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A 12 Month Core Study to Assess the Efficacy and Safety of Ranibizumab (Intravitreal Injections) in Patients With Visual Impairment Due to Diabetic Macular Edema and a 24 Month Open-label Extension Study (RESTORE)

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ClinicalTrials.gov Identifier: NCT00687804
Recruitment Status : Completed
First Posted : June 2, 2008
Results First Posted : April 19, 2011
Last Update Posted : April 1, 2013
Sponsor:
Information provided by (Responsible Party):
Novartis

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Diabetic Macular Edema
Interventions Drug: Ranibizumab
Procedure: Laser
Procedure: Sham laser
Drug: Sham to ranibizumab
Enrollment 345
Recruitment Details  
Pre-assignment Details Participants who completed the 12 month randomized core study CRFB002D2301 were eligible to participate in the 24 month open-label extension study CRFB002D2301E1. The reporting groups for the participants in the extension study are according to their assigned treatment groups in the core study.
Arm/Group Title Ranibizumab 0.5 mg Ranibizumab 0.5 mg + Laser Laser
Hide Arm/Group Description

Ranibizumab 0.5 mg was administered monthly by intravitreal injection in the study eye for 3 months. After the third injection, treatment was suspended if either one of the following criteria was met:

Improvement in best corrected visual acuity (BCVA) could not be attributed to treatment at the last 2 visits, in the opinion of the investigator, or BCVA > 84 letters (approximate Snellen equivalent of 20/20) was observed at the last 2 last visits.

Patients also received sham laser treatment on Day 1 and subsequently at intervals of at least 3 months, if deemed necessary by the evaluating physician.

Active/sham laser treatment was always administered before (sham) intravitreal injections. The minimum interval between the 2 treatments was 30 minutes.

In the extension study at the investigator's discretion, patients received open-label ranibizumab 0.5 mg intravitreal injections once a month until stable vision was reached (a maximum of 24 injections) and could receive laser therapy.

Ranibizumab 0.5 mg was administered monthly by intravitreal injection in the study eye for 3 months. After the third injection, treatment was suspended if either one of the following criteria was met:

Improvement in best corrected visual acuity (BCVA) could not be attributed to treatment at the last 2 visits, in the opinion of the investigator, or BCVA > 84 letters (approximate Snellen equivalent of 20/20) was observed at the last 2 last visits.

Patients also received active laser treatment on Day 1 and subsequently at intervals of at least 3 months, if deemed necessary by the physician.

Active/sham laser treatment was always administered before (sham) intravitreal injections. The minimum interval between the 2 treatments was 30 minutes.

In the extension study at the investigator's discretion, patients received open-label ranibizumab 0.5 mg intravitreal injections once a month until stable vision was reached (a maximum of 24 injections) and could receive laser therapy.

Active laser photocoagulation treatment was administered on Day 1 and at intervals of at least 3 months, if deemed necessary by the evaluating physician. Patients also received monthly sham intravitreal injection in the study eye for 3 consecutive months. After the third injection, treatment was suspended if either one of the following criteria was met:

Improvement in best corrected visual acuity (BCVA) could not be attributed to treatment at the last 2 visits, in the opinion of the investigator, or BCVA > 84 letters (approximate Snellen equivalent of 20/20) was observed at the last 2 last visits.

Active/sham laser treatment was always administered before (sham) intravitreal injections. The minimum interval between the 2 treatments was 30 minutes.

In the extension study at the investigator's discretion, patients received open-label ranibizumab 0.5 mg intravitreal injections once a month until stable vision was reached (a maximum of 24 injections) and could receive laser therapy.

Period Title: Core Study
Started 116 118 111
Completed 102 103 98
Not Completed 14 15 13
Reason Not Completed
Adverse Event             5             3             3
Abnormal laboratory value(s)             1             0             0
Lack of Efficacy             1             1             1
Withdrawal by Subject             4             7             7
Lost to Follow-up             0             1             0
Death             2             2             2
Protocol Violation             1             1             0
Period Title: Open-Label Extension Study
Started 83 83 74
Did Not Receive Ranibizumab in Extension 16 21 15
Completed 73 72 63
Not Completed 10 11 11
Reason Not Completed
Adverse Event             2             2             2
Subject withdrew consent             3             4             4
Lost to Follow-up             2             1             2
Administrative problems             1             1             0
Death             2             3             3
Arm/Group Title Ranibizumab 0.5 mg Ranibizumab 0.5 mg + Laser Laser Total
Hide Arm/Group Description

Ranibizumab 0.5 mg was administered monthly by intravitreal injection in the study eye for 3 months. After the third injection, treatment was suspended if either one of the following criteria was met:

Improvement in best corrected visual acuity (BCVA) could not be attributed to treatment at the last 2 visits, in the opinion of the investigator, or BCVA > 84 letters (approximate Snellen equivalent of 20/20) was observed at the last 2 last visits.

Patients also received sham laser treatment on Day 1 and subsequently at intervals of at least 3 months, if deemed necessary by the evaluating physician.

Active/sham laser treatment was always administered before (sham) intravitreal injections. The minimum interval between the 2 treatments was 30 minutes.

Ranibizumab 0.5 mg was administered monthly by intravitreal injection in the study eye for 3 months. After the third injection, treatment was suspended if either one of the following criteria was met:

Improvement in best corrected visual acuity (BCVA) could not be attributed to treatment at the last 2 visits, in the opinion of the investigator, or BCVA > 84 letters (approximate Snellen equivalent of 20/20) was observed at the last 2 last visits.

Patients also received active laser treatment on Day 1 and subsequently at intervals of at least 3 months, if deemed necessary by the evaluating physician.

Active/sham laser treatment was always administered before (sham) intravitreal injections. The minimum interval between the 2 treatments was 30 minutes.

Laser photocoagulation treatment was administered on Day 1 and subsequently at intervals of at least 3 months, if deemed necessary by the evaluating physician. Patients also received monthly sham intravitreal injection in the study eye for 3 consecutive months. After the third injection, treatment was suspended if either one of the following criteria was met:

Improvement in best corrected visual acuity (BCVA) could not be attributed to treatment at the last 2 visits, in the opinion of the investigator, or BCVA > 84 letters (approximate Snellen equivalent of 20/20) was observed at the last 2 last visits.

Active/sham laser treatment was always administered before (sham) intravitreal injections. The minimum interval between the 2 treatments was 30 minutes.

Total of all reporting groups
Overall Number of Baseline Participants 116 118 111 345
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 116 participants 118 participants 111 participants 345 participants
62.9  (9.29) 64.0  (8.15) 63.5  (8.81) 63.5  (8.75)
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 116 participants 118 participants 111 participants 345 participants
< 55 years 24 14 13 51
55 - <65 years 41 42 53 136
65 - <75 years 40 53 31 124
>=75 years 11 9 14 34
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 116 participants 118 participants 111 participants 345 participants
Female
43
  37.1%
48
  40.7%
53
  47.7%
144
  41.7%
Male
73
  62.9%
70
  59.3%
58
  52.3%
201
  58.3%
1.Primary Outcome
Title Core Study: Difference Between the Baseline Level of Visual Acuity (Letters) of the Study Eye and the Mean Visual Acuity Averaged Over All Monthly Post-baseline Assessments From Month 1 to Month 12
Hide Description Visual acuity (VA) was assessed on both eyes during every study visit using best correction determined from protocol refraction. VA measurements (number of letters correctly identified) were performed with the patient in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like visual acuity testing charts at a testing distance of 4 meters.
Time Frame Baseline through the end of study (Month 12)
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set consists of all patients who received at least one application of study treatment and had at least one post-baseline assessment for BCVA. Following the intent to treat principle, patients were analyzed according to the treatment assigned. Last Observation Carried Forward (LOCF) imputation was utilized.
Arm/Group Title Ranibizumab 0.5 mg Ranibizumab 0.5 mg + Laser Laser
Hide Arm/Group Description:

Ranibizumab 0.5 mg was administered monthly by intravitreal injection in the study eye for 3 months. After the third injection, treatment was suspended if either one of the following criteria was met:

Improvement in best corrected visual acuity (BCVA) could not be attributed to treatment at the last 2 visits, in the opinion of the investigator, or BCVA > 84 letters (approximate Snellen equivalent of 20/20) was observed at the last 2 last visits.

Patients also received sham laser treatment on Day 1 and subsequently at intervals of at least 3 months, if deemed necessary by the evaluating physician.

Active/sham laser treatment was always administered before (sham) intravitreal injections. The minimum interval between the 2 treatments was 30 minutes.

Ranibizumab 0.5 mg was administered monthly by intravitreal injection in the study eye for 3 months. After the third injection, treatment was suspended if either one of the following criteria was met:

Improvement in best corrected visual acuity (BCVA) could not be attributed to treatment at the last 2 visits, in the opinion of the investigator, or BCVA > 84 letters (approximate Snellen equivalent of 20/20) was observed at the last 2 last visits.

Patients also received active laser treatment on Day 1 and subsequently at intervals of at least 3 months, if deemed necessary by the evaluating physician.

Active/sham laser treatment was always administered before (sham) intravitreal injections. The minimum interval between the 2 treatments was 30 minutes.

Laser photocoagulation treatment was administered on Day 1 and subsequently at intervals of at least 3 months, if deemed necessary by the evaluating physician. Patients also received monthly sham intravitreal injection in the study eye for 3 consecutive months. After the third injection, treatment was suspended if either one of the following criteria was met:

Improvement in best corrected visual acuity (BCVA) could not be attributed to treatment at the last 2 visits, in the opinion of the investigator, or BCVA > 84 letters (approximate Snellen equivalent of 20/20) was observed at the last 2 last visits.

Active/sham laser treatment was always administered before (sham) intravitreal injections. The minimum interval between the 2 treatments was 30 minutes.

Overall Number of Participants Analyzed 115 118 110
Mean (Standard Deviation)
Unit of Measure: Letters
Baseline 64.7  (10.07) 63.4  (9.99) 62.6  (11.01)
Average Month 1 to month 12 70.8  (10.53) 69.2  (11.44) 63.4  (12.26)
Change from Baseline 6.1  (6.43) 5.9  (7.92) 0.8  (8.56)
2.Primary Outcome
Title Extension Study: Percentage of Participants With Ocular Adverse Events (AEs) in the Study Eye in the 24 Month Extension Study
Hide Description

Participants with ocular (occurring in the eye) serious adverse events (SAEs) and non-serious AEs in the study eye. The study eye is the eye that received the treatment. AEs are the appearance or worsening of any undesirable sign, symptom, or medical condition occurring after starting the study drug even if the event is not considered to be related to study drug. A serious adverse event is defined as an event that is fatal or life-threatening, results in persistent or significant disability/incapacity, constitutes a congenital anomaly/birth defect, requires inpatient hospitalization or prolongation of existing hospitalization or is medically significant.

Additional information about adverse events can be found in the Adverse Event section.

Time Frame Extension baseline (Month 12 -end of core study) to Month 36 (end of extension study) [24 Months]
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population included all participants who entered the extension and who had at least one safety assessment in the extension study. Participants were grouped according to the treatment assigned in the Core study.
Arm/Group Title Ranibizumab 0.5 mg Ranibizumab 0.5 mg + Laser Laser With Ranibizumab in Extension Laser Without Ranibizumab in Extension
Hide Arm/Group Description:

Ranibizumab 0.5 mg was administered monthly by intravitreal injection in the study eye for 3 months. After the third injection, treatment was suspended if either one of the following criteria was met:

Improvement in best corrected visual acuity (BCVA) could not be attributed to treatment at the last 2 visits, in the opinion of the investigator, or BCVA > 84 letters (approximate Snellen equivalent of 20/20) was observed at the last 2 last visits.

Patients also received sham laser treatment on Day 1 and subsequently at intervals of at least 3 months, if deemed necessary by the evaluating physician.

Active/sham laser treatment was always administered before (sham) intravitreal injections. The minimum interval between the 2 treatments was 30 minutes.

In the extension study at the investigator's discretion, patients received open-label ranibizumab 0.5 mg intravitreal injections once a month until stable vision was reached (a maximum of 24 injections) and could receive laser therapy.

Ranibizumab 0.5 mg was administered monthly by intravitreal injection in the study eye for 3 months. After the third injection, treatment was suspended if either one of the following criteria was met:

Improvement in best corrected visual acuity (BCVA) could not be attributed to treatment at the last 2 visits, in the opinion of the investigator, or BCVA > 84 letters (approximate Snellen equivalent of 20/20) was observed at the last 2 last visits.

Patients also received active laser treatment on Day 1 and subsequently at intervals of at least 3 months, if deemed necessary by the physician.

Active/sham laser treatment was always administered before (sham) intravitreal injections. The minimum interval between the 2 treatments was 30 minutes.

In the extension study at the investigator's discretion, patients received open-label ranibizumab 0.5 mg intravitreal injections once a month until stable vision was reached (a maximum of 24 injections) and could receive laser therapy.

Active laser photocoagulation treatment was administered on Day 1 and at intervals of at least 3 months, if deemed necessary by the evaluating physician. Patients also received monthly sham intravitreal injection in the study eye for 3 consecutive months. After the third injection, treatment was suspended if either one of the following criteria was met:

Improvement in best corrected visual acuity (BCVA) could not be attributed to treatment at the last 2 visits, in the opinion of the investigator, or BCVA > 84 letters (approximate Snellen equivalent of 20/20) was observed at the last 2 last visits.

Active/sham laser treatment was always administered before (sham) intravitreal injections. The minimum interval between the 2 treatments was 30 minutes.

In the extension study at the investigator's discretion, patients received open-label ranibizumab 0.5 mg intravitreal injections once a month until stable vision was reached (a maximum of 24 injections) and could receive laser therapy.

Active laser photocoagulation treatment was administered on Day 1 and at intervals of at least 3 months, if deemed necessary by the evaluating physician. Patients also received monthly sham intravitreal injection in the study eye for 3 consecutive months. After the third injection, treatment was suspended if either one of the following criteria was met:

Improvement in best corrected visual acuity (BCVA) could not be attributed to treatment at the last 2 visits, in the opinion of the investigator, or BCVA > 84 letters (approximate Snellen equivalent of 20/20) was observed at the last 2 last visits.

Active/sham laser treatment was always administered before (sham) intravitreal injections. The minimum interval between the 2 treatments was 30 minutes.

In the extension study at the investigator's discretion, patients received open-label ranibizumab 0.5 mg intravitreal injections once a month until stable vision was reached (a maximum of 24 injections) and could receive laser therapy.

Overall Number of Participants Analyzed 83 83 59 15
Measure Type: Number
Unit of Measure: Percentage of participants
Adverse Events 56.6 56.6 52.5 40.0
Serious Adverse Events 2.4 1.2 1.7 0.0
3.Primary Outcome
Title Extension Study: Percentage of Participants With Non-Ocular Adverse Events (AEs) in the 24 Month Extension Study
Hide Description

Participants with non-ocular (not occurring in the eye) serious adverse events (SAEs) and non-serious AEs. AEs are the appearance or worsening of of any undesirable sign, symptom, or medical condition occurring after starting the study drug even if the event is not considered to be related to study drug. A serious adverse event is defined as an event that is fatal or life-threatening, results in persistent or significant disability/incapacity, constitutes a congenital anomaly/birth defect, requires inpatient hospitalization or prolongation of existing hospitalization or is medically significant.

Additional information about adverse events can be found in the Adverse Event section.

Time Frame Extension baseline (Month 12 -end of core study) to Month 36 (end of extension study) [24 Months]
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population included all participants who entered the extension and who had at least one safety assessment in the extension study. Participants were grouped according to the treatment assigned in the Core study.
Arm/Group Title Ranibizumab 0.5 mg Ranibizumab 0.5 mg + Laser Laser With Ranibizumab in Extension Laser Without Ranibizumab in Extension
Hide Arm/Group Description:

Ranibizumab 0.5 mg was administered monthly by intravitreal injection in the study eye for 3 months. After the third injection, treatment was suspended if either one of the following criteria was met:

Improvement in best corrected visual acuity (BCVA) could not be attributed to treatment at the last 2 visits, in the opinion of the investigator, or BCVA > 84 letters (approximate Snellen equivalent of 20/20) was observed at the last 2 last visits.

Patients also received sham laser treatment on Day 1 and subsequently at intervals of at least 3 months, if deemed necessary by the evaluating physician.

Active/sham laser treatment was always administered before (sham) intravitreal injections. The minimum interval between the 2 treatments was 30 minutes.

In the extension study at the investigator's discretion, patients received open-label ranibizumab 0.5 mg intravitreal injections once a month until stable vision was reached (a maximum of 24 injections) and could receive laser therapy.

Ranibizumab 0.5 mg was administered monthly by intravitreal injection in the study eye for 3 months. After the third injection, treatment was suspended if either one of the following criteria was met:

Improvement in best corrected visual acuity (BCVA) could not be attributed to treatment at the last 2 visits, in the opinion of the investigator, or BCVA > 84 letters (approximate Snellen equivalent of 20/20) was observed at the last 2 last visits.

Patients also received active laser treatment on Day 1 and subsequently at intervals of at least 3 months, if deemed necessary by the physician.

Active/sham laser treatment was always administered before (sham) intravitreal injections. The minimum interval between the 2 treatments was 30 minutes.

In the extension study at the investigator's discretion, patients received open-label ranibizumab 0.5 mg intravitreal injections once a month until stable vision was reached (a maximum of 24 injections) and could receive laser therapy.

Active laser photocoagulation treatment was administered on Day 1 and at intervals of at least 3 months, if deemed necessary by the evaluating physician. Patients also received monthly sham intravitreal injection in the study eye for 3 consecutive months. After the third injection, treatment was suspended if either one of the following criteria was met:

Improvement in best corrected visual acuity (BCVA) could not be attributed to treatment at the last 2 visits, in the opinion of the investigator, or BCVA > 84 letters (approximate Snellen equivalent of 20/20) was observed at the last 2 last visits.

Active/sham laser treatment was always administered before (sham) intravitreal injections. The minimum interval between the 2 treatments was 30 minutes.

In the extension study at the investigator's discretion, patients received open-label ranibizumab 0.5 mg intravitreal injections once a month until stable vision was reached (a maximum of 24 injections) and could receive laser therapy.

Active laser photocoagulation treatment was administered on Day 1 and at intervals of at least 3 months, if deemed necessary by the evaluating physician. Patients also received monthly sham intravitreal injection in the study eye for 3 consecutive months. After the third injection, treatment was suspended if either one of the following criteria was met:

Improvement in best corrected visual acuity (BCVA) could not be attributed to treatment at the last 2 visits, in the opinion of the investigator, or BCVA > 84 letters (approximate Snellen equivalent of 20/20) was observed at the last 2 last visits.

Active/sham laser treatment was always administered before (sham) intravitreal injections. The minimum interval between the 2 treatments was 30 minutes.

In the extension study at the investigator's discretion, patients received open-label ranibizumab 0.5 mg intravitreal injections once a month until stable vision was reached (a maximum of 24 injections) and could receive laser therapy.

Overall Number of Participants Analyzed 83 83 59 15
Measure Type: Number
Unit of Measure: Percentage of participants
Adverse Events 73.5 73.5 71.2 73.3
Serious Adverse Events 27.7 30.1 37.3 13.3
4.Secondary Outcome
Title Core Study: Categorized Change in Visual Acuity (Letters) of the Study Eye From Baseline at Month 12
Hide Description Visual acuity (VA) was assessed on both eyes during every study visit using best correction determined from protocol refraction. VA measurements (number of letters correctly identified) were performed with the patient in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like visual acuity testing charts at a testing distance of 4 meters.
Time Frame Baseline to Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set consists of all patients who received at least one application of study treatment and had at least one post-baseline assessment for BCVA. Following the intent to treat principle, patients were analyzed according to the treatment assigned. Last Observation Carried Forward (LOCF) imputation was utilized.
Arm/Group Title Ranibizumab 0.5 mg Ranibizumab 0.5 mg + Laser Laser
Hide Arm/Group Description:

Ranibizumab 0.5 mg was administered monthly by intravitreal injection in the study eye for 3 months. After the third injection, treatment was suspended if either one of the following criteria was met:

Improvement in best corrected visual acuity (BCVA) could not be attributed to treatment at the last 2 visits, in the opinion of the investigator, or BCVA > 84 letters (approximate Snellen equivalent of 20/20) was observed at the last 2 last visits.

Patients also received sham laser treatment on Day 1 and subsequently at intervals of at least 3 months, if deemed necessary by the evaluating physician.

Active/sham laser treatment was always administered before (sham) intravitreal injections. The minimum interval between the 2 treatments was 30 minutes.

Ranibizumab 0.5 mg was administered monthly by intravitreal injection in the study eye for 3 months. After the third injection, treatment was suspended if either one of the following criteria was met:

Improvement in best corrected visual acuity (BCVA) could not be attributed to treatment at the last 2 visits, in the opinion of the investigator, or BCVA > 84 letters (approximate Snellen equivalent of 20/20) was observed at the last 2 last visits.

Patients also received active laser treatment on Day 1 and subsequently at intervals of at least 3 months, if deemed necessary by the evaluating physician.

Active/sham laser treatment was always administered before (sham) intravitreal injections. The minimum interval between the 2 treatments was 30 minutes.

Laser photocoagulation treatment was administered on Day 1 and subsequently at intervals of at least 3 months, if deemed necessary by the evaluating physician. Patients also received monthly sham intravitreal injection in the study eye for 3 consecutive months. After the third injection, treatment was suspended if either one of the following criteria was met:

Improvement in best corrected visual acuity (BCVA) could not be attributed to treatment at the last 2 visits, in the opinion of the investigator, or BCVA > 84 letters (approximate Snellen equivalent of 20/20) was observed at the last 2 last visits.

Active/sham laser treatment was always administered before (sham) intravitreal injections. The minimum interval between the 2 treatments was 30 minutes.

Overall Number of Participants Analyzed 115 118 110
Measure Type: Number
Unit of Measure: Participants
Gain of ≥ 10 letters 43 51 17
Loss of ≥ 10 letters 4 5 14
Gain of ≥ 15 letters 26 27 9
Loss of ≥ 15 letters 1 4 9
5.Secondary Outcome
Title Core Study: Mean Change From Baseline in Visual Acuity (Letters) of the Study Eye Over Time
Hide Description Visual acuity (VA) was assessed on both eyes during every study visit using best correction determined from protocol refraction. VA measurements (number of letters correctly identified) were performed with the patient in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like visual acuity testing charts at a testing distance of 4 meters.
Time Frame Baseline to Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set, utilizing last observation carried forward.
Arm/Group Title Ranibizumab 0.5 mg Ranibizumab 0.5 mg + Laser Laser
Hide Arm/Group Description:

Ranibizumab 0.5 mg was administered monthly by intravitreal injection in the study eye for 3 months. After the third injection, treatment was suspended if either one of the following criteria was met:

Improvement in best corrected visual acuity (BCVA) could not be attributed to treatment at the last 2 visits, in the opinion of the investigator, or BCVA > 84 letters (approximate Snellen equivalent of 20/20) was observed at the last 2 last visits.

Patients also received sham laser treatment on Day 1 and subsequently at intervals of at least 3 months, if deemed necessary by the evaluating physician.

Active/sham laser treatment was always administered before (sham) intravitreal injections. The minimum interval between the 2 treatments was 30 minutes.

Ranibizumab 0.5 mg was administered monthly by intravitreal injection in the study eye for 3 months. After the third injection, treatment was suspended if either one of the following criteria was met:

Improvement in best corrected visual acuity (BCVA) could not be attributed to treatment at the last 2 visits, in the opinion of the investigator, or BCVA > 84 letters (approximate Snellen equivalent of 20/20) was observed at the last 2 last visits.

Patients also received active laser treatment on Day 1 and subsequently at intervals of at least 3 months, if deemed necessary by the evaluating physician.

Active/sham laser treatment was always administered before (sham) intravitreal injections. The minimum interval between the 2 treatments was 30 minutes.

Laser photocoagulation treatment was administered on Day 1 and subsequently at intervals of at least 3 months, if deemed necessary by the evaluating physician. Patients also received monthly sham intravitreal injection in the study eye for 3 consecutive months. After the third injection, treatment was suspended if either one of the following criteria was met:

Improvement in best corrected visual acuity (BCVA) could not be attributed to treatment at the last 2 visits, in the opinion of the investigator, or BCVA > 84 letters (approximate Snellen equivalent of 20/20) was observed at the last 2 last visits.

Active/sham laser treatment was always administered before (sham) intravitreal injections. The minimum interval between the 2 treatments was 30 minutes.

Overall Number of Participants Analyzed 115 118 110
Mean (Standard Error)
Unit of Measure: Letters
Month 1 2.9  (0.49) 3.1  (0.56) 0.5  (0.64)
Month 2 4.4  (0.64) 4.9  (0.56) 0.4  (0.84)
Month 3 5.9  (0.65) 5.8  (0.65) -0.5  (0.92)
Month 4 5.3  (0.68) 5.4  (0.69) 0.5  (0.92)
Month 5 5.9  (0.68) 5.7  (0.76) 0.9  (0.88)
Month 6 6.7  (0.68) 6.2  (0.78) 0.9  (0.94)
Month 7 7.0  (0.72) 6.5  (0.84) 1.1  (0.98)
Month 8 7.1  (0.75) 6.4  (1.06) 1.3  (0.96)
Month 9 6.8  (0.76) 6.8  (1.05) 1.4  (0.90)
Month 10 7.3  (0.77) 6.4  (1.04) 0.8  (1.00)
Month 11 6.9  (0.79) 6.8  (1.10) 1.4  (0.95)
Month 12 6.8  (0.77) 6.4  (1.08) 0.9  (1.09)
6.Secondary Outcome
Title Core Study: Mean Change From Baseline at Month 12 in Central Retinal Thickness of the Study Eye
Hide Description Retinal thickness was measured using Optical Coherence Tomography (OCT). The images were reviewed by a central reading center to ensure a standardized evaluation.
Time Frame Baseline to Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
The number analyzed is the Full Analysis Set, including patients with a value at both baseline and the Month 12 visit. Last Observation Carried Forward imputation was utilized.
Arm/Group Title Ranibizumab 0.5 mg Ranibizumab 0.5 mg + Laser Laser
Hide Arm/Group Description:

Ranibizumab 0.5 mg was administered monthly by intravitreal injection in the study eye for 3 months. After the third injection, treatment was suspended if either one of the following criteria was met:

Improvement in best corrected visual acuity (BCVA) could not be attributed to treatment at the last 2 visits, in the opinion of the investigator, or BCVA > 84 letters (approximate Snellen equivalent of 20/20) was observed at the last 2 last visits.

Patients also received sham laser treatment on Day 1 and subsequently at intervals of at least 3 months, if deemed necessary by the evaluating physician.

Active/sham laser treatment was always administered before (sham) intravitreal injections. The minimum interval between the 2 treatments was 30 minutes.

Ranibizumab 0.5 mg was administered monthly by intravitreal injection in the study eye for 3 months. After the third injection, treatment was suspended if either one of the following criteria was met:

Improvement in best corrected visual acuity (BCVA) could not be attributed to treatment at the last 2 visits, in the opinion of the investigator, or BCVA > 84 letters (approximate Snellen equivalent of 20/20) was observed at the last 2 last visits.

Patients also received active laser treatment on Day 1 and subsequently at intervals of at least 3 months, if deemed necessary by the evaluating physician.

Active/sham laser treatment was always administered before (sham) intravitreal injections. The minimum interval between the 2 treatments was 30 minutes.

Laser photocoagulation treatment was administered on Day 1 and subsequently at intervals of at least 3 months, if deemed necessary by the evaluating physician. Patients also received monthly sham intravitreal injection in the study eye for 3 consecutive months. After the third injection, treatment was suspended if either one of the following criteria was met:

Improvement in best corrected visual acuity (BCVA) could not be attributed to treatment at the last 2 visits, in the opinion of the investigator, or BCVA > 84 letters (approximate Snellen equivalent of 20/20) was observed at the last 2 last visits.

Active/sham laser treatment was always administered before (sham) intravitreal injections. The minimum interval between the 2 treatments was 30 minutes.

Overall Number of Participants Analyzed 113 116 108
Mean (Standard Deviation)
Unit of Measure: Micrometers
Baseline 427.1  (118.42) 416.4  (119.91) 412.4  (124.53)
Value at Month 12 308.4  (112.26) 288.2  (90.11) 351.1  (139.91)
Change from Baseline -118.7  (115.07) -128.3  (114.34) -61.3  (132.29)
7.Secondary Outcome
Title Core Study: Mean Change From Baseline in Patient-reported Visual Functioning
Hide Description The National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) was used to measure a patient's subjective assessment of vision-related quality of life. The 12 subscales in the VFQ-25 are general health, general vision, ocular pain, near activities, distance activities, social function, mental health, role difficulties, dependency, driving, color vision, and peripheral vision. The scores on the subscales were added together for a total score, which ranged from 0 to 100. A higher score indicated improvement in quality of life due to vision function.
Time Frame Baseline to Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
The number analyzed is the Full Analysis Set, including the number of patients with a value at both baseline and the Month 12 visit. Last Observation Carried Forward imputation was utilized.
Arm/Group Title Ranibizumab 0.5 mg Ranibizumab 0.5 mg + Laser Laser
Hide Arm/Group Description:

Ranibizumab 0.5 mg was administered monthly by intravitreal injection in the study eye for 3 months. After the third injection, treatment was suspended if either one of the following criteria was met:

Improvement in best corrected visual acuity (BCVA) could not be attributed to treatment at the last 2 visits, in the opinion of the investigator, or BCVA > 84 letters (approximate Snellen equivalent of 20/20) was observed at the last 2 last visits.

Patients also received sham laser treatment on Day 1 and subsequently at intervals of at least 3 months, if deemed necessary by the evaluating physician.

Active/sham laser treatment was always administered before (sham) intravitreal injections. The minimum interval between the 2 treatments was 30 minutes.

Ranibizumab 0.5 mg was administered monthly by intravitreal injection in the study eye for 3 months. After the third injection, treatment was suspended if either one of the following criteria was met:

Improvement in best corrected visual acuity (BCVA) could not be attributed to treatment at the last 2 visits, in the opinion of the investigator, or BCVA > 84 letters (approximate Snellen equivalent of 20/20) was observed at the last 2 last visits.

Patients also received active laser treatment on Day 1 and subsequently at intervals of at least 3 months, if deemed necessary by the evaluating physician.

Active/sham laser treatment was always administered before (sham) intravitreal injections. The minimum interval between the 2 treatments was 30 minutes.

Laser photocoagulation treatment was administered on Day 1 and subsequently at intervals of at least 3 months, if deemed necessary by the evaluating physician. Patients also received monthly sham intravitreal injection in the study eye for 3 consecutive months. After the third injection, treatment was suspended if either one of the following criteria was met:

Improvement in best corrected visual acuity (BCVA) could not be attributed to treatment at the last 2 visits, in the opinion of the investigator, or BCVA > 84 letters (approximate Snellen equivalent of 20/20) was observed at the last 2 last visits.

Active/sham laser treatment was always administered before (sham) intravitreal injections. The minimum interval between the 2 treatments was 30 minutes.

Overall Number of Participants Analyzed 114 116 108
Mean (Standard Deviation)
Unit of Measure: Units on a scale
Baseline 72.8  (16.91) 74.1  (18.06) 73.5  (18.18)
Month 12 77.8  (19.19) 79.5  (17.29) 74.1  (18.80)
Change from Baseline 5.0  (12.97) 5.4  (11.14) 0.6  (12.56)
8.Secondary Outcome
Title Extension Study: Percentage of Participants With Ocular Adverse Events (AEs) in the Study Eye in the 36 Months of the Core and Extension Studies
Hide Description

Participants with ocular (occurring in the eye) serious adverse events (SAEs) and non-serious AEs in the study eye. The study eye is the eye that received the treatment. AEs are the appearance or worsening of any undesirable sign, symptom, or medical condition occurring after starting the study drug even if the event is not considered to be related to study drug. A serious adverse event is defined as an event that is fatal or life-threatening, results in persistent or significant disability/incapacity, constitutes a congenital anomaly/birth defect, requires inpatient hospitalization or prolongation of existing hospitalization or is medically significant.

Additional information about adverse events can be found in the Adverse Event section.

Time Frame Core baseline (Day 1 of the core study) to Month 36 (end of extension study) [36 months]
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population included all participants who entered the extension and who had at least one safety assessment in the extension study. Participants were grouped according to the treatment assigned in the Core study.
Arm/Group Title Ranibizumab 0.5 mg Ranibizumab 0.5 mg + Laser Laser With Ranibizumab in Extension Laser Without Ranibizumab in Extension
Hide Arm/Group Description:

Ranibizumab 0.5 mg was administered monthly by intravitreal injection in the study eye for 3 months. After the third injection, treatment was suspended if either one of the following criteria was met:

Improvement in best corrected visual acuity (BCVA) could not be attributed to treatment at the last 2 visits, in the opinion of the investigator, or BCVA > 84 letters (approximate Snellen equivalent of 20/20) was observed at the last 2 last visits.

Patients also received sham laser treatment on Day 1 and subsequently at intervals of at least 3 months, if deemed necessary by the evaluating physician.

Active/sham laser treatment was always administered before (sham) intravitreal injections. The minimum interval between the 2 treatments was 30 minutes.

In the extension study at the investigator's discretion, patients received open-label ranibizumab 0.5 mg intravitreal injections once a month until stable vision was reached (a maximum of 24 injections) and could receive laser therapy.

Ranibizumab 0.5 mg was administered monthly by intravitreal injection in the study eye for 3 months. After the third injection, treatment was suspended if either one of the following criteria was met:

Improvement in best corrected visual acuity (BCVA) could not be attributed to treatment at the last 2 visits, in the opinion of the investigator, or BCVA > 84 letters (approximate Snellen equivalent of 20/20) was observed at the last 2 last visits.

Patients also received active laser treatment on Day 1 and subsequently at intervals of at least 3 months, if deemed necessary by the physician.

Active/sham laser treatment was always administered before (sham) intravitreal injections. The minimum interval between the 2 treatments was 30 minutes.

In the extension study at the investigator's discretion, patients received open-label ranibizumab 0.5 mg intravitreal injections once a month until stable vision was reached (a maximum of 24 injections) and could receive laser therapy.

Active laser photocoagulation treatment was administered on Day 1 and at intervals of at least 3 months, if deemed necessary by the evaluating physician. Patients also received monthly sham intravitreal injection in the study eye for 3 consecutive months. After the third injection, treatment was suspended if either one of the following criteria was met:

Improvement in best corrected visual acuity (BCVA) could not be attributed to treatment at the last 2 visits, in the opinion of the investigator, or BCVA > 84 letters (approximate Snellen equivalent of 20/20) was observed at the last 2 last visits.

Active/sham laser treatment was always administered before (sham) intravitreal injections. The minimum interval between the 2 treatments was 30 minutes.

In the extension study at the investigator's discretion, patients received open-label ranibizumab 0.5 mg intravitreal injections once a month until stable vision was reached (a maximum of 24 injections) and could receive laser therapy.

Active laser photocoagulation treatment was administered on Day 1 and at intervals of at least 3 months, if deemed necessary by the evaluating physician. Patients also received monthly sham intravitreal injection in the study eye for 3 consecutive months. After the third injection, treatment was suspended if either one of the following criteria was met:

Improvement in best corrected visual acuity (BCVA) could not be attributed to treatment at the last 2 visits, in the opinion of the investigator, or BCVA > 84 letters (approximate Snellen equivalent of 20/20) was observed at the last 2 last visits.

Active/sham laser treatment was always administered before (sham) intravitreal injections. The minimum interval between the 2 treatments was 30 minutes.

In the extension study at the investigator's discretion, patients received open-label ranibizumab 0.5 mg intravitreal injections once a month until stable vision was reached (a maximum of 24 injections) and could receive laser therapy.

Overall Number of Participants Analyzed 83 83 59 15
Measure Type: Number
Unit of Measure: Percentage of participants
Adverse Events 66.3 67.5 64.4 46.7
Serious Adverse Events 2.4 3.6 5.1 0.0
9.Secondary Outcome
Title Extension Study: Percentage of Participants With Non-Ocular Adverse Events (AEs) in the 36 Months of the Core and Extension Studies
Hide Description

Participants with non-ocular (not occurring in the eye) serious adverse events (SAEs) and non-serious AEs. AEs are the appearance or worsening of of any undesirable sign, symptom, or medical condition occurring after starting the study drug even if the event is not considered to be related to study drug. A serious adverse event is defined as an event that is fatal or life-threatening, results in persistent or significant disability/incapacity, constitutes a congenital anomaly/birth defect, requires inpatient hospitalization or prolongation of existing hospitalization or is medically significant.

Additional information about Adverse Events can be found in the Adverse Event section.

Time Frame Core baseline (Day 1 of the core study) to Month 36 (end of extension study) [36 Months]
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population included all participants who entered the extension and who had at least one safety assessment in the extension study. Participants were grouped according to the treatment assigned in the Core study.
Arm/Group Title Ranibizumab 0.5 mg Ranibizumab 0.5 mg + Laser Laser With Ranibizumab in Extension Laser Without Ranibizumab in Extension
Hide Arm/Group Description:

Ranibizumab 0.5 mg was administered monthly by intravitreal injection in the study eye for 3 months. After the third injection, treatment was suspended if either one of the following criteria was met:

Improvement in best corrected visual acuity (BCVA) could not be attributed to treatment at the last 2 visits, in the opinion of the investigator, or BCVA > 84 letters (approximate Snellen equivalent of 20/20) was observed at the last 2 last visits.

Patients also received sham laser treatment on Day 1 and subsequently at intervals of at least 3 months, if deemed necessary by the evaluating physician.

Active/sham laser treatment was always administered before (sham) intravitreal injections. The minimum interval between the 2 treatments was 30 minutes.

In the extension study at the investigator's discretion, patients received open-label ranibizumab 0.5 mg intravitreal injections once a month until stable vision was reached (a maximum of 24 injections) and could receive laser therapy.

Ranibizumab 0.5 mg was administered monthly by intravitreal injection in the study eye for 3 months. After the third injection, treatment was suspended if either one of the following criteria was met:

Improvement in best corrected visual acuity (BCVA) could not be attributed to treatment at the last 2 visits, in the opinion of the investigator, or BCVA > 84 letters (approximate Snellen equivalent of 20/20) was observed at the last 2 last visits.

Patients also received active laser treatment on Day 1 and subsequently at intervals of at least 3 months, if deemed necessary by the physician.

Active/sham laser treatment was always administered before (sham) intravitreal injections. The minimum interval between the 2 treatments was 30 minutes.

In the extension study at the investigator's discretion, patients received open-label ranibizumab 0.5 mg intravitreal injections once a month until stable vision was reached (a maximum of 24 injections) and could receive laser therapy.

Active laser photocoagulation treatment was administered on Day 1 and at intervals of at least 3 months, if deemed necessary by the evaluating physician. Patients also received monthly sham intravitreal injection in the study eye for 3 consecutive months. After the third injection, treatment was suspended if either one of the following criteria was met:

Improvement in best corrected visual acuity (BCVA) could not be attributed to treatment at the last 2 visits, in the opinion of the investigator, or BCVA > 84 letters (approximate Snellen equivalent of 20/20) was observed at the last 2 last visits.

Active/sham laser treatment was always administered before (sham) intravitreal injections. The minimum interval between the 2 treatments was 30 minutes.

In the extension study at the investigator's discretion, patients received open-label ranibizumab 0.5 mg intravitreal injections once a month until stable vision was reached (a maximum of 24 injections) and could receive laser therapy.

Active laser photocoagulation treatment was administered on Day 1 and at intervals of at least 3 months, if deemed necessary by the evaluating physician. Patients also received monthly sham intravitreal injection in the study eye for 3 consecutive months. After the third injection, treatment was suspended if either one of the following criteria was met:

Improvement in best corrected visual acuity (BCVA) could not be attributed to treatment at the last 2 visits, in the opinion of the investigator, or BCVA > 84 letters (approximate Snellen equivalent of 20/20) was observed at the last 2 last visits.

Active/sham laser treatment was always administered before (sham) intravitreal injections. The minimum interval between the 2 treatments was 30 minutes.

In the extension study at the investigator's discretion, patients received open-label ranibizumab 0.5 mg intravitreal injections once a month until stable vision was reached (a maximum of 24 injections) and could receive laser therapy.

Overall Number of Participants Analyzed 83 83 59 15
Measure Type: Number
Unit of Measure: Percentage of participants
Adverse Events 83.1 81.9 84.7 73.3
Serious Adverse Events 36.1 37.3 42.4 13.3
10.Secondary Outcome
Title Extension Study: Mean Change From Extension Study Baseline in Best Corrected Visual Acuity (BCVA) at Month 36
Hide Description Visual acuity (VA) was assessed on both eyes during every study visit using best correction determined from protocol refraction. VA measurements (number of letters correctly identified) were performed with the patient in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like visual acuity testing charts at a testing distance of 4 meters. An increase in the number of letters read correctly indicates improvement.
Time Frame Extension baseline (Month12 -end of core study), Month 36 (end of extension study)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants from the Safety Population that included all participants who entered the extension and who had at least one safety assessment in the extension study with data available for analyses. Participants were grouped according to the treatment assigned in the Core study.
Arm/Group Title Ranibizumab 0.5 mg Ranibizumab 0.5 mg + Laser Active Laser
Hide Arm/Group Description:

Ranibizumab 0.5 mg was administered monthly by intravitreal injection in the study eye for 3 months. After the third injection, treatment was suspended if either one of the following criteria was met:

Improvement in best corrected visual acuity (BCVA) could not be attributed to treatment at the last 2 visits, in the opinion of the investigator, or BCVA > 84 letters (approximate Snellen equivalent of 20/20) was observed at the last 2 last visits.

Patients also received sham laser treatment on Day 1 and subsequently at intervals of at least 3 months, if deemed necessary by the evaluating physician.

Active/sham laser treatment was always administered before (sham) intravitreal injections. The minimum interval between the 2 treatments was 30 minutes.

In the extension study at the investigator's discretion, patients received open-label ranibizumab 0.5 mg intravitreal injections once a month until stable vision was reached (a maximum of 24 injections) and could receive laser therapy.

Ranibizumab 0.5 mg was administered monthly by intravitreal injection in the study eye for 3 months. After the third injection, treatment was suspended if either one of the following criteria was met:

Improvement in best corrected visual acuity (BCVA) could not be attributed to treatment at the last 2 visits, in the opinion of the investigator, or BCVA > 84 letters (approximate Snellen equivalent of 20/20) was observed at the last 2 last visits.

Patients also received active laser treatment on Day 1 and subsequently at intervals of at least 3 months, if deemed necessary by the physician.

Active/sham laser treatment was always administered before (sham) intravitreal injections. The minimum interval between the 2 treatments was 30 minutes.

In the extension study at the investigator's discretion, patients received open-label ranibizumab 0.5 mg intravitreal injections once a month until stable vision was reached (a maximum of 24 injections) and could receive laser therapy.

Active laser photocoagulation treatment was administered on Day 1 and at intervals of at least 3 months, if deemed necessary by the evaluating physician. Patients also received monthly sham intravitreal injection in the study eye for 3 consecutive months. After the third injection, treatment was suspended if either one of the following criteria was met:

Improvement in best corrected visual acuity (BCVA) could not be attributed to treatment at the last 2 visits, in the opinion of the investigator, or BCVA > 84 letters (approximate Snellen equivalent of 20/20) was observed at the last 2 last visits.

Active/sham laser treatment was always administered before (sham) intravitreal injections. The minimum interval between the 2 treatments was 30 minutes.

In the extension study at the investigator's discretion, patients received open-label ranibizumab 0.5 mg intravitreal injections once a month until stable vision was reached (a maximum of 24 injections) and could receive laser therapy.

Overall Number of Participants Analyzed 83 80 74
Mean (Standard Deviation)
Unit of Measure: Letters
0.1  (9.10) -0.5  (9.19) 3.7  (6.88)
11.Secondary Outcome
Title Extension Study: Mean Change From Core Study Baseline in Best Corrected Visual Acuity (BCVA) at Month 36
Hide Description Visual acuity (VA) was assessed on both eyes during every study visit using best correction determined from protocol refraction. VA measurements (number of letters correctly identified) were performed with the patient in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like visual acuity testing charts at a testing distance of 4 meters. An increase in the number of letters read correctly indicates improvement.
Time Frame Core baseline (Day 1 of the core study), Month 36 (end of extension study)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population included all participants who entered the extension and who had at least one safety assessment in the extension study. Participants were grouped according to the treatment assigned in the Core study.
Arm/Group Title Ranibizumab 0.5 mg Ranibizumab 0.5 mg + Laser Active Laser
Hide Arm/Group Description:

Ranibizumab 0.5 mg was administered monthly by intravitreal injection in the study eye for 3 months. After the third injection, treatment was suspended if either one of the following criteria was met:

Improvement in best corrected visual acuity (BCVA) could not be attributed to treatment at the last 2 visits, in the opinion of the investigator, or BCVA > 84 letters (approximate Snellen equivalent of 20/20) was observed at the last 2 last visits.

Patients also received sham laser treatment on Day 1 and subsequently at intervals of at least 3 months, if deemed necessary by the evaluating physician.

Active/sham laser treatment was always administered before (sham) intravitreal injections. The minimum interval between the 2 treatments was 30 minutes.

In the extension study at the investigator's discretion, patients received open-label ranibizumab 0.5 mg intravitreal injections once a month until stable vision was reached (a maximum of 24 injections) and could receive laser therapy.

Ranibizumab 0.5 mg was administered monthly by intravitreal injection in the study eye for 3 months. After the third injection, treatment was suspended if either one of the following criteria was met:

Improvement in best corrected visual acuity (BCVA) could not be attributed to treatment at the last 2 visits, in the opinion of the investigator, or BCVA > 84 letters (approximate Snellen equivalent of 20/20) was observed at the last 2 last visits.

Patients also received active laser treatment on Day 1 and subsequently at intervals of at least 3 months, if deemed necessary by the physician.

Active/sham laser treatment was always administered before (sham) intravitreal injections. The minimum interval between the 2 treatments was 30 minutes.

In the extension study at the investigator's discretion, patients received open-label ranibizumab 0.5 mg intravitreal injections once a month until stable vision was reached (a maximum of 24 injections) and could receive laser therapy.

Active laser photocoagulation treatment was administered on Day 1 and at intervals of at least 3 months, if deemed necessary by the evaluating physician. Patients also received monthly sham intravitreal injection in the study eye for 3 consecutive months. After the third injection, treatment was suspended if either one of the following criteria was met:

Improvement in best corrected visual acuity (BCVA) could not be attributed to treatment at the last 2 visits, in the opinion of the investigator, or BCVA > 84 letters (approximate Snellen equivalent of 20/20) was observed at the last 2 last visits.

Active/sham laser treatment was always administered before (sham) intravitreal injections. The minimum interval between the 2 treatments was 30 minutes.

In the extension study at the investigator's discretion, patients received open-label ranibizumab 0.5 mg intravitreal injections once a month until stable vision was reached (a maximum of 24 injections) and could receive laser therapy.

Overall Number of Participants Analyzed 83 83 74
Mean (Standard Deviation)
Unit of Measure: Letters
8.0  (10.09) 6.7  (9.59) 6.0  (9.35)
Time Frame [Not Specified]
Adverse Event Reporting Description Safety Population included all randomized treated participants. Participants are grouped according to the treatment actually received in the Core Study.
 
Arm/Group Title Ranibizumab 0.5 mg Ranibizumab 0.5 mg + Laser Laser With Ranibizumab in Extension Laser Without Ranibizumab in Extension
Hide Arm/Group Description

Ranibizumab 0.5 mg was administered monthly by intravitreal injection in the study eye for 3 months. After the third injection, treatment was suspended if either one of the following criteria was met:

Improvement in best corrected visual acuity (BCVA) could not be attributed to treatment at the last 2 visits, in the opinion of the investigator, or BCVA > 84 letters (approximate Snellen equivalent of 20/20) was observed at the last 2 last visits.

Patients also received sham laser treatment on Day 1 and subsequently at intervals of at least 3 months, if deemed necessary by the evaluating physician.

Active/sham laser treatment was always administered before (sham) intravitreal injections. The minimum interval between the 2 treatments was 30 minutes.

In the extension study at the investigator's discretion, patients received open-label ranibizumab 0.5 mg intravitreal injections once a month until stable vision was reached (a maximum of 24 injections) and could receive laser therapy.

Ranibizumab 0.5 mg was administered monthly by intravitreal injection in the study eye for 3 months. After the third injection, treatment was suspended if either one of the following criteria was met:

Improvement in best corrected visual acuity (BCVA) could not be attributed to treatment at the last 2 visits, in the opinion of the investigator, or BCVA > 84 letters (approximate Snellen equivalent of 20/20) was observed at the last 2 last visits.

Patients also received active laser treatment on Day 1 and subsequently at intervals of at least 3 months, if deemed necessary by the evaluating physician.

Active/sham laser treatment was always administered before (sham) intravitreal injections. The minimum interval between the 2 treatments was 30 minutes.

In the extension study at the investigator's discretion, patients received open-label ranibizumab 0.5 mg intravitreal injections once a month until stable vision was reached (a maximum of 24 injections) and could receive laser therapy

Active laser photocoagulation treatment was administered on Day 1 and at intervals of at least 3 months, if deemed necessary by the evaluating physician. Patients also received monthly sham intravitreal injection in the study eye for 3 consecutive months. After the third injection, treatment was suspended if either one of the following criteria was met:

Improvement in best corrected visual acuity (BCVA) could not be attributed to treatment at the last 2 visits, in the opinion of the investigator, or BCVA > 84 letters (approximate Snellen equivalent of 20/20) was observed at the last 2 last visits.

Active/sham laser treatment was always administered before (sham) intravitreal injections. The minimum interval between the 2 treatments was 30 minutes.

In the extension study at the investigator's discretion, patients received open-label ranibizumab 0.5 mg intravitreal injections once a month until stable vision was reached (a maximum of 24 injections) and could receive laser therapy.

Active laser photocoagulation treatment was administered on Day 1 and at intervals of at least 3 months, if deemed necessary by the evaluating physician. Patients also received monthly sham intravitreal injection in the study eye for 3 consecutive months. After the third injection, treatment was suspended if either one of the following criteria was met:

Improvement in best corrected visual acuity (BCVA) could not be attributed to treatment at the last 2 visits, in the opinion of the investigator, or BCVA > 84 letters (approximate Snellen equivalent of 20/20) was observed at the last 2 last visits.

Active/sham laser treatment was always administered before (sham) intravitreal injections. The minimum interval between the 2 treatments was 30 minutes.

In the extension study at the investigator's discretion, patients received open-label ranibizumab 0.5 mg intravitreal injections once a month until stable vision was reached (a maximum of 24 injections) and could receive laser therapy.

All-Cause Mortality
Ranibizumab 0.5 mg Ranibizumab 0.5 mg + Laser Laser With Ranibizumab in Extension Laser Without Ranibizumab in Extension
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/-- 
Hide Serious Adverse Events
Ranibizumab 0.5 mg Ranibizumab 0.5 mg + Laser Laser With Ranibizumab in Extension Laser Without Ranibizumab in Extension
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   41/115 (35.65%)   43/120 (35.83%)   28/59 (47.46%)   7/51 (13.73%) 
Blood and lymphatic system disorders         
Anaemia  1  1/115 (0.87%)  1/120 (0.83%)  1/59 (1.69%)  0/51 (0.00%) 
Febrile neutropenia  1  0/115 (0.00%)  0/120 (0.00%)  1/59 (1.69%)  0/51 (0.00%) 
Hypochromic anaemia  1  0/115 (0.00%)  1/120 (0.83%)  0/59 (0.00%)  0/51 (0.00%) 
Lymphadenopathy  1  0/115 (0.00%)  0/120 (0.00%)  1/59 (1.69%)  0/51 (0.00%) 
Spleen disorder  1  1/115 (0.87%)  0/120 (0.00%)  0/59 (0.00%)  0/51 (0.00%) 
Splenic infarction  1  0/115 (0.00%)  1/120 (0.83%)  0/59 (0.00%)  0/51 (0.00%) 
Cardiac disorders         
Acute myocardial infarction  1  1/115 (0.87%)  0/120 (0.00%)  2/59 (3.39%)  0/51 (0.00%) 
Angina pectoris  1  3/115 (2.61%)  1/120 (0.83%)  0/59 (0.00%)  0/51 (0.00%) 
Angina unstable  1  0/115 (0.00%)  0/120 (0.00%)  1/59 (1.69%)  0/51 (0.00%) 
Aortic valve stenosis  1  1/115 (0.87%)  0/120 (0.00%)  0/59 (0.00%)  0/51 (0.00%) 
Arrhythmia  1  0/115 (0.00%)  1/120 (0.83%)  0/59 (0.00%)  0/51 (0.00%) 
Atrial fibrillation  1  1/115 (0.87%)  0/120 (0.00%)  0/59 (0.00%)  0/51 (0.00%) 
Cardiac disorder  1  0/115 (0.00%)  0/120 (0.00%)  0/59 (0.00%)  1/51 (1.96%) 
Cardiac failure  1  1/115 (0.87%)  1/120 (0.83%)  4/59 (6.78%)  1/51 (1.96%) 
Cardiac failure congestive  1  0/115 (0.00%)  0/120 (0.00%)  1/59 (1.69%)  0/51 (0.00%) 
Cardiogenic shock  1  1/115 (0.87%)  0/120 (0.00%)  0/59 (0.00%)  0/51 (0.00%) 
Cardiopulmonary failure  1  1/115 (0.87%)  0/120 (0.00%)  0/59 (0.00%)  0/51 (0.00%) 
Coronary artery disease  1  3/115 (2.61%)  1/120 (0.83%)  1/59 (1.69%)  0/51 (0.00%) 
Coronary artery occlusion  1  0/115 (0.00%)  1/120 (0.83%)  0/59 (0.00%)  0/51 (0.00%) 
Mitral valve incompetence  1  0/115 (0.00%)  0/120 (0.00%)  1/59 (1.69%)  0/51 (0.00%) 
Myocardial infarction  1  1/115 (0.87%)  4/120 (3.33%)  3/59 (5.08%)  0/51 (0.00%) 
Myocardial ischaemia  1  1/115 (0.87%)  1/120 (0.83%)  0/59 (0.00%)  0/51 (0.00%) 
Right ventricular failure  1  1/115 (0.87%)  0/120 (0.00%)  0/59 (0.00%)  0/51 (0.00%) 
Tachyarrhythmia  1  0/115 (0.00%)  0/120 (0.00%)  1/59 (1.69%)  0/51 (0.00%) 
Congenital, familial and genetic disorders         
Spinocerebellar ataxia  1  0/115 (0.00%)  1/120 (0.83%)  0/59 (0.00%)  0/51 (0.00%) 
Ear and labyrinth disorders         
Deafness  1  1/115 (0.87%)  0/120 (0.00%)  0/59 (0.00%)  0/51 (0.00%) 
Vertigo  1  0/115 (0.00%)  0/120 (0.00%)  1/59 (1.69%)  0/51 (0.00%) 
Eye disorders         
Cataract (Fellow eye)  1  2/115 (1.74%)  1/120 (0.83%)  1/59 (1.69%)  0/51 (0.00%) 
Cataract (Study eye)  1  0/115 (0.00%)  3/120 (2.50%)  2/59 (3.39%)  0/51 (0.00%) 
Cataract subcapsular (Fellow eye)  1  1/115 (0.87%)  0/120 (0.00%)  0/59 (0.00%)  0/51 (0.00%) 
Conjunctival haemorrhage (Study eye)  1  1/115 (0.87%)  0/120 (0.00%)  0/59 (0.00%)  0/51 (0.00%) 
Corneal oedema (Study eye)  1  1/115 (0.87%)  0/120 (0.00%)  0/59 (0.00%)  0/51 (0.00%) 
Diabetic retinal oedema (Fellow eye)  1  1/115 (0.87%)  1/120 (0.83%)  1/59 (1.69%)  0/51 (0.00%) 
Lenticular opacities (Study eye)  1  1/115 (0.87%)  0/120 (0.00%)  0/59 (0.00%)  0/51 (0.00%) 
Vitreous adhesions (Study eye)  1  0/115 (0.00%)  0/120 (0.00%)  1/59 (1.69%)  0/51 (0.00%) 
Vitreous haemorrhage (Fellow eye)  1  2/115 (1.74%)  0/120 (0.00%)  1/59 (1.69%)  1/51 (1.96%) 
Vitreous haemorrhage (Study eye)  1  0/115 (0.00%)  0/120 (0.00%)  1/59 (1.69%)  0/51 (0.00%) 
Gastrointestinal disorders         
Abdominal hernia  1  1/115 (0.87%)  0/120 (0.00%)  0/59 (0.00%)  0/51 (0.00%) 
Abdominal pain  1  0/115 (0.00%)  1/120 (0.83%)  0/59 (0.00%)  0/51 (0.00%) 
Abdominal pain upper  1  0/115 (0.00%)  0/120 (0.00%)  1/59 (1.69%)  0/51 (0.00%) 
Colonic polyp  1  1/115 (0.87%)  0/120 (0.00%)  0/59 (0.00%)  0/51 (0.00%) 
Constipation  1  0/115 (0.00%)  1/120 (0.83%)  0/59 (0.00%)  0/51 (0.00%) 
Diarrhoea  1  0/115 (0.00%)  1/120 (0.83%)  1/59 (1.69%)  0/51 (0.00%) 
Gastric haemorrhage  1  0/115 (0.00%)  0/120 (0.00%)  0/59 (0.00%)  1/51 (1.96%) 
Gastric ulcer  1  0/115 (0.00%)  0/120 (0.00%)  0/59 (0.00%)  1/51 (1.96%) 
Gastrointestinal necrosis  1  0/115 (0.00%)  0/120 (0.00%)  1/59 (1.69%)  0/51 (0.00%) 
Gastrointestinal obstruction  1  0/115 (0.00%)  1/120 (0.83%)  0/59 (0.00%)  0/51 (0.00%) 
Hernial eventration  1  0/115 (0.00%)  1/120 (0.83%)  0/59 (0.00%)  0/51 (0.00%) 
Intestinal obstruction  1  1/115 (0.87%)  0/120 (0.00%)  0/59 (0.00%)  0/51 (0.00%) 
Nausea  1  0/115 (0.00%)  0/120 (0.00%)  1/59 (1.69%)  0/51 (0.00%) 
Oesophagitis  1  1/115 (0.87%)  0/120 (0.00%)  0/59 (0.00%)  0/51 (0.00%) 
Pancreatitis acute  1  0/115 (0.00%)  0/120 (0.00%)  0/59 (0.00%)  1/51 (1.96%) 
Subileus  1  0/115 (0.00%)  1/120 (0.83%)  0/59 (0.00%)  0/51 (0.00%) 
Umbilical hernia  1  0/115 (0.00%)  1/120 (0.83%)  0/59 (0.00%)  0/51 (0.00%) 
Vomiting  1  1/115 (0.87%)  0/120 (0.00%)  1/59 (1.69%)  0/51 (0.00%) 
General disorders         
Chest discomfort  1  0/115 (0.00%)  0/120 (0.00%)  1/59 (1.69%)  0/51 (0.00%) 
Malaise  1  0/115 (0.00%)  1/120 (0.83%)  0/59 (0.00%)  0/51 (0.00%) 
Multi-organ failure  1  1/115 (0.87%)  0/120 (0.00%)  0/59 (0.00%)  0/51 (0.00%) 
Oedema peripheral  1  0/115 (0.00%)  1/120 (0.83%)  0/59 (0.00%)  0/51 (0.00%) 
Polyserositis  1  0/115 (0.00%)  1/120 (0.83%)  0/59 (0.00%)  0/51 (0.00%) 
Pyrexia  1  0/115 (0.00%)  1/120 (0.83%)  0/59 (0.00%)  0/51 (0.00%) 
Hepatobiliary disorders         
Bile duct obstruction  1  0/115 (0.00%)  1/120 (0.83%)  0/59 (0.00%)  0/51 (0.00%) 
Cholecystitis  1  0/115 (0.00%)  1/120 (0.83%)  0/59 (0.00%)  0/51 (0.00%) 
Cholelithiasis  1  1/115 (0.87%)  1/120 (0.83%)  0/59 (0.00%)  0/51 (0.00%) 
Hepatic function abnormal  1  0/115 (0.00%)  1/120 (0.83%)  0/59 (0.00%)  0/51 (0.00%) 
Infections and infestations         
Appendicitis  1  2/115 (1.74%)  0/120 (0.00%)  0/59 (0.00%)  0/51 (0.00%) 
Biliary sepsis  1  1/115 (0.87%)  0/120 (0.00%)  0/59 (0.00%)  0/51 (0.00%) 
Bronchitis  1  1/115 (0.87%)  0/120 (0.00%)  0/59 (0.00%)  0/51 (0.00%) 
Cellulitis  1  0/115 (0.00%)  0/120 (0.00%)  1/59 (1.69%)  0/51 (0.00%) 
Cholecystitis infective  1  1/115 (0.87%)  0/120 (0.00%)  0/59 (0.00%)  0/51 (0.00%) 
Gas gangrene  1  0/115 (0.00%)  1/120 (0.83%)  0/59 (0.00%)  0/51 (0.00%) 
Gastroenteritis  1  1/115 (0.87%)  1/120 (0.83%)  0/59 (0.00%)  0/51 (0.00%) 
Gastroenteritis norovirus  1  0/115 (0.00%)  1/120 (0.83%)  0/59 (0.00%)  0/51 (0.00%) 
Infection  1  0/115 (0.00%)  1/120 (0.83%)  0/59 (0.00%)  0/51 (0.00%) 
Localised infection  1  0/115 (0.00%)  0/120 (0.00%)  1/59 (1.69%)  0/51 (0.00%) 
Lower respiratory tract infection  1  0/115 (0.00%)  0/120 (0.00%)  1/59 (1.69%)  0/51 (0.00%) 
Mediastinitis  1  1/115 (0.87%)  0/120 (0.00%)  0/59 (0.00%)  0/51 (0.00%) 
Osteomyelitis  1  1/115 (0.87%)  0/120 (0.00%)  0/59 (0.00%)  0/51 (0.00%) 
Otitis media  1  0/115 (0.00%)  0/120 (0.00%)  1/59 (1.69%)  0/51 (0.00%) 
Pneumonia  1  0/115 (0.00%)  1/120 (0.83%)  3/59 (5.08%)  0/51 (0.00%) 
Pneumonia cytomegaloviral  1  0/115 (0.00%)  0/120 (0.00%)  1/59 (1.69%)  0/51 (0.00%) 
Pseudomonas infection  1  1/115 (0.87%)  0/120 (0.00%)  0/59 (0.00%)  0/51 (0.00%) 
Sepsis  1  1/115 (0.87%)  1/120 (0.83%)  0/59 (0.00%)  0/51 (0.00%) 
Soft tissue infection  1  0/115 (0.00%)  0/120 (0.00%)  1/59 (1.69%)  0/51 (0.00%) 
Staphylococcal infection  1  0/115 (0.00%)  1/120 (0.83%)  0/59 (0.00%)  0/51 (0.00%) 
Systemic candida  1  0/115 (0.00%)  0/120 (0.00%)  1/59 (1.69%)  0/51 (0.00%) 
Urinary tract infection  1  1/115 (0.87%)  0/120 (0.00%)  0/59 (0.00%)  0/51 (0.00%) 
Injury, poisoning and procedural complications         
Back injury  1  1/115 (0.87%)  0/120 (0.00%)  0/59 (0.00%)  0/51 (0.00%) 
Contusion  1  1/115 (0.87%)  0/120 (0.00%)  0/59 (0.00%)  0/51 (0.00%) 
Coronary artery restenosis  1  0/115 (0.00%)  1/120 (0.83%)  0/59 (0.00%)  0/51 (0.00%) 
Eye injury (Fellow eye)  1  1/115 (0.87%)  0/120 (0.00%)  0/59 (0.00%)  0/51 (0.00%) 
Eye injury (Study eye)  1  1/115 (0.87%)  0/120 (0.00%)  0/59 (0.00%)  0/51 (0.00%) 
Eyelid injury (Study eye)  1  1/115 (0.87%)  0/120 (0.00%)  0/59 (0.00%)  0/51 (0.00%) 
Fall  1  3/115 (2.61%)  0/120 (0.00%)  0/59 (0.00%)  0/51 (0.00%) 
Femoral neck fracture  1  1/115 (0.87%)  0/120 (0.00%)  0/59 (0.00%)  0/51 (0.00%) 
Femur fracture  1  0/115 (0.00%)  1/120 (0.83%)  0/59 (0.00%)  0/51 (0.00%) 
Head injury  1  1/115 (0.87%)  0/120 (0.00%)  0/59 (0.00%)  0/51 (0.00%) 
Lower limb fracture  1  1/115 (0.87%)  2/120 (1.67%)  0/59 (0.00%)  0/51 (0.00%) 
Lumbar vertebral fracture  1  1/115 (0.87%)  0/120 (0.00%)  0/59 (0.00%)  0/51 (0.00%) 
Meniscus lesion  1  1/115 (0.87%)  0/120 (0.00%)  0/59 (0.00%)  0/51 (0.00%) 
Open wound  1  1/115 (0.87%)  0/120 (0.00%)  0/59 (0.00%)  0/51 (0.00%) 
Periorbital haematoma (Study eye)  1  1/115 (0.87%)  0/120 (0.00%)  0/59 (0.00%)  0/51 (0.00%) 
Post procedural complication  1  0/115 (0.00%)  0/120 (0.00%)  1/59 (1.69%)  0/51 (0.00%) 
Radius fracture  1  0/115 (0.00%)  1/120 (0.83%)  0/59 (0.00%)  0/51 (0.00%) 
Road traffic accident  1  1/115 (0.87%)  0/120 (0.00%)  0/59 (0.00%)  0/51 (0.00%) 
Spinal cord injury  1  1/115 (0.87%)  0/120 (0.00%)  0/59 (0.00%)  0/51 (0.00%) 
Tendon rupture  1  1/115 (0.87%)  0/120 (0.00%)  0/59 (0.00%)  0/51 (0.00%) 
Investigations         
Blood calcium increased  1  0/115 (0.00%)  1/120 (0.83%)  0/59 (0.00%)  0/51 (0.00%) 
Blood glucose increased  1  0/115 (0.00%)  1/120 (0.83%)  0/59 (0.00%)  0/51 (0.00%) 
Blood urea increased  1  1/115 (0.87%)  0/120 (0.00%)  0/59 (0.00%)  0/51 (0.00%) 
Body temperature decreased  1  1/115 (0.87%)  0/120 (0.00%)  0/59 (0.00%)  0/51 (0.00%) 
Metabolism and nutrition disorders         
Dehydration  1  0/115 (0.00%)  0/120 (0.00%)  1/59 (1.69%)  0/51 (0.00%) 
Diabetes mellitus  1  0/115 (0.00%)  2/120 (1.67%)  0/59 (0.00%)  0/51 (0.00%) 
Diabetic foot  1  2/115 (1.74%)  0/120 (0.00%)  3/59 (5.08%)  1/51 (1.96%) 
Hyperglycaemia  1  0/115 (0.00%)  1/120 (0.83%)  0/59 (0.00%)  0/51 (0.00%) 
Hyperkalaemia  1  0/115 (0.00%)  1/120 (0.83%)  0/59 (0.00%)  0/51 (0.00%) 
Hyperuricaemia  1  0/115 (0.00%)  1/120 (0.83%)  0/59 (0.00%)  0/51 (0.00%) 
Hypoglycaemia  1  1/115 (0.87%)  0/120 (0.00%)  1/59 (1.69%)  0/51 (0.00%) 
Obesity  1  1/115 (0.87%)  0/120 (0.00%)  0/59 (0.00%)  0/51 (0.00%) 
Type 2 diabetes mellitus  1  1/115 (0.87%)  0/120 (0.00%)  0/59 (0.00%)  0/51 (0.00%) 
Musculoskeletal and connective tissue disorders         
Intervertebral disc protrusion  1  0/115 (0.00%)  3/120 (2.50%)  1/59 (1.69%)  0/51 (0.00%) 
Lumbar spinal stenosis  1  1/115 (0.87%)  0/120 (0.00%)  0/59 (0.00%)  0/51 (0.00%) 
Osteoarthritis  1  0/115 (0.00%)  0/120 (0.00%)  1/59 (1.69%)  0/51 (0.00%) 
Osteochondrosis  1  1/115 (0.87%)  0/120 (0.00%)  0/59 (0.00%)  0/51 (0.00%) 
Spinal column stenosis  1  1/115 (0.87%)  0/120 (0.00%)  0/59 (0.00%)  0/51 (0.00%) 
Spinal osteoarthritis  1  1/115 (0.87%)  0/120 (0.00%)  0/59 (0.00%)  0/51 (0.00%) 
Spondylolisthesis  1  1/115 (0.87%)  0/120 (0.00%)  0/59 (0.00%)  0/51 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
Colon cancer  1  1/115 (0.87%)  0/120 (0.00%)  0/59 (0.00%)  0/51 (0.00%) 
Gastric cancer  1  0/115 (0.00%)  0/120 (0.00%)  1/59 (1.69%)  0/51 (0.00%) 
Hepatic neoplasm  1  0/115 (0.00%)  0/120 (0.00%)  1/59 (1.69%)  0/51 (0.00%) 
Malignant neoplasm of ampulla of Vater  1  0/115 (0.00%)  1/120 (0.83%)  0/59 (0.00%)  0/51 (0.00%) 
Multiple myeloma  1  0/115 (0.00%)  1/120 (0.83%)  0/59 (0.00%)  0/51 (0.00%) 
Pancreatic carcinoma  1  0/115 (0.00%)  1/120 (0.83%)  0/59 (0.00%)  0/51 (0.00%) 
Prostate cancer  1  1/115 (0.87%)  0/120 (0.00%)  1/59 (1.69%)  0/51 (0.00%) 
Rectal cancer  1  0/115 (0.00%)  1/120 (0.83%)  0/59 (0.00%)  0/51 (0.00%) 
Renal cancer  1  0/115 (0.00%)  1/120 (0.83%)  0/59 (0.00%)  0/51 (0.00%) 
Urethral neoplasm  1  1/115 (0.87%)  0/120 (0.00%)  0/59 (0.00%)  0/51 (0.00%) 
Uterine leiomyoma  1  1/115 (0.87%)  0/120 (0.00%)  0/59 (0.00%)  0/51 (0.00%) 
Nervous system disorders         
Carotid artery stenosis  1  1/115 (0.87%)  0/120 (0.00%)  0/59 (0.00%)  1/51 (1.96%) 
Cerebral artery embolism  1  1/115 (0.87%)  0/120 (0.00%)  0/59 (0.00%)  0/51 (0.00%) 
Cerebrovascular accident  1  3/115 (2.61%)  1/120 (0.83%)  1/59 (1.69%)  0/51 (0.00%) 
Cerebrovascular disorder  1  0/115 (0.00%)  1/120 (0.83%)  0/59 (0.00%)  0/51 (0.00%) 
Diabetic neuropathy  1  0/115 (0.00%)  0/120 (0.00%)  1/59 (1.69%)  0/51 (0.00%) 
Dizziness  1  0/115 (0.00%)  0/120 (0.00%)  1/59 (1.69%)  0/51 (0.00%) 
Embolic stroke  1  0/115 (0.00%)  1/120 (0.83%)  0/59 (0.00%)  0/51 (0.00%) 
Hepatic encephalopathy  1  1/115 (0.87%)  0/120 (0.00%)  0/59 (0.00%)  0/51 (0.00%) 
Loss of consciousness  1  1/115 (0.87%)  0/120 (0.00%)  0/59 (0.00%)  0/51 (0.00%) 
Subarachnoid haemorrhage  1  2/115 (1.74%)  0/120 (0.00%)  0/59 (0.00%)  0/51 (0.00%) 
Syncope  1  1/115 (0.87%)  0/120 (0.00%)  1/59 (1.69%)  0/51 (0.00%) 
Transient ischaemic attack  1  0/115 (0.00%)  0/120 (0.00%)  1/59 (1.69%)  0/51 (0.00%) 
Psychiatric disorders         
Depression  1  0/115 (0.00%)  0/120 (0.00%)  1/59 (1.69%)  0/51 (0.00%) 
Renal and urinary disorders         
Acute prerenal failure  1  0/115 (0.00%)  0/120 (0.00%)  1/59 (1.69%)  0/51 (0.00%) 
Bladder prolapse  1  1/115 (0.87%)  0/120 (0.00%)  0/59 (0.00%)  0/51 (0.00%) 
Calculus urinary  1  0/115 (0.00%)  0/120 (0.00%)  1/59 (1.69%)  0/51 (0.00%) 
Nephrolithiasis  1  0/115 (0.00%)  0/120 (0.00%)  1/59 (1.69%)  0/51 (0.00%) 
Polyuria  1  0/115 (0.00%)  0/120 (0.00%)  1/59 (1.69%)  0/51 (0.00%) 
Renal colic  1  0/115 (0.00%)  0/120 (0.00%)  1/59 (1.69%)  0/51 (0.00%) 
Renal failure  1  0/115 (0.00%)  1/120 (0.83%)  0/59 (0.00%)  0/51 (0.00%) 
Renal failure acute  1  1/115 (0.87%)  1/120 (0.83%)  0/59 (0.00%)  0/51 (0.00%) 
Renal failure chronic  1  0/115 (0.00%)  1/120 (0.83%)  0/59 (0.00%)  1/51 (1.96%) 
Reproductive system and breast disorders         
Benign prostatic hyperplasia  1  0/115 (0.00%)  1/120 (0.83%)  0/59 (0.00%)  0/51 (0.00%) 
Respiratory, thoracic and mediastinal disorders         
Dyspnoea  1  1/115 (0.87%)  1/120 (0.83%)  1/59 (1.69%)  0/51 (0.00%) 
Epistaxis  1  2/115 (1.74%)  0/120 (0.00%)  0/59 (0.00%)  0/51 (0.00%) 
Nasal septum deviation  1  0/115 (0.00%)  1/120 (0.83%)  0/59 (0.00%)  0/51 (0.00%) 
Pulmonary embolism  1  2/115 (1.74%)  1/120 (0.83%)  0/59 (0.00%)  0/51 (0.00%) 
Pulmonary haematoma  1  1/115 (0.87%)  0/120 (0.00%)  0/59 (0.00%)  0/51 (0.00%) 
Pulmonary oedema  1  0/115 (0.00%)  0/120 (0.00%)  1/59 (1.69%)  0/51 (0.00%) 
Respiratory arrest  1  0/115 (0.00%)  1/120 (0.83%)  0/59 (0.00%)  0/51 (0.00%) 
Sleep apnoea syndrome  1  0/115 (0.00%)  0/120 (0.00%)  0/59 (0.00%)  1/51 (1.96%) 
Skin and subcutaneous tissue disorders         
Acute febrile neutrophilic dermatosis  1  0/115 (0.00%)  0/120 (0.00%)  1/59 (1.69%)  0/51 (0.00%) 
Dermatitis  1  0/115 (0.00%)  1/120 (0.83%)  0/59 (0.00%)  0/51 (0.00%) 
Skin hypertrophy  1  1/115 (0.87%)  0/120 (0.00%)  0/59 (0.00%)  0/51 (0.00%) 
Skin ulcer  1  0/115 (0.00%)  1/120 (0.83%)  0/59 (0.00%)  0/51 (0.00%) 
Vascular disorders         
Arterial thrombosis limb  1  1/115 (0.87%)  0/120 (0.00%)  0/59 (0.00%)  0/51 (0.00%) 
Deep vein thrombosis  1  0/115 (0.00%)  0/120 (0.00%)  1/59 (1.69%)  0/51 (0.00%) 
Hypertension  1  1/115 (0.87%)  2/120 (1.67%)  1/59 (1.69%)  0/51 (0.00%) 
Hypertensive crisis  1  0/115 (0.00%)  0/120 (0.00%)  1/59 (1.69%)  0/51 (0.00%) 
Hypotension  1  1/115 (0.87%)  0/120 (0.00%)  1/59 (1.69%)  0/51 (0.00%) 
Peripheral arterial occlusive disease  1  1/115 (0.87%)  1/120 (0.83%)  1/59 (1.69%)  0/51 (0.00%) 
Varicose vein  1  1/115 (0.87%)  0/120 (0.00%)  0/59 (0.00%)  0/51 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Ranibizumab 0.5 mg Ranibizumab 0.5 mg + Laser Laser With Ranibizumab in Extension Laser Without Ranibizumab in Extension
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   79/115 (68.70%)   83/120 (69.17%)   50/59 (84.75%)   31/51 (60.78%) 
Blood and lymphatic system disorders         
Anaemia  1  2/115 (1.74%)  6/120 (5.00%)  3/59 (5.08%)  1/51 (1.96%) 
Eye disorders         
Blepharitis (Fellow eye)  1  1/115 (0.87%)  1/120 (0.83%)  3/59 (5.08%)  1/51 (1.96%) 
Cataract (Fellow eye)  1  10/115 (8.70%)  12/120 (10.00%)  7/59 (11.86%)  5/51 (9.80%) 
Cataract (Study eye)  1  9/115 (7.83%)  17/120 (14.17%)  9/59 (15.25%)  4/51 (7.84%) 
Conjunctival haemorrhage (Study eye)  1  9/115 (7.83%)  13/120 (10.83%)  0/59 (0.00%)  0/51 (0.00%) 
Conjunctival hyperaemia (Study eye)  1  9/115 (7.83%)  8/120 (6.67%)  5/59 (8.47%)  2/51 (3.92%) 
Conjunctivitis (Fellow eye)  1  4/115 (3.48%)  6/120 (5.00%)  3/59 (5.08%)  1/51 (1.96%) 
Diabetic retinal oedema (Fellow eye)  1  12/115 (10.43%)  19/120 (15.83%)  11/59 (18.64%)  3/51 (5.88%) 
Diabetic retinal oedema (Study eye)  1  7/115 (6.09%)  6/120 (5.00%)  3/59 (5.08%)  1/51 (1.96%) 
Diabetic retinopathy (Fellow eye)  1  4/115 (3.48%)  6/120 (5.00%)  4/59 (6.78%)  2/51 (3.92%) 
Diabetic retinopathy (Study eye)  1  3/115 (2.61%)  8/120 (6.67%)  3/59 (5.08%)  2/51 (3.92%) 
Dry eye (Fellow eye)  1  5/115 (4.35%)  4/120 (3.33%)  3/59 (5.08%)  3/51 (5.88%) 
Dry eye (Study eye)  1  5/115 (4.35%)  4/120 (3.33%)  3/59 (5.08%)  3/51 (5.88%) 
Eye discharge (Study eye)  1  4/115 (3.48%)  6/120 (5.00%)  1/59 (1.69%)  1/51 (1.96%) 
Eye haemorrhage (Fellow eye)  1  2/115 (1.74%)  3/120 (2.50%)  3/59 (5.08%)  0/51 (0.00%) 
Eye haemorrhage (Study eye)  1  2/115 (1.74%)  3/120 (2.50%)  3/59 (5.08%)  0/51 (0.00%) 
Eye irritation (Study eye)  1  3/115 (2.61%)  2/120 (1.67%)  3/59 (5.08%)  0/51 (0.00%) 
Eye pain (Study eye)  1  15/115 (13.04%)  11/120 (9.17%)  13/59 (22.03%)  2/51 (3.92%) 
Eye pruritus (Study eye)  1  3/115 (2.61%)  3/120 (2.50%)  5/59 (8.47%)  1/51 (1.96%) 
Foreign body sensation in eyes (Study eye)  1  5/115 (4.35%)  8/120 (6.67%)  2/59 (3.39%)  0/51 (0.00%) 
Lacrimation increased (Study eye)  1  3/115 (2.61%)  6/120 (5.00%)  5/59 (8.47%)  0/51 (0.00%) 
Macular fibrosis (Study eye)  1  2/115 (1.74%)  2/120 (1.67%)  5/59 (8.47%)  0/51 (0.00%) 
Punctate keratitis (Fellow eye)  1  1/115 (0.87%)  6/120 (5.00%)  0/59 (0.00%)  0/51 (0.00%) 
Retinal aneurysm (Study eye)  1  0/115 (0.00%)  3/120 (2.50%)  3/59 (5.08%)  1/51 (1.96%) 
Retinal exudates (Fellow eye)  1  7/115 (6.09%)  3/120 (2.50%)  3/59 (5.08%)  1/51 (1.96%) 
Retinal exudates (Study eye)  1  4/115 (3.48%)  2/120 (1.67%)  5/59 (8.47%)  1/51 (1.96%) 
Retinal haemorrhage (Fellow eye)  1  4/115 (3.48%)  8/120 (6.67%)  2/59 (3.39%)  0/51 (0.00%) 
Vision blurred (Study eye)  1  2/115 (1.74%)  4/120 (3.33%)  3/59 (5.08%)  2/51 (3.92%) 
Visual acuity reduced (Fellow eye)  1  4/115 (3.48%)  3/120 (2.50%)  3/59 (5.08%)  2/51 (3.92%) 
Visual acuity reduced (Study eye)  1  1/115 (0.87%)  2/120 (1.67%)  1/59 (1.69%)  3/51 (5.88%) 
Vitreous haemorrhage (Study eye)  1  1/115 (0.87%)  1/120 (0.83%)  3/59 (5.08%)  0/51 (0.00%) 
Gastrointestinal disorders         
Gastrooesophageal reflux disease  1  3/115 (2.61%)  0/120 (0.00%)  3/59 (5.08%)  0/51 (0.00%) 
Nausea  1  6/115 (5.22%)  5/120 (4.17%)  2/59 (3.39%)  3/51 (5.88%) 
Vomiting  1  2/115 (1.74%)  1/120 (0.83%)  2/59 (3.39%)  3/51 (5.88%) 
Infections and infestations         
Bronchitis  1  6/115 (5.22%)  4/120 (3.33%)  1/59 (1.69%)  2/51 (3.92%) 
Influenza  1  12/115 (10.43%)  8/120 (6.67%)  8/59 (13.56%)  5/51 (9.80%) 
Nasopharyngitis  1  18/115 (15.65%)  21/120 (17.50%)  15/59 (25.42%)  8/51 (15.69%) 
Pneumonia  1  2/115 (1.74%)  2/120 (1.67%)  0/59 (0.00%)  3/51 (5.88%) 
Injury, poisoning and procedural complications         
Fall  1  4/115 (3.48%)  5/120 (4.17%)  4/59 (6.78%)  1/51 (1.96%) 
Investigations         
Blood glucose increased  1  1/115 (0.87%)  3/120 (2.50%)  3/59 (5.08%)  1/51 (1.96%) 
Intraocular pressure increased (Fellow eye)  1  3/115 (2.61%)  6/120 (5.00%)  0/59 (0.00%)  1/51 (1.96%) 
Musculoskeletal and connective tissue disorders         
Arthralgia  1  6/115 (5.22%)  1/120 (0.83%)  3/59 (5.08%)  0/51 (0.00%) 
Back pain  1  7/115 (6.09%)  5/120 (4.17%)  8/59 (13.56%)  1/51 (1.96%) 
Muscle spasms  1  0/115 (0.00%)  1/120 (0.83%)  4/59 (6.78%)  0/51 (0.00%) 
Pain in extremity  1  6/115 (5.22%)  1/120 (0.83%)  0/59 (0.00%)  0/51 (0.00%) 
Nervous system disorders         
Dizziness  1  2/115 (1.74%)  2/120 (1.67%)  3/59 (5.08%)  1/51 (1.96%) 
Headache  1  4/115 (3.48%)  5/120 (4.17%)  5/59 (8.47%)  1/51 (1.96%) 
Renal and urinary disorders         
Renal failure  1  1/115 (0.87%)  2/120 (1.67%)  4/59 (6.78%)  1/51 (1.96%) 
Respiratory, thoracic and mediastinal disorders         
Cough  1  3/115 (2.61%)  4/120 (3.33%)  4/59 (6.78%)  1/51 (1.96%) 
Vascular disorders         
Hypertension  1  15/115 (13.04%)  11/120 (9.17%)  6/59 (10.17%)  6/51 (11.76%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Study Director
Organization: Novartis Pharmaceuticals
Phone: 862 778-8300
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Novartis
ClinicalTrials.gov Identifier: NCT00687804    
Obsolete Identifiers: NCT00906464
Other Study ID Numbers: CRFB002D2301
EUDRACT: 2007-004877-24
First Submitted: May 27, 2008
First Posted: June 2, 2008
Results First Submitted: January 19, 2011
Results First Posted: April 19, 2011
Last Update Posted: April 1, 2013