Phase I RVC With Ocriplasmin for CRVO
Condition: Central Retinal Vein Occlusion
MeSH terms: Retinal Vein Occlusion
Study type: Interventional
Phase: Phase 1

Summary: 
      In central retinal vein occlusion (CRVO) a blood clot blocks the venous outflow of the entire
      retinal circulation. This leads to retinal and vitreous hemorrhages, retinal edema and
      neovascularization. The development of a microneedle and surgical stabilizer made it possible
      to perform a prolonged (10 minutes) retinal vein cannulation with infusion of Ocriplasmin.
      Ocriplasmin has the advantage over tissue Plasminogen Activator (tPA) that it already is an
      active enzyme and a strong fibrinolyticum. This study aims to investigate the feasibility and
      safety of local intravenous Ocriplasmin for CRVO.
    

Detailed description: 
      Central retinal vein occlusion (CRVO) is the second most common source of permanent blindness
      in the Western world after diabetic retinopathy. By blocking the outflow pathway for the
      retinal circulation, visual prognosis is bad on the short and long term. Currently, treatment
      is mostly focused on treating the secondary effects: macular edema and neovascularization
      with antiVEGF and/or corticosteroid intravitreal injections and retinal laser
      photocoagulation. There is however a surgical treatment aimed at displacing the blood clot; a
      radial optic neurotomy. During this surgical treatment, the vitreous is removed by
      vitrectomy, after which a radial incision is made in the optic disc. The target of this
      incision is to open the canal in the lamina cribrosa to improve the blood flow in the central
      retinal vein. Since the outcome of this procedure is variable and has its inherent risks,
      mainly because the incision can damage the central retinal artery which is adjacent to the
      central vein, this procedure is not routinely performed in all vitreoretinal centers.

      Following the recent development of a surgical stabilizer and microneedle suitable for
      retinal vein cannulations, the option for local intravenous administration of fibrinolytic
      drugs exists. This phase I study aims to investigate the feasibility and safety of surgical
      stabilizer assisted retinal vein cannulation with local intravenous infusion of Ocriplasmin
      to dissolve the clot clogging the central retinal vein. Ocriplasmin is the small active part
      of the larger plasmin molecule. Plasmin itself is formed by enzymatic conversion from
      plasminogen, a process that is mediated by tissue plasminogen activator (tPA). The amount of
      plasmin that can be produced is thus highly dependent on the amount of plasminogen that is
      present nearby the clot. By using Ocriplasmin, this intermediate step can be skipped and the
      clot will be targeted directly and during the entire time of infusion. By being able to get
      infusion times up to 10 minutes, abundant clot exposure to Ocriplasmin is guaranteed.

      Inclusion will be offered to patients presenting with a recent CRVO, a vitrectomy will be
      performed augmented with retinal vein cannulation and infusion of ocriplasmin during 10
      minutes.

      Patients presenting with a recent CRVO (<2weeks) will be offered inclusion to undergo a
      vitrectomy with subsequent prolonged retinal vein cannulation and infusion of Ocirplasmin.
      The surgery is done by placing a microneedle in one of the branch retinal veins at the border
      of the optic disc. To increase the safety of this procedure a surgical stabilizer was
      developed. This procedure was abundantly tested and refined in multiple in vivo porcine
      experiments and the medication (Ocriplasmin) has already been tested for fibrinolytic
      activity used in 100-fold higher dosis intravenously and intra-arterially.

      After the surgery, standard of care follow up with a comprehensive ophthalmological
      examination and technical investigations is foreseen. The primary outcome measures of this
      safety and feasiblity study are: technical success to cannulate the retinal vein and inject
      ocriplasmin to remove the blood clot, number of intervention-related (surgical or
      pharmacological) complications, duration of infusion.

      If necessary; depending on the disease evolution, additional interventions like intravitreal
      antiVEGF, steroids or laser photocoagulation can be performed.
    

Intervention name(s): Ocriplasmin intravenously
Intervention type(s): Drug
Intervention description(s): Retinal vein cannulation with Ocriplasmin infusion
Other intervention name(s): Jetrea
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Central retinal vein occlusion; Retinal endovascular surgery; Retinal vein cannulation; Ocriplasmin