Trial Outcomes & Findings for A Study of Ranibizumab Administered Monthly or on an As-needed Basis in Patients With Subfoveal Neovascular Age-related Macular Degeneration (HARBOR) (NCT NCT00891735)

Last Updated: 2013-01-18

Results Overview

BCVA was measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity (VA) chart starting at a test distance of 4 meters. The BCVA score is the number of letters read correctly by the patient. A decrease in the BCVA score indicates a worsening of vision. A positive change score indicates improvement.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

1097 participants

Primary outcome timeframe

Baseline to Month 12

Results posted on

2013-01-18

Participant Flow

Participant milestones

Participant milestones
Measure	Ranibizumab 0.5 mg Monthly Patients received ranibizumab 0.5 mg monthly administered intravitreally for 12 months.	Ranibizumab 2.0 mg Monthly Patients received ranibizumab 2.0 mg monthly administered intravitreally for 12 months.	Ranibizumab 0.5 mg As-needed (Pro re Nata [PRN]) Patients received ranibizumab 0.5 mg monthly administered intravitreally for 3 months. Thereafter, patients' visual acuity and eye disease activity were assessed monthly for an additional 9 months. If study defined criteria were met at a monthly assessment, patients received ranibizumab 0.5 mg administered intravitreally.	Ranibizumab 2.0 mg As-needed (Pro re Nata [PRN]) Patients received ranibizumab 2.0 mg monthly administered intravitreally for 3 months. Thereafter, patients' visual acuity and eye disease activity were assessed monthly for an additional 9 months. If study defined criteria were met at a monthly assessment, patients received ranibizumab 2.0 mg administered intravitreally.
Overall Study STARTED	275	274	275	273
Overall Study COMPLETED	258	258	263	258
Overall Study NOT COMPLETED	17	16	12	15

Reasons for withdrawal

Reasons for withdrawal
Measure	Ranibizumab 0.5 mg Monthly Patients received ranibizumab 0.5 mg monthly administered intravitreally for 12 months.	Ranibizumab 2.0 mg Monthly Patients received ranibizumab 2.0 mg monthly administered intravitreally for 12 months.	Ranibizumab 0.5 mg As-needed (Pro re Nata [PRN]) Patients received ranibizumab 0.5 mg monthly administered intravitreally for 3 months. Thereafter, patients' visual acuity and eye disease activity were assessed monthly for an additional 9 months. If study defined criteria were met at a monthly assessment, patients received ranibizumab 0.5 mg administered intravitreally.	Ranibizumab 2.0 mg As-needed (Pro re Nata [PRN]) Patients received ranibizumab 2.0 mg monthly administered intravitreally for 3 months. Thereafter, patients' visual acuity and eye disease activity were assessed monthly for an additional 9 months. If study defined criteria were met at a monthly assessment, patients received ranibizumab 2.0 mg administered intravitreally.
Overall Study Adverse Event	2	0	2	0
Overall Study Death	8	5	4	5
Overall Study Lost to Follow-up	2	2	2	2
Overall Study Physician's decision to withdraw patient	1	0	0	0
Overall Study Patient's decision to withdraw	4	9	4	8

Baseline Characteristics

A Study of Ranibizumab Administered Monthly or on an As-needed Basis in Patients With Subfoveal Neovascular Age-related Macular Degeneration (HARBOR)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ranibizumab 0.5 mg Monthly n=275 Participants Patients received ranibizumab 0.5 mg monthly administered intravitreally for 12 months.	Ranibizumab 2.0 mg Monthly n=274 Participants Patients received ranibizumab 2.0 mg monthly administered intravitreally for 12 months.	Ranibizumab 0.5 mg As-needed (Pro re Nata [PRN]) n=275 Participants Patients received ranibizumab 0.5 mg monthly administered intravitreally for 3 months. Thereafter, patients' visual acuity and eye disease activity were assessed monthly for an additional 9 months. If study defined criteria were met at a monthly assessment, patients received ranibizumab 0.5 mg administered intravitreally.	Ranibizumab 2.0 mg As-needed (Pro re Nata [PRN]) n=273 Participants Patients received ranibizumab 2.0 mg monthly administered intravitreally for 3 months. Thereafter, patients' visual acuity and eye disease activity were assessed monthly for an additional 9 months. If study defined criteria were met at a monthly assessment, patients received ranibizumab 2.0 mg administered intravitreally.	Total n=1097 Participants Total of all reporting groups
Age Continuous	78.8 years STANDARD_DEVIATION 8.4 • n=99 Participants	79.3 years STANDARD_DEVIATION 8.3 • n=107 Participants	78.5 years STANDARD_DEVIATION 8.3 • n=206 Participants	78.3 years STANDARD_DEVIATION 8.3 • n=7 Participants	78.7 years STANDARD_DEVIATION 8.3 • n=31 Participants
Sex: Female, Male Female	162 Participants n=99 Participants	170 Participants n=107 Participants	163 Participants n=206 Participants	156 Participants n=7 Participants	651 Participants n=31 Participants
Sex: Female, Male Male	113 Participants n=99 Participants	104 Participants n=107 Participants	112 Participants n=206 Participants	117 Participants n=7 Participants	446 Participants n=31 Participants

PRIMARY outcome

Timeframe: Baseline to Month 12

Population: Intent-to-treat population: All randomized patients. Missing data were imputed using the last observation carried forward method.

Outcome measures

Outcome measures
Measure	Ranibizumab 0.5 mg Monthly n=275 Participants Patients received ranibizumab 0.5 mg monthly administered intravitreally for 12 months.	Ranibizumab 2.0 mg Monthly n=274 Participants Patients received ranibizumab 2.0 mg monthly administered intravitreally for 12 months.	Ranibizumab 0.5 mg As-needed (Pro re Nata [PRN]) n=275 Participants Patients received ranibizumab 0.5 mg monthly administered intravitreally for 3 months. Thereafter, patients' visual acuity and eye disease activity were assessed monthly for an additional 9 months. If study defined criteria were met at a monthly assessment, patients received ranibizumab 0.5 mg administered intravitreally.	Ranibizumab 2.0 mg As-needed (Pro re Nata [PRN]) n=273 Participants Patients received ranibizumab 2.0 mg monthly administered intravitreally for 3 months. Thereafter, patients' visual acuity and eye disease activity were assessed monthly for an additional 9 months. If study defined criteria were met at a monthly assessment, patients received ranibizumab 2.0 mg administered intravitreally.
Change From Baseline in Best Corrected Visual Acuity (BCVA) at Month 12	10.1 Letters Standard Deviation 13.3	9.2 Letters Standard Deviation 14.6	8.2 Letters Standard Deviation 13.3	8.6 Letters Standard Deviation 13.8

SECONDARY outcome

Timeframe: Baseline to Month 12

Population: All treated patients. Observed data were used with no imputation.

Outcome measures

Outcome measures
Measure	Ranibizumab 0.5 mg Monthly n=274 Participants Patients received ranibizumab 0.5 mg monthly administered intravitreally for 12 months.	Ranibizumab 2.0 mg Monthly n=274 Participants Patients received ranibizumab 2.0 mg monthly administered intravitreally for 12 months.	Ranibizumab 0.5 mg As-needed (Pro re Nata [PRN]) n=275 Participants Patients received ranibizumab 0.5 mg monthly administered intravitreally for 3 months. Thereafter, patients' visual acuity and eye disease activity were assessed monthly for an additional 9 months. If study defined criteria were met at a monthly assessment, patients received ranibizumab 0.5 mg administered intravitreally.	Ranibizumab 2.0 mg As-needed (Pro re Nata [PRN]) n=272 Participants Patients received ranibizumab 2.0 mg monthly administered intravitreally for 3 months. Thereafter, patients' visual acuity and eye disease activity were assessed monthly for an additional 9 months. If study defined criteria were met at a monthly assessment, patients received ranibizumab 2.0 mg administered intravitreally.
Number of Ranibizumab Injections up to But Not Including Month 12	11.3 Injections Standard Deviation 1.8	11.2 Injections Standard Deviation 2.1	7.7 Injections Standard Deviation 2.7	6.9 Injections Standard Deviation 2.4

SECONDARY outcome

Timeframe: Baseline to Month 12

Population: Intent-to-treat population: All randomized patients. Missing data were imputed using the last observation carried forward method.

BCVA was measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity (VA) chart starting at a test distance of 4 meters. The BCVA score is the number of letters read correctly by the patient. An increase in the BCVA score indicates an improvement of vision.

Outcome measures

Outcome measures
Measure	Ranibizumab 0.5 mg Monthly n=275 Participants Patients received ranibizumab 0.5 mg monthly administered intravitreally for 12 months.	Ranibizumab 2.0 mg Monthly n=274 Participants Patients received ranibizumab 2.0 mg monthly administered intravitreally for 12 months.	Ranibizumab 0.5 mg As-needed (Pro re Nata [PRN]) n=275 Participants Patients received ranibizumab 0.5 mg monthly administered intravitreally for 3 months. Thereafter, patients' visual acuity and eye disease activity were assessed monthly for an additional 9 months. If study defined criteria were met at a monthly assessment, patients received ranibizumab 0.5 mg administered intravitreally.	Ranibizumab 2.0 mg As-needed (Pro re Nata [PRN]) n=273 Participants Patients received ranibizumab 2.0 mg monthly administered intravitreally for 3 months. Thereafter, patients' visual acuity and eye disease activity were assessed monthly for an additional 9 months. If study defined criteria were met at a monthly assessment, patients received ranibizumab 2.0 mg administered intravitreally.
Percentage of Patients Who Gained ≥ 15 Letters in Best Corrected Visual Acuity (BCVA) From Baseline at Month 12	34.5 Percentage of patients Interval 28.9 to 40.2	36.1 Percentage of patients Interval 30.4 to 41.8	30.2 Percentage of patients Interval 24.8 to 35.6	33.0 Percentage of patients Interval 27.4 to 38.5

SECONDARY outcome

Timeframe: Month 12

Population: Intent-to-treat population: All randomized patients. Missing data were imputed using the last observation carried forward method.

VA was measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity chart starting at a test distance of 4 meters. An increase in the number of lines read correctly by the patient in the ETDRS chart indicates an improvement of vision. The Snellen equivalent of 20/40 is 14 lines correctly read in the EDTRS chart.

Outcome measures

Outcome measures
Measure	Ranibizumab 0.5 mg Monthly n=275 Participants Patients received ranibizumab 0.5 mg monthly administered intravitreally for 12 months.	Ranibizumab 2.0 mg Monthly n=274 Participants Patients received ranibizumab 2.0 mg monthly administered intravitreally for 12 months.	Ranibizumab 0.5 mg As-needed (Pro re Nata [PRN]) n=275 Participants Patients received ranibizumab 0.5 mg monthly administered intravitreally for 3 months. Thereafter, patients' visual acuity and eye disease activity were assessed monthly for an additional 9 months. If study defined criteria were met at a monthly assessment, patients received ranibizumab 0.5 mg administered intravitreally.	Ranibizumab 2.0 mg As-needed (Pro re Nata [PRN]) n=273 Participants Patients received ranibizumab 2.0 mg monthly administered intravitreally for 3 months. Thereafter, patients' visual acuity and eye disease activity were assessed monthly for an additional 9 months. If study defined criteria were met at a monthly assessment, patients received ranibizumab 2.0 mg administered intravitreally.
Percentage of Patients With a Visual Acuity (VA) Snellen Equivalent of 20/40 or Better at Month 12	52.4 Percentage of patients Interval 46.5 to 58.3	50.0 Percentage of patients Interval 44.1 to 55.9	46.2 Percentage of patients Interval 40.3 to 52.1	43.6 Percentage of patients Interval 37.7 to 49.5

SECONDARY outcome

Timeframe: Month 12

Population: Intent-to-treat population: All randomized patients. Missing data were imputed using the last observation carried forward method.

The presence of fluid from choroidal neovascularization (CNV) was assessed by spectral domain optical coherence tomography (SD-OCT). No evidence of fluid was defined as no subretinal fluid thickness, no cystoid spaces, no intraretinal fluid, no pigment epithelial defect thickness, and average central subfield thickness \< 270 µm.

Outcome measures

Outcome measures
Measure	Ranibizumab 0.5 mg Monthly n=275 Participants Patients received ranibizumab 0.5 mg monthly administered intravitreally for 12 months.	Ranibizumab 2.0 mg Monthly n=274 Participants Patients received ranibizumab 2.0 mg monthly administered intravitreally for 12 months.	Ranibizumab 0.5 mg As-needed (Pro re Nata [PRN]) n=275 Participants Patients received ranibizumab 0.5 mg monthly administered intravitreally for 3 months. Thereafter, patients' visual acuity and eye disease activity were assessed monthly for an additional 9 months. If study defined criteria were met at a monthly assessment, patients received ranibizumab 0.5 mg administered intravitreally.	Ranibizumab 2.0 mg As-needed (Pro re Nata [PRN]) n=273 Participants Patients received ranibizumab 2.0 mg monthly administered intravitreally for 3 months. Thereafter, patients' visual acuity and eye disease activity were assessed monthly for an additional 9 months. If study defined criteria were met at a monthly assessment, patients received ranibizumab 2.0 mg administered intravitreally.
Percentage of Patients With no Evidence of Fluid From Choroidal Neovascularization (CNV) at Month 12	5.1 Percentage of patients Interval 2.5 to 7.7	5.8 Percentage of patients Interval 3.1 to 8.6	2.9 Percentage of patients Interval 0.9 to 4.9	4.8 Percentage of patients Interval 2.2 to 7.3

SECONDARY outcome

Timeframe: Baseline to Day 7 and Months 1, 2, 3, 4, 6, 9, and 12

Population: Intent-to-treat population: All randomized patients. Missing data were imputed using the last observation carried forward method.

Central foveal thickness was assessed by spectral domain optical coherence tomography (SD-OCT).

Outcome measures

Outcome measures
Measure	Ranibizumab 0.5 mg Monthly n=275 Participants Patients received ranibizumab 0.5 mg monthly administered intravitreally for 12 months.	Ranibizumab 2.0 mg Monthly n=274 Participants Patients received ranibizumab 2.0 mg monthly administered intravitreally for 12 months.	Ranibizumab 0.5 mg As-needed (Pro re Nata [PRN]) n=275 Participants Patients received ranibizumab 0.5 mg monthly administered intravitreally for 3 months. Thereafter, patients' visual acuity and eye disease activity were assessed monthly for an additional 9 months. If study defined criteria were met at a monthly assessment, patients received ranibizumab 0.5 mg administered intravitreally.	Ranibizumab 2.0 mg As-needed (Pro re Nata [PRN]) n=273 Participants Patients received ranibizumab 2.0 mg monthly administered intravitreally for 3 months. Thereafter, patients' visual acuity and eye disease activity were assessed monthly for an additional 9 months. If study defined criteria were met at a monthly assessment, patients received ranibizumab 2.0 mg administered intravitreally.
Change From Baseline in Central Foveal Thickness at Day 7 and Months 1, 2, 3, 4, 6, 9, and 12 Day 7	-104.9 µm Standard Deviation 130.3	-84.9 µm Standard Deviation 111.3	-103.5 µm Standard Deviation 141.3	-100.6 µm Standard Deviation 123.4
Change From Baseline in Central Foveal Thickness at Day 7 and Months 1, 2, 3, 4, 6, 9, and 12 Month 1	-141.5 µm Standard Deviation 137.5	-128.6 µm Standard Deviation 133.3	-132.6 µm Standard Deviation 148.2	-146.0 µm Standard Deviation 144.3
Change From Baseline in Central Foveal Thickness at Day 7 and Months 1, 2, 3, 4, 6, 9, and 12 Month 2	-152.5 µm Standard Deviation 142.4	-140.3 µm Standard Deviation 131.1	-142.9 µm Standard Deviation 141.6	-156.9 µm Standard Deviation 145.0
Change From Baseline in Central Foveal Thickness at Day 7 and Months 1, 2, 3, 4, 6, 9, and 12 Month 3	-157.0 µm Standard Deviation 143.8	-147.9 µm Standard Deviation 134.3	-154.5 µm Standard Deviation 147.9	-164.9 µm Standard Deviation 144.5
Change From Baseline in Central Foveal Thickness at Day 7 and Months 1, 2, 3, 4, 6, 9, and 12 Month 4	-164.0 µm Standard Deviation 146.6	-151.8 µm Standard Deviation 143.3	-142.7 µm Standard Deviation 153.6	-159.7 µm Standard Deviation 148.8
Change From Baseline in Central Foveal Thickness at Day 7 and Months 1, 2, 3, 4, 6, 9, and 12 Month 6	-162.0 µm Standard Deviation 150.0	-149.2 µm Standard Deviation 144.0	-147.5 µm Standard Deviation 151.9	-159.1 µm Standard Deviation 149.6
Change From Baseline in Central Foveal Thickness at Day 7 and Months 1, 2, 3, 4, 6, 9, and 12 Month 9	-164.5 µm Standard Deviation 151.8	-153.1 µm Standard Deviation 144.8	-153.5 µm Standard Deviation 147.1	-157.8 µm Standard Deviation 155.6
Change From Baseline in Central Foveal Thickness at Day 7 and Months 1, 2, 3, 4, 6, 9, and 12 Month 12	-172.0 µm Standard Deviation 150.5	-163.3 µm Standard Deviation 142.6	-161.2 µm Standard Deviation 152.3	-172.4 µm Standard Deviation 148.6

SECONDARY outcome

Timeframe: Baseline to Day 7 and Months 1, 2, 3, 4, 6, 9, and 12

Population: Intent-to-treat population: All randomized patients. Missing data were imputed using the last observation carried forward method.

Macular volume was assessed by spectral domain optical coherence tomography (SD-OCT).

Outcome measures

Outcome measures
Measure	Ranibizumab 0.5 mg Monthly n=275 Participants Patients received ranibizumab 0.5 mg monthly administered intravitreally for 12 months.	Ranibizumab 2.0 mg Monthly n=274 Participants Patients received ranibizumab 2.0 mg monthly administered intravitreally for 12 months.	Ranibizumab 0.5 mg As-needed (Pro re Nata [PRN]) n=275 Participants Patients received ranibizumab 0.5 mg monthly administered intravitreally for 3 months. Thereafter, patients' visual acuity and eye disease activity were assessed monthly for an additional 9 months. If study defined criteria were met at a monthly assessment, patients received ranibizumab 0.5 mg administered intravitreally.	Ranibizumab 2.0 mg As-needed (Pro re Nata [PRN]) n=273 Participants Patients received ranibizumab 2.0 mg monthly administered intravitreally for 3 months. Thereafter, patients' visual acuity and eye disease activity were assessed monthly for an additional 9 months. If study defined criteria were met at a monthly assessment, patients received ranibizumab 2.0 mg administered intravitreally.
Change From Baseline in Macular Volume at Day 7 and Months 1, 2, 3, 4, 6, 9, and 12 Day 7	-0.79 mm^3 Standard Deviation 0.80	-0.80 mm^3 Standard Deviation 0.76	-0.72 mm^3 Standard Deviation 0.87	-0.81 mm^3 Standard Deviation 0.76
Change From Baseline in Macular Volume at Day 7 and Months 1, 2, 3, 4, 6, 9, and 12 Month 1	-1.26 mm^3 Standard Deviation 1.06	-1.30 mm^3 Standard Deviation 1.15	-1.16 mm^3 Standard Deviation 1.03	-1.38 mm^3 Standard Deviation 1.18
Change From Baseline in Macular Volume at Day 7 and Months 1, 2, 3, 4, 6, 9, and 12 Month 2	-1.34 mm^3 Standard Deviation 1.17	-1.49 mm^3 Standard Deviation 1.31	-1.30 mm^3 Standard Deviation 1.13	-1.47 mm^3 Standard Deviation 1.25
Change From Baseline in Macular Volume at Day 7 and Months 1, 2, 3, 4, 6, 9, and 12 Month 3	-1.42 mm^3 Standard Deviation 1.25	-1.51 mm^3 Standard Deviation 1.32	-1.43 mm^3 Standard Deviation 1.33	-1.55 mm^3 Standard Deviation 1.28
Change From Baseline in Macular Volume at Day 7 and Months 1, 2, 3, 4, 6, 9, and 12 Month 4	-1.42 mm^3 Standard Deviation 1.22	-1.56 mm^3 Standard Deviation 1.31	-1.31 mm^3 Standard Deviation 1.24	-1.48 mm^3 Standard Deviation 1.27
Change From Baseline in Macular Volume at Day 7 and Months 1, 2, 3, 4, 6, 9, and 12 Month 6	-1.47 mm^3 Standard Deviation 1.25	-1.61 mm^3 Standard Deviation 1.34	-1.35 mm^3 Standard Deviation 1.33	-1.48 mm^3 Standard Deviation 1.36
Change From Baseline in Macular Volume at Day 7 and Months 1, 2, 3, 4, 6, 9, and 12 Month 9	-1.55 mm^3 Standard Deviation 1.41	-1.67 mm^3 Standard Deviation 1.34	-1.35 mm^3 Standard Deviation 1.31	-1.48 mm^3 Standard Deviation 1.33
Change From Baseline in Macular Volume at Day 7 and Months 1, 2, 3, 4, 6, 9, and 12 Month 12	-1.54 mm^3 Standard Deviation 1.31	-1.66 mm^3 Standard Deviation 1.37	-1.41 mm^3 Standard Deviation 1.36	-1.49 mm^3 Standard Deviation 1.35

SECONDARY outcome

Timeframe: Baseline to Month 12

Population: Intent-to-treat population: All randomized patients. Missing data were imputed using the last observation carried forward method.

The total area of choroidal neovascularization (CNV) and choroidal neovascular leakage was assessed with fluorescein angiography (FA). Area was measured in disc area units; 1 disc area unit = 2.54 mm\^2.

Outcome measures

Outcome measures
Measure	Ranibizumab 0.5 mg Monthly n=275 Participants Patients received ranibizumab 0.5 mg monthly administered intravitreally for 12 months.	Ranibizumab 2.0 mg Monthly n=274 Participants Patients received ranibizumab 2.0 mg monthly administered intravitreally for 12 months.	Ranibizumab 0.5 mg As-needed (Pro re Nata [PRN]) n=275 Participants Patients received ranibizumab 0.5 mg monthly administered intravitreally for 3 months. Thereafter, patients' visual acuity and eye disease activity were assessed monthly for an additional 9 months. If study defined criteria were met at a monthly assessment, patients received ranibizumab 0.5 mg administered intravitreally.	Ranibizumab 2.0 mg As-needed (Pro re Nata [PRN]) n=273 Participants Patients received ranibizumab 2.0 mg monthly administered intravitreally for 3 months. Thereafter, patients' visual acuity and eye disease activity were assessed monthly for an additional 9 months. If study defined criteria were met at a monthly assessment, patients received ranibizumab 2.0 mg administered intravitreally.
Change From Baseline in the Total Area of Choroidal Neovascularization (CNV) and Choroidal Neovascular Leakage at Month 12 Change in the total area of CNV	-2.14 Disc area units Standard Deviation 2.40	-2.42 Disc area units Standard Deviation 2.38	-1.74 Disc area units Standard Deviation 2.22	-1.98 Disc area units Standard Deviation 2.39
Change From Baseline in the Total Area of Choroidal Neovascularization (CNV) and Choroidal Neovascular Leakage at Month 12 Change in the total area of CNV leakage	-2.35 Disc area units Standard Deviation 2.39	-2.63 Disc area units Standard Deviation 2.34	-2.01 Disc area units Standard Deviation 2.28	-2.22 Disc area units Standard Deviation 2.48

Adverse Events

Ranibizumab 0.5 mg Monthly

Serious events: 66 serious events

Other events: 240 other events

Deaths: 0 deaths

Ranibizumab 2.0 mg Monthly

Serious events: 54 serious events

Other events: 243 other events

Deaths: 0 deaths

Ranibizumab 0.5 mg As-needed (Pro re Nata [PRN])

Serious events: 57 serious events

Other events: 250 other events

Deaths: 0 deaths

Ranibizumab 2.0 mg As-needed (Pro re Nata [PRN])

Serious events: 54 serious events

Other events: 239 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Ranibizumab 0.5 mg Monthly n=274 participants at risk Patients received ranibizumab 0.5 mg monthly administered intravitreally for 12 months.	Ranibizumab 2.0 mg Monthly n=274 participants at risk Patients received ranibizumab 2.0 mg monthly administered intravitreally for 12 months.	Ranibizumab 0.5 mg As-needed (Pro re Nata [PRN]) n=275 participants at risk Patients received ranibizumab 0.5 mg monthly administered intravitreally for 3 months. Thereafter, patients' visual acuity and eye disease activity were assessed monthly for an additional 9 months. If study defined criteria were met at a monthly assessment, patients received ranibizumab 0.5 mg administered intravitreally.	Ranibizumab 2.0 mg As-needed (Pro re Nata [PRN]) n=272 participants at risk Patients received ranibizumab 2.0 mg monthly administered intravitreally for 3 months. Thereafter, patients' visual acuity and eye disease activity were assessed monthly for an additional 9 months. If study defined criteria were met at a monthly assessment, patients received ranibizumab 2.0 mg administered intravitreally.
Infections and infestations Urinary tract infection	5.5% 15/274 • Adverse events were recorded from Baseline (first treatment day) through Month 12. Safety population: All patients who received at least 1 study treatment. Adverse events reported here include ocular adverse events in the study eye and fellow eye, as well as non-ocular adverse events.	5.1% 14/274 • Adverse events were recorded from Baseline (first treatment day) through Month 12. Safety population: All patients who received at least 1 study treatment. Adverse events reported here include ocular adverse events in the study eye and fellow eye, as well as non-ocular adverse events.	6.2% 17/275 • Adverse events were recorded from Baseline (first treatment day) through Month 12. Safety population: All patients who received at least 1 study treatment. Adverse events reported here include ocular adverse events in the study eye and fellow eye, as well as non-ocular adverse events.	5.9% 16/272 • Adverse events were recorded from Baseline (first treatment day) through Month 12. Safety population: All patients who received at least 1 study treatment. Adverse events reported here include ocular adverse events in the study eye and fellow eye, as well as non-ocular adverse events.
Injury, poisoning and procedural complications Fall	5.1% 14/274 • Adverse events were recorded from Baseline (first treatment day) through Month 12. Safety population: All patients who received at least 1 study treatment. Adverse events reported here include ocular adverse events in the study eye and fellow eye, as well as non-ocular adverse events.	4.4% 12/274 • Adverse events were recorded from Baseline (first treatment day) through Month 12. Safety population: All patients who received at least 1 study treatment. Adverse events reported here include ocular adverse events in the study eye and fellow eye, as well as non-ocular adverse events.	2.9% 8/275 • Adverse events were recorded from Baseline (first treatment day) through Month 12. Safety population: All patients who received at least 1 study treatment. Adverse events reported here include ocular adverse events in the study eye and fellow eye, as well as non-ocular adverse events.	7.7% 21/272 • Adverse events were recorded from Baseline (first treatment day) through Month 12. Safety population: All patients who received at least 1 study treatment. Adverse events reported here include ocular adverse events in the study eye and fellow eye, as well as non-ocular adverse events.
Respiratory, thoracic and mediastinal disorders Cough	1.8% 5/274 • Adverse events were recorded from Baseline (first treatment day) through Month 12. Safety population: All patients who received at least 1 study treatment. Adverse events reported here include ocular adverse events in the study eye and fellow eye, as well as non-ocular adverse events.	3.6% 10/274 • Adverse events were recorded from Baseline (first treatment day) through Month 12. Safety population: All patients who received at least 1 study treatment. Adverse events reported here include ocular adverse events in the study eye and fellow eye, as well as non-ocular adverse events.	2.2% 6/275 • Adverse events were recorded from Baseline (first treatment day) through Month 12. Safety population: All patients who received at least 1 study treatment. Adverse events reported here include ocular adverse events in the study eye and fellow eye, as well as non-ocular adverse events.	5.1% 14/272 • Adverse events were recorded from Baseline (first treatment day) through Month 12. Safety population: All patients who received at least 1 study treatment. Adverse events reported here include ocular adverse events in the study eye and fellow eye, as well as non-ocular adverse events.
Vascular disorders Hypertension	5.1% 14/274 • Adverse events were recorded from Baseline (first treatment day) through Month 12. Safety population: All patients who received at least 1 study treatment. Adverse events reported here include ocular adverse events in the study eye and fellow eye, as well as non-ocular adverse events.	7.3% 20/274 • Adverse events were recorded from Baseline (first treatment day) through Month 12. Safety population: All patients who received at least 1 study treatment. Adverse events reported here include ocular adverse events in the study eye and fellow eye, as well as non-ocular adverse events.	7.6% 21/275 • Adverse events were recorded from Baseline (first treatment day) through Month 12. Safety population: All patients who received at least 1 study treatment. Adverse events reported here include ocular adverse events in the study eye and fellow eye, as well as non-ocular adverse events.	5.5% 15/272 • Adverse events were recorded from Baseline (first treatment day) through Month 12. Safety population: All patients who received at least 1 study treatment. Adverse events reported here include ocular adverse events in the study eye and fellow eye, as well as non-ocular adverse events.
Eye disorders Macular degeneration	4.4% 12/274 • Adverse events were recorded from Baseline (first treatment day) through Month 12. Safety population: All patients who received at least 1 study treatment. Adverse events reported here include ocular adverse events in the study eye and fellow eye, as well as non-ocular adverse events.	2.9% 8/274 • Adverse events were recorded from Baseline (first treatment day) through Month 12. Safety population: All patients who received at least 1 study treatment. Adverse events reported here include ocular adverse events in the study eye and fellow eye, as well as non-ocular adverse events.	6.5% 18/275 • Adverse events were recorded from Baseline (first treatment day) through Month 12. Safety population: All patients who received at least 1 study treatment. Adverse events reported here include ocular adverse events in the study eye and fellow eye, as well as non-ocular adverse events.	5.5% 15/272 • Adverse events were recorded from Baseline (first treatment day) through Month 12. Safety population: All patients who received at least 1 study treatment. Adverse events reported here include ocular adverse events in the study eye and fellow eye, as well as non-ocular adverse events.
Eye disorders Retinal haemorrhage	2.2% 6/274 • Adverse events were recorded from Baseline (first treatment day) through Month 12. Safety population: All patients who received at least 1 study treatment. Adverse events reported here include ocular adverse events in the study eye and fellow eye, as well as non-ocular adverse events.	2.6% 7/274 • Adverse events were recorded from Baseline (first treatment day) through Month 12. Safety population: All patients who received at least 1 study treatment. Adverse events reported here include ocular adverse events in the study eye and fellow eye, as well as non-ocular adverse events.	5.1% 14/275 • Adverse events were recorded from Baseline (first treatment day) through Month 12. Safety population: All patients who received at least 1 study treatment. Adverse events reported here include ocular adverse events in the study eye and fellow eye, as well as non-ocular adverse events.	4.4% 12/272 • Adverse events were recorded from Baseline (first treatment day) through Month 12. Safety population: All patients who received at least 1 study treatment. Adverse events reported here include ocular adverse events in the study eye and fellow eye, as well as non-ocular adverse events.
Eye disorders Vitreous detachment	8.0% 22/274 • Adverse events were recorded from Baseline (first treatment day) through Month 12. Safety population: All patients who received at least 1 study treatment. Adverse events reported here include ocular adverse events in the study eye and fellow eye, as well as non-ocular adverse events.	7.7% 21/274 • Adverse events were recorded from Baseline (first treatment day) through Month 12. Safety population: All patients who received at least 1 study treatment. Adverse events reported here include ocular adverse events in the study eye and fellow eye, as well as non-ocular adverse events.	5.8% 16/275 • Adverse events were recorded from Baseline (first treatment day) through Month 12. Safety population: All patients who received at least 1 study treatment. Adverse events reported here include ocular adverse events in the study eye and fellow eye, as well as non-ocular adverse events.	9.9% 27/272 • Adverse events were recorded from Baseline (first treatment day) through Month 12. Safety population: All patients who received at least 1 study treatment. Adverse events reported here include ocular adverse events in the study eye and fellow eye, as well as non-ocular adverse events.
Eye disorders Age-related macular degeneration	2.9% 8/274 • Adverse events were recorded from Baseline (first treatment day) through Month 12. Safety population: All patients who received at least 1 study treatment. Adverse events reported here include ocular adverse events in the study eye and fellow eye, as well as non-ocular adverse events.	5.5% 15/274 • Adverse events were recorded from Baseline (first treatment day) through Month 12. Safety population: All patients who received at least 1 study treatment. Adverse events reported here include ocular adverse events in the study eye and fellow eye, as well as non-ocular adverse events.	5.5% 15/275 • Adverse events were recorded from Baseline (first treatment day) through Month 12. Safety population: All patients who received at least 1 study treatment. Adverse events reported here include ocular adverse events in the study eye and fellow eye, as well as non-ocular adverse events.	4.8% 13/272 • Adverse events were recorded from Baseline (first treatment day) through Month 12. Safety population: All patients who received at least 1 study treatment. Adverse events reported here include ocular adverse events in the study eye and fellow eye, as well as non-ocular adverse events.
Eye disorders Conjunctival haemorrhage	23.0% 63/274 • Adverse events were recorded from Baseline (first treatment day) through Month 12. Safety population: All patients who received at least 1 study treatment. Adverse events reported here include ocular adverse events in the study eye and fellow eye, as well as non-ocular adverse events.	18.6% 51/274 • Adverse events were recorded from Baseline (first treatment day) through Month 12. Safety population: All patients who received at least 1 study treatment. Adverse events reported here include ocular adverse events in the study eye and fellow eye, as well as non-ocular adverse events.	17.5% 48/275 • Adverse events were recorded from Baseline (first treatment day) through Month 12. Safety population: All patients who received at least 1 study treatment. Adverse events reported here include ocular adverse events in the study eye and fellow eye, as well as non-ocular adverse events.	15.1% 41/272 • Adverse events were recorded from Baseline (first treatment day) through Month 12. Safety population: All patients who received at least 1 study treatment. Adverse events reported here include ocular adverse events in the study eye and fellow eye, as well as non-ocular adverse events.
Eye disorders Detachment of retinal pigment epithelium	1.5% 4/274 • Adverse events were recorded from Baseline (first treatment day) through Month 12. Safety population: All patients who received at least 1 study treatment. Adverse events reported here include ocular adverse events in the study eye and fellow eye, as well as non-ocular adverse events.	1.5% 4/274 • Adverse events were recorded from Baseline (first treatment day) through Month 12. Safety population: All patients who received at least 1 study treatment. Adverse events reported here include ocular adverse events in the study eye and fellow eye, as well as non-ocular adverse events.	6.2% 17/275 • Adverse events were recorded from Baseline (first treatment day) through Month 12. Safety population: All patients who received at least 1 study treatment. Adverse events reported here include ocular adverse events in the study eye and fellow eye, as well as non-ocular adverse events.	4.0% 11/272 • Adverse events were recorded from Baseline (first treatment day) through Month 12. Safety population: All patients who received at least 1 study treatment. Adverse events reported here include ocular adverse events in the study eye and fellow eye, as well as non-ocular adverse events.
Eye disorders Eye pain	5.5% 15/274 • Adverse events were recorded from Baseline (first treatment day) through Month 12. Safety population: All patients who received at least 1 study treatment. Adverse events reported here include ocular adverse events in the study eye and fellow eye, as well as non-ocular adverse events.	9.1% 25/274 • Adverse events were recorded from Baseline (first treatment day) through Month 12. Safety population: All patients who received at least 1 study treatment. Adverse events reported here include ocular adverse events in the study eye and fellow eye, as well as non-ocular adverse events.	5.8% 16/275 • Adverse events were recorded from Baseline (first treatment day) through Month 12. Safety population: All patients who received at least 1 study treatment. Adverse events reported here include ocular adverse events in the study eye and fellow eye, as well as non-ocular adverse events.	8.5% 23/272 • Adverse events were recorded from Baseline (first treatment day) through Month 12. Safety population: All patients who received at least 1 study treatment. Adverse events reported here include ocular adverse events in the study eye and fellow eye, as well as non-ocular adverse events.
Eye disorders Vitreous floaters	9.5% 26/274 • Adverse events were recorded from Baseline (first treatment day) through Month 12. Safety population: All patients who received at least 1 study treatment. Adverse events reported here include ocular adverse events in the study eye and fellow eye, as well as non-ocular adverse events.	5.5% 15/274 • Adverse events were recorded from Baseline (first treatment day) through Month 12. Safety population: All patients who received at least 1 study treatment. Adverse events reported here include ocular adverse events in the study eye and fellow eye, as well as non-ocular adverse events.	4.0% 11/275 • Adverse events were recorded from Baseline (first treatment day) through Month 12. Safety population: All patients who received at least 1 study treatment. Adverse events reported here include ocular adverse events in the study eye and fellow eye, as well as non-ocular adverse events.	6.2% 17/272 • Adverse events were recorded from Baseline (first treatment day) through Month 12. Safety population: All patients who received at least 1 study treatment. Adverse events reported here include ocular adverse events in the study eye and fellow eye, as well as non-ocular adverse events.
Infections and infestations Nasopharyngitis	6.2% 17/274 • Adverse events were recorded from Baseline (first treatment day) through Month 12. Safety population: All patients who received at least 1 study treatment. Adverse events reported here include ocular adverse events in the study eye and fellow eye, as well as non-ocular adverse events.	3.6% 10/274 • Adverse events were recorded from Baseline (first treatment day) through Month 12. Safety population: All patients who received at least 1 study treatment. Adverse events reported here include ocular adverse events in the study eye and fellow eye, as well as non-ocular adverse events.	6.2% 17/275 • Adverse events were recorded from Baseline (first treatment day) through Month 12. Safety population: All patients who received at least 1 study treatment. Adverse events reported here include ocular adverse events in the study eye and fellow eye, as well as non-ocular adverse events.	8.5% 23/272 • Adverse events were recorded from Baseline (first treatment day) through Month 12. Safety population: All patients who received at least 1 study treatment. Adverse events reported here include ocular adverse events in the study eye and fellow eye, as well as non-ocular adverse events.
Infections and infestations Sinusitis	4.4% 12/274 • Adverse events were recorded from Baseline (first treatment day) through Month 12. Safety population: All patients who received at least 1 study treatment. Adverse events reported here include ocular adverse events in the study eye and fellow eye, as well as non-ocular adverse events.	2.6% 7/274 • Adverse events were recorded from Baseline (first treatment day) through Month 12. Safety population: All patients who received at least 1 study treatment. Adverse events reported here include ocular adverse events in the study eye and fellow eye, as well as non-ocular adverse events.	9.8% 27/275 • Adverse events were recorded from Baseline (first treatment day) through Month 12. Safety population: All patients who received at least 1 study treatment. Adverse events reported here include ocular adverse events in the study eye and fellow eye, as well as non-ocular adverse events.	2.9% 8/272 • Adverse events were recorded from Baseline (first treatment day) through Month 12. Safety population: All patients who received at least 1 study treatment. Adverse events reported here include ocular adverse events in the study eye and fellow eye, as well as non-ocular 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