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DOI: 10.1055/s-0028-1109650
© Georg Thieme Verlag KG Stuttgart · New York
Neue therapeutische Ansätze in der Behandlung der Frühgeborenenretinopathie
New Therapeutic Approaches in the Treatment of Retinopathy of PrematurityPublikationsverlauf
Eingegangen: 20.4.2009
Angenommen: 22.6.2009
Publikationsdatum:
01. Oktober 2009 (online)

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.
Schlüsselwörter
RPM - Bevacizumab - Avastin - Anti-VEGF-Therapie
Key words
ROP - bevacizumab - avastin - antiangiogenic therapy
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
MissingFormLabel
- 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
MissingFormLabel
- 3
Brennan R, Gnanaraj L, Cottrell D G.
Retinopathy of prematurity in practice. I: screening for threshold disease.
Eye.
2003;
17
183-188
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 6
Capone Jr A, Trese M T.
Stage 5 retinopathy of prematurity: then and now.
Retina.
2006;
26
721-723
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 9
Coats D, Saunders R.
The dilemma of exercising clinical judgement in the treatment of retinopathy of prematurity.
Arch Ophthalmol.
2005;
123
408-409
MissingFormLabel
- 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
MissingFormLabel
- 11
Cryotherapy for Retinopathy of Prematurity Cooperative Group .
Multicenter trial of cryotherapy for retinopathy of prematurity. Preliminary results.
Arch Ophthalmol.
1988;
106
471-479
MissingFormLabel
- 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
MissingFormLabel
- 13
Cunningham S, Fleck B W, Elton R A. et al .
Transcutaneous oxygen levels in retinopathy of prematurity.
Lancet.
1995;
346
1464-1465
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 17
Fleck B W, McIntosh N.
Pathogenesis of retinopathy of prematurity and possible preventive strategies.
Early Human Development.
2008;
84
83-88
MissingFormLabel
- 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
MissingFormLabel
- 19
Greven C, Tasman W.
Scleral buckling in stages 4B and 5 retinopathy of prematurity.
Ophthalmology.
1990;
97
817-820
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 26
Katz X, Kychenthal A, Dorta P.
Zone I retinopathy of prematurity.
J AAPOS.
2000;
4
373-376
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 31
Lad E, Nguyen T, Morton J. et al .
Retinopathy of prematurity in the United States.
Br J Ophthalmol.
2008;
92
320-325
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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)
MissingFormLabel
- 41
Mintz-Hittner H, Best L.
Antivascular endothelial growth factor for retinopathy of prematurity.
Retina.
2009;
21
182-187
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 51
The Committee for the Classification of Retinopathy of Prematurity .
An international classification of retinopathy of prematurity.
Arch Ophthalmol.
1984;
102
1130-1134
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 57
The Laser ROP Study Group .
Laser therapy for retinopathy of prematurity.
Arch Ophthalmol.
1994;
112
154-156
MissingFormLabel
- 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
MissingFormLabel
- 59
Trese M.
BLOCK ROP: ClinicalTrials.gov Identifier: NCT00702819;2009.
, http://www. Clinicaltrials.gov (Stand: Phase II recruiting)
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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]
MissingFormLabel
- 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
MissingFormLabel
Dr. Claudia Jandeck
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