Neue therapeutische Ansätze in der Behandlung der Frühgeborenenretinopathie

 

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Zusammenfassung

Dieser Übersichtsartikel beschreibt die neuesten Entwicklungen im Bereich der Therapie der Frühgeborenenretinopathie (RPM). Kenntnisse über dieses meist bei extrem unreifen Säuglingen auftretende Krankheitsbild sind weiterhin wichtig, da trotz verbesserter neonatologischer Intensivmedizin die RPM weiterhin auftritt und durch eine Therapie zum optimalen Zeitpunkt das Erblindungsrisiko deutlich reduziert werden kann. Die aktuelle deutsche Richtlinie zur Screening-Untersuchung und Therapie wird beschrieben. Die verschiedenen aktuellen Therapiemöglichkeiten und Behandlungsergebnisse werden diskutiert. Es erfolgt eine Übersicht über die derzeitigen Studien und Fallberichte der zukünftigen möglichen, vielversprechenden Behandlungsmethode mit dem Anti-VEGF-Medikament Bevacizumab.

Abstract

This review highlights recent advances in clinical research on the therapy for retinopathy of prematurity (ROP). This disease is still important, because improvements in neonatal intensive care during the last years have increased the survival of the most immature newborns, but have not diminished the ROP frequency. Laser treatment at the optimal time for advanced ROP mostly prevents blindness. This paper describes the classification, current German screening criteria and the modern concept of ROP pathophysiology. The therapeutic treatment strategies and the treatment results, as well the possible promising future therapy with anti-VEGF (bevacizumab) is discussed.

Literatur

• 1 Arevalo J F, Maia M, Flynn H W. et al . Tractional retinal detachment following intravitreal bevacizumab (Avastin) in patients with severe proliferative diabetic retinopathy.  Br J Ophthalmol. 2008;  92 213-216
  Google Scholar
• 2 Axer-Siegel Jr R, Maharshak I, Snir M. et al . Diode laser treatment of retinopathy of prematurity: anatomical and refractive outcomes.  Retina. 2008;  28 839-846
  Google Scholar
• 3 Brennan R, Gnanaraj L, Cottrell D G. Retinopathy of prematurity in practice. I: screening for threshold disease.  Eye. 2003;  17 183-188
  Google Scholar
• 4 Capone Jr A, Diaz-Rohena R, Sternberg Jr P. et al . Diode-laser photocoagulation for zone 1 threshold retinopathy of prematurity.  Am J Ophthalmol. 1993;  116 444-450
  Google Scholar
• 5 Capone Jr A, Trese M T. Lens-sparing vitreous surgery for tractional stage 4A retinopathy of prematurity retinal detachments.  Ophthalmology. 2001;  108 2068-2070
  Google Scholar
• 6 Capone Jr A, Trese M T. Stage 5 retinopathy of prematurity: then and now.  Retina. 2006;  26 721-723
  Google Scholar
• 7 Chiang M F, Jiang L, Gelman R. et al . Interexpert agreement of plus disease diagnosis in retinopathy of prematurity.  Arch Ophthalmol. 2007;  125 875-880
  Google Scholar
• 8 Chung E J, Kim J H, Ahn H S. et al . Combination of laser photocoagulation and intravitreal bevacizumab (Avastin) for aggressive zone I retinopathy of prematurity.  Graefes Arch Clin Exp Ophthalmol. 2007;  245 1727-1730
  Google Scholar
• 9 Coats D, Saunders R. The dilemma of exercising clinical judgement in the treatment of retinopathy of prematurity.  Arch Ophthalmol. 2005;  123 408-409
  Google Scholar
• 10 Connolly B P, Ng E Y, McNamara J A. et al . A comparison of laser photocoagulation with cryotherapy for threshold retinopathy of prematurity at 10 years: part 2. Refractive outcome.  Ophthalmology. 2002;  109 936-941
  Google Scholar
• 11 Cryotherapy for Retinopathy of Prematurity Cooperative Group . Multicenter trial of cryotherapy for retinopathy of prematurity. Preliminary results.  Arch Ophthalmol. 1988;  106 471-479
  Google Scholar
• 12 Cryotherapy for Retinopathy of Prematurity Cooperative Group . Multicenter trial of cryotherapy for retinopathy of prematurity. Final results. 15-Year Outcomes Following Threshold Retinopathy.  Arch Ophthalmol. 2005;  123 311-318
  Google Scholar
• 13 Cunningham S, Fleck B W, Elton R A. et al . Transcutaneous oxygen levels in retinopathy of prematurity.  Lancet. 1995;  346 1464-1465
  Google Scholar
• 14 Cusick M, Charles M K, Agrón E. et al . Anatomical and visual results of vitreoretinal surgery for stage 5 retinopathy of prematurity.  Retina. 2006;  26 729-735
  Google Scholar
• 15 Davitt B V, Dobson V, Quinn G E. et al . Astigmatism in the Early Treatment for Retinopathy of Prematurity Study: findings to 3 years of age.  Ophthalmology. 2009;  116 332-339
  Google Scholar
• 16 Field D, Dorling J, Manktelow B. et al . Survival of extreme premature babies in a geographically defined population: prospective cohort study of 1994 – 9 compared with 2000 – 5.  BMJ. 2008;  336 1221-1223
  Google Scholar
• 17 Fleck B W, McIntosh N. Pathogenesis of retinopathy of prematurity and possible preventive strategies.  Early Human Development. 2008;  84 83-88
  Google Scholar
• 18 Giannantonio C, Papacci P, Molle F. et al . An epidemiological analysis of retinopathy or prematurity over ten years.  J Pediatr Ophthalmol Strabismus. 2008;  45 162-167
  Google Scholar
• 19 Greven C, Tasman W. Scleral buckling in stages 4B and 5 retinopathy of prematurity.  Ophthalmology. 1990;  97 817-820
  Google Scholar
• 20 Holmstrom G, el Azazi M, Kugelberg U. Ophthalmological follow up of preterm infants: a population based, prospective study of visual acuity and strabismus.  Br J Ophthalmol. 1999;  83 143-50
  Google Scholar
• 21 Honda S, Hirabayashi H, Tsukahara Y. et al . Acute contraction of the proliferative membrane after an intravitreal injection of bevacizumab for advanced retinopathy of prematurity.  Graefes Arch Clin Exp Ophthalmol. 2008;  246 1061-1063
  Google Scholar
• 22 Hughes S, Yang H, Chan-Ling T. Vascularization of the human fetal retina: roles of vasculogenesis and angiogenesis.  Invest Ophthalmol Vis Sci. 2000;  41 1217-1228
  Google Scholar
• 23 Jandeck C, Kellner U, Heimann H. et al . Koagulationstherapie der Frühgeborenenretinopathie: Vergleich der anatomischen und funktionellen Ergebnisse nach Laser- oder Kryokoagulation.  Ophthalmologe. 2005;  102 33-38
  Google Scholar
• 24 Jandeck C, Kellner U, Heimann H. et al . Frühgeborenenretinopathie-Screening: Ergebnisse eines Zentrums zwischen 1991 und 2002.  Klin Monatsbl Augenheilkd. 2005;  222 577-585
  Google Scholar
• 25 Jandeck C, Kellner U, Lorenz B. et al . Arbeitsgruppe der Retinologischen Gesellschaft zur Erstellung der Leitlinie zur augenärztlichen Screening-Untersuchung von Frühgeborenen. Augenärztliche Screening-Untersuchung von Frühgeborenen.  Klin Mbl Augenheilkd. 2008;  225 123-130
  Google Scholar
• 26 Katz X, Kychenthal A, Dorta P. Zone I retinopathy of prematurity.  J AAPOS. 2000;  4 373-376
  Google Scholar
• 27 Kim M J, Kim S -J, Yu Y S. The risk for retinale detachment associated with hemorrhages pre and postlaser treatment in retinopathy of prematurity.  Retina. 2008;  28 1451-1457
  Google Scholar
• 28 Kong L, Mintz-Hittner H, Penland R. et al . Intravitreal bevacizumab as anti-vascular endothelial growth factor therapy for retinopathy of prematurity: a morphologic study.  Arch Ophthalmol. 2008;  126 1161-1163
  Google Scholar
• 29 Koreen S, Lopez R, Jokl D H. et al . Variation in appearance of severe zone 1 retinopathy of prematurity during wide-angle contact photography.  Arch Ophthalmol. 2008;  126 736-737
  Google Scholar
• 30 Kusaka S, Shima C, Wada K. et al . Efficacy of intravitreal injection of bevacizumab for severe retinopathy of prematurity: a pilot study.  Br J Ophthalmol. 2008;  92 1450-1455
  Google Scholar
• 31 Lad E, Nguyen T, Morton J. et al . Retinopathy of prematurity in the United States.  Br J Ophthalmol. 2008;  92 320-325
  Google Scholar
• 32 Lalwani G, Berrocal A, Murray T G. et al . Off-Label use of intravitreal bevacizumab (Avastin) for salvage treatment in progressive threshold retinopathy of prematurity.  Retina. 2008;  28 513-518
  Google Scholar
• 33 Lakhanpal R R, Sun R L, Albini T A. et al . Anatomic success rate after 3-port lens-sparing vitrectomy in stage 4A or 4B retinopathy of prematurity.  Ophthalmology. 2005;  112 1569-1573
  Google Scholar
• 34 Larsson E, Carle-Petrelius B, Cernerud G. et al . Incidence of ROP in two consecutive Swedish population based studies.  Br J Ophthalmol. 2002;  86 1122-1126
  Google Scholar
• 35 Löfqvist C, Andersson E, Sigurdsson J. et al . Longitudinal postnatal weight and Insulin-like Growth Factor I measurements in prediction Retinopathy of Prematurity.  Arch Ophthalmol. 2006;  124 1711-1718
  Google Scholar
• 36 McColm J R, Cunningham S, Wade J. et al . Hypoxic oxygen fluctuations produce less severe retinopathy than hyperoxic fluctuations in a rat model of retinopathy of prematurity.  Pediatr Res. 2004;  55 107-113
  Google Scholar
• 37 McLoone E M, O’Keefe M, McLoone S F. et al . Long-term refractive and biometric outcomes following diode laser therapy for retinopathy of prematurity.  J AAPOS. 2006;  10 454-459
  Google Scholar
• 38 Mintz-Hittner H A, O’Malley R E, Kretzer F L. Long-term form identification vision after early, closed, lensectomy-vitrectomy for stage 5 retinopathy of prematurity.  Ophthalmology. 1997;  104 454-459
  Google Scholar
• 39 Mintz-Hittner H, Kuffel R. Intravitreal injection of bevacizumab (Avastin) for treatment of stage 3 retinopathy of prematurity in zone I or posterior zone II.  Retina. 2008;  28 831-838
  Google Scholar
• 40 Mintz-Hittner H. BEAT-ROP Studie (bevacizumab eleminates the angiogenic threat of ROP: Clinical trials.gov Identifier: NCT00622726).  , http://www. Clinicaltrials.gov 2009 (Stand: Phase II recruiting)
  Google Scholar
• 41 Mintz-Hittner H, Best L. Antivascular endothelial growth factor for retinopathy of prematurity.  Retina. 2009;  21 182-187
  Google Scholar
• 42 Moshfeghi A A, Banach M J, Salam G A. et al . Lens-sparing vitrectomy for progressive tractional retinal detachments associated with stage 4A retinopathy of prematurity.  Arch Ophthalmol. 2004;  122 1816-1818
  Google Scholar
• 43 Ng E Y, Connolly B P, McNamara J A. 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;  109 928-934, discussion 35
  Google Scholar
• 44 Paysse E A, Lindsey J L, Coats D K. et al . Therapeutic outcomes of cryotherapy versus transpupillary diode laser photocoagulation for threshold retinopathy of prematurity.  J AAPOS. 1999;  3 234-240
  Google Scholar
• 45 Quinn G E, Dobson V, Davitt B V. et al . Progression of myopia and high myopia in the early treatment for retinopathy of prematurity study: findings to 3 years of age.  Ophthalmology. 2008;  115 1058-1064
  Google Scholar
• 46 Quiroz-Mercado H, Martinez-Castellanos M A, Hernandez-Rojas M L. et al . Antiangiogenic therapy with intravitreal bevacizumab for retinopathy of prematurity.  Retina. 2008;  28 (Suppl 3) S19-25, Erratum in Retina 2009;29:127
  Google Scholar
• 47 Reynolds J D, Dobson V, Quinn G E. CRYO-ROP and LIGHT-ROP Cooperative Study Groups . Evidence-based screening criteria for retinopathy of prematurity: natural history data from the CRYO-ROP and LIGHT-ROP studies.  Arch Ophthalmol. 2002;  120 1470-1476
  Google Scholar
• 48 Shah P K, Narendran V, Tawansy K A. et al . Intravitreal bevacizumab (Avastin) for post laser anterior segment ischemia in aggressive posterior retinopathy of prematurity.  Indian J Ophthalmol. 2007;  55 75-76
  Google Scholar
• 49 Smith L E. Through the eyes of a child: understanding retinopathy through ROP the Friedenwald lecture.  Invest Ophthalmol Vis Sci. 2008;  49 5177-5182
  Google Scholar
• 50 Sonmez K, Drenser K, Capone A. et al . Vitreous levels of stromal cell-derived factor 1 and vascular endothelial growth factor in patients with retinopathy of prematurity.  Ophthalmology. 2008;  115 1065-1070
  Google Scholar
• 51 The Committee for the Classification of Retinopathy of Prematurity . An international classification of retinopathy of prematurity.  Arch Ophthalmol. 1984;  102 1130-1134
  Google Scholar
• 52 The Early Treatment for Retinopathy of Prematurity Cooperative Group . Revised indications for treatment of retinopathy of prematurity: results of the early treatment for retinopathy of prematurity randomized trial.  Arch Ophthalmol. 2003;  121 1684-1696
  Google Scholar
• 53 The Early Treatment for Retinopathy of Prematurity Cooperative Group . The Early Treatment for Retinopathy Of Prematurity Study: structural findings at age 2 years.  British Journal of Ophthalmology. 2006;  90 1378-1382
  Google Scholar
• 54 The International Committee for the Classification of the Late Stages of Retinopathy of Prematurity . An international classification of retinopathy of prematurity. II. The classification of retinal detachment.  Arch Ophthalmol. 1987;  105 906-912
  Google Scholar
• 55 The International Committee for the Classification of the Late Stages of Retinopathy of Prematurity . An international classification of retinopathy of prematurity. II. The classification of retinal detachment.  Pediatrics. 1988;  82 37-43
  Google Scholar
• 56 The International Committee for the Classification of Retinopathy of Prematurity . An international classification of retinopathy of prematurity revisited.  Arch Ophthalmol. 2005;  123 991-999
  Google Scholar
• 57 The Laser ROP Study Group . Laser therapy for retinopathy of prematurity.  Arch Ophthalmol. 1994;  112 154-156
  Google Scholar
• 58 Travassos A, Teixeira S, Ferreira P. et al . Intravitreal bevacizumab in aggressive posterior retinopathy of prematurity.  Ophthalmic Surg Laser Imaging. 2007;  38 233-237
  Google Scholar
• 59 Trese M. BLOCK ROP: ClinicalTrials.gov Identifier: NCT00702819;2009.  , http://www. Clinicaltrials.gov (Stand: Phase II recruiting)
  Google Scholar
• 60 Vander J F, Handa J, McNamara J A. et al . Early treatment of posterior retinopathy of prematurity: a controlled trial.  Ophthalmology. 1997;  104 1731-1735, discussion 1735 – 1736
  Google Scholar
• 61 Wallace D K, Quinn G E, Freedman S F. et al . Agreement among pediatric ophthalmologists in diagnosing plus and pre-plus disease in retinopathy of prematurity.  J AAPOS. 2008;  12 352-356
  Google Scholar
• 62 White J E, Repka M X. Randomized comparison of diode laser photocoagulation versus cryotherapy for threshold retinopathy of prematurity: 3-year outcome.  J Pediatr Ophthalmol Strabismus. 1997;  34 83-87
  Google Scholar
• 63 Yang C S, Wang A G, Sung C S. et al . Long-term visual outcomes of laser-treated threshold retinopathy of prematurity: a study of refractive status at 7 years.  Eye. 2009;  [Epub ahead of print]
  Google Scholar
• 64 Zhang S, Leske D A, Uhl J R. et al . Retinopathy associated with enterococcus enteropathy in the neonatal rat.  Invest Ophthalmol Vis Sci. 1999;  40 1305-1309
  Google Scholar

Dr. Claudia Jandeck

Augenheilkunde, Artemis Zentren Frankfurt

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60596 Frankfurt

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