Dimanche des Quinze-Vingts, 21 janvier 2007

1. Néovaisseaux sous rétiniens : ce que les anti-VEGF ont changé JF.Girmens *, C.Français, MH.Errera, C.Laurens, M.Ullern, JA.Sahel * Service IV & C.I.C.

15. Cibles JAMA 2005;293(12):1509-13 Angiogénèse VEGF Anti-VEGF Aux XV-XX… Conclusion

16. Cibles Angiogénèse VEGF Anti-VEGF Aux XV-XX… Conclusion

20. Etude « VISION » Angiogénèse VEGF Anti-VEGF Aux XV-XX… Conclusion

21. Préserver la vision Angiogénèse VEGF Anti-VEGF Aux XV-XX… Conclusion

22. Quelle que soit la forme de néovaisseau Angiogénèse VEGF Anti-VEGF Aux XV-XX… Conclusion

23. Evolution de l’AV Angiogénèse VEGF Anti-VEGF Aux XV-XX… Conclusion

24. Tolérance Angiogénèse VEGF Anti-VEGF Aux XV-XX… Conclusion

27. Etudes en cours Angiogénèse VEGF Anti-VEGF Aux XV-XX… Conclusion

28. Etudes en cours

30. Design Sham PDT Ranibizumab 0.3 mg (n=140) Ranibizumab 0.5 mg (n=140) Lecture centralisée des angiographies NV visibles prédominants (n=423) Randomisation 1:1:1 PDT Sham PDT Sham injection (n=143) Screening

31. Calendrier Evaluation Groupe 1 0 1 2 3 4 5 6 7 8 9 10 11 12 Groupe 3 Mois Groupe 2 0.5 mg ranibizumab 0.3 mg ranibizumab Sham injection Sham PDT PDT *selon diffusion angiographique * * * * * * * * * * * *

32. Patients perdant moins de 15 lettres * P <0.0001 vs. PDT PDT (n=143) Ranibizumab 0.3 mg (n=140) Ranibizumab 0.5 mg (n=139) %* %* % of subjects %

33. Patients perdant ≥ 30 lettres PDT (n=143) Ranibizumab 0.3 mg (n=140) Ranibizumab 0.5 mg (n=139) % of Subjects %* %* % * P <0.0001 vs. PDT

34. Gain ≥15 Lettres % of Subjects PDT (n=143) Ranibizumab 0.3 mg (n=140) Ranibizumab 0.5 mg (n=139) % * % * % * P <0.0001 vs. PDT

35. Gain ≥ 30 lettres % of Subjects PDT (n=143) Ranibizumab 0.3 mg (n=140) Ranibizumab 0.5 mg (n=139) % † % * % * P =0.0018 vs. PDT † P <0.0001 vs. PDT

36. Evolution de l’AV ETDRS letters Note: Vertical bars are ± one standard error of the mean. PDT (n=143) – 9.5 Month

37. Evolution de l’AV +11.3 +8.5 – 9.5 20.8 lettres 18.0 lettres * P < 0.0001 PDT (n=143) Ranibizumab 0.3 mg (n=140) Ranibizumab 0.5 mg (n=139) ETDRS letters Month

38. Design Ranibizumab 0.3 mg (n=238) Ranibizumab 0.5 mg (n=240) “ Minimally classic” ou occultes (n=716) Lecture centralisée des angiographies Randomisation 1:1:1 Screening Sham (n=238)

39. Calendrier Mois Ranibizumab 0.5 mg Sham 0 1 2 3 4 5 6 7 8 9 10 11 12 23 24 Visite finale Evaluation Ranibizumab 0.3 mg

40. Primary endpoint: Patients perdant < 15 lettres *p <0.0001 vs sham Patients (%) Sham (n=238) Ranibizumab 0.3 mg (n=238) Ranibizumab 0.5 mg (n=240) * * 62.2% 94.5% 94.6% 0 50 100

41. Patients perdant > 30 lettres * p <0.0001 vs sham Sham (n=238) Ranibizumab 0.3 mg (n=238) Ranibizumab 0.5 mg (n=240) Patients (%) 100 14.3% 0.8% 1.2% 0 20 40 * *

42. Secondary endpoint Patients gagnant > 15 lettres * p <0.0001 vs sham Patients (%) Sham (n=238) Ranibizumab 0.3 mg (n=238) Ranibizumab 0.5 mg (n=240) * * 100 4.6% 24.8% 33.8% 0 10 20 30 40 50

43. Evolution de l’AV * p < 0.0001 + 17.7 lettres + 17.0 lettres Sham (n=238) Ranibizumab 0.3 mg (n=238) Ranibizumab 0.5 mg (n=240) +6.5 +7.2 2 3 4 5 6 7 8 9 10 11 12 -10 -8 -6 -4 -2 0 2 4 6 8 10 ETDRS letters 1 Mois Lettres ETDRS -10.5

44. Tolérance ophtalmologique 1 (0.7%) 1 (0.7%) † 0 0 0 0 Presumed Endophthalmitis* Culture Positive Culture Not Done 0 1 (0.7%) 0 Vitreous Hemorrhage 0 0 0 Retinal Tear 0 0 0 Lens Damage 0 1 (0.7%) 1 (0.7%) ‡ Rheg. Retinal Detachment 1 (0.7%) † 0 0 Uveitis Ranibizumab 0.5 mg (n=140) Ranibizumab 0.3 mg (n=137) PDT (n=143) 0 2 (0.8%) † 0 1 (0.4%) 0 0 Presumed Endophthalmitis* Culture positive Culture negative 1 (0.4%) 1 (0.4%) 0 Vitreous hemorrhage 1 (0.4%) 1 (0.4%) 0 Retinal tear 1 (0.4%) 0 0 Lens damage 0 0 0 Rheg. retinal detachment 1 (0.4%) ‡ 2 (0.8%) 0 Uveitis Ranibizumab 0.5 mg (n=239) Ranibizumab 0.3 mg (n=238) Angiogénèse VEGF Anti-VEGF Aux XV-XX… Conclusion

45. Tolérance systémique 6 (4.3%) 3 (2.2%) 3 (2.1%) Total 0 0 0 AVC hémorragique 1 (0.7%) 1 (0.7%) 1 (0.7%) AVC ischémique 3 (2.1%) 1 (0.7%) 1 (0.7%) Infarctus du myocarde 2 (1.4%) 1 (0.7%) 1 (0.7%) Décès Ranibizumab 0.5 mg (n=140) Ranibizumab 0.3 mg (n=137) PDT (n=143) Angiogénèse VEGF Anti-VEGF Aux XV-XX… Conclusion

46. Tolérance systémique 4 (1.7%) 2 (0.8%) 2 (0.8%) Accidents thrombo-emboliques -4 / -1 -1 / -2 -2 / -2 Variations moyennes (mmHg) 1 (0.4%) 1 (0.4%) 1 (0.4%) Infarctus du myocarde 20 (8.4%) 20 (8.4%) 23 (9.7%) Hypertension 3 (1.3%) 1 (0.4%) 1 (0.4%) AVC 2 (0.8%) † 1 (0.4%)* 0 Décès Ranibizumab 0.5 mg (n=239) Ranibizumab 0.3 mg (n=238) Sham (n=236) Angiogénèse VEGF Anti-VEGF Aux XV-XX… Conclusion

51. Avastin IV Angiogénèse VEGF Anti-VEGF Aux XV-XX… Conclusion

52. Acuité visuelle Angiogénèse VEGF Anti-VEGF Aux XV-XX… Conclusion

54. 1 patient traité aux XV-XX © JFGirmens Krypton PDT Triamcinolone

55. 1 patient traité aux XV-XX Krypton PDT Triamcinolone Début Janvier 2006 Score ETDRS = 30 (20/250) © JFGirmens

56. 1 patient traité aux XV-XX © JFGirmens

57. 17 jan. 2006 24 jan. 2006 (J+5) 31 jan. 2006 (J+12) Angiogénèse VEGF Anti-VEGF Aux XV-XX… Conclusion

67. Surveillance Angiogénèse VEGF Anti-VEGF Aux XV-XX… Conclusion

69. Avastin aux XV-XX: Préparation Angiogénèse VEGF Anti-VEGF Aux XV-XX… Conclusion

70. Angiogénèse VEGF Anti-VEGF Aux XV-XX… Conclusion

71. Angiogénèse VEGF Anti-VEGF Aux XV-XX… Conclusion

72. Angiogénèse VEGF Anti-VEGF Aux XV-XX… Conclusion

79. Tolérance Angiogénèse VEGF Anti-VEGF Aux XV-XX… Conclusion