Klin Monbl Augenheilkd 2009; 226(6): 496-502
DOI: 10.1055/s-0028-1109463
Klinische Studie

© Georg Thieme Verlag KG Stuttgart · New York

Photodynamische Therapie mit Verteporfin kombiniert mit intravitrealer Injektion von Ranibizumab zur Behandlung okkulter und klassischer choroidaler Neovaskularisationen bei AMD

Photodynamic Therapy with Verteporfin Combined with Intravitreal Injection of Ranibizumab for Occult and Classic CNV in AMDM. M. Maier1 , N. Feucht1 , B. Fiore1 , C. Winkler von Mohrenfels1 , P. Kook1 , C. Fegert1 , C. Lohmann1
  • 1Augenklinik der Technischen Universität München, Klinikum rechts der Isar
Further Information

Publication History

Eingegangen: 22.12.2008

Angenommen: 21.4.2009

Publication Date:
08 June 2009 (online)

Zusammenfassung

Hintergrund: Untersucht wird der Effekt einer Kombination von photodynamischer Therapie (PDT) und intravitrealer Behandlung mit Ranibizumab (0,5 mg) bei okkulter und klassischer choroidaler Neovaskularisation (CNV) bei AMD. Methoden: In einer Pilotstudie wurden 28 Patienten mit okkulter oder klassischer CNV bei AMD mit intravitrealer Injektion von Ranibizumab (0,5 mg) 12 bis 24 Stunden nach Standard-PDT behandelt. Es folgten 2 weitere Injektionen nach 1 und 2 Monaten. Vor, 3 und 6 Monate nach Behandlung wurden die Sehschärfe und die Netzhautdicke mit dem OCT untersucht sowie eine Fluoreszenzangiografie durchgeführt. Ergebnisse: Die mittlere Sehschärfe verbesserte sich im Vergleich zur Ausgangssehschärfe und war nach 3 Monaten signifikant besser (Visus vor Behandlung = 0,27, nach 3 Monaten 0,39, nach 6 Monaten 0,37). Wir fanden keine choroidale Hypoperfusion und keinen RPE-Riss. Die OCT-Untersuchung vor, 3 and 6 Monate nach Kombinationstherapie zeigte eine Reduktion der Netzhautdicke (Baseline: 307 µm, nach 1 Monat: 210 µm nach 3 Monaten: 228 µm und nach 6 Monaten 282 µm). Die Fluoreszenzangiografie zeigte eine Reduktion der Leckage im Vergleich zum Ausgangsbefund. Schlussfolgerung: Die photodynamische Therapie kombiniert mit intravitrealer Applikation von Ranibizumab wurde gut vertragen und ergab eine Visusstabilisierung bei 96 % der Patienten. Unsere Kurzzeitergebnisse sind vielversprechend. Weitere Untersuchungen sind nötig, um den Langzeiteffekt der Kombinationstherapie von PDT und intravitrealer Anti-VEGF-Therapie zu überprüfen.

Abstract

Purpose: The aim of this study is to discuss the effect and outcome of a combined photodynamic therapy and intravitreal injection of ranibizumab (0.5 mg) in occult CNV with recent disease progression and in classic choroidal neovascularization (CNV) due to AMD. Methods: In a pilot study in 28 patients (17 classic, 11 occult CNV) an intravitreal injection of ranibizumab was administered within 12 to 24 hours after standard PDT, followed by 2 injections of ranibizumab after 1 and 2 months. Before as well as 3 and 6 months after treatment visual acuity, OCT examinations (retinal thickness) and fluorescein angiography were performed. Results: Mean visual acuity was significantly improved compared to baseline after 3 months (VA baseline 20 / 80, after 3 months 20 / 50, and 20 / 63 after 6 months). We found no choroidal hypoperfusion and no RPE rip. OCT and fluorescein angiography in patients with occult and classic choroidal neovascularisation after the combination therapy showed a reduced retinal thickness (baseline: 307 µm, after 1 month: 210 µm, after 3 months: 228 µm and after 6 months 281 µm) and a reduction of leakage compared to baseline. Conclusions: Photodynamic therapy combined with injection of intravitreal ranibizumab was well tolerated and is effective. We found a stabilisation of VA in 96 % of patients. Our short-term results are very promising. Further studies are necessary to show the long-term effect of the PDT and anti-VEGF combination therapy.

Literatur

  • 1 Aiello L P, Brucker A J, Chang S. et al . Evolving guidelines for intravitreous injections.  Retina. 2004;  24 3-19
  • 2 Antoszyk A N, Tuomi L, Chung C Y. et al . Ranibizumab combined with verteporfin photodynamic therapy in neovascular age-related macular degeneration (FOCUS): Year 2 results.  Am J Ophthalmol. 2008;  145 (5) 862-874
  • 3 Augustin A J, Schmidt-Erfurth U. Verteporfin therapy combined with intravitreal triamcinolone in all types of choroidal neovascularization due to age-related macular degeneration.  Ophthalmology. 2006;  113 14-22
  • 4 Avery R L, Pieramici D J, Rabena M D. et al . Intravitreal bevacizumab (Avastin) for neovascular age-related macular degeneration.  Ophthalmology. 2006;  113 363-372
  • 5 Blinder K J, Bradley S, Bressler N M. et al . Effekt of lesion size, visual acuity and lesion composition on visual acuity change with and without verteporfin therapy for choridal neovascularization secondary to age-related macular degeneration: TAP and VIP report no. 1.  Am J Ophthalmol. 2003;  136 407-418
  • 6 Brown D M, Kaiser P K, Michels M. et al . Ranibizumab versus verteporfin for neovascular age-related macular degeneration.  N Engl J Med. 2006;  355 (14) 1432-1444
  • 7 Chan C K, Meyer C H, Gross J G. et al . Retinal pigment epithelial tears after intravitreal bevacizumab injection for neovascular age-related macular degeneration.  Retina. 2007;  27 (5) 541-551
  • 8 Dhalla M S, Shah G K, Blinder K J. et al . Combined photodynamic therapy with verteporfin and intravitreal bevazicumab for choroidal neovascularization in age-related macular degeneration.  Retina. 2006;  26 (9) 988-993
  • 9 Goldstein M, Heilweil G, Barak A. et al . Retinal pigment epithelial tear following photodynamic therapy for choroidal neovascularization secondary to AMD.  Eye. 2005;  19 (12) 1315-1324
  • 10 Gragoudas E S, Adamis A P, Cunningham E T Jr. et al . Pegaptanib for neovascular age-related macular degeneration.  N Engl J Med. 2004;  351 (27) 2805-2816
  • 11 Heier J S, Boyer D S, Ciulla T A. et al . Ranibizumab combined with verteporfin photodynamic therapy in neovascular age-related macular degeneration: year 1 results of the FOCUS Study.  Arch Ophthalmol. 2006;  124 (11) 1532-1542
  • 12 Heier J S, Antoszyk A N, Pavan P R. et al . Ranibizumab for treatment of neovascular age-related macular degeneration: a phase I/II multicenter, controlled, multidose study.  Ophthalmology. 2006;  113 (642) e1-e4
  • 13 Hussain D, Kramer M, Kenny A G. et al . Effects of photodynamic therapy using verteporfin on experimental choroidal neovascularization and normal retina and choroid up to 7 weeks after treatment.  Invest Ophthalmol Vis Sci. 1999;  40 2322-2331
  • 14 Hussain D, Kim I, Gauthier D. et al . Safety and efficacy of intravitreal injection of ranibizumab in combination with verteporfin PDT on experimental choroidal neovascularization in the monkey.  Arch Ophthalmol. 2005;  123 509-516
  • 15 Jaissle G B, Szurman P, Bartz-Schmidt K U. Recommendation for implementation of intravitreal injections – statement of the German Retina Society, the German Society of Ophthalmology (DOG) and the German professional Association of Ophthalmologists (BVA).  Klin Monatsbl Augenheilkd. 2005;  222 390-395
  • 16 Jonas J B. Intravitreal triamcinolone acetonide for treatment of intraocular oedematous and neovasular diseases.  Acta Ophthamol Scand. 2005;  83 645-663
  • 17 Kim I K, Husain D, Michaud N. et al . Effekt of intravitreal injection of ranibizumab in combination with verteporfin PDT on normal primate retina and choroid.  Invest Ophthalmol Vis Sci. 2006;  47 357-363
  • 18 Koch F, Scholtz S, Singh P. et al . Combined intravitreal therapy for age-related macular disease.  Klin Monatsbl Augenheilkd. 2008;  225 (12) 1003-1008
  • 19 Kumar A, Gopalakrishnan K, Sinha S. Combination photodynamic therapy and intravitreal ranibizumab in neovascular AMD in a north Indian population: a pilot study.  Retina. 2008;  28 (8) 1132-1137
  • 20 Lazic R, Gabric N, Dekaris I. et al . Photodynamic therapy combined with intravitreal bevacizumab (Avastin) in treatment of choroidal neovascularization secondary to age-related macular degeneration.  Coll Antropol. 2007;  31 (Suppl 1) 71-75
  • 21 Ladewig M S, Karl S E, Hamelmann V. et al . Combined intravitreal bevacizumab and photodynamic therapy for neovascular age-related macular degeneration.  Graefes Arch Clin Exp Ophthalmol. 2008;  246 (1) 17-25
  • 22 Lanzetta P. The Mont Blanc Study Group. Italy Mont Blanc: Verteporfin PDT in combination with Ranibizumab for the treatment of subfoveal CNV due to AMD (Summit trial programme). Presented at the 8th Euretina Congress;. Vienna; 22.5.2008
  • 23 Maier M, Haas K, Feucht N. et al . Photodynamische Therapie kombiniert mit intravitrealer Injektion von Bevacizumab zur Behandlung okkulter und klassischer choroidaler Neovaskularisationen bei AMD.  Klin Monatsbl Augenheilkd. 2008;  225 653-659
  • 24 Maier M, Feucht N, Haas K. et al . Bevacizumab intravitreal zur Behandlung okkulter und minimal klassischer choroidaler Neovaskularisation (CNV) bei AMD.  Klin Monatsbl Augenheilkd. 2008;  225 818-824
  • 25 Mennel S, Hausmann N, Meyer C H. et al . Transient visual decrease after photodynamic therapy.  Ophthalmologe. 2005;  102 (1) 58-63
  • 26 Mennel S, Meyer C H, Eggarter F. et al . Transient serous retinal detachment in classic and occult choroidal neovascularization after photodynamic therapy.  Am J Ophthalmol. 2005;  140 (4) 758-760
  • 27 Mennel S, Peter S, Meyer C H. et al . Effect of photodynamic therapy on the function of the outer blood-retinal barrier in an in vitro model.  Graefes Arch Clin Exp Ophthalmol. 2006;  244 (8) 1015-1021
  • 28 Michels S, Hansmann F, Geitzenauer W. et al . Influence of treatment parameters on selectivity of verteporfin therapy.  Invest Ophthalmol Vis Sci. 2006;  47 371-376
  • 29 Michels S, Rosenfeld P J, Puliafito C A. et al . Systemic bevacizumab (Avastin) therapy for neovascular age-related macular degeneration: twelve-week results of an uncontrolled open-label clinical study.  Ophthalmology. 2005;  112 1035-1047
  • 30 Miedl R, von Winkler Mohrenfels C, Maier M. et al . Comparison of central retinal thickness measured with Zeiss OCT III and Heidelberg Spectralis OCT.  ARVO. 2008;  Abstract 3219
  • 31 Moshfegi D M, Kaiser P K, Grossniklaus H E. et al . Clinicopathologic study after submacular removal of choroidal neovascular membranes treated with verteporfin ocular photodynamic therapie.  Am J Ophthalmol. 2003;  135 343-350
  • 32 Rechtman E, Danis R P, Pratt L M. et al . Intravitreal triamcinolone with photodynamic therapy for subfoveal choroidal neovascularization in age related macular degeneration.  Br J Ophthalmol. 2004;  88 344-347
  • 33 Regillo C D, Brown D M, Abraham P. et al . Randomized, double-masked, sham-controlled trial of ranibizumab for neovascular age-related macular degeneration: PIER Study year 1.  Am J Ophthalmol. 2008;  145 239-248
  • 34 Rosenfeld P J, Moshfeghi A A, Puliafito C A. Optical coherence tomography findings after an intravitreal injection of bevacizumab (Avastin) for neovascular age-related macular degeneration.  Ophthalmic Surg Lasers Imaging. 2005;  36 331-335
  • 35 Rosenfeld P J, Brown D M, Heier J S. et al . Ranibizumab for neovascular age-related macular degeneration.  N Engl J Med. 2006;  355 1419-1431
  • 36 Rosenfeld P J, Rich R M, Lalwani G A. Ranibizumab: Phase III clinical trial results.  Ophthalmol Clin North Am. 2006;  19 (3) 361-372
  • 37 Position of the Retinological Society, the German Ophthalmological Society and the Professional Association of Ophthalmologists in Germany on the current therapeutic possibilities for neovascular age-related macular degeneration.  Klin Monatsbl Augenheilkd. 2007;  224 (7) 559-566
  • 38 Schmidt-Erfurth U, Miller J W, Sickenberg M. et al . Photodynamic therapy with verteporfin for choroidal neovascularization caused by age-related macular degeneration: results of retreatments in a phase 1 and 2 study.  Arch Ophthalmol. 1999;  117 1177-1187
  • 39 Schmidt-Erfurth U, Wolf S. and PROTECT Study Group . Same-day administration of verteporfin and ranibizumab 0.5 mg in patients with choroidal neovascularization due to age-related macular degeneration.  Br J Ophthalmol. published online 4.9.2008; 
  • 40 Schmidt-Erfurth U, Hassan T. Mechanisms of action of photodynamic therapy with verteporfin for the treatment of age-related macular degeneration.  Surv Ophthalmol. 2000;  45 (3) 195-214
  • 41 Schmidt-Erfurth U, Laqua H, Schlotzer-Schrehard U. et al . Histopathological changes following photodynamic therapy in human eyes.  Arch Ophthalmol. 2002;  120 835-844
  • 42 Schmidt-Erfurth U, Schlotzer-Schrehard U, Cursiefen C. et al . Influence of photodynamic therapy on expression of vascular endothelial growth factor (VEGF), VEGF receptor 3, and pigment epithelium-derived factor.  Invest Ophthalmol Vis Sci. 2003;  44 4473-4480
  • 43 Spaide R F, Sorenson J, Maranan L. Photodynamic therapy with verteporfin combined with intravitreal injection of triamcinolone acetonide for choroidal neovascularization.  Ophthalmology. 2005;  112 301-304
  • 44 Spaide R F, Laud K, Fine H F. et al . Intravitreal bevazicumab treatment of choroidal neovascularization secondary to age-related macular degeneration.  Retina. 2006;  26 383-390
  • 45 TAP Treatment of Age-Related Macular Degeneration with Photodynamic Therapy (TAP) Study Group . Photodynamic therapy of subfoveal choroidal neovascularization in age-related macular degeneration with verteporfin: two year results of 2 randomized clinical trials-TAP Report 2.  Arch Ophthalmol. 2002;  119 198-207
  • 46 Tzekov R, Lin T, Zhang K M. et al . Ocular changes after photodynamic therapy.  Invest Ophthalmol Vis Sci. 2006;  47 (1) 377-385
  • 47 VEGF Inhibition Study in Ocular Neovascularization (V. I. S. I. O.N.) Clinical Trial Group . Year 2 efficacy results of 2 randomized controlled clinical trials of pegaptanib for neovascular age-related macular degeneration.  Ophthalmology. 2006;  113 (9) 1508.e1-e25. Epub 7.7.2006

Mathias M. Maier

Augenklinik der TUM, Klinikum rechts der Isar

Ismaningerstr. 22

81675 Munich

Phone: ++ 49/89/41 40 23 40

Fax: ++ 49/89/41 40 48 58

Email: M.Maier@lrz.tum.de