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Pharmakologische Therapie der Frühgeborenenretinopathie

Pharmacological treatment for retinopathy of prematurity

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Zusammenfassung

Ein verbindlich festgelegtes Screening durch erfahrene Ophthalmologen ist nach wie vor die wichtigste Säule im Management der Frühgeborenenretinopathie (ROP). Den derzeitigen Goldstandard zur Therapie der proliferativen ROP stellt nach wie vor die panretinale Laserkoagulation dar, je nach Schwere ggf. in Kombination mit vitreoretinaler Chirurgie. Die ersten Fallserien zur „off-label“ durchgeführten intravitrealen Anti-VEGF-Therapie sind ermutigend. Neben der intravitrealen Anti-VEGF-Therapie stellen auch Behandlungskonzepte wie die Supplementation von IGF-1 oder ω3-Fettsäuren interessante pharmakologische Ansätze zur Behandlung der ROP dar. Allerdings müssen auch diese systemischen Therapieansätze ihren Nutzen und ihre Sicherheit erst in größeren kontrollierten Studien unter Beweis stellen.

Abstract

Mandatory screening performed by an experience ophthalmologist remains the most important pillar in the management of retinopathy of prematurity (ROP). The current gold standard for treatment of proliferative ROP is still panretinal laser photocoagulation, depending on severity, in combination with vitreoretinal surgery if necessary. The first case series of off-label intravitreal anti-VEGF treatment are encouraging. In addition to intravitreal anti-VEGF therapy, other treatment concepts such as supplementation with IGF-1 or omega-3 fatty acids also represent interesting pharmacological approaches to the management of ROP. However, larger controlled trials are required to validate the benefits and safety of these systemic treatment approaches.

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Literatur

  1. Aiello LP, Pierce EA, Foley ED et al (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 U S A 92:10457–10461

    Article  PubMed  CAS  Google Scholar 

  2. Atchaneeyasakul LO, Trinavarat A (2010) Choroidal ruptures after adjuvant intravitreal injection of bevacizumab for aggressive posterior retinopathy of prematurity. J Perinatol 30:497–499

    Article  PubMed  Google Scholar 

  3. Bainbridge JW, Mistry A, De Alwis M et al (2002) Inhibition of retinal neovascularisation by gene transfer of soluble VEGF receptor sFlt-1. Gene Ther 9:320–326

    Article  PubMed  CAS  Google Scholar 

  4. Brown DM, Kaiser PK, Michels M et al (2006) Ranibizumab versus verteporfin for neovascular age-related macular degeneration. N Engl J Med 355:1432–1444

    Article  PubMed  CAS  Google Scholar 

  5. Bush RA, Malnoe A, Reme CE, Williams TP (1994) Dietary deficiency of N-3 fatty acids alters rhodopsin content and function in the rat retina. Invest Ophthalmol Vis Sci 35:91–100

    PubMed  CAS  Google Scholar 

  6. Calder PC, Jensen GL, Koletzko BV et al (2010) Lipid emulsions in parenteral nutrition of intensive care patients: current thinking and future directions. Intensive Care Med 36:735–749

    Article  PubMed  CAS  Google Scholar 

  7. Caufriez A, Frankenne F, Englert Y et al (1990) Placental growth hormone as a potential regulator of maternal IGF-I during human pregnancy. Am J Physiol 258:E1014–E1019

    PubMed  CAS  Google Scholar 

  8. Chen J, Stahl A, Hellstrom A, Smith LE (2011) Current update on retinopathy of prematurity: screening and treatment. Curr Opin Pediatr 23(2):173–178

    Article  PubMed  Google Scholar 

  9. Cheung HM, Lam HS, Tam YH et al (2009) Rescue treatment of infants with intestinal failure and parenteral nutrition-associated cholestasis (PNAC) using a parenteral fish-oil-based lipid. Clin Nutr 28:209–212

    Article  PubMed  CAS  Google Scholar 

  10. Chung EJ, Kim JH, Ahn HS, Koh HJ (2007) Combination of laser photocoagulation and intravitreal bevacizumab (Avastin) for aggressive zone I retinopathy of prematurity. Graefes Arch Clin Exp Ophthalmol 245:1727–1730

    Article  PubMed  CAS  Google Scholar 

  11. Connor KM, Krah NM, Dennison RJ et al (2009) Quantification of oxygen-induced retinopathy in the mouse: a model of vessel loss, vessel regrowth and pathological angiogenesis. Nat Protoc 4:1565–1573

    Article  PubMed  CAS  Google Scholar 

  12. Connor KM, SanGiovanni JP, Lofqvist C et al (2007) Increased dietary intake of omega-3-polyunsaturated fatty acids reduces pathological retinal angiogenesis. Nat Med 13:868–873

    Article  PubMed  CAS  Google Scholar 

  13. Crawford MA, Costeloe K, Ghebremeskel K et al (1997) Are deficits of arachidonic and docosahexaenoic acids responsible for the neural and vascular complications of preterm babies? Am J Clin Nutr 66:1032S–1041S

    PubMed  CAS  Google Scholar 

  14. Lucena D da R, Ribeiro JA, Costa RA et al (2009) Intraoperative bleeding during vitrectomy for diabetic tractional retinal detachment with versus without preoperative intravitreal bevacizumab (IBeTra study). Br J Ophthalmol 93:688–691

    Article  Google Scholar 

  15. Meijer VE de, Gura KM, Le HD et al (2009) Fish oil-based lipid emulsions prevent and reverse parenteral nutrition-associated liver disease: the Boston experience. JPEN J Parenter Enteral Nutr 33:541–547

    Article  PubMed  Google Scholar 

  16. Engstrom E, Niklasson A, Wikland KA et al (2005) The role of maternal factors, postnatal nutrition, weight gain, and gender in regulation of serum IGF-I among preterm infants. Pediatr Res 57:605–610

    Article  PubMed  Google Scholar 

  17. Fortes Filho JB, Bonomo PP, Maia M, Procianoy RS (2009) Weight gain measured at 6 weeks after birth as a predictor for severe retinopathy of prematurity: study with 317 very low birth weight preterm babies. Graefes Arch Clin Exp Ophthalmol 247:831–836

    Article  Google Scholar 

  18. Heckmann M (2008) Pathogenesis of retinopathy of prematurity. Ophthalmologe 105:1101–1107

    Article  PubMed  CAS  Google Scholar 

  19. Hellstrom A, Engstrom E, Hard AL et al (2003) Postnatal serum insulin-like growth factor I deficiency is associated with retinopathy of prematurity and other complications of premature birth. Pediatrics 112:1016–1020

    Article  PubMed  Google Scholar 

  20. Hellstrom A, Ley D, Hansen-Pupp I et al (2010) New insights into the development of retinopathy of prematurity – importance of early weight gain. Acta Paediatr 99:502–508

    Article  PubMed  CAS  Google Scholar 

  21. Hellstrom A, Perruzzi C, Ju M et al (2001) Low IGF-I suppresses VEGF-survival signaling in retinal endothelial cells: direct correlation with clinical retinopathy of prematurity. Proc Natl Acad Sci U S A 98:5804–5808

    Article  PubMed  CAS  Google Scholar 

  22. Hoang QV, Kiernan DF, Chau FY et al (2010) Fluorescein angiography of recurrent retinopathy of prematurity after initial intravitreous bevacizumab treatment. Arch Ophthalmol 128:1080–1081

    Article  PubMed  Google Scholar 

  23. Honda S, Hirabayashi H, Tsukahara Y, Negi A (2008) Acute contraction of the proliferative membrane after an intravitreal injection of bevacizumab for advanced retinopathy of prematurity. Graefes Arch Clin Exp Ophthalmol 246:1061–1063

    Article  PubMed  CAS  Google Scholar 

  24. Jandeck C (2009) New therapeutic approaches in the treatment of retinopathy of prematurity. Klin Monatsbl Augenheilkd 226:914–920

    Article  PubMed  CAS  Google Scholar 

  25. Jandeck C, Kellner U, Lorenz B, Seiberth V (2008) Guidelines for ophthalmological screening of premature infants in Germany. Klin Monatsbl Augenheilkd 225:123–130

    Article  PubMed  CAS  Google Scholar 

  26. Jang SY, Choi KS, Lee SJ (2010) Delayed-onset retinal detachment after an intravitreal injection of ranibizumab for zone 1 plus retinopathy of prematurity. J AAPOS 14:457–459

    Article  PubMed  Google Scholar 

  27. Kelly DA (2006) Intestinal failure-associated liver disease: what do we know today? Gastroenterology 130:S70–S77

    Article  PubMed  CAS  Google Scholar 

  28. Kusaka S, Shima C, Wada K et al (2008) Efficacy of intravitreal injection of bevacizumab for severe retinopathy of prematurity: a pilot study. Br J Ophthalmol 92:1450–1455

    Article  PubMed  CAS  Google Scholar 

  29. Kychenthal A, Dorta P (2010) Vitrectomy after intravitreal bevacizumab (Avastin) for retinal detachment in retinopathy of prematurity. Retina 30:S32–S36

    Article  PubMed  Google Scholar 

  30. Lalwani GA, Berrocal AM, Murray TG et al (2008) Off-label use of intravitreal bevacizumab (Avastin) for salvage treatment in progressive threshold retinopathy of prematurity. Retina 28:S13–S18

    Article  PubMed  Google Scholar 

  31. Lee JY, Chae JB, Yang SJ et al (2010) Effects of intravitreal bevacizumab and laser in retinopathy of prematurity therapy on the development of peripheral retinal vessels. Graefes Arch Clin Exp Ophthalmol 248:1257–1262

    Article  PubMed  CAS  Google Scholar 

  32. Lofqvist C, Andersson E, Sigurdsson J et al (2006) Longitudinal postnatal weight and insulin-like growth factor I measurements in the prediction of retinopathy of prematurity. Arch Ophthalmol 124:1711–1718

    Article  PubMed  Google Scholar 

  33. Lorenz B (2008) Current ophthalmic aspects of acute retinopathy of prematurity. Ophthalmologe 105:1092–1100

    Article  PubMed  CAS  Google Scholar 

  34. Marneros AG, Fan J, Yokoyama Y et al (2005) Vascular endothelial growth factor expression in the retinal pigment epithelium is essential for choriocapillaris development and visual function. Am J Pathol 167:1451–1459

    Article  PubMed  CAS  Google Scholar 

  35. McLeod DS, Taomoto M, Cao J et al (2002) Localization of VEGF receptor-2 (KDR/Flk-1) and effects of blocking it in oxygen-induced retinopathy. Invest Ophthalmol Vis Sci 43:474–482

    PubMed  Google Scholar 

  36. McLoone E, O’Keefe M, McLoone S, Lanigan B (2006) Long term functional and structural outcomes of laser therapy for retinopathy of prematurity. Br J Ophthalmol 90:754–759

    Article  PubMed  CAS  Google Scholar 

  37. Mintz-Hittner HA, Best LM (2009) Antivascular endothelial growth factor for retinopathy of prematurity. Curr Opin Pediatr 21:182–187

    Article  PubMed  Google Scholar 

  38. Mintz-Hittner HA, Kennedy KA, Chuang AZ (2011) Efficacy of intravitreal bevacizumab for stage 3+ retinopathy of prematurity. N Engl J Med 364:603–615

    Article  PubMed  CAS  Google Scholar 

  39. Mintz-Hittner HA, Kuffel RR Jr (2008) Intravitreal injection of bevacizumab (avastin) for treatment of stage 3 retinopathy of prematurity in zone I or posterior zone II. Retina 28:831–838

    Article  PubMed  Google Scholar 

  40. Nazari H, Modarres M, Parvaresh MM, Falavarjani KG (2010) Intravitreal bevacizumab in combination with laser therapy for the treatment of severe retinopathy of prematurity (ROP) associated with vitreous or retinal hemorrhage. Graefes Arch Clin Exp Ophthalmol 248:1713–1718

    Article  PubMed  CAS  Google Scholar 

  41. Nguyen CT, Vingrys AJ, Bui BV (2008) Dietary omega-3 fatty acids and ganglion cell function. Invest Ophthalmol Vis Sci 49:3586–3594

    Article  PubMed  Google Scholar 

  42. Nishijima K, Ng YS, Zhong L et al (2007) Vascular endothelial growth factor-A is a survival factor for retinal neurons and a critical neuroprotectant during the adaptive response to ischemic injury. Am J Pathol 171:53–67

    Article  PubMed  CAS  Google Scholar 

  43. Nonobe NI, Kachi S, Kondo M et al (2009) Concentration of vascular endothelial growth factor in aqueous humor of eyes with advanced retinopathy of prematurity before and after intravitreal injection of bevacizumab. Retina 29:579–585

    Article  PubMed  Google Scholar 

  44. Ozaki H, Seo MS, Ozaki K et al (2000) Blockade of vascular endothelial cell growth factor receptor signaling is sufficient to completely prevent retinal neovascularization. Am J Pathol 156:697–707

    Article  PubMed  CAS  Google Scholar 

  45. Pelken L, Maier RF (2008) Risk factors and prevention of retinopathy of prematurity. Ophthalmologe 105:1108–1113

    Article  PubMed  CAS  Google Scholar 

  46. Perez-Munuzuri A, Fernandez-Lorenzo JR, Couce-Pico ML et al (2010) Serum levels of IGF1 are a useful predictor of retinopathy of prematurity. Acta Paediatr 99:519–525

    Article  PubMed  CAS  Google Scholar 

  47. Pieh C, Agostini H, Buschbeck C et al (2008) VEGF-A, VEGFR-1, VEGFR-2 and Tie2 levels in plasma of premature infants: relationship to retinopathy of prematurity. Br J Ophthalmol 92:689–693

    Article  PubMed  CAS  Google Scholar 

  48. Pieh C, Kruger M, Lagreze WA et al (2010) Plasma sE-selectin in premature infants: a possible surrogate marker of retinopathy of prematurity. Invest Ophthalmol Vis Sci 51:3709–3713

    Article  PubMed  Google Scholar 

  49. Pierce EA, Avery RL, Foley ED et al (1995) Vascular endothelial growth factor/vascular permeability factor expression in a mouse model of retinal neovascularization. Proc Natl Acad Sci U S A 92:905–909

    Article  PubMed  CAS  Google Scholar 

  50. Pierce EA, Foley ED, Smith LE (1996) Regulation of vascular endothelial growth factor by oxygen in a model of retinopathy of prematurity. Arch Ophthalmol 114:1219–1228

    PubMed  CAS  Google Scholar 

  51. Quiroz-Mercado H, Martinez-Castellanos MA, Hernandez-Rojas ML et al (2008) Antiangiogenic therapy with intravitreal bevacizumab for retinopathy of prematurity. Retina 28:S19–S25

    Article  PubMed  Google Scholar 

  52. Robinson GS, Pierce EA, Rook SL et al (1996) Oligodeoxynucleotides inhibit retinal neovascularization in a murine model of proliferative retinopathy. Proc Natl Acad Sci U S A 93:4851–4856

    Article  PubMed  CAS  Google Scholar 

  53. Rosenfeld PJ, Brown DM, Heier JS et al (2006) Ranibizumab for neovascular age-related macular degeneration. N Engl J Med 355:1419–1431

    Article  PubMed  CAS  Google Scholar 

  54. SanGiovanni JP, Chew EY (2005) The role of omega-3 long-chain polyunsaturated fatty acids in health and disease of the retina. Prog Retin Eye Res 24:87–138

    Article  PubMed  CAS  Google Scholar 

  55. Sapieha P, Stahl A, Chen J et al (2011) 5-lipoxygenase metabolite 4-HDHA is a mediator of the antiangiogenic effect of {omega}-3 polyunsaturated fatty acids. Sci Transl Med 3:69ra12

    PubMed  Google Scholar 

  56. Sato T, Kusaka S, Shimojo H, Fujikado T (2009) Vitreous levels of erythropoietin and vascular endothelial growth factor in eyes with retinopathy of prematurity. Ophthalmology 116:1599–1603

    Article  PubMed  Google Scholar 

  57. Sato T, Shima C, Kusaka S (2011) Vitreous levels of angiopoietin-1 and angiopoietin-2 in eyes with retinopathy of prematurity. Am J Ophthalmol 151:353–357, e35

    Article  PubMed  CAS  Google Scholar 

  58. Shah PK, Morris RJ, Narendran V, Kalpana N (2011) Visual acuity and electroretinography findings 3 (1/2) years after the first intravitreal injection of bevacizumab (Avastin) in aggressive posterior retinopathy of prematurity. Indian J Ophthalmol 59:73–74

    Article  PubMed  Google Scholar 

  59. Shyu KG, Manor O, Magner M et al (1998) Direct intramuscular injection of plasmid DNA encoding angiopoietin-1 but not angiopoietin-2 augments revascularization in the rabbit ischemic hindlimb. Circulation 98:2081–2087

    PubMed  CAS  Google Scholar 

  60. Silveira RC, Fortes Filho JB, Procianoy RS (2010) Assessment of the contribution of cytokine plasma levels to detect retinopathy of prematurity in very low birth weight infants. Invest Ophthalmol Vis Sci

  61. Singer D, Muhlfeld C (2007) Perinatal adaptation in mammals: the impact of metabolic rate. Comp Biochem Physiol A Mol Integr Physiol 148:780–784

    Article  PubMed  Google Scholar 

  62. Skouroliakou M, Konstantinou D, Koutri K et al (2010) A double-blind, randomized clinical trial of the effect of omega-3 fatty acids on the oxidative stress of preterm neonates fed through parenteral nutrition. Eur J Clin Nutr 64:940–947

    Article  PubMed  CAS  Google Scholar 

  63. Smith LE (2008) Through the eyes of a child: understanding retinopathy through ROP the Friedenwald lecture. Invest Ophthalmol Vis Sci 49:5177–5182

    Article  PubMed  Google Scholar 

  64. Smith LE, Shen W, Perruzzi C et al (1999) Regulation of vascular endothelial growth factor-dependent retinal neovascularization by insulin-like growth factor-1 receptor. Nat Med 5:1390–1395

    Article  PubMed  CAS  Google Scholar 

  65. Smith LE, Wesolowski E, McLellan A et al (1994) Oxygen-induced retinopathy in the mouse. Invest Ophthalmol Vis Sci 35:101–111

    PubMed  CAS  Google Scholar 

  66. Stahl A, Buchwald A, Martin G et al (2010) Vitreal levels of erythropoietin are increased in patients with retinal vein occlusion and correlate with vitreal VEGF and the extent of macular edema. Retina 30:1524–1529

    Article  PubMed  Google Scholar 

  67. Stahl A, Chen J, Sapieha P et al (2010) Postnatal weight gain modifies severity and functional outcome of oxygen-induced proliferative retinopathy. Am J Pathol 177:2715–2723

    Article  PubMed  Google Scholar 

  68. Stahl A, Connor KM, Sapieha P et al (2010) The mouse retina as an angiogenesis model. Invest Ophthalmol Vis Sci 51:2813–2826

    Article  PubMed  Google Scholar 

  69. Stahl A, Sapieha P, Connor KM et al (2010) Short communication: PPAR gamma mediates a direct antiangiogenic effect of omega 3-PUFAs in proliferative retinopathy. Circ Res 107:495–500

    Article  PubMed  CAS  Google Scholar 

  70. Travassos A, Teixeira S, Ferreira P et al (2007) Intravitreal bevacizumab in aggressive posterior retinopathy of prematurity. Ophthalmic Surg Lasers Imaging 38:233–237

    PubMed  Google Scholar 

  71. Vanhaesebrouck S, Daniels H, Moons L et al (2009) Oxygen-induced retinopathy in mice: amplification by neonatal IGF-I deficit and attenuation by IGF-I administration. Pediatr Res 65:307–310

    Article  PubMed  CAS  Google Scholar 

  72. Wu WC, Yeh PT, Chen SN et al (2011) Effects and complications of bevacizumab use in patients with retinopathy of prematurity: a multicenter study in taiwan. Ophthalmology 118:176–183

    Article  PubMed  Google Scholar 

  73. Young TL, Anthony DC, Pierce E et al (1997) Histopathology and vascular endothelial growth factor in untreated and diode laser-treated retinopathy of prematurity. J AAPOS 1:105–110

    Article  PubMed  CAS  Google Scholar 

  74. Zepeda-Romero LC, Liera-Garcia JA, Gutierrez-Padilla JA et al (2010) Paradoxical vascular-fibrotic reaction after intravitreal bevacizumab for retinopathy of prematurity. Eye (Lond) 24:931–933

    Google Scholar 

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  1. Universitätsaugenklinik Freiburg, Killianstr. 5, 79106, Freiburg, Deutschland

    A. Stahl, H. Agostini & W. Lagrèze

  2. Artemis Kliniken, Frankfurt am Main, Deutschland

    C. Jandeck

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  1. A. Stahl
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Stahl, A., Agostini, H., Jandeck, C. et al. Pharmakologische Therapie der Frühgeborenenretinopathie. Ophthalmologe 108, 777–787 (2011). https://doi.org/10.1007/s00347-011-2371-4

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