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CompletedNCT00444600LRT for DMEUpdated Oct 7, 2019Results posted

Laser-Ranibizumab-Triamcinolone for Diabetic Macular Edema

A Phase 3 interventional study of Triamcinolone Acetonide + laser and Ranibizumab + laser in Diabetic Retinopathy and Diabetic Macular Edema, sponsored by Jaeb Center for Health Research. Completed at 50 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2019-10-07.

Sponsored by Jaeb Center for Health Research · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
691
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study summary

The purpose of the study is to find out which is a better treatment for diabetic macular edema (DME): laser alone, laser combined with an intravitreal injection of triamcinolone, laser combined with an intravitreal injection of ranibizumab, or intravitreal injection of ranibizumab alone. At the present time, it is not known whether intravitreal steroid or anti-vascular endothelial growth factor (anti-VEGF) injections, with or without laser treatment, are better than just laser by itself. It is possible that one or both of the types of injections, with or without laser treatment, will improve vision more often than will laser without injections. However, even if better vision outcomes are seen with injections, side effects may be more of a problem with the injections than with laser. Therefore, this study is conducted to find out whether the benefits of the injections will outweigh the risks.

Read the detailed description

Thus far the only demonstrated means to reduce the risk of vision loss from diabetic macular edema are laser photocoagulation, intensive glycemic control, and blood pressure control. Earlier studies have shown that photocoagulation, although effective in reducing the risk of moderate vision loss, can eventually result in retinal and retinal pigment epithelium atrophy resulting in loss of central vision, central scotomata, and decreased color vision. Consequently, many retinal specialists today tend to treat diabetic macular edema (DME) with lighter, less intense laser burns than was originally specified in the Early Treatment Diabetic Retinopathy Study (ETDRS). The additional unsatisfactory outcome from treatments with laser photocoagulation in a significant proportion of eyes with DME has prompted interest in other treatment modalities. One such treatment is pars plana vitrectomy. Studies suggest that vitreomacular traction may play a role in increased retinal vascular permeability, and that removal of the vitreous, or relief of mechanical traction with vitrectomy and membrane stripping may substantially improve macular edema and visual acuity. However, this treatment may be applicable only to a specific subset of eyes with a component of vitreomacular traction secondary to edema. Other treatment modalities such as pharmacologic therapy with oral protein kinase C inhibitors and intravitreal corticosteroids are under investigation.

The use of antibodies targeted at vascular endothelial growth factor (VEGF) is another treatment modality that needs to be further explored for its potential benefits. Increased VEGF levels have been demonstrated in the retina and vitreous of human eyes with diabetic retinopathy. VEGF, also knows as vascular permeability factor, has been shown to increase retinal vascular permeability in in vivo models. Therapy that inhibits VEGF, therefore, may represent a useful therapeutic modality which targets the underlying pathogenesis of diabetic macular edema. Ranibizumab is a promising anti-VEGF drug. Its efficacy and safety have been demonstrated in treatment of age-related macular degeneration. Reports of its use and that of other anti-VEGF drugs in DME have suggested sufficient benefit to warrant evaluation of efficacy and safety in a phase III trial. Corticosteroids, a class of substances with anti-inflammatory properties, have also been demonstrated to inhibit the expression of the VEGF gene. The Diabetic Retinopathy Clinical Research Network (DRCR.net) is currently conducting a phase III randomized clinical trial comparing focal photocoagulation to intravitreal corticosteroids (triamcinolone acetonide) for diabetic macular edema. However, even if triamcinolone or ranibizumab are proven to be efficacious, a major concern, based on clinical observations with intravitreal corticosteroids, is that DME will recur as the effect of the intravitreal drug wears off, necessitating repetitive injections long-term. Combining an intravitreal drug (triamcinolone or ranibizumab) with photocoagulation provides hope that one could get the short-term benefit of the intravitreal drug (decreased retinal thickening and decreased fluid leakage) and the long-term reduction in fluid leakage as a result of photocoagulation. In addition, it is possible that the worsening of macular edema immediately following focal photocoagulation, a known complication of this treatment, could be decreased if an intravitreal drug was present at the time of photocoagulation. This might result in an increased likelihood of vision improvement following photocoagulation and a decreased likelihood of vision loss.

This study is designed to determine if ranibizumab alone or ranibizumab added to laser photocoagulation is more efficacious than photocoagulation alone, and if so, to determine if combining ranibizumab with photocoagulation reduces the total number of injections needed to obtain these benefits. Furthermore, this study is designed to determine if combining photocoagulation with corticosteroids, the only other class of drugs currently being considered for treatment of DME, is efficacious in the population being enrolled.

Subjects will be randomly assigned to one of the following 4 groups:

  1. Group A: Sham injection plus focal (macular) photocoagulation
  2. Group B: 0.5 mg injection of intravitreal ranibizumab plus focal photocoagulation
  3. Group C: 0.5 mg injection of intravitreal ranibizumab plus deferred focal photocoagulation
  4. Group D: 4 mg intravitreal triamcinolone plus focal photocoagulation

In groups A, B and D, laser will be given 7-10 days after the initial injection at the time of the injection follow-up safety visit. During the first year, subjects are evaluated for retreatment every 4 weeks. The injection for group A is a sham and for groups B and C ranibizumab. For group D, a triamcinolone injection is given if one has not been given in the prior 15 weeks; otherwise a sham injection is given. For Groups A, B, and D, focal photocoagulation will be given 7 to 10 days later following each injection unless focal photocoagulation has been given in the past 15 weeks or no macular edema is present. In Years 2 and 3, subjects continue to be evaluated for retreatment every 4 weeks unless injections are discontinued due to failure. In that case, follow-up visits occur every 4 months and treatment is at investigator discretion.

02

Conditions studied

  • Diabetic Retinopathy
  • Diabetic Macular Edema

Keywords

  • Diabetic Retinopathy
  • Diabetic Macular Edema
  • Lucentis
  • Ranibizumab
  • Triamcinolone
  • Laser photocoagulation
  • Combination Therapy
03

In context

Macular Edema

841 studies on the registry are indexed under Macular Edema; 56 are open to participants now.

This study's enrollment of 691 is above the median of 50 across 619 interventional studies indexed under Macular Edema.

Browse Macular Edema studies →

Lead sponsor

Jaeb Center for Health Research is the lead sponsor of 126 studies on the registry; 17 are open to participants now.

Of its 16 completed or terminated interventional studies of FDA-regulated products, 14 (88%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Eligibility criteria

General Inclusion Criteria

To be eligible, the following inclusion criteria (1-5) must be met:

  • Age >= 18 years
  • Diagnosis of diabetes mellitus (type 1 or type 2)
  • At least one eye meets the study eye criteria
  • Fellow eye (if not a study eye) meets criteria
  • Able and willing to provide informed consent

General Exclusion Criteria

A subject is not eligible if any of the following exclusion criteria are present:

  • Significant renal disease, defined as a history of chronic renal failure requiring dialysis or kidney transplant.
  • A condition that, in the opinion of the investigator, would preclude participation in the study (e.g., unstable medical status including blood pressure, cardiovascular disease, and glycemic control).
  • Participation in an investigational trial within 30 days of randomization that involved treatment with any drug that has not received regulatory approval at the time of study entry.
  • Known allergy to any component of the study drug.
  • Blood pressure > 180/110 (systolic above 180 OR diastolic above 110).
  • Major surgery within 28 days prior to randomization or major surgery planned during the next 6 months.
  • Myocardial infarction, other cardiac event requiring hospitalization, stroke, transient ischemic attack, or treatment for acute congestive heart failure within 4 months prior to randomization.
  • Systemic anti-vascular growth factor (anti-VEGF) or pro-VEGF treatment within 4 months prior to randomization.
  • For women of child-bearing potential: pregnant or lactating or intending to become pregnant within the next 12 months.
  • Subject is expecting to move out of the area of the clinical center to an area not covered by another clinical center during the first 12 months of the study.

Study Eye Inclusion Criteria

The subject must have one eye meeting all of the inclusion criteria and none of the exclusion criteria listed below. A subject may have two study eyes only if both are eligible at the time of randomization.

  • Best corrected electronic Early Treatment Diabetic Retinopathy (E-ETDRS) visual acuity letter score \<= 78 (i.e., 20/32 or worse) and >= 24 (i.e., 20/320 or better) within 8 days of randomization.
  • On clinical exam, definite retinal thickening due to diabetic macular edema involving the center of the macula.
  • Ocular coherence tomography (OCT) central subfield >=250 microns within 8 days of randomization.
  • Media clarity, pupillary dilation, and subject cooperation sufficient for adequate fundus photographs.
  • If prior macular photocoagulation has been performed, the investigator believes that the study eye may possibly benefit from additional photocoagulation.

Study Eye Exclusion Criteria

The following exclusions apply to the study eye only (i.e., they may be present for the nonstudy eye):

  • Macular edema is considered to be due to a cause other than diabetic macular edema.
  • An ocular condition is present such that, in the opinion of the investigator, visual acuity loss would not improve from resolution of macular edema (e.g., foveal atrophy, pigment abnormalities, dense subfoveal hard exudates, nonretinal condition).
  • An ocular condition is present (other than diabetes) that, in the opinion of the investigator, might affect macular edema or alter visual acuity during the course of the study (e.g., vein occlusion, uveitis or other ocular inflammatory disease, neovascular glaucoma, etc.)
  • Substantial cataract that, in the opinion of the investigator, is likely to be decreasing visual acuity by 3 lines or more (i.e., cataract would be reducing acuity to 20/40 or worse if eye was otherwise normal).
  • History of treatment for diabetic macular edema at any time in the past 4 months (such as focal/grid macular photocoagulation, intravitreal or peribulbar corticosteroids, anti-VEGF drugs, or any other treatment).
  • History of panretinal (scatter) photocoagulation (PRP) within 4 months prior to randomization.
  • Anticipated need for PRP in the 6 months following randomization.
  • History of major ocular surgery (including vitrectomy, cataract extraction, scleral buckle, any intraocular surgery, etc.) within prior 4 months or anticipated within the next 6 months following randomization.
  • History of yttrium aluminum garnet (YAG) capsulotomy performed within 2 months prior to randomization.
  • Aphakia.
  • Intraocular pressure >= 25 mmHg.
  • History of open-angle glaucoma (either primary open-angle glaucoma or other cause of open-angle glaucoma; note: history of angle-closure glaucoma is not an exclusion criterion).
  • History of steroid-induced intraocular pressure (IOP) elevation that required IOP-lowering treatment.
  • History of prior herpetic ocular infection.
  • Exam evidence of ocular toxoplasmosis.
  • Exam evidence of pseudoexfoliation.
  • Exam evidence of external ocular infection, including conjunctivitis, chalazion, or significant blepharitis.
05

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Double (Participant, Outcomes assessor)
Enrollment
691 participants (actual)

Study arms

  • Experimental
    0.5mg Ranibizumab plus laser

    Drug: Ranibizumab + laser

  • Experimental
    0.5 mg Ranibizumab plus deferred laser

    Drug: Ranibizumab + deferred laser

  • Experimental
    4 mg Triamcinolone plus laser

    Drug: Triamcinolone Acetonide + laser

  • Active comparator
    Sham plus laser

    Drug: Sham injection + laser

Interventions

  • DrugTriamcinolone Acetonide + 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.

    Also known as: corticosteroid

  • DrugRanibizumab + 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.

    Also known as: Lucentis, anti-VEGF drug

  • DrugSham injection + 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.

    Also known as: placebo

  • DrugRanibizumab + 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.

    Also known as: Lucentis, anti-VEGF drug

06

What researchers measure

Primary outcomes

  1. Mean Change in Visual Acuity (Letters) From Baseline to 1 Year Adjusted for Baseline Visual Acuity

    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

  2. Distribution of Change in Visual Acuity (Letters) From Baseline to 1 Year

    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

  3. Change in Visual Acuity From Baseline to 1 Year Among Eyes That Were Pseudophakic at Baseline

    Time frame: from baseline to 1 Year

  4. 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

  5. Change in Visual Acuity From Baseline to 1 Year Grouped by Baseline Visual Acuity Letter Score

    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

  6. Change in Visual Acuity From Baseline to 1 Year Grouped by Optical Coherence Tomography Central Subfield Thickness

    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

  7. Change in Visual Acuity From Baseline to 1 Year Grouped by Diabetic Retinopathy Severity

    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

  8. Change in Visual Acuity From Baseline to 1 Year Grouped by Diffuse vs. Focal Edema as Characterized by the Investigator

    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

Secondary outcomes

  1. Change in Retinal Thickening of Central Subfield on Optical Coherence Tomography From Baseline to 1 Year

    Negative change denotes an improvement.

    Time frame: from baseline to 1 year

  2. Number of Injections in First Year

    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

  3. Number of Laser Treatments Received Prior to the 1 Year Visit

    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

  4. Percentage of Eyes Receiving Laser at the 48 Week Visit (%)

    Time frame: 1 Year

  5. Mean Optical Coherence Tomography Retinal Volume at 1 Year

    Time frame: 1 Year

  6. Mean Change in Optical Coherence Tomography Retinal Volume From Baseline to 1 Year

    Time frame: from baseline to 1 Year

Other outcomes

  1. Central Subfield Thickness < 250 With at Least a 25 Micron Decrease From Baseline to 1 Year

    Time frame: 1 Year

  2. Distribution of Logarithmic Transformation of Optical Coherence Tomography (LogOCT) Improvement and Worsening

    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

  3. Eyes With Alternative Treatments Prior to the 1-year Visit

    Each combination of treatment only counted once.

    Time frame: 1 Year

  4. Change From Moderately Severe Non-proliferative Diabetic Retinopathy or Better From Baseline to 1-year

    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

  5. Change From Severe Non-proliferative Diabetic Retinopathy or Worse From Baseline to 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, 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

  6. Cardiovascular Events According to Antiplatelet Trialists' Collaboration Through 1 Year

    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

  7. Major Ocular Adverse Events During First Year of Follow-Up

    Time frame: 1 Year

07

Results

Posted Jul 12, 2011

Participant flow

Fifty two academic and community based sites across the United States recruited 691 study participants from March 2007 to December 2008.

Participant flow — Overall Study
MilestoneSham+Prompt Laser0.5 mg Ranibizumab+Prompt Laser0.5 mg Ranibizumab+Deferred Laser4 mg Triamcinolone+Prompt Laser
Started293187188186
Completed274171178176
Not completed19161010
Withdrew: Death7532
Withdrew: Dropped111177
Withdrew: Missed visit1001

Outcome measures

SecondaryChange in Retinal Thickening of Central Subfield on Optical Coherence Tomography From Baseline to 1 Year

Negative change denotes an improvement.

Time frame:
from baseline to 1 year
Reported as:
Mean · microns
Change in Retinal Thickening of Central Subfield on Optical Coherence Tomography From Baseline to 1 Year
micronsSham+Prompt Laser0.5 mg Ranibizumab+Prompt Laser0.5 mg Ranibizumab+Deferred Laser4 mg Triamcinolone+Prompt Laser
Change in Retinal Thickening of Central Subfield on Optical Coherence Tomography From Baseline to 1 Year-102 ± 151-131 ± 129-137 ± 136-127 ± 140
Statistical analysis
  • Sham+Prompt Laser vs 0.5 mg Ranibizumab+Prompt Laser · ANCOVA · p = <0.001 (Confidence intervals are adjusted for multiple comparisons.) · Difference in mean change: -55 · 95% CI -78 to -32Adjusted for baseline retinal thickness and visual acuity and correlation between two study eyes.
  • Sham+Prompt Laser vs 0.5 mg Ranibizumab+Deferred Laser · ANCOVA · p = <0.001 (Confidence intervals are adjusted for multiple comparisons.) · Difference in mean change: -49 · 95% CI -72 to -26Adjusted for baseline retinal thickness and visual acuity and correlation between two study eyes.
  • Sham+Prompt Laser vs 4 mg Triamcinolone+Prompt Laser · ANCOVA · p = <0.001 (Confidence interval is adjusted for multiple comparisons) · Difference in mean change: -52 · 95% CI -75 to -29Adjusted for baseline retinal thickness and visual acuity and correlation between two study eyes.
SecondaryNumber of Injections in First Year

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
Reported as:
Median · Injections
Number of Injections in First Year
InjectionsSham+Prompt Laser0.5 mg Ranibizumab+Prompt Laser0.5 mg Ranibizumab+Deferred Laser4 mg Triamcinolone+Prompt Laser
Number of Injections in First Year11 (8 to 13)8 (6 to 10)9 (6 to 11)3 (2 to 4)
PrimaryMean Change in Visual Acuity (Letters) From Baseline to 1 Year Adjusted for Baseline Visual Acuity

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
Reported as:
Mean · Letters
Mean Change in Visual Acuity (Letters) From Baseline to 1 Year Adjusted for Baseline Visual Acuity
LettersSham+Prompt Laser0.5 mg Ranibizumab+Prompt Laser0.5 mg Ranibizumab+Deferred Laser4 mg Triamcinolone+Prompt Laser
Mean Change in Visual Acuity (Letters) From Baseline to 1 Year Adjusted for Baseline Visual Acuity3 ± 139 ± 119 ± 124 ± 13
Statistical analysis
  • Sham+Prompt Laser vs 0.5 mg Ranibizumab+Prompt Laser · ANCOVA · p = <0.001 (Adjusted for multiple comparisons.) · Mean difference (final values): 5.8 · 95% CI 3.2 to 8.5Adjusted for baseline visual acuity and correlation between 2 study eyes.
  • Sham+Prompt Laser vs 0.5 mg Ranibizumab+Deferred Laser · ANCOVA · p = <0.001 (Adjusted for multiple comparisons.) · Mean difference (final values): 6.0 · 95% CI 3.4 to 8.6Adjusted for baseline visual acuity and correlation between 2 study eyes.
  • Sham+Prompt Laser vs 4 mg Triamcinolone+Prompt Laser · ANCOVA · p = 0.31 (Adjusted for multiple comparisons.) · Mean difference (final values): 1.1 · 95% CI -1.5 to 3.7Adjusted for baseline visual acuity and correlation between 2 study eyes.
PrimaryDistribution of Change in Visual Acuity (Letters) From Baseline to 1 Year

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
Reported as:
Number · Eyes
Distribution of Change in Visual Acuity (Letters) From Baseline to 1 Year
EyesSham+Prompt Laser0.5 mg Ranibizumab+Prompt Laser0.5 mg Ranibizumab+Deferred Laser4 mg Triamcinolone+Prompt Laser
≥15 letter improvement43575239
14-10 letter improvement38383622
9-5 letter improvement67345432
Same ±4 letters86383554
5-9 letters worse2014512
10-14 letters worse163212
≥15 letters worse233415
Statistical analysis
  • Sham+Prompt Laser vs 0.5 mg Ranibizumab+Prompt Laser · Binomial regression · Proportion: 23 · 95% CI 13 to 34Adjusted for correlation between 2 study eyes and multiple comparisons.
  • Sham+Prompt Laser vs 0.5 mg Ranibizumab+Deferred Laser · Binomial regression · Proportion: 19 · 95% CI 9 to 29Adjusted for correlation between 2 study eyes and multiple comparisons.
  • Sham+Prompt Laser vs 4 mg Triamcinolone+Prompt Laser · Binomial regression · Proportion: 6 · 95% CI -4 to 16Adjusted for correlation between 2 study eyes and multiple comparisons.
  • Sham+Prompt Laser vs 0.5 mg Ranibizumab+Prompt Laser · Log-Binomial Regression · p = <0.001 (Confidence intervals are adjusted for multiple comparisons.) · Risk ratio (rr): 1.84 · 95% CI 1.40 to 2.42Adjusted for correlation between 2 study eyes and multiple comparisons.
  • Sham+Prompt Laser vs 0.5 mg Ranibizumab+Deferred Laser · Log-Binomial Regression · p = <0.001 (Confidence intervals are adjusted for multiple comparisons.) · Risk ratio (rr): 1.68 · 95% CI 1.27 to 2.21Adjusted for correlation between 2 study eyes and multiple comparisons.
  • Sham+Prompt Laser vs 4 mg Triamcinolone+Prompt Laser · Log-Binomial Regression · p = 0.16 (Confidence intervals are adjusted for multiple comparisons.) · Risk ratio (rr): 1.21 · 95% CI 0.88 to 1.66Eyes were analyzed.
  • Sham+Prompt Laser vs 0.5 mg Ranibizumab+Prompt Laser · Binomial Regression · Proportion: -10 · 95% CI -16 to -5Adjusted for correlation between 2 study eyes and multiple comparisons.
  • Sham+Prompt Laser vs 0.5 mg Ranibizumab+Deferred Laser · Binomial Regression · Proportion: -10 · 95% CI -16 to -4Adjusted for correlation between 2 study eyes and multiple comparisons.
  • Sham+Prompt Laser vs 4 mg Triamcinolone+Prompt Laser · Binomial Regression · Proportion: 1 · 95% CI -7 to 9Adjusted for correlation between 2 study eyes and multiple comparisons.
  • Sham+Prompt Laser vs 0.5 mg Ranibizumab+Prompt Laser · Log-Binomial Regression · p = <0.001 (Confidence intervals are adjusted for multiple comparisons.) · Risk ratio (rr): 0.24 · 95% CI 0.09 to 0.65Adjusted for correlation between 2 study eyes and multiple comparisons.
  • Sham+Prompt Laser vs 0.5 mg Ranibizumab+Deferred Laser · Log-Binomial Regression · p = 0.001 (Confidence intervals are adjusted for multiple comparisons.) · Risk ratio (rr): 0.24 · 95% CI 0.08 to 0.68Adjusted for correlation between 2 study eyes and multiple comparisons.
  • Sham+Prompt Laser vs 4 mg Triamcinolone+Prompt Laser · Log-Binomial Regression · p = 0.75 (Confidence intervals are adjusted for multiple comparisons.) · Risk ratio (rr): 1.08 · 95% CI 0.62 to 1.87Adjusted for correlation between 2 study eyes and multiple comparisons.
  • Sham+Prompt Laser vs 0.5 mg Ranibizumab+Prompt Laser · Binomial Regression · Proportion: 16 · 95% CI 6 to 26Adjusted for correlation between to study eyes.
  • Sham+Prompt Laser vs 0.5 mg Ranibizumab+Deferred Laser · Binomial Regression · Proportion: 13 · 95% CI 4 to 22Adjusted for correlation between 2 study eyes and multiple comparisons.
  • Sham+Prompt Laser vs 4 mg Triamcinolone+Prompt Laser · Binomial Regression · Proportion: 6 · 95% CI -2 to 15Adjusted for correlation between 2 study eyes and multiple comparisons.
  • Sham+Prompt Laser vs 0.5 mg Ranibizumab+Prompt Laser · Log-Binomial Regression · p = <0.001 · Risk ratio (rr): 2.09 · 95% CI 1.35 to 3.22Adjusted for correlation between 2 study eyes and multiple comparisons.
  • Sham+Prompt Laser vs 0.5 mg Ranibizumab+Deferred Laser · Log-Binomial Regression · p = <0.001 (Confidence intervals are adjusted for multiple comparisons.) · Risk ratio (rr): 1.89 · 95% CI 1.25 to 2.87Adjusted for correlation between 2 study eyes and multiple comparisons.
  • Sham+Prompt Laser vs 4 mg Triamcinolone+Prompt Laser · Log-Binomial Regression · p = 0.07 (Confidence intervals are adjusted for multiple comparisons.) · Risk ratio (rr): 1.43 · 95% CI 0.90 to 2.29Adjusted for correlation between 2 study eyes and multiple comparisons.
  • Sham+Prompt Laser vs 0.5 mg Ranibizumab+Prompt Laser · Binomial Regression · Proportion: -6 · 95% CI -11 to -2Adjusted for correlation between 2 study eyes and multiple comparisons.
  • Sham+Prompt Laser vs 0.5 mg Ranibizumab+Deferred Laser · Binomial Regression · Proportion: -6 · 95% CI -10 to -1Adjusted for correlation between 2 study eyes and multiple comparisons.
  • Sham+Prompt Laser vs 4 mg Triamcinolone+Prompt Laser · Binomial Regression · Proportion: 0 · 95% CI -6 to 6Adjusted for correlation between 2 study eyes and multiple comparisons.
  • Sham+Prompt Laser vs 0.5 mg Ranibizumab+Prompt Laser · Log-Binomial Regression · p = 0.009 · Risk ratio (rr): 0.21 · 95% CI 0.05 to 0.87Adjusted for correlation between 2 study eyes and multiple comparisons.
  • Sham+Prompt Laser vs 0.5 mg Ranibizumab+Deferred Laser · Log-Binomial Regression · p = 0.01 · Risk ratio (rr): 0.28 · 95% CI 0.08 to 0.97Adjusted for correlation between 2 study eyes and multiple comparisons.
  • Sham+Prompt Laser vs 4 mg Triamcinolone+Prompt Laser · Log-Binomial Regression · p = 0.95 · Risk ratio (rr): 1.02 · 95% CI 0.47 to 2.20Adjusted for correlation between 2 study eyes and multiple comparisons.
Other pre-specifiedCentral Subfield Thickness < 250 With at Least a 25 Micron Decrease From Baseline to 1 Year
Time frame:
1 Year
Reported as:
Number · Eyes
Central Subfield Thickness < 250 With at Least a 25 Micron Decrease From Baseline to 1 Year
EyesSham+Prompt Laser0.5 mg Ranibizumab+Prompt Laser0.5 mg Ranibizumab+Deferred Laser4 mg Triamcinolone+Prompt Laser
Central Subfield Thickness < 250 With at Least a 25 Micron Decrease From Baseline to 1 Year72917482
Statistical analysis
  • Sham+Prompt Laser vs 0.5 mg Ranibizumab+Prompt Laser · Regression, Logistic · p = <0.001 (Confidence intervals are adjusted for multiple comparisons.) · Risk ratio (rr): 2.00 · 95% CI 1.52 to 2.64Adjusted for correlation between 2 study eyes and multiple comparisons.
  • Sham+Prompt Laser vs 0.5 mg Ranibizumab+Deferred Laser · Regression, Logistic · p = 0.001 (Confidence intervals adjusted for multiple comparisons) · Risk ratio (rr): 1.55 · 95% CI 1.13 to 2.13Adjusted for correlation between 2 study eyes and multiple comparisons.
  • Sham+Prompt Laser vs 4 mg Triamcinolone+Prompt Laser · Regression, Logistic · p = <0.001 (Confidence intervals adjusted for multiple comparisons.) · Risk ratio (rr): 1.76 · 95% CI 1.31 to 2.36Adjusted for correlation between 2 study eyes and multiple comparisons.
Other pre-specifiedDistribution of Logarithmic Transformation of Optical Coherence Tomography (LogOCT) Improvement and Worsening

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
Reported as:
Number · Eyes
Distribution of Logarithmic Transformation of Optical Coherence Tomography (LogOCT) Improvement and Worsening
EyesSham+Prompt Laser0.5 mg Ranibizumab+Prompt Laser0.5 mg Ranibizumab+Deferred Laser4 mg Triamcinolone+Prompt Laser
≥2 step improvement81727165
≥2 step worsening6104
PrimaryChange in Visual Acuity From Baseline to 1 Year Among Eyes That Were Pseudophakic at Baseline
Time frame:
from baseline to 1 Year
Reported as:
Mean · Letters
Change in Visual Acuity From Baseline to 1 Year Among Eyes That Were Pseudophakic at Baseline
LettersSham+Prompt Laser0.5 mg Ranibizumab+Prompt Laser0.5 mg Ranibizumab+Deferred Laser4 mg Triamcinolone+Prompt Laser
Not pseudophakic at baseline2 ± 139 ± 1010 ± 142 ± 14
Pseudophakic at baseline4 ± 148 ± 127 ± 98 ± 9
PrimaryChange 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
Reported as:
Mean · Letters
Change in Visual Acuity From Baseline to 1 Year Among Eyes That Had Prior Treatment for Diabetic Macular Edema
LettersSham+Prompt Laser0.5 mg Ranibizumab+Prompt Laser0.5 mg Ranibizumab+Deferred Laser4 mg Triamcinolone+Prompt Laser
No2 ± 149 ± 1211 ± 133 ± 13
Yes3 ± 139 ± 108 ± 125 ± 13
PrimaryChange in Visual Acuity From Baseline to 1 Year Grouped by Baseline Visual Acuity Letter Score

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
Reported as:
Mean · Letters
Change in Visual Acuity From Baseline to 1 Year Grouped by Baseline Visual Acuity Letter Score
LettersSham+Prompt Laser0.5 mg Ranibizumab+Prompt Laser0.5 mg Ranibizumab+Deferred Laser4 mg Triamcinolone+Prompt Laser
≥66 (better than 20/50)1 ± 126 ± 105 ± 131 ± 11
≤65 (20/50 or worse)5 ± 1412 ± 1113 ± 107 ± 14
PrimaryChange in Visual Acuity From Baseline to 1 Year Grouped by Optical Coherence Tomography Central Subfield Thickness

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
Reported as:
Mean · Letters
Change in Visual Acuity From Baseline to 1 Year Grouped by Optical Coherence Tomography Central Subfield Thickness
LettersSham+Prompt Laser0.5 mg Ranibizumab+Prompt Laser0.5 mg Ranibizumab+Deferred Laser4 mg Triamcinolone+Prompt Laser
<400 microns3 ± 117 ± 117 ± 123 ± 12
≥400 microns3 ± 1511 ± 1011 ± 136 ± 14
PrimaryChange in Visual Acuity From Baseline to 1 Year Grouped by Diabetic Retinopathy Severity

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
Reported as:
Mean · Letters
Change in Visual Acuity From Baseline to 1 Year Grouped by Diabetic Retinopathy Severity
LettersSham+Prompt Laser0.5 mg Ranibizumab+Prompt Laser0.5 mg Ranibizumab+Deferred Laser4 mg Triamcinolone+Prompt Laser
Moderately severe non-proliferative DR or better3 ± 1310 ± 119 ± 123 ± 14
Severe non-proliferative DR or worse2 ± 158 ± 109 ± 135 ± 12
PrimaryChange in Visual Acuity From Baseline to 1 Year Grouped by Diffuse vs. Focal Edema as Characterized by the Investigator

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
Reported as:
Mean · Letters
Change in Visual Acuity From Baseline to 1 Year Grouped by Diffuse vs. Focal Edema as Characterized by the Investigator
LettersSham+Prompt Laser0.5 mg Ranibizumab+Prompt Laser0.5 mg Ranibizumab+Deferred Laser4 mg Triamcinolone+Prompt Laser
Typical/predominantly focal3 ± 138 ± 118 ± 133 ± 11
Neither predominantly focal nor diffuse2 ± 1410 ± 98 ± 153 ± 13
Typical/predominantly diffuse3 ± 139 ± 1210 ± 105 ± 14
SecondaryNumber of Laser Treatments Received Prior to the 1 Year Visit

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
Reported as:
Number · Eyes
Number of Laser Treatments Received Prior to the 1 Year Visit
EyesSham+Prompt Laser0.5 mg Ranibizumab+Prompt Laser0.5 mg Ranibizumab+Deferred Laser4 mg Triamcinolone+Prompt Laser
0101241
135533646
275541753
310746149
45618027
Other pre-specifiedEyes With Alternative Treatments Prior to the 1-year Visit

Each combination of treatment only counted once.

Time frame:
1 Year
Reported as:
Number · Eyes
Eyes With Alternative Treatments Prior to the 1-year Visit
EyesSham+Prompt Laser0.5 mg Ranibizumab+Prompt Laser0.5 mg Ranibizumab+Deferred Laser4 mg Triamcinolone+Prompt Laser
Intravitreal bevacizumab3001
Intravitreal triamcinolone acetonide5000
Vitrectomy2000
Intravitreal bevacizumab+triamcinolone acetonide4000
Total number of eyes with alternative treatments14101
Total number of treatments applied25101
Total per protocol treatments applied5101
Total deviations from protocol treatments applied9000
Other pre-specifiedChange From Moderately Severe Non-proliferative Diabetic Retinopathy or Better From Baseline to 1-year

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
Reported as:
Number · Eyes
Change From Moderately Severe Non-proliferative Diabetic Retinopathy or Better From Baseline to 1-year
EyesShamRanibizumabTriamcinolone
Improved by 2 or more levels64620
Worsened by 2 or more levels1152
Statistical analysis
  • Sham vs Ranibizumab · GEE repeated measures · p = 0.08
  • Sham vs Triamcinolone · GEE repeated measures · p = 0.17
Other pre-specifiedChange From Severe Non-proliferative Diabetic Retinopathy or Worse From Baseline to 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, 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
Reported as:
Number · Eyes
Change From Severe Non-proliferative Diabetic Retinopathy or Worse From Baseline to 1-year
EyesShamRanibizumabTriamcinolone
Improved by 2 or more levels10186
Worsened by 2 or more levels712
Statistical analysis
  • Sham vs Ranibizumab · GEE repeated measures · p = 0.03
  • Sham vs Triamcinolone · GEE repeated measures · p = 0.17
SecondaryPercentage of Eyes Receiving Laser at the 48 Week Visit (%)
Time frame:
1 Year
Reported as:
Number · Eyes
Percentage of Eyes Receiving Laser at the 48 Week Visit (%)
EyesSham+Prompt Laser0.5 mg Ranibizumab+Prompt Laser0.5 mg Ranibizumab+Deferred Laser4 mg Triamcinolone+Prompt Laser
Percentage of Eyes Receiving Laser at the 48 Week Visit (%)2616821
Other pre-specifiedCardiovascular Events According to Antiplatelet Trialists' Collaboration Through 1 Year

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
Reported as:
Number · Participants
Cardiovascular Events According to Antiplatelet Trialists' Collaboration Through 1 Year
ParticipantsShamRanibizumabTriamcinolone
Nonfatal myocardial infarction312
Nonfatal cerebrovascular accident531
Vascular death472
Any ATC cardiovascular event10115
SecondaryMean Optical Coherence Tomography Retinal Volume at 1 Year
Time frame:
1 Year
Reported as:
Mean · mm^3
Mean Optical Coherence Tomography Retinal Volume at 1 Year
mm^3Sham+Prompt Laser0.5 mg Ranibizumab+Prompt Laser0.5 mg Ranibizumab+Deferred Laser4 mg Triamcinolone+Prompt Laser
Mean Optical Coherence Tomography Retinal Volume at 1 Year8.1 ± 1.47.3 ± 1.07.4 ± 1.27.5 ± 1.3
SecondaryMean Change in Optical Coherence Tomography Retinal Volume From Baseline to 1 Year
Time frame:
from baseline to 1 Year
Reported as:
Mean · mm^3
Mean Change in Optical Coherence Tomography Retinal Volume From Baseline to 1 Year
mm^3Sham+Prompt Laser0.5 mg Ranibizumab+Prompt Laser0.5 mg Ranibizumab+Deferred Laser4 mg Triamcinolone+Prompt Laser
Mean Change in Optical Coherence Tomography Retinal Volume From Baseline to 1 Year-1.0 ± 1.4-1.4 ± 1.4-1.5 ± 1.5-1.4 ± 1.6
Statistical analysis
  • Sham+Prompt Laser vs 0.5 mg Ranibizumab+Prompt Laser · ANCOVA · p = <0.001 (Confidence intervals are adjusted for multiple comparisons.) · Mean difference (net): -0.73 · 95% CI -1.01 to -0.44Adjusted for baseline optical coherence tomography (OCT) retinal volume, OCT retinal thickness and visual acuity and correlation between 2 study eyes.
  • Sham+Prompt Laser vs 0.5 mg Ranibizumab+Deferred Laser · ANCOVA · p = <0.001 (Confidence intervals adjusted for multiple comparisons.) · Mean difference (net): -0.68 · 95% CI -0.96 to -0.41Adjusted for baseline optical coherence tomography (OCT) retinal volume, OCT retinal thickness and visual acuity and correlation between 2 study eyes.
  • Sham+Prompt Laser vs 4 mg Triamcinolone+Prompt Laser · ANCOVA · p = <0.001 (Confidence intervals are adjusted for multiple comparisons.) · Mean difference (net): -0.62 · 95% CI -0.91 to -0.34Adjusted for baseline optical coherence tomography (OCT) retinal volume, OCT retinal thickness and visual acuity and correlation between 2 study eyes.
Other pre-specifiedMajor Ocular Adverse Events During First Year of Follow-Up
Time frame:
1 Year
Reported as:
Number · Eyes
Major Ocular Adverse Events During First Year of Follow-Up
EyesSham+Prompt Laser0.5 mg Ranibizumab+Prompt Laser0.5 mg Ranibizumab+Deferred Laser4 mg Triamcinolone+Prompt Laser
Endophthalmitis1110
Pseudoendophthalmitis1001
Ocular vascular event1102
Retinal detachment0010
Vitrectomy7030
Vitreous hemorrhage15342
Increase in intraocular pressure >=10 mmHg1610570
Intraocular pressure >=30 mmHg32446
Initiation of intraocular lowering medication2312779
Glaucoma surgery0000
Cataract surgery116819

Adverse events

Collected over 1 Year. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Sham + Prompt Laser—53/130 (40.8%)139/139 (100%)
Ranibizumab + Prompt Laser—46/131 (35.1%)97/97 (100%)
Ranibizumab + Deferred Laser—41/132 (31.1%)105/105 (100%)
Triamcinolone + Prompt Laser—57/135 (42.2%)145/145 (100%)
Sham + Ranibizumab + Laser—21/56 (37.5%)—
Sham + Ranibizumab + Deferred Laser—20/56 (35.7%)—
Sham + Triamcinolone + Laser—12/51 (23.5%)—
Most frequent serious events
Showing 10 of 112
Most frequent serious events
EventSham + Prompt LaserRanibizumab + Prompt LaserRanibizumab + Deferred LaserTriamcinolone + Prompt LaserSham + Ranibizumab + LaserSham + Ranibizumab + Deferred LaserSham + Triamcinolone + Laser
Cardiac failure congestiveCardiac disorders2/1308/1310/1324/1354/563/560/51
hypoglycaemiaGeneral disorders0/1300/1311/1320/1351/560/562/51
Chest painGeneral disorders5/1300/1313/1322/1352/560/560/51
CardiomegalyCardiac disorders0/1300/1310/1320/1350/562/560/51
Localised infectionInfections and infestations0/1300/1312/1323/1352/560/560/51
Renal failureRenal and urinary disorders1/1303/1311/1321/1350/562/561/51
Ischaemic strokeVascular disorders3/1300/1310/1320/1350/561/560/51
Myocardial infacrtionCardiac disorders3/1300/1311/1322/1350/560/560/51
HypertensionVascular disorders1/1300/1312/1323/1350/560/561/51
Diabetes mellitus inadequate controlEndocrine disorders0/1300/1310/1321/1350/560/561/51
Most frequent other events
Showing 10 of 18
Most frequent other events
EventSham + Prompt LaserRanibizumab + Prompt LaserRanibizumab + Deferred LaserTriamcinolone + Prompt LaserSham + Ranibizumab + LaserSham + Ranibizumab + Deferred LaserSham + Triamcinolone + Laser
Intraocular pressure increasedEye disorders7/1394/977/10555/145———
Vision BlurredEye disorders39/13916/9720/10532/145———
Conjunctival haemorrhageEye disorders4/13921/9725/10517/145———
Eye painEye disorders22/13923/9720/10512/145———
CataractEye disorders12/1399/9710/10531/145———
MaculopathyEye disorders24/13912/9714/1059/145———
Cataract subcapsularEye disorders7/1395/974/10523/145———
Vitreous floatersEye disorders9/13913/9711/10523/145———
Lacrimation increasedEye disorders9/1396/9716/1055/145———
MyodesopsiaEye disorders8/1394/9710/10519/145———

Baseline characteristics

Age, Continuous
Age, Continuous(years)Sham+Prompt Laser0.5 mg Ranibizumab+Prompt Laser0.5 mg Ranibizumab+Deferred Laser4 mg Triamcinolone+Prompt LaserTotal
Median63 (57 to 69)62 (56 to 70)64 (58 to 70)62 (55 to 70)63 (56 to 70)
Sex: Female, Male
Sex: Female, Male(Participants)Sham+Prompt Laser0.5 mg Ranibizumab+Prompt Laser0.5 mg Ranibizumab+Deferred Laser4 mg Triamcinolone+Prompt LaserTotal
Female123857886372
Male170102110100482
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)Sham+Prompt Laser0.5 mg Ranibizumab+Prompt Laser0.5 mg Ranibizumab+Deferred Laser4 mg Triamcinolone+Prompt LaserTotal
White202131134134601
African American51302532138
Hispanic or Latino3421251595
Asian412411
Native Hawaiian/Other Pacific Islander01001
More than one race11103
Unknown/not reported12115
Visual Acuity Letter Score (approximate Snellen equivalent) by randomization strata
Visual Acuity Letter Score (approximate Snellen equivalent) by randomization strata(Eyes)Sham+Prompt Laser0.5 mg Ranibizumab+Prompt Laser0.5 mg Ranibizumab+Deferred Laser4 mg Triamcinolone+Prompt LaserTotal
≥66 (better than 20/50)146959593429
≤65 (20/50 or worse)147929393425
Classification of diabetic macular edema
Classification of diabetic macular edema(Eyes)Sham+Prompt Laser0.5 mg Ranibizumab+Prompt Laser0.5 mg Ranibizumab+Deferred Laser4 mg Triamcinolone+Prompt LaserTotal
Predominantly focal78606853259
Neither predominantly focal or diffuse71464148206
Predominantly diffuse144817985389
Number of study eyes
Number of study eyes(Participants)Sham+Prompt Laser0.5 mg Ranibizumab+Prompt Laser0.5 mg Ranibizumab+Deferred Laser4 mg Triamcinolone+Prompt LaserTotal
1 study eye130131132135528
2 study eyes163565651326
Diabetes Type
Diabetes Type(Participants)Sham+Prompt Laser0.5 mg Ranibizumab+Prompt Laser0.5 mg Ranibizumab+Deferred Laser4 mg Triamcinolone+Prompt LaserTotal
Type 12511151465
Type 2260172170166768
Uncertain843621
Duration of diabetes
Duration of diabetes(Years)Sham+Prompt Laser0.5 mg Ranibizumab+Prompt Laser0.5 mg Ranibizumab+Deferred Laser4 mg Triamcinolone+Prompt LaserTotal
Median16 (9 to 22)18 (12 to 24)17 (11 to 22)17 (11 to 24)16 (10 to 23)

19 further baseline measures are reported on the registry.

08

Study locations

50 sites
  • Sall Research Medical Center
    Artesia, California 90701, United States
  • Retina-Vitreous Associates Medical Group
    Beverly Hills, California 90211, United States
  • University of California, Irvine
    Irvine, California 92697, United States
  • Loma Linda University Health Care, Dept. of Ophthalmology
    Loma Linda, California 92354, United States
  • Southern California Desert Retina Consultants, MC
    Palm Springs, California 92262, United States
  • California Retina Consultants
    Santa Barbara, California 93103, United States
  • Bay Area Retina Associates
    Walnut Creek, California 94598, United States
  • Retina Vitreous Consultants
    Fort Lauderdale, Florida 33334, United States
  • Retina Consultants of Southwest Florida
    Fort Myers, Florida 33912, United States
  • University of Florida College of Med., Department of Ophthalmology
    Jacksonville, Florida 32209, United States
  • Central Florida Retina Institute
    Lakeland, Florida 33805, United States
  • Southeast Retina Center, P.C.
    Augusta, Georgia 30909, United States
  • Illinois Retina Associates
    Joliet, Illinois 60435, United States
  • Raj K. Maturi, M.D., P.C.
    Indianapolis, Indiana 46280, United States
  • John-Kenyon American Eye Institute
    New Albany, Indiana 47150, United States
  • Medical Associates Clinic, P.C.
    Dubuque, Iowa 52002, United States
  • Retina and Vitreous Associates of Kentucky
    Lexington, Kentucky 40509-1802, United States
  • Paducah Retinal Center
    Paducah, Kentucky 42001, United States
  • Elman Retina Group, P.A.
    Baltimore, Maryland 21237, United States
  • Wilmer Eye Institute at Johns Hopkins
    Baltimore, Maryland 21287-9277, United States
  • Retina Consultants of Delmarva, P.A.
    Salisbury, Maryland 21801, United States
  • Ophthalmic Consultants of Boston
    Boston, Massachusetts 02114, United States
  • Joslin Diabetes Center
    Boston, Massachusetts 02215, United States
  • Retina Center, PA
    Minneapolis, Minnesota 55404, United States
  • Eyesight Ophthalmic Services, PA
    Portsmouth, New Hampshire 03801, United States
  • The New York Eye and Ear Infirmary/Faculty Eye Practice
    New York, New York 10003, United States
  • Retina-Vitreous Surgeons of Central New York, PC
    Syracuse, New York 13224, United States
  • University of North Carolina, Dept of Ophthalmology
    Chapel Hill, North Carolina 27599-7040, United States
  • Charlotte Eye, Ear, Nose and Throat Assoc., PA
    Charlotte, North Carolina 28210, United States
  • Wake Forest University Eye Center
    Winston-Salem, North Carolina 27157, United States
  • Retina Associates of Cleveland, Inc.
    Beachwood, Ohio 44122, United States
  • Case Western Reserve University
    Cleveland, Ohio 44106, United States
  • Retina Northwest, PC
    Portland, Oregon 97210, United States
  • Casey Eye Institute
    Portland, Oregon 97239, United States
  • Penn State College of Medicine
    Hershey, Pennsylvania 17033, United States
  • University of Pennsylvania Scheie Eye Institute
    Philadelphia, Pennsylvania 19104, United States
  • Retina Consultants
    Providence, Rhode Island 02903, United States
  • Palmetto Retina Center
    Columbia, South Carolina 29169, United States
  • Carolina Retina Center
    Columbia, South Carolina 29223, United States
  • Southeastern Retina Associates, PC
    Kingsport, Tennessee 37660, United States
  • Southeastern Retina Associates, P.C.
    Knoxville, Tennessee 37909, United States
  • West Texas Retina Consultants P.A.
    Abilene, Texas 79605, United States
  • Retina Research Center
    Austin, Texas 78705, United States
  • Texas Retina Associates
    Dallas, Texas 75231, United States
  • Retina and Vitreous of Texas
    Houston, Texas 77025, United States
  • Vitreoretinal Consultants
    Houston, Texas 77030, United States
  • Texas Retina Associates
    Lubbock, Texas 79424, United States
  • University of Washington Medical Center
    Seattle, Washington 98195, United States
  • University of Wisconsin-Madison, Dept of Ophthalmology/Retina Service
    Madison, Wisconsin 53705, United States
  • Medical College of Wisconsin
    Milwaukee, Wisconsin 53226, United States
09

References and documents

Publications

  • Elman MJ, Bressler NM, Qin H, Beck RW, Ferris FL 3rd, Friedman SM, Glassman AR, Scott IU, Stockdale CR, Sun JK; Diabetic Retinopathy Clinical Research Network. Expanded 2-year follow-up of ranibizumab plus prompt or deferred laser or triamcinolone plus prompt laser for diabetic macular edema. Ophthalmology. 2011 Apr;118(4):609-14. doi: 10.1016/j.ophtha.2010.12.033. PubMed 21459214 ↗
  • Diabetic Retinopathy Clinical Research Network; Writing Committee; Aiello LP, Beck RW, Bressler NM, Browning DJ, Chalam KV, Davis M, Ferris FL 3rd, Glassman AR, Maturi RK, Stockdale CR, Topping TM. Rationale for the diabetic retinopathy clinical research network treatment protocol for center-involved diabetic macular edema. Ophthalmology. 2011 Dec;118(12):e5-14. doi: 10.1016/j.ophtha.2011.09.058. PubMed 22136692 ↗
  • Glassman AR, Stockdale CR, Beck RW, Baker C, Bressler NM; Diabetic Retinopathy Clinical Research Network. Evaluation of masking study participants to intravitreal injections in a randomized clinical trial. Arch Ophthalmol. 2012 Feb;130(2):190-4. doi: 10.1001/archophthalmol.2011.387. PubMed 22332211 ↗
  • Bressler SB, Qin H, Beck RW, Chalam KV, Kim JE, Melia M, Wells JA 3rd; Diabetic Retinopathy Clinical Research Network. Factors associated with changes in visual acuity and central subfield thickness at 1 year after treatment for diabetic macular edema with ranibizumab. Arch Ophthalmol. 2012 Sep;130(9):1153-61. doi: 10.1001/archophthalmol.2012.1107. PubMed 22965591 ↗
  • Bressler SB, Qin H, Melia M, Bressler NM, Beck RW, Chan CK, Grover S, Miller DG; Diabetic Retinopathy Clinical Research Network. Exploratory analysis of the effect of intravitreal ranibizumab or triamcinolone on worsening of diabetic retinopathy in a randomized clinical trial. JAMA Ophthalmol. 2013 Aug;131(8):1033-40. doi: 10.1001/jamaophthalmol.2013.4154. PubMed 23807371 ↗
  • Bressler SB, Almukhtar T, Aiello LP, Bressler NM, Ferris FL 3rd, Glassman AR, Greven CM; Diabetic Retinopathy Clinical Research Network. Green or yellow laser treatment for diabetic macular edema: exploratory assessment within the Diabetic Retinopathy Clinical Research Network. Retina. 2013 Nov-Dec;33(10):2080-8. doi: 10.1097/IAE.0b013e318295f744. PubMed 23792486 ↗
  • Bressler SB, Almukhtar T, Bhorade A, Bressler NM, Glassman AR, Huang SS, Jampol LM, Kim JE, Melia M; Diabetic Retinopathy Clinical Research Network Investigators. Repeated intravitreous ranibizumab injections for diabetic macular edema and the risk of sustained elevation of intraocular pressure or the need for ocular hypotensive treatment. JAMA Ophthalmol. 2015 May;133(5):589-97. doi: 10.1001/jamaophthalmol.2015.186. PubMed 25719991 ↗
  • Bressler SB, Odia I, Glassman AR, Danis RP, Grover S, Hampton GR, Jampol LM, Maguire MG, Melia M. CHANGES IN DIABETIC RETINOPATHY SEVERITY WHEN TREATING DIABETIC MACULAR EDEMA WITH RANIBIZUMAB: DRCR.net Protocol I 5-Year Report. Retina. 2018 Oct;38(10):1896-1904. doi: 10.1097/IAE.0000000000002302. PubMed 30234859 ↗
  • Bressler SB, Melia M, Glassman AR, Almukhtar T, Jampol LM, Shami M, Berger BB, Bressler NM; Diabetic Retinopathy Clinical Research Network. RANIBIZUMAB PLUS PROMPT OR DEFERRED LASER FOR DIABETIC MACULAR EDEMA IN EYES WITH VITRECTOMY BEFORE ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY. Retina. 2015 Dec;35(12):2516-28. doi: 10.1097/IAE.0000000000000617. PubMed 26035510 ↗
  • Bressler SB, Ayala AR, Bressler NM, Melia M, Qin H, Ferris FL 3rd, Flaxel CJ, Friedman SM, Glassman AR, Jampol LM, Rauser ME; Diabetic Retinopathy Clinical Research Network. Persistent Macular Thickening After Ranibizumab Treatment for Diabetic Macular Edema With Vision Impairment. JAMA Ophthalmol. 2016 Mar;134(3):278-85. doi: 10.1001/jamaophthalmol.2015.5346. PubMed 26746868 ↗
  • Diabetic Retinopathy Clinical Research Network; Elman MJ, Aiello LP, Beck RW, Bressler NM, Bressler SB, Edwards AR, Ferris FL 3rd, Friedman SM, Glassman AR, Miller KM, Scott IU, Stockdale CR, Sun JK. Randomized trial evaluating ranibizumab plus prompt or deferred laser or triamcinolone plus prompt laser for diabetic macular edema. Ophthalmology. 2010 Jun;117(6):1064-1077.e35. doi: 10.1016/j.ophtha.2010.02.031. Epub 2010 Apr 28. PubMed 20427088 ↗
  • Diabetic Retinopathy Clinical Research Network; Elman MJ, Qin H, Aiello LP, Beck RW, Bressler NM, Ferris FL 3rd, Glassman AR, Maturi RK, Melia M. Intravitreal ranibizumab for diabetic macular edema with prompt versus deferred laser treatment: three-year randomized trial results. Ophthalmology. 2012 Nov;119(11):2312-8. doi: 10.1016/j.ophtha.2012.08.022. Epub 2012 Sep 19. Erratum In: Ophthalmology. 2014 Mar;121(3):805. PubMed 22999634 ↗
  • Bressler SB, Glassman AR, Almukhtar T, Bressler NM, Ferris FL, Googe JM Jr, Gupta SK, Jampol LM, Melia M, Wells JA 3rd; Diabetic Retinopathy Clinical Research Network. Five-Year Outcomes of Ranibizumab With Prompt or Deferred Laser Versus Laser or Triamcinolone Plus Deferred Ranibizumab for Diabetic Macular Edema. Am J Ophthalmol. 2016 Apr;164:57-68. doi: 10.1016/j.ajo.2015.12.025. Epub 2016 Jan 21. PubMed 26802783 ↗
  • Elman MJ, Ayala A, Bressler NM, Browning D, Flaxel CJ, Glassman AR, Jampol LM, Stone TW; Diabetic Retinopathy Clinical Research Network. Intravitreal Ranibizumab for diabetic macular edema with prompt versus deferred laser treatment: 5-year randomized trial results. Ophthalmology. 2015 Feb;122(2):375-81. doi: 10.1016/j.ophtha.2014.08.047. Epub 2014 Oct 28. PubMed 25439614 ↗
  • Gangaputra S, Almukhtar T, Glassman AR, Aiello LP, Bressler N, Bressler SB, Danis RP, Davis MD; Diabetic Retinopathy Clinical Research Network. Comparison of film and digital fundus photographs in eyes of individuals with diabetes mellitus. Invest Ophthalmol Vis Sci. 2011 Aug 3;52(9):6168-73. doi: 10.1167/iovs.11-7321. PubMed 21571677 ↗
  • Bhavsar AR, Googe JM Jr, Stockdale CR, Bressler NM, Brucker AJ, Elman MJ, Glassman AR; Diabetic Retinopathy Clinical Research Network. Risk of endophthalmitis after intravitreal drug injection when topical antibiotics are not required: the diabetic retinopathy clinical research network laser-ranibizumab-triamcinolone clinical trials. Arch Ophthalmol. 2009 Dec;127(12):1581-3. doi: 10.1001/archophthalmol.2009.304. PubMed 20008710 ↗
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Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Oct 7, 2019, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
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Registry details

Key details

Study ID
NCT00444600
Lead sponsor
Jaeb Center for Health Research
Collaborators
National Eye Institute (NEI), Allergan, Genentech, Inc.
Responsible party
Sponsor
First posted
Mar 8, 2007
Start date
Mar 2007
Primary completion
Dec 2009
Completion
Feb 2014
Results posted
Jul 12, 2011
Last update
Oct 7, 2019

Study contacts

Michael J. Elman, M.D.
study chair · Elman Retina Group, PA

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

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This study is completed, as verified in Sep 2019. You cannot join it, but the record below documents what was studied.

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