title: Ocriplasmin for diabetic retinopathy.
abstract: BACKGROUND
  Diabetic retinopathy is a serious public health concern. Vision impairment follows from intraocular vascular proliferation known as proliferative diabetic retinopathy (PDR) and/or from diabetic macular edema (DME). Clinical acumen and a recent meta-analysis of published studies suggest that the presence of a posterior vitreous detachment (PVD) reduces the risk of developing PDR, and has a favourable impact on DME. Pharmacologic vitreolysis by ocriplasmin or other agents may provide a minimally invasive method of achieving a PVD. If demonstrated in appropriate clinical studies including randomized trials, it would provide an interesting approach to prevent advanced and blinding stages of diabetic retinopathy, particularly in areas where access to care is limited.
  
  
  METHODS
  The current epidemiology of diabetic retinopathy is reviewed as well as the role of the vitreous and its separation from the retina known as a PVD in DR based on a recent meta-analysis of published literature regarding the contribution of complete, partial or absent PVD to PDR and DME. The principles underlying vitreolysis and the induction of PVD are reviewed as well as the challenges faced by a pharmacologic approach. The results of clinical trials on the use of ocriplasmin are analyzed regarding its possible use in DR.
  
  
  CONCLUSIONS
  Ocriplasmin has the ability to liquefy the vitreous and induce a PVD in a statistically significant number of patients. However, current studies on patients with vitreomacular adhesion and traction suggest that the majority of patients would not achieve a PVD with a single injection. As shown in the meta-analysis, a complete PVD is required to significantly reduce the risk of PDR, while a partial PVD may worsen the prognosis. If a strategy can be developed that insures a complete PVD within an appropriate time interval, the prevention of PDR might become a realistic target for ocriplasmin or other vitreolytic agents. In DME, release of traction whether complete or partial is associated with a reduction in DME, which in several cases has resulted in improved vision. While no studies have been conducted on the use of ocriplasmin or other vitreolytic agents in DR, a few studies using plasmin indicate that it is likely to have a beneficial effect in DME. Based on the information available, randomized clinical trials would be required to evaluate the clinical relevance of ocriplasmin and other potential vitreolytic agents in both forms of DR. Such trials could determine the efficacy of this strategy as compared to prophylatic laser particularly in high-risk populations. New follow-up and treatment strategies would also be required should initial studies be encouraging.
authors.affiliation: Retina and Inflammation division, MIOS sa , Avenue du Léman 32, Lausanne 1005 , Switzerland mddesmet1@mac.com.
authors.forename: Marc D
authors.initials: MD
authors.lastname: de Smet
authors.forename: Miguel
authors.initials: M
authors.lastname: Castilla
mesh_terms: D002986:Clinical Trials as Topic; D003930:Diabetic Retinopathy / Q000628:therapy*; D004341:Drug Evaluation; D005341:Fibrinolysin / Q000627:therapeutic use*; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D006801:Humans; D010446:Peptide Fragments / Q000627:therapeutic use*
chemical_list: D005343:Fibrinolytic Agents; D010446:Peptide Fragments; C054561:microplasmin; D005341:Fibrinolysin