Vitreous pp 223-240 | Cite as

III.A. Congenital Vascular Vitreoretinopathies

  • Ronald Paul Hobbs
  • Mary Elizabeth Hartnett


Congenital vitreoretinopathies manifest in the pediatric or adult population in a variety of ways and cause varying levels of vision loss. These conditions can also be influenced by environmental factors, as in retinopathy of prematurity (ROP), or be associated with inheritance involving autosomal dominant, autosomal recessive, or X-linked patterns or be sporadic, as with familial exudative vitreoretinopathy (FEVR). As more is learned regarding gene associations, it is anticipated that complex genetic interactions may also play a role in the pathophysiology. Given the rarity of the diseases and their variable manifestations, along with the difficulty of obtaining longitudinal clinical information in the pediatric population, correct diagnosis and treatment can be quite challenging.


Retinopathy of prematurity (ROP) Neovascularization Angiogenesis Vasculogenesis Bevacizumab Pharmacologic vitreolysis Persistent fetal vasculature (PFV) Hyaloid vessels Familial exudative vitreoretinopathy (FEVR) Retinal detachment 


  1. 1.
    NEI press release. October 2009.
  2. 2.
    Patz A, Hoeck LE, DeLaCruz E. Studies on the effect of high oxygen administration in retrolental fibroplasias. I. Nursery observations. Am J Ophthalmol. 1952;35:1248–53.PubMedGoogle Scholar
  3. 3.
    Kinsey VE. Cooperative study of retrolental fibroplasia and the use of oxygen. Arch Ophthalmol. 1956;56:481–543.Google Scholar
  4. 4.
    Crosse VM, Evans PJ. Prevention of retrolental fibroplasias. AMA Arch Ophthalmol. 1952;48(1):83–7.PubMedGoogle Scholar
  5. 5.
    Gilbert C, Fielder A, Gordillo L, Quinn G, Semiglia R, Visintin P, et al. Characteristics of infants with severe retinopathy of prematurity in countries with low, moderate, and high levels of development: implication for screening programs. Pediatrics. 2005;115:e510–25.Google Scholar
  6. 6.
    Schaffer DB, Palmer EA, Plotsky DF, Metz HS, Flynn JT, Tung B, et al. Prognostic factors in the natural course of retinopathy of prematurity. The Cryotherapy for Retinopathy of Prematurity Cooperative Group. Ophthalmology. 1993;100:230–7.PubMedGoogle Scholar
  7. 7.
    Early Treatment for Retinopathy of Prematurity Cooperative Group, Good WV, Hardy RJ, et al. Final visual acuity results in the early treatment for retinopathy of prematurity study. Arch Ophthalmol. 2010;128:663–71.Google Scholar
  8. 8.
    Early Treatment for Retinopathy of Prematurity Cooperative Group, Dobson V, Quinn GE, et al. Grating visual acuity results in the early treatment for retinopathy of prematurity study. Arch Ophthalmol. 2011;129:840–6.Google Scholar
  9. 9.
    Chen J, Smith LE. Retinopathy of prematurity. Angiogenesis. 2007;10(2):133–40.PubMedGoogle Scholar
  10. 10.
    Chan-Ling T, Gock B, Stone J. Supplemental oxygen therapy: basis for noninvasive treatment of retinopathy of prematurity. Invest Ophthalmol Vis Sci. 1995;36:1215–30.Google Scholar
  11. 11.
    Ashton N. Retinal angiogenesis in the human embryo. Br Med Bull. 1970;26:103–6.PubMedGoogle Scholar
  12. 12.
    Hasegawa T, McLeod DS, Prow T, Merges C, Grebe R, Lutty GA. Vascular precursors in developing human retina. Invest Ophthalmol Vis Sci. 2008;49:2178–92.PubMedGoogle Scholar
  13. 13.
    Chan-Ling T, Gock B, Stone J. The effect of oxygen on vasoformative cell division: evidence that ‘physiological hypoxia’ is the stimulus for normal retinal vasculogenesis. Invest Ophthalmol Vis Sci. 1995;36:1201–14.PubMedGoogle Scholar
  14. 14.
    Hellstrom A, Carlsson B, Niklassen A, et al. IGF-1 is critical for normal vascularization of the human retina. J Clin Endocrinol Metab. 2002;87:3413–6.PubMedGoogle Scholar
  15. 15.
    Smith LE. IGF-1 and retinopathy of prematurity in the preterm infant. Biol Neonate. 2005;88:237–44.PubMedGoogle Scholar
  16. 16.
    Hartmann JS, Thompson H, Wang H, Kanekar S, Huang W, Budd SJ, Hartnett ME. Expression of vascular endothelial growth factor and pigment epithelial-derived factor in a rat model of retinopathy of prematurity. Mol Vis. 2011;17:1577–87.PubMedPubMedCentralGoogle Scholar
  17. 17.
    Hartnett ME. Studies on the pathogenesis of avascular retina and neovascularization into the vitreous in peripheral severe retinopathy of prematurity (an american ophthalmological society thesis). Trans Am Ophthalmol Soc. 2010;108:96–119.PubMedPubMedCentralGoogle Scholar
  18. 18.
    Hartnett ME, Penn JS. Mechanisms and management of retinopathy of prematurity. N Engl J Med. 2012;367(26):2515–26.PubMedPubMedCentralGoogle Scholar
  19. 19.
    Wang H, Byfield G, Jiang Y, Smith GW, McCloskey M, Hartnett ME. VEGF-mediated STAT3 activation inhibits retinal vascularization by down-regulating local erythropoietin expression. Am J Pathol. 2012;180(3):1243–53.PubMedPubMedCentralGoogle Scholar
  20. 20.
    Evolution of Stage 4 Retinopathy of Prematuirty Capone A and Trese MT in Pediatric Retina, volume 2 Lippincott Wolters Kluwer. Chapter 44, 2013;568–573.Google Scholar
  21. 21.
    Hartnett ME, McColm JR. Retinal features predictive of progression to stage 4 ROP. Retina. 2004;24:237–41.PubMedPubMedCentralGoogle Scholar
  22. 22.
    Coats DK. Retinopathy of prematurity: involution, factors predisposing to retinal detachment, and expected utility of preemptive surgical reintervention. Trans Am Ophthalmol Soc. 2005;103:281–312.PubMedPubMedCentralGoogle Scholar
  23. 23.
    Sebag J. Imaging vitreous. Eye. 2002;16(4):429–39.PubMedGoogle Scholar
  24. 24.
    Ueno N, Sebag J, Hirokawa H, Chakrabarti B. Effects of visible-light irradiation on vitreous structure in the presence of a photosensitizer. Exp Eye Res. 1987;44(6):863–70.PubMedGoogle Scholar
  25. 25.
    Raymond L, Jacobson B. Isolation and identification of stimulatory and inhibitory cell growth factors in bovine vitreous. Exp Eye Res. 1982;34(2):267.PubMedGoogle Scholar
  26. 26.
    Lutty GA, Mello RJ, Chandler C, Fait C, Bennett A, Patz A. Regulation of cell growth by vitreous humour. J Cell Sci. 1985;76(1):53–65.PubMedGoogle Scholar
  27. 27.
    Jacobson B, Dorfman T, Basu P, Hasany S. Inhibition of vascular endothelial cell growth and trypsin activity by vitreous. Exp Eye Res. 1985;41(5):581–95.PubMedGoogle Scholar
  28. 28.
    Machemer R. Description and pathogenesis of late stages of retinopathy of prematurity. Ophthalmology. 1985;92(8):1000.PubMedGoogle Scholar
  29. 29.
    Foos R. Chronic retinopathy of prematurity. Ophthalmology. 1985;92(4):563–74.PubMedGoogle Scholar
  30. 30.
    Cunningham S, Fleck BW, Elton RA, et al. Transcutaneous oxygen levels in retinopathy of prematurity. Lancet. 1995;346: 1464–5.PubMedGoogle Scholar
  31. 31.
    Seiberth V, Linderkamp O. Risk factors in retinopathy of prematurity. A multivariate statistical analysis. Ophthalmologica. 2000;214:131–5.PubMedGoogle Scholar
  32. 32.
    Vintzileos AM, Ananth CV, Smulian JC, et al. The impact of prenatal care in the United States on preterm births in the presence and absence of antenatal high-risk conditions. Am J Obstet Gynecol. 2002;187:1254–7.PubMedGoogle Scholar
  33. 33.
    Akinbami LJ, Schoendorf KC, Kiely JL. Risk of preterm birth in multiparous teenagers. Arch Pediatr Adolesc Med. 2000;154: 1101–7.PubMedGoogle Scholar
  34. 34.
    Datta-Bhutada S, Johnson HL, Rosen TS. Intrauterine cocaine and crack exposure: neonatal outcome. J Perinatol. 1998;18:183–8.PubMedGoogle Scholar
  35. 35.
    The STOP-ROP Multicenter Study Group. Supplemental therapeutic oxygen for prethreshold retinopathy of prematurity (STOP-ROP), a randomized, controlled trial. I: Primary outcomes. Pediatrics. 2000;105:295–310.Google Scholar
  36. 36.
    Chow LC, Wright KW, CSMC Oxygen Administration Study Group. Can changes in clinical practice decrease the incidence of severe retinopathy of prematurity in very low birth weight infants? Pediatrics. 2003;111(2):339–45.PubMedGoogle Scholar
  37. 37.
    VanderVeen DK, Mansfield TA, Eichenwald EC. Lower oxygen saturation alarm limits decrease the severity of retinopathy of prematurity. J AAPOS. 2006;10(5):445–8.PubMedGoogle Scholar
  38. 38.
    Britt MT, Sandoval M, Siegel LM. Decreased incidence of laser surgery for severe retinopathy of prematurity with supplemental oxygen protocol. J AAPOS. 2005;9(1):89.Google Scholar
  39. 39.
    Lane RH, Hartnett ME. Effects of oxygen on the development and severity of retinopathy of prematurity. J AAPOS. 2013;17(3):229–34.Google Scholar
  40. 40.
    Raju TNK, Langenberg P, Bhutani V, et al. Vitamin E prophylaxis to reduce retinopathy of prematurity: a reappraisal of published trials. J Pediatr. 1997;131:844–50.PubMedGoogle Scholar
  41. 41.
    Johnson L, Bowen Jr FW, Abbasi S, et al. Relationship of prolonged pharmacologic serum levels of Vitamin E to incidence of sepsis and incidence of necrotizing enterocolitis in infants with birth weight 1500 grams or less. Pediatrics. 1985;75:619–38.PubMedGoogle Scholar
  42. 42.
    Phelps DL, Lakatos L, Watts JL. D-Penicillamine for preventing retinopathy of prematurity in preterm infants. Cochrane Database Syst Rev. 2001;(1):CD001073.Google Scholar
  43. 43.
    Christensen RD, Alder SC, Richard SC, et al. D-Penicillamine administration and the incidence of retinopathy of prematurity. J Perinatol. 2007;27(2):103–11.PubMedGoogle Scholar
  44. 44.
    Tandon M, Dutta S, Dogra MR, Gupta A. Oral D-Penicillamine for the prevention of retinopathy of prematurity in very low birth weight infants: a randomized, placebo controlled trial. Acta Paediatr. 2010;99(9):1324–8.PubMedGoogle Scholar
  45. 45.
    Siatkowksi RM, Yanovitch TL, Ash JD, Moreau A. The effects of D-penicillamine on a murine model of oxygen-induced retinopathy. J AAPOS. 2001;15(4):370–3.Google Scholar
  46. 46.
    May CA. The influence of triamcinolone on endostatin-like proteins in oxygen-induced retinopathy of prematurity. Exp Eye Res. 2012;100:86–7.PubMedGoogle Scholar
  47. 47.
    Zhang HB, Sun NX, Liang HC, et al. 17-Alpha-estradiol ameliorating oxygen induced retinopathy in a murine model. Jpn J Ophthalmol. 2012;56(4):407–15.PubMedGoogle Scholar
  48. 48.
    American Academy of Pediatrics Section on Ophthalmology, American Academy of Ophthalmology, American Association for Pediatric Ophthalmology and Strabismus, American Association of Certified Orthoptists. Screening examination of premature infants for retinopathy of prematurity. Pediatrics. 2013;131:189–95.Google Scholar
  49. 49.
    Early Treatment For Retinopathy Of Prematurity Cooperative Group. Revised indications for the treatment of retinopathy of prematurity: results for the early treatment of retinopathy of prematurity randomized trial. Arch Ophthalmol. 2003;121:1684–94.PubMedGoogle Scholar
  50. 50.
    Lofqvist C, Hansen-Pupp I, Anderssen E, et al. Validation of a new retinopathy of prematurity screening method monitoring longitudinal postnatal weight and insulin-like growth factor I. Arch Ophthalmol. 2009;127:622–7.PubMedGoogle Scholar
  51. 51.
    Hellstrom A, Hard AL, Engstrom E, et al. Early weight gain predicts retinopathy in preterm infants: new, simple, efficient approach to screening. Pediatrics. 2009;123:e638–45.PubMedGoogle Scholar
  52. 52.
    Wu C, Lofqvist C, Smith LE, et al. Importance of early postnatal weight gain for normal retinal angiogenesis in very preterm infants: a multicenter study analyzing weight velocity deviations for the prediction of retinopathy of prematurity. Arch Ophthalmol. 2012;130:992–9.PubMedPubMedCentralGoogle Scholar
  53. 53.
    Wu C, Vanderveen DK, Hellstrom A, et al. Longitudinal postnatal weight gain measurements for the prediction of retinopathy of prematurity. Arch Ophthalmol. 2010;128:443–7.PubMedPubMedCentralGoogle Scholar
  54. 54.
    Binenbaum G, Ying GS, Quinn GE, et al. The CHOP postnatal weight gain, birth weight, and gestational age retinopathy of prematurity risk model. Arch Ophthalmol. 2012;130:1560–5.PubMedGoogle Scholar
  55. 55.
    Binenbaum G, Ying GS, Quinn GE, et al. A clinical prediction model to stratify retinopathy of prematurity using postnatal weight gain. Pediatrics. 2011;127:e607–14.PubMedPubMedCentralGoogle Scholar
  56. 56.
    O’Keefe M, Kirwan C. Screening for retinopathy of prematurity. Early Hum Dev. 2008;84:89–94.PubMedGoogle Scholar
  57. 57.
    Good WV, Hardy RJ, Dobson V, et al. Early Treatment for Retinopathy of Prematurity Cooperative Group. Final visual acuity results in the early treatment for retinopathy of prematurity study. Arch Ophthalmol. 2010;128(6):663–71.PubMedGoogle Scholar
  58. 58.
    Quinn GE, Dobson V, Hardy R, et al. Visual field extent at 6 years of age in children who had high-risk prethreshold retinopathy of prematurity. Arch Ophthalmol. 2011;129:127–32.PubMedGoogle Scholar
  59. 59.
    Alme AM, Mulhern ML, Hejkal TW, et al. Outcome of retinopathy of prematurity patients following adoption of revised indications for treatment. BMC Ophthalmol. 2008;8(1):23.PubMedPubMedCentralGoogle Scholar
  60. 60.
    Simpson JL, Melia M, Yang MB, et al. Current role of cryotherapy in retinopathy of prematurity: a report by the American Academy of Ophthalmology. Ophthalmology. 2012;119:873–7.PubMedGoogle Scholar
  61. 61.
    Palmer EA, Hardy RJ, Dobson V, et al. 15 year outcomes following threshold retinopathy of prematurity: final results from the multicenter trial of cryotherapy for retinopathy of prematurity. Arch Ophthalmol. 2005;123:311–8.PubMedGoogle Scholar
  62. 62.
    Banach MJ, Ferrone PJ, Trese MT. A comparison of dense versus less dense diode laser photocoagulation patterns for threshold retinopathy of prematurity. Ophthalmology. 2000;107:324–8.PubMedGoogle Scholar
  63. 63.
    Paysse EA, Lindsey JL, Coats DK, et al. Therapeutic outcomes of cryotherapy versus transpupillary diode laser photocoagulation for threshold retinopathy of prematurity. J AAPOS. 1999;3(4):234–40.PubMedGoogle Scholar
  64. 64.
    Ng EY, Connolly BP, McNamara JA, et al. A comparison of laser photocoagulation with cryotherapy for threshold retinopathy of prematurity at 10 years: part 1. Visual function and structural outcome. Ophthalmology. 2002;109(5):928–34.PubMedGoogle Scholar
  65. 65.
    Connolly BP, Ng EY, McNamara JA, et al. A comparison of laser photocoagulation with cryotherapy for threshold retinopathy of prematurity at 10 years: part 2. Refractive outcome. Ophthalmology. 2002;109(5):936–41.PubMedGoogle Scholar
  66. 66.
    Andersen CC, Phelps DL. Peripheral retinal ablation for threshold retinopathy of prematurity in preterm infants. Cochrane Database Syst Rev. 2000;(2): CD001693.Google Scholar
  67. 67.
    Matsuyama K, Ogata N, Matsuoka M, Wada M, Takahashi K, Nishimura T. Plasma levels of vascular endothelial growth factor and pigment epithelium-derived factor before and after intravitreal injection of bevacizumab. Br J Ophthalmol. 2010;94:1215–8.PubMedGoogle Scholar
  68. 68.
    Mintz-Hittner HA, Kennedy KA, Chuang AZ, BEAT-ROP Cooperative Group. Efficacy of intravitreal bevacizumab for stage 3+ retinopathy of prematurity. N Engl J Med. 2011;364:603–15.PubMedPubMedCentralGoogle Scholar
  69. 69.
    Hu J, Blair MP, Shapiro MJ, et al. Reactivation of retinopathy of prematurity after bevacizumab injection. Arch Ophthalmol. 2012;130:1000–6.PubMedGoogle Scholar
  70. 70.
    McCloskey M, Wang H, Jiang Y, Smith GW, Strange J, Hartnett ME. Anti-VEGF antibody leads to later atypical intravitreous neovascularization and activation of angiogenic pathways in a rat model of retinopathy of prematurity. Invest Ophthalmol Vis Sci. 2013;54(3):2020–6.PubMedPubMedCentralGoogle Scholar
  71. 71.
    Gaudreault J, Fei D, Rusit J, Suboc P, Shiu V. Preclinical pharmacokinetics of ranibizumab (rhuFabV2) after a single intravitreal administration. Invest Opthalmol Vis Sci. 2005;46:726–33.Google Scholar
  72. 72.
    Miyake T, Sawada O, Kakinoki M, Sawada T, Kawamura H, Ogasawara K, et al. Pharmacokinetics of bevacizumab and its effect on vascular endothelial growth factor after intravitreal injection of bevacizumab in macaque eyes. Invest Ophthalmol Vis Sci. 2010;51:1606–8.PubMedGoogle Scholar
  73. 73.
    Sato T, Wada K, Arahori H, et al. Serum concentrations of bevacizumab (avastin) and vascular endothelial growth factor in infants with retinopathy of prematurity. Am J Ophthalmol. 2012;153(2):327–33.PubMedGoogle Scholar
  74. 74.
    Zehetner C, Kirchmair R, Huber S, et al. Plasma levels of vascular endothelial growth factor before and after intravitreal injection of bevacizumab, ranibizumab and pegaptanib in patients with age-related macular degeneration, and in patients with diabetic macular oedema. Br J Ophthalmol. 2013;97(4):454–9.PubMedGoogle Scholar
  75. 75.
    Hoerster R, Muether P, Dahlke C, et al. Serum concentrations of vascular endothelial growth factor in an infant treated with ranibizumab for retinopathy of prematurity. Acta Ophthalmol. 2013;91(1):e74–5.PubMedGoogle Scholar
  76. 76.
    Sebag J. Pharmacologic vitreolysis. Retina. 1998;18(1):1–3.PubMedGoogle Scholar
  77. 77.
    Sebag J. Pharmacologic vitreolysis – premise and promise of the first decade. Retina. 2009;29(7):871–4.PubMedGoogle Scholar
  78. 78.
    Stenzel D, Lundkvist A, Sauvaget D, et al. Integrin-dependent and -independent functions of astrocytic fibronectin in retinal angiogenesis. Development. 2011;138:4451–63.PubMedPubMedCentralGoogle Scholar
  79. 79.
    Pepper MS. Role of the matrix metalloproteinase and plasminogen activator-plasmin systems in angiogenesis. Arterioscler Thromb Vasc Biol. 2001;21:1104–17.PubMedGoogle Scholar
  80. 80.
    Wu W-C, Drenser KA, Lai M, Capone A, Trese MT. Plasmin enzyme-assisted vitrectomy for primary and reoperated eyes with stage 5 retinopathy of prematurity. Retina. 2008;28:S75–80. doi: 10.1097/IAE.0b013e318158ea0e.PubMedGoogle Scholar
  81. 81.
    Wong SCC, Jr A. Microplasmin (ocriplasmin) in pediatric vitreoretinal surgery: update and review. Retina. 2013;33:339–48.PubMedGoogle Scholar
  82. 82.
    Coats DK, Miller AM, Hussein MA, et al. Involution of retinopathy of prematurity after laser treatment: factors associated with development of retinal detachment. Am J Ophthalmol. 2005;140:214–22.PubMedGoogle Scholar
  83. 83.
    Trese MT, Droste PJ. Long-term postoperative results of a consecutive series of stages 4 and 5 retinopathy of prematurity. Ophthalmology. 1998;105:992–7.PubMedGoogle Scholar
  84. 84.
    Hartnett ME. Features associated with surgical outcome in patients with stages 4 and 5 retinopathy of prematurity. Retina. 2003;23(3):322–9.PubMedGoogle Scholar
  85. 85.
    Clark D, Mandal K. Treatment of retinopathy of prematurity. Early Hum Dev. 2008;84:95–9.PubMedGoogle Scholar
  86. 86.
    Hartnett ME, Maguluri S, Thompson HW, McColm JR. Comparison of retinal outcomes after scleral buckle or lens-sparing vitrectomy for stage 4 retinopathy of prematurity. Retina. 2004;24:753–7.PubMedGoogle Scholar
  87. 87.
    Ferrone PJ, Harrison C, Trese MT. Lens clarity after lens-sparing vitrectomy in a pediatric population. Ophthalmology. 1997;104:273–8.PubMedGoogle Scholar
  88. 88.
    Lakhanpal RR, Davis GH, Sun RL, et al. Lens clarity after three port lens-sparing vitrectomy in stage 4A and 4B retinal detachments secondary to retinopathy of prematurity. Arch Ophthalmol. 2006;124(1):20–3.PubMedGoogle Scholar
  89. 89.
    Mann I. The development of the human eye. New York: Grune& Stratton Inc.; 1950.Google Scholar
  90. 90.
    Hamming NA, et al. Ultrastructure of the hyaloid vasculature in primates. Invest Ophthalmol Vis Sci. 1977;16:408–15.PubMedGoogle Scholar
  91. 91.
    Gergely K, Gerinec A. A consonant construction of the hyaloids and retinal vascular systems by the angiogenic process. Bratisl Lek Listy. 2011;112(3):143–51.PubMedGoogle Scholar
  92. 92.
    Alvarez Y, et al. Genetic determinants of hyaloid and retinal vasculature in zebrafish. BMC Dev Biol. 2007;7:114.PubMedPubMedCentralGoogle Scholar
  93. 93.
    Jack RL. Regression of the hyaloid artery system: an ultrastructural analysis. Am J Ophthalmol. 1972;74:261–72.PubMedGoogle Scholar
  94. 94.
    Latker CH, Kuwabara T. Regression of the tunica vasculosalentis in the postnatal rat. Invest Ophthalmol Vis Sci. 1981;21:689–99.PubMedGoogle Scholar
  95. 95.
    Duke-Elder S. System of ophthalmology. Vol. 3. Normal and abnormal development. Part 1: embryology. St. Louis: The C.V. Mosby Company, 1964. In: Hamming NA, Apple DJ, Gieser DK, Vygantas CM. Ultrastructure of the hyaloid vasculature in primates. Invest Ophthalmol Vis Sci. 1977;16:408–15.Google Scholar
  96. 96.
    Delaney WV. Prepapillary hemorrhage and persistent hyaloid artery. Am J Ophthalmol. 1980;90:419–21.PubMedGoogle Scholar
  97. 97.
    Renz B, Vygantas C. Hyaloid vascular remnants in human neonates. Ann Ophthalmol. 1977;9:179–84.PubMedGoogle Scholar
  98. 98.
    Mets MB. Childhood blindness and visual loss: an assessment at two institutions including a “new” cause. Trans Am Ophthalmol Soc. 1999;97:653–96.PubMedPubMedCentralGoogle Scholar
  99. 99.
    Gans B. The pupillary membrane in premature infants. Arch Dis Child. 1959;34:292–7.PubMedPubMedCentralGoogle Scholar
  100. 100.
    Hollenberg MJ, Dickson DH. Scanning electron microscopy of the tunica vasculosa lentis of the rat. Can J Ophthalmol. 1971;6:301–10.PubMedGoogle Scholar
  101. 101.
    Meisels H, Goldberg MF. Vascular anastomoses between the iris and persistent hyperplastic primary vitreous. Am J Ophthalmol. 1979;88:179–85.PubMedGoogle Scholar
  102. 102.
    Goldberg MF. Clinical manifestations of ectopia lentis et pupillae in 16 patients. Ophthalmology. 1988;95:1080–7.PubMedGoogle Scholar
  103. 103.
    Gifford SR, Latta JS. Pseudoglioma and remains of the tunica vasculosalentis. Am J Ophthalmol. 1923;6:565–71.Google Scholar
  104. 104.
    Sellheyer K, Spitznas M. Ultrastructure of the human posterior tunica vasculosalentis during early gestation. Graefes Arch Clin Exp Ophthalmol. 1987;225:377–83.PubMedGoogle Scholar
  105. 105.
    Hittner HM, Hirsch NJ, Rudolph HJ. Assessment of gestational age by examination of the anterior vascular capsule of the lens. J Pediatr. 1977;91:455–8.PubMedGoogle Scholar
  106. 106.
    Pollard ZF. Persistent hyperplastic primary vitreous, diagnosis, treatment, and results. Am Ophthalmol Soc. 1997;95:487–549.Google Scholar
  107. 107.
    Goldberg MF. Persistent fetal vasculature (PFV): an integrated interpretation of signs and symptoms associated with persistent hyperplastic primary vitreous (PHPV) LIV Edward Jackson Memorial Lecture. Am J Ophthalmol. 1997;124:587–626.PubMedGoogle Scholar
  108. 108.
    Xu O, Wang YS, Dabdoub A, et al. Vascular development in the retina and inner ear: control by norrin and frizzled 4, a high affinity ligand receptor pair. Cell. 2004;116:883–95.PubMedGoogle Scholar
  109. 109.
    Prasov L, et al. ATOH7 mutations cause autosomal recessive persistent hyperplasia of the primary vitreous. Hum Mol Genet. 2012;21(16):3681–94.PubMedPubMedCentralGoogle Scholar
  110. 110.
    Edward MM, Mcleon DS, Grebe R, Heng C, Lefebvre O, Lutty GA. Lama1 mutations lead to vitreoretinal blood vessel formation, persistence of fetal vasculature, and epiretinal membrane formation in mice. BMC Dev Biol. 2011;11:60.Google Scholar
  111. 111.
    Martin AC, Thornton JD, Liu J, et al. Pathogenesis of persistent hyperplastic primary vitreous in mice lacking the arf tumor suppressor gene. Invest Ophathlmol Vis Sci. 2004;45:3387–96.Google Scholar
  112. 112.
    Reichel MB, Ali RR, D’Esposito F, et al. High frequency of persistent hyperplastic primary vitreous and cataracts in p-53 deficient mice. Cell Death Differ. 1998;5:156–62.PubMedGoogle Scholar
  113. 113.
    Zhang J, Fuhrmann S, Vetter ML. A nonautonomous role for retinal frizzled-5 in regulating hyaloids vitreous vasculature development. Invest Ophathlmol Vis Sci. 2008;49:5561–7.Google Scholar
  114. 114.
    Rutland CS, Mitchell CA, Nasir M, Konerding MA, Drexler HC. Microphthalmia, persistent hyperplastic hyaloid vasculature and lens anomalies following overexpression of VEGF-A188 from the alpha A-crystallin promoter. Mol Vis. 2007;13:47–56.PubMedPubMedCentralGoogle Scholar
  115. 115.
    Criswick VG, Schepens CL. Familial exudative vitreoretinopathy. Am J Ophthalmol. 1969;68:578–94.PubMedGoogle Scholar
  116. 116.
    Ranchod TM, Ho LY, Drenser KA, Capone Jr A, Trese MT. Clinical presentation of familial exudative vitreoretinopathy. Ophathalmology. 2011;118:2070–5.Google Scholar
  117. 117.
    Benson WE. Familial exudative vitreoretinopathy. Trans Am Ophthalmol Soc. 1995;93:473–521.PubMedPubMedCentralGoogle Scholar
  118. 118.
    Tasman W, Augsburger JJ, Shields JA, et al. Familial exudative vitreoretinopathy. Trans Am Ophthalmol Soc. 1981;79:211–26.PubMedPubMedCentralGoogle Scholar
  119. 119.
    Miyakubo H, Inohara N, Hashimot K. Retinal involvement in familial exudative vitreoretinopathy. Ophthalmologica. 1982;185:125–35.PubMedGoogle Scholar
  120. 120.
    Van Nouhuys CE. Dominant exudative vitreoretinopathy and other vascular developmental disorders of the peripheral retina [thesis]. Doc Opahthalol. 1982;54:1–415.Google Scholar
  121. 121.
    Trese MT, Capone Jr A. Familial exudative vitreoretinopathy. In: Pediatric retina. Philadelphia: Lippincott Williams & Wilkins; 2005. p. 425–8.Google Scholar
  122. 122.
    Pendergast SD, Trese MT. Familial exudative vitreoretinopathy: results of surgical management. Ophathalmology. 1998;105:1015–23.Google Scholar
  123. 123.
    Toomes C, Downey L. Familial exudative vitreoretinopathy: autosomal dominant. GeneReviews. Available at Accessed Mar 2013.
  124. 124.
    Shukla D, Singh J, Sudheer G, et al. Familial exudative vitreoretinopathy (FEVR). Clinical profile and management. Indian J Ophthalmol. 2003;51:323–8.PubMedGoogle Scholar
  125. 125.
    Toomes C, Bottomley HM, Jackson RM, et al. Mutations in LRP5 or FZD4 underlie the common familial exudative vitreoretinopathy locus on chromosome 11q. Am J Hum Genet. 2004;74:721–30.PubMedPubMedCentralGoogle Scholar
  126. 126.
    Ikeda T, Tano Y, Tsujikawa K, et al. Vitrectomy for rhegmatogenous or tractional retinal detachment with familial exudative vitreoretinopathy. Ophthalmology. 1999;106:1081–5.PubMedGoogle Scholar
  127. 127.
    Glazer LC, Maguir A, Blumenkranz MS, et al. Improved surgical treatment of familial exudative vitreoretinopathy in children. Am J Ophthalmol. 1995;120:471–9.PubMedGoogle Scholar
  128. 128.
    Chen SN, Hwang JF, Lin CJ. Clinical characteristics and surgical management of familial exudative vitreoretinopathy-associated rhegmatogenous retinal detachment. Retina. 2012;32(2):220–5.PubMedGoogle Scholar
  129. 129.
    Williams JG, Trese MT, Williams GA, et al. Autologous plasmin enzyme in the surgical management of diabetic retinopathy. Ophthalmology. 2001;108:1902–5.PubMedGoogle Scholar
  130. 130.
    Wu WC, Drenser KA, Trese MT, et al. Pediatric traumatic macular hole: results of autologous plasmin enzyme-assisted vitrectomy. Am J Ophthalmol. 2007;144(5):668–72.PubMedGoogle Scholar
  131. 131.
    Tagami M, Kusuhara S, Honda S, et al. Rapid regression of retinal hemorrhage and neovascularization in a case of familial exudative vitreoretinopathy treated with intravitreal bevacizumab. Graefes Arch Clin Exp Ophthalmol. 2008;246(12):1787–9.PubMedGoogle Scholar
  132. 132.
    Sebag J, Nguyen N. Vitreous embryology and vitreo-retinal developmental disorders. In: Hartnett ME et al., editors. Pediatric retina. Philadelphia: Lippincott; 2005. p. 13–28.Google Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  1. 1.Vitreoretinal FellowUniversity of Utah, John A Moran Eye CenterSalt Lake CityUSA
  2. 2.Vitreoretinal Service and Surgery, Retinal Angiogenesis LaboratoryUniversity of Utah, John A. Moran Eye CenterSalt Lake CityUSA

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