ITAP – 6-Monats-Ergebnisse einer prospektiven und randomisierten Phase-3-Studie zur Evaluation der Kombinationstherapie aus PDT und intravitrealem Triamcinolon bei der exsudativen AMD

Zusammenfassung

Hintergrund: Die Kombinationstherapie aus photodynamischer Therapie (PDT) und intravitrealer Triamcinolon-Eingabe (IVTA) bei choroidalen Neovaskularisationen (CNV) im Rahmen der AMD scheint die Prognose dieser Erkrankung zu verbessern. Diese Annahme war jedoch bislang auf nicht randomisierte und retrospektive Studien basiert. Wir stellen hier die 6-Monats-Ergebnisse der prospektiven und randomisierten multizentrischen ITAP-Studie (Intravitreal Triamcinolone And PDT) zur Evaluation der PDT-IVTA-Kombinationstherapie im Vergleich zur PDT-Monotherapie vor. Patienten: Prospektive und randomisierte multizentrische Phase-III-Studie zur Evaluation der Wirksamkeit und Sicherheit der PDT-IVTA-Kombinationstherapie im Vergleich zur PDT-Monotherapie. 3 randomisierte Therapiegruppen (A: nur PDT; B: IVTA am selben Tag 1 Stunde nach PDT; C: IVTA 1 Woche vor PDT) wurden 1 Jahr lang beobachtet. Eingeschlossen wurden Patienten mit überwiegend klassischer CNV, minimal klassischer CNV (< 4 Papillendurchmesser) oder okkulter CNV mit akuter Visusverschlechterung. Die Behandlung wurde wiederholt, wenn bei der Kontrolluntersuchung eine persistierende Leckage der CNV sichtbar war. Primäre Endpunkte waren der Endvisus im Vergleich zwischen Kombinationstherapie und PDT-Monotherapie sowie der Endvisus im Vergleich zwischen beiden Gruppen der Kombinationstherapie. Ergebnisse: 92 Patienten wurden in die Studie eingeschlossen. Vor Beginn der Therapie betrug der mittlere best-korrigierte ETDRS-Visus 52, 53 und 51 Buchstaben in den Gruppen A, B und C, bei der 6-Monats-Kontrolle entsprechend 40, 47 und 47 Buchstaben. Lediglich Gruppe A verliert im Mittel mehr als 10 Buchstaben, die Änderung ist jedoch zwischen den Gruppen statistisch nicht signifikant. Die mittlere Netzhautdicke, gemessen mittels optischer Kohärenztomografie, verminderte sich in allen Gruppen statistisch signifikant, insbesondere in den Kombinationsgruppen. Die Anzahl der Wiederholungsbehandlungen ist zwischen den drei Gruppen nach 6 Monaten nicht signifikant unterschiedlich, eine operationswürdige Kataraktprogression konnte während der ersten 6 Monate nicht nachgewiesen werden. Schlussfolgerung: Die 6-Monats-Ergebnisse dieser prospektiven und randomisierten Studie zeigen nach 6 Monaten keinen statistisch signifikanten Unterschied im Visusverlauf zwischen Mono- und Kombinationstherapie.

Abstract

Background: Combination therapy of photodynamic therapy (PDT) with intravitreal triamcinolone (IVTA) for choroidal neovascularisation (CNV) in age-related macular degeneration is thought to improve the prognosis. It is therefore widely used, although results are mostly based upon non-randomised and retrospective studies. Here we present the 6-month results of our prospective, randomised, multicentre ITAP trial (Intravitreal Triamcinolone and PDT) for the evaluation of the combination therapy as compared to PDT alone. Patients: This prospective, randomised, multicentre phase III trial was performed for the evaluation of the efficacy and safety of combination therapy (PDT and IVTA) as compared to PDT alone. Three randomised therapy groups (A: PDT alone, B: IVTA on the same day 1 hour after PDT C: IVTA 1 week before PDT) were monitored over 1 year. The patients included had wet AMD with predominantly classic CNV, minimal classic CNV smaller than 4 papillary diameters or occult CNV with recent disease progression. Re-treatment was performed when persistent leakage of the CNV was visible at follow-up. Primary outcome criteria were the comparison between combination therapy and PDT monotherapy concerning visual acuity, and, second, the comparison between the two groups of combination therapy. Results: 92 patients were included in the study. Before treatment, mean best corrected ETDRS letter score was 52, 53 and 51 in groups A, B and C, respectively. At the 6 months follow-up, mean best corrected letter score was 40, 47 and 47, respectively, with only group A loosing more than 10 letters. This change, however, was not statistically significant between the groups. Mean retinal thickness as measured with optical coherence tomography decreased in all groups, and reached statistical significance in both combination groups. Re-treatment rates did not differ significantly between the three groups at 6 months follow-up, nor was there a significant cataract progression requiring operation. Conclusion: At 6 months there was no significant difference between mono- and combination therapy groups concerning visual acuity.

Schlüsselwörter

Retina - altersabhängige Makuladegeneration - photodynamische Therapie - Triamcinolon - intravitreale Therapie - randomisierte Studie

Key words

retina - age-related macular degeneration - photodynamic therapy - Triamcinolone - intravitreal injection - randomised study

Literatur

• 1 Arias L, Garcia-Arumi J, Ramon J M. et al . Photodynamic therapy with intravitreal triaminolone in predominantly classic choroidal neovascularization: one-year results of a randomized study.  Ophthalmology. 2006;  113 (12) 2243-2250
• 2 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 (1) 14-22
• 3 Brown D M, Kaiser P K, Michels M. et al . ANCHOR Study Group. Ranibizumab versus verteporfin for neovascular age-related macular degeneration.  N Engl J Med. 2006;  355 1432-1444
• 4 Chan W M, Lai T Y, Wong A L. et al . Combined photodynamic therapy and intravitreal triamcinolone acetonide for the treatment of subfoveal choroidal neovascularization in age-related macular degeneration: a comparative study.  Br J Ophthalmol. 2006;  90 (3) 337-341
• 5 Chandler D B, Rozakis G, Juan de E. et al . The effect of triamcinolone acetonide on a refined experimental model of proliferative vitreoretinopathy.  Am J Ophthalmol. 1985;  99 686-690
• 6 Chaudhary Jr V, Mao A, Hooper P L. et al . Triamcinolone acetonide as adjunctive treatment to verteporfin in neovascular age-related macular degeneration: a prospective randomized trial.  Ophthalmology. 2007;  114 (12) 2183-2189
• 7 Florman N, Zor U. Mechanism of steroid action in ocular inflammation: Inhibition of prostaglandin production.  Invest Opthalmol Vis Sci. 1977;  16 (1) 69-73
• 8 Gillies M C, Simpson J M, Luo W. et al . A randomized clinical trial of a single dose of intravitreal triamcinolone acetonide for neovascular age-related macular degeneration: one-year results.  Arch Ophthalmol. 2003;  121 (5) 667-673
• 9 Gragoudas E S, Adamis A P, Cunningham E T. et al . VEGF Inhibition Study in Ocular Nevascularization Clinical Trial Group. Pegaptanib for neovascular age-related macular degeneration.  N Engl J Med. 2004;  351 (27) 2805-2816
• 10 Hahn Jr R, Sacu S, Michels S. et al . Intravitreal bevacizumab versus verteporfin and intravitreal triamcinolone acetonide in patients with neovascular age-related macular degeneration.  Ophthalmologe. 2007;  104 (7) 588-593
• 11 Ishibashi T, Miki K, Sorgente N. et al . Effects of intravitreal administration of steroids on experimental subretinal neovascularization in the subhuman primate.  Arch Ophthalmol. 1985;  103 708-711
• 12 Jaissle G B, Szurman P, Barzt-Schmidt K U. Nebenwirkungen und Komplikationen der intravitrealen Triamcinolonacetonid-Therapie.  Ophthalmologe. 2004;  101 121-128
• 13 Jaissle G B, Szurman P, Bartz-Schmidt K U. et al . 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 (BVA).  Klin Monatsbl Augenheilkd. 2005;  222 (5) 390-395
• 14 Jonas J B, Hayler J K, Panda-Jonas S. Intravitreal injection of crystalline cortisone as adjunctive treatment of proliferative vitreoretinopathy.  Br J Ophthalmol. 2000;  84 (9) 1064-1067
• 15 Jonas J B, Degenring R F, Kreissig I. et al . Exudative age-related macular degeneration treated by intravitreal triamcinolone acetonide. A prospective comparative nonrandomized study.  Eye. 2005;  19 (2) 163-170
• 16 Kaiser for the TAP-Study Group K. Verteporfin therapy of subfoveal horoidal neovascularization in age-related macular degeneration: 5-year results of two randomized clinical trials with an open-label extension: TAP Report no. 8.  Graefe‘s Arch Clin Exp Ophthalmol. 2006;  244 (9) 1132-1142
• 17 Kvanta A, Algvere P V, Berglin L. et al . Subfoveal fibrovascular membranes in age-related macular degeneration express vascular endothelial growth factor.  Invest Ophthalmol Vis Sci. 1996;  37 1929-1934
• 18 Lee J, Freeman W R, Azen S P. et al . Prospective, randomized clinical trial of intravitreal triamcinolone treatment of neovascular age-related macular degeneration: one-year results.  Retina. 2007;  27 (9) 1205-1213
• 19 Penfold P L, Gyory J F, Hunyor A B. et al . Exudative macular degeneration and intravitreal triamcinolone. A pilot study.  Aust N Z J Ophthalmol. 1995;  23 (4) 293-298
• 20 Penfold P L, Wen L, Madigan M C. et al . Triamcinolone acetonide modulates permeability and intercellular adhesion molecule-1 (ICAM-1) expression of the EVC304 cell line: implications for macular degeneration.  Clin Exp Immunol. 2000;  121 (3) 458-465
• 21 Rosenfeld P J, Brown D M, Heier J S. et al . MARINA Study Group. Ranibizumab for neovascular age-related macular degeneration.  N Engl J Med. 2006;  355 1419-1431
• 22 Schadlu R, Kymes S M, Apte R S. Combined photodynamic therapy and intravitreal triamcinolone for neovascular age-related macular degeneration: effect of initial visual acuity on treatment response.  Graefe‘s Arch Clin Exp Ophthalmol. 2007;  245 (11) 1667-1672
• 23 Spaide R F, Sorenson J, Maranan L. Combined photodynamic therapy with verteporfin and intravitreal triamcinolone acetonide for choroidal neovascularization.  Ophthalmology. 2003;  110 (8) 1517-1525
• 24 Spaide R F, Sorenson J, Maranan L. Photodynamic therapy with verteporfin combined with intravitreal injection of triamcinolone acetonide for choroidal neovascularization.  Ophthalmology. 2005;  112 (2) 301-304
• 25 Spaide R F, Laud K, Fine H F. et al . Intravitreal bevacizumab treatment of choroidal neovascularization secondary to age-related macular degeneration.  Retina. 2006;  26 383-390
• 26 Tano Y, Chandler D, Machemer R. Treatment of intraocular proliferation with intravitreal injection of triamcinolone acetonide.  Am J Ophthalmol. 1980;  90 (6) 810-816
• 27 Tatar O, Adam A, Shinoda K. et al . Expression of VEGF and PEDF in choroidal neovascular membranes following verteporfin photodynamic therapy.  Am J Ophthalmol. 2006;  142 (1) 95-104
• 28 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: one-year-results of 2 randomized clinical trials – TAP report 1.  Arch Ophthalmol. 1999;  117 1329-1345
• 29 Verteporfin in photodynamic therapy study group . Verteporfin therapy of subfoveal choroidal neovascularization in age-related macular degeneration: two-year results of a randomized clinical trial including lesions with occult with no classic choroidal neovascularization – Verteporfin in Photodynamic Therapy report 2.  Am J Ophthalmol. 2001;  131 541-560
• 30 Visudyne in minimally classic choroidal neovascularization study group. . Verteporfin therapy of subfoveal minimally classic choroidal neovascularization in age-related macular degeneration: 2-year results of a randomized clinical trial.  Arch Ophthalmol. 2005;  123 448-457
• 31 Weigert G, Michels S, Sacu S. et al . Intravitreal bevacizumab (Avastin) therapy versus photodynamic therapy plus intravitreal triamcinolone for neovascular age-related macular degeneration: 6-month results of a prospective, randomised, controlled clinical study.  Br J Ophthalmol. 2008;  92 (3) 356-360
• 32 Wilson C A, Berkowitz B A, Sato Y. et al . Treatment with intravitreal steroid reduces blood-retinal barrier breakdown due to retinal photocoagulation.  Arch Ophthalmol. 1992;  110 (8) 1155-1159