Spontaneous posterior vitreous detachment (PVD) has been seen in some patients following injection of microplasmin (ThromboGenics, Leuven, Belgium). Prof. Peter Stalmans, of University Hospitals, Leuven, Belgium, presented data from the phase 2a Microplasmin in Surgical Vitrectomy (MIVI-IIT) trial, a randomized, double-masked, sham-controlled study in which 30 patients were assigned to receive either 75- or 125-µg microplasmin or sham injection. Prof. Stalmans spoke at the American Society of Retina Specialists 25th Annual Meeting in Indian Wells, California.1

Among the patients who were recruited across Europe, 24 received microplasmin, and six received sham injections. According to a news release from ThromboGenics, the trial showed clear benefits from therapy, with nine of the 24 microplasmin-treated patients having resolution of vitreomacular traction—including macular hole closure in two of the four macular hole cases—without the need for vitrectomy (Figures 1 through 8).

UNMASKING AT 1 MONTH
Included patients had vitreous traction on macula, according to Prof. Stalmans, macular thickness of ≥250 µm, visual acuity of ²20/40 in the study eye, and ≥20/400 in the fellow eye. The follow-up was 6 months, with unmasking at 1 month.

Microplasmin therapy was safe and well tolerated in the trial. There were no retinal tears, retinal detachments, cases of endophthalmitis, or other adverse events related to the study agent. According to the company, the safety results from clinical data to date have led to a decision to recruit 15 additional patients to evaluate a higher dose (175 µg) of microplasmin.

Microplasmin alone may be sufficient to induce PVD—preventing the need for vitrectomy—and be beneficial in the prevention of serious posterior segment disorders, including macular holes, diabetic retinopathy (DR), and diabetic macular edema (DME).

Microplasmin is a truncated form of plasmin, an enzyme that dissolves protein formations that are crucial to thrombus formation; similar protein formations are seen linking the vitreous to the retina in the eye.

Prof. Stalmans, the study's principal investigator, said: "The results from the study . . . clearly indicate the potential for microplasmin to become a more convenient, less invasive, hence more patient-friendly treatment for vitreomacular traction. The fact that we have been able to clearly show that microplasmin can achieve clinically important outcomes such as traction release and macular hole closure without surgery augurs well for the future development of this novel treatment."

CLINICAL TRIAL BACKGROUND
A phase 2 trial with microplasmin as a surgical adjunct for vitrectomy and the induction of PVD has been completed. This trial, MIVI I, demonstrated that microplasmin was generally well tolerated, with PVD induction observed in some patients (including five of 10 patients in whom microplasmin was injected 7 days before surgery).

Macular hole occurs in about 0.14% of the general population, leading to estimates of approximately 400,000 cases in the United States and up to 1 million in the industrialized world, according to the company. Potential nonsurgical applications for microplasmin include treatment of DME and DR. DR is the leading cause of blindness among working-age adults, whereas DME is the leading cause of decreased vision in patients with DR. Aproximately 750,000 patients in the United States suffer from DME.

MIVI III TRIAL
David M. Brown, MD, an investigator for the MIVI III trial, presented cases from this trial at the Retina Society Annual Meeting in Boston.2 MIVI III is a placebo-controlled trial being performed in the United States among patients scheduled to undergo vitrectomy.

Options in these patients consist of continued observation, pars plana vitrectomy with a hyaloid peel, or enrollment in the MIVI III phase 2b trial, in which the patient would be randomized to one of three dilutions of microplasmin or normal saline intravitreal injection.

Postmortem and in vivo experiments with microplasmin in four separate animal models demonstrated safety and dose-dependent efficacy, Dr. Brown said. Pharmacologic vitreolysis was achieved, showing detachment of vitreous from retinal surface and liquefaction of the vitreous gel.

Patients with nonproliferative vitreoretinal disease, in whom vitrectomy is indicated, are being randomized in a placebo-controlled, double-masked, parallel-group, dose-ranging study. The 120 patients are being randomized to one of four arms: placebo, 25 µg, 75 µg, and 125 µg. A pars plana vitrectomy will be performed 7 days after injection (unless the induction of a PVD prior to surgery accomplishes the anatomic goal without surgery). Patients are followed for 6 months, and the primary analysis will be based on a 28-day postoperative time point (subsequent secondary analysis for safety based on 6-month follow-up time point).

There will be continued follow-up of the US and worldwide studies for safety and efficacy, Dr. Brown said. This treatment could potentially be used as first-line therapy for cases of vitreomacular traction and impending macular hole, as an adjunct for vitreoretinal surgery, as well as play a role in the diabetic vitreous.

Peter Stalmans, MD, PhD, is in the Department of Ophthalmology, University Hospitals of Leuven, Leuven, Belgium. Prof. Stalmans states that he has no financial interest in the company or product mentioned. He may be reached at peter.stalmans@uzleuven.be.

David M. Brown, MD, is with Greater Houston Retina Research and the Methodist Hospital, Houston. He states that he recieves research support from ThromboGenics; he may be reached at dmbmd@houstonretina.com.