Trial Outcomes & Findings for Ocriplasmin for Treatment for Symptomatic Vitreomacular Adhesion Including Macular Hole (NCT NCT01429441)

NCT ID: NCT01429441

Last Updated: 2016-03-14

Results Overview

Pharmacological VMA resolution without anatomical defect, based on SD-OCT and determined by the masked central reading center (CRC), with post-resolution vitrectomy considered as a failure. Missing data were imputed using the last observation carried forward (LOCF) method.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 220 participants
• Primary outcome timeframe: Day 28
• Results posted on: 2016-03-14

Participant Flow

This study was conducted at 25 study sites in the United States. The first subject was enrolled on 02 November 2011 and the last subject completed the study on 22 October 2014.

Participant milestones

Measure	Ocriplasmin Subjects in the ocriplasmin group received a single intravitreal injection of ocriplasmin 0.125mg	Sham Subjects in the sham group received a single sham injection
Overall Study STARTED	146	74
Overall Study COMPLETED	108	51
Overall Study NOT COMPLETED	38	23

Reasons for withdrawal

Measure	Ocriplasmin Subjects in the ocriplasmin group received a single intravitreal injection of ocriplasmin 0.125mg	Sham Subjects in the sham group received a single sham injection
Overall Study Adverse Event	5	1
Overall Study Death	0	2
Overall Study Lost to Follow-up	5	2
Overall Study Physician Decision	1	0
Overall Study Withdrawal by Subject	27	18

Baseline Characteristics

Ocriplasmin for Treatment for Symptomatic Vitreomacular Adhesion Including Macular Hole

Baseline characteristics by cohort

Measure	Ocriplasmin n=146 Participants Subjects in the ocriplasmin group received a single intravitreal injection of ocriplasmin 0.125mg	Sham n=74 Participants Subjects in the sham group received a single sham injection	Total n=220 Participants Total of all reporting groups
Age, Continuous	69.4 years STANDARD_DEVIATION 9.99 • n=5 Participants	68.5 years STANDARD_DEVIATION 10.94 • n=7 Participants	69.1 years STANDARD_DEVIATION 10.30 • n=5 Participants
Sex: Female, Male Female	103 Participants n=5 Participants	45 Participants n=7 Participants	148 Participants n=5 Participants
Sex: Female, Male Male	43 Participants n=5 Participants	29 Participants n=7 Participants	72 Participants n=5 Participants

PRIMARY outcome

Timeframe: Day 28

Population: Full Analysis Set (FAS): The FAS is the set of all randomized subjects who received the initial treatment, and for whom data of at least 1 post-injection efficacy assessment was present. Two (2) subjects (1 in each treatment group) were excluded from the FAS as they withdrew consent and did not attend any of the post-injection visits.

Pharmacological VMA resolution without anatomical defect, based on SD-OCT and determined by the masked central reading center (CRC), with post-resolution vitrectomy considered as a failure. Missing data were imputed using the last observation carried forward (LOCF) method.

Outcome measures

Measure	Ocriplasmin n=145 Participants Subjects in the ocriplasmin group received a single intravitreal injection of ocriplasmin 0.125mg	Sham n=73 Participants Subjects in the sham group received a single sham injection
Proportion of Subjects With Pharmacological Vitreomacular Adhesion (VMA) / (Vitreomacular Traction [VMT]) Resolution at Day 28	41.7 Percentage (weighted across strata) Interval 33.7 to 49.8	6.2 Percentage (weighted across strata) Interval 0.9 to 11.6

SECONDARY outcome

Timeframe: Month 24

Population: FAS. 1 subject did not have BCVA results at baseline and was excluded from this analysis.

≥2 lines improvement in BCVA from baseline, irrespective of vitrectomy. Missing data were imputed using the LOCF method.

Outcome measures

Measure	Ocriplasmin n=144 Participants Subjects in the ocriplasmin group received a single intravitreal injection of ocriplasmin 0.125mg	Sham n=73 Participants Subjects in the sham group received a single sham injection
Proportion of Subjects With a ≥2 Lines Improvement in Best-corrected Visual Acuity (BCVA) From Baseline at Month 24	50.5 Percentage (weighted across strata) Interval 42.4 to 58.5	39.1 Percentage (weighted across strata) Interval 28.3 to 49.9

Adverse Events

Ocriplasmin

Serious events: 49 serious events

Other events: 132 other events

Deaths: 0 deaths

Sham

Serious events: 27 serious events

Other events: 57 other events

Deaths: 0 deaths

Serious adverse events

Measure	Ocriplasmin n=146 participants at risk Subjects in the ocriplasmin group received a single intravitreal injection of ocriplasmin 0.125mg	Sham n=74 participants at risk Subjects in the sham group received a single sham injection
Eye disorders Macular hole	14.4% 21/146 • Number of events 21 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.	12.2% 9/74 • Number of events 9 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.
Eye disorders Retinal detachment	2.1% 3/146 • Number of events 3 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.	1.4% 1/74 • Number of events 1 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.
Eye disorders Vitreous adhesions	1.4% 2/146 • Number of events 2 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.	2.7% 2/74 • Number of events 2 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.
Eye disorders Blindness transient	0.68% 1/146 • Number of events 1 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.	0.00% 0/74 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.
Eye disorders Iridocyclitis	0.68% 1/146 • Number of events 1 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.	0.00% 0/74 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.
Eye disorders Night blindness	0.68% 1/146 • Number of events 1 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.	0.00% 0/74 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.
Eye disorders Pupillary reflex impaired	0.68% 1/146 • Number of events 1 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.	0.00% 0/74 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.
Eye disorders Retinal tear	0.68% 1/146 • Number of events 1 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.	2.7% 2/74 • Number of events 2 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.
Eye disorders Retinal toxicity	0.68% 1/146 • Number of events 1 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.	0.00% 0/74 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.
Eye disorders Retinal vasculitis	0.68% 1/146 • Number of events 1 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.	0.00% 0/74 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.
Eye disorders Visual acuity reduced	0.00% 0/146 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.	1.4% 1/74 • Number of events 1 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.
Cardiac disorders Acute myocardial infarction	0.68% 1/146 • Number of events 1 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.	0.00% 0/74 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.
Cardiac disorders Angina pectoris	0.68% 1/146 • Number of events 1 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.	0.00% 0/74 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.
Cardiac disorders Atrial fibrillation	0.68% 1/146 • Number of events 2 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.	0.00% 0/74 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.
Cardiac disorders Myocardial infarction	0.68% 1/146 • Number of events 1 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.	0.00% 0/74 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.
Cardiac disorders Cardiac failure	0.00% 0/146 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.	1.4% 1/74 • Number of events 1 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.
Cardiac disorders Cardiac failure congestive	0.00% 0/146 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.	1.4% 1/74 • Number of events 1 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.
Infections and infestations Cellulitis	0.68% 1/146 • Number of events 1 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.	1.4% 1/74 • Number of events 1 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.
Infections and infestations Diverticulitis	0.68% 1/146 • Number of events 1 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.	0.00% 0/74 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.
Infections and infestations Lobar pneumonia	0.68% 1/146 • Number of events 1 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.	0.00% 0/74 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.
Infections and infestations Localized infection	0.68% 1/146 • Number of events 1 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.	0.00% 0/74 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.
Infections and infestations Coccidioidomycosis	0.00% 0/146 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.	1.4% 1/74 • Number of events 1 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.
Infections and infestations Influenza	0.00% 0/146 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.	1.4% 1/74 • Number of events 1 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.
Infections and infestations Pneumonia	0.00% 0/146 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.	1.4% 1/74 • Number of events 1 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.
Infections and infestations Sepsis	0.00% 0/146 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.	1.4% 1/74 • Number of events 1 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.
Infections and infestations Urinary tract infection	0.00% 0/146 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.	1.4% 1/74 • Number of events 3 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.
Investigations Intraocular pressure increased	2.1% 3/146 • Number of events 3 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.	2.7% 2/74 • Number of events 4 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.
Investigations Retinogram abnormal	0.68% 1/146 • Number of events 1 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.	0.00% 0/74 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adrenal gland cancer	0.68% 1/146 • Number of events 1 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.	0.00% 0/74 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adrenocortical carcinoma	0.68% 1/146 • Number of events 1 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.	0.00% 0/74 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gastrointestinal stromal tumor	0.68% 1/146 • Number of events 1 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.	0.00% 0/74 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma	0.68% 1/146 • Number of events 1 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.	0.00% 0/74 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder neoplasm	0.00% 0/146 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.	1.4% 1/74 • Number of events 1 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Chronic myelomonocytic leukemia	0.00% 0/146 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.	1.4% 1/74 • Number of events 1 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Endometrial cancer stage II	0.00% 0/146 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.	1.4% 1/74 • Number of events 1 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Intraductal proliferative breast lesion	0.00% 0/146 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.	1.4% 1/74 • Number of events 1 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.
Nervous system disorders Cerebrovascular accident	2.1% 3/146 • Number of events 3 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.	0.00% 0/74 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.
Nervous system disorders Dizziness	0.00% 0/146 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.	1.4% 1/74 • Number of events 1 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.
Nervous system disorders Transient ischemic attack	0.00% 0/146 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.	1.4% 1/74 • Number of events 1 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.
Gastrointestinal disorders Inguinal hernia	0.68% 1/146 • Number of events 1 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.	0.00% 0/74 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.
Gastrointestinal disorders Small intestinal obstruction	0.68% 1/146 • Number of events 1 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.	0.00% 0/74 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.
Gastrointestinal disorders Large intestinal stenosis	0.00% 0/146 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.	1.4% 1/74 • Number of events 1 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.
Injury, poisoning and procedural complications Burns third degree	0.68% 1/146 • Number of events 1 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.	0.00% 0/74 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.
Injury, poisoning and procedural complications Hip fracture	0.68% 1/146 • Number of events 1 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.	0.00% 0/74 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.
Injury, poisoning and procedural complications Abdominal wound dehiscence	0.00% 0/146 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.	1.4% 1/74 • Number of events 1 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.
Injury, poisoning and procedural complications Anastomotic leak	0.00% 0/146 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.	1.4% 1/74 • Number of events 1 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.
Injury, poisoning and procedural complications Humerus fracture	0.00% 0/146 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.	1.4% 1/74 • Number of events 1 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.
Injury, poisoning and procedural complications Rib fracture	0.00% 0/146 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.	1.4% 1/74 • Number of events 1 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.
Metabolism and nutrition disorders Hyperkalemia	0.68% 1/146 • Number of events 1 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.	0.00% 0/74 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.
Metabolism and nutrition disorders Hypoglycemia	0.68% 1/146 • Number of events 2 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.	0.00% 0/74 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.
Respiratory, thoracic and mediastinal disorders Acute pulmonary edema	0.68% 1/146 • Number of events 1 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.	0.00% 0/74 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.68% 1/146 • Number of events 1 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.	0.00% 0/74 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.00% 0/146 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.	1.4% 1/74 • Number of events 1 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.
Surgical and medical procedures Adrenalectomy	0.68% 1/146 • Number of events 1 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.	0.00% 0/74 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.
Surgical and medical procedures Hip surgery	0.68% 1/146 • Number of events 1 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.	0.00% 0/74 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.
Vascular disorders Aortic stenosis	0.68% 1/146 • Number of events 1 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.	0.00% 0/74 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.
Vascular disorders Hypertension	0.68% 1/146 • Number of events 1 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.	0.00% 0/74 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.
Vascular disorders Femoral artery occlusion	0.00% 0/146 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.	1.4% 1/74 • Number of events 1 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.
Ear and labyrinth disorders Vertigo	0.68% 1/146 • Number of events 1 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.	0.00% 0/74 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.
Musculoskeletal and connective tissue disorders Lumbar spinal stenosis	0.68% 1/146 • Number of events 1 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.	0.00% 0/74 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.
Musculoskeletal and connective tissue disorders Spinal osteoarthritis	0.00% 0/146 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.	1.4% 1/74 • Number of events 1 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.
Psychiatric disorders Anxiety	0.68% 1/146 • Number of events 1 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.	0.00% 0/74 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.
Renal and urinary disorders Renal failure	0.68% 1/146 • Number of events 1 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.	0.00% 0/74 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.
Renal and urinary disorders Hematuria	0.00% 0/146 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.	1.4% 1/74 • Number of events 1 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.
Renal and urinary disorders Renal failure acute	0.00% 0/146 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.	1.4% 1/74 • Number of events 1 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.
Reproductive system and breast disorders Ovarian cyst	0.68% 1/146 • Number of events 1 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.	0.00% 0/74 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.
General disorders Non-cardiac chest pain	0.00% 0/146 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.	1.4% 1/74 • Number of events 1 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.

Other adverse events

Measure	Ocriplasmin n=146 participants at risk Subjects in the ocriplasmin group received a single intravitreal injection of ocriplasmin 0.125mg	Sham n=74 participants at risk Subjects in the sham group received a single sham injection
Eye disorders Vitreous floaters	39.0% 57/146 • Number of events 75 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.	8.1% 6/74 • Number of events 6 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.
Eye disorders Photopsia	30.1% 44/146 • Number of events 53 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.	8.1% 6/74 • Number of events 7 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.
Eye disorders Vision blurred	19.2% 28/146 • Number of events 34 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.	5.4% 4/74 • Number of events 6 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.
Eye disorders Cataract nuclear	15.8% 23/146 • Number of events 30 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.	13.5% 10/74 • Number of events 11 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.
Eye disorders Cataract	15.1% 22/146 • Number of events 26 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.	13.5% 10/74 • Number of events 10 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.
Eye disorders Macular fibrosis	15.1% 22/146 • Number of events 26 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.	10.8% 8/74 • Number of events 8 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.
Eye disorders Visual acuity reduced	15.1% 22/146 • Number of events 25 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.	24.3% 18/74 • Number of events 26 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.
Eye disorders Visual impairment	14.4% 21/146 • Number of events 38 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.	5.4% 4/74 • Number of events 6 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.
Eye disorders Eye pain	13.7% 20/146 • Number of events 22 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.	8.1% 6/74 • Number of events 10 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.
Eye disorders Photophobia	13.0% 19/146 • Number of events 22 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.	0.00% 0/74 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.
Eye disorders Posterior capsule opacification	11.6% 17/146 • Number of events 20 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.	4.1% 3/74 • Number of events 4 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.
Eye disorders Subretinal fluid	11.6% 17/146 • Number of events 18 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.	5.4% 4/74 • Number of events 4 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.
Eye disorders Chromatopsia	11.0% 16/146 • Number of events 18 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.	2.7% 2/74 • Number of events 3 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.
Eye disorders Conjunctival hemorrhage	10.3% 15/146 • Number of events 17 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.	2.7% 2/74 • Number of events 2 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.
Eye disorders Metamorphopsia	9.6% 14/146 • Number of events 15 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.	6.8% 5/74 • Number of events 6 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.
Eye disorders Retinal hemorrhage	8.2% 12/146 • Number of events 12 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.	5.4% 4/74 • Number of events 7 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.
Eye disorders Retinal pigment epitheliopathy	7.5% 11/146 • Number of events 12 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.	4.1% 3/74 • Number of events 3 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.
Eye disorders Macular hole	6.2% 9/146 • Number of events 9 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.	1.4% 1/74 • Number of events 1 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.
Eye disorders Ocular discomfort	6.2% 9/146 • Number of events 10 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.	2.7% 2/74 • Number of events 2 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.
Eye disorders Cystoid macular edema	5.5% 8/146 • Number of events 10 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.	2.7% 2/74 • Number of events 2 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.
Eye disorders Lacrimation increased	5.5% 8/146 • Number of events 10 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.	2.7% 2/74 • Number of events 3 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.
Eye disorders Foreign body sensation in eyes	3.4% 5/146 • Number of events 5 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.	8.1% 6/74 • Number of events 6 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.
Eye disorders Retinal tear	1.4% 2/146 • Number of events 2 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.	5.4% 4/74 • Number of events 5 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.
Eye disorders Cataract cortical	0.68% 1/146 • Number of events 1 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.	5.4% 4/74 • Number of events 4 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.
Investigations Color vision tests abnormal	29.5% 43/146 • Number of events 89 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.	18.9% 14/74 • Number of events 18 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.
Investigations Ophthalmological examination abnormal	19.9% 29/146 • Number of events 44 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.	20.3% 15/74 • Number of events 21 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.
Investigations Intraocular pressure increased	6.8% 10/146 • Number of events 10 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.	12.2% 9/74 • Number of events 11 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.
Investigations Visual acuity tests abnormal	6.2% 9/146 • Number of events 10 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.	2.7% 2/74 • Number of events 2 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.
Vascular disorders Hypertension	6.8% 10/146 • Number of events 12 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.	1.4% 1/74 • Number of events 1 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.
Nervous system disorders Headache	6.2% 9/146 • Number of events 10 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.	5.4% 4/74 • Number of events 4 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.
Infections and infestations Sinusitis	5.5% 8/146 • Number of events 10 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.	2.7% 2/74 • Number of events 2 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.
Gastrointestinal disorders Nausea	3.4% 5/146 • Number of events 6 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.	8.1% 6/74 • Number of events 6 • Adverse events were collected from the injection day (Day 0) up to discontinuation from the study or completion of the study (Month 24). The Safety Set consisted of all subjects who received study treatment and was used for all safety analyses. All subjects were included in the Safety Set: 146 subjects in the ocriplasmin group and 74 subjects in the sham group.

Additional Information

Dr. Petra Kozma-Wiebe

ThromboGenics N.V.

Phone: +32 16 751 497

Email: petra.kozma@thrombogenics.com

Results disclosure agreements

• Principal investigator is a sponsor employee Sponsor shall have the right to the 1st publication of the Study results (joint, multi-center publication in conjunction with PI). Following the 1st publication, PI may publish data/results from the Study; provided that PI submits the proposed publication to Sponsor for review at least 60 days prior to the date of the proposed publication. Sponsor may request that Confidential/Proprietary Information be deleted and/or publication be postponed to protect Sponsor's intellectual property rights.
• Publication restrictions are in place

Restriction type: OTHER