Pharmacologic Vitreolysis: New Perspectives, Future Directions

Part of the Essentials in Ophthalmology book series (ESSENTIALS)


Ocriplasmin is currently the only approved pharmacologic agent for the release of vitreo-macular traction. Its success rate in releasing vitreo-macular traction under optimal conditions is about 40 %. Traction is present in a number of processes leading to macular disease, which suggests that its prophylactic release might have significant clinical relevance. Release of traction or vitreous adhesion in conditions such as macular edema from diabetes or retinal vein occlusion, vascular proliferation, or retinal degeneration or neovascularization can be considered under appropriate circumstances. To this end, the biology of the particular disease process must be considered. Partial release of the posterior hyaloid in pre-proliferative diabetic retinopathy may be associated with an increase risk of proliferation, while in macular edema, early intervention may be required for success.

A challenge will be the development of a treatment regimen that enhances the rate with which complete PVD is achieved either with a single or multiple injections or by combination with other pharmacologic agents. It will also be important to develop means of improving the visualization of the interface between the retina and vitreous. Specific scanning techniques and algorithms currently being developed for the OCT and new ultrasonographic probes are likely to facilitate such visualization and help in the diagnostic and therapeutic management of patients with diseases at the vitreoretinal interface.


Macular Edema Macular Hole Proliferative Diabetic Retinopathy Retinal Vein Occlusion Posterior Vitreous Detachment 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



  1. Aerts F, Noppen B, Fonteyn L et al (2012) Mechanism of inactivation of ocriplasmin in porcine vitreous. Biophys Chem 165–166:30–38. doi: 10.1016/j.bpc.2012.03.002 PubMedCrossRefGoogle Scholar
  2. Akiba J, Arzabe CW, Trempe CL (1990) Posterior vitreous detachment and neovascularization in diabetic retinopathy. Ophthalmology 97:889–891PubMedCrossRefGoogle Scholar
  3. Asami T, Wong SC, Mitchell PC et al (2012) A novel quadraport needle with improved intravitreal drug dispersion. Retina 32:1222–1225PubMedCrossRefGoogle Scholar
  4. Barak Y, Ihnen MA, Schaal S (2012) Spectral domain optical coherence tomography in the diagnosis and management of vitreoretinal interface pathologies. J Ophthalmol 2012:876472. doi: 10.1155/2012/876472 Google Scholar
  5. Barteselli G, Bartsch DU, El-Emam S et al (2013) Combined depth imaging technique on spectral-domain optical coherence tomography. Am J Ophthalmol 155:727–732. doi: 10.1016/j.ajo.2012.10.019 Google Scholar
  6. Boon C, Crama N, Klevering B et al (2008) Reflux after intravitreal injection of bevacizumab. Ophthalmology 115:1268CrossRefGoogle Scholar
  7. Chan CK, Wessels IF, Friedrichsen EJ (1995) Treatment of idiopathic macular holes by induced posterior vitreous detachment. Ophthalmology 102:757–767PubMedCrossRefGoogle Scholar
  8. De Croos FC, Toth CA, Folgar FA et al (2012) Characterization of vitreoretinal interface disorders using OCT in the interventional phase 3 trials of ocriplasmin. Invest Ophthalmol Vis Sci 53:6504–6511. doi: 10.1167/iovs.12-10370 CrossRefGoogle Scholar
  9. de Smet MD, Gandorfer A, Stalmans P et al (2009) Microplasmin intravitreal administration in patients with vitreomacular traction scheduled for vitrectomy: the MIVI I trial. Ophthalmology 116:1349–1355PubMedCrossRefGoogle Scholar
  10. de Smet MD, Gad El Kareem A, Zwinderman AH (2013) The vitreous, the retinal interface in ocular health and disease. Ophthalmologica in press. doi:  10.1159/000353447 Google Scholar
  11. de Smet MD, Jonckx B, Vanhove M et al (2012) Pharmacokinetics of ocriplasmin in vitreous. Invest Ophthalmol Vis Sci 53:8208–8213. doi: 10.1167/iovs.12-10148 PubMedCrossRefGoogle Scholar
  12. Falkner-Radler CI, Glittenberg C, Hagen S et al (2010) Spectral-domain optical coherence tomography for monitoring epiretinal membrane surgery. Ophthalmology 117:798–805. doi: 10.1016/j.ophtha.2009.08.034 PubMedCrossRefGoogle Scholar
  13. Faulborn J, Bowald S (1985) Microproliferations in proliferative diabetic retinopathy and their relationship to the vitreous: corresponding light and electron microscopic studies. Graefes Arch Clin Exp Ophthalmol 223:130–138PubMedCrossRefGoogle Scholar
  14. Folgar FA, Toth CA, DeCroos FC et al (2012) Assessment of retinal morphology with spectral and time domain OCT in the phase III trials of enzymatic vitreolysis. Invest Ophthalmol Vis Sci 53:7395–7401. doi: 10.1167/iovs.12-10379 PubMedCrossRefGoogle Scholar
  15. Gad El Kareem AM, Willikens B, Stassen JM et al (2010) Differential vitreous dye diffusion following microplasmin or plasmin pre-treatment. Curr Eye Res 35:235–241CrossRefGoogle Scholar
  16. Gad El Kareem A, Zwinderman AH, Mateo-Montoya A, et al (2013) The vitreous and its retinal interface in ocular health and disease. Ophthalmologica (in press)Google Scholar
  17. Gao BB, Chen X, Timothy N et al (2008) Characterization of the vitreous proteome in diabetes without diabetic retinopathy and diabetes with proliferative diabetic retinopathy. J Proteome Res 7:2516–2525PubMedCrossRefGoogle Scholar
  18. Hong SW, Jee D (2012) Effect of the honan intraocular pressure reducer to prevent vitreous reflux after intravitreal bevacizumab injection. Eur J Ophthalmol 22:615–619PubMedCrossRefGoogle Scholar
  19. Hubschman JP, Coffee RE, Bourges JL et al (2010) Experimental model of intravitreal injection techniques. Retina 30:167–173PubMedCrossRefGoogle Scholar
  20. Johnson MW (2012) Posterior vitreous detachment. Evolution and role in macular disease. Retina 32:S174–S178PubMedCrossRefGoogle Scholar
  21. Johnson MW (2013) How should we release vitreomacular traction: surgically, pharmacologically, or pneumatically? Am J Ophthalmol 155:203–205.e1. doi: 10.1016/j.ajo.2012.10.016 PubMedCrossRefGoogle Scholar
  22. Mojana F, Kozak I, Oster SF et al (2010) Observations by spectral-domain optical coherence tomography combined with simultaneous scanning laser ophthalmoscopy: imaging of the vitreous. Am J Ophthalmol 149:641–650. doi: 10.1016/j.ajo.2009.11.016 PubMedCrossRefGoogle Scholar
  23. NasrAllah FP, Jalkh AE, Van Coppenolle F et al (1988) The role of the vitreous in diabetic macular edema. Ophthalmology 95:1335–1339PubMedCrossRefGoogle Scholar
  24. Ochoa-Contreras E, Delsol-Coronado L, Buitrago ME et al (2000) Induced posterior vitreous detachment by intravitreal sulfur hexafluoride (SF6) injection in patients with nonproliferative diabetic retinopathy. Acta Ophthalmol Scand 78:687–688PubMedCrossRefGoogle Scholar
  25. Ono R, Kakehashi A, Yamagami H et al (2005) Prospective assessment of proliferative diabetic retinopathy with observations of posterior vitreous detachment. Int Ophthalmol 26:15–19PubMedCrossRefGoogle Scholar
  26. Rodrigues EB, Meyer CH, Grumann A Jr et al (2007) Tunelled incision to prevent vitreous reflux after intravitreal injection. Am J Ophthalmol 143:1035–1037PubMedCrossRefGoogle Scholar
  27. Rodrigues EB, Grumann A Jr, Penha FM et al (2011) Effect of needle type and injection technique on pain level and vitreal reflux in intravitreal injection. J Ocul Pharmacol Ther 27:197–203. doi: 10.1089/jop.2010.0082 PubMedCrossRefGoogle Scholar
  28. Rodrigues IA, Stangos AN, McHugh DA et al (2013) Intravitreal injection of expansile perfluoropropane (c(3)f(8)) for the treatment of vitreomacular traction. Am J Ophthalmol 155:270–276.e2. doi: 10.1016/j.ajo.2012.08.018 PubMedCrossRefGoogle Scholar
  29. Schneider EW, Johnson MW (2011) Emerging nonsurgical methods for the treatment of vitreomacular adhesion: a review. Clin Ophthalmol 5:1151–1165. doi: 10.2147/OPTH.S14840 PubMedCrossRefGoogle Scholar
  30. Sebag J (2007) Pharmacologic vitreolysis—premise and promise of the first decade. Retina 29:871–874CrossRefGoogle Scholar
  31. Sebag J (2008) Vitreoschisis. Graefes Arch Clin Exp Ophthalmol 246:329–332. doi: 10.1007/s00417-007-0743-x PubMedCrossRefGoogle Scholar
  32. Sebag J, Ansari R, Suh K (2007) Pharmacologic vitreolysis with microplasmin increases vitreous diffusion coefficients. Graefes Arch Clin Exp Ophthalmol 245:576–580PubMedCrossRefGoogle Scholar
  33. Stalmans P, de Laey C, de Smet M et al (2010) Intravitreal injection of microplasmin for treatment of vitreomacular adhesion: results of a prospective, randomized, sham-controlled phase II trial (the MIVI-IIT trial). Retina 30:1122–1127PubMedCrossRefGoogle Scholar
  34. Stalmans P, Benz MS, Gandorfer A et al (2012) Enzymatic vitreolysis with ocriplasmin for vitreomacular traction and macular holes. N Engl J Med 367:606–615. doi: 10.1056/NEJMoa1110823 PubMedCrossRefGoogle Scholar
  35. Tagawa H, McMeel JW, Furukawa H et al (1986) Role of the vitreous in diabetic retinopathy. 1. Vitreous changes in diabetic retinopathy and in physiologic aging. Ophthalmology 93:596–601PubMedCrossRefGoogle Scholar
  36. Takahashi M, Trempe CL, Maguire K et al (1981) Vitreoretinal relationship in diabetic retinopathy: a biomicroscopic evaluation. Arch Ophthalmol 99:241–245PubMedCrossRefGoogle Scholar
  37. Tammewar AM, Bartsch DU, Kozak I et al (2009) Imaging vitreomacular interface abnormalities in the coronal plane by simultaneous combined scanning laser and optical coherence tomography. Br J Ophthalmol 93:366–372PubMedCrossRefGoogle Scholar
  38. Thresher RJ, Ehrenberg M, Machemer R (1984) Gas-mediated vitreous compression: an experimental alternative to mechanized vitrectomy. Graefes Arch Clin Exp Ophthalmol 221:192–198PubMedCrossRefGoogle Scholar
  39. Usman Saeed M, Batra R, Qureshi F et al (2011) Reflux of drug during intra-vitreal anti-VEGF therapies. Semin Ophthalmol 26:357–360. doi: 10.3109/08820538.2011.588648 PubMedCrossRefGoogle Scholar
  40. Wang Z-LM, Zhang XM, Xu XM et al (2005) PVD following plasmin but not hyaluronidase: implications for combination pharmacologic vitreolysis therapy. Retina 25:38–43PubMedCrossRefGoogle Scholar
  41. Wang MY, Nguyen D, Hindoyan N et al (2009) Vitreo-papillary adhesion in macular hole and macular pucker. Retina 29:644–650PubMedCrossRefGoogle Scholar
  42. Zhi-Liang W, Wo-Dong S, Min L et al (2009) Pharmacologic vitreolysis with plasmin and hyaluronidase in diabetic rats. Retina 29:269–274PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  1. 1.Retina and Ocular InflammationMIOS, Specialized Eye Center in Uveitis and RetinaLausanneSwitzerland
  2. 2.Vitreoretinal Surgery UnitClinique de MontchoisiLausanneSwitzerland
  3. 3.Gavin Herbert Eye InstituteUniversity of CaliforniaIrvineUSA

Personalised recommendations