Skip to main content
SpringerLink
Log in

Pharmacologic Vitreolysis with Ocriplasmin: Rationale for Use and Therapeutic Potential in Vitreo-Retinal Disorders

  • Current Opinion
  • Published:
BioDrugs Aims and scope Submit manuscript

Abstract

With increased knowledge about the origins and pathophysiology of vitreo-retinal disorders—and, in particular, the central role of anomalous posterior vitreous detachment in vitreo-maculopathies—a paradigm shift from surgery to pharmacotherapy is taking place with the development of pharmacologic vitreolysis. The first approved agent for pharmacologic vitreolysis therapy is ocriplasmin, a truncated form of the nonspecific serine protease plasmin. Twelve studies comprise the current ocriplasmin clinical trial program, demonstrating the efficacy and safety of a single intravitreal injection of ocriplasmin for the treatment of patients with symptomatic vitreo-macular adhesion or vitreo-macular traction, including patients with macular holes. Although post-approval implementation of ocriplamsin in clinical practice has shown success rates of up to 78 %, there have been recent case reports of acute, transient visual dysfunction. There are thus new initiatives to further refine clinical indications for case selection and to identify possible untoward effects. Although more studies are warranted, it appears that ocriplasmin offers a good alternative to surgery. The future lies in pharmacologic vitreolysis, and the future of pharmacologic vitreolysis lies in prevention. Thus, long-term studies are needed to define a role for pharmacologic vitreolysis, in particular with ocriplasmin, in the prevention of progressive diabetic retinopathy and age-related macular degeneration.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

  1. Sebag J. Pharmacologic vitreolysis (Guest Editorial). Retina. 1998;18:1–3.

    Article  CAS  PubMed  Google Scholar 

  2. Sebag J. Is pharmacologic vitreolysis brewing? (Guest Editorial). Retina. 2002;22:1–3.

    Article  CAS  PubMed  Google Scholar 

  3. Sebag J. Molecular biology of pharmacologic vitreolysis. Trans Am Ophthalmol Soc. 2005;103:473–94.

    PubMed Central  CAS  PubMed  Google Scholar 

  4. Sebag J. Pharmacologic vitreolysis—premise and promise of the first decade (Guest Editorial). Retina. 2009;29:871–4.

    Article  CAS  PubMed  Google Scholar 

  5. Sebag J. The emerging role of pharmacologic vitreolysis. Retinal Physician. 2010;7(2):52–6.

    Google Scholar 

  6. Sebag J. Pharmacologic vitreolysis. In: Sebag J, editor. Vitreous in health and disease, chapter VI.A. New York: Springer; 2014.

  7. Sebag J, Yee KMP. Vitreous—from biochemistry to clinical relevance. In: Tasman W, Jaeger EA, editors. Duane’s foundations of clinical ophthalmology, vol. 1, Ch 16. Philadelphia: Lippincott Williams & Wilkins; 2007.

  8. Crafoord S, Ghosh F, Sebag J. Vitreous biochemistry and artificial vitreous. In: Sebag J, editor. Vitreous—in health and disease, Ch I.F. New York: Springer; 2014.

  9. Sebag J. Anomalous PVD—a unifying concept in vitreo-retinal diseases. Graefes Arch Clin Exp Ophthalmol. 2004;242:690–8.

    Article  CAS  PubMed  Google Scholar 

  10. Sebag J. Vitreous anatomy, aging, and anomalous posterior vitreous detachment. In: Dartt, Besharse, Dana, editors. Encyclopedia of the eye. Oxford: Elsevier; 2010. pp. 307–315.

  11. Steel DH, Lotery AJ. Idiopathic vitreomacular traction and macular hole: a comprehensive review of pathophysiology, diagnosis, and treatment. Eye. 2013;27(1):212.

    Google Scholar 

  12. Gandorfer A, Rohleder M, Grosselfinger S, Haritoglou C, Ulbig M, Kampik A. Epiretinal pathology of diffuse diabetic macular edema associated with vitreomacular traction. Am J Ophthalmol. 2005;139(4):638–52.

    Article  PubMed  Google Scholar 

  13. Krebs I, Brannath W, Glittenberg K, Zeiler F, Sebag J, Binder S. Posterior vitreo-macular adhesion: a potential risk factor for exudative age-related macular degeneration. Am J Ophthalmol. 2007;144:741–6.

    Article  PubMed  Google Scholar 

  14. Robison C, Krebs I, Binder S, Barbazetto IA, Kostolis AI, Yannuzzi LA, Sadun AA, Sebag J. Vitreo-macular adhesion in active and end-stage age-related macular degeneration. Am J Ophthalmol. 2009;148:79–82.

    Article  PubMed  Google Scholar 

  15. Parel JMP. The history of vitrectomy. In: Sebag J, editor. Vitreous in health and disease, Ch V.B.1. New York: Springer; 2014.

  16. Parel JMP, Sebag J. Recalling the development of vitreo-retinal therapeutics from vitrectomy to pharmacologic vitreolysis. Retina Times. 2014;32(3):22–6.

    Google Scholar 

  17. Tezel TH, Del Priore LH, Kaplan HJ: Pharmacologic vitreolysis with purified dispase (Vitreolysin™). In: Sebag J, editor. Vitreous—in health and disease, Ch VI.G. New York: Springer; 2014.

  18. Liotta LA, Goldfarb RH, Brundage R. Effect of plasminogen activator (urokinase), plasmin, and thrombin on glycoprotein and collagenous components of basement membrane. Cancer Res. 1981;41(11):4629–36.

    CAS  PubMed  Google Scholar 

  19. Kohno T, Sorgente N, Ishibashi T. Immunofluorescent studies of fibronectin and laminin in the human eye. Investig Ophthalmol Vis Sci. 1987;28(3):506–14.

    CAS  Google Scholar 

  20. Kohno T, Sorgente N, Patterson R, Ryan SJ. Fibronectin and laminin distribution in bovine eye. Jpn J Ophthalmol. 1983;27(3):496–505.

    CAS  PubMed  Google Scholar 

  21. Russell SR, Shepherd JD, Hageman GS. Distribution of glycoconjugates in the human retinal internal limiting membrane. Investig Ophthalmol Vis Sci. 1991;32(7):1986–95.

    CAS  Google Scholar 

  22. Verstraeten TC, Chapman C, Hartzer M, Winkler BS, Trese MT, Williams GA. Pharmacologic induction of posterior vitreous detachment in the rabbit. Arch Ophthalmol. 1993;111(6):849–54.

    Article  CAS  PubMed  Google Scholar 

  23. Hikichi T, Yanagiya N, Kado M, Akiba J, Yoshida A. Posterior vitreous detachment induced by injection of plasmin and sulfur hexafluoride in the rabbit vitreous. Retina. 1999;19(1):55–8.

    Article  CAS  PubMed  Google Scholar 

  24. Kim NJ, Yu HG, Yu YS, Chung H. Long-term effect of plasmin on the vitreolysis in rabbit eyes. Korean J Ophthalmol. 2004;18(1):35–40.

    Article  PubMed  Google Scholar 

  25. Gandorfer A, Putz E, Welge-Lüßen U, Grüterich M, Ulbig M, Kampik A. Ultrastructure of the vitreoretinal interface following plasmin assisted vitrectomy. Br J Ophthalmol. 2001;85(1):6–10.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  26. Gandorfer A, Priglinger S, Schebitz K, et al. Vitreoretinal morphology of plasmin-treated human eyes. Am J Ophthalmol. 2002;133(1):156–9.

    Article  PubMed  Google Scholar 

  27. Li X, Shi X, Fan J. Posterior vitreous detachment with plasmin in the isolated human eye. Graefes Arch Clin Exp Ophthalmol. 2002;240(1):56–62.

    Article  CAS  PubMed  Google Scholar 

  28. Uemura A, Nakamura M, Kachi S, et al. Effect of plasmin on laminin and fibronectin during plasmin-assisted vitrectomy. Arch Ophthalmol. 2005;123(2):209–13.

    Article  CAS  PubMed  Google Scholar 

  29. Plantner JJ, Smine A, Quinn TA. Matrix metalloproteinases and metalloproteinase inhibitors in human interphotoreceptor matrix and vitreous. Curr Eye Res. 1998;17(2):132–40.

    Article  CAS  PubMed  Google Scholar 

  30. Takano A, Hirata A, Inomata Y, Kawaji T, Nakagawa K, Nagata S, Tanihara H. Intravitreal plasmin injection activates endogenous matrix metalloproteinase-2 in rabbit and human vitreous. Am J Ophthalmol. 2005;140(4):654–60.

    Article  CAS  PubMed  Google Scholar 

  31. Brown DJ, Bishop P, Hamdi H, Kenney MC. Cleavage of structural components of mammalian vitreous by endogenous matrix metalloproteinase-2. Curr Eye Res. 1996;15(4):439–45.

    Article  CAS  PubMed  Google Scholar 

  32. Monea S, Lehti K, Keski-Oja J, Mignatti P. Plasmin activates pro-matrix metalloproteinase-2 with a membrane-type 1 matrix metalloproteinase-dependent mechanism. J Cell Physiol. 2002;192(2):160–70.

    Article  CAS  PubMed  Google Scholar 

  33. Gandorfer A, Kampik A. Intravitreal plasmin injection activates endogenous matrix metalloproteinase-2 in rabbit and human vitreous. Am J Ophthalmol. 2006;141(4):784–5.

    Article  CAS  PubMed  Google Scholar 

  34. Sivak JM, Fini ME. MMPs in the eye: emerging roles for matrix metalloproteinases in ocular physiology. Prog Retin Eye Res. 2002;21(1):1–14.

    Article  CAS  PubMed  Google Scholar 

  35. Staubach F, Nober V, Janknecht P. Enzyme-assisted vitrectomy in enucleated pig eyes: a comparison of hyaluronidase, chondroitinase, and plasmin. Curr Eye Res. 2004;29(4–5):261–8.

    Article  CAS  PubMed  Google Scholar 

  36. Hermel M, Prenner J, Alabdulrazza M, Dailey W, Hartzer M. Effect of intravitreal plasmin on vitreous removal through a 25-gauge cutting system in the rabbit in vivo. Graefe’s Arch Clin Exp Ophthalmol. 2009;247(3):331–4.

    Article  CAS  Google Scholar 

  37. Sebag J, Ansari RR, Suh KI. Pharmacologic vitreolysis with microplasmin increases vitreous diffusion coefficients. Graefes Arch Clin Exp Ophthalmol. 2007;245(4):576–80.

    Article  CAS  PubMed  Google Scholar 

  38. Gandorfer A, Rohleder M, Sethi C, et al. Posterior vitreous detachment induced by microplasmin. Investig Ophthalmol Vis Sci. 2004;45(2):641–7.

    Article  Google Scholar 

  39. De Smet MD, Valmaggia C, Zarranz-Ventura J, Willekens B. Microplasmin: ex vivo characterization of its activity in porcine vitreous. Invest Ophthalmol Vis Sci. 2009;50(2):814–9.

    Article  PubMed  Google Scholar 

  40. Sakuma T, Tanaka M, Mizota A, Inoue J, Pakola S. Safety of in vivo pharmacologic vitreolysis with recombinant microplasmin in rabbit eyes. Invest Ophthalmol Vis Sci. 2005;46(9):3295–9.

    Article  PubMed  Google Scholar 

  41. Chen W, Huang X, Ma XW, Mo W, Wang WJ, Song HY. Enzymatic vitreolysis with recombinant microplasminogen and tissue plasminogen activator. Eye. 2008;22(2):300–7.

    Article  CAS  PubMed  Google Scholar 

  42. De Smet MD, Gandorfer A, Stalmans P, et al. Microplasmin intravitreal administration in patients with vitreomacular traction scheduled for vitrectomy: the MIVI-I trial. Ophthalmology. 2009;116(7):1349–55, 1355.e1341–2.

  43. Stalmans P, Delaey C, de Smet MD, et al. Intravitreal injection of microplasmin for treatment of vitreomacular adhesion: results of a prospective, randomized, sham-controlled phase II trial (the MIVI-IIT trial). Retina. 2010;30(7):1122–7.

    Article  PubMed  Google Scholar 

  44. Benz MS, Packo KH, Gonzalez V, et al. A placebo-controlled trial of microplasmin intravitreous injection to facilitate posterior vitreous detachment before vitrectomy. Ophthalmology. 2010;117(4):791–7.

    Article  PubMed  Google Scholar 

  45. Stalmans P, Benz MS, Gandorfer A, et al. Enzymatic vitreolysis with Ocriplasmin for vitreomacular traction and macular holes. N Engl J Med. 2012;367(7):606–15.

    Article  CAS  PubMed  Google Scholar 

  46. Sebag J, Buckingham B, Charles MA, Reiser K. Biochemical abnormalities in vitreous of humans with proliferative diabetic retinopathy. Arch Ophthalmol. 1992;110:1472–9.

    Article  CAS  PubMed  Google Scholar 

  47. Sebag J. Abnormalities of human vitreous structure in diabetes. Graefes Arch Clin Exp Ophthalmol. 1993;231:257–60.

    Article  CAS  PubMed  Google Scholar 

  48. Sebag J. Diabetic Vitreopathy (Guest Editorial). Ophthalmology. 1996;103:205–6.

    Article  CAS  PubMed  Google Scholar 

  49. Sebag J. Vitreoschisis in diabetic macular edema. Invest Ophthalmol Vis Sci. 2011;52(11):8455–6.

    Article  CAS  PubMed  Google Scholar 

  50. Novack RL, Staurenghi G, Girach A, Narendran N, Tolentino M. Safety of intravitreal Ocriplasmin for focal vitreo-macular adhesion in patients with exudative age-related macular degeneration. Ophthalmology. 2014. doi:10.1016/j.ophtha.2014.10.006.

  51. National Institute for Health and Care Excellence (NICE). Ocriplasmin for treating vitreomacular traction. London: National Institute for Health and Care Excellence (NICE); 2013. p. 52 (Technology appraisal guidance; no. 297).

  52. Stalmans P: Pharmacologic vitreolysis with ocriplasmin—clinical studies. In: Sebag J, editor. Vitreous—in health and disease, Ch VI.E.2. New York: Springer; 2014.

  53. Tibbetts MD, Reichel E, Witkin AJ. Vision loss after intravitreal Ocriplasmin: correlation of spectral-domain coherence tomography and electroretinography. JAMA Ophthalmol. 2014;132:487–90.

    Article  PubMed  Google Scholar 

  54. Fahim AT, Khan NW, Johnson MW. Acute panretinal structural and functional abnormalities after intravitreous Ocriplasmin injection. JAMA Ophthalmol. 2014;132:484–6.

    Article  CAS  PubMed  Google Scholar 

  55. Kim JE. Safety and complications of ocriplasmin: ocriplasmin, ocriplasmin; oh, how safe art thou? JAMA Ophthalmol. 2014;132(4):379–80.

    Article  PubMed  Google Scholar 

  56. Singh RP, Li A, Bedi R, Srivastava S, Sears JE, Ehlers JP, et al. Anatomical and visual outcomes following ocriplasmin treatment for symptomatic vitreomacular traction syndrome. Br J Ophthalmol. 2014;98:356–60.

    Article  PubMed  Google Scholar 

  57. Nudleman E, Ruby AAJ, Wolfe J. Ocriplasmin for vitreomacular adhesion: aftermarket experience and finding. Invest Ophthalmol Vis Sci. 2014 (ARVO);55:E-Abstract 301.

  58. Sebag J. The vitreous: structure, function, and pathobiology. New York: Springer; 1989.

    Book  Google Scholar 

  59. Stallmans P. Pharmacologic vitreolysis with ocriplasmin: clinical studies. In: Sebag J, editor. Vitreous in health and disease. New York: Springer; 2014. p. 853–61.

    Google Scholar 

Download references

Conflicts of interest

Matin Khoshnevis has no conflicts of interest that are relevant to the content of this article. Jerry Sebag has been a consultant to ThromboGenics, LLC, and is currently a speaker for Alcon, Inc. and ThromboGenics, LLC.

Author contributions

Matin Khoshnevis provided scientific content, as well drafting, reviewing, and revising the manuscript. Jerry Sebag made a substantial intellectual contribution by participating in drafting, reviewing, revising, and approving the manuscript. Dr. Sebag is the guarantor for the overall content.

Author information

Authors and Affiliations

  1. VMR Institute for Vitreous Macula Retina, 7677 Center Avenue, Suite 400, Huntington Beach, CA, 92647, USA

    Matin Khoshnevis & J Sebag MD, FACS, FRCOphth, FARVO

  2. University of California, Irvine School of Medicine, Irvine, CA, USA

    Matin Khoshnevis

Authors
  1. Matin Khoshnevis
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J Sebag MD, FACS, FRCOphth, FARVO
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to J Sebag MD, FACS, FRCOphth, FARVO.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Khoshnevis, M., Sebag, J. Pharmacologic Vitreolysis with Ocriplasmin: Rationale for Use and Therapeutic Potential in Vitreo-Retinal Disorders. BioDrugs 29, 103–112 (2015). https://doi.org/10.1007/s40259-015-0120-y

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40259-015-0120-y

Keywords

Search

Navigation