Now Available: Final Rule for FDAAA 801 and NIH Policy on Clinical Trial Reporting

Laser-Ranibizumab-Triamcinolone for Diabetic Macular Edema (LRT for DME)

This study has been completed.
Sponsor:
Collaborators:
National Eye Institute (NEI)
Allergan
Genentech, Inc.
Information provided by (Responsible Party):
Jaeb Center for Health Research
ClinicalTrials.gov Identifier:
NCT00444600
First received: March 6, 2007
Last updated: August 25, 2016
Last verified: August 2016
Results First Received: January 14, 2011  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Outcomes Assessor);   Primary Purpose: Treatment
Conditions: Diabetic Retinopathy
Diabetic Macular Edema
Interventions: Drug: Triamcinolone Acetonide + laser
Drug: Ranibizumab + laser
Drug: Sham injection + laser
Drug: Ranibizumab + deferred laser

  Participant Flow
  Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Fifty two academic and community based sites across the United States recruited 691 study participants from March 2007 to December 2008.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Participants with two study eyes enrolled each eye in a different treatment group. Therefore, each treatment group/arm includes no more than one study eye for a given participant, and thus the numbers of eyes is equal to the number of participants in each arm.

Reporting Groups
  Description
Sham+Prompt Laser Sham injection at randomization plus focal photocoagulation 1 week post-injection. Injections are repeated every 4 weeks with focal photocoagulation given post-injection every 16 weeks. Retreatment starting at 16 weeks depends on visual acuity and OCT.
0.5 mg Ranibizumab+Prompt Laser 0.5 mg intravitreal ranibizumab at randomization plus focal photocoagulation 1 week post-injection. Injections are repeated every 4 weeks with focal photocoagulation given post-injection every 16 weeks. Retreatment starting at 16 weeks depends on visual acuity and OCT.
0.5 mg Ranibizumab+Deferred Laser 0.5 mg intravitreal ranibizumab at randomization, repeated every 4 weeks. Retreatment starting at 16 weeks depends on visual acuity and OCT. If improvement has not occured from injections alone, laser can be given starting at the 24 week visit.
4 mg Triamcinolone+Prompt Laser 4 mg intravitreal triamcinolone at randomization plus focal photocoagulation 1 week post-injection, repeated every 16 weeks with sham injections at 4-week intervals in-between. Retreatment starting at 16 weeks depends on visual acuity and OCT.

Participant Flow:   Overall Study
    Sham+Prompt Laser   0.5 mg Ranibizumab+Prompt Laser   0.5 mg Ranibizumab+Deferred Laser   4 mg Triamcinolone+Prompt Laser
STARTED   293 [1]   187 [1]   188 [1]   186 [1] 
COMPLETED   274 [1]   171 [1]   178 [1]   176 [1] 
NOT COMPLETED   19   16   10   10 
Death                7                5                3                2 
Dropped                11                11                7                7 
Missed visit                1                0                0                1 
[1] Number of eyes



  Baseline Characteristics
  Hide Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Sham+Prompt Laser Sham injection at randomization plus focal photocoagulation 1 week post-injection. Injections are repeated every 4 weeks with focal photocoagulation given post-injection every 16 weeks. Retreatment starting at 16 weeks depends on visual acuity and OCT.
0.5 mg Ranibizumab+Prompt Laser 0.5 mg intravitreal ranibizumab at randomization plus focal photocoagulation 1 week post-injection. Injections are repeated every 4 weeks with focal photocoagulation given post-injection every 16 weeks. Retreatment starting at 16 weeks depends on visual acuity and OCT.
0.5 mg Ranibizumab+Deferred Laser 0.5 mg intravitreal ranibizumab at randomization, repeated every 4 weeks. Retreatment starting at 16 weeks depends on visual acuity and OCT. If improvement has not occured from injections alone, laser can be given starting at the 24 week visit.
4 mg Triamcinolone+Prompt Laser 4 mg intravitreal triamcinolone at randomization plus focal photocoagulation 1 week post-injection, repeated every 16 weeks with sham injections at 4-week intervals in-between. Retreatment starting at 16 weeks depends on visual acuity and OCT.
Total Total of all reporting groups

Baseline Measures
   Sham+Prompt Laser   0.5 mg Ranibizumab+Prompt Laser   0.5 mg Ranibizumab+Deferred Laser   4 mg Triamcinolone+Prompt Laser   Total 
Overall Participants Analyzed 
[Units: Participants]
 293   187   188   186   854 
Age 
[Units: Years]
Median (Inter-Quartile Range)
 63 
 (57 to 69) 
 62 
 (56 to 70) 
 64 
 (58 to 70) 
 62 
 (55 to 70) 
 63 
 (56 to 70) 
Gender 
[Units: Participants]
         
Female   123   85   78   86   372 
Male   170   102   110   100   482 
Race/Ethnicity, Customized 
[Units: Participants]
         
White   202   131   134   134   601 
African American   51   30   25   32   138 
Hispanic or Latino   34   21   25   15   95 
Asian   4   1   2   4   11 
Native Hawaiian/Other Pacific Islander   0   1   0   0   1 
More than one race   1   1   1   0   3 
Unknown/not reported   1   2   1   1   5 
Visual Acuity Letter Score (approximate Snellen equivalent) by randomization strata 
[Units: Eyes]
         
≥66 (better than 20/50)   146   95   95   93   429 
≤65 (20/50 or worse)   147   92   93   93   425 
Classification of diabetic macular edema [1] 
[Units: Eyes]
         
Predominantly focal   78   60   68   53   259 
Neither predominantly focal or diffuse   71   46   41   48   206 
Predominantly diffuse   144   81   79   85   389 
[1] Based on clinical exam.
Number of study eyes 
[Units: Participants]
         
1 study eye   130   131   132   135   528 
2 study eyes   163   56   56   51   326 
Diabetes Type 
[Units: Participants]
         
Type 1   25   11   15   14   65 
Type 2   260   172   170   166   768 
Uncertain   8   4   3   6   21 
Duration of diabetes 
[Units: Years]
Median (Inter-Quartile Range)
 16 
 (9 to 22) 
 18 
 (12 to 24) 
 17 
 (11 to 22) 
 17 
 (11 to 24) 
 16 
 (10 to 23) 
HbA1c [1] 
[Units: Percentage]
Median (Inter-Quartile Range)
 7.3 
 (6.6 to 8.3) 
 7.3 
 (6.6 to 8.4) 
 7.5 
 (6.7 to 8.4) 
 7.4 
 (6.5 to 8.6) 
 7.3 
 (6.6 to 8.4) 
[1] Missing HbA1c data for 17, 3, 7 and 8 study participants in the sham+prompt laser, ranibizumab+prompt laser, ranibizumab+deferred laser and triamcinolone+prompt laser groups, respectively.
Prior cardiovascular event [1] 
[Units: Participants]
         
Yes   93   66   61   61   281 
No   200   121   127   125   573 
[1] Based on medical history of condition.
Hypertension 
[Units: Participants]
         
Yes   240   154   156   148   698 
No   53   33   32   38   156 
Prior Panretinal Photocoagulation 
[Units: Eyes]
         
Yes   48   36   31   37   152 
No   245   151   157   149   702 
Prior treatment for diabetic macular edema 
[Units: Eyes]
         
No   105   74   74   61   314 
Yes   188   113   114   125   540 
Prior laser for diabetic macular edema 
[Units: Eyes]
         
Yes   173   101   101   114   489 
No   120   86   87   72   365 
Prior IVT for diabetic macular edema [1] 
[Units: Eyes]
         
Yes   39   22   36   31   128 
No   254   165   152   155   726 
[1] IVT = intravitreal triamcinolone
Prior vitrectomy for diabetic macular edema 
[Units: Eyes]
         
Yes   15   7   5   12   39 
No   278   180   183   174   815 
Prior peribulbar triamcinolone for diabetic macular edema 
[Units: Eyes]
         
Yes   12   9   5   5   31 
No   281   178   183   181   823 
Prior anti-VEGF for diabetic macular edema [1] 
[Units: Eyes]
         
Yes   24   24   21   20   89 
No   269   163   167   166   765 
[1] VEGF = vascular endothelial growth factor
Intraocular pressure 
[Units: mmHg]
Median (Inter-Quartile Range)
 16 
 (14 to 18) 
 16 
 (14 to 18) 
 16 
 (14 to 18) 
 16 
 (14 to 18) 
 16 
 (14 to 18) 
Currently on intraocular pressure lowering medicine for glaucoma or ocular hypertension 
[Units: Eyes]
         
Yes   5   6   4   2   17 
No   288   181   184   184   837 
Lens status [1] 
[Units: Eyes]
         
Phakic   192   131   134   124   581 
Anterior Chamber Intraocular Lense   3   1   1   0   5 
Posterior Chamber Intraocular Lense   98   55   53   62   268 
[1] Based on clinical exam.
E-ETDRS Visual Acuity Letter Score [1] 
[Units: Letter Score]
Median (Inter-Quartile Range)
 65 
 (56 to 73) 
 66 
 (55 to 72) 
 66 
 (58 to 72) 
 66 
 (57 to 72) 
 66 
 (56 to 72) 
[1] Best corrected visual acuity letter score as measured by a certified tester using an electronic visual acuity testing machine based on the Early Treatment Diabetic Retinopathy Study (ETDRS) method. Best value on the scale 97, worst 0.
Central subfield thickness on optical coherence tomography 
[Units: Microns]
Median (Inter-Quartile Range)
 407 
 (309 to 505) 
 371 
 (302 to 464) 
 382 
 (298 to 488) 
 374 
 (298 to 463) 
 381 
 (306 to 485) 
Retinal volume on optical coherence tomography 
[Units: Microns]
Median (Inter-Quartile Range)
 8.7 
 (7.8 to 10.0) 
 8.4 
 (7.5 to 9.6) 
 8.4 
 (7.4 to 9.8) 
 8.5 
 (7.8 to 9.7) 
 8.5 
 (7.7 to 9.7) 
Optical coherence tomography cystoid abnormality 
[Units: Eyes]
         
No evidence   19   13   12   8   52 
Questionable or definite   274   171   174   177   796 
Cannot grade or missing   0   3   2   1   6 
Optical coherence tomography subretinal fluid present 
[Units: Eyes]
         
No evidence   222   149   140   146   657 
Questionable or definite   70   36   45   38   189 
Cannot grade   1   2   3   2   8 
ETDRS retinopathy severity level (ETDRS description) [1] 
[Units: Eyes]
         
Diabetic retinopathy absent   5   4   3   1   13 
Minimal non-proliferative DR   2   2   3   3   10 
Mild to moderately severe non-proliferative DR   171   103   107   95   476 
Severe non-proliferative DR   22   16   11   15   64 
Scars of full or partial PRP present;PDR absent   38   30   30   29   127 
Mild to moderate proliferative DR   33   24   22   34   113 
High risk proliferative DR   7   4   1   3   15 
Cannot grade   10   1   2   4   17 
Missing   5   3   9   2   19 
[1]

ETDRS = Early Treatment Diabetic Retinopathy Study; DR = diabetic retinopathy; PDR = proliferative diabetic retinopathy.

Criteria are based on the ETDRS fundus photographic risk factors for the progression of diabetic retinopathy. ETDRS report no. 12. Ophthalmology 1991; 98:823-833



  Outcome Measures
  Hide All Outcome Measures

1.  Primary:   Mean Change in Visual Acuity (Letters) From Baseline to 1 Year Adjusted for Baseline Visual Acuity   [ Time Frame: from baseline to 1 Year ]

Measure Type Primary
Measure Title Mean Change in Visual Acuity (Letters) From Baseline to 1 Year Adjusted for Baseline Visual Acuity
Measure Description Change in best correct visual acuity letter score from baseline to one year as measured by a certified tester using an electronic visual acuity testing machine based on the Early Treatment Diabetic Retinopathy Study (ETDRS) method. A positive change denotes an improvement. Best value on the scale 97, worst 0.
Time Frame from baseline to 1 Year  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
For eyes without any 1-year data the last observation carried forward method was used to impute data for the primary analysis. followed intention to treat principle.

Reporting Groups
  Description
Sham+Prompt Laser Sham injection at randomization plus focal photocoagulation 1 week post-injection. Injections are repeated every 4 weeks with focal photocoagulation given post-injection every 16 weeks. Retreatment starting at 16 weeks depends on visual acuity and OCT.
0.5 mg Ranibizumab+Prompt Laser 0.5 mg intravitreal ranibizumab at randomization plus focal photocoagulation 1 week post-injection. Injections are repeated every 4 weeks with focal photocoagulation given post-injection every 16 weeks. Retreatment starting at 16 weeks depends on visual acuity and OCT.
0.5 mg Ranibizumab+Deferred Laser 0.5 mg intravitreal ranibizumab at randomization, repeated every 4 weeks. Retreatment starting at 16 weeks depends on visual acuity and OCT. If improvement has not occured from injections alone, laser can be given starting at the 24 week visit.
4 mg Triamcinolone+Prompt Laser 4 mg intravitreal triamcinolone at randomization plus focal photocoagulation 1 week post-injection, repeated every 16 weeks with sham injections at 4-week intervals in-between. Retreatment starting at 16 weeks depends on visual acuity and OCT.

Measured Values
   Sham+Prompt Laser   0.5 mg Ranibizumab+Prompt Laser   0.5 mg Ranibizumab+Deferred Laser   4 mg Triamcinolone+Prompt Laser 
Participants Analyzed 
[Units: Participants]
 293   187   188   186 
Units Analyzed (Eyes) 
[Units: Eyes]
 293   187   188   186 
Mean Change in Visual Acuity (Letters) From Baseline to 1 Year Adjusted for Baseline Visual Acuity 
[Units: Letters]
Mean (Standard Deviation)
 3  (13)   9  (11)   9  (12)   4  (13) 


Statistical Analysis 1 for Mean Change in Visual Acuity (Letters) From Baseline to 1 Year Adjusted for Baseline Visual Acuity
Groups [1] Sham+Prompt Laser vs. 0.5 mg Ranibizumab+Prompt Laser
Method [2] ANCOVA
P Value [3] <0.001
Mean Difference (Final Values) [4] 5.8
95% Confidence Interval 3.2 to 8.5
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  Adjusted for baseline visual acuity and correlation between 2 study eyes.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Adjusted for multiple comparisons.
[4] Other relevant estimation information:
  No text entered.

Statistical Analysis 2 for Mean Change in Visual Acuity (Letters) From Baseline to 1 Year Adjusted for Baseline Visual Acuity
Groups [1] Sham+Prompt Laser vs. 0.5 mg Ranibizumab+Deferred Laser
Method [2] ANCOVA
P Value [3] <0.001
Mean Difference (Final Values) [4] 6.0
95% Confidence Interval 3.4 to 8.6
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  Adjusted for baseline visual acuity and correlation between 2 study eyes.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Adjusted for multiple comparisons.
[4] Other relevant estimation information:
  No text entered.

Statistical Analysis 3 for Mean Change in Visual Acuity (Letters) From Baseline to 1 Year Adjusted for Baseline Visual Acuity
Groups [1] Sham+Prompt Laser vs. 4 mg Triamcinolone+Prompt Laser
Method [2] ANCOVA
P Value [3] 0.31
Mean Difference (Final Values) [4] 1.1
95% Confidence Interval -1.5 to 3.7
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  Adjusted for baseline visual acuity and correlation between 2 study eyes.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Adjusted for multiple comparisons.
[4] Other relevant estimation information:
  No text entered.



2.  Primary:   Distribution of Change in Visual Acuity (Letters) From Baseline to 1 Year   [ Time Frame: from baseline to 1 Year ]

Measure Type Primary
Measure Title Distribution of Change in Visual Acuity (Letters) From Baseline to 1 Year
Measure Description Change in best correct visual acuity letter score as measured by a certified tester using an electronic visual acuity testing machine based on the Early Treatment Diabetic Retinopathy Study (ETDRS) method.
Time Frame from baseline to 1 Year  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
For eyes without any 1-year data the last observation carried forward method was used to impute data for the primary analysis.

Reporting Groups
  Description
Sham+Prompt Laser Sham injection at randomization plus focal photocoagulation 1 week post-injection. Injections are repeated every 4 weeks with focal photocoagulation given post-injection every 16 weeks. Retreatment starting at 16 weeks depends on visual acuity and OCT.
0.5 mg Ranibizumab+Prompt Laser 0.5 mg intravitreal ranibizumab at randomization plus focal photocoagulation 1 week post-injection. Injections are repeated every 4 weeks with focal photocoagulation given post-injection every 16 weeks. Retreatment starting at 16 weeks depends on visual acuity and OCT.
0.5 mg Ranibizumab+Deferred Laser 0.5 mg intravitreal ranibizumab at randomization, repeated every 4 weeks. Retreatment starting at 16 weeks depends on visual acuity and OCT. If improvement has not occured from injections alone, laser can be given starting at the 24 week visit.
4 mg Triamcinolone+Prompt Laser 4 mg intravitreal triamcinolone at randomization plus focal photocoagulation 1 week post-injection, repeated every 16 weeks with sham injections at 4-week intervals in-between. Retreatment starting at 16 weeks depends on visual acuity and OCT.

Measured Values
   Sham+Prompt Laser   0.5 mg Ranibizumab+Prompt Laser   0.5 mg Ranibizumab+Deferred Laser   4 mg Triamcinolone+Prompt Laser 
Participants Analyzed 
[Units: Participants]
 293   187   188   186 
Units Analyzed (Eyes) 
[Units: Eyes]
 293   187   188   186 
Distribution of Change in Visual Acuity (Letters) From Baseline to 1 Year 
[Units: Eyes]
       
≥15 letter improvement   43   57   52   39 
14-10 letter improvement   38   38   36   22 
9-5 letter improvement   67   34   54   32 
Same ±4 letters   86   38   35   54 
5-9 letters worse   20   14   5   12 
10-14 letters worse   16   3   2   12 
≥15 letters worse   23   3   4   15 


Statistical Analysis 1 for Distribution of Change in Visual Acuity (Letters) From Baseline to 1 Year
Groups [1] Sham+Prompt Laser vs. 0.5 mg Ranibizumab+Prompt Laser
Method [2] Binomial regression
Proportion [3] 23
95% Confidence Interval 13 to 34
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Difference in proportion with ≥10 letter improvement for sham+prompt laser at 1 year
[2] Other relevant method information, such as adjustments or degrees of freedom:
  Adjusted for correlation between 2 study eyes and multiple comparisons.
[3] Other relevant estimation information:
  No text entered.

Statistical Analysis 2 for Distribution of Change in Visual Acuity (Letters) From Baseline to 1 Year
Groups [1] Sham+Prompt Laser vs. 0.5 mg Ranibizumab+Deferred Laser
Method [2] Binomial regression
Proportion [3] 19
95% Confidence Interval 9 to 29
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Difference in proportion with ≥10 letter improvement from sham+prompt laser at 1 year
[2] Other relevant method information, such as adjustments or degrees of freedom:
  Adjusted for correlation between 2 study eyes and multiple comparisons.
[3] Other relevant estimation information:
  No text entered.

Statistical Analysis 3 for Distribution of Change in Visual Acuity (Letters) From Baseline to 1 Year
Groups [1] Sham+Prompt Laser vs. 4 mg Triamcinolone+Prompt Laser
Method [2] Binomial regression
Proportion [3] 6
95% Confidence Interval -4 to 16
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Difference in proportion with ≥10 letter improvement from sham+prompt laser at 1 year
[2] Other relevant method information, such as adjustments or degrees of freedom:
  Adjusted for correlation between 2 study eyes and multiple comparisons.
[3] Other relevant estimation information:
  No text entered.

Statistical Analysis 4 for Distribution of Change in Visual Acuity (Letters) From Baseline to 1 Year
Groups [1] Sham+Prompt Laser vs. 0.5 mg Ranibizumab+Prompt Laser
Method [2] Log-Binomial Regression
P Value [3] <0.001
Risk Ratio (RR) [4] 1.84
95% Confidence Interval 1.40 to 2.42
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Relative risk for ≥10 letter improvement comparison with sham+prompt laser at 1 year
[2] Other relevant method information, such as adjustments or degrees of freedom:
  Adjusted for correlation between 2 study eyes and multiple comparisons.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Confidence intervals are adjusted for multiple comparisons.
[4] Other relevant estimation information:
  No text entered.

Statistical Analysis 5 for Distribution of Change in Visual Acuity (Letters) From Baseline to 1 Year
Groups [1] Sham+Prompt Laser vs. 0.5 mg Ranibizumab+Deferred Laser
Method [2] Log-Binomial Regression
P Value [3] <0.001
Risk Ratio (RR) [4] 1.68
95% Confidence Interval 1.27 to 2.21
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Relative risk for ≥10 letter improvement comparison with sham+prompt laser at 1 year
[2] Other relevant method information, such as adjustments or degrees of freedom:
  Adjusted for correlation between 2 study eyes and multiple comparisons.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Confidence intervals are adjusted for multiple comparisons.
[4] Other relevant estimation information:
  No text entered.

Statistical Analysis 6 for Distribution of Change in Visual Acuity (Letters) From Baseline to 1 Year
Groups [1] Sham+Prompt Laser vs. 4 mg Triamcinolone+Prompt Laser
Method [2] Log-Binomial Regression
P Value [3] 0.16
Risk Ratio (RR) [4] 1.21
95% Confidence Interval 0.88 to 1.66
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Relative risk for ≥10 letter improvement comparison with sham+prompt laser at 1 year
[2] Other relevant method information, such as adjustments or degrees of freedom:
  Adjusted for correlation between 2 study eyes and multiple comparisons.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Confidence intervals are adjusted for multiple comparisons.
[4] Other relevant estimation information:
  Eyes were analyzed.

Statistical Analysis 7 for Distribution of Change in Visual Acuity (Letters) From Baseline to 1 Year
Groups [1] Sham+Prompt Laser vs. 0.5 mg Ranibizumab+Prompt Laser
Method [2] Binomial Regression
Proportion [3] -10
95% Confidence Interval -16 to -5
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Difference in proportion with ≥10 letter worsening from sham+prompt laser at 1 year
[2] Other relevant method information, such as adjustments or degrees of freedom:
  Adjusted for correlation between 2 study eyes and multiple comparisons.
[3] Other relevant estimation information:
  No text entered.

Statistical Analysis 8 for Distribution of Change in Visual Acuity (Letters) From Baseline to 1 Year
Groups [1] Sham+Prompt Laser vs. 0.5 mg Ranibizumab+Deferred Laser
Method [2] Binomial Regression
Proportion [3] -10
95% Confidence Interval -16 to -4
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Difference in proportion with ≥10 letter worsening from sham+prompt laser at 1 year
[2] Other relevant method information, such as adjustments or degrees of freedom:
  Adjusted for correlation between 2 study eyes and multiple comparisons.
[3] Other relevant estimation information:
  No text entered.

Statistical Analysis 9 for Distribution of Change in Visual Acuity (Letters) From Baseline to 1 Year
Groups [1] Sham+Prompt Laser vs. 4 mg Triamcinolone+Prompt Laser
Method [2] Binomial Regression
Proportion [3] 1
95% Confidence Interval -7 to 9
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Difference in proportion with ≥10 letter worsening from sham+prompt laser at 1 year
[2] Other relevant method information, such as adjustments or degrees of freedom:
  Adjusted for correlation between 2 study eyes and multiple comparisons.
[3] Other relevant estimation information:
  No text entered.

Statistical Analysis 10 for Distribution of Change in Visual Acuity (Letters) From Baseline to 1 Year
Groups [1] Sham+Prompt Laser vs. 0.5 mg Ranibizumab+Prompt Laser
Method [2] Log-Binomial Regression
P Value [3] <0.001
Risk Ratio (RR) [4] 0.24
95% Confidence Interval 0.09 to 0.65
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Relative risk for ≥10 letter worsening comparison with sham+prompt laser at 1 year
[2] Other relevant method information, such as adjustments or degrees of freedom:
  Adjusted for correlation between 2 study eyes and multiple comparisons.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Confidence intervals are adjusted for multiple comparisons.
[4] Other relevant estimation information:
  No text entered.

Statistical Analysis 11 for Distribution of Change in Visual Acuity (Letters) From Baseline to 1 Year
Groups [1] Sham+Prompt Laser vs. 0.5 mg Ranibizumab+Deferred Laser
Method [2] Log-Binomial Regression
P Value [3] 0.001
Risk Ratio (RR) [4] 0.24
95% Confidence Interval 0.08 to 0.68
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Relative risk for ≥10 letter worsening comparison with sham+prompt laser at 1 year
[2] Other relevant method information, such as adjustments or degrees of freedom:
  Adjusted for correlation between 2 study eyes and multiple comparisons.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Confidence intervals are adjusted for multiple comparisons.
[4] Other relevant estimation information:
  No text entered.

Statistical Analysis 12 for Distribution of Change in Visual Acuity (Letters) From Baseline to 1 Year
Groups [1] Sham+Prompt Laser vs. 4 mg Triamcinolone+Prompt Laser
Method [2] Log-Binomial Regression
P Value [3] 0.75
Risk Ratio (RR) [4] 1.08
95% Confidence Interval 0.62 to 1.87
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Relative risk for ≥10 letter worsening comparison with sham+prompt laser at 1 year
[2] Other relevant method information, such as adjustments or degrees of freedom:
  Adjusted for correlation between 2 study eyes and multiple comparisons.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Confidence intervals are adjusted for multiple comparisons.
[4] Other relevant estimation information:
  No text entered.

Statistical Analysis 13 for Distribution of Change in Visual Acuity (Letters) From Baseline to 1 Year
Groups [1] Sham+Prompt Laser vs. 0.5 mg Ranibizumab+Prompt Laser
Method [2] Binomial Regression
Proportion [3] 16
95% Confidence Interval 6 to 26
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Difference in proportion with ≥15 letter improvement from sham+prompt laser at 1 year
[2] Other relevant method information, such as adjustments or degrees of freedom:
  Adjusted for correlation between to study eyes.
[3] Other relevant estimation information:
  No text entered.

Statistical Analysis 14 for Distribution of Change in Visual Acuity (Letters) From Baseline to 1 Year
Groups [1] Sham+Prompt Laser vs. 0.5 mg Ranibizumab+Deferred Laser
Method [2] Binomial Regression
Proportion [3] 13
95% Confidence Interval 4 to 22
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Difference in proportion with ≥15 letter improvement from sham+prompt laser at 1 year
[2] Other relevant method information, such as adjustments or degrees of freedom:
  Adjusted for correlation between 2 study eyes and multiple comparisons.
[3] Other relevant estimation information:
  No text entered.

Statistical Analysis 15 for Distribution of Change in Visual Acuity (Letters) From Baseline to 1 Year
Groups [1] Sham+Prompt Laser vs. 4 mg Triamcinolone+Prompt Laser
Method [2] Binomial Regression
Proportion [3] 6
95% Confidence Interval -2 to 15
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Difference in proportion with ≥15 letter improvement from sham+prompt laser at 1 year
[2] Other relevant method information, such as adjustments or degrees of freedom:
  Adjusted for correlation between 2 study eyes and multiple comparisons.
[3] Other relevant estimation information:
  No text entered.

Statistical Analysis 16 for Distribution of Change in Visual Acuity (Letters) From Baseline to 1 Year
Groups [1] Sham+Prompt Laser vs. 0.5 mg Ranibizumab+Prompt Laser
Method [2] Log-Binomial Regression
P Value [3] <0.001
Risk Ratio (RR) [4] 2.09
95% Confidence Interval 1.35 to 3.22
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Relative risk for ≥15 letter improvement comparison with sham+prompt laser at 1 year
[2] Other relevant method information, such as adjustments or degrees of freedom:
  Adjusted for correlation between 2 study eyes and multiple comparisons.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.

Statistical Analysis 17 for Distribution of Change in Visual Acuity (Letters) From Baseline to 1 Year
Groups [1] Sham+Prompt Laser vs. 0.5 mg Ranibizumab+Deferred Laser
Method [2] Log-Binomial Regression
P Value [3] <0.001
Risk Ratio (RR) [4] 1.89
95% Confidence Interval 1.25 to 2.87
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Relative risk for ≥15 letter improvement comparison with sham+prompt laser at 1 year
[2] Other relevant method information, such as adjustments or degrees of freedom:
  Adjusted for correlation between 2 study eyes and multiple comparisons.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Confidence intervals are adjusted for multiple comparisons.
[4] Other relevant estimation information:
  No text entered.

Statistical Analysis 18 for Distribution of Change in Visual Acuity (Letters) From Baseline to 1 Year
Groups [1] Sham+Prompt Laser vs. 4 mg Triamcinolone+Prompt Laser
Method [2] Log-Binomial Regression
P Value [3] 0.07
Risk Ratio (RR) [4] 1.43
95% Confidence Interval 0.90 to 2.29
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Relative risk for ≥15 letter improvement comparison with sham+prompt laser at 1 year
[2] Other relevant method information, such as adjustments or degrees of freedom:
  Adjusted for correlation between 2 study eyes and multiple comparisons.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Confidence intervals are adjusted for multiple comparisons.
[4] Other relevant estimation information:
  No text entered.

Statistical Analysis 19 for Distribution of Change in Visual Acuity (Letters) From Baseline to 1 Year
Groups [1] Sham+Prompt Laser vs. 0.5 mg Ranibizumab+Prompt Laser
Method [2] Binomial Regression
Proportion [3] -6
95% Confidence Interval -11 to -2
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Difference in proportion with ≥15 letter worsening from sham+prompt laser at 1 year
[2] Other relevant method information, such as adjustments or degrees of freedom:
  Adjusted for correlation between 2 study eyes and multiple comparisons.
[3] Other relevant estimation information:
  No text entered.

Statistical Analysis 20 for Distribution of Change in Visual Acuity (Letters) From Baseline to 1 Year
Groups [1] Sham+Prompt Laser vs. 0.5 mg Ranibizumab+Deferred Laser
Method [2] Binomial Regression
Proportion [3] -6
95% Confidence Interval -10 to -1
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Difference in proportion with ≥15 letter worsening from sham+prompt laser at 1 year
[2] Other relevant method information, such as adjustments or degrees of freedom:
  Adjusted for correlation between 2 study eyes and multiple comparisons.
[3] Other relevant estimation information:
  No text entered.

Statistical Analysis 21 for Distribution of Change in Visual Acuity (Letters) From Baseline to 1 Year
Groups [1] Sham+Prompt Laser vs. 4 mg Triamcinolone+Prompt Laser
Method [2] Binomial Regression
Proportion [3] 0
95% Confidence Interval -6 to 6
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Difference in proportion with ≥15 letter worsening from sham+prompt laser at 1 year
[2] Other relevant method information, such as adjustments or degrees of freedom:
  Adjusted for correlation between 2 study eyes and multiple comparisons.
[3] Other relevant estimation information:
  No text entered.

Statistical Analysis 22 for Distribution of Change in Visual Acuity (Letters) From Baseline to 1 Year
Groups [1] Sham+Prompt Laser vs. 0.5 mg Ranibizumab+Prompt Laser
Method [2] Log-Binomial Regression
P Value [3] 0.009
Risk Ratio (RR) [4] 0.21
95% Confidence Interval 0.05 to 0.87
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Relative risk for ≥15 letter worsening comparison with sham+prompt laser at 1 year
[2] Other relevant method information, such as adjustments or degrees of freedom:
  Adjusted for correlation between 2 study eyes and multiple comparisons.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.

Statistical Analysis 23 for Distribution of Change in Visual Acuity (Letters) From Baseline to 1 Year
Groups [1] Sham+Prompt Laser vs. 0.5 mg Ranibizumab+Deferred Laser
Method [2] Log-Binomial Regression
P Value [3] 0.01
Risk Ratio (RR) [4] 0.28
95% Confidence Interval 0.08 to 0.97
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Relative risk for ≥15 letter worsening comparison with sham+prompt laser at 1 year
[2] Other relevant method information, such as adjustments or degrees of freedom:
  Adjusted for correlation between 2 study eyes and multiple comparisons.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.

Statistical Analysis 24 for Distribution of Change in Visual Acuity (Letters) From Baseline to 1 Year
Groups [1] Sham+Prompt Laser vs. 4 mg Triamcinolone+Prompt Laser
Method [2] Log-Binomial Regression
P Value [3] 0.95
Risk Ratio (RR) [4] 1.02
95% Confidence Interval 0.47 to 2.20
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Relative risk for ≥15 letter worsening comparison with sham+prompt laser at 1 year
[2] Other relevant method information, such as adjustments or degrees of freedom:
  Adjusted for correlation between 2 study eyes and multiple comparisons.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.



3.  Primary:   Change in Visual Acuity From Baseline to 1 Year Among Eyes That Were Pseudophakic at Baseline   [ Time Frame: from baseline to 1 Year ]

Measure Type Primary
Measure Title Change in Visual Acuity From Baseline to 1 Year Among Eyes That Were Pseudophakic at Baseline
Measure Description No text entered.
Time Frame from baseline to 1 Year  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Sham+Prompt Laser Sham injection at randomization plus focal photocoagulation 1 week post-injection. Injections are repeated every 4 weeks with focal photocoagulation given post-injection every 16 weeks. Retreatment starting at 16 weeks depends on visual acuity and OCT.
0.5 mg Ranibizumab+Prompt Laser 0.5 mg intravitreal ranibizumab at randomization plus focal photocoagulation 1 week post-injection. Injections are repeated every 4 weeks with focal photocoagulation given post-injection every 16 weeks. Retreatment starting at 16 weeks depends on visual acuity and OCT.
0.5 mg Ranibizumab+Deferred Laser 0.5 mg intravitreal ranibizumab at randomization, repeated every 4 weeks. Retreatment starting at 16 weeks depends on visual acuity and OCT. If improvement has not occured from injections alone, laser can be given starting at the 24 week visit.
4 mg Triamcinolone+Prompt Laser 4 mg intravitreal triamcinolone at randomization plus focal photocoagulation 1 week post-injection, repeated every 16 weeks with sham injections at 4-week intervals in-between. Retreatment starting at 16 weeks depends on visual acuity and OCT.

Measured Values
   Sham+Prompt Laser   0.5 mg Ranibizumab+Prompt Laser   0.5 mg Ranibizumab+Deferred Laser   4 mg Triamcinolone+Prompt Laser 
Participants Analyzed 
[Units: Participants]
 293   187   188   186 
Units Analyzed (Eyes) 
[Units: Eyes]
 293   187   188   186 
Change in Visual Acuity From Baseline to 1 Year Among Eyes That Were Pseudophakic at Baseline 
[Units: Letters]
Mean (Standard Deviation)
       
Not pseudophakic at baseline   2  (13)   9  (10)   10  (14)   2  (14) 
Pseudophakic at baseline   4  (14)   8  (12)   7  (9)   8  (9) 

No statistical analysis provided for Change in Visual Acuity From Baseline to 1 Year Among Eyes That Were Pseudophakic at Baseline



4.  Primary:   Change in Visual Acuity From Baseline to 1 Year Among Eyes That Had Prior Treatment for Diabetic Macular Edema   [ Time Frame: from baseline to 1 Year ]

Measure Type Primary
Measure Title Change in Visual Acuity From Baseline to 1 Year Among Eyes That Had Prior Treatment for Diabetic Macular Edema
Measure Description No text entered.
Time Frame from baseline to 1 Year  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Sham+Prompt Laser Sham injection at randomization plus focal photocoagulation 1 week post-injection. Injections are repeated every 4 weeks with focal photocoagulation given post-injection every 16 weeks. Retreatment starting at 16 weeks depends on visual acuity and OCT.
0.5 mg Ranibizumab+Prompt Laser 0.5 mg intravitreal ranibizumab at randomization plus focal photocoagulation 1 week post-injection. Injections are repeated every 4 weeks with focal photocoagulation given post-injection every 16 weeks. Retreatment starting at 16 weeks depends on visual acuity and OCT.
0.5 mg Ranibizumab+Deferred Laser 0.5 mg intravitreal ranibizumab at randomization, repeated every 4 weeks. Retreatment starting at 16 weeks depends on visual acuity and OCT. If improvement has not occured from injections alone, laser can be given starting at the 24 week visit.
4 mg Triamcinolone+Prompt Laser 4 mg intravitreal triamcinolone at randomization plus focal photocoagulation 1 week post-injection, repeated every 16 weeks with sham injections at 4-week intervals in-between. Retreatment starting at 16 weeks depends on visual acuity and OCT.

Measured Values
   Sham+Prompt Laser   0.5 mg Ranibizumab+Prompt Laser   0.5 mg Ranibizumab+Deferred Laser   4 mg Triamcinolone+Prompt Laser 
Participants Analyzed 
[Units: Participants]
 293   187   188   186 
Change in Visual Acuity From Baseline to 1 Year Among Eyes That Had Prior Treatment for Diabetic Macular Edema 
[Units: Letters]
Mean (Standard Deviation)
       
No   2  (14)   9  (12)   11  (13)   3  (13) 
Yes   3  (13)   9  (10)   8  (12)   5  (13) 

No statistical analysis provided for Change in Visual Acuity From Baseline to 1 Year Among Eyes That Had Prior Treatment for Diabetic Macular Edema



5.  Primary:   Change in Visual Acuity From Baseline to 1 Year Grouped by Baseline Visual Acuity Letter Score   [ Time Frame: from baseline to 1 Year ]

Measure Type Primary
Measure Title Change in Visual Acuity From Baseline to 1 Year Grouped by Baseline Visual Acuity Letter Score
Measure Description Change in best correct visual acuity letter score as measured by a certified tester using an electronic visual acuity testing machine based on the Early Treatment Diabetic Retinopathy Study (ETDRS) method. A positive change denotes an improvement. Best value on the scale 97, worst 0.
Time Frame from baseline to 1 Year  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Sham+Prompt Laser Sham injection at randomization plus focal photocoagulation 1 week post-injection. Injections are repeated every 4 weeks with focal photocoagulation given post-injection every 16 weeks. Retreatment starting at 16 weeks depends on visual acuity and OCT.
0.5 mg Ranibizumab+Prompt Laser 0.5 mg intravitreal ranibizumab at randomization plus focal photocoagulation 1 week post-injection. Injections are repeated every 4 weeks with focal photocoagulation given post-injection every 16 weeks. Retreatment starting at 16 weeks depends on visual acuity and OCT.
0.5 mg Ranibizumab+Deferred Laser 0.5 mg intravitreal ranibizumab at randomization, repeated every 4 weeks. Retreatment starting at 16 weeks depends on visual acuity and OCT. If improvement has not occured from injections alone, laser can be given starting at the 24 week visit.
4 mg Triamcinolone+Prompt Laser 4 mg intravitreal triamcinolone at randomization plus focal photocoagulation 1 week post-injection, repeated every 16 weeks with sham injections at 4-week intervals in-between. Retreatment starting at 16 weeks depends on visual acuity and OCT.

Measured Values
   Sham+Prompt Laser   0.5 mg Ranibizumab+Prompt Laser   0.5 mg Ranibizumab+Deferred Laser   4 mg Triamcinolone+Prompt Laser 
Participants Analyzed 
[Units: Participants]
 293   187   188   186 
Change in Visual Acuity From Baseline to 1 Year Grouped by Baseline Visual Acuity Letter Score 
[Units: Letters]
Mean (Standard Deviation)
       
≥66 (better than 20/50)   1  (12)   6  (10)   5  (13)   1  (11) 
≤65 (20/50 or worse)   5  (14)   12  (11)   13  (10)   7  (14) 

No statistical analysis provided for Change in Visual Acuity From Baseline to 1 Year Grouped by Baseline Visual Acuity Letter Score



6.  Primary:   Change in Visual Acuity From Baseline to 1 Year Grouped by Optical Coherence Tomography Central Subfield Thickness   [ Time Frame: from baseline to 1 Year ]

Measure Type Primary
Measure Title Change in Visual Acuity From Baseline to 1 Year Grouped by Optical Coherence Tomography Central Subfield Thickness
Measure Description Change in best correct visual acuity letter score from baseline to one year as measured by a certified tester using an electronic visual acuity testing machine based on the Early Treatment Diabetic Retinopathy Study (ETDRS) method. A positive change denotes an improvement. Best value on the scale 97, worst 0.
Time Frame from baseline to 1 Year  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Sham+Prompt Laser Sham injection at randomization plus focal photocoagulation 1 week post-injection. Injections are repeated every 4 weeks with focal photocoagulation given post-injection every 16 weeks. Retreatment starting at 16 weeks depends on visual acuity and OCT.
0.5 mg Ranibizumab+Prompt Laser 0.5 mg intravitreal ranibizumab at randomization plus focal photocoagulation 1 week post-injection. Injections are repeated every 4 weeks with focal photocoagulation given post-injection every 16 weeks. Retreatment starting at 16 weeks depends on visual acuity and OCT.
0.5 mg Ranibizumab+Deferred Laser 0.5 mg intravitreal ranibizumab at randomization, repeated every 4 weeks. Retreatment starting at 16 weeks depends on visual acuity and OCT. If improvement has not occured from injections alone, laser can be given starting at the 24 week visit.
4 mg Triamcinolone+Prompt Laser 4 mg intravitreal triamcinolone at randomization plus focal photocoagulation 1 week post-injection, repeated every 16 weeks with sham injections at 4-week intervals in-between. Retreatment starting at 16 weeks depends on visual acuity and OCT.

Measured Values
   Sham+Prompt Laser   0.5 mg Ranibizumab+Prompt Laser   0.5 mg Ranibizumab+Deferred Laser   4 mg Triamcinolone+Prompt Laser 
Participants Analyzed 
[Units: Participants]
 293   187   188   186 
Units Analyzed (Eyes) 
[Units: Eyes]
 293   187   188   186 
Change in Visual Acuity From Baseline to 1 Year Grouped by Optical Coherence Tomography Central Subfield Thickness 
[Units: Letters]
Mean (Standard Deviation)
       
<400 microns   3  (11)   7  (11)   7  (12)   3  (12) 
≥400 microns   3  (15)   11  (10)   11  (13)   6  (14) 

No statistical analysis provided for Change in Visual Acuity From Baseline to 1 Year Grouped by Optical Coherence Tomography Central Subfield Thickness



7.  Primary:   Change in Visual Acuity From Baseline to 1 Year Grouped by Diabetic Retinopathy Severity   [ Time Frame: from baseline to 1 Year ]

Measure Type Primary
Measure Title Change in Visual Acuity From Baseline to 1 Year Grouped by Diabetic Retinopathy Severity
Measure Description Change in best correct visual acuity letter score from baseline to one year as measured by a certified tester using an electronic visual acuity testing machine based on the Early Treatment Diabetic Retinopathy Study (ETDRS) method. A positive change denotes an improvement. Best value on the scale 97, worst 0.
Time Frame from baseline to 1 Year  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Sham+Prompt Laser Sham injection at randomization plus focal photocoagulation 1 week post-injection. Injections are repeated every 4 weeks with focal photocoagulation given post-injection every 16 weeks. Retreatment starting at 16 weeks depends on visual acuity and OCT.
0.5 mg Ranibizumab+Prompt Laser 0.5 mg intravitreal ranibizumab at randomization plus focal photocoagulation 1 week post-injection. Injections are repeated every 4 weeks with focal photocoagulation given post-injection every 16 weeks. Retreatment starting at 16 weeks depends on visual acuity and OCT.
0.5 mg Ranibizumab+Deferred Laser 0.5 mg intravitreal ranibizumab at randomization, repeated every 4 weeks. Retreatment starting at 16 weeks depends on visual acuity and OCT. If improvement has not occured from injections alone, laser can be given starting at the 24 week visit.
4 mg Triamcinolone+Prompt Laser 4 mg intravitreal triamcinolone at randomization plus focal photocoagulation 1 week post-injection, repeated every 16 weeks with sham injections at 4-week intervals in-between. Retreatment starting at 16 weeks depends on visual acuity and OCT.

Measured Values
   Sham+Prompt Laser   0.5 mg Ranibizumab+Prompt Laser   0.5 mg Ranibizumab+Deferred Laser   4 mg Triamcinolone+Prompt Laser 
Participants Analyzed 
[Units: Participants]
 293   187   188   186 
Units Analyzed (Eyes) 
[Units: Eyes]
 293   187   188   186 
Change in Visual Acuity From Baseline to 1 Year Grouped by Diabetic Retinopathy Severity 
[Units: Letters]
Mean (Standard Deviation)
       
Moderately severe non-proliferative DR or better   3  (13)   10  (11)   9  (12)   3  (14) 
Severe non-proliferative DR or worse   2  (15)   8  (10)   9  (13)   5  (12) 

No statistical analysis provided for Change in Visual Acuity From Baseline to 1 Year Grouped by Diabetic Retinopathy Severity



8.  Primary:   Change in Visual Acuity From Baseline to 1 Year Grouped by Diffuse vs. Focal Edema as Characterized by the Investigator   [ Time Frame: from baseline to 1 Year ]

Measure Type Primary
Measure Title Change in Visual Acuity From Baseline to 1 Year Grouped by Diffuse vs. Focal Edema as Characterized by the Investigator
Measure Description Change in best correct visual acuity letter score from baseline to one year as measured by a certified tester using an electronic visual acuity testing machine based on the Early Treatment Diabetic Retinopathy Study (ETDRS) method. A positive change denotes an improvement. Best value on the scale 97, worst 0.
Time Frame from baseline to 1 Year  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Sham+Prompt Laser Sham injection at randomization plus focal photocoagulation 1 week post-injection. Injections are repeated every 4 weeks with focal photocoagulation given post-injection every 16 weeks. Retreatment starting at 16 weeks depends on visual acuity and OCT.
0.5 mg Ranibizumab+Prompt Laser 0.5 mg intravitreal ranibizumab at randomization plus focal photocoagulation 1 week post-injection. Injections are repeated every 4 weeks with focal photocoagulation given post-injection every 16 weeks. Retreatment starting at 16 weeks depends on visual acuity and OCT.
0.5 mg Ranibizumab+Deferred Laser 0.5 mg intravitreal ranibizumab at randomization, repeated every 4 weeks. Retreatment starting at 16 weeks depends on visual acuity and OCT. If improvement has not occured from injections alone, laser can be given starting at the 24 week visit.
4 mg Triamcinolone+Prompt Laser 4 mg intravitreal triamcinolone at randomization plus focal photocoagulation 1 week post-injection, repeated every 16 weeks with sham injections at 4-week intervals in-between. Retreatment starting at 16 weeks depends on visual acuity and OCT.

Measured Values
   Sham+Prompt Laser   0.5 mg Ranibizumab+Prompt Laser   0.5 mg Ranibizumab+Deferred Laser   4 mg Triamcinolone+Prompt Laser 
Participants Analyzed 
[Units: Participants]
 293   187   188   186 
Units Analyzed (Eyes) 
[Units: Eyes]
 293   187   188   186 
Change in Visual Acuity From Baseline to 1 Year Grouped by Diffuse vs. Focal Edema as Characterized by the Investigator 
[Units: Letters]
Mean (Standard Deviation)
       
Typical/predominantly focal   3  (13)   8  (11)   8  (13)   3  (11) 
Neither predominantly focal nor diffuse   2  (14)   10  (9)   8  (15)   3  (13) 
Typical/predominantly diffuse   3  (13)   9  (12)   10  (10)   5  (14) 

No statistical analysis provided for Change in Visual Acuity From Baseline to 1 Year Grouped by Diffuse vs. Focal Edema as Characterized by the Investigator



9.  Secondary:   Change in Retinal Thickening of Central Subfield on Optical Coherence Tomography From Baseline to 1 Year   [ Time Frame: from baseline to 1 year ]

Measure Type Secondary
Measure Title Change in Retinal Thickening of Central Subfield on Optical Coherence Tomography From Baseline to 1 Year
Measure Description Negative change denotes an improvement.
Time Frame from baseline to 1 year  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Sham+Prompt Laser Sham injection at randomization plus focal photocoagulation 1 week post-injection. Injections are repeated every 4 weeks with focal photocoagulation given post-injection every 16 weeks. Retreatment starting at 16 weeks depends on visual acuity and OCT.
0.5 mg Ranibizumab+Prompt Laser 0.5 mg intravitreal ranibizumab at randomization plus focal photocoagulation 1 week post-injection. Injections are repeated every 4 weeks with focal photocoagulation given post-injection every 16 weeks. Retreatment starting at 16 weeks depends on visual acuity and OCT.
0.5 mg Ranibizumab+Deferred Laser 0.5 mg intravitreal ranibizumab at randomization, repeated every 4 weeks. Retreatment starting at 16 weeks depends on visual acuity and OCT. If improvement has not occured from injections alone, laser can be given starting at the 24 week visit.
4 mg Triamcinolone+Prompt Laser 4 mg intravitreal triamcinolone at randomization plus focal photocoagulation 1 week post-injection, repeated every 16 weeks with sham injections at 4-week intervals in-between. Retreatment starting at 16 weeks depends on visual acuity and OCT.

Measured Values
   Sham+Prompt Laser   0.5 mg Ranibizumab+Prompt Laser   0.5 mg Ranibizumab+Deferred Laser   4 mg Triamcinolone+Prompt Laser 
Participants Analyzed 
[Units: Participants]
 271   171   175   173 
Units Analyzed (Eyes) 
[Units: Eyes]
 271   171   175   173 
Change in Retinal Thickening of Central Subfield on Optical Coherence Tomography From Baseline to 1 Year 
[Units: Microns]
Mean (Standard Deviation)
 -102  (151)   -131  (129)   -137  (136)   -127  (140) 


Statistical Analysis 1 for Change in Retinal Thickening of Central Subfield on Optical Coherence Tomography From Baseline to 1 Year
Groups [1] Sham+Prompt Laser vs. 0.5 mg Ranibizumab+Prompt Laser
Method [2] ANCOVA
P Value [3] <0.001
Difference in mean change [4] -55
95% Confidence Interval -78 to -32
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Difference in central subfield thickness mean change from sham+prompt laser
[2] Other relevant method information, such as adjustments or degrees of freedom:
  Adjusted for baseline retinal thickness and visual acuity and correlation between two study eyes.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Confidence intervals are adjusted for multiple comparisons.
[4] Other relevant estimation information:
  No text entered.

Statistical Analysis 2 for Change in Retinal Thickening of Central Subfield on Optical Coherence Tomography From Baseline to 1 Year
Groups [1] Sham+Prompt Laser vs. 0.5 mg Ranibizumab+Deferred Laser
Method [2] ANCOVA
P Value [3] <0.001
Difference in mean change [4] -49
95% Confidence Interval -72 to -26
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Difference in optical coherence tomography central subfield thickness mean change from sham+prompt laser
[2] Other relevant method information, such as adjustments or degrees of freedom:
  Adjusted for baseline retinal thickness and visual acuity and correlation between two study eyes.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Confidence intervals are adjusted for multiple comparisons.
[4] Other relevant estimation information:
  No text entered.

Statistical Analysis 3 for Change in Retinal Thickening of Central Subfield on Optical Coherence Tomography From Baseline to 1 Year
Groups [1] Sham+Prompt Laser vs. 4 mg Triamcinolone+Prompt Laser
Method [2] ANCOVA
P Value [3] <0.001
Difference in mean change [4] -52
95% Confidence Interval -75 to -29
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Difference in optical coherence tomography central subfield thickness mean change from sham+prompt laser
[2] Other relevant method information, such as adjustments or degrees of freedom:
  Adjusted for baseline retinal thickness and visual acuity and correlation between two study eyes.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Confidence interval is adjusted for multiple comparisons
[4] Other relevant estimation information:
  No text entered.



10.  Secondary:   Number of Injections in First Year   [ Time Frame: from baseline to 1 year ]

Measure Type Secondary
Measure Title Number of Injections in First Year
Measure Description Maximum possible number of injections for each of the following groups: sham+prompt laser=13 sham injections;ranibizumab+prompt laser=13 ranibizumab injections; ranibizumab+deferred laser=13 ranibizumab injections; triamcinolone+prompt laser=4 triamcinolone injections and 9 sham injections.
Time Frame from baseline to 1 year  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Sham+prompt laser group listed median excludes 56 eyes among 163 participants with 2 study eyes that were unmasked at baseline because the participant's other eye was in the ranibizumab+deferred laser group, precluding sham injections for the study eye assigned to sham+prompt laser.

Reporting Groups
  Description
Sham+Prompt Laser Sham injection at randomization plus focal photocoagulation 1 week post-injection. Injections are repeated every 4 weeks with focal photocoagulation given post-injection every 16 weeks. Retreatment starting at 16 weeks depends on visual acuity and OCT.
0.5 mg Ranibizumab+Prompt Laser 0.5 mg intravitreal ranibizumab at randomization plus focal photocoagulation 1 week post-injection. Injections are repeated every 4 weeks with focal photocoagulation given post-injection every 16 weeks. Retreatment starting at 16 weeks depends on visual acuity and OCT.
0.5 mg Ranibizumab+Deferred Laser 0.5 mg intravitreal ranibizumab at randomization, repeated every 4 weeks. Retreatment starting at 16 weeks depends on visual acuity and OCT. If improvement has not occured from injections alone, laser can be given starting at the 24 week visit.
4 mg Triamcinolone+Prompt Laser 4 mg intravitreal triamcinolone at randomization plus focal photocoagulation 1 week post-injection, repeated every 16 weeks with sham injections at 4-week intervals in-between. Retreatment starting at 16 weeks depends on visual acuity and OCT.

Measured Values
   Sham+Prompt Laser   0.5 mg Ranibizumab+Prompt Laser   0.5 mg Ranibizumab+Deferred Laser   4 mg Triamcinolone+Prompt Laser 
Participants Analyzed 
[Units: Participants]
 274   171   178   176 
Units Analyzed (Eyes) 
[Units: Eyes]
 274   171   178   176 
Number of Injections in First Year 
[Units: Injections]
Median (Inter-Quartile Range)
 11 
 (8 to 13) 
 8 
 (6 to 10) 
 9 
 (6 to 11) 
 3 
 (2 to 4) 

No statistical analysis provided for Number of Injections in First Year



11.  Secondary:   Number of Laser Treatments Received Prior to the 1 Year Visit   [ Time Frame: 1 Year ]

Measure Type Secondary
Measure Title Number of Laser Treatments Received Prior to the 1 Year Visit
Measure Description One eye in the sham+prompt laser group did not receive laser until post 1-year due to an adverse event unrelated to study treatment. One eye in the triamcinolone+prompt laser did not receive laser until after 1-year due to missing 2 consecutive visits at the time of required laser treatment.
Time Frame 1 Year  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Number who completed the 1-year visit.

Reporting Groups
  Description
Sham+Prompt Laser Sham injection at randomization plus focal photocoagulation 1 week post-injection. Injections are repeated every 4 weeks with focal photocoagulation given post-injection every 16 weeks. Retreatment starting at 16 weeks depends on visual acuity and OCT.
0.5 mg Ranibizumab+Prompt Laser 0.5 mg intravitreal ranibizumab at randomization plus focal photocoagulation 1 week post-injection. Injections are repeated every 4 weeks with focal photocoagulation given post-injection every 16 weeks. Retreatment starting at 16 weeks depends on visual acuity and OCT.
0.5 mg Ranibizumab+Deferred Laser 0.5 mg intravitreal ranibizumab at randomization, repeated every 4 weeks. Retreatment starting at 16 weeks depends on visual acuity and OCT. If improvement has not occured from injections alone, laser can be given starting at the 24 week visit.
4 mg Triamcinolone+Prompt Laser 4 mg intravitreal triamcinolone at randomization plus focal photocoagulation 1 week post-injection, repeated every 16 weeks with sham injections at 4-week intervals in-between. Retreatment starting at 16 weeks depends on visual acuity and OCT.

Measured Values
   Sham+Prompt Laser   0.5 mg Ranibizumab+Prompt Laser   0.5 mg Ranibizumab+Deferred Laser   4 mg Triamcinolone+Prompt Laser 
Participants Analyzed 
[Units: Participants]
 274   171   178   176 
Units Analyzed (Eyes) 
[Units: Eyes]
 274   171   178   176 
Number of Laser Treatments Received Prior to the 1 Year Visit 
[Units: Eyes]
       
 1   0   124   1 
 35   53   36   46 
 75   54   17   53 
 107   46   1   49 
 56   18   0   27 

No statistical analysis provided for Number of Laser Treatments Received Prior to the 1 Year Visit



12.  Secondary:   Percentage of Eyes Receiving Laser at the 48 Week Visit (%)   [ Time Frame: 1 Year ]

Measure Type Secondary
Measure Title Percentage of Eyes Receiving Laser at the 48 Week Visit (%)
Measure Description No text entered.
Time Frame 1 Year  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Sham+Prompt Laser Sham injection at randomization plus focal photocoagulation 1 week post-injection. Injections are repeated every 4 weeks with focal photocoagulation given post-injection every 16 weeks. Retreatment starting at 16 weeks depends on visual acuity and OCT.
0.5 mg Ranibizumab+Prompt Laser 0.5 mg intravitreal ranibizumab at randomization plus focal photocoagulation 1 week post-injection. Injections are repeated every 4 weeks with focal photocoagulation given post-injection every 16 weeks. Retreatment starting at 16 weeks depends on visual acuity and OCT.
0.5 mg Ranibizumab+Deferred Laser 0.5 mg intravitreal ranibizumab at randomization, repeated every 4 weeks. Retreatment starting at 16 weeks depends on visual acuity and OCT. If improvement has not occured from injections alone, laser can be given starting at the 24 week visit.
4 mg Triamcinolone+Prompt Laser 4 mg intravitreal triamcinolone at randomization plus focal photocoagulation 1 week post-injection, repeated every 16 weeks with sham injections at 4-week intervals in-between. Retreatment starting at 16 weeks depends on visual acuity and OCT.

Measured Values
   Sham+Prompt Laser   0.5 mg Ranibizumab+Prompt Laser   0.5 mg Ranibizumab+Deferred Laser   4 mg Triamcinolone+Prompt Laser 
Participants Analyzed 
[Units: Participants]
 274   171   178   176 
Units Analyzed (Eyes) 
[Units: Eyes]
 274   171   178   176 
Percentage of Eyes Receiving Laser at the 48 Week Visit (%) 
[Units: Eyes]
 26   16   8   21 

No statistical analysis provided for Percentage of Eyes Receiving Laser at the 48 Week Visit (%)



13.  Secondary:   Mean Optical Coherence Tomography Retinal Volume at 1 Year   [ Time Frame: 1 Year ]

Measure Type Secondary
Measure Title Mean Optical Coherence Tomography Retinal Volume at 1 Year
Measure Description No text entered.
Time Frame 1 Year  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Sham+Prompt Laser Sham injection at randomization plus focal photocoagulation 1 week post-injection. Injections are repeated every 4 weeks with focal photocoagulation given post-injection every 16 weeks. Retreatment starting at 16 weeks depends on visual acuity and OCT.
0.5 mg Ranibizumab+Prompt Laser 0.5 mg intravitreal ranibizumab at randomization plus focal photocoagulation 1 week post-injection. Injections are repeated every 4 weeks with focal photocoagulation given post-injection every 16 weeks. Retreatment starting at 16 weeks depends on visual acuity and OCT.
0.5 mg Ranibizumab+Deferred Laser 0.5 mg intravitreal ranibizumab at randomization, repeated every 4 weeks. Retreatment starting at 16 weeks depends on visual acuity and OCT. If improvement has not occured from injections alone, laser can be given starting at the 24 week visit.
4 mg Triamcinolone+Prompt Laser 4 mg intravitreal triamcinolone at randomization plus focal photocoagulation 1 week post-injection, repeated every 16 weeks with sham injections at 4-week intervals in-between. Retreatment starting at 16 weeks depends on visual acuity and OCT.

Measured Values
   Sham+Prompt Laser   0.5 mg Ranibizumab+Prompt Laser   0.5 mg Ranibizumab+Deferred Laser   4 mg Triamcinolone+Prompt Laser 
Participants Analyzed 
[Units: Participants]
 293   187   188   186 
Units Analyzed (Eyes) 
[Units: Eyes]
 293   187   188   186 
Mean Optical Coherence Tomography Retinal Volume at 1 Year 
[Units: Mm^3]
Mean (Standard Deviation)
 8.1  (1.4)   7.3  (1.0)   7.4  (1.2)   7.5  (1.3) 

No statistical analysis provided for Mean Optical Coherence Tomography Retinal Volume at 1 Year



14.  Secondary:   Mean Change in Optical Coherence Tomography Retinal Volume From Baseline to 1 Year   [ Time Frame: from baseline to 1 Year ]

Measure Type Secondary
Measure Title Mean Change in Optical Coherence Tomography Retinal Volume From Baseline to 1 Year
Measure Description No text entered.
Time Frame from baseline to 1 Year  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Sham+Prompt Laser Sham injection at randomization plus focal photocoagulation 1 week post-injection. Injections are repeated every 4 weeks with focal photocoagulation given post-injection every 16 weeks. Retreatment starting at 16 weeks depends on visual acuity and OCT.
0.5 mg Ranibizumab+Prompt Laser 0.5 mg intravitreal ranibizumab at randomization plus focal photocoagulation 1 week post-injection. Injections are repeated every 4 weeks with focal photocoagulation given post-injection every 16 weeks. Retreatment starting at 16 weeks depends on visual acuity and OCT.
0.5 mg Ranibizumab+Deferred Laser 0.5 mg intravitreal ranibizumab at randomization, repeated every 4 weeks. Retreatment starting at 16 weeks depends on visual acuity and OCT. If improvement has not occured from injections alone, laser can be given starting at the 24 week visit.
4 mg Triamcinolone+Prompt Laser 4 mg intravitreal triamcinolone at randomization plus focal photocoagulation 1 week post-injection, repeated every 16 weeks with sham injections at 4-week intervals in-between. Retreatment starting at 16 weeks depends on visual acuity and OCT.

Measured Values
   Sham+Prompt Laser   0.5 mg Ranibizumab+Prompt Laser   0.5 mg Ranibizumab+Deferred Laser   4 mg Triamcinolone+Prompt Laser 
Participants Analyzed 
[Units: Participants]
 293   187   188   186 
Units Analyzed (Eyes) 
[Units: Eyes]
 293   187   188   186 
Mean Change in Optical Coherence Tomography Retinal Volume From Baseline to 1 Year 
[Units: Mm^3]
Mean (Standard Deviation)
 -1.0  (1.4)   -1.4  (1.4)   -1.5  (1.5)   -1.4  (1.6) 


Statistical Analysis 1 for Mean Change in Optical Coherence Tomography Retinal Volume From Baseline to 1 Year
Groups [1] Sham+Prompt Laser vs. 0.5 mg Ranibizumab+Prompt Laser
Method [2] ANCOVA
P Value [3] <0.001
Mean Difference (Net) [4] -0.73
95% Confidence Interval -1.01 to -0.44
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Difference in mean change from sham+prompt laser
[2] Other relevant method information, such as adjustments or degrees of freedom:
  Adjusted for baseline optical coherence tomography (OCT) retinal volume, OCT retinal thickness and visual acuity and correlation between 2 study eyes.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Confidence intervals are adjusted for multiple comparisons.
[4] Other relevant estimation information:
  No text entered.

Statistical Analysis 2 for Mean Change in Optical Coherence Tomography Retinal Volume From Baseline to 1 Year
Groups [1] Sham+Prompt Laser vs. 0.5 mg Ranibizumab+Deferred Laser
Method [2] ANCOVA
P Value [3] <0.001
Mean Difference (Net) [4] -0.68
95% Confidence Interval -0.96 to -0.41
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Difference in mean change from sham+prompt laser
[2] Other relevant method information, such as adjustments or degrees of freedom:
  Adjusted for baseline optical coherence tomography (OCT) retinal volume, OCT retinal thickness and visual acuity and correlation between 2 study eyes.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Confidence intervals adjusted for multiple comparisons.
[4] Other relevant estimation information:
  No text entered.

Statistical Analysis 3 for Mean Change in Optical Coherence Tomography Retinal Volume From Baseline to 1 Year
Groups [1] Sham+Prompt Laser vs. 4 mg Triamcinolone+Prompt Laser
Method [2] ANCOVA
P Value [3] <0.001
Mean Difference (Net) [4] -0.62
95% Confidence Interval -0.91 to -0.34
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Difference in mean change from sham+prompt laser
[2] Other relevant method information, such as adjustments or degrees of freedom:
  Adjusted for baseline optical coherence tomography (OCT) retinal volume, OCT retinal thickness and visual acuity and correlation between 2 study eyes.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Confidence intervals are adjusted for multiple comparisons.
[4] Other relevant estimation information:
  No text entered.



15.  Other Pre-specified:   Central Subfield Thickness < 250 With at Least a 25 Micron Decrease From Baseline to 1 Year   [ Time Frame: 1 Year ]

Measure Type Other Pre-specified
Measure Title Central Subfield Thickness < 250 With at Least a 25 Micron Decrease From Baseline to 1 Year
Measure Description No text entered.
Time Frame 1 Year  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Sham+Prompt Laser Sham injection at randomization plus focal photocoagulation 1 week post-injection. Injections are repeated every 4 weeks with focal photocoagulation given post-injection every 16 weeks. Retreatment starting at 16 weeks depends on visual acuity and OCT.
0.5 mg Ranibizumab+Prompt Laser 0.5 mg intravitreal ranibizumab at randomization plus focal photocoagulation 1 week post-injection. Injections are repeated every 4 weeks with focal photocoagulation given post-injection every 16 weeks. Retreatment starting at 16 weeks depends on visual acuity and OCT.
0.5 mg Ranibizumab+Deferred Laser 0.5 mg intravitreal ranibizumab at randomization, repeated every 4 weeks. Retreatment starting at 16 weeks depends on visual acuity and OCT. If improvement has not occured from injections alone, laser can be given starting at the 24 week visit.
4 mg Triamcinolone+Prompt Laser 4 mg intravitreal triamcinolone at randomization plus focal photocoagulation 1 week post-injection, repeated every 16 weeks with sham injections at 4-week intervals in-between. Retreatment starting at 16 weeks depends on visual acuity and OCT.

Measured Values
   Sham+Prompt Laser   0.5 mg Ranibizumab+Prompt Laser   0.5 mg Ranibizumab+Deferred Laser   4 mg Triamcinolone+Prompt Laser 
Participants Analyzed 
[Units: Participants]
 271   171   175   173 
Units Analyzed (Eyes) 
[Units: Eyes]
 271   171   175   173 
Central Subfield Thickness < 250 With at Least a 25 Micron Decrease From Baseline to 1 Year 
[Units: Eyes]
 72   91   74   82 


Statistical Analysis 1 for Central Subfield Thickness < 250 With at Least a 25 Micron Decrease From Baseline to 1 Year
Groups [1] Sham+Prompt Laser vs. 0.5 mg Ranibizumab+Prompt Laser
Method [2] Regression, Logistic
P Value [3] <0.001
Risk Ratio (RR) [4] 2.00
95% Confidence Interval 1.52 to 2.64
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Relative risk for comparison with sham+prompt laser
[2] Other relevant method information, such as adjustments or degrees of freedom:
  Adjusted for correlation between 2 study eyes and multiple comparisons.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Confidence intervals are adjusted for multiple comparisons.
[4] Other relevant estimation information:
  No text entered.

Statistical Analysis 2 for Central Subfield Thickness < 250 With at Least a 25 Micron Decrease From Baseline to 1 Year
Groups [1] Sham+Prompt Laser vs. 0.5 mg Ranibizumab+Deferred Laser
Method [2] Regression, Logistic
P Value [3] 0.001
Risk Ratio (RR) [4] 1.55
95% Confidence Interval 1.13 to 2.13
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Relative risk for comparison with sham+prompt laser
[2] Other relevant method information, such as adjustments or degrees of freedom:
  Adjusted for correlation between 2 study eyes and multiple comparisons.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Confidence intervals adjusted for multiple comparisons
[4] Other relevant estimation information:
  No text entered.

Statistical Analysis 3 for Central Subfield Thickness < 250 With at Least a 25 Micron Decrease From Baseline to 1 Year
Groups [1] Sham+Prompt Laser vs. 4 mg Triamcinolone+Prompt Laser
Method [2] Regression, Logistic
P Value [3] <0.001
Risk Ratio (RR) [4] 1.76
95% Confidence Interval 1.31 to 2.36
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Relative risk for comparison with sham+prompt laser
[2] Other relevant method information, such as adjustments or degrees of freedom:
  Adjusted for correlation between 2 study eyes and multiple comparisons.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Confidence intervals adjusted for multiple comparisons.
[4] Other relevant estimation information:
  No text entered.



16.  Other Pre-specified:   Distribution of Logarithmic Transformation of Optical Coherence Tomography (LogOCT) Improvement and Worsening   [ Time Frame: 1 Year ]

Measure Type Other Pre-specified
Measure Title Distribution of Logarithmic Transformation of Optical Coherence Tomography (LogOCT) Improvement and Worsening
Measure Description Logarithmic transformation of optical coherence tomography central subfield thickness is calculated by taking the log base 10 of the ratio of the central subfield thickness divided by 200 and rounding to the nearest hundredth. The change is the change in the log values.
Time Frame 1 Year  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Sham+Prompt Laser Sham injection at randomization plus focal photocoagulation 1 week post-injection. Injections are repeated every 4 weeks with focal photocoagulation given post-injection every 16 weeks. Retreatment starting at 16 weeks depends on visual acuity and OCT.
0.5 mg Ranibizumab+Prompt Laser 0.5 mg intravitreal ranibizumab at randomization plus focal photocoagulation 1 week post-injection. Injections are repeated every 4 weeks with focal photocoagulation given post-injection every 16 weeks. Retreatment starting at 16 weeks depends on visual acuity and OCT.
0.5 mg Ranibizumab+Deferred Laser 0.5 mg intravitreal ranibizumab at randomization, repeated every 4 weeks. Retreatment starting at 16 weeks depends on visual acuity and OCT. If improvement has not occured from injections alone, laser can be given starting at the 24 week visit.
4 mg Triamcinolone+Prompt Laser 4 mg intravitreal triamcinolone at randomization plus focal photocoagulation 1 week post-injection, repeated every 16 weeks with sham injections at 4-week intervals in-between. Retreatment starting at 16 weeks depends on visual acuity and OCT.

Measured Values
   Sham+Prompt Laser   0.5 mg Ranibizumab+Prompt Laser   0.5 mg Ranibizumab+Deferred Laser   4 mg Triamcinolone+Prompt Laser 
Participants Analyzed 
[Units: Participants]
 271   171   175   173 
Units Analyzed (Eyes) 
[Units: Eyes]
 271   171   175   173 
Distribution of Logarithmic Transformation of Optical Coherence Tomography (LogOCT) Improvement and Worsening 
[Units: Eyes]
       
≥2 step improvement   81   72   71   65 
≥2 step worsening   6   1   0   4 

No statistical analysis provided for Distribution of Logarithmic Transformation of Optical Coherence Tomography (LogOCT) Improvement and Worsening



17.  Other Pre-specified:   Eyes With Alternative Treatments Prior to the 1-year Visit   [ Time Frame: 1 Year ]

Measure Type Other Pre-specified
Measure Title Eyes With Alternative Treatments Prior to the 1-year Visit
Measure Description Each combination of treatment only counted once.
Time Frame 1 Year  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Sham+Prompt Laser Sham injection at randomization plus focal photocoagulation 1 week post-injection. Injections are repeated every 4 weeks with focal photocoagulation given post-injection every 16 weeks. Retreatment starting at 16 weeks depends on visual acuity and OCT.
0.5 mg Ranibizumab+Prompt Laser 0.5 mg intravitreal ranibizumab at randomization plus focal photocoagulation 1 week post-injection. Injections are repeated every 4 weeks with focal photocoagulation given post-injection every 16 weeks. Retreatment starting at 16 weeks depends on visual acuity and OCT.
0.5 mg Ranibizumab+Deferred Laser 0.5 mg intravitreal ranibizumab at randomization, repeated every 4 weeks. Retreatment starting at 16 weeks depends on visual acuity and OCT. If improvement has not occured from injections alone, laser can be given starting at the 24 week visit.
4 mg Triamcinolone+Prompt Laser 4 mg intravitreal triamcinolone at randomization plus focal photocoagulation 1 week post-injection, repeated every 16 weeks with sham injections at 4-week intervals in-between. Retreatment starting at 16 weeks depends on visual acuity and OCT.

Measured Values
   Sham+Prompt Laser   0.5 mg Ranibizumab+Prompt Laser   0.5 mg Ranibizumab+Deferred Laser   4 mg Triamcinolone+Prompt Laser 
Participants Analyzed 
[Units: Participants]
 293   187   188   186 
Units Analyzed (Eyes) 
[Units: Eyes]
 293   187   188   186 
Eyes With Alternative Treatments Prior to the 1-year Visit 
[Units: Eyes]
       
Intravitreal bevacizumab   3   0   0   1 
Intravitreal triamcinolone acetonide   5   0   0   0 
Vitrectomy   2   0   0   0 
Intravitreal bevacizumab+triamcinolone acetonide   4   0   0   0 
Total number of eyes with alternative treatments   14   1   0   1 
Total number of treatments applied   25   1   0   1 
Total per protocol treatments applied   5   1   0   1 
Total deviations from protocol treatments applied   9   0   0   0 

No statistical analysis provided for Eyes With Alternative Treatments Prior to the 1-year Visit



18.  Other Pre-specified:   Change From Moderately Severe Non-proliferative Diabetic Retinopathy or Better From Baseline to 1-year   [ Time Frame: from baseline to 1 Year ]

Measure Type Other Pre-specified
Measure Title Change From Moderately Severe Non-proliferative Diabetic Retinopathy or Better From Baseline to 1-year
Measure Description 113 eyes had missing or ungradable photos at 1 year. Criteria are based on the ETDRS fundus photographic risk factors for the progression of diabetic retinopathy. ETDRS report no. 12. Ophthalmology 1991; 98:823-833
Time Frame from baseline to 1 Year  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Sham No text entered.
Ranibizumab No text entered.
Triamcinolone No text entered.

Measured Values
   Sham   Ranibizumab   Triamcinolone 
Participants Analyzed 
[Units: Participants]
 150   182   80 
Units Analyzed (Eyes) 
[Units: Eyes]
 150   182   80 
Change From Moderately Severe Non-proliferative Diabetic Retinopathy or Better From Baseline to 1-year 
[Units: Eyes]
     
Improved by 2 or more levels   6   46   20 
Worsened by 2 or more levels   11   5   2 


Statistical Analysis 1 for Change From Moderately Severe Non-proliferative Diabetic Retinopathy or Better From Baseline to 1-year
Groups [1] Sham vs. Ranibizumab
Method [2] GEE repeated measures
P Value [3] 0.08
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  P value for comparison with sham
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.

Statistical Analysis 2 for Change From Moderately Severe Non-proliferative Diabetic Retinopathy or Better From Baseline to 1-year
Groups [1] Sham vs. Triamcinolone
Method [2] GEE repeated measures
P Value [3] 0.17
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  P value for comparison with sham
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.



19.  Other Pre-specified:   Change From Severe Non-proliferative Diabetic Retinopathy or Worse From Baseline to 1-year   [ Time Frame: from baseline to 1 Year ]

Measure Type Other Pre-specified
Measure Title Change From Severe Non-proliferative Diabetic Retinopathy or Worse From Baseline to 1-year
Measure Description Criteria are based on the ETDRS fundus photographic risk factors for the progression of diabetic retinopathy. ETDRS report no. 12. Ophthalmology 1991; 98:823-833, ETDRS Severity Scale = Diabetic retinopathy absent, minimal non-proliferative diabetic retinopathy (PDR), mild to moderately severe non-PDR, severe non-PDR, scars of full pr partial panretinal photocoagulation present PDR absent, mild to moderate PDR, high risk PDR, cannot grade, missing.
Time Frame from baseline to 1 Year  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Sham No text entered.
Ranibizumab No text entered.
Triamcinolone No text entered.

Measured Values
   Sham   Ranibizumab   Triamcinolone 
Participants Analyzed 
[Units: Participants]
 83   121   70 
Units Analyzed (Eyes) 
[Units: Eyes]
 83   121   70 
Change From Severe Non-proliferative Diabetic Retinopathy or Worse From Baseline to 1-year 
[Units: Eyes]
     
Improved by 2 or more levels   10   18   6 
Worsened by 2 or more levels   7   1   2 


Statistical Analysis 1 for Change From Severe Non-proliferative Diabetic Retinopathy or Worse From Baseline to 1-year
Groups [1] Sham vs. Ranibizumab
Method [2] GEE repeated measures
P Value [3] 0.03
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  P value for comparison with sham
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.

Statistical Analysis 2 for Change From Severe Non-proliferative Diabetic Retinopathy or Worse From Baseline to 1-year
Groups [1] Sham vs. Triamcinolone
Method [2] GEE repeated measures
P Value [3] 0.17
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  P value for comparison with sham
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.



20.  Other Pre-specified:   Cardiovascular Events According to Antiplatelet Trialists' Collaboration Through 1 Year   [ Time Frame: 1 Year ]

Measure Type Other Pre-specified
Measure Title Cardiovascular Events According to Antiplatelet Trialists' Collaboration Through 1 Year
Measure Description Antiplatelet Trialists' Collaboration is a collaborative overview of randomised trials of antiplatelet therapy - I: Prevention of death, myocardial infarction, and stroke by prolonged antiplatelet therapy in various categories of patients. Antiplatelet Trialists' Collaboration. MBJ 1994; 308:81-106. Nonfatal cerebrovascular accident includes ischemic or hemorrhagic or unknown events. Vascular death includes death from any potential vascular or unknown cause.
Time Frame 1 Year  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Study participants with 2 study eyes are assigned to the non-sham group. Multiple events within a study participant are only counted once per event.

Reporting Groups
  Description
Sham No text entered.
Ranibizumab No text entered.
Triamcinolone No text entered.

Measured Values
   Sham   Ranibizumab   Triamcinolone 
Participants Analyzed 
[Units: Participants]
 130   375   186 
Cardiovascular Events According to Antiplatelet Trialists' Collaboration Through 1 Year 
[Units: Participants]
     
Nonfatal myocardial infarction   3   1   2 
Nonfatal cerebrovascular accident   5   3   1 
Vascular death   4   7   2 
Any ATC cardiovascular event   10   11   5 

No statistical analysis provided for Cardiovascular Events According to Antiplatelet Trialists' Collaboration Through 1 Year



21.  Other Pre-specified:   Major Ocular Adverse Events During First Year of Follow-Up   [ Time Frame: 1 Year ]

Measure Type Other Pre-specified
Measure Title Major Ocular Adverse Events During First Year of Follow-Up
Measure Description No text entered.
Time Frame 1 Year  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Sham+Prompt Laser Sham injection at randomization plus focal photocoagulation 1 week post-injection. Injections are repeated every 4 weeks with focal photocoagulation given post-injection every 16 weeks. Retreatment starting at 16 weeks depends on visual acuity and OCT.
0.5 mg Ranibizumab+Prompt Laser 0.5 mg intravitreal ranibizumab at randomization plus focal photocoagulation 1 week post-injection. Injections are repeated every 4 weeks with focal photocoagulation given post-injection every 16 weeks. Retreatment starting at 16 weeks depends on visual acuity and OCT.
0.5 mg Ranibizumab+Deferred Laser 0.5 mg intravitreal ranibizumab at randomization, repeated every 4 weeks. Retreatment starting at 16 weeks depends on visual acuity and OCT. If improvement has not occured from injections alone, laser can be given starting at the 24 week visit.
4 mg Triamcinolone+Prompt Laser 4 mg intravitreal triamcinolone at randomization plus focal photocoagulation 1 week post-injection, repeated every 16 weeks with sham injections at 4-week intervals in-between. Retreatment starting at 16 weeks depends on visual acuity and OCT.

Measured Values
   Sham+Prompt Laser   0.5 mg Ranibizumab+Prompt Laser   0.5 mg Ranibizumab+Deferred Laser   4 mg Triamcinolone+Prompt Laser 
Participants Analyzed 
[Units: Participants]
 293   187   188   186 
Units Analyzed (Eyes) 
[Units: Eyes]
 293   187   188   186 
Major Ocular Adverse Events During First Year of Follow-Up 
[Units: Eyes]
       
Endophthalmitis   1   1   1   0 
Pseudoendophthalmitis   1   0   0   1 
Ocular vascular event   1   1   0   2 
Retinal detachment   0   0   1   0 
Vitrectomy   7   0   3   0 
Vitreous hemorrhage   15   3   4   2 
Increase in intraocular pressure >=10 mmHg   16   10   5   70 
Intraocular pressure >=30 mmHg   3   2   4   46 
Initiation of intraocular lowering medication   23   12   7   79 
Glaucoma surgery   0   0   0   0 
Cataract surgery   11   6   8   19 

No statistical analysis provided for Major Ocular Adverse Events During First Year of Follow-Up




  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.


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