Comparison of Age-related Macular Degeneration Treatments Trials: Lucentis-Avastin Trial

• Sponsor: University of Pennsylvania (Other)
• Overall Status: Completed
• CT.gov ID: NCT00593450
• Collaborator: National Eye Institute (NEI) (NIH)
• Enrollment: 1,208
• Locations: 59
• Arms: 4
• Actual Duration (Months): 85.9
• Patients Per Site: 20.5
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The purpose of the study is to evaluate the relative efficacy and safety of treatment of neovascular AMD with Lucentis on a fixed schedule, Avastin on a fixed schedule, Lucentis on a variable schedule, and Avastin on a variable schedule.

A five year follow-up visit is being conducted in 2014 to gather information on long term outcomes.

Condition or Disease	Intervention/Treatment	Phase
Age Related Macular Degeneration	Drug: ranibizumab; Drug: bevacizumab	Phase 3

Detailed Description

Age related macular degeneration (AMD) is the leading cause of severe vision loss in people over the age of 65 in the United States and other Western countries. More than 1.6 million people in the US currently have one or both eyes affected by the advanced stage of AMD.

Lucentis® is the most effective treatment for neovascular AMD studied to date. Bevacizumab (Avastin®) and Lucentis® are derived from the same monoclonal antibody. Following the encouraging clinical trial results with Lucentis®, several investigators began evaluating intravitreal Avastin® for the treatment of CNV. Given its molecular similarity to Lucentis, its low cost, and its availability, the interest in Avastin® has been considerable. Avastin® has not been evaluated relative to Lucentis®.

In addition, previous studies do not answer the question of whether a reduced dosing schedule is as effective as a fixed schedule of monthly injections. Treatment dependent on clinical response has the potential to reduce the treatment burden to patients as well as to reduce the overall cost of therapy.

Only a single eye in each patient was analyzed.

At the five year follow-up visit, the subjects will undergo the same examinations and procedures as in the original study; however, the five year follow-up visit deos not involve any study treatment.

Study Design

• Study Type: Interventional
• Actual Enrollment: 1208 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Comparison of Age-related Macular Degeneration Treatments Trials: Lucentis-Avastin Trial (CATT)
• Actual Study Start Date: Feb 1, 2008
• Actual Primary Completion Date: Dec 1, 2010
• Actual Study Completion Date: Apr 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 1 Lucentis® on a fixed schedule of every 4 weeks for 1 year; at 1 year, re-randomization to Lucentis® every 4 weeks or to variable dosing.	Drug: ranibizumab; • 0.5 mg (0.05 mL)intravitreal injection; Other Names: Lucentis
Experimental: 2 Avastin® on a fixed schedule of every 4 weeks for 1 year; at 1 year, re-randomization to Avastin® every 4 weeks or to variable dosing.	Drug: bevacizumab; • 1.25 mg (0.05 mL)intravitreal injection; Other Names: Avastin
Experimental: 3 Lucentis® on a variable dosing schedule for 2 years; i.e., after initial treatment, monthly evaluation for treatment based on signs of lesion activity.	Drug: ranibizumab; • 0.5 mg (0.05 mL)intravitreal injection; Other Names: Lucentis
Experimental: 4 Avastin® on a variable dosing schedule for 2 years; i.e., after initial treatment, monthly evaluation for treatment based on signs of lesion activity.	Drug: bevacizumab; • 1.25 mg (0.05 mL)intravitreal injection; Other Names: Avastin

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Visual-acuity Score (Continuous) [Baseline and 1 Year]

   Visual acuity testing was performed with the Electronic Visual Tester (EVA) following the ETDRS protocol. VA score is measured as number of letters read correctly. The VA score change is the difference of the VA score at 1 Year and the VA score at baseline. In this study, the outcome VA score change is ranged from -71 to 52, with the higher VA score change the better visual acuity improvement.

Secondary Outcome Measures

1. Change From Baseline Visual-acuity Score (Frequency) [Baseline and 1 Year]

2. Visual-acuity Score and Snellen Equivalent (Frequency) [at 1 Year]

3. Visual-acuity Score and Snellen Equivalent (Continuous) [at 1 Year]

   Visual acuity testing was performed with the Electronic Visual Tester (EVA) following the ETDRS protocol. VA score is measured as number of letters read correctly. In this study, the outcome VA score is ranged from 0 to 97, with the higher score the better visual acuity.

4. Number of Treatments [1 Year]

   Cumulative over the 1 year of trial

5. Average Cost of Drug/Patient [at 1 Year]

6. Total Thickness at Fovea [at 1 Year]

7. Total Thickness Change From Baseline at Fovea [Baseline and 1 Year]

8. Retinal Thickness Plus Subfoveal-fluid Thickness at Fovea [at 1 Year]

9. Retinal Thickness Plus Subfoveal-fluid Thickness Change From Baseline at Fovea [Baseline and 1 Year]

10. Fluid on Optical Coherence Tomography [at 1 Year]

11. Dye Leakage on Angiogram [at 1 Year]

12. Area of Lesion [at 1 Year]

13. Area of Lesion Change From Baseline [Baseline and 1 Year]

14. Change in Systolic Blood Pressure From Baseline [Baseline and 1 Year]

15. Change in Diastolic Blood Pressure From Baseline [Baseline and 1 Year]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 50 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Active, subfoveal choroidal neovascularization (CNV)

• Fibrosis < 50% of total lesion area

• Visual acuity (VA) 20/25-20/320

• Age ≥ 50 yrs

• At least 1 drusen (>63μ) in either eye or late AMD in fellow eye

Exclusion Criteria:

• Previous treatment for CNV in study eye

• Other progressive retinal disease likely to compromise VA

• Contraindications to injections with Lucentis or Avastin

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Retina Consultants of Arizona	Mesa	Arizona	United States	85210
2	Retinal Consultants of Arizona	Phoenix	Arizona	United States	85064
3	Retina Associates Southwest, P.C.	Tucson	Arizona	United States	85710
4	California Retina Consultants	Bakersfield	California	United States	93309
5	Retina-Vitreous Associates Medical Group	Beverly Hills	California	United States	90211
6	University of California-Davis Medical Center	Sacramento	California	United States	95817
7	Retinal Consultants Medical Group, Inc.	Sacramento	California	United States	95819
8	West Coast Retina Medical Group, Inc.	San Francisco	California	United States	94107
9	California Retinal Consultants	Santa Barbara	California	United States	93103
10	West Coast Retina Medical Group, Inc.	Walnut Creek	California	United States	94596
11	Colorado Retina Associates	Denver	Colorado	United States	80457
12	Retina Group of Florida	Fort Lauderdale	Florida	United States	33334
13	National Ophthalmic Research Institute	Fort Myers	Florida	United States	33912
14	Emory Eye Center	Atlanta	Georgia	United States	30322
15	Illinois Retina Associates	Flossmoor	Illinois	United States	60422
16	Ingalls Memorial Hospital/Illinois Retina Associates	Harvey	Illinois	United States	60426
17	Illinois Retina Associates	Joliet	Illinois	United States	60435
18	Midwest Eye Institute	Indianapolis	Indiana	United States	46280
19	University of Iowa Hospitals and Clinics	Iowa City	Iowa	United States	52242
20	Retina Associates of Kentucky	Lexington	Kentucky	United States	40509
21	University of Louisville School of Medicine	Louisville	Kentucky	United States	40202
22	Elman Retina Group, P.A.	Baltimore	Maryland	United States	21237
23	The Retina Group of Washington	Chevy Chase	Maryland	United States	20815
24	Retina Specialists	Towson	Maryland	United States	21204
25	Massachusetts Eye & Ear Infirmary	Boston	Massachusetts	United States	02114
26	Opthalmic Consultants of Boston	Boston	Massachusetts	United States	02114
27	Harvard Vanguard Medical Associates	Boston	Massachusetts	United States	02459
28	Vision Research Foundation/Associated Retinal Consultants, P.C.	Grand Rapids	Michigan	United States	49546
29	Vision Research Foundation/Associated Retinal Consultants, P.C.	Royal Oak	Michigan	United States	48073
30	Vision research Foundation/Associated Retinal Consultants. P.C.	Traverse City	Michigan	United States	49684
31	VitreoRetinal Surgery	Edina	Minnesota	United States	55435
32	Mayo Clinic	Rochester	Minnesota	United States	55905
33	Barnes Retina Institute	Saint Louis	Missouri	United States	63110
34	Retina Vitreous Center, PA	New Brunswick	New Jersey	United States	08901
35	Retina Vitreous Center, PA	Toms River	New Jersey	United States	08755
36	Long Island Vitreoretinal Consultants	Great Neck	New York	United States	11021
37	Long Island Vitreoretinal Consultants	Riverhead	New York	United States	11902
38	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina	United States	27599
39	Charlotte Eye, Ear, nose & Throat Associates	Charlotte	North Carolina	United States	28210
40	Duke University Eye Center	Durham	North Carolina	United States	27710
41	Charlotte Eye,Ear, Nose & Throat Associates	Monroe	North Carolina	United States	28112
42	Retina Associates of Cleveland	Beachwood	Ohio	United States	44122
43	Ohio State University Eye Physicians & Surgeons-Retina Division	Dublin	Ohio	United States	43016
44	Retina Associates of Cleveland, Inc.	Lakewood	Ohio	United States	44107
45	Dean A. McGee Eye Institute	Oklahoma City	Oklahoma	United States	73104
46	Retina Northwest, P.C.	Portland	Oregon	United States	97210
47	Casey Eye Institute	Portland	Oregon	United States	97239
48	Retina Diagnostic and Treatment Associates, LLC	Philadelphia	Pennsylvania	United States	19107
49	Retina Vitreous Consultants	Pittsburgh	Pennsylvania	United States	15213
50	Palmetto Retina Center	West Columbia	South Carolina	United States	29169
51	Southeastern Retina Associates	Knoxville	Tennessee	United States	37920
52	Southeastern Retina Associates	Knoxville	Tennessee	United States	38909
53	Retina Vitreous Associates, P.C.	Nashville	Tennessee	United States	37203
54	Texas Retina Associates	Arlington	Texas	United States	76012
55	Texas Retina Associates	Dallas	Texas	United States	75231
56	Retina and Vitreous of Texas	Houston	Texas	United States	77025
57	Vitreoretinal Consultants	Houston	Texas	United States	77030
58	The Retina Group of Washington	Fairfax	Virginia	United States	22310
59	University of Wisconsin	Madison	Wisconsin	United States	53705

Sponsors and Collaborators

• University of Pennsylvania
• National Eye Institute (NEI)

Investigators

• Study Chair: Daniel F Martin, MD, The Cleveland Clinic
• Study Chair: Stuart L Fine, MD, Study Vice-Chair, University of Pennsylvania
• Study Director: Maureen G Maguire, PhD, Director of Coordinating Center, University of Pennsylvania
• Study Director: Glenn Jaffe,, MD, Director of OCT Reading Center, Duke University
• Principal Investigator: Juan E Grunwald, MD, Principal Investigator of Photography Reading Center, Universisty of Pennsylvania

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Click here for more information about this study: Comparison of AMD Treatments Trials (CATT)
• NEI Clinical Studies Database

Publications

• Martin DF, Maguire MG, Fine SL. Identifying and eliminating the roadblocks to comparative-effectiveness research. N Engl J Med. 2010 Jul 8;363(2):105-7. doi: 10.1056/NEJMp1001201. Epub 2010 Jun 2.

• Responsible Party: University of Pennsylvania
• ClinicalTrials.gov Identifier: NCT00593450
• Other Study ID Numbers: NEI-137; U10EY017823
• First Posted: Jan 15, 2008
• Last Update Posted: Aug 21, 2017
• Last Verified: Jul 1, 2017

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by University of Pennsylvania: bevacizumab; ranibizumab; choroidal neovascularization
• Additional relevant MeSH terms: Macular Degeneration; Bevacizumab; Ranibizumab

Study Results

Participant Flow

Pre-assignment Detail	Note: The Data and Safety Monitoring Committee for CATT recommended excluding the data for all patients (N=23) from one center because of serious protocol non-compliance. Unless specified otherwise, only the 1185 patients enrolled by the remaining 43 centers are included in analyses.

Arm/Group Title	1-Lucentis Monthly	2-Avastin Monthly	3-Lucentis as Needed	4-Avastin as Needed
Arm/Group Description	Lucentis® on a fixed schedule of every 4 weeks for 1 year; at 1 year, re-randomization to Lucentis® every 4 weeks or to variable dosing.	Avastin® on a fixed schedule of every 4 weeks for 1 year; at 1 year, re-randomization to Avastin® every 4 weeks or to variable dosing.	Lucentis® on a variable dosing schedule for 2 years; i.e., after initial treatment, monthly evaluation for treatment based on signs of lesion activity.	Avastin® on a variable dosing schedule for 2 years; i.e., after initial treatment, monthly evaluation for treatment based on signs of lesion activity.
Period Title: Overall Study
STARTED	301	286	298	300
COMPLETED	284	265	285	271
NOT COMPLETED	17	21	13	29

Baseline Characteristics

Arm/Group Title	1-Lucentis Monthly	2-Avastin Monthly	3-Lucentis as Needed	4-Avastin as Needed	Total
Arm/Group Description	Lucentis® on a fixed schedule of every 4 weeks for 1 year; at 1 year, re-randomization to Lucentis® every 4 weeks or to variable dosing.	Avastin® on a fixed schedule of every 4 weeks for 1 year; at 1 year, re-randomization to Avastin® every 4 weeks or to variable dosing.	Lucentis® on a variable dosing schedule for 2 years; i.e., after initial treatment, monthly evaluation for treatment based on signs of lesion activity.	Avastin® on a variable dosing schedule for 2 years; i.e., after initial treatment, monthly evaluation for treatment based on signs of lesion activity.	Total of all reporting groups
Overall Participants	301	286	298	300	1185
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	79.2 (7.4)	80.1 (7.3)	78.4 (7.8)	79.3 (7.6)	79.3 (7.5)
Age, Customized (participants) [Number]
50-59 years	2 0.7%	1 0.3%	6 2%	2 0.7%	11 0.9%
60-69 years	33 11%	28 9.8%	31 10.4%	34 11.3%	126 10.6%
70-79 years	102 33.9%	84 29.4%	115 38.6%	103 34.3%	404 34.1%
80-89 years	142 47.2%	150 52.4%	126 42.3%	142 47.3%	560 47.3%
>=90 years	22 7.3%	23 8%	20 6.7%	19 6.3%	84 7.1%
Sex: Female, Male (Count of Participants)
Female	183 60.8%	180 62.9%	185 62.1%	184 61.3%	732 61.8%
Male	118 39.2%	106 37.1%	113 37.9%	116 38.7%	453 38.2%
Race/Ethnicity, Customized (Number) [Number]
White	297 98.7%	281 98.3%	296 99.3%	294 98%	1168 98.6%
Other	4 1.3%	5 1.7%	2 0.7%	6 2%	17 1.4%
History of myocardial infarction (Number) [Number]
Yes	34 11.3%	40 14%	30 10.1%	36 12%	140 11.8%
No	267 88.7%	246 86%	268 89.9%	264 88%	1045 88.2%
History of stroke (Number) [Number]
Yes	14 4.7%	18 6.3%	22 7.4%	16 5.3%	70 5.9%
No	287 95.3%	268 93.7%	276 92.6%	284 94.7%	1115 94.1%
History of transient ischemic attack (Number) [Number]
Yes	12 4%	25 8.7%	12 4%	19 6.3%	68 5.7%
No	289 96%	261 91.3%	286 96%	281 93.7%	1117 94.3%
Systolic blood pressure (mm Hg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mm Hg]	134 (18)	135 (19)	136 (17)	135 (17)	135 (18)
Diastolic blood pressure (mm Hg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mm Hg]	75 (10)	75 (10)	76 (9)	75 (10)	75 (10)
Visual-acuity score and Snellen equivalent (Number) [Number]
68-82 letters, 20/25-40	111 36.9%	94 32.9%	116 38.9%	103 34.3%	424 35.8%
53-67 letters, 20/50-80	98 32.6%	118 41.3%	108 36.2%	119 39.7%	443 37.4%
38-52 letters, 20/100-160	67 22.3%	53 18.5%	58 19.5%	58 19.3%	236 19.9%
23-37 letters, 20/200-320	25 8.3%	21 7.3%	16 5.4%	20 6.7%	82 6.9%
Visual-acuity score and Snellen equivalent (Letters) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Letters]	60.1 (14.3)	60.2 (13.1)	61.5 (13.2)	60.4 (13.4)	60.5 (13.5)
Total thickness at fovea (μm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [μm]	458 (184)	463 (196)	458 (193)	461 (175)	460 (187)
Retinal thickness plus subfoveal-fluid thickness at fovea (microns) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [microns]	251 (122)	254 (121)	247 (122)	252 (115)	251 (120)
Foveal center involvement (Number) [Number]
Choroidal neovacularization	176 58.5%	153 53.5%	176 59.1%	183 61%	688 58.1%
Fluid	85 28.2%	81 28.3%	77 25.8%	72 24%	315 26.6%
Hemorrhage	20 6.6%	24 8.4%	24 8.1%	25 8.3%	93 7.8%
Other	18 6%	20 7%	15 5%	18 6%	71 6%
No choroidal neovascularization or can't grade	2 0.7%	8 2.8%	6 2%	2 0.7%	18 1.5%

Outcome Measures

1. Secondary Outcome

Title	Change From Baseline Visual-acuity Score (Frequency)
Time Frame	Baseline and 1 Year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	1-Lucentis Monthly	2-Avastin Monthly	3-Lucentis as Needed	4-Avastin as Needed
Arm/Group Description	Lucentis® on a fixed schedule of every 4 weeks for 1 year; at 1 year, re-randomization to Lucentis® every 4 weeks or to variable dosing.	Avastin® on a fixed schedule of every 4 weeks for 1 year; at 1 year, re-randomization to Avastin® every 4 weeks or to variable dosing.	Lucentis® on a variable dosing schedule for 2 years; i.e., after initial treatment, monthly evaluation for treatment based on signs of lesion activity.	Avastin® on a variable dosing schedule for 2 years; i.e., after initial treatment, monthly evaluation for treatment based on signs of lesion activity.
Measure Participants	284	265	285	271
Increase of ≥15 letters	97 32.2%	83 29%	71 23.8%	76 25.3%
Increase of 5-14 letters	90 29.9%	98 34.3%	103 34.6%	90 30%
Change of ≤4 letters	62 20.6%	50 17.5%	75 25.2%	59 19.7%
Decrease of 5-14 letters	19 6.3%	18 6.3%	23 7.7%	23 7.7%
Decrease of ≥15 letters	16 5.3%	16 5.6%	13 4.4%	23 7.7%

2. Primary Outcome

Title	Change From Baseline in Visual-acuity Score (Continuous)
Description	Visual acuity testing was performed with the Electronic Visual Tester (EVA) following the ETDRS protocol. VA score is measured as number of letters read correctly. The VA score change is the difference of the VA score at 1 Year and the VA score at baseline. In this study, the outcome VA score change is ranged from -71 to 52, with the higher VA score change the better visual acuity improvement.
Time Frame	Baseline and 1 Year

Outcome Measure Data

Analysis Population Description

All patients who had VA measured at week 52 were included in the analysis. All analyses were performed on the basis of the intention-to-treat principle. The Data and Safety Monitoring Committee recommended that data for all 23 patients at one center be excluded because of serious protocol noncompliance.

Arm/Group Title	1-Lucentis Monthly	2-Avastin Monthly	3-Lucentis as Needed	4-Avastin as Needed
Arm/Group Description	Lucentis® on a fixed schedule of every 4 weeks for 1 year; at 1 year, re-randomization to Lucentis® every 4 weeks or to variable dosing.	Avastin® on a fixed schedule of every 4 weeks for 1 year; at 1 year, re-randomization to Avastin® every 4 weeks or to variable dosing.	Lucentis® on a variable dosing schedule for 2 years; i.e., after initial treatment, monthly evaluation for treatment based on signs of lesion activity.	Avastin® on a variable dosing schedule for 2 years; i.e., after initial treatment, monthly evaluation for treatment based on signs of lesion activity.
Measure Participants	284	265	285	271
Mean (Standard Deviation) [No. of Letters]	8.5 (14.1)	8.0 (15.8)	6.8 (13.1)	5.9 (15.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	1-Lucentis Monthly, 2-Avastin Monthly
	Comments	The study was designed as a non-inferiority trial among four study groups, with the ability to test for superiority if a treatment was found to be non-inferior. Assuming a standard deviation for changes in visual acuity for 15 letters, we determined that a sample of 277 patients per group (which was increased to 300 to allow for a rate of death or dropout of 8%) would provide a power of 90%.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	The non-inferiority limit for the difference between study groups in the mean change in visual acuity at 1 year was 5 letters (i.e., one line on the Early Treatment Diabetic Retinopathy Study [ETDRS] visual-acuity chart)
Statistical Test of Hypothesis	p-Value	0.16
	Comments	This p-value is for the test of overall difference among 4 treatment groups. The p-value for pairwise comparison was not performed, because this is a non-inferiority trial.
	Method	ANOVA
	Comments	We calcularted of two-sided 99.2% confidence intervals. We used Bonferroni approach to accommodate six pairwise treatment comparisons.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.5
	Confidence Interval	(2-Sided) 99.2%; -3.9 to 2.9
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.7
	Estimation Comments	Estimate = Mean VA Change in Avastin Monthly Group - Mean VA Change in Lucentis Monthly Group

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	3-Lucentis as Needed, 4-Avastin as Needed
	Comments	The study was designed as a non-inferiority trial among four study groups, with the ability to test for superiority if a treatment was found to be non-inferior. Assuming a standard deviation for changes in visual acuity for 15 letters, we determined that a sample of 277 patients per group (which was increased to 300 to allow for a rate of death or dropout of 8%) would provide a power of 90%.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	The non-inferiority limit for the difference between study groups in the mean change in visual acuity at 1 year was 5 letters (i.e., one line on the Early Treatment Diabetic Retinopathy Study [ETDRS] visual-acuity chart)
Statistical Test of Hypothesis	p-Value	0.16
	Comments	This p-value is for the test of overall difference among 4 treatment groups. The p-value for pairwise comparison was not performed, because this is a non-inferiority trial.
	Method	ANOVA
	Comments	We calcularted of two-sided 99.2% confidence intervals. We used Bonferroni approach to accommodate six pairwise treatment comparisons.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.8
	Confidence Interval	(2-Sided) 99.2%; -4.1 to 2.4
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.6
	Estimation Comments	Estimate = Mean VA Change in Avastin as Needed Group - Mean VA Change in Lucentis as Needed Group

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	1-Lucentis Monthly, 3-Lucentis as Needed
	Comments	The study was designed as a non-inferiority trial among four study groups, with the ability to test for superiority if a treatment was found to be non-inferior. Assuming a standard deviation for changes in visual acuity for 15 letters, we determined that a sample of 277 patients per group (which was increased to 300 to allow for a rate of death or dropout of 8%) would provide a power of 90%.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	The non-inferiority limit for the difference between study groups in the mean change in visual acuity at 1 year was 5 letters (i.e., one line on the Early Treatment Diabetic Retinopathy Study [ETDRS] visual-acuity chart)
Statistical Test of Hypothesis	p-Value	0.16
	Comments	This p-value is for the test of overall difference among 4 treatment groups. The p-value for pairwise comparison was not performed, because this is a non-inferiority trial.
	Method	ANOVA
	Comments	We calcularted of two-sided 99.2% confidence intervals. We used Bonferroni approach to accommodate six pairwise treatment comparisons.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-1.7
	Confidence Interval	(2-Sided) 99.2%; -4.7 to 1.3
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.5
	Estimation Comments	Estimate = Mean VA Change in Lucentis as Needed Group - Mean VA Change in Lucentis Monthly Group

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	2-Avastin Monthly, 4-Avastin as Needed
	Comments	The study was designed as a non-inferiority trial among four study groups, with the ability to test for superiority if a treatment was found to be non-inferior. Assuming a standard deviation for changes in visual acuity for 15 letters, we determined that a sample of 277 patients per group (which was increased to 300 to allow for a rate of death or dropout of 8%) would provide a power of 90%.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	The non-inferiority limit for the difference between study groups in the mean change in visual acuity at 1 year was 5 letters (i.e., one line on the Early Treatment Diabetic Retinopathy Study [ETDRS] visual-acuity chart)
Statistical Test of Hypothesis	p-Value	0.16
	Comments	This p-value is for the test of overall difference among 4 treatment groups. The p-value for pairwise comparison was not performed, because this is a non-inferiority trial.
	Method	ANOVA
	Comments	We calcularted of two-sided 99.2% confidence intervals. We used Bonferroni approach to accommodate six pairwise treatment comparisons.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-2.1
	Confidence Interval	(2-Sided) 99.2%; -5.7 to 1.6
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.9
	Estimation Comments	Estimate = Mean VA Change in Avastin as Needed Group - Mean VA Change in Avastin Monthly Group

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	2-Avastin Monthly, 3-Lucentis as Needed
	Comments	The study was designed as a non-inferiority trial among four study groups, with the ability to test for superiority if a treatment was found to be non-inferior. Assuming a standard deviation for changes in visual acuity for 15 letters, we determined that a sample of 277 patients per group (which was increased to 300 to allow for a rate of death or dropout of 8%) would provide a power of 90%.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	The non-inferiority limit for the difference between study groups in the mean change in visual acuity at 1 year was 5 letters (i.e., one line on the Early Treatment Diabetic Retinopathy Study [ETDRS] visual-acuity chart)
Statistical Test of Hypothesis	p-Value	0.16
	Comments	This p-value is for the test of overall difference among 4 treatment groups. The p-value for pairwise comparison was not performed, because this is a non-inferiority trial.
	Method	ANOVA
	Comments	We calcularted of two-sided 99.2% confidence intervals. We used Bonferroni approach to accommodate six pairwise treatment comparisons.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-1.2
	Confidence Interval	(2-Sided) 99.2%; -4.5 to 2.1
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.7
	Estimation Comments	Estimate = Mean VA Change in Lucentis as Needed Group - Mean VA Change in Avastin Monthly Group

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	1-Lucentis Monthly, 4-Avastin as Needed
	Comments	The study was designed as a non-inferiority trial among four study groups, with the ability to test for superiority if a treatment was found to be non-inferior. Assuming a standard deviation for changes in visual acuity for 15 letters, we determined that a sample of 277 patients per group (which was increased to 300 to allow for a rate of death or dropout of 8%) would provide a power of 90%.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	The non-inferiority limit for the difference between study groups in the mean change in visual acuity at 1 year was 5 letters (i.e., one line on the Early Treatment Diabetic Retinopathy Study [ETDRS] visual-acuity chart)
Statistical Test of Hypothesis	p-Value	0.16
	Comments	This p-value is for the test of overall difference among 4 treatment groups. The p-value for pairwise comparison was not performed, because this is a non-inferiority trial.
	Method	ANOVA
	Comments	We calcularted of two-sided 99.2% confidence intervals. We used Bonferroni approach to accommodate six pairwise treatment comparisons.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-2.6
	Confidence Interval	(2-Sided) 99.2%; -5.9 to 0.8
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.7
	Estimation Comments	Estimate = Mean VA Change in Avastin as Needed Group - Mean VA Change in Lucentis Monthly Group

3. Secondary Outcome

Title	Visual-acuity Score and Snellen Equivalent (Frequency)
Time Frame	at 1 Year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	1-Lucentis Monthly	2-Avastin Monthly	3-Lucentis as Needed	4-Avastin as Needed
Arm/Group Description	Lucentis® on a fixed schedule of every 4 weeks for 1 year; at 1 year, re-randomization to Lucentis® every 4 weeks or to variable dosing.	Avastin® on a fixed schedule of every 4 weeks for 1 year; at 1 year, re-randomization to Avastin® every 4 weeks or to variable dosing.	Lucentis® on a variable dosing schedule for 2 years; i.e., after initial treatment, monthly evaluation for treatment based on signs of lesion activity.	Avastin® on a variable dosing schedule for 2 years; i.e., after initial treatment, monthly evaluation for treatment based on signs of lesion activity.
Measure Participants	284	265	285	271
83-97 letters, 20/12-20	42 14%	45 15.7%	38 12.8%	40 13.3%
68-82 letters, 20/25-40	149 49.5%	134 46.9%	141 47.3%	127 42.3%
53-67 letters, 20/50-80	52 17.3%	47 16.4%	66 22.1%	57 19%
38-52 letters, 20/100-160	23 7.6%	21 7.3%	23 7.7%	24 8%
≤37 letters, ≤20/200	18 6%	18 6.3%	17 5.7%	23 7.7%

4. Secondary Outcome

Title	Visual-acuity Score and Snellen Equivalent (Continuous)
Description	Visual acuity testing was performed with the Electronic Visual Tester (EVA) following the ETDRS protocol. VA score is measured as number of letters read correctly. In this study, the outcome VA score is ranged from 0 to 97, with the higher score the better visual acuity.
Time Frame	at 1 Year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	1-Lucentis Monthly	2-Avastin Monthly	3-Lucentis as Needed	4-Avastin as Needed
Arm/Group Description	Lucentis® on a fixed schedule of every 4 weeks for 1 year; at 1 year, re-randomization to Lucentis® every 4 weeks or to variable dosing.	Avastin® on a fixed schedule of every 4 weeks for 1 year; at 1 year, re-randomization to Avastin® every 4 weeks or to variable dosing.	Lucentis® on a variable dosing schedule for 2 years; i.e., after initial treatment, monthly evaluation for treatment based on signs of lesion activity.	Avastin® on a variable dosing schedule for 2 years; i.e., after initial treatment, monthly evaluation for treatment based on signs of lesion activity.
Measure Participants	284	265	285	271
Mean (Standard Deviation) [No. of Letters]	68.8 (17.7)	68.4 (18.2)	68.4 (16.4)	66.5 (19.0)

5. Secondary Outcome

Title	Number of Treatments
Description	Cumulative over the 1 year of trial
Time Frame	1 Year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	1-Lucentis Monthly	2-Avastin Monthly	3-Lucentis as Needed	4-Avastin as Needed
Arm/Group Description	Lucentis® on a fixed schedule of every 4 weeks for 1 year; at 1 year, re-randomization to Lucentis® every 4 weeks or to variable dosing.	Avastin® on a fixed schedule of every 4 weeks for 1 year; at 1 year, re-randomization to Avastin® every 4 weeks or to variable dosing.	Lucentis® on a variable dosing schedule for 2 years; i.e., after initial treatment, monthly evaluation for treatment based on signs of lesion activity.	Avastin® on a variable dosing schedule for 2 years; i.e., after initial treatment, monthly evaluation for treatment based on signs of lesion activity.
Measure Participants	284	265	285	271
Mean (Standard Error) [Number of Treatments]	11.7 (1.5)	11.9 (1.2)	6.9 (3.0)	7.7 (3.5)

6. Secondary Outcome

Title	Average Cost of Drug/Patient
Time Frame	at 1 Year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	1-Lucentis Monthly	2-Avastin Monthly	3-Lucentis as Needed	4-Avastin as Needed
Arm/Group Description	Lucentis® on a fixed schedule of every 4 weeks for 1 year; at 1 year, re-randomization to Lucentis® every 4 weeks or to variable dosing.	Avastin® on a fixed schedule of every 4 weeks for 1 year; at 1 year, re-randomization to Avastin® every 4 weeks or to variable dosing.	Lucentis® on a variable dosing schedule for 2 years; i.e., after initial treatment, monthly evaluation for treatment based on signs of lesion activity.	Avastin® on a variable dosing schedule for 2 years; i.e., after initial treatment, monthly evaluation for treatment based on signs of lesion activity.
Measure Participants	284	265	285	271
Mean (Standard Deviation) [US dollars per patient]	23400 (3000)	595 (60)	13800 (6000)	385 (175)

7. Secondary Outcome

Title	Total Thickness at Fovea
Time Frame	at 1 Year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	1-Lucentis Monthly	2-Avastin Monthly	3-Lucentis as Needed	4-Avastin as Needed
Arm/Group Description	Lucentis® on a fixed schedule of every 4 weeks for 1 year; at 1 year, re-randomization to Lucentis® every 4 weeks or to variable dosing.	Avastin® on a fixed schedule of every 4 weeks for 1 year; at 1 year, re-randomization to Avastin® every 4 weeks or to variable dosing.	Lucentis® on a variable dosing schedule for 2 years; i.e., after initial treatment, monthly evaluation for treatment based on signs of lesion activity.	Avastin® on a variable dosing schedule for 2 years; i.e., after initial treatment, monthly evaluation for treatment based on signs of lesion activity.
Measure Participants	280	261	281	265
Mean (Standard Deviation) [μm]	266 (125)	300 (149)	294 (139)	308 (127)

8. Secondary Outcome

Title	Total Thickness Change From Baseline at Fovea
Time Frame	Baseline and 1 Year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	1-Lucentis Monthly	2-Avastin Monthly	3-Lucentis as Needed	4-Avastin as Needed
Arm/Group Description	Lucentis® on a fixed schedule of every 4 weeks for 1 year; at 1 year, re-randomization to Lucentis® every 4 weeks or to variable dosing.	Avastin® on a fixed schedule of every 4 weeks for 1 year; at 1 year, re-randomization to Avastin® every 4 weeks or to variable dosing.	Lucentis® on a variable dosing schedule for 2 years; i.e., after initial treatment, monthly evaluation for treatment based on signs of lesion activity.	Avastin® on a variable dosing schedule for 2 years; i.e., after initial treatment, monthly evaluation for treatment based on signs of lesion activity.
Measure Participants	280	260	278	265
Mean (Standard Deviation) [μm]	-196 (176)	-164 (181)	-168 (186)	-152 (178)

9. Secondary Outcome

Title	Retinal Thickness Plus Subfoveal-fluid Thickness at Fovea
Time Frame	at 1 Year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	1-Lucentis Monthly	2-Avastin Monthly	3-Lucentis as Needed	4-Avastin as Needed
Arm/Group Description	Lucentis® on a fixed schedule of every 4 weeks for 1 year; at 1 year, re-randomization to Lucentis® every 4 weeks or to variable dosing.	Avastin® on a fixed schedule of every 4 weeks for 1 year; at 1 year, re-randomization to Avastin® every 4 weeks or to variable dosing.	Lucentis® on a variable dosing schedule for 2 years; i.e., after initial treatment, monthly evaluation for treatment based on signs of lesion activity.	Avastin® on a variable dosing schedule for 2 years; i.e., after initial treatment, monthly evaluation for treatment based on signs of lesion activity.
Measure Participants	280	261	281	265
Mean (Standard Deviation) [μm]	152 (57)	172 (81)	166 (66)	172 (68)

10. Secondary Outcome

Title	Retinal Thickness Plus Subfoveal-fluid Thickness Change From Baseline at Fovea
Time Frame	Baseline and 1 Year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	1-Lucentis Monthly	2-Avastin Monthly	3-Lucentis as Needed	4-Avastin as Needed
Arm/Group Description	Lucentis® on a fixed schedule of every 4 weeks for 1 year; at 1 year, re-randomization to Lucentis® every 4 weeks or to variable dosing.	Avastin® on a fixed schedule of every 4 weeks for 1 year; at 1 year, re-randomization to Avastin® every 4 weeks or to variable dosing.	Lucentis® on a variable dosing schedule for 2 years; i.e., after initial treatment, monthly evaluation for treatment based on signs of lesion activity.	Avastin® on a variable dosing schedule for 2 years; i.e., after initial treatment, monthly evaluation for treatment based on signs of lesion activity.
Measure Participants	280	260	278	265
Mean (Standard Deviation) [μm]	-100 (130)	-79 (132)	-81 (134)	-79 (123)

11. Secondary Outcome

Title	Fluid on Optical Coherence Tomography
Time Frame	at 1 Year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	1-Lucentis Monthly	2-Avastin Monthly	3-Lucentis as Needed	4-Avastin as Needed
Arm/Group Description	Lucentis® on a fixed schedule of every 4 weeks for 1 year; at 1 year, re-randomization to Lucentis® every 4 weeks or to variable dosing.	Avastin® on a fixed schedule of every 4 weeks for 1 year; at 1 year, re-randomization to Avastin® every 4 weeks or to variable dosing.	Lucentis® on a variable dosing schedule for 2 years; i.e., after initial treatment, monthly evaluation for treatment based on signs of lesion activity.	Avastin® on a variable dosing schedule for 2 years; i.e., after initial treatment, monthly evaluation for treatment based on signs of lesion activity.
Measure Participants	284	265	285	271
Absent	124 41.2%	69 24.1%	68 22.8%	52 17.3%
Present	151 50.2%	188 65.7%	203 68.1%	214 71.3%
Data missing	9 3%	8 2.8%	14 4.7%	5 1.7%

12. Secondary Outcome

Title	Dye Leakage on Angiogram
Time Frame	at 1 Year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	1-Lucentis Monthly	2-Avastin Monthly	3-Lucentis as Needed	4-Avastin as Needed
Arm/Group Description	Lucentis® on a fixed schedule of every 4 weeks for 1 year; at 1 year, re-randomization to Lucentis® every 4 weeks or to variable dosing.	Avastin® on a fixed schedule of every 4 weeks for 1 year; at 1 year, re-randomization to Avastin® every 4 weeks or to variable dosing.	Lucentis® on a variable dosing schedule for 2 years; i.e., after initial treatment, monthly evaluation for treatment based on signs of lesion activity.	Avastin® on a variable dosing schedule for 2 years; i.e., after initial treatment, monthly evaluation for treatment based on signs of lesion activity.
Measure Participants	284	265	285	271
Absent	167 55.5%	153 53.5%	133 44.6%	111 37%
Present	97 32.2%	100 35%	137 46%	145 48.3%
Data missing	20 6.6%	12 4.2%	15 5%	15 5%

13. Secondary Outcome

Title	Area of Lesion
Time Frame	at 1 Year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	1-Lucentis Monthly	2-Avastin Monthly	3-Lucentis as Needed	4-Avastin as Needed
Arm/Group Description	Lucentis® on a fixed schedule of every 4 weeks for 1 year; at 1 year, re-randomization to Lucentis® every 4 weeks or to variable dosing.	Avastin® on a fixed schedule of every 4 weeks for 1 year; at 1 year, re-randomization to Avastin® every 4 weeks or to variable dosing.	Lucentis® on a variable dosing schedule for 2 years; i.e., after initial treatment, monthly evaluation for treatment based on signs of lesion activity.	Avastin® on a variable dosing schedule for 2 years; i.e., after initial treatment, monthly evaluation for treatment based on signs of lesion activity.
Measure Participants	256	243	265	249
Mean (Standard Deviation) [mm^2]	6.6 (6.8)	6.5 (6.7)	7.3 (6.5)	7.0 (7.5)

14. Secondary Outcome

Title	Area of Lesion Change From Baseline
Time Frame	Baseline and 1 Year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	1-Lucentis Monthly	2-Avastin Monthly	3-Lucentis as Needed	4-Avastin as Needed
Arm/Group Description	Lucentis® on a fixed schedule of every 4 weeks for 1 year; at 1 year, re-randomization to Lucentis® every 4 weeks or to variable dosing.	Avastin® on a fixed schedule of every 4 weeks for 1 year; at 1 year, re-randomization to Avastin® every 4 weeks or to variable dosing.	Lucentis® on a variable dosing schedule for 2 years; i.e., after initial treatment, monthly evaluation for treatment based on signs of lesion activity.	Avastin® on a variable dosing schedule for 2 years; i.e., after initial treatment, monthly evaluation for treatment based on signs of lesion activity.
Measure Participants	250	238	259	241
Mean (Standard Deviation) [mm^2]	-0.1 (5.2)	0.3 (4.9)	0.6 (6.2)	1.3 (6.6)

15. Secondary Outcome

Title	Change in Systolic Blood Pressure From Baseline
Time Frame	Baseline and 1 Year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	1-Lucentis Monthly	2-Avastin Monthly	3-Lucentis as Needed	4-Avastin as Needed
Arm/Group Description	Lucentis® on a fixed schedule of every 4 weeks for 1 year; at 1 year, re-randomization to Lucentis® every 4 weeks or to variable dosing.	Avastin® on a fixed schedule of every 4 weeks for 1 year; at 1 year, re-randomization to Avastin® every 4 weeks or to variable dosing.	Lucentis® on a variable dosing schedule for 2 years; i.e., after initial treatment, monthly evaluation for treatment based on signs of lesion activity.	Avastin® on a variable dosing schedule for 2 years; i.e., after initial treatment, monthly evaluation for treatment based on signs of lesion activity.
Measure Participants	239	226	250	232
Mean (Standard Deviation) [mm Hg]	-2.1 (22.4)	-5.4 (18.2)	-5.2 (20.3)	-4.5 (20.0)

16. Secondary Outcome

Title	Change in Diastolic Blood Pressure From Baseline
Time Frame	Baseline and 1 Year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	1-Lucentis Monthly	2-Avastin Monthly	3-Lucentis as Needed	4-Avastin as Needed
Arm/Group Description	Lucentis® on a fixed schedule of every 4 weeks for 1 year; at 1 year, re-randomization to Lucentis® every 4 weeks or to variable dosing.	Avastin® on a fixed schedule of every 4 weeks for 1 year; at 1 year, re-randomization to Avastin® every 4 weeks or to variable dosing.	Lucentis® on a variable dosing schedule for 2 years; i.e., after initial treatment, monthly evaluation for treatment based on signs of lesion activity.	Avastin® on a variable dosing schedule for 2 years; i.e., after initial treatment, monthly evaluation for treatment based on signs of lesion activity.
Measure Participants	239	226	250	232
Mean (Standard Deviation) [mm Hg]	-0.9 (11.9)	-1.4 (11.2)	-1.9 (10.2)	-2.1 (10.8)

Adverse Events

Time Frame	Adverse events were collected at 1 year.
Adverse Event Reporting Description	Adverse events were ascertained through monthly questioning of patients by study coordinators who were aware of study-group assignments; events were coded according to the Medical Dictionary for Regulatory Activities (MedDRA) system, version 10. A medical monitor who was unaware of study-group assignments reviewed serious adverse events.
Arm/Group Title	1-Lucentis Monthly		2-Avastin Monthly		3-Lucentis as Needed		4-Avastin as Needed
Arm/Group Description	Lucentis® on a fixed schedule of every 4 weeks for 1 year; at 1 year, re-randomization to Lucentis® every 4 weeks or to variable dosing.		Avastin® on a fixed schedule of every 4 weeks for 1 year; at 1 year, re-randomization to Avastin® every 4 weeks or to variable dosing.		Lucentis® on a variable dosing schedule for 2 years; i.e., after initial treatment, monthly evaluation for treatment based on signs of lesion activity.		Avastin® on a variable dosing schedule for 2 years; i.e., after initial treatment, monthly evaluation for treatment based on signs of lesion activity.
All Cause Mortality
	1-Lucentis Monthly		2-Avastin Monthly		3-Lucentis as Needed		4-Avastin as Needed
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	1-Lucentis Monthly		2-Avastin Monthly		3-Lucentis as Needed		4-Avastin as Needed
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	53/301 (17.6%)		64/286 (22.4%)		61/298 (20.5%)		77/300 (25.7%)
Blood and lymphatic system disorders
Death from vascular causes	2/301 (0.7%)		2/286 (0.7%)		2/298 (0.7%)		5/300 (1.7%)
Hypertension	0/301 (0%)		2/286 (0.7%)		0/298 (0%)		0/300 (0%)
Venous thrombotic event	0/301 (0%)		4/286 (1.4%)		2/298 (0.7%)		1/300 (0.3%)
Cardiac disorders
Cardiac disorder	10/301 (3.3%)		16/286 (5.6%)		12/298 (4%)		13/300 (4.3%)
Nonfatal myocardial infarction	2/301 (0.7%)		2/286 (0.7%)		3/298 (1%)		1/300 (0.3%)
Nonfatal stroke	3/301 (1%)		2/286 (0.7%)		1/298 (0.3%)		2/300 (0.7%)
Transient ischemic attack	1/301 (0.3%)		0/286 (0%)		2/298 (0.7%)		3/300 (1%)
Gastrointestinal disorders
Gastrointestinal disorder	3/301 (1%)		6/286 (2.1%)		2/298 (0.7%)		9/300 (3%)
General disorders
Any other system organ class	18/301 (6%)		26/286 (9.1%)		16/298 (5.4%)		28/300 (9.3%)
Death from any cause	4/301 (1.3%)		4/286 (1.4%)		5/298 (1.7%)		11/300 (3.7%)
Infections and infestations
Infection	6/301 (2%)		11/286 (3.8%)		12/298 (4%)		18/300 (6%)
Injury, poisoning and procedural complications
Injury or procedural complication	7/301 (2.3%)		11/286 (3.8%)		8/298 (2.7%)		9/300 (3%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Benignor malignant neoplasm	7/301 (2.3%)		5/286 (1.7%)		10/298 (3.4%)		9/300 (3%)
Nervous system disorders
Nervous system disorder	6/301 (2%)		9/286 (3.1%)		12/298 (4%)		9/300 (3%)
Surgical and medical procedures
Surgical or medical procedure	4/301 (1.3%)		6/286 (2.1%)		4/298 (1.3%)		8/300 (2.7%)
Other (Not Including Serious) Adverse Events
	1-Lucentis Monthly		2-Avastin Monthly		3-Lucentis as Needed		4-Avastin as Needed
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/301 (1%)		4/286 (1.4%)		0/298 (0%)		0/300 (0%)
Eye disorders
Endophthalmitis	2/301 (0.7%)		4/286 (1.4%)		0/298 (0%)		0/300 (0%)
Pseudoendophthalmitis	1/301 (0.3%)		0/286 (0%)		0/298 (0%)		0/300 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Dr. Grunwald reports receiving consulting fees from GlaxoSmithKline; and Dr. Jaffe, consulting fees from Neurotech and SurModics. No other potential conflict of interest relevant to this article was reported.