Surgical Stabilizer Assisted RVC With rtPA for CRVO

Study Overview
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Brief Summary
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This phase Ib study investigates the safety and efficacy of performing a retinal vein cannulation with recombinant tissue Plasminogen Activator infusion into a retinal vein with the help of an updated dedicated surgical stabiliser for the treatment of central retinal vein occlusion.

Detailed Description
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Investigator-initiated, unmasked, single-arm, mono-center, prospective, interventional case series phase Ib trial. In line with the previous phase I trial, this trial will be biphasic; first 3 patients will be included, when the procedure and product prove to be safe and an added value is noted from the intra-operative OCT-angiography, another 3 will be included afterwards (≥21 days between last inclusion of the first group and first inclusion of the second group).

Official Title
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Phase Ib Study on Surgical Stabilizer Assisted Retinal Vein Cannulation (RVC) With tPA Infusion Confirmed by Intraoperative Angio-optical Coherence Tomography (Angio-OCT) for the Treatment of Central Retinal Vein Occlusion (CRVO).

Conditions
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Central Retinal Vein Occlusion

Intervention / Treatment
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* Procedure: Vitrectomy with retinal vein cannulation and intravenous rtPA (Actilyse) infusion up to 1mg.
* Drug: Intravenous Infusion


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients aged over 18 years Recent diagnosis (<8 weeks) of CRVO Recent onset of symptoms (<12 weeks) Visual acuity < 5/10 in study eye Visual acuity >1/10 in fellow eye Central macular thickness >250µm Signed informed consent prior to inclusion Exclusion Criteria: Fluorescein allergy Active neovascularization Eye disease other than CRVO or Cataract decreasing central vision History of retinal surgery High myopia (> -10D) Contraindication for the use of systemic anticoagulant medication Extensive macular ischemia noted on fluo-angiography

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RVC with tPA for CRVO<br>Single arm phase I open label study were CRVO patients will have a vitrectomy with retinal vein cannulation and a single infusion of tPA (0.25mg/ml) intravenously with a maximum dose of 1mg. | Procedure: Vitrectomy with retinal vein cannulation and intravenous rtPA (Actilyse) infusion up to 1mg.<br>* Standard 3-port pars plana vitrectomy with surgical stabilizer assisted ( surgical robot) retinal vein cannulation with recombinant tissue Plasminogen Activator (Actilyse-0.25mg/ml) infusion with a maximal dose of 1mg..<br>Drug: Intravenous Infusion<br>* Intravenous infusion in a retinal vein with rtPA (Actilyse 0.25mg/ml).<br>* Other names: Recombinant tissue Plasminogen Activator (rtPA);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Success rate of retinal vein cannulation | successful cannulation defined as peroperatively seen washout of blood in the cannulated retinal vein. The success rate is defined as the number of successful cannulations divided by the total number of cannulation attempts. | 10 min | 
| number of intervention-related surgical complications | These exist of the intra-operative occurence of: retinal vein tear (visually seen by the surgeon) uncontrollable vitreous cavity hemorrhage (as seen by the surgeon) retinal tear in the proximity of the cannulation site (as seen by the surgeon) intra-/subretinal injection (as seen by the surgeon) breakage of the needle (as seen by the surgeon) failure of stabilizer in holding the instrument immobilized in a certain position (as seen by the surgeon) | 7 days | 
| duration of infusion | The time of infusion measured during surgery with a maximum of 10 minutes | 10 minutes | 
| number of intervention-related non-surgical complications | The postoperative occurence of: hemorrhagic cerebrovascular accidents due to rtPA (confirmed by CT-scan and neurological examination after referral to the neurologist) large hemorrhage elsewhere to be related with the use of rtPA (as confirmed by clinical examination and/or CT-scan/ultrasound after referral to vascular surgeon) | 7 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change in visual acuity after 6 to 8 weeks | best corrected visual acuity tested with ETDRS chart | 6-8 weeks | 
| change in central macular thickness after 6 to 8 weeks | measurement of central macular thickness with spectral domain-OCT | 6-8 weeks | 
| intra-/postoperative complications not related to the surgical stabilizer / retinal vein cannulation / rtPA | - complications of intraocular surgery: wound leak tested with concentrated fluorescein (Seidel effect present/absent) endophthalmitis as seen with the slit lamp/ultrasonography post-operative macular edema objectivated with OCT imaging vitreous hemorrhage > 2 weeks after intervention as seen at the slit lamp and confirmed with ultrasonography development of neovascularization as seen at the slit lamp / fluorescein angiogram | 7 days | 
| intra-/postoperative complications not related to the surgical stabilizer / retinal vein cannulation / rtPA | - complications during cataract surgery: iris hemorrhage as seen through the surgical microscope (present/absent) choroidal swelling as seen through the surgical microscope (present/absent) suprachoroidal hemorrhage as seen through the surgical microscope (present/absent) capsule tear as seen through the surgical microscope (present/absent) dropped lens/intraocular lens (IOL). Recombinant tissue Plasminogen Activator (rtPA) as seen through the surgical microscope (occurred/not occurred) | 7 days | 
| intra-/postoperative complications not related to the surgical stabilizer / retinal vein cannulation / rtPA | - complications during vitrectomy: retinal tears as seen through the surgical microscope (occurred/not occurred) vitreous hemorrhage as seen through the surgical microscope (occurred/not occurred) choroidal swelling as seen through the surgical microscope (present/absent) suprachoroidal hemorrhage as seen through the surgical microscope (present/absent) | 7 days | 
| change in retinal flow intraoperatively visualized with OCT-angiography | OCT-angiography visualized flow inside the retinal veins with the intraoperative OCT device; if there is flow the blood vessel is imaged in bright white, if there is no flow the blood vessel is not visible with angio-OCT. | 1 hour |