Retinal Vascular Disease

  • Fiona Roberts
  • Chee Koon Thum


Ischaemic retinal vascular diseases ultimately lead to glaucoma and are found in the globes that are enucleated to relieve intractable pain in a blind eye. The clinical diagnosis is usually “neovascular glaucoma” with the addition of “central retinal vein occlusion” or “diabetes,” but occasionally, rarer entities such as retinopathy of prematurity or Coats’ disease will be seen at this end stage. Angiogenic factors released by the ischaemic retina are important in the pathogenesis of these retinal vascular diseases. Central retinal artery occlusion, posterior ciliary artery occlusion, ophthalmic artery occlusion, hypertension and disseminated intravascular coagulation are rarely associated with neovascular glaucoma. Choroidal neovascularisation (disciform degeneration) and age related macular degeneration are included in this chapter although they do not per se lead to anterior segment neovascularisation.


Vascular Endothelial Growth Factor Diabetic Retinopathy Retinal Pigment Epithelium Retinal Detachment Retinal Pigment Epithelium Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Bek T. Capillary closure secondary to retinal vein occlusion. A morphological, histopathological, and immunohistochemical study. Acta Ophthalmol Scand. 1998;76:643–8.PubMedGoogle Scholar
  2. 2.
    Schultz GS, Grant MB. Neovascular growth factors. Eye. 1991;5:170–80.PubMedGoogle Scholar
  3. 3.
    Pierce EA, Avery RL, Foley ED, Aiello LP, Smith LE. Vascular endothelial growth factor/vascular permeability factor expression in a mouse model of retinal neovascularization. Proc Natl Acad Sci U S A. 1995;92(3):905–9.PubMedGoogle Scholar
  4. 4.
    Petty RG, Pearson JD, Morgan DML, Mahler RFB. Stimulation of endothelial cell growth by sera from diabetic patients with retinopathy. Lancet. 1988;i(8579):208–11.Google Scholar
  5. 5.
    Aiello LP, Northrup JM, Keyt BA, Tagaki H, Iwamoto MA. Hypoxic regulation of vascular endothelial growth factor in retinal cells. Arch Ophthalmol. 1995;13:1538–44.Google Scholar
  6. 6.
    Casey R, Li WW. Factors controlling ocular angiogenesis. Am J Ophthalmol. 1997;124:521–9.PubMedGoogle Scholar
  7. 7.
    Lopez PF, Sippy BD, Lambert HM, Thach AB, Hinton DR. 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. 1996;37(5):855–68.PubMedGoogle Scholar
  8. 8.
    Kliffen M, Sharma HS, Mooy CM, Kerkvliet S, de Jong PT. Increased expression of angiogenic growth factors in age-related maculopathy. Br J Ophthalmol. 1997;81(2):154–62.PubMedGoogle Scholar
  9. 9.
    Aiello LP, Avery RL, Arrigg PG, Keyt BA, Jampel HD, Shah ST, et al. Vascular endothelial growth factor in ocular fluid of patients with diabetic retinopathy and other retinal disorders. N Engl J Med. 1994;331(22):1480–7.PubMedGoogle Scholar
  10. 10.
    Adamis AP, Miller JW, Bernal MT, D’Amico DJ, Folkman J, Yeo TK, et al. Increased vascular endothelial growth factor levels in the vitreous of eyes with proliferative diabetic retinopathy. Am J Ophthalmol. 1994;118(4):445–50.PubMedGoogle Scholar
  11. 11.
    Miller JW, Adamis AP, Shima DT, D’Amore PA, Moulton RS, O’Reilly MS, et al. Vascular endothelial growth factor/vascular permeability factor is temporally and spatially correlated with ocular angiogenesis in a primate model. Am J Pathol. 1994;145(3):574–84.PubMedGoogle Scholar
  12. 12.
    Boyd SR, Zachary I, Chakravarthy U, Allen GJ, Wisdom GB, Cree IA, et al. Correlation of increased vascular endothelial growth factor with neovascularization and permeability in ischemic central vein occlusion. Arch Ophthalmol. 2002;120(12):1644–50.PubMedGoogle Scholar
  13. 13.
    Noma H, Minamoto A, Funatsu H, Tsukamoto H, Nakano K, Yamashita H, et al. Intravitreal levels of vascular endothelial growth factor and interleukin-6 are correlated with macular edema in branch retinal vein occlusion. Graefes Arch Clin Exp Ophthalmol. 2006;244(3):309–15.PubMedGoogle Scholar
  14. 14.
    Murata T, Ishibashi T, Khalil A, Hata Y, Yoshikawa H, Inomata H. Vascular endothelial growth factor plays a role in hyperpermeability of diabetic retinal vessels. Ophthalmic Res. 1995;27(1):48–52.PubMedGoogle Scholar
  15. 15.
    Mathews MK, Merges C, McLeod DS, Lutty GA. Vascular endothelial growth factor and vascular permeability changes in human diabetic retinopathy. Invest Ophthalmol Vis Sci. 1997;38(13):2729–41.PubMedGoogle Scholar
  16. 16.
    Ferrara N, Gerber HP, LeCouter J. The biology of VEGF and its receptors. Nat Med. 2003;9:669–76.PubMedGoogle Scholar
  17. 17.
    Gragoudas ES, Adamis AP, Cunningham Jr ET, Feinsod M, Guyer DR. VEGF inhibition study in ocular neovascularization clinical trial group: pegaptanib for neovascular age-related macular degeneration. N Engl J Med. 2004;351:2805–16.PubMedGoogle Scholar
  18. 18.
    Rosenfeld PJ, Brown DM, Heier JS, Boyer DS, Kaiser PK, Chung CY, Kim RY. MARINA Study Group: Ranibizumab for neovascular age-related macular degeneration. N Engl J Med. 2006;355:1419–31.PubMedGoogle Scholar
  19. 19.
    Brown DM, Michels M, Kaiser PK, Heier JS, Sy JP, Ianchulev T. ANCHOR Study Group: Ranibizumab versus verteporfin photodynamic therapy for neovascular age-related macular degeneration: two-year results of the ANCHOR study. Ophthalmology. 2009;116:57–65.PubMedGoogle Scholar
  20. 20.
    Elman MJ, Aiello LP, Beck RW, Bressler NM, Bressler SB, Edwards AR, et al. Randomized trial evaluating ranibizumab plus prompt or deferred laser or triamcinolone plus prompt laser for diabetic macular edema. Ophthalmology. 2010;117:1064–77.PubMedGoogle Scholar
  21. 21.
    Andreoli CM, Miller JW. Anti-vascular endothelial growth factor therapy for ocular neovascular disease. Curr Opin Ophthalmol. 2007;18:502–8.PubMedGoogle Scholar
  22. 22.
    Bashshur ZF, Haddad ZA, Schakal AR, Jaafar RF, Saad A, Noureddin BN. Intravitreal bevacizumab for treatment of neovascular age-related macular degeneration: the second year of a prospective study. Am J Ophthalmol. 2009;148(1):59–65.e1. Epub 2009 Apr 18.PubMedGoogle Scholar
  23. 23.
    Wang H, Chhablani J, Freeman WR, Chan CK, Kozak I, Bartsch DU, Cheng L. Characterization of diabetic microaneurysms by simultaneous fluorescein angiography and spectral-domain optical coherence tomography. Am J Ophthal. 2012;153(5):861–7.e1. Epub 2012 Feb 1.PubMedGoogle Scholar
  24. 24.
    Park UC, Park KH, Kim DM, Yu HG. Ahmed glaucoma valve implantation for neovascular glaucoma after vitrectomy for proliferative diabetic retinopathy. J Glaucoma. 2011;20(7):433–8.PubMedGoogle Scholar
  25. 25.
    Nassiri N, Kamali G, Rahnavardi M, Mohammadi B, Nassiri S, Rahmani L, Nassiri N. Ahmed glaucoma valve and single-plate Molteno implants in treatment of refractory glaucoma: a comparative study. Am J Ophthalmol. 2010;149(6):893–902.PubMedGoogle Scholar
  26. 26.
    Ehlers JP, Spirn MJ, Lam A, Sivalingam A, Samuel MA, Tasman W. Combination intravitreal bevacizumab/panretinal photocoagulation versus panretinal photocoagulation alone in the treatment of neovascular glaucoma. Retina. 2008;28(5):696–702.PubMedGoogle Scholar
  27. 27.
    Ciftci S, Sakalar YB, Unlu K, Keklikci U, Caca I, Dogan E. Intravitreal bevacizumab combined with panretinal photocoagulation in the treatment of open angle neovascular glaucoma. Eur J Ophthal. 2009;19(6):1028–33.Google Scholar
  28. 28.
    Davidorf FH, Mouser JG, Derick RJ. Rapid improvement of rubeosis iridis from a single bevacizumab (Avastin) injection. Retina. 2006;26:354–6.PubMedGoogle Scholar
  29. 29.
    Wakabayashi T, Oshima Y, Sakaguchi H, Ikuno Y, Miki A, Gomi F, et al. Intravitreal bevacizumab to treat iris neovascularization and neovascular glaucoma secondary to ischemic retinal disease in 41 consecutive cases. Ophthalmology. 2008;115(9):1571–80.PubMedGoogle Scholar
  30. 30.
    Moraczewski AL, Lee RK, Palmberg PF, Rosenfeld PJ, Feuer WJ. Outcomes of treatment of neovascular glaucoma with intravitreal bevacizumab. Br J Ophthalmol. 2009;93:589–93.PubMedGoogle Scholar
  31. 31.
    Yazdani S, Hendi K, Pakravan M, Mahdavi M, Yaseri M. Intravitreal bevacizumab for neovascular glaucoma: a randomized controlled trial. J Glaucoma. 2009;18(8):632–7.PubMedGoogle Scholar
  32. 32.
    Saito Y, Higashide T, Takeda H, Ohkubo S, Sugiyama K. Beneficial effects of preoperative intravitreal bevacizumab on trabeculectomy outcomes in neovascular glaucoma. Acta Ophthalmol. 2010;88(1):96–102.PubMedGoogle Scholar
  33. 33.
    Takihara Y, Inatani M, Kawaji T, Fukushima M, Iwao K, Iwao M, et al. Combined intravitreal bevacizumab and trabeculectomy with mitomycin C versus trabeculectomy with mitomycin C alone for neovascular glaucoma. J Glaucoma. 2011;20(3):196–201.PubMedGoogle Scholar
  34. 34.
    Manschot WA, Lee WR. Retinal neovascularisation arising from hyalinised blood vessels. Graefes Arch Clin Exp Ophthalmol. 1984;222:63–70.PubMedGoogle Scholar
  35. 35.
    Hiscott P, Cooling RJ, Rosen P, Garner A. The pathology of abortive neovascular outgrowths from the retina. Graefes Arch Clin Exp Ophthalmol. 1992;230:531–6.PubMedGoogle Scholar
  36. 36.
    Marshall GE, Konstas AG, Lee WR. Ultrastructural distribution of collagens types I–VI in ageing human retinal vessels. Br J Ophthalmol. 1990;74:228–32.PubMedGoogle Scholar
  37. 37.
    Cugati S, Wang JJ, Rochtchina E, Mitchell P. Ten-year incidence of retinal vein occlusion in an older population: the Blue Mountains Eye Study. Arch Ophthalmol. 2006;124:726–32.PubMedGoogle Scholar
  38. 38.
    Bunce C, Xing W, Wormald R. Causes of blind and partial sight certifications in England and Wales: April 2007–March 2008. Eye (Lond). 2010;24(11):1692–9.Google Scholar
  39. 39.
    Green WR, Chan CC, Hutchins GM, Terry JM. Central retinal vein occlusion, a prospective study of 29 eyes of 28 cases. Retina. 1981;1:27–55.PubMedGoogle Scholar
  40. 40.
    Taylor AW, Sehu KW, Lee WR, Williamson TW. Morphometric assessment of the central retinal artery and vein in the optic nerve head. Can J Ophthalmol. 1993;28:320–4.PubMedGoogle Scholar
  41. 41.
    Williamson TH. Central retinal vein occlusion: what’s the story? Br J Ophthalmol. 1997;81:691–7.Google Scholar
  42. 42.
    Bowers DK, Finklelstein D, Wolff SM, Green WR. Branch retinal vein occlusion. A clinicopathologic case report. Retina. 1987;7:252–9.PubMedGoogle Scholar
  43. 43.
    Bunce C, Wormald R. Causes of blind certifications in England and Wales: April 1999–March 2000. Eye (Lond). 2008;22(7):905–11.Google Scholar
  44. 44.
    The Royal College of Ophthalmologists. Preferred practice guidelines. Diabetic retinopathy screening (DRS) and the ophthalmology clinic set up in England. 2010. Accessed 9 Oct 2012.
  45. 45.
    Bresnick GH. Background diabetic retinopathy. In: Ryan SJ, editor. Retina. St. Louis: CV Mosby; 1989. p. 327–66.Google Scholar
  46. 46.
    Archer DB. Diabetic retinopathy: some cellular, molecular and therapeutic considerations. Eye. 1999;13:497–523.PubMedGoogle Scholar
  47. 47.
    Antonetti DA, Lieth E, Barber AJ, Gardner TW. Molecular mechanisms of vascular permeability in diabetic retinopathy. Semin Ophthalmol. 1999;14(4):240–8. Review.PubMedGoogle Scholar
  48. 48.
    Davis MD. Proliferative diabetic retinopathy. In: Ryan SJ, editor. Retina. St. Louis: CV Mosby; 1989. p. 367–402.Google Scholar
  49. 49.
    Michael JC, de Veneccia G, Bresnick GH. Macular heterotopia in proliferative diabetic retinopathy. Arch Ophthalmol. 1994;112:1455–9.PubMedGoogle Scholar
  50. 50.
    Faulborn J, Ardjomand N. Tractional retinoschisis in proliferative diabetic retinopathy: a histopathological study. Graefes Arch Clin Exp Ophthalmol. 2000;238:40–4.PubMedGoogle Scholar
  51. 51.
    Ishibashi T, Murata T, Kohno T, Ohnishi Y, Inomata H. Peripheral choriovitreal neovascularization in proliferative diabetic retinopathy: histopathologic and ultrastructural study. Ophthalmologica. 1999;213:154–8.PubMedGoogle Scholar
  52. 52.
    Anderson HR, Stitt AW, Gardiner TA, Archer DB. Diabetic retinopathy: morphometric analysis of basement membrane thickening of capillaries in different retinal layers within arterial and venous environments. Br J Ophthalmol. 1995;79:1120–3.PubMedGoogle Scholar
  53. 53.
    Attawia MA, Nayak RC. Circulating antipericyte autoantibodies in diabetic retinopathy. Retina. 1999;19:390–400.PubMedGoogle Scholar
  54. 54.
    Kohner EM. Diabetic retinopathy. Br Med J. 1993;307:1195–9.Google Scholar
  55. 55.
    Stefansson E. Ocular oxygenation and the treatment of diabetic retinopathy. Surv Ophthalmol. 2006;51:364–80.PubMedGoogle Scholar
  56. 56.
    Chistiakov DA. Diabetic retinopathy: Pathogenic mechanisms and current treatments. Diabetes Metab Syndr. 2011;5(3):165–72.PubMedGoogle Scholar
  57. 57.
    Tremolada G, Del Turco C, Lattanzio R, Maestroni S, Maestroni A, Bandello F, Zerbini G. The role of angiogenesis in the development of proliferative diabetic retinopathy: impact of intravitreal anti-VEGF treatment. Exp Diabetes Res. 2012;728325. Epub 2012 Apr 11. ReviewGoogle Scholar
  58. 58.
    Ferris FLIII, Davis MD, Aiello LM. Treatment of diabetic retinopathy. N Engl J Med. 1999;341:667–78.PubMedGoogle Scholar
  59. 59.
    Wallow IHL, Davis MD. Clinicopathological correlation of xenon arc and argon laser photocoagulation. Arch Ophthalmol. 1979;97:2308–15.PubMedGoogle Scholar
  60. 60.
    Wallow IH, Sponsel WE, Stevens TS. Clinicopathologic correlation of diode laser burns in monkeys. Arch Ophthalmol. 1991;109:648–53.PubMedGoogle Scholar
  61. 61.
    Mirshahi A, Roohipoor R, Lashay A, Mohammadi SF, Abdoallahi A, Faghihi H. Bevacizumab-augmented retinal laser photocoagulation in proliferative diabetic retinopathy: a randomized double-masked clinical trial. Eur J Ophthalmol. 2008;2:263–9.Google Scholar
  62. 62.
    Tonello M, Costa RA, Almeida FP, Barbosa JC, Scott IU, Jorge R. Panretinal photocoagulation versus PRP plus intravitreal bevacizumab for high-risk proliferative diabetic retinopathy (IBeHi study). Acta Ophthalmol. 2008;86:385–9.PubMedGoogle Scholar
  63. 63.
    Moradian S, Ahmadieh H, Malihi M, Soheilian M, Dehghan MH, Azarmina M. Intravitreal bevacizumab in active progressive proliferative diabetic retinopathy. Graefes Arch Clin Exp Ophthalmol. 2008;246(12):1699–705.PubMedGoogle Scholar
  64. 64.
    Yeh PT, Yang CM, Lin YC, Chen MS, Yang CH. Bevacizumab pretreatment in vitrectomy with silicone oil for severe diabetic retinopathy. Retina. 2009;29(6):768–74.PubMedGoogle Scholar
  65. 65.
    Ahmadieh H, Shoeibi N, Entezari M, Monshizadeh R. Intravitreal bevacizumab for prevention of early postvitrectomy hemorrhage in diabetic patients: a randomized clinical trial. Ophthalmology. 2009;116:1943–8.PubMedGoogle Scholar
  66. 66.
    Erdol H, Turk A, Akyol N, Imamoglu HI. The results of intravitreal bevacizumab injections for persistent neovascularizations in proliferative diabetic retinopathy after photocoagulation therapy. Retina. 2010;30:570–7.PubMedGoogle Scholar
  67. 67.
    De Juan E, Machemer R. Ultrastructural characteristics of new vessels in proliferative diabetic retinopathy. Am J Ophthalmol. 1988;105:491–9.PubMedGoogle Scholar
  68. 68.
    Nork TM, Wallow IHL, Sramek SJ, Anderson G. Müller’s cell involvement in proliferative diabetic retinopathy. Arch Ophthalmol. 1987;105:1424–9.PubMedGoogle Scholar
  69. 69.
    Jones JH, Kroll AJ, Lou PL, Ryan EA. Coats’ disease. Int Ophthalmol Clin. 2001;41:189–98.PubMedGoogle Scholar
  70. 70.
    Shields JA, Shields CL, Honavar SG, Demirci H, Cater J. Classification and management of Coats disease: the 2000 Proctor lecture. Am J Ophthalmol. 2001;131:572–83.PubMedGoogle Scholar
  71. 71.
    Shienbaum G, Tasman WS. Coats disease: a lifetime disease. Retina. 2006;26:422–4.PubMedGoogle Scholar
  72. 72.
    Andonegui J, Aranguren M, Berástegui L. Coats disease of adult onset. Arch Soc Esp Oftalmol. 2008;83(117):120.Google Scholar
  73. 73.
    Wang KY, Cheng CK. A combination of intravitreal bevacizumab injection with tunable argon yellow laser photocoagulation as a treatment for adult-onset Coats’ disease. J Ocul Pharmacol Ther. 2011;27:525–30.PubMedGoogle Scholar
  74. 74.
    Shields JA, Shields CL, Honavar SG, Demirci H. Clinical variations and complications of Coats disease in 150 cases: the 2000 Sanford Gifford Memorial Lecture. Am J Ophthalmol. 2001;131:561–71.PubMedGoogle Scholar
  75. 75.
    Couvillion SS, Margolis R, Mavrofjides E, Hess D, Murray TG. Laser treatment of Coats’ disease. J Pediatr Ophthalmol Strabismus. 2005;42:367–8.PubMedGoogle Scholar
  76. 76.
    Mulvihill A, Morris B. A population-based study of Coats disease in the United Kingdom. II. Investigation, treatment, and outcomes. Eye. 2010;24:1802–7.PubMedGoogle Scholar
  77. 77.
    Ozdamar Y, Berker N, Batman C, Zilelioglu O. Vitreoretinal surgery in advanced Coats disease. Retin Cases Brief Rep. 2009;3:57–9.Google Scholar
  78. 78.
    Yamashita T, Kawamura H, Kojo N, Ohji M. A case of Coats’ disease with visual recovery from no light perception vision after vitrectomy. Jpn J Ophthalmol. 2011;55:78–80.PubMedGoogle Scholar
  79. 79.
    Bergstrom CS, Hubbard 3rd GB. Combination intravitreal triamcinolone injection and cryotherapy for exudative retinal detachments in severe Coats disease. Retina. 2008;28:33–7.Google Scholar
  80. 80.
    Othman IS, Moussa M, Bouhaimed M. Management of lipid exudates in Coats disease by adjuvant intravitreal triamcinolone: effects and complications. Br J Ophthalmol. 2010;94:606–10.PubMedGoogle Scholar
  81. 81.
    Lin CJ, Hwang JF, Chen YT, Chen SN. The effect of intravitreal bevacizumab in the treatment of Coats disease in children. Retina. 2010;30:617–22.PubMedGoogle Scholar
  82. 82.
    Wells JR, Hubbard 3rd GB. The effect of intravitreal bevacizumab in the treatment of Coats disease in children. Retina. 2011;31:427–8.PubMedGoogle Scholar
  83. 83.
    Goel N, Kumar V, Seth A, Raina UK, Ghosh B. Role of intravitreal bevacizumab in adult onset Coats’ disease. Int Ophthalmol. 2011;31:183–90.PubMedGoogle Scholar
  84. 84.
    Zhao T, Wang K, Ma Y, Jiang YR. Resolution of total retinal detachment in Coats’ disease with intravitreal injection of bevacizumab. Graefes Arch Clin Exp Ophthalmol. 2011;249:1745–6.PubMedGoogle Scholar
  85. 85.
    Steidl SM, Hirose T, Sang D, Hartnett ME. Difficulties in excluding the diagnosis of retinoblastoma in cases of advanced Coats’ disease: a clinicopathologic report. Ophthalmologica. 1996;210:336–40.PubMedGoogle Scholar
  86. 86.
    Fernandes BF, Odashiro AN, Maloney S, Zajdenweber ME, Lopes AG, Burnier Jr MN. Clinical -histopathological correlation in a case of Coats’ disease. Diagn Pathol. 2006;1:24.PubMedGoogle Scholar
  87. 87.
    Mottow-Lippa L, Tso MOM, Peyman GA, Chejfec G. Von Hippel angiomatosis. A light, electron microscopic and immunoperoxidase characterisation. Ophthalmology. 1983;90:848–55.PubMedGoogle Scholar
  88. 88.
    Grossniklaus HE, Thomas JW, Vigneswaran N, Jarrett II WH. Retinal hemangioblastoma. A histologic, immunohistochemical, and ultrastructural evaluation. Ophthalmology. 1992;99:140–5.PubMedGoogle Scholar
  89. 89.
    Nowilaty SR, Al-Shamsi HN, Al-Khars W. Idiopathic juxtafoveolar retinal telangiectasis: a current review. Middle East Afr J Ophthalmol. 2010;17(3):224–41.PubMedGoogle Scholar
  90. 90.
    Gass JD, Blodi BA. Idiopathic juxtafoveolar retinal telangiectasis. Update of classification and follow-up study. Ophthalmology. 1993;100:1536–46.PubMedGoogle Scholar
  91. 91.
    Gamulescu MA, Walter A, Sachs H, Helbig H. Bevacizumab in the treatment of idiopathic macular telangiectasia. Graefes Arch Clin Exp Ophthalmol. 2008;246:1189–93.PubMedGoogle Scholar
  92. 92.
    Yannuzzi LA, Bardal AM, Freund KB, Chen KJ, Eandi CM, Blodi B. Idiopathic macular telangiectasia. Arch Ophthalmol. 2006;124:450–60.PubMedGoogle Scholar
  93. 93.
    Eliassi-Rad B, Green WR. Histopathologic study of presumed parafoveal telangiectasis. Retina. 1999;19:332–5.PubMedGoogle Scholar
  94. 94.
    Mandal S, Venkatesh P, Abbas Z, Vohra R, Garg S. Intravitreal bevacizumab (Avastin) for subretinal neovascularization secondary to type 2A idiopathic juxtafoveal telangiectasia. Graefes Arch Clin Exp Ophthalmol. 2007;245:1825–9.PubMedGoogle Scholar
  95. 95.
    Ruys J, De Laey JJ, Vanderhaeghen Y, Van Aken EH. Intravitreal bevacizumab (Avastin) for the treatment of bilateral acquired juxtafoveal retinal telangiectasis associated with choroidal neovascular membrane. Eye (Lond). 2007;21:1433–4.Google Scholar
  96. 96.
    Mavrakanas N, Mendrinos E, Pournaras CJ, Salzmann J. Intravitreal ranibizumab and bevacizumab for bilateral subretinal neovascularization secondary to idiopathic juxtafoveal telangiectasia type 2A. Acta Ophthalmol. 2009;87:930–2.PubMedGoogle Scholar
  97. 97.
    Smith LE. Pathogenesis of retinopathy of prematurity. Semin Neonatol. 2003;8:469–73.PubMedGoogle Scholar
  98. 98.
    Tasman W, Patz A, McNamara JA, Kaiser RS, Trese MT, Smith BT. Retinopathy of prematurity: the life of a lifetime disease. Am J Ophthalmol. 2006;141:167–74.PubMedGoogle Scholar
  99. 99.
    Jin J, Feng J, Gu MH, Shi CP, Zheng XY, Zhu HH, et al. Analysis on the result of retinopathy of prematurity screening in 1225 premature infants. Zhonghua Er Ke Za Zhi. 2010;48(11):829–33. Chinese.PubMedGoogle Scholar
  100. 100.
    Stone J, Chan-Ling T, Pe’er J, Itin A, Gnessin H, Keshet E. Roles of vascular endothelial growth factor and astrocyte degeneration in the genesis of retinopathy of prematurity. Invest Ophthalmol Vis Sci. 1996;37:290–9.PubMedGoogle Scholar
  101. 101.
    Gariano RF, Kalina RE, Hendrikson AE. Normal and pathological mechanisms in retinal vascular development. Surv Ophthalmol. 1996;40:481–90.PubMedGoogle Scholar
  102. 102.
    Hellström A, Carlsson B, Niklasson A, Segnestam K, Boguszewski M, de Lacerda L, et al. IGF-I is critical for normal vascularisation of the human retina. J Clin Endocrinol Metab. 2002;87:3413–6.PubMedGoogle Scholar
  103. 103.
    Chen J, Smith LEH. Retinopathy of prematurity. Angiogenesis. 2007;10(2):133–40.PubMedGoogle Scholar
  104. 104.
    CCRP—Committee for the Classification of Retinopathy of Prematurity. An international classification of retinopathy of prematurity. Arch Ophthalmol. 1984;102:1130–4.Google Scholar
  105. 105.
    CCRPG. Multicentre trial of cryotherapy for ROP. Arch Ophthalmol. 1988;106:471–9.Google Scholar
  106. 106.
    International Committee for the Classification of Retinopathy of Prematurity. The international classification of retinopathy of prematurity revisited. Arch Ophthalmol. 2005;123:991–9.Google Scholar
  107. 107.
    Altinsoy HI, Mutlu FM, Gungor R, Sarici SU. Combination of laser photocoagulation and intravitreal bevacizumab in aggressive posterior retinopathy of prematurity. Ophthalmic Surg Lasers Imaging. 2010;9:1–5.Google Scholar
  108. 108.
    Law JC, Recchia FM, Morrison DG, Donahue SP, Estes RL. Intravitreal bevacizumab as adjunctive treatment for retinopathy of prematurity. J AAPOS. 2010;14:6–10.PubMedGoogle Scholar
  109. 109.
    Lee JY, Chae JB, Yang SJ, Yoon YH, Kim JG. Effects of intravitreal bevacizumab and laser in retinopathy of prematurity therapy on the development of peripheral retinal vessels. Graefes Arch Clin Exp Ophthalmol. 2010;248:1257–62.PubMedGoogle Scholar
  110. 110.
    Foos RY. Retinopathy of prematurity. Pathologic correlation of clinical stages. Retina. 1987;7:260–76.PubMedGoogle Scholar
  111. 111.
    McLeod DS, Merges C, Fukushima A, Goldberg MF, Lutty GA. Histopathologic features of neovascularization in sickle cell retinopathy. Am J Ophthalmol. 1997;124:455–72.PubMedGoogle Scholar
  112. 112.
    Nagpal KC, Patrianakos D, Asdourian GK, Goldberg MF, Rabb M, Jampol L. Spontaneous regression (autoinfarction) of proliferative sickle retinopathy. Am J Ophthalmol. 1975;80:885–92.PubMedGoogle Scholar
  113. 113.
    Condon PI, Serjeant GR. Behaviour of untreated proliferative sickle retinopathy. Br J Ophthalmol. 1980;64:404–11.PubMedGoogle Scholar
  114. 114.
    Fox PD, Vessey SJ, Forshaw ML, Serjeant GR. Influence of genotype on the natural history of untreated proliferative sickle retinopathy—an angiographic study. Br J Ophthalmol. 1991;75:229–31.PubMedGoogle Scholar
  115. 115.
    Siqueira RC, Costa RA, Scott IU, Cintra LP, Jorge R. Intravitreal bevacizumab (Avastin) injection associated with regression of retinal neovascularization caused by sickle cell retinopathy. Acta Ophthalmol Scand. 2006;84:834–5.PubMedGoogle Scholar
  116. 116.
    Shaikh S. Intravitreal bevacizumab (Avastin) for the treatment of proliferative sickle retinopathy. Indian J Ophthalmol. 2008;256:259.Google Scholar
  117. 117.
    Gupta A, Dhawahir-Scala F, Smith A, Young L, Charles S. Radiation retinopathy: case report and review. BMC Ophthalmol. 2007;7:6.PubMedGoogle Scholar
  118. 118.
    Gupta A, Muecke JS. Treatment of radiation maculopathy with intravitreal injection of bevacizumab (Avastin). Retina. 2008;28:964–8.PubMedGoogle Scholar
  119. 119.
    Finger PT, Mukkamala SK. Intravitreal anti-VEGF bevacizumab (Avastin) for external beam related radiation retinopathy. Eur J Ophthalmol. 2011;21(4):446–51.PubMedGoogle Scholar
  120. 120.
    Warburg M. Norrie disease: a congenital oculo-acoustico-cerebral degeneration. Acta Ophthalmol. 1966;89(Suppl):1–147.Google Scholar
  121. 121.
    Berger W. Molecular dissection of Norrie disease. Acta Anat (Basel). 1998;162:95–100.Google Scholar
  122. 122.
    Berger W, van de PD, Warburg M, Gal A, Bleeker-Wagemakers L, de Silva H, et al. Mutations in the candidate gene for Norrie disease. Hum Mol Genet. 1992;1:461–5.PubMedGoogle Scholar
  123. 123.
    Meindl A, Berger W, Meitinger T, van de Pol D, Achatz H, Dörner C, et al. Norrie disease is caused by mutations in an extracellular protein resembling C-terminal globular domain of mucins. Nat Genet. 1992;2:139–43.PubMedGoogle Scholar
  124. 124.
    Ye X, Wang Y, Cahill H, Yu M, Badea TC, Smallwood PM, et al. Norrin, frizzled-4, and Lrp5 signaling in endothelial cells controls a genetic program for retinal vascularization. Cell. 2009;139:285–98.PubMedGoogle Scholar
  125. 125.
    Ohlmann A, Seitz R, Braunger B, Seitz D, Bösl MR, Tamm ER. Norrin promotes vascular regrowth after oxygen induced retinal vessel loss and suppresses retinopathy in mice. J Neurosci. 2010;30:183–93.PubMedGoogle Scholar
  126. 126.
    Ohlmann A, Scholz M, Goldwich A, Chauhan BK, Hudl K, Ohlmann AV, et al. Ectopic norrin induces growth of ocular capillaries and restores normal retinal angiogenesis in Norrie disease mutant mice. J Neurosci. 2005;25:1701–10.PubMedGoogle Scholar
  127. 127.
    Seitz R, Hackl S, Seibuchner T, Tamm ER, Ohlmann A. Norrin mediates neuroprotective effects on retinal ganglion cells via activation of the Wnt/beta-Catenin signaling pathway and the induction of neuroprotective growth factors in Müller cells. J Neurosci. 2010;30:5998–6010.PubMedGoogle Scholar
  128. 128.
    Blodi FC, Hunter WS. Norrie’s disease in North America. Doc Ophthalmol. 1969;26:434–50.PubMedGoogle Scholar
  129. 129.
    Nadol JB, Eavey RD, Liberfarb RM, Merlchant SN, Williams R, Climenhager D, Albert DM. Histopathology of the ears, eyes and brain in Norrie’s disease (oculoacousticocerebral degeneration). Am J Otolaryngol. 1990;11:112–24.PubMedGoogle Scholar
  130. 130.
    Enyedi LB, de Juan E, Gaitan A. Ultrastructural study of Norrie’s disease. Am J Ophthalmol. 1991;111:439–45.PubMedGoogle Scholar
  131. 131.
    Chow CC, Kiernan DF, Chau FY, Blair MP, Ticho BH, Galasso JM, Shapiro MJ. Laser photocoagulation at birth prevents blindness in Norrie’s disease diagnosed using amniocentesis. Ophthalmology. 2010;117(12):2402–6.PubMedGoogle Scholar
  132. 132.
    Kiernan DF, Blair MP, Shapiro MJ. In utero diagnosis of Norrie disease and early laser preserves visual acuity. Arch Ophthalmol. 2010;128(10):1382.PubMedGoogle Scholar
  133. 133.
    Ko MK, Kim DS. Posterior segment neovascularization associated with acute ophthalmic artery obstruction. Retina. 2000;20:384–8.PubMedGoogle Scholar
  134. 134.
    Triplett DA, Asherson RA. Pathophysiology of the catastrophic antiphospholipid syndrome. Am J Haematol. 2000;65:154–9.Google Scholar
  135. 135.
    Delaney WV, Torrisi PF, Hampton GR. Haemorrhagic peripheral pigment epithelial disease. Arch Ophthalmol. 1988;106:646–50.PubMedGoogle Scholar
  136. 136.
    Edwards AO, Ritter RIII, Abel KJ, Manning A, Panhuysen C, Farrer LA. Complement factor H polymorphism and age-related macular degeneration. Science. 2005;308:421–4.PubMedGoogle Scholar
  137. 137.
    Issa PC, Change NV, Scholl HPN. The significance of the complement system for the pathogenesis of age-related macular degeneration—current evidence and translation into clinical application. Graefes Arch Clin Exp Ophthalmol. 2011;249:163–74.Google Scholar
  138. 138.
    Nowak JZ. Age-related macular degeneration (AMD): pathogenesis and therapy. Pharmacol Rep. 2006;58:353–63.PubMedGoogle Scholar
  139. 139.
    Grisanti S, Tatar O. The role of vascular endothelial growth factor and other endogenous interplayers in age-related macular degeneration. Prog Retin Eye Res. 2008;27:372–90.PubMedGoogle Scholar
  140. 140.
    Nozaki M, Raisler BJ, Sakurai E, Sarma JV, Barnum SR, Lambris JD, Chen Y, Zhang K, Ambati BK, Baffi JZ, Ambati J. Drusen complement components C3a and C5a promote choroidal neovascularization. Proc Natl Acad Sci U S A. 2006;103:2328–33.PubMedGoogle Scholar
  141. 141.
    Rohrer B, Long Q, Coughlin B, Wilson RB, Huang Y, Qiao F, Tang PH, Kunchithapautham K, Gilkeson GS, Tomlinson S. A targeted inhibitor of the alternative complement pathway reduces angiogenesis in a mouse model of age-related macular degeneration. Invest Ophthalmol Vis Sci. 2009;50:3056–64.PubMedGoogle Scholar
  142. 142.
    Pons M, Marin-Castano ME. Cigarette smoke-related hydroquinone dysregulates MCP-1, VEGF and PEDF expression in retinal pigment epithelium in vitro and in vivo. PLoS One. 2011;6(2):e16722.PubMedGoogle Scholar
  143. 143.
    Beatty S, Koh H-H, Henson D, Boulton M. The role of oxidative stress in the pathogenesis of age related macular degeneration. Surv Ophthalmol. 2000;45:115–34.PubMedGoogle Scholar
  144. 144.
    Age-Related Eye Disease Study Research Group. A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E, beta carotene, and zinc for age-related macular degeneration and vision loss: AREDS report no. 8. Arch Ophthalmol. 2001;119:1417–36.Google Scholar
  145. 145.
    Green WR, Macdonnel PY, Yeo JH. Pathologic features of senile macular degeneration. Ophthalmology. 1985;92:615–27.PubMedGoogle Scholar
  146. 146.
    Bressler SH, Silva JC, Bressler NM. Clinicopathological correlation of occult choroidal neovascularisation in age-related macular degeneration. Arch Ophthalmol. 1992;110:827–32.PubMedGoogle Scholar
  147. 147.
    Feeney Burns L, Burns RP, Gao C-L. Age related macular changes in humans over 90 years old. Am J Ophthalmol. 1990;109:265–78.PubMedGoogle Scholar
  148. 148.
    Klein R, Meuer SM, Knudtson MD, Iyengar SK, Klein BE. The epidemiology of retinal reticular drusen. Am J Ophthalmol. 2008;145:317–26.PubMedGoogle Scholar
  149. 149.
    Zweifel SA, Imamura Y, Spaide TC, Fujiwara T, Spaide RF. Prevalence and significance of subretinal drusenoid deposits (reticular pseudodrusen) in age-related macular degeneration. Ophthalmology. 2010;117:1775–81.PubMedGoogle Scholar
  150. 150.
    Abdelsalam A, Del Priore L, Zarbin MA. Drusen in age related macular degeneration: pathogenesis, natural course and laser photocoagulation-induced regression. Surv Ophthalmol. 1999;44:1–29.PubMedGoogle Scholar
  151. 151.
    Spraul CW, Lang GE, Grossniklaus HE, Lang GK. Histologic and morphometric analysis of the choroid, Bruch’s membrane, and retinal pigment epithelium in post-mortem eyes with age related macular degeneration and histologic examination of surgically excised choroidal neovascular membranes. Surv Ophthalmol. 1999;44 Suppl 1:S10–32.PubMedGoogle Scholar
  152. 152.
    Sarks JP, Sarks SH, Killingsworth MC. Evolution of soft drusen in age-related macular degeneration. Eye. 1994;8:269–83.PubMedGoogle Scholar
  153. 153.
    Green WR, Enger C. Age-related macular degeneration histopathologic study. Ophthalmology. 1993;100:1519–35.PubMedGoogle Scholar
  154. 154.
    Loeffler KU, Lee WR. Basal linear deposit in the human macula. Graefes Arch Clin Exp Ophthalmol. 1986;224:493–501.Google Scholar
  155. 155.
    Killingsworth MC. Age related components of Bruch’s membrane in the human eye. Graefes Arch Clin Exp Ophthalmol. 1987;225:406–12.PubMedGoogle Scholar
  156. 156.
    Killingsworth MC, Sarks P, Sarks SH. Macrophages related to Bruch’s membrane in age related macular degeneration. Eye. 1990;4:613–21.PubMedGoogle Scholar
  157. 157.
    Sarks JP, Sarks SH, Killingsworth MC. Morphology of early choroidal neovascularisation in age-related macular degeneration: correlation with activity. Eye. 1997;11:515–22.PubMedGoogle Scholar
  158. 158.
    Loeffler KU, Lee WR. Terminology of sub-RPE deposits: do we all speak the same language? Br J Ophthalmol. 1998;82:1104–5.PubMedGoogle Scholar
  159. 159.
    Holz FG, Sheraidah G, Pauleikhoff D, Bird AC. Analysis of lipid deposits extracted from human macular and peripheral Bruch’s membrane. Arch Ophthalmol. 1994;112:402–6.PubMedGoogle Scholar
  160. 160.
    Bressler NM. Treatment of age-related macular degeneration with photodynamic therapy: 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;119:198–207.PubMedGoogle Scholar
  161. 161.
    CATT Research Group, Martin DF, Maguire MG, Ying GS, Grunwald JE, Fine SL, Jaffe GJ. Ranibizumab and bevacizumab for neovascular age-related macular degeneration. N Engl J Med. 2011;364:1897–908.PubMedGoogle Scholar
  162. 162.
    Grossniklaus HE, Gass JDM. Clinicopathologic correlations of surgically excised Type 1 and Type 2 submacular choroidal neovascular membranes. Am J Ophthalmol. 1998;126:56–9.Google Scholar
  163. 163.
    Lafaut BA, Bartz-Schmidt KU, Vanden Broecke C, Aisenbrey S, De Laey JJ, Heimann K. Clinicopathologic correlation in exudative age related macular degeneration: histological differentiation between classic and occult choroidal neovascularisation. Br J Ophthalmol. 2000;84(3):239–43.PubMedGoogle Scholar
  164. 164.
    Thomas MA, Grand MG, Williams DF, Lee CM, Pesin SR, Lowe MA. Surgical management of subfoveal choroidal neovascularisation. Ophthalmology. 1992;99:952–68.PubMedGoogle Scholar
  165. 165.
    Gass JDM. Biomicroscopic and histopathologic considerations regarding the feasibility of surgical excision of subfoveal neovascular membranes. Am J Ophthalmol. 1994;118:L285–98.Google Scholar
  166. 166.
    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;81:481–9.PubMedGoogle Scholar
  167. 167.
    Castellarin AO, Nasir MA, Sugino IK, Zarbin MA. Clinicopathological correlation of primary and recurrent choroidal neovascularisation following surgical excision in age related macular degeneration. Br J Ophthalmol. 1998;82:480–7.PubMedGoogle Scholar
  168. 168.
    Thomas MA, Kaplan HJ. Surgical removal of subfoveal neovascularisation in the presumed ocular histoplasmosis syndrome. Am J Ophthalmol. 1991;111:1–7.PubMedGoogle Scholar
  169. 169.
    Reddy VM, Zamora RL, Kaplan HJ. Distribution of growth factors in subfoveal neovascular membranes in age-related macular degeneration and presumed ocular histoplasmosis syndrome. Am J Ophthalmol. 1995;120(3):291–301.PubMedGoogle Scholar
  170. 170.
    Sehu KW, Lee WR, editors. Ophthalmic pathology: an illustrated guide for clinicians. Malden: Blackwell Publishing Ltd; 2008. ISBN 9780727917799.Google Scholar

Copyright information

© Springer-Verlag London 2014

Authors and Affiliations

  • Fiona Roberts
    • 1
  • Chee Koon Thum
    • 2
  1. 1.Southern General HospitalGlasgowUK
  2. 2.Western General HospitalEdinburghUK

Personalised recommendations