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Monitoring von AMD-Patienten unter Anti-VEGF-Therapie

Praktische Hinweise zu funktionellen und anatomischen Untersuchungsparametern aus Zulassungsstudien, Fachinformationen und Fallserien

Monitoring of AMD patients on Anti-Vascular Endothelial Growth Factor (VEGF) Treatment

Practial notes on functional and anatomical examination parameters from Drug approval studies, specialist information and case series

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Zusammenfassung

Die altersabhängige Makuladegeneration (AMD) gehört zu den häufigsten Ursachen einer Erblindung in westlichen Industrienationen. Die meisten AMD-Patienten leiden an der trockenen Frühform der AMD, die feuchte AMD mit ihrer choroidalen Neovaskularisation (CNV) stellt die Haupterblindungsursache aller AMD-Patienten dar. Neue Perspektiven in der Therapie der AMD wurden mit pharmakologischen Verfahren entwickelt, die zur Behandlung aller Subtypen der exsudativen AMD zur Verfügung stehen. In der Pathophysiologie der feuchten AMD ist eine Vielzahl von inhibierenden und induzierenden Wachstumsfaktoren wie der vaskuläre endotheliale Wachstumsfaktor (VEGF) besonders wichtig. Das sezernierte VEGF scheint durch seine angiogene und permeabilitätssteigernde Wirkung eine entscheidende Rolle bei der Pathogenese von CNV und Makulaödemen zu haben. Diese Erkenntnisse führten zu dem heute verwendeten therapeutischen Ansatz, eine kompetitive VEGF-Blockade durch intravitreal applizierte Anti-VEGF-Medikamente zu erreichen. Durch die Anti-VEGF-Medikamente kommt es zur raschen Abnahme der retinalen Dicke. Die optische Kohärenztomographie (OCT) ist ein wertvolles Instrument in der Verlaufskontrolle, darf aber nur als Entscheidungshilfe gelten. Die klinische Nachkontrolle der Patienten und die weitere Therapieempfehlung müssen sich immer am klinischen Gesamtbild orientieren. Als entscheidendes Kriterium für eine erneute Behandlung gilt der Visus.

Abstract

Age-related macular degeneration (AMD) is one of the most common causes of blindness in western industrialised nations. Most AMD patients suffer from the dry early form of AMD; however, wet AMD with choroidal neovascularization (CNV) is the main cause of blindness in all AMD patients. New prospects have been developed in AMD treatment using pharmacological methods available for treating all subtypes of exudative AMD. A number of inhibiting and inducing growth factors, such as vascular endothelial growth factor (VEGF), are particularly important in the pathophysiology of wet AMD. The secreted VEGF appears to play a crucial role in the pathogenesis of CNV and macular edemas as a result of its angiogenetic and permeability-enhancing effect. This recognition led to the treatment approach now used, i.e., competitive VEGF blocking through intravitreal adminsitration of anti-VEGF drugs. The anti-VEGF durgs lead to a rapid decrease in retinal thickness. Optical coherence tomography (OCT) is a valuable monitoring tool, but may only be used to assist in decision-making. Clinical follow-up of patients and further treatment recommendations must always be guided by the overall clinical picture. Visual acuity is regarded as the decisive criterion for repeat treatment.

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Notes

  1. Persönliche Kommunikation Dr. Tim U. Krohne, Univ. Bonn.

Literatur

  1. Aisenbrey S, Ziemssen F, Volker M et al. (2007) Intravitreal bevacizumab (Avastin) for occult choroidal neovascularization in age-related macular degeneration. Graefes Arch Clin Exp Ophthalmol 245: 941–948

    Article  PubMed  CAS  Google Scholar 

  2. Ahlers C, Geitzenauer W, Simader C et al. (2007) Hochauflösende optische Kohärenztomographie bei altersbedingter Makuladegeneration. Ophthalmologe (online Sep 27)

  3. Avery RL, Pieramici DJ, Rabena MD et al. (2006) Intravitreal bevacizumab (Avastin) for neovascular age-related macular degeneration. Ophthalmology 113: 363–372

    Article  PubMed  Google Scholar 

  4. Bach M (1995) Der Freiburger Visustest. Automatisierte Sehschärfenbestimmung. Ophthalmologe 92: 174–178

    PubMed  CAS  Google Scholar 

  5. Bakri SJ, Snyder MR, Reid JM et al. (2007) Pharmacokinetics of intravitreal bevacizumab (Avastin). Ophthalmology 114: 855–859

    Article  PubMed  Google Scholar 

  6. Beck RW, Moke PS, Turpin AH et al. (2003) A computerized method of visual acuity testing: adaptation of the early treatment of diabetic retinopathy study testing protocol. Am J Ophthalmol 135: 194–205

    Article  PubMed  Google Scholar 

  7. Beer PM, Wong SJ, Hammad AM et al. (2006) Vitreous levels of unbound bevacizumab and unbound vascular endothelial growth factor in two patients. Retina 26: 871–876

    Article  PubMed  Google Scholar 

  8. 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 

  9. Boyer DS, Antoszyk AN, Awh CC et al. (2007) Subgroup analysis of the MARINA study of ranibizumab in neovascular age-related macular degeneration. Ophthalmology 114: 246–252

    Article  PubMed  Google Scholar 

  10. Chan CK, Meyer CH, Gross JG et al. (2007) Retinal pigment epithelial tears after intravitreal bevacizumab injection for neovascular age-related macular degeneration. Retina 27: 541–551

    Article  PubMed  Google Scholar 

  11. Cheung CM, Peh KK, Yang Y (2007) Estimating the potential impact of using intravitreal angiostatic agents for wet macular degeneration on service capacity in a large retinal referral centre. Eye 21: 1121–1122

    Article  PubMed  CAS  Google Scholar 

  12. Cotter SA, Chu RH, Chandler DL et al. (2003) Reliability of the electronic early treatment diabetic retinopathy study testing protocol in children 7 to <13 years old. Am J Ophthalmol 136: 655–661

    Article  PubMed  Google Scholar 

  13. Degenring RF, Jonas JB (2004) Serum levels of triamcinolone acetonide after intravitreal injection. Am J Ophthalmol 137: 1142–1143

    Article  PubMed  CAS  Google Scholar 

  14. Deutsche Ophthalmologische Gesellschaft, Retinologische Gesellschaft, Berufsverband der Augenärzte (2007) Stellungnahme der Deutsche Ophthalmologische Gesellschaft, der Retinologische Gesellschaft, des Berufsverbandes der Augenärzte Deutschlands zu aktuellen therapeutischen Möglichkeiten bei der neovaskulären altersabhängigen Makuladegeneration. Klin Monatsbl Augenheilkd 224: 559–566

    Article  Google Scholar 

  15. Emerson GG, Flaxel CJ, Lauer AK et al. (2007) Optical coherence tomography findings during pegaptanib therapy for neovascular age-related macular degeneration. Retina 27: 724–729

    Article  PubMed  Google Scholar 

  16. Eter N, Bindewald A, Roth F, Holz FG (2004) OCT bei altersabhängiger Makuladegneration. Ophthalmologe 101: 794–803

    PubMed  CAS  Google Scholar 

  17. Eter N, Krohne TU, Holz FG (2006) New pharmacologic approaches to therapy for age-related macular degeneration. BioDrugs 20: 167–179

    Article  PubMed  CAS  Google Scholar 

  18. Falkenstein IA, Cheng L, Morrison VL et al. (2007) Standardized visual acuity results associated with primary versus secondary bevacizumab (avastin) treatment for choroidal neovascularization in age-related macular degeneration. Retina 27: 701–706

    Article  PubMed  Google Scholar 

  19. Fielder AR, Gilbert C, Ells A, Quinn GE (2006) Internet-based eye care. Lancet 28(367): 300–301

    Article  Google Scholar 

  20. Fink W, Sadun AA (2004) Three-dimensional computer-automated threshold Amsler grid test. J Biomed Opt 9: 149–153

    Article  PubMed  Google Scholar 

  21. Fung AE, Lalwani GA, Rosenfeld PJ et al. (2007) An optical coherence tomography-guided, variable dosing regimen with intravitreal ranibizumab (Lucentis) for neovascular age-related macular degeneration. Am J Ophthalmol 143: 566–583

    Article  PubMed  CAS  Google Scholar 

  22. Gaudreault J, Fei D, Rusit J et al. (2005) Preclinical pharmacokinetics of Ranibizumab (rhuFabV2) after a single intravitreal administration. Invest Ophthalmol Vis Sci 46: 726–733

    Article  PubMed  Google Scholar 

  23. Gragoudas ES, Adamis AP, Cunningham ET Jr et al. (2004) Pegaptanib for neovascular age-related macular degeneration. N Engl J Med 351: 2805–2816

    Article  PubMed  CAS  Google Scholar 

  24. Heiduschka P, Fietz H, Hofmeister S et al. (2007) Penetration of bevacizumab through the retina after intravitreal injection in the monkey. Invest Ophthalmol Vis Sci 48: 2814–2823

    Article  PubMed  Google Scholar 

  25. Holz F, Pauleikhoff D, Klein R et al. (2004) Pathogenesis of lesions in late age-related macular disease. Am J Ophthalmol 137: 504–510

    Article  PubMed  Google Scholar 

  26. Huber C (1985) Sehprogramm für Augenärzte auf Apple II, IIe and IIc Computer. Klin Monatsbl Augenheilkd 186: 227–230

    Article  PubMed  CAS  Google Scholar 

  27. Hughes MS, Sang DN (2006) Safety and efficacy of intravitreal bevacizumab followed by pegaptanib maintenance as a treatment regimen for age-related macular degeneration. Ophthalmic Surg Lasers Imaging 37: 446–454

    PubMed  Google Scholar 

  28. Jaissle GB, Ziemssen F, Petermeier K et al. (2006) Bevacizumab zur Therapie des sekundären Makulaödems nach venösen Gefäßverschlüssen. Ophthalmologe 103: 471–475

    Article  PubMed  CAS  Google Scholar 

  29. Jaissle GB, Szurman P, Bartz-Schmidt KU et al. (2005) Recommendation for the implementation of intravitreal injections – statement of the German Retina Society, the German Society of Ophthalmology (DOG) and the German Professional Association of Ophthalmologists (visual acuity). Klin Monatsbl Augenheilkd 222: 390–395

    Article  PubMed  CAS  Google Scholar 

  30. Joeres S, Kaplowitz K, Brubaker JW et al. (2007) Quantitative comparison of optical coherence tomography after pegaptanib or bevacizumab in neovascular age-related macular degeneration. Ophthalmology Jul 11 (online)

  31. Krieglstein TR, Kampik A, Ulbig M (2006) Intravitreal triamcinolone and laser photocoagulation for retinal angiomatous proliferation. Br J Ophthalmol 90: 1357–1360

    Article  PubMed  CAS  Google Scholar 

  32. Kroll P, Meyer CH (2006) Which treatment is best for which AMD patient? Br J Ophthalmol 90: 128–130

    Article  PubMed  CAS  Google Scholar 

  33. Kuchenbecker J, Lindner H, Behrens-Baumann W (2002) Möglichkeiten und Grenzen der Testung visueller Funktionen mittels Internet. Ophthalmologe 99: 866–871

    Article  PubMed  CAS  Google Scholar 

  34. Kuerzinger GR, Lang GK, Lang GE (2006) Retinale angiomatöse Proliferation bei altersbezogener Makuladegeneration. Klin Monatsbl Augenheilkd 223: 691–695

    Article  PubMed  CAS  Google Scholar 

  35. Ladewig MS, Ziemssen F, Jaissle G et al. (2006) Intravitreales Bevacizumab bei der neovaskulären altersabhängigen Makuladegeneration. Ophthalmologe 103: 463–470

    Article  PubMed  CAS  Google Scholar 

  36. Ladewig MS, Karl SE, Hamelmann V et al. (2008) Combined intravitreal bevacizumab and photodynamic therapy for neovascular age-related macular degeneration. Graefes Arch Clin Exp Ophthalmol 246: 17–25

    Article  PubMed  CAS  Google Scholar 

  37. Lai JC, Lapolice DJ, Stinnett SS et al. (2002) Visual outcomes following macular translocation with 360-degree peripheral retinectomy. Arch Ophthalmol 120: 1317–1324

    PubMed  Google Scholar 

  38. Laidlaw D A H, Abbott A, Rosser DA (2003) Development of a clinically feasible logMAR alternative to the Snellen chart: performance of the ‚‚compact reduced logMAR’‘ visual acuity chart in amblyopic children. Br J Ophthalmol 87: 1232–1234

    Article  PubMed  CAS  Google Scholar 

  39. Lenne RC, Vingrys AJ, Smith G (1995) Using computers to test visual acuity. J Am Optom Assoc 66: 766–774

    PubMed  CAS  Google Scholar 

  40. Leinonen J, Laakkonen E, Laatikainen L (2005) Random measurement error in visual acuity measurement in clinical settings. Acta Ophthalmol Scand 83: 328–332

    Article  PubMed  Google Scholar 

  41. Luke M, Januschowski K, Warga M et al. (2007) The retinal tolerance to bevacizumab in co-application with a recombinant tissue plasminogen activator. Br J Ophthalmol 91: 1077–1082

    Article  PubMed  Google Scholar 

  42. Mennel S, Hausmann N, Meyer CH et al. (2005) Transient visual decrease after photodynamic therapy. Ophthalmologe 102: 58–63

    Article  PubMed  CAS  Google Scholar 

  43. Mennel S, Meyer CH (2005) Transient visual disturbance after photodynamic therapy. Am J Ophthalmol 139: 748–749

    Article  PubMed  Google Scholar 

  44. Mennel S, Peter S, Meyer CH, Thumann G (2006) Effect of photodynamic therapy on the function of the outer blood-retinal barrier in an in-vitro model. Graefes Arch Clin Exp Ophthalmol 244: 1015–1021

    Article  PubMed  CAS  Google Scholar 

  45. Mennel S, Barbazetto I, Meyer CH et al. (2007) Ocular photodynamic therapy – standard applications and new indications (part 1). Review of the literature and personal experience. Ophthalmologica 221: 216–226

    Article  PubMed  Google Scholar 

  46. Meyer CH, Mennel S, Schmidt JC (2005) Intravitreal triamcinolone acetonide may increase the intraocular pressure even in vitrectomized eyes after more than 3 months. Am J Ophthalmol 140: 766–777

    Article  PubMed  Google Scholar 

  47. Meyer CH (2007) Current treatment approaches in diabetic macular edema. Ophthalmologica 221: 118–131

    Article  PubMed  Google Scholar 

  48. Meyer CH, Lapolice DJ, Fekrat S (2005) Functional changes after photodynamic therapy with verteporfin. Am J Ophthalmol 139: 214–215

    Article  PubMed  Google Scholar 

  49. Meyer CH, Lapolice DJ (2008) Computer-based visual evaluation as a screening tool after intravitreal injections of vascular endothelial growth factor (VEGF)-inhibitors. Ophthalmologica (in press)

  50. Meyer CH, Scholl HP, Eter N et al. (2008) Combined treatment of acute subretinal hemorrhages with intravitreal recombined tissue plasminogen activator, expansile gas and bevacizumab – a retrospective pilot study. Acta Scandinavica Ophthalmol (online Jan 24)

  51. Michels S, Rosenfeld PJ (2005) Therapie des neovaskulären altersbedingten Makuladegeneration mit Ranibizumab/Lucentis. Klin Monatsbl Augenheilkd 222: 480–484

    Article  PubMed  CAS  Google Scholar 

  52. Mordenti J, Cuthbertson RA, Ferrara N et al. (1999) Comparisons of the intraocular tissue distribution, pharmacokinetics, and safety of 125I-labeled full-length and Fab antibodies in rhesus monkeys following intravitreal administration. Toxicol Pathol 27: 536–544

    Article  PubMed  CAS  Google Scholar 

  53. Niemeyer M, Hefner L, Jochmann C, Wiedemann P (2007) Intravitreales Bevacizumab bei rezidivierender idiopatischer choroidaler Neovaskularisation. Ophthalmologe 104: 158–160

    Article  PubMed  CAS  Google Scholar 

  54. Peters S, Heiduschka P, Julien S et al. (2007) Ultrastructural findings in the primate eye after intravitreal injection of bevacizumab. Am J Ophthalmol 143: 995–1002

    Article  PubMed  CAS  Google Scholar 

  55. Peters S, Julien S, Heiduschka P et al. (2007) Antipermeability and antiproliferative effects of standard and frozen bevacizumab on choroidal endothelial cells. Br J Ophthalmol 91: 827–831

    Article  PubMed  Google Scholar 

  56. Rosenfeld PJ, Moshfeghi AA, Puliafito CA (2005) Optical coherence tomography findings after an intravitreal injection of bevacizumab (avastin) for neovascular age-related macular degeneration. Ophthalmic Surg Lasers Imaging 36: 331–335

    PubMed  Google Scholar 

  57. Rosenfeld PJ, Brown DM, Heier J et al. (2006) Ranibizumab for neovascular age-related macular degeneration: results of the MARINA study. New Engl J Med 355: 1419–1431

    Article  PubMed  CAS  Google Scholar 

  58. Ruamviboonsuk P, Tiensuwan M, Kunawut C, Masayaanon P (2003) Repeatability of an automated Landolt C test, compared with the early treatment of diabetic retinopathy study (ETDRS) chart testing. Am J Ophthalmol 136: 662–669

    Article  PubMed  Google Scholar 

  59. Schmidt JC, Meyer CH, Hörle S (2004) Massive subretinale Blutungen. Eine Herausforderung an den Glaskörperchirurgen. Ophthalmologe 101: 584–588

    PubMed  CAS  Google Scholar 

  60. Schulze-Bonsel K, Feltgen N, Burau H et al. (2006) Visual acuities „hand motion“ and „counting fingers“ can be quantified with the freiburg visual acuity test. Invest Ophthalmol Vis Sci 47: 1236–1240

    Article  PubMed  Google Scholar 

  61. Spaide RF, Laud K, Fine HF et al. (2006) Intravitreal bevacizumab treatment of choroidal neovascularization secondary to age-related macular degeneration. Retina 26: 383–390

    Article  PubMed  Google Scholar 

  62. Spaide R (2007) Ranibizumab according to need: a treatment for age-related macular degeneration. Am J Ophthalmol 143: 679–680

    Article  PubMed  Google Scholar 

  63. Strauss RW, Scholz F, Ulbig MW et al. (2007) Artefakte bei der Bildgebung der Netzhaut mittels optischer Kohärenz Tomographie (OCT). Monatsbl Augenheilkd 224: 47–51

    Article  CAS  Google Scholar 

  64. Takeda AL, Colquitt JL, Clegg AJ, Jones J (2007) Pegaptanib and ranibizumab for neovascular age-related macular degeneration: a systematic review. Br J Ophthalmol 91: 1177–1182

    Article  PubMed  CAS  Google Scholar 

  65. Ting TD, Oh M, Cox TA et al. (2002) Decreased visual acuity associated with cystoid macular edema in neovascular age-related macular degeneration. Arch Ophthalmol 120: 731–737

    PubMed  Google Scholar 

  66. VEGF Inhibition Study in Ocular Neovascularization (V.I.S.I.O.N.) Clinical Trial Group, D’Amico DJ, Masonson HN, Patel M, Adamis AP et al. (2006) Pegaptanib sodium for neovascular age-related macular degeneration: two-year safety results of the two prospective, multicenter, controlled clinical trials. Ophthalmology 113: 992–1001

    Article  Google Scholar 

  67. Völcker M, Peters S, Inhoffen W, Ziemssen F (2006) Früher antiexsudativer Effekt – OCT-Monitoring nach intravitrealer Bevacizumab-Applikation. Ophthalmologe 103: 476–483

    Article  PubMed  CAS  Google Scholar 

  68. Wolf S (2007) Ranibizumab zur Behandlung der altersbedingten Makuladegeneration. Schweiz Med Forum 7: 589–585

    Google Scholar 

  69. Yanyali A, Aytug B, Horozoglu F, Nohutcu AF (2007) Bevacizumab (Avastin) for diabetic macular edema in previously vitrectomized eyes. Am J Ophthalmol 144: 124–126

    Article  PubMed  CAS  Google Scholar 

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Interessenkonflikt

Der korrespondierende Autor weist auf folgende Beziehungen hin: Nicole Eter und Carsten H. Meyer wurden von Novartis Pharma AG, Nürnberg, und Pfizer GmbH, Karlsruhe, für Vorträge und die Teilnahme an Advisory Boards finanziell unterstützt. Die Augenklinik der Universität Bonn nimmt an diversen wissenschaftlichen Studien zu verschiedenen AMD-Therapien teil.

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Meyer, C., Helb, HM. & Eter, N. Monitoring von AMD-Patienten unter Anti-VEGF-Therapie. Ophthalmologe 105, 125–142 (2008). https://doi.org/10.1007/s00347-008-1702-6

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