The Microplasmin for Intravitreal Injection-Traction Release Without Surgical Treatment (MIVI-TRUST) Studies
Phase III data is available from two multicenter, randomized, double-blind, placebo-controlled clinical trials, referred to collectively as the MIVI-TRUST studies, completed between 2008 and 2010 [
6]. Outcomes revealed statistically significant non-surgical achievement of primary and secondary study endpoints as well as improvement in visual acuity and visual function compared to placebo. Based on these results, the U.S. Food and Drug Administration approved use of intravitreal ocriplasmin for the treatment of VMT in 2012.
In the MIVI-TRUST studies, 464 of the 652 enrolled eyes received a single intravitreal injection of 0.125 mg ocriplasmin with follow-up to 6 months. At the day 28 post injection time-point, eyes receiving ocriplasmin exhibited greater release of VMA (primary endpoint, 26.5% vs. 10.1%,
p < 0.001), closure of macular hole (40.6% vs. 10.6%,
p < 0.001), and presence of full posterior vitreous detachment (13.4% vs. 3.7%,
p < 0.001) compared to eyes receiving vehicle injection [
6].
Visual function, as measured by the National Eye Institute Visual Function Questionnaire (NEI VFQ-25), improved in eyes treated with ocriplasmin in the MIVI-TRUST trials. Varma et al. revealed that eyes treated with ocriplasmin had greater mean improvement in baseline NEI VFQ-25 scores (mean change +3.4 versus 0.7,
p = 0.005) and were more likely to have a >5-point improvement in VFQ-25 scores (36.0% versus 27.2%,
p = 0.03) compared to eyes treated with vehicle injection [
7]. In addition, eyes treated with ocriplasmin had greater improvement in multiple VFQ-25 sub-scale scores, including general vision (
p = 0.003), distance vision activities (
p = 0.03), and driving difficulty (
p = 0.03), and were less likely to have >5-point worsening of VFQ-25 composite scores (15.0% vs. 24.3%,
p = 0.005) compared to the placebo group [
7].
Gandorfer et al. similarly analyzed visual function in eyes enrolled in the MIVI-TRUST trials, with added insight as to best-corrected visual acuity (BCVA) [
8]. The authors noted that ≥2-line improvement in BCVA was more likely in eyes treated with ocriplasmin at month 6 compared to vehicle injection (28.0% vs. 17.1%,
p = 0.003). Moreover, achievement of VMA release or nonsurgical FTMH closure was strongly associated with visual acuity gains. Multivariate analysis revealed that in eyes with VMT treated with ocriplasmin, resolution of VMA at day 28 was associated with ≥2-line improvement in BCVA [
p = 0.006, odds ratio (OR) 2.023]. This was also true in eyes with FTMH, as nonsurgical hole closure at day 28 was associated with ≥2-line improvement in BCVA (
p < 0.001, OR 6.716).
Haller et al. performed post hoc subgroup analysis of the MIVI-TRUST data to better identify features associated with VMA release with ocriplasmin treatment [
9]. The authors reported age younger than 65, VMA adhesion diameter ≤1500 μm, phakic status, presence of FTMH, and absence of ERM as factors associated with nonsurgical resolution of VMA at day 28. In regards to FTMH, non-surgical hole closure at month 6 was correlated strongly with hole size, as closure was achieved in 58.3% of holes ≤250 μm (
p < 0.001 versus vehicle), 36.8% of holes >250 and ≤400 μm (
p = 0.009 versus vehicle), and in 0% of holes >400 μm.
Ocriplasmin for Treatment for Symptomatic Vitreomacular Adhesion Including Macular Hole (OASIS)
Additional clinical trial data is available from the OASIS study [
10]. In this trial, 220 eyes were randomized in a 2:1 fashion to either a single injection of 0.125 mg ocriplasmin (146 eyes) or vehicle injection (74 eyes). Follow-up in this study was 24 months, considerably longer than that of the MIVI-TRUST trials. In this study, statistically significant nonsurgical release of VMT was observed in eyes treated with ocriplasmin compared to vehicle injection (41.7% versus 6.2%,
p < 0.01), similar to the findings of the MIVI-TRUST trials. While FTMH closure occurred at a higher rate in the ocriplasmin group, this did not reach statistical significance (30% versus 15.4%,
p = 0.163) [
10].
OASIS data, with longer follow-up, also revealed that the statistically significant difference in VMT release rate with ocriplasmin was maintained to 24 months post-treatment. In addition, eyes initially treated with ocriplasmin were more likely to achieve a ≥2-line gain in visual acuity at 2 years (50.5% versus 39.1%, p = 0.114), regardless of initial VMT release and need for subsequent vitrectomy, though this did not achieve statistical significance.