Trial Outcomes & Findings for A Study of the Efficacy and Safety of Ranibizumab Injection in Patients With Macular Edema Secondary to Central Retinal Vein Occlusion (CRUISE) (NCT NCT00485836)

Last Updated: 2017-07-28

Results Overview

BCVA score in the study eye was based on the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity charts (number of correct letters) and assessed at a starting distance of 4 meters.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

392 participants

Primary outcome timeframe

Baseline and 6 months

Results posted on

2017-07-28

Participant Flow

Please note that although the table below is titled "Overall Study," the completion rates are for the 6-month Treatment Period only (i.e., does not include the 6-month Observation Period data).

Participant milestones

Participant milestones
Measure	Sham Injection Sham injection in a single-dose regimen given every month (Day 0 through the Month 5 visit), for a total of six sham injections.	Ranibizumab Injection 0.3 mg Ranibizumab injection 0.3 mg in a single-dose regimen given every month (Day 0 through the Month 5 visit), for a total of six injections.	Ranibizumab Injection 0.5 mg Ranibizumab injection 0.5 mg in a single-dose regimen given every month (Day 0 through the Month 5 visit), for a total of six injections.
Overall Study STARTED	130	132	130
Overall Study Received Study Drug (Safety Population)	129	132	129
Overall Study COMPLETED	115	129	119
Overall Study NOT COMPLETED	15	3	11

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Study of the Efficacy and Safety of Ranibizumab Injection in Patients With Macular Edema Secondary to Central Retinal Vein Occlusion (CRUISE)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Sham Injection n=130 Participants Sham injection in a single-dose regimen given every month (Day 0 through the Month 5 visit), for a total of six sham injections.	Ranibizumab Injection 0.3 mg n=132 Participants Ranibizumab injection 0.3 mg in a single-dose regimen given every month (Day 0 through the Month 5 visit), for a total of six injections.	Ranibizumab Injection 0.5 mg n=130 Participants Ranibizumab injection 0.5 mg in a single-dose regimen given every month (Day 0 through the Month 5 visit), for a total of six injections.	Total n=392 Participants Total of all reporting groups
Age, Continuous	65.4 years STANDARD_DEVIATION 13.1 • n=5 Participants	69.7 years STANDARD_DEVIATION 11.6 • n=7 Participants	67.6 years STANDARD_DEVIATION 12.4 • n=5 Participants	67.6 years STANDARD_DEVIATION 12.5 • n=4 Participants
Age, Customized < 45 years	10 participants n=5 Participants	5 participants n=7 Participants	5 participants n=5 Participants	20 participants n=4 Participants
Age, Customized 45 to < 65 years	50 participants n=5 Participants	36 participants n=7 Participants	46 participants n=5 Participants	132 participants n=4 Participants
Age, Customized 65 to < 85 years	67 participants n=5 Participants	80 participants n=7 Participants	71 participants n=5 Participants	218 participants n=4 Participants
Age, Customized ≥ 85 years	3 participants n=5 Participants	11 participants n=7 Participants	8 participants n=5 Participants	22 participants n=4 Participants
Sex: Female, Male Female	58 Participants n=5 Participants	61 Participants n=7 Participants	50 Participants n=5 Participants	169 Participants n=4 Participants
Sex: Female, Male Male	72 Participants n=5 Participants	71 Participants n=7 Participants	80 Participants n=5 Participants	223 Participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline and 6 months

Population: Intent to treat (randomized) population. Missing values were imputed using the last-observation-carried-forward (LOCF) method.

BCVA score in the study eye was based on the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity charts (number of correct letters) and assessed at a starting distance of 4 meters.

Outcome measures

Outcome measures
Measure	Sham Injection n=130 Participants Sham injection in a single-dose regimen given every month (Day 0 through the Month 5 visit), for a total of six sham injections.	Ranibizumab Injection 0.3 mg n=132 Participants Ranibizumab injection 0.3 mg in a single-dose regimen given every month (Day 0 through the Month 5 visit), for a total of six injections.	Ranibizumab Injection 0.5 mg n=130 Participants Ranibizumab injection 0.5 mg in a single-dose regimen given every month (Day 0 through the Month 5 visit), for a total of six injections.
Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) Score at 6 Months Baseline	49.2 Units on a scale Standard Deviation 14.7	47.4 Units on a scale Standard Deviation 14.8	48.1 Units on a scale Standard Deviation 14.6
Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) Score at 6 Months Mean Change from Baseline at Month 6	0.8 Units on a scale Standard Deviation 16.2	12.7 Units on a scale Standard Deviation 15.9	14.9 Units on a scale Standard Deviation 13.2

SECONDARY outcome

Timeframe: Baseline and 6 months

Population: Intent to treat (randomized) population. Missing values were imputed using the LOCF method.

BCVA score based on the ETDRS visual acuity charts (number of correct letters) and assessed at a starting distance of 4 meters.

Outcome measures

Outcome measures
Measure	Sham Injection n=130 Participants Sham injection in a single-dose regimen given every month (Day 0 through the Month 5 visit), for a total of six sham injections.	Ranibizumab Injection 0.3 mg n=132 Participants Ranibizumab injection 0.3 mg in a single-dose regimen given every month (Day 0 through the Month 5 visit), for a total of six injections.	Ranibizumab Injection 0.5 mg n=130 Participants Ranibizumab injection 0.5 mg in a single-dose regimen given every month (Day 0 through the Month 5 visit), for a total of six injections.
Percentage of Participants Who Gained ≥ 15 Letters in BCVA Score at Month 6 Compared With Baseline	16.9 Percentage of participants Interval 10.5 to 23.4	46.2 Percentage of participants Interval 37.7 to 54.7	47.7 Percentage of participants Interval 39.1 to 56.3

SECONDARY outcome

Timeframe: Baseline and 6 months

Population: Intent to treat (randomized) population. Missing values were imputed using the LOCF method.

BCVA score based on the ETDRS visual acuity charts (number of correct letters) and assessed at a starting distance of 4 meters.

Outcome measures

Outcome measures
Measure	Sham Injection n=130 Participants Sham injection in a single-dose regimen given every month (Day 0 through the Month 5 visit), for a total of six sham injections.	Ranibizumab Injection 0.3 mg n=132 Participants Ranibizumab injection 0.3 mg in a single-dose regimen given every month (Day 0 through the Month 5 visit), for a total of six injections.	Ranibizumab Injection 0.5 mg n=130 Participants Ranibizumab injection 0.5 mg in a single-dose regimen given every month (Day 0 through the Month 5 visit), for a total of six injections.
Percentage of Participants Who Lost < 15 Letters in BCVA Score at Month 6 Compared With Baseline	84.6 Percentage of participants Interval 78.4 to 90.8	96.2 Percentage of participants Interval 93.0 to 99.5	98.5 Percentage of participants Interval 96.3 to 100.0

SECONDARY outcome

Timeframe: 6 months

Population: Intent to treat (randomized) population. Missing values were imputed using the LOCF method.

A central reading center assessed all optical coherence tomography (OCT) images. Central foveal thickness was defined as the center point thickness.

Outcome measures

Outcome measures
Measure	Sham Injection n=130 Participants Sham injection in a single-dose regimen given every month (Day 0 through the Month 5 visit), for a total of six sham injections.	Ranibizumab Injection 0.3 mg n=132 Participants Ranibizumab injection 0.3 mg in a single-dose regimen given every month (Day 0 through the Month 5 visit), for a total of six injections.	Ranibizumab Injection 0.5 mg n=130 Participants Ranibizumab injection 0.5 mg in a single-dose regimen given every month (Day 0 through the Month 5 visit), for a total of six injections.
Percentage of Participants With a Central Foveal Thickness of ≤ 250 μm at Month 6	23.1 Percentage of participants Interval 15.8 to 30.3	75.0 Percentage of participants Interval 67.6 to 82.4	76.9 Percentage of participants Interval 69.7 to 84.2

SECONDARY outcome

Timeframe: Baseline and 6 months

Population: Intent to treat (randomized) population. Missing values were imputed using the LOCF method.

A central reading center assessed all OCT images. Central foveal thickness was defined as the center point thickness.

Outcome measures

Outcome measures
Measure	Sham Injection n=129 Participants Sham injection in a single-dose regimen given every month (Day 0 through the Month 5 visit), for a total of six sham injections.	Ranibizumab Injection 0.3 mg n=131 Participants Ranibizumab injection 0.3 mg in a single-dose regimen given every month (Day 0 through the Month 5 visit), for a total of six injections.	Ranibizumab Injection 0.5 mg n=130 Participants Ranibizumab injection 0.5 mg in a single-dose regimen given every month (Day 0 through the Month 5 visit), for a total of six injections.
Mean Absolute Change From Baseline in Central Foveal Thickness at Month 6 Baseline	687.0 μm Standard Deviation 237.6	679.9 μm Standard Deviation 242.2	688.7 μm Standard Deviation 253.1
Mean Absolute Change From Baseline in Central Foveal Thickness at Month 6 Mean Absolute Change from Baseline at Month 6	-167.7 μm Standard Deviation 308.4	-433.7 μm Standard Deviation 295.9	-452.3 μm Standard Deviation 257.6

SECONDARY outcome

Timeframe: Baseline and 6 months

Population: Intent to treat (randomized) population; however, patients without a baseline score were excluded from analysis.

The NEI VFQ-25 (v. 2000; Interviewer Format) consisted of the base set of 25 questions, plus the optional additional questions (where questions A3, A4, and A5 pertained to the Near Activities Subscale). Scores ranged from 0 to 100; a higher score represented better functioning.

Outcome measures

Outcome measures
Measure	Sham Injection n=127 Participants Sham injection in a single-dose regimen given every month (Day 0 through the Month 5 visit), for a total of six sham injections.	Ranibizumab Injection 0.3 mg n=130 Participants Ranibizumab injection 0.3 mg in a single-dose regimen given every month (Day 0 through the Month 5 visit), for a total of six injections.	Ranibizumab Injection 0.5 mg n=128 Participants Ranibizumab injection 0.5 mg in a single-dose regimen given every month (Day 0 through the Month 5 visit), for a total of six injections.
Mean Change From Baseline in the National Eye Institute Visual Functioning Questionnaire-25 (NEI VFQ-25) Near Activities Subscale Score at Month 6 Baseline at Month 6	69.9 Points on the NEI VFQ-25 subscale Standard Deviation 22.6	71.2 Points on the NEI VFQ-25 subscale Standard Deviation 22.2	70.7 Points on the NEI VFQ-25 subscale Standard Deviation 20.3
Mean Change From Baseline in the National Eye Institute Visual Functioning Questionnaire-25 (NEI VFQ-25) Near Activities Subscale Score at Month 6 Change from baseline at Month 6	5.1 Points on the NEI VFQ-25 subscale Standard Deviation 17.1	10.2 Points on the NEI VFQ-25 subscale Standard Deviation 17.4	9.3 Points on the NEI VFQ-25 subscale Standard Deviation 18.1

SECONDARY outcome

Timeframe: Baseline and 6 months

Population: Intent to treat (randomized) population; however, patients without a baseline score were excluded from analysis.

The NEI VFQ-25 (v. 2000; Interviewer Format) consisted of the base set of 25 questions, plus the optional additional questions (where questions A6, A7, and A8 pertained to the Distance Activities Subscale). Scores ranged from 0 to 100; a higher score represented better functioning.

Outcome measures

Outcome measures
Measure	Sham Injection n=127 Participants Sham injection in a single-dose regimen given every month (Day 0 through the Month 5 visit), for a total of six sham injections.	Ranibizumab Injection 0.3 mg n=130 Participants Ranibizumab injection 0.3 mg in a single-dose regimen given every month (Day 0 through the Month 5 visit), for a total of six injections.	Ranibizumab Injection 0.5 mg n=128 Participants Ranibizumab injection 0.5 mg in a single-dose regimen given every month (Day 0 through the Month 5 visit), for a total of six injections.
Mean Change From Baseline in the NEI VFQ-25 Distance Activities Subscale Score at Month 6 Baseline at Month 6	77.0 Points on the NEI VFQ-25 subscale Standard Deviation 22.5	77.3 Points on the NEI VFQ-25 subscale Standard Deviation 19.8	77.0 Points on the NEI VFQ-25 subscale Standard Deviation 19.7
Mean Change From Baseline in the NEI VFQ-25 Distance Activities Subscale Score at Month 6 Change from baseline at Month 6	2.8 Points on the NEI VFQ-25 subscale Standard Deviation 15.6	8.9 Points on the NEI VFQ-25 subscale Standard Deviation 13.7	6.7 Points on the NEI VFQ-25 subscale Standard Deviation 16.3

Adverse Events

Sham Injection

Serious events: 13 serious events

Other events: 116 other events

Deaths: 0 deaths

Ranibizumab Injection 0.3 mg

Serious events: 16 serious events

Other events: 113 other events

Deaths: 0 deaths

Ranibizumab Injection 0.5 mg

Serious events: 13 serious events

Other events: 111 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Medical Communications

Genentech, Inc.

Phone: 800-821-8590

Results disclosure agreements

Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Publication restrictions are in place

Restriction type: OTHER

Serious adverse events
Measure	Sham Injection n=129 participants at risk Sham injection in a single-dose regimen given every month (Day 0 through the Month 5 visit), for a total of six sham injections.	Ranibizumab Injection 0.3 mg n=132 participants at risk Ranibizumab injection 0.3 mg in a single-dose regimen given every month (Day 0 through the Month 5 visit), for a total of six injections.	Ranibizumab Injection 0.5 mg n=129 participants at risk Ranibizumab injection 0.5 mg in a single-dose regimen given every month (Day 0 through the Month 5 visit), for a total of six injections.
Cardiac disorders Cardiomyopathy	0.00% 0/129 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.76% 1/132 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.00% 0/129 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.
Cardiac disorders Arteriosclerosis Coronary Artery	0.00% 0/129 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.00% 0/132 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.78% 1/129 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.
Cardiac disorders Coronary Artery Disease	1.6% 2/129 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.76% 1/132 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.78% 1/129 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.
Cardiac disorders Cardiac Failure Congestive	0.00% 0/129 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.76% 1/132 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.00% 0/129 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.
Cardiac disorders Acute Coronary Syndrome	0.78% 1/129 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.00% 0/132 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.00% 0/129 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.
Cardiac disorders Angina Pectoris	0.00% 0/129 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.00% 0/132 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.78% 1/129 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.
Cardiac disorders Myocardial Infarction	0.00% 0/129 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.76% 1/132 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.78% 1/129 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.
Cardiac disorders Atrial Fibrillation	0.00% 0/129 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.00% 0/132 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.78% 1/129 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.
Cardiac disorders Supraventricular Tachycardia	0.78% 1/129 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.00% 0/132 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.00% 0/129 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.
Endocrine disorders Inappropriate Antidiuretic Hormone Secretion	0.00% 0/129 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.76% 1/132 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.00% 0/129 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.
Eye disorders Blindness Unilateral	0.00% 0/129 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.00% 0/132 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.78% 1/129 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.
Eye disorders Vitreous Hemorrhage	0.78% 1/129 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.00% 0/132 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.00% 0/129 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.
Eye disorders Corneal Edema	0.00% 0/129 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.76% 1/132 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.00% 0/129 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.
Eye disorders Iris Neovascularization	0.00% 0/129 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.00% 0/132 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.78% 1/129 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.
Eye disorders Retinal Disorder	0.00% 0/129 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.76% 1/132 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.00% 0/129 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.
Eye disorders Macular Ischemia	0.78% 1/129 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.00% 0/132 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.00% 0/129 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.
Eye disorders Retinal Artery Occlusion	0.00% 0/129 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.76% 1/132 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.00% 0/129 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.
Eye disorders Retinal Vascular Disorder	0.00% 0/129 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.76% 1/132 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.00% 0/129 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.
Eye disorders Retinal Vascular Occlusion	0.00% 0/129 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.00% 0/132 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.78% 1/129 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.
Eye disorders Retinal Vein Occlusion	1.6% 2/129 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.76% 1/132 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.78% 1/129 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.
Eye disorders Maculopathy	0.00% 0/129 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.76% 1/132 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.00% 0/129 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.
Eye disorders Retinal Depigmentation	0.00% 0/129 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.76% 1/132 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.00% 0/129 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.
Eye disorders Macular Edema	1.6% 2/129 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	1.5% 2/132 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.00% 0/129 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.
Gastrointestinal disorders Colitis	0.00% 0/129 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.76% 1/132 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.78% 1/129 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.
Gastrointestinal disorders Umbilical Hernia	0.00% 0/129 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.76% 1/132 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.00% 0/129 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.
General disorders Chest Pain	0.00% 0/129 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.76% 1/132 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.00% 0/129 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.
Immune system disorders Food Allergy	0.00% 0/129 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.00% 0/132 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.78% 1/129 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.
Infections and infestations Diverticulitis	0.78% 1/129 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.00% 0/132 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.78% 1/129 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.
Infections and infestations Cellulitis	0.00% 0/129 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.76% 1/132 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.00% 0/129 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.
Infections and infestations Bronchitis	0.00% 0/129 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.76% 1/132 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.00% 0/129 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.
Injury, poisoning and procedural complications Lead Dislodgement	0.00% 0/129 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.00% 0/132 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.78% 1/129 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.
Injury, poisoning and procedural complications Hip Fracture	0.78% 1/129 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.00% 0/132 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.00% 0/129 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.
Injury, poisoning and procedural complications Humerus Fracture	0.00% 0/129 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.00% 0/132 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.78% 1/129 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.
Metabolism and nutrition disorders Hyponatremia	0.00% 0/129 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.76% 1/132 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.00% 0/129 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.
Musculoskeletal and connective tissue disorders Spinal Osteoarthritis	0.00% 0/129 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.00% 0/132 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.78% 1/129 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.
Musculoskeletal and connective tissue disorders Lumbar Spinal Stenosis	0.00% 0/129 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.00% 0/132 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.78% 1/129 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon Cancer	0.78% 1/129 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.00% 0/132 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.00% 0/129 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gastric Cancer	0.78% 1/129 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.00% 0/132 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.00% 0/129 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Uterine Leiomyoma	0.00% 0/129 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.00% 0/132 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.78% 1/129 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.
Nervous system disorders Syncope	0.00% 0/129 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	1.5% 2/132 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.00% 0/129 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.

Other adverse events
Measure	Sham Injection n=129 participants at risk Sham injection in a single-dose regimen given every month (Day 0 through the Month 5 visit), for a total of six sham injections.	Ranibizumab Injection 0.3 mg n=132 participants at risk Ranibizumab injection 0.3 mg in a single-dose regimen given every month (Day 0 through the Month 5 visit), for a total of six injections.	Ranibizumab Injection 0.5 mg n=129 participants at risk Ranibizumab injection 0.5 mg in a single-dose regimen given every month (Day 0 through the Month 5 visit), for a total of six injections.
Eye disorders Conjunctival Hemorrhage	33.3% 43/129 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	43.2% 57/132 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	41.1% 53/129 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.
Eye disorders Eye Irritation	4.7% 6/129 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	4.5% 6/132 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	7.8% 10/129 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.
Eye disorders Eye Pain	10.9% 14/129 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	9.1% 12/132 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	18.6% 24/129 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.
Eye disorders Foreign Body Sensation in Eyes	3.9% 5/129 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	3.0% 4/132 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	7.0% 9/129 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.
Eye disorders Iris Neovascularization	7.0% 9/129 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	1.5% 2/132 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.78% 1/129 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.
Eye disorders Macular Edema	8.5% 11/129 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	5.3% 7/132 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	3.1% 4/129 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.
Eye disorders Maculopathy	10.1% 13/129 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	15.9% 21/132 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	14.7% 19/129 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.
Eye disorders Myodesopsia	3.9% 5/129 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	6.8% 9/132 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	9.3% 12/129 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.
Eye disorders Ocular Vascular Disorder	0.00% 0/129 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	1.5% 2/132 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	6.2% 8/129 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.
Eye disorders Optic Disc Vascular Disorder	6.2% 8/129 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	5.3% 7/132 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	1.6% 2/129 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.
Eye disorders Retinal Depigmentation	6.2% 8/129 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	9.1% 12/132 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	7.8% 10/129 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.
Eye disorders Retinal Exudates	14.0% 18/129 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	27.3% 36/132 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	19.4% 25/129 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.
Eye disorders Retinal Hemorrhage	13.2% 17/129 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	11.4% 15/132 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	12.4% 16/129 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.
Eye disorders Retinal Pigmentation	3.1% 4/129 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	5.3% 7/132 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	1.6% 2/129 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.
Eye disorders Retinal Vascular Disorder	14.7% 19/129 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	15.9% 21/132 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	14.7% 19/129 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.
Eye disorders Vitreous Detachment	4.7% 6/129 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	0.76% 1/132 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	6.2% 8/129 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.
Eye disorders Vitreous Hemorrhage	6.2% 8/129 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	3.8% 5/132 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	5.4% 7/129 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.
Infections and infestations Nasopharyngitis	2.3% 3/129 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	6.1% 8/132 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	5.4% 7/129 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.
Investigations Intraocular Pressure Increased	3.9% 5/129 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	8.3% 11/132 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	8.5% 11/129 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.
Vascular disorders Hypertension	6.2% 8/129 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	3.0% 4/132 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.	2.3% 3/129 • 6 months Investigators assessed the occurrence of AE/SAEs at all study visits. Summaries are for the safety-evaluable population and include events regardless of relation to study drug or location (e.g. non-study eye events are included). For each AE/SAE, the number of patients experiencing the event, not the number of occurrences of the event, is reported.