JS, Rajaratnam VS, Collier RJ, Clark AF (2001) The effect of an angiostatic steroid on neovascularization in a rat model of retinopathy of prematurity. Invest Ophthalmol Vis Sci 42: 283–290PubMedGoogle Scholar
  185. Peten EP, Garcia-Perez A, Terada Y, Woodrow D, Martin BM, Striker GE, Striker LJ (1992) Age-related changes in alpha 1-and alpha 2-chain type IV collagen mRNAs in adult mouse glomeruli: competitive PCR. Am J Physiol 263: F951–F957PubMedGoogle Scholar
  186. Pettit GR, Singh SB, Hamel E, Lin CM, Alberts DS, Garcia-Kendall D (1989) Isolation and structure of the strong cell growth and tubulin inhibitor combretastatin A-4. Experientia 45: 209–211CrossRefPubMedGoogle Scholar
  187. Pieramici DJ, Bressler SB (1998) Age-related macular degeneration and risk factors for the development of choroidal neovascularization in the fellow eye. Curr Opin Ophthalmol 9: 38–46PubMedGoogle Scholar
  188. Presta LG, Chen H, O’Connor SJ, Chisholm V, Meng YG, Krummen L, Winkler M, Ferrara N (1997) Humanization of an anti-vascular endothelial growth factor monoclonal antibody for the therapy of solid tumors and other disorders. Cancer Res 57: 4593–4599PubMedGoogle Scholar
  189. Pulido JS (2002) Multicenter prospective, randomized, double-masked, placebo-controlled study of rheopheresis to treat nonexudative age-related macular degeneration: interim analysis. Trans Am Ophthalmol Soc 100: 85–106; discussion 106–107PubMedGoogle Scholar
  190. Rao MN, Shinnar AE, Noecker LA, Chao TL, Feibush B, Snyder B, Sharkansky I, Sarkahian A, Zhang X, Jones SR, Kinney WA, Zasloff M (2000) Aminosterols from the dogfish shark Squalus acanthias. J Nat Prod 63: 631–635CrossRefPubMedGoogle Scholar
  191. Rasmussen H, Chu KW, Campochiaro P, Gehlbach PL, Haller JA, Handa JT, Nguyen QD, Sung JU (2001) Clinical protocol. An open-label, phase I, single administration, dose-escalation study of ADGVPEDF. 11D (ADPEDF) in neovascular age-related macular degeneration (AMD). Hum Gene Ther 12: 2029–2032PubMedGoogle Scholar
  192. Rechtman E, Allen VD, Danis RP, Pratt LM, Harris A, Speicher MA (2003) Intravitreal triamcinolone for choroidal neovascularization in ocular histoplasmosis syndrome. Am J Ophthalmol 136: 739–741CrossRefPubMedGoogle Scholar
  193. Reichel E, Berrocal AM, Ip M, Kroll AJ, Desai V, Duker JS, Puliafito CA (1999) Transpupillary thermotherapy of occult subfoveal choroidal neovascularization in patients with age-related macular degeneration. Ophthalmology 106: 1908–1914CrossRefPubMedGoogle Scholar
  194. Religa P, Bojakowski K, Maksymowicz M, Bojakowska M, Sirsjo A, Gaciong Z, Olszewski W, Hedin U, Thyberg J (2002) Smooth-muscle progenitor cells of bone marrow origin contribute to the development of neointimal thickenings in rat aortic allografts and injured rat carotid arteries. Transplantation 74: 1310–1315PubMedGoogle Scholar
  195. Renno RZ, Youssri AI, Michaud N, Gragoudas ES, Miller JW (2002) Expression of pigment epithelium-derived factor in experimental choroidal neovascularization. Invest Ophthalmol Vis Sci 43: 1574–1580PubMedGoogle Scholar
  196. Reynders S, Lafaut BA, Aisenbrey S, Broecke CV, Lucke K, Walter P, Kirchhof B, Bartz-Schmidt KU (2002) Clinicopathologic correlation in hemorrhagic agerelated macular degeneration. Graefes Arch Clin Exp Ophthalmol 240: 279–285PubMedGoogle Scholar
  197. Richer SP, Stiles W, Statkute L, et al. (2002) The Lutein Antioxidant Supplementation Trial. Invest Ophthalmol Vis Sci E (Abstract 2542)Google Scholar
  198. Rodanant N, Freeman WR, Musch DC, et al. (2002) Predictors of choroidal neovascularization in eyes treated with subthreshold diode grid laser therapy to prevent choroidal neovascularization. Results from the unilateral arm of PTAMD Study. Invest Ophthalmol Vis Sci E (Abstract 1211)Google Scholar
  199. Rogers AH, Reichel E (2001) Transpupillary thermotherapy of subfoveal occult choroidal neovascularization. Curr Opin Ophthalmol 12: 212–215CrossRefPubMedGoogle Scholar
  200. Ross R (1990) Mechanisms of atherosclerosis — a review. Adv Nephrol Necker Hosp 19: 79–86PubMedGoogle Scholar
  201. Ross R (1999) Atherosclerosis is an inflammatory disease. Am Heart J 138: S419–S420PubMedGoogle Scholar
  202. Ruckmann A von, Schmidt KG, Fitzke FW, Bird AC, Jacobi KW (1998) [Dynamics of accumulation and degradation of lipofuscin in retinal pigment epithelium in senile macular degeneration]. Klin Monatsbl Augenheilkd 213: 32–37CrossRefGoogle Scholar
  203. Sakurai E, Anand A, Ambati BK, Rooijen N van, Ambati J (2003) Macrophage depletion inhibits experimental choroidal neovascularization. Invest Ophthalmol Vis Sci 44: 3578–3585PubMedGoogle Scholar
  204. Sarks JP, Sarks SH, Killingsworth MC (1997) Morphology of early choroidal neovascularisation in age-related macular degeneration: correlation with activity. Eye 11: 515–522PubMedGoogle Scholar
  205. Schaft TL van der, Mooy CM, Bruijn WC de, Oron FG, Mulder PG, Jong PT de (1992) Histologic features of the early stages of age-related macular degeneration. A statistical analysis. Ophthalmology 99: 278–286PubMedGoogle Scholar
  206. Schaft TL van der, Mooy CM, Bruijn WC de, Bosman FT, Jong PT de (1994) Immunohistochemical light and electron microscopy of basal laminar deposit. Graefes Arch Clin Exp Ophthalmol 232: 40–46CrossRefPubMedGoogle Scholar
  207. Schlingemann RO (2004) Role of growth factors and the wound healing response in age-related macular degeneration. Graefes Arch Clin Exp Ophthalmol 242: 91–101CrossRefPubMedGoogle Scholar
  208. Schneider S, Greven CM, Green WR (1998) Photocoagulation of well-defined choroidal neovascularization in age-related macular degeneration: clinicopathologic correlation. Retina 18: 242–250PubMedGoogle Scholar
  209. Seddon JM, Gensler G, Milton RC, Klein ML, Rifai N (2004) Association between C-reactive protein and age-related macular degeneration. J Am Med Assoc 291: 704–710CrossRefGoogle Scholar
  210. Seibert K, Lefkowith J, Tripp C, Isakson P, Needleman P (1999) COX-2 inhibitors — is there cause for concern? Nat Med 5: 621–622CrossRefPubMedGoogle Scholar
  211. Sengupta N, Caballero S, Mames RN, Butler JM, Scott EW, Grant MB (2003) The role of adult bone marrow-derived stem cells in choroidal neovascularization. Invest Ophthalmol Vis Sci 44: 4908–4913CrossRefPubMedGoogle Scholar
  212. Shiraga F, Ojima Y, Matsuo T, Takasu I, Matsuo N (1998) Feeder vessel photocoagulation of subfoveal choroidal neovascularization secondary to age-related macular degeneration. Ophthalmology 105: 662–669PubMedGoogle Scholar
  213. Sills AK Jr, Williams JI, Tyler BM, Epstein DS, Sipos EP, Davis JD, McLane MP, Pitchford S, Cheshire K, Gannon FH, Kinney WA, Chao TL, Donowitz M, Laterra J, Zasloff M, Brem H (1998) Squalamine inhibits angiogenesis and solid tumor growth in vivo and perturbs embryonic vasculature. Cancer Res 58: 2784–2792PubMedGoogle Scholar
  214. Singerman LJ (1988) Current management of choroidal neovascularization. Ann Ophthalmol 20: 415–420, 423PubMedGoogle Scholar
  215. Slakter JS (2003) Anecortave acetate as monotherapy for treatment of subfoveal neovascularization in age-related macular degeneration: twelve-month clinical outcomes. Ophthalmology 110: 2372–2383PubMedGoogle Scholar
  216. Smith W, Mitchell P, Wang JJ (1997) Gender, oestrogen, hormone replacement and age-related macular degeneration: results from the Blue Mountains Eye Study. Aust NZ J Ophthalmol 25(Suppl 1): S13–S15Google Scholar
  217. Snow KK, Seddon JM (1999) Do age-related macular degeneration and cardiovascular disease share common antecedents? Ophthalmic Epidemiol 6: 125–143CrossRefPubMedGoogle Scholar
  218. Spaide RF, Sorenson J, Maranan L (2003) Combined photodynamic therapy with verteporfin and intravitreal triamcinolone acetonide for choroidal neovascularization. Ophthalmology 110: 1517–1525PubMedGoogle Scholar
  219. Spraul CW, Lang GE, Lang GK (1998) [Value of optical coherence tomography in diagnosis of age-related macular degeneration. Correlation of fluorescein angiography and OCT findings]. Klin Monatsbl Augenheilkd 212: 141–148PubMedCrossRefGoogle Scholar
  220. Staurenghi G, Orzalesi N, La Capria A, Aschero M (1998) Laser treatment of feeder vessels in subfoveal choroidal neovascular membranes: a revisitation using dynamic indocyanine green angiography. Ophthalmology 105: 2297–2305CrossRefPubMedGoogle Scholar
  221. Steen B, Sejersen S, Berglin L, Seregard S, Kvanta A (1998) Matrix metalloproteinases and metalloproteinase inhibitors in choroidal neovascular membranes. Invest Ophthalmol Vis Sci 39: 2194–2200PubMedGoogle Scholar
  222. Stone TW, Sternberg P Jr (2002) Submacular surgery trials update. Ophthalmol Clin North Am 15: 479–488CrossRefPubMedGoogle Scholar
  223. Strunnikova N, Baffi J, Gonzalez A, Silk W, Cousins SW, Csaky KG (2001) Regulated heat shock protein 27 expression in human retinal pigment epithelium. Invest Ophthalmol Vis Sci 42: 2130–2138PubMedGoogle Scholar
  224. Strunnikova NV, Baffi J, Zhang C, et al. (2003) Cellular and molecular responses to sublethal oxidative injury in retinal pigment epithelial cells (RPE). Invest Ophthalmol Vis Sci E (Abstract 3145)Google Scholar
  225. Stur M, Tittl M, Reitner A, Meisinger V (1996) Oral zinc and the second eye in age-related macular degeneration. Invest Ophthalmol Vis Sci 37: 1225–1235PubMedGoogle Scholar
  226. Submacular Surgery Trials Pilot Study (2000a) Submacular surgery trials randomized pilot trial of laser photocoagulation versus surgery for recurrent choroidal neovascularization secondary to age-related macular degeneration: 1. Ophthalmic outcomes submacular surgery trials pilot study report number 1. Am J Ophthalmol 130: 387–407Google Scholar
  227. Submacular Surgery Trials Pilot Study (2000b) Submacular surgery trials randomized pilot trial of laser photocoagulation versus surgery for recurrent choroidal neovascularization secondary to age-related macular degeneration: 2. Quality of life outcomes submacular surgery trials pilot study report number 2. Am J Ophthalmol 130: 408–418Google Scholar
  228. Subramanian ML, Reichel E (2003) Current indications of transpupillary thermotherapy for the treatment of posterior segment diseases. Curr Opin Ophthalmol 14: 155–158CrossRefPubMedGoogle Scholar
  229. Sullivan P, Filsecker L, Sears J (2002) Limited macular translocation with scleral retraction suture. Br J Ophthalmol 86: 434–439PubMedGoogle Scholar
  230. Suner IJ, Espinosa-Heidmann DG, Marin-Castano ME, Hernandez EP, Pereira-Simon S, Cousins SW (2004) Nicotine increases size and severity of experimental choroidal neovascularization. Invest Ophthalmol Vis Sci 45: 311–317CrossRefPubMedGoogle Scholar
  231. Takahashi K, Saishin Y, Saishin Y, Mori K, Ando A, Yamamoto S, Oshima Y, Nambu H, Melia MB, Bingaman DP, Campochiaro PA (2003) Topical nepafenac inhibits ocular neovascularization. Invest Ophthalmol Vis Sci 44: 409–415CrossRefPubMedGoogle Scholar
  232. TAP Study Group (1999) Photodynamic therapy of subfoveal choroidal neovascularization in age-related macular degeneration with verteporfin: one-year results of 2 randomized clinical trials — TAP report. Treatment of age-related macular degeneration with photodynamic therapy (TAP) Study Group. Arch Ophthalmol 117: 1329–1345Google Scholar
  233. TAP Study Group and VIP Study Group (Verteporfin Roundtable 2000 and 2001 Participants) (2002) Guidelines for using verteporfin (visudyne) in photodynamic therapy to treat choroidal neovascularization due to age-related macular degeneration and other causes. Retina 22: 6–18Google Scholar
  234. Taylor HR, Tikellis G, Robman LD, McCarty CA, McNeil JJ (2002) vitamin E supplementation and macular degeneration: randomised controlled trial. BMJ 325: 11PubMedGoogle Scholar
  235. Teicher BA, Williams JI, Takeuchi H, Ara G, Herbst RS, Buxton D (1998) Potential of the aminosterol, squalamine in combination therapy in the rat 13,762 mammary carcinoma and the murine Lewis lung carcinoma. Anticancer Res 18: 2567–2573PubMedGoogle Scholar
  236. Teikari JM, Laatikainen L, Virtamo J, Haukka J, Rautalahti M, Liesto K, Albanes D, Taylor P, Heinonen OP (1998) Six-year supplementation with alpha-tocopherol and beta-carotene and age-related maculopathy. Acta Ophthalmol Scand 76: 224–229PubMedGoogle Scholar
  237. Terasaki H (2001) Rescue of retinal function by macular translocation surgery in age-related macular degeneration and other diseases with subfoveal choroidal neovascularization. Nagoya J Med Sci 64: 1–9PubMedGoogle Scholar
  238. Tosetti F, Ferrari N, De Flora S, Albini A (2002) Angioprevention”: angiogenesis is a common and key target for cancer chemopreventive agents. FASEB J 16: 2–14CrossRefPubMedGoogle Scholar
  239. Toth CA, Freedman SF (2001) Macular translocation with 360-degree peripheral retinectomy impact of technique and surgical experience on visual outcomes. Retina 21: 293–303PubMedGoogle Scholar
  240. Tozer GM, Kanthou C, Parkins CS, Hill SA (2002) The biology of the combretastatins as tumour vascular targeting agents. Int J Exp Pathol 83: 21–38CrossRefPubMedGoogle Scholar
  241. Tracy RP (2003) Inflammation, the metabolic syndrome and cardiovascular risk. Int J Clin Pract Suppl 10–17Google Scholar
  242. Valmaggia C, Ries G, Ballinari P (2002) Radiotherapy for subfoveal choroidal neovascularization in agerelated macular degeneration: a randomized clinical trial. Am J Ophthalmol 133: 521–529CrossRefPubMedGoogle Scholar
  243. Vander JF, Federman JL, Greven C, Slusher MM, Gabel VP (1991) Surgical removal of massive subretinal hemorrhage associated with age-related macular degeneration. Ophthalmology 98: 23–27PubMedGoogle Scholar
  244. VIP (Verteporfin in Photodynamic Therapy) Study Group (2001) 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 131: 541–560Google Scholar
  245. Vizcarra C (2003) New perspectives and emerging therapies for immune-mediated inflammatory disorders. J Infus Nurs 26: 319–325PubMedGoogle Scholar
  246. Walsh DA, Pearson CI (2001) Angiogenesis in the pathogenesis of inflammatory joint and lung diseases. Arthritis Res 3: 147–153CrossRefPubMedGoogle Scholar
  247. Weimann JM, Charlton CA, Brazelton TR, Hackman RC, Blau HM (2003) Contribution of transplanted bone marrow cells to Purkinje neurons in human adult brains. Proc Natl Acad Sci USA 100: 2088–2093CrossRefPubMedGoogle Scholar
  248. Winkler BS, Boulton ME, Gottsch JD, Sternberg P (1999) Oxidative damage and age-related macular degeneration. Mol Vis 5: 32PubMedGoogle Scholar
  249. Witmer AN, Vrensen GF, Van Noorden CJ, Schlingemann RO (2003) Vascular endothelial growth factors and angiogenesis in eye disease. Prog Retin Eye Res 22: 1–29CrossRefPubMedGoogle Scholar
  250. Woods JA, Hadfield JA, Pettit GR, Fox BW, McGown AT (1995) The interaction with tubulin of a series of stilbenes based on combretastatin A-4. Br J Cancer 71: 705–711PubMedGoogle Scholar
  251. Wormald R, Evans J, Smeeth L, Henshaw K (2003) Photodynamic therapy for neovascular age-related macular degeneration. Cochrane Database Syst Rev CD002030Google Scholar
  252. Yamamoto Y (2003) Measurement of blood flow velocity in feeder vessels of choroidal neovascularization by a scanning laser ophthalmoscope and image analysis system. Jpn J Ophthalmol 47: 53–58CrossRefPubMedGoogle Scholar
  253. Yates JR, Moore AT (2000) Genetic susceptibility to age related macular degeneration. J Med Genet 37: 83–87CrossRefPubMedGoogle Scholar
  254. York J, Glaser B, Murphy R (2000) High-speed ICG. Used for pinpoint laser treatment of feeder vessels in wet AMD. J Ophthalmic Nurs Technol 19: 66–67PubMedGoogle Scholar
  255. Young RW (1987) Pathophysiology of age-related macular degeneration. Surv Ophthalmol 31: 291–306PubMedGoogle Scholar
  256. Zarbin MA (1998) Age-related macular degeneration: review of pathogenesis. Eur J Ophthalmol 8: 199–206PubMedGoogle Scholar
  257. Zimmer-Galler IE, Bressler NM, Bressler SB (1995) Treatment of choroidal neovascularization: updated information from recent macular photocoagulation study group reports. Int Ophthalmol Clin 35: 37–57PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2005

Authors and Affiliations

  • Scott W. Cousins
  • Karl G. Csaky
  • Diego G. Espinosa-Heidmann

There are no affiliations available

Personalised recommendations