MIVI‐IIT 2010.

Methods	Study design: RCT, single treated eye. Number randomised: 60 total; 48 microplasmin; 12 sham injection. Exclusions after randomisation: none. Number analysed: at 28 days and 6 months; 60 total; 48 microplasmin; 12 sham injection. Unit of analysis: eyes. Losses to follow‐up: 0 participants total. How was missing data handled? no missing data. Power calculation: not documented.
Participants	Country: Belgium. Mean age: 70.0 years overall; 69.9 years for ocriplasmin group; 70.0 years for sham injection group. Gender: 33/60 (55%) women, 27/60 (45%) men total; 27/48 (56%) women, 21/48 (44%) men in microplasmin group; 6/12 (50%) women, 6/12 (50%) men in sham injection group. Inclusion criteria: aged > 18 years; partial PVD on ultrasound examination; OCT evidence of at least a partial attachment in the foveal area, resulting in a macular thickness of ≥ 250 μm; BCVA ≤ 20/40 in study eye; BCVA ≥ 20/400 in fellow eye. Exclusion criteria: active PDR; high myopia (axial length > 26 mm); previous vitrectomy or uncontrolled glaucoma; previous intravitreal injections in the past 3 months in study eye; intraocular surgery or laser photocoagulation in the past 3 months in study eye; rhegmatogenous retinal detachment in either eye. Equivalence of baseline characteristics: no; more participants in microplasmin group had tractional diabetic macular oedema compared with sham injection group.
Interventions	Intervention 1: single intravitreal injection microplasmin 125 µg. Intervention 2: single intravitreal injection microplasmin 75 µg. Intervention 3: single intravitreal injection microplasmin 175 µg. Intervention 4: intravitreal injection of microplasmin 125 µg at baseline, followed by a further microplasmin 125 µg intravitreal injection at 28 days if VMA was still present, followed by a further microplasmin 125 µg intravitreal injection at 56 days after baseline if VMA was still present. Comparator: sham injection (conjunctiva touched with a blunt needle by a non‐masked investigator and no injection given). Length of follow‐up: planned 180 days, actual 180 days. As the recommended dose of ocriplasmin is 125 µg, and this is the subject of this review, only data from the first and fourth intervention arms were analysed.
Outcomes	Primary outcome, as defined in study reports: "the primary outcome of this study was total PVD induction at Day 14, as assessed by a central reading centre." Secondary outcomes, as defined in study reports: total PVD at other time points assessed by the central reading centre and investigators; resolution of index condition (VMA or MH); resolution of VMA; progression of PVD; need for vitrectomy; resolution of macular oedema; change in BCVA; BCVA 5‐, 10‐ and 15‐letter improvement. Adverse events reported: yes. Intervals at which outcomes assessed: 3, 7, 14, 28, 90 and 180 days.
Notes	Funding sources: study sponsored by ThromboGenics NV. Study period: 2 years; 2007‐2009. Reported subgroup analyses: yes. Full results of study were presented at EURetina 2009, Nice, France. NCT00435539.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Method of sequence generation for the MIVI‐IIT RCT not described. Quote: "Four cohorts of 15 patients were randomised as 4:1 to treatment or sham injection, resulting in 12 patients receiving microplasmin and 3 patients receiving the sham injection in each cohort." p. 1123.
Allocation concealment (selection bias)	Unclear risk	Insufficient information documented to assess allocation concealment. Quote: "Four cohorts of 15 patients were randomised as 4:1 to treatment or sham injection, resulting in 12 patients receiving microplasmin and 3 patients receiving the sham injection in each cohort." p. 1123.
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Sham injection was performed, rather than actual placebo injection. Quote: "In the patients receiving a sham injection, microplasmin was prepared in the same manner, but instead of an intraocular injection, the conjunctiva was touched with a blunt needle by a nonmasked investigator and no injection was given." p. 1123.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote: "All patient examinations before drug allocation and in the 6‐month follow‐up period after the last injection were performed by masked investigators and study personnel." p. 1123. "Posterior vitreous detachment status and macular thickness were assessed by the investigator as well as by a central reading center (CRC), located in Munich, Germany." p. 1124.
Incomplete outcome data (attrition bias) All outcomes	Low risk	No incomplete outcome data.
Selective reporting (reporting bias)	Low risk	All outcomes defined in trial registry were reported.
Other bias	Low risk