Bandello pharmacological treatment of vitreo macular traction
•
7 likes•1,843 views
http://www.tvrs.gr/
Recommended
More Related Content
What's hot
What's hot (20)
Similar to Bandello pharmacological treatment of vitreo macular traction
Similar to Bandello pharmacological treatment of vitreo macular traction (20)
More from Thessaloniki International Vitreo-Retinal Summer School
More from Thessaloniki International Vitreo-Retinal Summer School (20)
Recently uploaded
Recently uploaded (20)
Bandello pharmacological treatment of vitreo macular traction
- 1. Pharmacological Treatment of Vitreo-Macular Traction Francesco Bandello, MD, FEBO Lorenzo Iuliano, MD Department of Ophthalmology University Vita-Salute San Raffaele Scientific Institute Milan, Italy
- 2. Financial Disclosure Advisory Board Member for: • Alcon • Alimera • Allergan • Bausch and Lomb • Bayer • Genentech • Hossmann-La Roche • Novagali Pharma • Novartis • Pfizer • Sanofi-Aventis • Thea • Thrombogenics
- 3. • Vitreomacular adhesion – perifoveal hyaloid detachment with no detectable change in foveal contour or underlying retinal tissues • Vitreomacular traction – perifoveal hyaloid detachment associated with distortion of the foveal surface, intraretinal structural changes, retinal elevation above the RPE, but no full-thickness interruption of all retinal layers Definition
- 4. Physiologic PVD • PVD is the separation of the posterior vitreous from the ILM • Processes involved – Synchysis – Syneresis – Weakening of the V-R adhesion • PVD can be asymptomatic, although some patients report floaters Early liquefaction Extensive liquefaction Separation Johnson MW. Am J Ophthalmol 2010 Schneider EW et al. Clin Ophthalmol 2011 Sebag J. Graefes Arch Clin Exp Ophthalmol 2004 Hollands H et al. JAMA 2009
- 5. Anomalous PVD • Sufficient weakening at the V-R interface when the critical level of liquefaction has been achieved • If not, incomplete (anomalous) PVD can arise Sebag J. Graefes Arch Clin Exp Ophthalmol 2004 Dugel P. Retina Today 2012
- 6. Pathophysiology of Anomalous PVD Stalmans et al. Retina (2013)
- 7. Stalmans et al. Retina (2013) Pathophysiology of Anomalous PVD
- 8. • Vitreo-macular traction can coexist with other diseases Secondary VMT Bandello F et al. Ophthalmologica 2013
- 9. VMT classification Duker JS et al. Ophthalmology 2013
- 10. Natural History Carpineto P et al. Eur J Ophthalmol 2011 Guyer DR et al. Arch Ophthalmol 1992 Hikichi T et al. Br J Ophthalmol 1995 Kim JW et al. Am J Ophthalmol 1996 VMAVMA Total PVDTotal PVD Spontaneous resolution FTMH 3–12% spontaneous closure VMA, VMT non full thickness MH non FTMHnon FTMH 50–84% PVD
- 11. • Only 5% will have 20/50 BCVA or better • 55–58% will have BCVA of 20/100 or better • Approximately 40% will have BCVA of 20/200 or worse • If the FTMH closes (rare), BCVA can recover • Most patients retain a BCVA of 20/100 to 20/400 Macular Hole Prognosis AAO Retina Panel (2008) Preferred Practice Pattern® Idiopathic Macular Hole
- 12. The idea • Standard of care: • “Watchful waiting” • Vitrectomy • Alternative: • Pharmacologic vitreolysis
- 13. • Pharmacological vitreolysis was defined by J Sebag “Weaken or cleave V-R junction before or concurrently with liquefaction of core vitreous” • First animal experience of enzymatic vitreolysis are of 1998 Pharmacologic vitreolysis Sebag J. Retina 1998 Sebag J. Retina 2009
- 14. • Several agents have been tested to achieve vitreolysis • Classified accordingly to their biological effect Different agents Bandello F et al. Ophthalmologica 2013
- 15. • rtPA: safe only for sub-macular hemorrhages in nvAMD • Nattokinase: only animal models • Chondroitinase: no significant biological effect • Dispase: retinal toxicity, PVR • Hyaluronidase (Vitrase®): no FDA approval, just liquefactant • Collagenase: retinal toxicity, ILM damage Bandello F et al. Ophthalmologica 2013
- 16. • Most studied agent • Extracted from patient’s plasma-derived plasminogen • Action • Non-specific serine-protease • Degrades fibrin, fibronectin and laminin • Indirectly increases levels of matrix metalloproteinases • Safety (histology and electrophysiology) at different concentration (0.03-2 IU) Autologous Plasmin Enzyme (APE)
- 17. • Pediatric population: ROP, X-linked retinoschisis, traumatic macular hole • Assisting surgery • Diabetic macular edema • Retinal vein occlusion • Vitreo-macular traction Experience with APE Margherio AR et al. Ophthalmology 1998 Wu WC et al. Am J Ophthalmol 2007 Tsukahara Y et al. Am J Ophthalmol 2007 Wu WC et al. Retina 2008 Wu WC et al. Retina 2007 Trese MT et al. Am J Ophthalmol 2000 Rizzo S et al. Retina 2006 Sakuma T et al. Eur J Ophthalmol 2005 Asami T et al. Ophthalmology 2004 Azzolini et al. Am J Ophthalmol 2004 Sakuma T et al. Eur J Ophthalmol 2006 Hirata A et al. Sakuma T et al. Retina 2006 Udaondo P et al. Arch Ophthalmol 2011 Codenotti M et al. Eye 2013
- 18. Codenotti M et al. Eye 2013 intravitreal APE 7 days 30 days Surgery 24h
- 19. Form APE to ocriplasmin • Recombinant truncated form of the active enzyme • 1/3 molecular weight • Retains the catalytic activity Nagai N et al. J Thromb Haemost 2007 de Smet et al. IOVS 2009
- 20. • Targets fibronectin, laminin and collagen • Induces vitreous liquefaction and separation of V-R interface • Cleanly separate hyaloid from ILM Form APE to ocriplasmin Collagen Laminin, Fibronectin Collagen Gandorfer et al. IOVS 2004
- 21. • Phase I/II, 60 pts • Safe • Well tolerated MIVI studies • Phase II, 60 pts • Best dose of 125 µg • Capable of PVD inducing de Smet M et al. Ophthalmology 2009 Stalmans P et al. Retina 2010 Stalmans P et al. NEJM 2012 • Phase III, 652 pts • Dose of 125 µg • Superior than sham inj.
- 22. The definitive approval Two multicenter, randomized, double-masked, placebo-controlled, phase III studies Randomized (N=652) Ocriplasmin 125 µg (n=464) Placebo (n=188) Assessments at baseline, injection day, and Days 7, 14, 28, 90, and 180 after injection Patients with symptomatic VMA confirmed by optical coherence tomography Stalmans P et al. NEJM 2012
- 23. ocriplasmin placebo VMT resolution 26.5% 10.1% PVD induction 13.4% 3.7% MH closure 40.6% 10.6% P<0.001 (all) Stalmans P et al. NEJM 2012 The definitive approval
- 24. p<0.001 p=0.113 VMA resolution at day 28 according to adhesion size Ocriplasmin Placebo n= 123 314 41 102 Patientswith resolutionofVMA(%) ThromboGenics NV. JETREA (ocriplasmin) Summary of Product Characteristics. 2013 Post-hoc studies
- 25. N=35 N=86 N=33 N=98 N=68 N=184 Study 006 Study 007 Study 006 Study 007 Combined data N=72 N=128 N=47 N=142 N=119 N=270 Epiretinal membrane No epiretinal membrane p<0.001 p<0.001 p=0.046 p=0.180 p=0.289 p<0.003 Combined data VMA resolution at day 28 according to epiretinal membrane presence Stalmans P et al. NEJM 2012
- 26. N=35 N=86 N=33 N=98 N=68 N=184 Study 006 Study 007 Study 006 Study 007 Combined data N=72 N=128 N=47 N=142 N=119 N=270 Epiretinal membrane No epiretinal membrane p<0.001 p<0.001 p=0.046 p=0.180 p=0.289 p<0.003 Combined data VMA resolution at day 28 according to epiretinal membrane presence Stalmans P et al. NEJM 2012
- 27. Non-surgical MH closure at day 28 according to MH size Stalmans P et al. NEJM 2012
- 28. p<0.001 n = 4 28 5 28 Day 28 6 Months >250 µm p=0.002 p=0.200p=0.031 n = 1 14 3 14 %Patients %Patients Day 28 6 Months ≤250 µm Non-surgical MH closure at day 28 according to MH size Stalmans P et al. NEJM 2012
- 29. • Requirement of vitrectomy at day 180 – 17.7% (ocriplasmin) vs 26.6% (sham); p=0.02 • BCVA improvement – >2 lines: 28% (ocriplasmin) vs 17.1% (sham); p=0.003 – >3 lines: 12.3% (ocriplasmin) vs 6.4% (sham); p=0.024 Stalmans P et al. NEJM 2012
- 30. • Focal VMT • Symptomatic VMA • Non full thickness macular hole • Full thickness macular hole <400 µm Actual indications
- 31. Side effects • The difference in the proportion of patients experiencing AEs was driven primarily by those associated with vitreous detachment • The majority of AEs were transient and mild in severity Placebo (n=187) Ocriplasmin (n=465) p Any ocular AE, n (%) 100 (53.5) 318 (68.4) <0.001 Any ocular serious AE, n (%) 20 (10.7) 36 (7.7) 0.26 Stalmans P et al. NEJM 2012
- 32. Event, n (%) Placebo (n=187) Ocriplasmin (n=465) p Any serious AE 20 (10.7) 36 (7.7) 0.26 Macular hole 16 (8.6) 24 (5.2) 0.15 Retinal detachment 3 (1.6) 2 (0.4) 0.16 Reduced VA 1 (0.5) 3 (0.6) 0.94 Stalmans P et al. NEJM 2012 Side effects
- 33. Safety concerns Kim JE. JAMA Ophth 2014 • ERG abnormalities in 7.8% of pts • Dyschromatopsia (yellowing vision) in 2% of pts • 1% of these with ERG changes • Reports of vision loss and panretinal abnormalities Tibbets M et al. JAMA Ophth 2014 Fahim AT et al. JAMA Ophth 2014 • Judicious use • Careful follow-up Phase IV studies
- 34. • Eyes with nvAMD have more than twice chance (OR 2.54) to have concurrent VMT • Anti-VEGF + ocriplasmin? Jackson TL et al. Retina 2013 VMT and Neovascular AMD
- 35. Conclusion • “Watchful waiting” of VMT can lead to irreversible retinal damage, cysts and macular hole formation • Spontaneous separation of VMT occurs rarely • Vitrectomy indicated if VA loss or disease progression, but surgery is not risk-free • Pharmacologic vitreolysis may induce VMT resolution and improve vision