PURPOSE: To evaluate the safety and preliminary efficacy of 4 doses and several exposure times of intravitreal microplasmin given before pars plana vitrectomy for vitreomacular traction maculopathy.
DESIGN: A multicenter, prospective, uncontrolled, dose-escalation, phase I/II clinical trial.
PARTICIPANTS: Sixty patients enrolled into 6 successive cohorts.
INTERVENTION: A single intravitreal injection of microplasmin at 1 of 4 doses (25, 50, 75, or 125 microg in 100 microl) administered either 1 to 2 hours, 24 hours, or 7 days before planned pars plana vitrectomy.
MAIN OUTCOME MEASURES: For safety, a complete ophthalmologic examination, fundus photography, fluorescein angiography, Humphrey visual fields, and electrophysiology; for efficacy, posterior vitreous detachment (PVD) induction as assessed by B-scan ultrasound and ease of PVD induction at the time of vitrectomy.
RESULTS: The use of microplasmin led to a progressively higher incidence of PVD induction on ultrasonography with increasing time exposure. A PVD before surgery was observed with 25 microg microplasmin in 0, 2, and 5 patients with increasing exposures (2 hours, 24 hours, 7 days). With increasing dose, a PVD before surgery was observed by ultrasound as follows: 25 microg, 0; 50 microg, 1; 75 microg, 2; 125 microg, 3. However, at surgery, with a 125-microg dose, these patients had a discontinuous layer of vitreous present on the retinal surface resulting from the induction of an anomalous PVD in the form of vitreoschisis. One retinal detachment developed shortly after administration of microplasmin. Two developed after surgery. There were no other safety concerns.
CONCLUSIONS: Results from this initial clinical trial evaluating intravitreal microplasmin show the drug to be well tolerated and capable of inducing a pharmacologic PVD in some patients. These results warrant evaluation of microplasmin in larger, controlled trials.
|Pages (from-to)||1349-55, 1355.e1-2|
|Publication status||Published - Jul 2009|
- Aged, 80 and over
- Eye Diseases/diagnosis
- Fibrinolysin/administration & dosage
- Fluorescein Angiography
- Macula Lutea/drug effects
- Middle Aged
- Peptide Fragments/administration & dosage
- Prospective Studies
- Recombinant Proteins/administration & dosage
- Retinal Diseases/diagnosis
- Vitreous Body/drug effects
- Vitreous Detachment/diagnostic imaging