LRT for DME: Laser-Ranibizumab-Triamcinolone for Diabetic Macular Edema

Sponsor
Jaeb Center for Health Research (Other)
Overall Status
Completed
CT.gov ID
NCT00444600
Collaborator
National Eye Institute (NEI) (NIH), Allergan (Industry), Genentech, Inc. (Industry)
691
Enrollment
50
Locations
4
Arms
83.1
Duration (Months)
13.8
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or DiseaseIntervention/TreatmentPhase
  • Drug: Triamcinolone Acetonide + laser
  • Drug: Ranibizumab + laser
  • Drug: Sham injection + laser
  • Drug: Ranibizumab + deferred laser
Phase 3

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
691 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
Intravitreal Ranibizumab or Triamcinolone Acetonide in Combination With Laser Photocoagulation for Diabetic Macular Edema
Study Start Date :
Mar 1, 2007
Actual Primary Completion Date :
Dec 1, 2009
Actual Study Completion Date :
Feb 1, 2014

Arms and Interventions

ArmIntervention/Treatment
Experimental: 0.5mg Ranibizumab plus laser

Drug: Ranibizumab + 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.
Other Names:
  • Lucentis, anti-VEGF drug
  • Experimental: 0.5 mg Ranibizumab plus deferred laser

    Drug: 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.
    Other Names:
  • Lucentis, anti-VEGF drug
  • Experimental: 4 mg Triamcinolone plus laser

    Drug: Triamcinolone 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.
    Other Names:
  • corticosteroid
  • Active Comparator: Sham plus laser

    Drug: Sham 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.
    Other Names:
  • placebo
  • Outcome Measures

    Primary Outcome Measures

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

      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.

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

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

    5. Change in Visual Acuity From Baseline to 1 Year Grouped by Baseline Visual Acuity Letter Score [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. A positive change denotes an improvement. Best value on the scale 97, worst 0.

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

      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.

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

      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.

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

      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.

    Secondary Outcome Measures

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

      Negative change denotes an improvement.

    2. Number of Injections in First Year [from baseline to 1 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.

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

      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.

    4. Percentage of Eyes Receiving Laser at the 48 Week Visit (%) [1 Year]

    5. Mean Optical Coherence Tomography Retinal Volume at 1 Year [1 Year]

    6. Mean Change in Optical Coherence Tomography Retinal Volume From Baseline to 1 Year [from baseline to 1 Year]

    Other Outcome Measures

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

    2. Distribution of Logarithmic Transformation of Optical Coherence Tomography (LogOCT) Improvement and Worsening [1 Year]

      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.

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

      Each combination of treatment only counted once.

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

    5. Change From Severe Non-proliferative Diabetic Retinopathy or Worse From Baseline to 1-year [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.

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

    7. Major Ocular Adverse Events During First Year of Follow-Up [1 Year]

    Eligibility Criteria

    Criteria

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

    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.

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1Sall Research Medical CenterArtesiaCaliforniaUnited States90701
    2Retina-Vitreous Associates Medical GroupBeverly HillsCaliforniaUnited States90211
    3University of California, IrvineIrvineCaliforniaUnited States92697
    4Loma Linda University Health Care, Dept. of OphthalmologyLoma LindaCaliforniaUnited States92354
    5Southern California Desert Retina Consultants, MCPalm SpringsCaliforniaUnited States92262
    6California Retina ConsultantsSanta BarbaraCaliforniaUnited States93103
    7Bay Area Retina AssociatesWalnut CreekCaliforniaUnited States94598
    8Retina Vitreous ConsultantsFort LauderdaleFloridaUnited States33334
    9Retina Consultants of Southwest FloridaFort MyersFloridaUnited States33912
    10University of Florida College of Med., Department of OphthalmologyJacksonvilleFloridaUnited States32209
    11Central Florida Retina InstituteLakelandFloridaUnited States33805
    12Southeast Retina Center, P.C.AugustaGeorgiaUnited States30909
    13Illinois Retina AssociatesJolietIllinoisUnited States60435
    14Raj K. Maturi, M.D., P.C.IndianapolisIndianaUnited States46280
    15John-Kenyon American Eye InstituteNew AlbanyIndianaUnited States47150
    16Medical Associates Clinic, P.C.DubuqueIowaUnited States52002
    17Retina and Vitreous Associates of KentuckyLexingtonKentuckyUnited States40509-1802
    18Paducah Retinal CenterPaducahKentuckyUnited States42001
    19Elman Retina Group, P.A.BaltimoreMarylandUnited States21237
    20Wilmer Eye Institute at Johns HopkinsBaltimoreMarylandUnited States21287-9277
    21Retina Consultants of Delmarva, P.A.SalisburyMarylandUnited States21801
    22Ophthalmic Consultants of BostonBostonMassachusettsUnited States02114
    23Joslin Diabetes CenterBostonMassachusettsUnited States02215
    24Retina Center, PAMinneapolisMinnesotaUnited States55404
    25Eyesight Ophthalmic Services, PAPortsmouthNew HampshireUnited States03801
    26The New York Eye and Ear Infirmary/Faculty Eye PracticeNew YorkNew YorkUnited States10003
    27Retina-Vitreous Surgeons of Central New York, PCSyracuseNew YorkUnited States13224
    28University of North Carolina, Dept of OphthalmologyChapel HillNorth CarolinaUnited States27599-7040
    29Charlotte Eye, Ear, Nose and Throat Assoc., PACharlotteNorth CarolinaUnited States28210
    30Wake Forest University Eye CenterWinston-SalemNorth CarolinaUnited States27157
    31Retina Associates of Cleveland, Inc.BeachwoodOhioUnited States44122
    32Case Western Reserve UniversityClevelandOhioUnited States44106
    33Retina Northwest, PCPortlandOregonUnited States97210
    34Casey Eye InstitutePortlandOregonUnited States97239
    35Penn State College of MedicineHersheyPennsylvaniaUnited States17033
    36University of Pennsylvania Scheie Eye InstitutePhiladelphiaPennsylvaniaUnited States19104
    37Retina ConsultantsProvidenceRhode IslandUnited States02903
    38Palmetto Retina CenterColumbiaSouth CarolinaUnited States29169
    39Carolina Retina CenterColumbiaSouth CarolinaUnited States29223
    40Southeastern Retina Associates, PCKingsportTennesseeUnited States37660
    41Southeastern Retina Associates, P.C.KnoxvilleTennesseeUnited States37909
    42West Texas Retina Consultants P.A.AbileneTexasUnited States79605
    43Retina Research CenterAustinTexasUnited States78705
    44Texas Retina AssociatesDallasTexasUnited States75231
    45Retina and Vitreous of TexasHoustonTexasUnited States77025
    46Vitreoretinal ConsultantsHoustonTexasUnited States77030
    47Texas Retina AssociatesLubbockTexasUnited States79424
    48University of Washington Medical CenterSeattleWashingtonUnited States98195
    49University of Wisconsin-Madison, Dept of Ophthalmology/Retina ServiceMadisonWisconsinUnited States53705
    50Medical College of WisconsinMilwaukeeWisconsinUnited States53226

    Sponsors and Collaborators

    • Jaeb Center for Health Research
    • National Eye Institute (NEI)
    • Allergan
    • Genentech, Inc.

    Investigators

    • Study Chair: Michael J. Elman, M.D., Elman Retina Group, PA

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    Responsible Party:
    Jaeb Center for Health Research
    ClinicalTrials.gov Identifier:
    NCT00444600
    Other Study ID Numbers:
    • NEI-133
    • U10EY018817-03
    • U10EY014229-07
    • U10EY014231-09
    First Posted:
    Mar 8, 2007
    Last Update Posted:
    Oct 7, 2019
    Last Verified:
    Sep 1, 2019

    Study Results

    Participant Flow

    Recruitment DetailsFifty two academic and community based sites across the United States recruited 691 study participants from March 2007 to December 2008.
    Pre-assignment DetailParticipants 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.
    Arm/Group TitleSham+Prompt Laser0.5 mg Ranibizumab+Prompt Laser0.5 mg Ranibizumab+Deferred Laser4 mg Triamcinolone+Prompt Laser
    Arm/Group DescriptionSham 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 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 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 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.
    Period Title: Overall Study
    STARTED293187188186
    COMPLETED274171178176
    NOT COMPLETED19161010

    Baseline Characteristics

    Arm/Group TitleSham+Prompt Laser0.5 mg Ranibizumab+Prompt Laser0.5 mg Ranibizumab+Deferred Laser4 mg Triamcinolone+Prompt LaserTotal
    Arm/Group DescriptionSham 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 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 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 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 of all reporting groups
    Overall Participants293187188186854
    Age (years) [Median (Inter-Quartile Range) ]
    Median (Inter-Quartile Range) [years]
    63
    62
    64
    62
    63
    Sex: Female, Male (Count of Participants)
    Female
    123
    42%
    85
    45.5%
    78
    41.5%
    86
    46.2%
    372
    43.6%
    Male
    170
    58%
    102
    54.5%
    110
    58.5%
    100
    53.8%
    482
    56.4%
    Race/Ethnicity, Customized (Number) [Number]
    White
    202
    68.9%
    131
    70.1%
    134
    71.3%
    134
    72%
    601
    70.4%
    African American
    51
    17.4%
    30
    16%
    25
    13.3%
    32
    17.2%
    138
    16.2%
    Hispanic or Latino
    34
    11.6%
    21
    11.2%
    25
    13.3%
    15
    8.1%
    95
    11.1%
    Asian
    4
    1.4%
    1
    0.5%
    2
    1.1%
    4
    2.2%
    11
    1.3%
    Native Hawaiian/Other Pacific Islander
    0
    0%
    1
    0.5%
    0
    0%
    0
    0%
    1
    0.1%
    More than one race
    1
    0.3%
    1
    0.5%
    1
    0.5%
    0
    0%
    3
    0.4%
    Unknown/not reported
    1
    0.3%
    2
    1.1%
    1
    0.5%
    1
    0.5%
    5
    0.6%
    Visual Acuity Letter Score (approximate Snellen equivalent) by randomization strata (Eyes) [Number]
    ≥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 (Eyes) [Number]
    Predominantly focal
    78
    60
    68
    53
    259
    Neither predominantly focal or diffuse
    71
    46
    41
    48
    206
    Predominantly diffuse
    144
    81
    79
    85
    389
    Number of study eyes (Number) [Number]
    1 study eye
    130
    44.4%
    131
    70.1%
    132
    70.2%
    135
    72.6%
    528
    61.8%
    2 study eyes
    163
    55.6%
    56
    29.9%
    56
    29.8%
    51
    27.4%
    326
    38.2%
    Diabetes Type (Number) [Number]
    Type 1
    25
    8.5%
    11
    5.9%
    15
    8%
    14
    7.5%
    65
    7.6%
    Type 2
    260
    88.7%
    172
    92%
    170
    90.4%
    166
    89.2%
    768
    89.9%
    Uncertain
    8
    2.7%
    4
    2.1%
    3
    1.6%
    6
    3.2%
    21
    2.5%
    Duration of diabetes (Years) [Median (Inter-Quartile Range) ]
    Median (Inter-Quartile Range) [Years]
    16
    18
    17
    17
    16
    HbA1c (Percentage) [Median (Inter-Quartile Range) ]
    Median (Inter-Quartile Range) [Percentage]
    7.3
    7.3
    7.5
    7.4
    7.3
    Prior cardiovascular event (Number) [Number]
    Yes
    93
    31.7%
    66
    35.3%
    61
    32.4%
    61
    32.8%
    281
    32.9%
    No
    200
    68.3%
    121
    64.7%
    127
    67.6%
    125
    67.2%
    573
    67.1%
    Hypertension (Number) [Number]
    Yes
    240
    81.9%
    154
    82.4%
    156
    83%
    148
    79.6%
    698
    81.7%
    No
    53
    18.1%
    33
    17.6%
    32
    17%
    38
    20.4%
    156
    18.3%
    Prior Panretinal Photocoagulation (Eyes) [Number]
    Yes
    48
    36
    31
    37
    152
    No
    245
    151
    157
    149
    702
    Prior treatment for diabetic macular edema (Eyes) [Number]
    No
    105
    74
    74
    61
    314
    Yes
    188
    113
    114
    125
    540
    Prior laser for diabetic macular edema (Eyes) [Number]
    Yes
    173
    101
    101
    114
    489
    No
    120
    86
    87
    72
    365
    Prior IVT for diabetic macular edema (Eyes) [Number]
    Yes
    39
    22
    36
    31
    128
    No
    254
    165
    152
    155
    726
    Prior vitrectomy for diabetic macular edema (Eyes) [Number]
    Yes
    15
    7
    5
    12
    39
    No
    278
    180
    183
    174
    815
    Prior peribulbar triamcinolone for diabetic macular edema (Eyes) [Number]
    Yes
    12
    9
    5
    5
    31
    No
    281
    178
    183
    181
    823
    Prior anti-VEGF for diabetic macular edema (Eyes) [Number]
    Yes
    24
    24
    21
    20
    89
    No
    269
    163
    167
    166
    765
    Intraocular pressure (mmHg) [Median (Inter-Quartile Range) ]
    Median (Inter-Quartile Range) [mmHg]
    16
    16
    16
    16
    16
    Currently on intraocular pressure lowering medicine for glaucoma or ocular hypertension (Eyes) [Number]
    Yes
    5
    6
    4
    2
    17
    No
    288
    181
    184
    184
    837
    Lens status (Eyes) [Number]
    Phakic
    192
    131
    134
    124
    581
    Anterior Chamber Intraocular Lense
    3
    1
    1
    0
    5
    Posterior Chamber Intraocular Lense
    98
    55
    53
    62
    268
    E-ETDRS Visual Acuity Letter Score (Letter Score) [Median (Inter-Quartile Range) ]
    Median (Inter-Quartile Range) [Letter Score]
    65
    66
    66
    66
    66
    Central subfield thickness on optical coherence tomography (microns) [Median (Inter-Quartile Range) ]
    Median (Inter-Quartile Range) [microns]
    407
    371
    382
    374
    381
    Retinal volume on optical coherence tomography (microns) [Median (Inter-Quartile Range) ]
    Median (Inter-Quartile Range) [microns]
    8.7
    8.4
    8.4
    8.5
    8.5
    Optical coherence tomography cystoid abnormality (Eyes) [Number]
    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 (Eyes) [Number]
    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) (Eyes) [Number]
    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

    Outcome Measures

    1. Secondary Outcome
    TitleChange in Retinal Thickening of Central Subfield on Optical Coherence Tomography From Baseline to 1 Year
    DescriptionNegative change denotes an improvement.
    Time Framefrom baseline to 1 year

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleSham+Prompt Laser0.5 mg Ranibizumab+Prompt Laser0.5 mg Ranibizumab+Deferred Laser4 mg Triamcinolone+Prompt Laser
    Arm/Group DescriptionSham 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 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 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 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.
    Measure Participants271171175173
    Measure Eyes271171175173
    Mean (Standard Deviation) [microns]
    -102
    (151)
    -131
    (129)
    -137
    (136)
    -127
    (140)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Sham+Prompt Laser, 0.5 mg Ranibizumab+Prompt Laser
    Comments Difference in central subfield thickness mean change from sham+prompt laser
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesisp-Value<0.001
    CommentsConfidence intervals are adjusted for multiple comparisons.
    MethodANCOVA
    CommentsAdjusted for baseline retinal thickness and visual acuity and correlation between two study eyes.
    Method of EstimationEstimation ParameterDifference in mean change
    Estimated Value-55
    Confidence Interval (2-Sided) 95%
    -78 to -32
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Sham+Prompt Laser, 0.5 mg Ranibizumab+Deferred Laser
    Comments Difference in optical coherence tomography central subfield thickness mean change from sham+prompt laser
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesisp-Value<0.001
    CommentsConfidence intervals are adjusted for multiple comparisons.
    MethodANCOVA
    CommentsAdjusted for baseline retinal thickness and visual acuity and correlation between two study eyes.
    Method of EstimationEstimation ParameterDifference in mean change
    Estimated Value-49
    Confidence Interval (2-Sided) 95%
    -72 to -26
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Sham+Prompt Laser, 4 mg Triamcinolone+Prompt Laser
    Comments Difference in optical coherence tomography central subfield thickness mean change from sham+prompt laser
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesisp-Value<0.001
    CommentsConfidence interval is adjusted for multiple comparisons
    MethodANCOVA
    CommentsAdjusted for baseline retinal thickness and visual acuity and correlation between two study eyes.
    Method of EstimationEstimation ParameterDifference in mean change
    Estimated Value-52
    Confidence Interval (2-Sided) 95%
    -75 to -29
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    2. Secondary Outcome
    TitleNumber of Injections in First Year
    DescriptionMaximum 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 Framefrom baseline to 1 year

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group TitleSham+Prompt Laser0.5 mg Ranibizumab+Prompt Laser0.5 mg Ranibizumab+Deferred Laser4 mg Triamcinolone+Prompt Laser
    Arm/Group DescriptionSham 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 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 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 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.
    Measure Participants274171178176
    Measure Eyes274171178176
    Median (Inter-Quartile Range) [Injections]
    11
    8
    9
    3
    3. Primary Outcome
    TitleMean Change in Visual Acuity (Letters) From Baseline to 1 Year Adjusted for Baseline Visual Acuity
    DescriptionChange 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 Framefrom baseline to 1 Year

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group TitleSham+Prompt Laser0.5 mg Ranibizumab+Prompt Laser0.5 mg Ranibizumab+Deferred Laser4 mg Triamcinolone+Prompt Laser
    Arm/Group DescriptionSham 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 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 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 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.
    Measure Participants293187188186
    Measure Eyes293187188186
    Mean (Standard Deviation) [Letters]
    3
    (13)
    9
    (11)
    9
    (12)
    4
    (13)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Sham+Prompt Laser, 0.5 mg Ranibizumab+Prompt Laser
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesisp-Value<0.001
    CommentsAdjusted for multiple comparisons.
    MethodANCOVA
    CommentsAdjusted for baseline visual acuity and correlation between 2 study eyes.
    Method of EstimationEstimation ParameterMean Difference (Final Values)
    Estimated Value5.8
    Confidence Interval (2-Sided) 95%
    3.2 to 8.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Sham+Prompt Laser, 0.5 mg Ranibizumab+Deferred Laser
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesisp-Value<0.001
    CommentsAdjusted for multiple comparisons.
    MethodANCOVA
    CommentsAdjusted for baseline visual acuity and correlation between 2 study eyes.
    Method of EstimationEstimation ParameterMean Difference (Final Values)
    Estimated Value6.0
    Confidence Interval (2-Sided) 95%
    3.4 to 8.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Sham+Prompt Laser, 4 mg Triamcinolone+Prompt Laser
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesisp-Value0.31
    CommentsAdjusted for multiple comparisons.
    MethodANCOVA
    CommentsAdjusted for baseline visual acuity and correlation between 2 study eyes.
    Method of EstimationEstimation ParameterMean Difference (Final Values)
    Estimated Value1.1
    Confidence Interval (2-Sided) 95%
    -1.5 to 3.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    4. Primary Outcome
    TitleDistribution of Change in Visual Acuity (Letters) From Baseline to 1 Year
    DescriptionChange 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 Framefrom baseline to 1 Year

    Outcome Measure Data

    Analysis Population Description
    For eyes without any 1-year data the last observation carried forward method was used to impute data for the primary analysis.
    Arm/Group TitleSham+Prompt Laser0.5 mg Ranibizumab+Prompt Laser0.5 mg Ranibizumab+Deferred Laser4 mg Triamcinolone+Prompt Laser
    Arm/Group DescriptionSham 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 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 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 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.
    Measure Participants293187188186
    Measure Eyes293187188186
    ≥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
    Statistical Analysis Overview Comparison Group Selection Sham+Prompt Laser, 0.5 mg Ranibizumab+Prompt Laser
    Comments Difference in proportion with ≥10 letter improvement for sham+prompt laser at 1 year
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesisp-Value
    Comments
    Method
    Comments
    Method of EstimationEstimation ParameterProportion
    Estimated Value23
    Confidence Interval (2-Sided) 95%
    13 to 34
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Sham+Prompt Laser, 0.5 mg Ranibizumab+Deferred Laser
    Comments Difference in proportion with ≥10 letter improvement from sham+prompt laser at 1 year
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesisp-Value
    Comments
    Method
    Comments
    Method of EstimationEstimation ParameterProportion
    Estimated Value19
    Confidence Interval (2-Sided) 95%
    9 to 29
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Sham+Prompt Laser, 4 mg Triamcinolone+Prompt Laser
    Comments Difference in proportion with ≥10 letter improvement from sham+prompt laser at 1 year
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesisp-Value
    Comments
    Method
    Comments
    Method of EstimationEstimation ParameterProportion
    Estimated Value6
    Confidence Interval (2-Sided) 95%
    -4 to 16
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Sham+Prompt Laser, 0.5 mg Ranibizumab+Prompt Laser
    Comments Relative risk for ≥10 letter improvement comparison with sham+prompt laser at 1 year
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesisp-Value<0.001
    CommentsConfidence intervals are adjusted for multiple comparisons.
    MethodLog-Binomial Regression
    CommentsAdjusted for correlation between 2 study eyes and multiple comparisons.
    Method of EstimationEstimation ParameterRisk Ratio (RR)
    Estimated Value1.84
    Confidence Interval (2-Sided) 95%
    1.40 to 2.42
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Sham+Prompt Laser, 0.5 mg Ranibizumab+Deferred Laser
    Comments Relative risk for ≥10 letter improvement comparison with sham+prompt laser at 1 year
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesisp-Value<0.001
    CommentsConfidence intervals are adjusted for multiple comparisons.
    MethodLog-Binomial Regression
    CommentsAdjusted for correlation between 2 study eyes and multiple comparisons.
    Method of EstimationEstimation ParameterRisk Ratio (RR)
    Estimated Value1.68
    Confidence Interval (2-Sided) 95%
    1.27 to 2.21
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Sham+Prompt Laser, 4 mg Triamcinolone+Prompt Laser
    Comments Relative risk for ≥10 letter improvement comparison with sham+prompt laser at 1 year
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesisp-Value0.16
    CommentsConfidence intervals are adjusted for multiple comparisons.
    MethodLog-Binomial Regression
    CommentsAdjusted for correlation between 2 study eyes and multiple comparisons.
    Method of EstimationEstimation ParameterRisk Ratio (RR)
    Estimated Value1.21
    Confidence Interval (2-Sided) 95%
    0.88 to 1.66
    Parameter Dispersion Type:
    Value:
    Estimation CommentsEyes were analyzed.
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Sham+Prompt Laser, 0.5 mg Ranibizumab+Prompt Laser
    Comments Difference in proportion with ≥10 letter worsening from sham+prompt laser at 1 year
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesisp-Value
    Comments
    Method
    Comments
    Method of EstimationEstimation ParameterProportion
    Estimated Value-10
    Confidence Interval (2-Sided) 95%
    -16 to -5
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Sham+Prompt Laser, 0.5 mg Ranibizumab+Deferred Laser
    Comments Difference in proportion with ≥10 letter worsening from sham+prompt laser at 1 year
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesisp-Value
    Comments
    Method
    Comments
    Method of EstimationEstimation ParameterProportion
    Estimated Value-10
    Confidence Interval (2-Sided) 95%
    -16 to -4
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection Sham+Prompt Laser, 4 mg Triamcinolone+Prompt Laser
    Comments Difference in proportion with ≥10 letter worsening from sham+prompt laser at 1 year
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesisp-Value
    Comments
    Method
    Comments
    Method of EstimationEstimation ParameterProportion
    Estimated Value1
    Confidence Interval (2-Sided) 95%
    -7 to 9
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection Sham+Prompt Laser, 0.5 mg Ranibizumab+Prompt Laser
    Comments Relative risk for ≥10 letter worsening comparison with sham+prompt laser at 1 year
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesisp-Value<0.001
    CommentsConfidence intervals are adjusted for multiple comparisons.
    MethodLog-Binomial Regression
    CommentsAdjusted for correlation between 2 study eyes and multiple comparisons.
    Method of EstimationEstimation ParameterRisk Ratio (RR)
    Estimated Value0.24
    Confidence Interval (2-Sided) 95%
    0.09 to 0.65
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection Sham+Prompt Laser, 0.5 mg Ranibizumab+Deferred Laser
    Comments Relative risk for ≥10 letter worsening comparison with sham+prompt laser at 1 year
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesisp-Value0.001
    CommentsConfidence intervals are adjusted for multiple comparisons.
    MethodLog-Binomial Regression
    CommentsAdjusted for correlation between 2 study eyes and multiple comparisons.
    Method of EstimationEstimation ParameterRisk Ratio (RR)
    Estimated Value0.24
    Confidence Interval (2-Sided) 95%
    0.08 to 0.68
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection Sham+Prompt Laser, 4 mg Triamcinolone+Prompt Laser
    Comments Relative risk for ≥10 letter worsening comparison with sham+prompt laser at 1 year
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesisp-Value0.75
    CommentsConfidence intervals are adjusted for multiple comparisons.
    MethodLog-Binomial Regression
    CommentsAdjusted for correlation between 2 study eyes and multiple comparisons.
    Method of EstimationEstimation ParameterRisk Ratio (RR)
    Estimated Value1.08
    Confidence Interval (2-Sided) 95%
    0.62 to 1.87
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection Sham+Prompt Laser, 0.5 mg Ranibizumab+Prompt Laser
    Comments Difference in proportion with ≥15 letter improvement from sham+prompt laser at 1 year
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesisp-Value
    Comments
    Method
    Comments
    Method of EstimationEstimation ParameterProportion
    Estimated Value16
    Confidence Interval (2-Sided) 95%
    6 to 26
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 14
    Statistical Analysis Overview Comparison Group Selection Sham+Prompt Laser, 0.5 mg Ranibizumab+Deferred Laser
    Comments Difference in proportion with ≥15 letter improvement from sham+prompt laser at 1 year
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesisp-Value
    Comments
    Method
    Comments
    Method of EstimationEstimation ParameterProportion
    Estimated Value13
    Confidence Interval (2-Sided) 95%
    4 to 22
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 15
    Statistical Analysis Overview Comparison Group Selection Sham+Prompt Laser, 4 mg Triamcinolone+Prompt Laser
    Comments Difference in proportion with ≥15 letter improvement from sham+prompt laser at 1 year
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesisp-Value
    Comments
    Method
    Comments
    Method of EstimationEstimation ParameterProportion
    Estimated Value6
    Confidence Interval (2-Sided) 95%
    -2 to 15
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 16
    Statistical Analysis Overview Comparison Group Selection Sham+Prompt Laser, 0.5 mg Ranibizumab+Prompt Laser
    Comments Relative risk for ≥15 letter improvement comparison with sham+prompt laser at 1 year
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesisp-Value<0.001
    Comments
    MethodLog-Binomial Regression
    CommentsAdjusted for correlation between 2 study eyes and multiple comparisons.
    Method of EstimationEstimation ParameterRisk Ratio (RR)
    Estimated Value2.09
    Confidence Interval (2-Sided) 95%
    1.35 to 3.22
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 17
    Statistical Analysis Overview Comparison Group Selection Sham+Prompt Laser, 0.5 mg Ranibizumab+Deferred Laser
    Comments Relative risk for ≥15 letter improvement comparison with sham+prompt laser at 1 year
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesisp-Value<0.001
    CommentsConfidence intervals are adjusted for multiple comparisons.
    MethodLog-Binomial Regression
    CommentsAdjusted for correlation between 2 study eyes and multiple comparisons.
    Method of EstimationEstimation ParameterRisk Ratio (RR)
    Estimated Value1.89
    Confidence Interval (2-Sided) 95%
    1.25 to 2.87
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 18
    Statistical Analysis Overview Comparison Group Selection Sham+Prompt Laser, 4 mg Triamcinolone+Prompt Laser
    Comments Relative risk for ≥15 letter improvement comparison with sham+prompt laser at 1 year
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesisp-Value0.07
    CommentsConfidence intervals are adjusted for multiple comparisons.
    MethodLog-Binomial Regression
    CommentsAdjusted for correlation between 2 study eyes and multiple comparisons.
    Method of EstimationEstimation ParameterRisk Ratio (RR)
    Estimated Value1.43
    Confidence Interval (2-Sided) 95%
    0.90 to 2.29
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 19
    Statistical Analysis Overview Comparison Group Selection Sham+Prompt Laser, 0.5 mg Ranibizumab+Prompt Laser
    Comments Difference in proportion with ≥15 letter worsening from sham+prompt laser at 1 year
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesisp-Value
    Comments
    Method
    Comments
    Method of EstimationEstimation ParameterProportion
    Estimated Value-6
    Confidence Interval (2-Sided) 95%
    -11 to -2
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 20
    Statistical Analysis Overview Comparison Group Selection Sham+Prompt Laser, 0.5 mg Ranibizumab+Deferred Laser
    Comments Difference in proportion with ≥15 letter worsening from sham+prompt laser at 1 year
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesisp-Value
    Comments
    Method
    Comments
    Method of EstimationEstimation ParameterProportion
    Estimated Value-6
    Confidence Interval (2-Sided) 95%
    -10 to -1
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 21
    Statistical Analysis Overview Comparison Group Selection Sham+Prompt Laser, 4 mg Triamcinolone+Prompt Laser
    Comments Difference in proportion with ≥15 letter worsening from sham+prompt laser at 1 year
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesisp-Value
    Comments
    Method
    Comments
    Method of EstimationEstimation ParameterProportion
    Estimated Value0
    Confidence Interval (2-Sided) 95%
    -6 to 6
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 22
    Statistical Analysis Overview Comparison Group Selection Sham+Prompt Laser, 0.5 mg Ranibizumab+Prompt Laser
    Comments Relative risk for ≥15 letter worsening comparison with sham+prompt laser at 1 year
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesisp-Value0.009
    Comments
    MethodLog-Binomial Regression
    CommentsAdjusted for correlation between 2 study eyes and multiple comparisons.
    Method of EstimationEstimation ParameterRisk Ratio (RR)
    Estimated Value0.21
    Confidence Interval (2-Sided) 95%
    0.05 to 0.87
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 23
    Statistical Analysis Overview Comparison Group Selection Sham+Prompt Laser, 0.5 mg Ranibizumab+Deferred Laser
    Comments Relative risk for ≥15 letter worsening comparison with sham+prompt laser at 1 year
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesisp-Value0.01
    Comments
    MethodLog-Binomial Regression
    CommentsAdjusted for correlation between 2 study eyes and multiple comparisons.
    Method of EstimationEstimation ParameterRisk Ratio (RR)
    Estimated Value0.28
    Confidence Interval (2-Sided) 95%
    0.08 to 0.97
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 24
    Statistical Analysis Overview Comparison Group Selection Sham+Prompt Laser, 4 mg Triamcinolone+Prompt Laser
    Comments Relative risk for ≥15 letter worsening comparison with sham+prompt laser at 1 year
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesisp-Value0.95
    Comments
    MethodLog-Binomial Regression
    CommentsAdjusted for correlation between 2 study eyes and multiple comparisons.
    Method of EstimationEstimation ParameterRisk Ratio (RR)
    Estimated Value1.02
    Confidence Interval (2-Sided) 95%
    0.47 to 2.20
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    5. Other Pre-specified Outcome
    TitleCentral Subfield Thickness < 250 With at Least a 25 Micron Decrease From Baseline to 1 Year
    Description
    Time Frame1 Year

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleSham+Prompt Laser0.5 mg Ranibizumab+Prompt Laser0.5 mg Ranibizumab+Deferred Laser4 mg Triamcinolone+Prompt Laser
    Arm/Group DescriptionSham 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 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 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 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.
    Measure Participants271171175173
    Measure Eyes271171175173
    Number [Eyes]
    72
    91
    74
    82
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Sham+Prompt Laser, 0.5 mg Ranibizumab+Prompt Laser
    Comments Relative risk for comparison with sham+prompt laser
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesisp-Value<0.001
    CommentsConfidence intervals are adjusted for multiple comparisons.
    MethodRegression, Logistic
    CommentsAdjusted for correlation between 2 study eyes and multiple comparisons.
    Method of EstimationEstimation ParameterRisk Ratio (RR)
    Estimated Value2.00
    Confidence Interval (2-Sided) 95%
    1.52 to 2.64
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Sham+Prompt Laser, 0.5 mg Ranibizumab+Deferred Laser
    Comments Relative risk for comparison with sham+prompt laser
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesisp-Value0.001
    CommentsConfidence intervals adjusted for multiple comparisons
    MethodRegression, Logistic
    CommentsAdjusted for correlation between 2 study eyes and multiple comparisons.
    Method of EstimationEstimation ParameterRisk Ratio (RR)
    Estimated Value1.55
    Confidence Interval (2-Sided) 95%
    1.13 to 2.13
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Sham+Prompt Laser, 4 mg Triamcinolone+Prompt Laser
    Comments Relative risk for comparison with sham+prompt laser
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesisp-Value<0.001
    CommentsConfidence intervals adjusted for multiple comparisons.
    MethodRegression, Logistic
    CommentsAdjusted for correlation between 2 study eyes and multiple comparisons.
    Method of EstimationEstimation ParameterRisk Ratio (RR)
    Estimated Value1.76
    Confidence Interval () 95%
    1.31 to 2.36
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    6. Other Pre-specified Outcome
    TitleDistribution of Logarithmic Transformation of Optical Coherence Tomography (LogOCT) Improvement and Worsening
    DescriptionLogarithmic 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 Frame1 Year

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleSham+Prompt Laser0.5 mg Ranibizumab+Prompt Laser0.5 mg Ranibizumab+Deferred Laser4 mg Triamcinolone+Prompt Laser
    Arm/Group DescriptionSham 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 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 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 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.
    Measure Participants271171175173
    Measure Eyes271171175173
    ≥2 step improvement
    81
    72
    71
    65
    ≥2 step worsening
    6
    1
    0
    4
    7. Primary Outcome
    TitleChange in Visual Acuity From Baseline to 1 Year Among Eyes That Were Pseudophakic at Baseline
    Description
    Time Framefrom baseline to 1 Year

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleSham+Prompt Laser0.5 mg Ranibizumab+Prompt Laser0.5 mg Ranibizumab+Deferred Laser4 mg Triamcinolone+Prompt Laser
    Arm/Group DescriptionSham 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 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 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 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.
    Measure Participants293187188186
    Measure Eyes293187188186
    Not pseudophakic at baseline
    2
    (13)
    9
    (10)
    10
    (14)
    2
    (14)
    Pseudophakic at baseline
    4
    (14)
    8
    (12)
    7
    (9)
    8
    (9)
    8. Primary Outcome
    TitleChange in Visual Acuity From Baseline to 1 Year Among Eyes That Had Prior Treatment for Diabetic Macular Edema
    Description
    Time Framefrom baseline to 1 Year

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleSham+Prompt Laser0.5 mg Ranibizumab+Prompt Laser0.5 mg Ranibizumab+Deferred Laser4 mg Triamcinolone+Prompt Laser
    Arm/Group DescriptionSham 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 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 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 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.
    Measure Participants293187188186
    No
    2
    (14)
    9
    (12)
    11
    (13)
    3
    (13)
    Yes
    3
    (13)
    9
    (10)
    8
    (12)
    5
    (13)
    9. Primary Outcome
    TitleChange in Visual Acuity From Baseline to 1 Year Grouped by Baseline Visual Acuity Letter Score
    DescriptionChange 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 Framefrom baseline to 1 Year

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleSham+Prompt Laser0.5 mg Ranibizumab+Prompt Laser0.5 mg Ranibizumab+Deferred Laser4 mg Triamcinolone+Prompt Laser
    Arm/Group DescriptionSham 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 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 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 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.
    Measure Participants293187188186
    ≥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)
    10. Primary Outcome
    TitleChange in Visual Acuity From Baseline to 1 Year Grouped by Optical Coherence Tomography Central Subfield Thickness
    DescriptionChange 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 Framefrom baseline to 1 Year

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleSham+Prompt Laser0.5 mg Ranibizumab+Prompt Laser0.5 mg Ranibizumab+Deferred Laser4 mg Triamcinolone+Prompt Laser
    Arm/Group DescriptionSham 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 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 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 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.
    Measure Participants293187188186
    Measure Eyes293187188186
    <400 microns
    3
    (11)
    7
    (11)
    7
    (12)
    3
    (12)
    ≥400 microns
    3
    (15)
    11
    (10)
    11
    (13)
    6
    (14)
    11. Primary Outcome
    TitleChange in Visual Acuity From Baseline to 1 Year Grouped by Diabetic Retinopathy Severity
    DescriptionChange 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 Framefrom baseline to 1 Year

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleSham+Prompt Laser0.5 mg Ranibizumab+Prompt Laser0.5 mg Ranibizumab+Deferred Laser4 mg Triamcinolone+Prompt Laser
    Arm/Group DescriptionSham 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 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 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 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.
    Measure Participants293187188186
    Measure eyes293187188186
    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)
    12. Primary Outcome
    TitleChange in Visual Acuity From Baseline to 1 Year Grouped by Diffuse vs. Focal Edema as Characterized by the Investigator
    DescriptionChange 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 Framefrom baseline to 1 Year

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleSham+Prompt Laser0.5 mg Ranibizumab+Prompt Laser0.5 mg Ranibizumab+Deferred Laser4 mg Triamcinolone+Prompt Laser
    Arm/Group DescriptionSham 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 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 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 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.
    Measure Participants293187188186
    Measure Eyes293187188186
    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)
    13. Secondary Outcome
    TitleNumber of Laser Treatments Received Prior to the 1 Year Visit
    DescriptionOne 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 Frame1 Year

    Outcome Measure Data

    Analysis Population Description
    Number who completed the 1-year visit.
    Arm/Group TitleSham+Prompt Laser0.5 mg Ranibizumab+Prompt Laser0.5 mg Ranibizumab+Deferred Laser4 mg Triamcinolone+Prompt Laser
    Arm/Group DescriptionSham 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 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 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 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.
    Measure Participants274171178176
    Measure Eyes274171178176
    0
    1
    0
    124
    1
    1
    35
    53
    36
    46
    2
    75
    54
    17
    53
    3
    107
    46
    1
    49
    4
    56
    18
    0
    27
    14. Other Pre-specified Outcome
    TitleEyes With Alternative Treatments Prior to the 1-year Visit
    DescriptionEach combination of treatment only counted once.
    Time Frame1 Year

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleSham+Prompt Laser0.5 mg Ranibizumab+Prompt Laser0.5 mg Ranibizumab+Deferred Laser4 mg Triamcinolone+Prompt Laser
    Arm/Group DescriptionSham 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 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 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 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.
    Measure Participants293187188186
    Measure Eyes293187188186
    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
    15. Other Pre-specified Outcome
    TitleChange From Moderately Severe Non-proliferative Diabetic Retinopathy or Better From Baseline to 1-year
    Description113 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 Framefrom baseline to 1 Year

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleShamRanibizumabTriamcinolone
    Arm/Group Description
    Measure Participants15018280
    Measure Eyes15018280
    Improved by 2 or more levels
    6
    46
    20
    Worsened by 2 or more levels
    11
    5
    2
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Sham+Prompt Laser, 0.5 mg Ranibizumab+Prompt Laser
    Comments P value for comparison with sham
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesisp-Value0.08
    Comments
    MethodGEE repeated measures
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Sham+Prompt Laser, 0.5 mg Ranibizumab+Deferred Laser
    Comments P value for comparison with sham
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesisp-Value0.17
    Comments
    MethodGEE repeated measures
    Comments
    16. Other Pre-specified Outcome
    TitleChange From Severe Non-proliferative Diabetic Retinopathy or Worse From Baseline to 1-year
    DescriptionCriteria 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 Framefrom baseline to 1 Year

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleShamRanibizumabTriamcinolone
    Arm/Group Description
    Measure Participants8312170
    Measure Eyes8312170
    Improved by 2 or more levels
    10
    18
    6
    Worsened by 2 or more levels
    7
    1
    2
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Sham+Prompt Laser, 0.5 mg Ranibizumab+Prompt Laser
    Comments P value for comparison with sham
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesisp-Value0.03
    Comments
    MethodGEE repeated measures
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Sham+Prompt Laser, 0.5 mg Ranibizumab+Deferred Laser
    Comments P value for comparison with sham
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesisp-Value0.17
    Comments
    MethodGEE repeated measures
    Comments
    17. Secondary Outcome
    TitlePercentage of Eyes Receiving Laser at the 48 Week Visit (%)
    Description
    Time Frame1 Year

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleSham+Prompt Laser0.5 mg Ranibizumab+Prompt Laser0.5 mg Ranibizumab+Deferred Laser4 mg Triamcinolone+Prompt Laser
    Arm/Group DescriptionSham 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 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 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 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.
    Measure Participants274171178176
    Measure Eyes274171178176
    Number [Eyes]
    26
    16
    8
    21
    18. Other Pre-specified Outcome
    TitleCardiovascular Events According to Antiplatelet Trialists' Collaboration Through 1 Year
    DescriptionAntiplatelet 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 Frame1 Year

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group TitleShamRanibizumabTriamcinolone
    Arm/Group Description
    Measure Participants130375186
    Nonfatal myocardial infarction
    3
    1%
    1
    0.5%
    2
    1.1%
    Nonfatal cerebrovascular accident
    5
    1.7%
    3
    1.6%
    1
    0.5%
    Vascular death
    4
    1.4%
    7
    3.7%
    2
    1.1%
    Any ATC cardiovascular event
    10
    3.4%
    11
    5.9%
    5
    2.7%
    19. Secondary Outcome
    TitleMean Optical Coherence Tomography Retinal Volume at 1 Year
    Description
    Time Frame1 Year

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleSham+Prompt Laser0.5 mg Ranibizumab+Prompt Laser0.5 mg Ranibizumab+Deferred Laser4 mg Triamcinolone+Prompt Laser
    Arm/Group DescriptionSham 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 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 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 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.
    Measure Participants293187188186
    Measure Eyes293187188186
    Mean (Standard Deviation) [mm^3]
    8.1
    (1.4)
    7.3
    (1.0)
    7.4
    (1.2)
    7.5
    (1.3)
    20. Secondary Outcome
    TitleMean Change in Optical Coherence Tomography Retinal Volume From Baseline to 1 Year
    Description
    Time Framefrom baseline to 1 Year

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleSham+Prompt Laser0.5 mg Ranibizumab+Prompt Laser0.5 mg Ranibizumab+Deferred Laser4 mg Triamcinolone+Prompt Laser
    Arm/Group DescriptionSham 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 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 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 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.
    Measure Participants293187188186
    Measure Eyes293187188186
    Mean (Standard Deviation) [mm^3]
    -1.0
    (1.4)
    -1.4
    (1.4)
    -1.5
    (1.5)
    -1.4
    (1.6)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Sham+Prompt Laser, 0.5 mg Ranibizumab+Prompt Laser
    Comments Difference in mean change from sham+prompt laser
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesisp-Value<0.001
    CommentsConfidence intervals are adjusted for multiple comparisons.
    MethodANCOVA
    CommentsAdjusted for baseline optical coherence tomography (OCT) retinal volume, OCT retinal thickness and visual acuity and correlation between 2 study eyes.
    Method of EstimationEstimation ParameterMean Difference (Net)
    Estimated Value-0.73
    Confidence Interval (2-Sided) 95%
    -1.01 to -0.44
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Sham+Prompt Laser, 0.5 mg Ranibizumab+Deferred Laser
    Comments Difference in mean change from sham+prompt laser
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesisp-Value<0.001
    CommentsConfidence intervals adjusted for multiple comparisons.
    MethodANCOVA
    CommentsAdjusted for baseline optical coherence tomography (OCT) retinal volume, OCT retinal thickness and visual acuity and correlation between 2 study eyes.
    Method of EstimationEstimation ParameterMean Difference (Net)
    Estimated Value-0.68
    Confidence Interval (2-Sided) 95%
    -0.96 to -0.41
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Sham+Prompt Laser, 4 mg Triamcinolone+Prompt Laser
    Comments Difference in mean change from sham+prompt laser
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesisp-Value<0.001
    CommentsConfidence intervals are adjusted for multiple comparisons.
    MethodANCOVA
    CommentsAdjusted for baseline optical coherence tomography (OCT) retinal volume, OCT retinal thickness and visual acuity and correlation between 2 study eyes.
    Method of EstimationEstimation ParameterMean Difference (Net)
    Estimated Value-0.62
    Confidence Interval (2-Sided) 95%
    -0.91 to -0.34
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    21. Other Pre-specified Outcome
    TitleMajor Ocular Adverse Events During First Year of Follow-Up
    Description
    Time Frame1 Year

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleSham+Prompt Laser0.5 mg Ranibizumab+Prompt Laser0.5 mg Ranibizumab+Deferred Laser4 mg Triamcinolone+Prompt Laser
    Arm/Group DescriptionSham 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 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 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 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.
    Measure Participants293187188186
    Measure Eyes293187188186
    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

    Adverse Events

    Time Frame1 Year
    Adverse Event Reporting Description All ocular adverse events are listed under treatment group drug. Participants with a systemic adverse event with two study eyes are listed under the sham/ranibizumab or triamcinolone combination.
    Arm/Group TitleSham + Prompt LaserRanibizumab + Prompt LaserRanibizumab + Deferred LaserTriamcinolone + Prompt LaserSham + Ranibizumab + LaserSham + Ranibizumab + Deferred LaserSham + Triamcinolone + Laser
    Arm/Group DescriptionLaser was given within 3 to 10 days after sham injections, Laser = Focal/grid photocoagulation0.5 mg intravitreal ranibizumab plus prompt (within 3-10 days after injection) focal/grid photocoagulation0.5 mg intravitreal ranibizumab with deferred (24 weeks) focal/grid photocoagulation4 mg intravitreal triamcinolone plus prompt (within 3-10 days after injection) focal/grid photocoagulationParticipants in this group had 2 study eyes, the right eye was assigned randomly with equal probability to one of the four groups (Sham + prompt laser, ranibizumab + prompt laser, ranibizumab + deferred laser, triamcinolone + prompt laser). If the right eye was assigned to a treatment group other than the sham + prompt laser group, then the left eye was assigned to the sham + prompt laser group. If the right eye was assigned to the sham prompt + prompt laser group, then the left eye was assigned randomly to one of the other three groups.Participants in this group had 2 study eyes, the right eye was assigned randomly with equal probability to one of the four groups (Sham + prompt laser, ranibizumab + prompt laser, ranibizumab + deferred laser, triamcinolone + prompt laser). If the right eye was assigned to a treatment group other than the sham + prompt laser group, then the left eye was assigned to the sham + prompt laser group. If the right eye was assigned to the sham prompt + prompt laser group, then the left eye was assigned randomly to one of the other three groups.Participants in this group had 2 study eyes, the right eye was assigned randomly with equal probability to one of the four groups (Sham + prompt laser, ranibizumab + prompt laser, ranibizumab + deferred laser, triamcinolone + prompt laser). If the right eye was assigned to a treatment group other than the sham + prompt laser group, then the left eye was assigned to the sham + prompt laser group. If the right eye was assigned to the sham prompt + prompt laser group, then the left eye was assigned randomly to one of the other three groups.
    All Cause Mortality
    Sham + Prompt LaserRanibizumab + Prompt LaserRanibizumab + Deferred LaserTriamcinolone + Prompt LaserSham + Ranibizumab + LaserSham + Ranibizumab + Deferred LaserSham + Triamcinolone + Laser
    Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total/ (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    Sham + Prompt LaserRanibizumab + Prompt LaserRanibizumab + Deferred LaserTriamcinolone + Prompt LaserSham + Ranibizumab + LaserSham + Ranibizumab + Deferred LaserSham + Triamcinolone + Laser
    Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total53/130 (40.8%) 46/131 (35.1%) 41/132 (31.1%) 57/135 (42.2%) 21/56 (37.5%) 20/56 (35.7%) 12/51 (23.5%)
    Cardiac disorders
    Arrhythmia1/130 (0.8%) 1/131 (0.8%) 0/132 (0%) 0/135 (0%) 0/56 (0%) 0/56 (0%) 0/51 (0%)
    Cardiac failure0/130 (0%) 1/131 (0.8%) 0/132 (0%) 1/135 (0.7%) 0/56 (0%) 0/56 (0%) 0/51 (0%)
    Cardiac failure congestive2/130 (1.5%) 8/131 (6.1%) 0/132 (0%) 4/135 (3%) 4/56 (7.1%) 3/56 (5.4%) 0/51 (0%)
    Cardio-respiratory arrest0/130 (0%) 0/131 (0%) 0/132 (0%) 0/135 (0%) 1/56 (1.8%) 0/56 (0%) 0/51 (0%)
    Cardiomegaly0/130 (0%) 0/131 (0%) 0/132 (0%) 0/135 (0%) 0/56 (0%) 2/56 (3.6%) 0/51 (0%)
    Heart rate increased0/130 (0%) 0/131 (0%) 1/132 (0.8%) 0/135 (0%) 0/56 (0%) 0/56 (0%) 0/51 (0%)
    Heart rate irregular0/130 (0%) 1/131 (0.8%) 0/132 (0%) 0/135 (0%) 0/56 (0%) 0/56 (0%) 0/51 (0%)
    Left ventricular hypertrophy0/130 (0%) 0/131 (0%) 0/132 (0%) 0/135 (0%) 0/56 (0%) 1/56 (1.8%) 0/51 (0%)
    Myocardial infacrtion3/130 (2.3%) 0/131 (0%) 1/132 (0.8%) 2/135 (1.5%) 0/56 (0%) 0/56 (0%) 0/51 (0%)
    Tachycardia0/130 (0%) 0/131 (0%) 0/132 (0%) 0/135 (0%) 0/56 (0%) 1/56 (1.8%) 0/51 (0%)
    Transient ischaemic attack2/130 (1.5%) 0/131 (0%) 0/132 (0%) 0/135 (0%) 0/56 (0%) 0/56 (0%) 0/51 (0%)
    Bradycardia0/130 (0%) 1/131 (0.8%) 0/132 (0%) 0/135 (0%) 0/56 (0%) 0/56 (0%) 0/51 (0%)
    Supraventricular tachycardia0/130 (0%) 0/131 (0%) 1/132 (0.8%) 0/135 (0%) 0/56 (0%) 0/56 (0%) 0/51 (0%)
    Arteriosclerosis coronary artery1/130 (0.8%) 0/131 (0%) 1/132 (0.8%) 2/135 (1.5%) 0/56 (0%) 0/56 (0%) 0/51 (0%)
    Endocrine disorders
    Diabetes mellitus0/130 (0%) 0/131 (0%) 0/132 (0%) 0/135 (0%) 1/56 (1.8%) 0/56 (0%) 0/51 (0%)
    Diabetes mellitus inadequate control0/130 (0%) 0/131 (0%) 0/132 (0%) 1/135 (0.7%) 0/56 (0%) 0/56 (0%) 1/51 (2%)
    Diabetic ketoacidosis0/130 (0%) 0/131 (0%) 0/132 (0%) 1/135 (0.7%) 1/56 (1.8%) 1/56 (1.8%) 0/51 (0%)
    Eye disorders
    Cataract1/130 (0.8%) 0/131 (0%) 0/132 (0%) 0/135 (0%) 0/56 (0%) 0/56 (0%) 0/51 (0%)
    Endophthalmitis2/130 (1.5%) 1/131 (0.8%) 0/132 (0%) 0/135 (0%) 0/56 (0%) 1/56 (1.8%) 0/51 (0%)
    Intraocular pressure increased0/130 (0%) 0/131 (0%) 0/132 (0%) 1/135 (0.7%) 0/56 (0%) 0/56 (0%) 0/51 (0%)
    Retinal vein occlusion0/130 (0%) 0/131 (0%) 0/132 (0%) 2/135 (1.5%) 0/56 (0%) 0/56 (0%) 0/51 (0%)
    Glaucoma0/130 (0%) 0/131 (0%) 0/132 (0%) 1/135 (0.7%) 0/56 (0%) 0/56 (0%) 0/51 (0%)
    Iris neovascularisation1/130 (0.8%) 0/131 (0%) 0/132 (0%) 0/135 (0%) 0/56 (0%) 0/56 (0%) 0/51 (0%)
    Gastrointestinal disorders
    Food poisoning0/130 (0%) 0/131 (0%) 0/132 (0%) 1/135 (0.7%) 1/56 (1.8%) 0/56 (0%) 0/51 (0%)
    Gastroenteritis0/130 (0%) 0/131 (0%) 0/132 (0%) 0/135 (0%) 0/56 (0%) 0/56 (0%) 1/51 (2%)
    Gastroesophageal reflux disease1/130 (0.8%) 0/131 (0%) 0/132 (0%) 0/135 (0%) 0/56 (0%) 0/56 (0%) 0/51 (0%)
    Impaired gastric emptying0/130 (0%) 0/131 (0%) 2/132 (1.5%) 0/135 (0%) 0/56 (0%) 0/56 (0%) 0/51 (0%)
    Diverticulitis2/130 (1.5%) 0/131 (0%) 0/132 (0%) 0/135 (0%) 0/56 (0%) 0/56 (0%) 0/51 (0%)
    Gastric bypass0/130 (0%) 0/131 (0%) 0/132 (0%) 0/135 (0%) 1/56 (1.8%) 0/56 (0%) 0/51 (0%)
    Gastrointestinal haemorrhage1/130 (0.8%) 0/131 (0%) 0/132 (0%) 0/135 (0%) 0/56 (0%) 0/56 (0%) 0/51 (0%)
    Vomiting0/130 (0%) 0/131 (0%) 0/132 (0%) 2/135 (1.5%) 0/56 (0%) 0/56 (0%) 0/51 (0%)
    General disorders
    Abdominal pain0/130 (0%) 0/131 (0%) 0/132 (0%) 1/135 (0.7%) 0/56 (0%) 0/56 (0%) 0/51 (0%)
    Anemia0/130 (0%) 1/131 (0.8%) 1/132 (0.8%) 1/135 (0.7%) 0/56 (0%) 0/56 (0%) 0/51 (0%)
    Angina pectoris1/130 (0.8%) 0/131 (0%) 0/132 (0%) 1/135 (0.7%) 0/56 (0%) 1/56 (1.8%) 0/51 (0%)
    Blood potassium increased1/130 (0.8%) 0/131 (0%) 2/132 (1.5%) 2/135 (1.5%) 0/56 (0%) 0/56 (0%) 0/51 (0%)
    Cellulitis0/130 (0%) 2/131 (1.5%) 0/132 (0%) 2/135 (1.5%) 0/56 (0%) 1/56 (1.8%) 0/51 (0%)
    Chest pain5/130 (3.8%) 0/131 (0%) 3/132 (2.3%) 2/135 (1.5%) 2/56 (3.6%) 0/56 (0%) 0/51 (0%)
    Convulsion0/130 (0%) 0/131 (0%) 0/132 (0%) 0/135 (0%) 1/56 (1.8%) 0/56 (0%) 0/51 (0%)
    Death2/130 (1.5%) 1/131 (0.8%) 2/132 (1.5%) 2/135 (1.5%) 1/56 (1.8%) 1/56 (1.8%) 0/51 (0%)
    Dehydration2/130 (1.5%) 0/131 (0%) 1/132 (0.8%) 0/135 (0%) 0/56 (0%) 0/56 (0%) 0/51 (0%)
    Dysarthria0/130 (0%) 0/131 (0%) 0/132 (0%) 0/135 (0%) 0/56 (0%) 0/56 (0%) 1/51 (2%)
    Dyspnoea1/130 (0.8%) 0/131 (0%) 0/132 (0%) 0/135 (0%) 0/56 (0%) 0/56 (0%) 0/51 (0%)
    Goitre0/130 (0%) 0/131 (0%) 0/132 (0%) 1/135 (0.7%) 0/56 (0%) 0/56 (0%) 0/51 (0%)
    Haematochezia1/130 (0.8%) 0/131 (0%) 0/132 (0%) 0/135 (0%) 0/56 (0%) 0/56 (0%) 0/51 (0%)
    Hernia0/130 (0%) 0/131 (0%) 0/132 (0%) 0/135 (0%) 0/56 (0%) 0/56 (0%) 1/51 (2%)
    Hyperglycaemia1/130 (0.8%) 0/131 (0%) 2/132 (1.5%) 0/135 (0%) 0/56 (0%) 1/56 (1.8%) 0/51 (0%)
    Oedema peripheral0/130 (0%) 1/131 (0.8%) 0/132 (0%) 2/135 (1.5%) 0/56 (0%) 0/56 (0%) 0/51 (0%)
    Pain in extremity0/130 (0%) 0/131 (0%) 0/132 (0%) 1/135 (0.7%) 0/56 (0%) 0/56 (0%) 1/51 (2%)
    Post procedural complications0/130 (0%) 0/131 (0%) 1/132 (0.8%) 1/135 (0.7%) 0/56 (0%) 0/56 (0%) 0/51 (0%)
    Presyncope0/130 (0%) 0/131 (0%) 0/132 (0%) 0/135 (0%) 1/56 (1.8%) 0/56 (0%) 0/51 (0%)
    Pulmonary oedema0/130 (0%) 1/131 (0.8%) 1/132 (0.8%) 0/135 (0%) 0/56 (0%) 0/56 (0%) 0/51 (0%)
    Rhabdomyolysis0/130 (0%) 0/131 (0%) 1/132 (0.8%) 0/135 (0%) 0/56 (0%) 0/56 (0%) 0/51 (0%)
    Syncope0/130 (0%) 2/131 (1.5%) 0/132 (0%) 1/135 (0.7%) 0/56 (0%) 1/56 (1.8%) 0/51 (0%)
    Vertigo2/130 (1.5%) 0/131 (0%) 0/132 (0%) 1/135 (0.7%) 0/56 (0%) 0/56 (0%) 0/51 (0%)
    Arthralgia1/130 (0.8%) 1/131 (0.8%) 0/132 (0%) 0/135 (0%) 0/56 (0%) 0/56 (0%) 0/51 (0%)
    Atrial fibrillation0/130 (0%) 1/131 (0.8%) 2/132 (1.5%) 0/135 (0%) 0/56 (0%) 0/56 (0%) 0/51 (0%)
    Anxiety0/130 (0%) 1/131 (0.8%) 0/132 (0%) 0/135 (0%) 0/56 (0%) 0/56 (0%) 0/51 (0%)
    Blood glucose decreased0/130 (0%) 0/131 (0%) 0/132 (0%) 1/135 (0.7%) 0/56 (0%) 0/56 (0%) 0/51 (0%)
    Cholecystitis acute0/130 (0%) 0/131 (0%) 1/132 (0.8%) 0/135 (0%) 0/56 (0%) 0/56 (0%) 0/51 (0%)
    Contusion0/130 (0%) 0/131 (0%) 0/132 (0%) 0/135 (0%) 1/56 (1.8%) 0/56 (0%) 0/51 (0%)
    Gout0/130 (0%) 0/131 (0%) 1/132 (0.8%) 0/135 (0%) 0/56 (0%) 0/56 (0%) 0/51 (0%)
    Hemiparesis1/130 (0.8%) 0/131 (0%) 0/132 (0%) 0/135 (0%) 0/56 (0%) 0/56 (0%) 0/51 (0%)
    Hypersensitivity0/130 (0%) 0/131 (0%) 0/132 (0%) 1/135 (0.7%) 0/56 (0%) 0/56 (0%) 0/51 (0%)
    Lymphoedema0/130 (0%) 1/131 (0.8%) 0/132 (0%) 0/135 (0%) 0/56 (0%) 0/56 (0%) 0/51 (0%)
    Nausea0/130 (0%) 0/131 (0%) 0/132 (0%) 1/135 (0.7%) 0/56 (0%) 0/56 (0%) 0/51 (0%)
    Migraine0/130 (0%) 2/131 (1.5%) 0/132 (0%) 0/135 (0%) 0/56 (0%) 0/56 (0%) 0/51 (0%)
    Salivary gland disorder0/130 (0%) 1/131 (0.8%) 0/132 (0%) 0/135 (0%) 0/56 (0%) 0/56 (0%) 0/51 (0%)
    hypoglycaemia0/130 (0%) 0/131 (0%) 1/132 (0.8%) 0/135 (0%) 1/56 (1.8%) 0/56 (0%) 2/51 (3.9%)
    Anaemia of Chronic disease0/130 (0%) 0/131 (0%) 1/132 (0.8%) 0/135 (0%) 0/56 (0%) 0/56 (0%) 0/51 (0%)
    Joint Injury0/130 (0%) 1/131 (0.8%) 0/132 (0%) 1/135 (0.7%) 0/56 (0%) 0/56 (0%) 0/51 (0%)
    Skin Ulcer1/130 (0.8%) 0/131 (0%) 1/132 (0.8%) 1/135 (0.7%) 0/56 (0%) 1/56 (1.8%) 0/51 (0%)
    Infections and infestations
    Infection1/130 (0.8%) 0/131 (0%) 0/132 (0%) 1/135 (0.7%) 0/56 (0%) 0/56 (0%) 0/51 (0%)
    Localised infection0/130 (0%) 0/131 (0%) 2/132 (1.5%) 3/135 (2.2%) 2/56 (3.6%) 0/56 (0%) 0/51 (0%)
    Musculoskeletal and connective tissue disorders
    Facial bones fracture0/130 (0%) 1/131 (0.8%) 0/132 (0%) 0/135 (0%) 0/56 (0%) 0/56 (0%) 0/51 (0%)
    Fracture0/130 (0%) 1/131 (0.8%) 0/132 (0%) 0/135 (0%) 1/56 (1.8%) 0/56 (0%) 1/51 (2%)
    Multiple fractures1/130 (0.8%) 0/131 (0%) 0/132 (0%) 0/135 (0%) 0/56 (0%) 0/56 (0%) 0/51 (0%)
    Osteomyelitis0/130 (0%) 1/131 (0.8%) 0/132 (0%) 0/135 (0%) 0/56 (0%) 0/56 (0%) 0/51 (0%)
    Hip fracture1/130 (0.8%) 0/131 (0%) 0/132 (0%) 0/135 (0%) 0/56 (0%) 0/56 (0%) 0/51 (0%)
    Intervertebral disc protrusion0/130 (0%) 0/131 (0%) 0/132 (0%) 1/135 (0.7%) 0/56 (0%) 0/56 (0%) 0/51 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Abdominal neoplasm1/130 (0.8%) 0/131 (0%) 0/132 (0%) 0/135 (0%) 0/56 (0%) 0/56 (0%) 0/51 (0%)
    Prostate cancer0/130 (0%) 0/131 (0%) 1/132 (0.8%) 0/135 (0%) 0/56 (0%) 0/56 (0%) 0/51 (0%)
    Throat cancer0/130 (0%) 0/131 (0%) 0/132 (0%) 0/135 (0%) 0/56 (0%) 1/56 (1.8%) 0/51 (0%)
    Boneneoplasm malignant0/130 (0%) 1/131 (0.8%) 0/132 (0%) 0/135 (0%) 0/56 (0%) 0/56 (0%) 0/51 (0%)
    Nervous system disorders
    Neuropathy0/130 (0%) 0/131 (0%) 1/132 (0.8%) 0/135 (0%) 0/56 (0%) 0/56 (0%) 0/51 (0%)
    Renal and urinary disorders
    Renal failure1/130 (0.8%) 3/131 (2.3%) 1/132 (0.8%) 1/135 (0.7%) 0/56 (0%) 2/56 (3.6%) 1/51 (2%)
    Renal failure chronic0/130 (0%) 1/131 (0.8%) 0/132 (0%) 0/135 (0%) 0/56 (0%) 0/56 (0%) 0/51 (0%)
    Renal failure acute0/130 (0%) 1/131 (0.8%) 0/132 (0%) 0/135 (0%) 0/56 (0%) 0/56 (0%) 0/51 (0%)
    Urinary tract infection1/130 (0.8%) 0/131 (0%) 0/132 (0%) 0/135 (0%) 0/56 (0%) 0/56 (0%) 0/51 (0%)
    Reproductive system and breast disorders
    Breast cancer0/130 (0%) 0/131 (0%) 1/132 (0.8%) 0/135 (0%) 0/56 (0%) 0/56 (0%) 0/51 (0%)
    Respiratory, thoracic and mediastinal disorders
    Bronchitis1/130 (0.8%) 0/131 (0%) 0/132 (0%) 0/135 (0%) 1/56 (1.8%) 0/56 (0%) 0/51 (0%)
    Influenza0/130 (0%) 0/131 (0%) 1/132 (0.8%) 1/135 (0.7%) 0/56 (0%) 0/56 (0%) 0/51 (0%)
    Pneumonia2/130 (1.5%) 1/131 (0.8%) 0/132 (0%) 0/135 (0%) 0/56 (0%) 0/56 (0%) 0/51 (0%)
    Lung cancer metastatic0/130 (0%) 1/131 (0.8%) 0/132 (0%) 0/135 (0%) 0/56 (0%) 0/56 (0%) 0/51 (0%)
    Skin and subcutaneous tissue disorders
    Skin Ulcer1/130 (0.8%) 0/131 (0%) 0/132 (0%) 1/135 (0.7%) 0/56 (0%) 1/56 (1.8%) 0/51 (0%)
    Surgical and medical procedures
    Arterial bypass operation0/130 (0%) 1/131 (0.8%) 0/132 (0%) 1/135 (0.7%) 0/56 (0%) 0/56 (0%) 0/51 (0%)
    Coronary arterial stent insertion0/130 (0%) 1/131 (0.8%) 1/132 (0.8%) 0/135 (0%) 0/56 (0%) 1/56 (1.8%) 0/51 (0%)
    Hysterectomy0/130 (0%) 0/131 (0%) 0/132 (0%) 1/135 (0.7%) 0/56 (0%) 0/56 (0%) 0/51 (0%)
    Knee operation0/130 (0%) 0/131 (0%) 0/132 (0%) 0/135 (0%) 0/56 (0%) 0/56 (0%) 1/51 (2%)
    Leg amputation1/130 (0.8%) 0/131 (0%) 0/132 (0%) 0/135 (0%) 0/56 (0%) 0/56 (0%) 0/51 (0%)
    Shoulder operation0/130 (0%) 0/131 (0%) 1/132 (0.8%) 0/135 (0%) 0/56 (0%) 0/56 (0%) 0/51 (0%)
    Stent placement1/130 (0.8%) 0/131 (0%) 0/132 (0%) 1/135 (0.7%) 0/56 (0%) 1/56 (1.8%) 1/51 (2%)
    Biopsy thyroid gland0/130 (0%) 0/131 (0%) 0/132 (0%) 1/135 (0.7%) 0/56 (0%) 0/56 (0%) 0/51 (0%)
    Vascular disorders
    Arteriosclerosis coronary artery1/130 (0.8%) 0/131 (0%) 1/132 (0.8%) 2/135 (1.5%) 0/56 (0%) 0/56 (0%) 0/51 (0%)
    cerebrovascular accident1/130 (0.8%) 0/131 (0%) 2/132 (1.5%) 1/135 (0.7%) 0/56 (0%) 0/56 (0%) 0/51 (0%)
    Coronary artery disease0/130 (0%) 1/131 (0.8%) 0/132 (0%) 1/135 (0.7%) 1/56 (1.8%) 0/56 (0%) 0/51 (0%)
    Hypertension1/130 (0.8%) 0/131 (0%) 2/132 (1.5%) 3/135 (2.2%) 0/56 (0%) 0/56 (0%) 1/51 (2%)
    Hypotension0/130 (0%) 1/131 (0.8%) 0/132 (0%) 0/135 (0%) 0/56 (0%) 0/56 (0%) 0/51 (0%)
    Ischaemic stroke3/130 (2.3%) 0/131 (0%) 0/132 (0%) 0/135 (0%) 0/56 (0%) 1/56 (1.8%) 0/51 (0%)
    Peripheral vascular disorder0/130 (0%) 1/131 (0.8%) 0/132 (0%) 0/135 (0%) 0/56 (0%) 0/56 (0%) 0/51 (0%)
    Arterial occlusive disease0/130 (0%) 0/131 (0%) 1/132 (0.8%) 0/135 (0%) 0/56 (0%) 0/56 (0%) 0/51 (0%)
    Embolism1/130 (0.8%) 0/131 (0%) 0/132 (0%) 0/135 (0%) 0/56 (0%) 0/56 (0%) 0/51 (0%)
    Pulmonary embolism0/130 (0%) 0/131 (0%) 0/132 (0%) 1/135 (0.7%) 0/56 (0%) 0/56 (0%) 0/51 (0%)
    Other (Not Including Serious) Adverse Events
    Sham + Prompt LaserRanibizumab + Prompt LaserRanibizumab + Deferred LaserTriamcinolone + Prompt LaserSham + Ranibizumab + LaserSham + Ranibizumab + Deferred LaserSham + Triamcinolone + Laser
    Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total139/139 (100%) 97/97 (100%) 105/105 (100%) 145/145 (100%) 0/0 (NaN) 0/0 (NaN) 0/0 (NaN)
    Eye disorders
    Cataract12/139 (8.6%) 9/97 (9.3%) 10/105 (9.5%) 31/145 (21.4%) 0/0 (NaN) 0/0 (NaN) 0/0 (NaN)
    Cataract subcapsular7/139 (5%) 5/97 (5.2%) 4/105 (3.8%) 23/145 (15.9%) 0/0 (NaN) 0/0 (NaN) 0/0 (NaN)
    Eye pain22/139 (15.8%) 23/97 (23.7%) 20/105 (19%) 12/145 (8.3%) 0/0 (NaN) 0/0 (NaN) 0/0 (NaN)
    Myodesopsia8/139 (5.8%) 4/97 (4.1%) 10/105 (9.5%) 19/145 (13.1%) 0/0 (NaN) 0/0 (NaN) 0/0 (NaN)
    Vitreous floaters9/139 (6.5%) 13/97 (13.4%) 11/105 (10.5%) 23/145 (15.9%) 0/0 (NaN) 0/0 (NaN) 0/0 (NaN)
    Conjunctival haemorrhage4/139 (2.9%) 21/97 (21.6%) 25/105 (23.8%) 17/145 (11.7%) 0/0 (NaN) 0/0 (NaN) 0/0 (NaN)
    Eye Irritation9/139 (6.5%) 8/97 (8.2%) 11/105 (10.5%) 10/145 (6.9%) 0/0 (NaN) 0/0 (NaN) 0/0 (NaN)
    Intraocular pressure increased7/139 (5%) 4/97 (4.1%) 7/105 (6.7%) 55/145 (37.9%) 0/0 (NaN) 0/0 (NaN) 0/0 (NaN)
    Lacrimation increased9/139 (6.5%) 6/97 (6.2%) 16/105 (15.2%) 5/145 (3.4%) 0/0 (NaN) 0/0 (NaN) 0/0 (NaN)
    Maculopathy24/139 (17.3%) 12/97 (12.4%) 14/105 (13.3%) 9/145 (6.2%) 0/0 (NaN) 0/0 (NaN) 0/0 (NaN)
    Ocular Hyperaemia6/139 (4.3%) 10/97 (10.3%) 5/105 (4.8%) 4/145 (2.8%) 0/0 (NaN) 0/0 (NaN) 0/0 (NaN)
    Vision Blurred39/139 (28.1%) 16/97 (16.5%) 20/105 (19%) 32/145 (22.1%) 0/0 (NaN) 0/0 (NaN) 0/0 (NaN)
    Visual Acuity Reduced13/139 (9.4%) 6/97 (6.2%) 8/105 (7.6%) 11/145 (7.6%) 0/0 (NaN) 0/0 (NaN) 0/0 (NaN)
    Visual Disturbance13/139 (9.4%) 7/97 (7.2%) 5/105 (4.8%) 13/145 (9%) 0/0 (NaN) 0/0 (NaN) 0/0 (NaN)
    Vitreous haemorrhage15/139 (10.8%) 3/97 (3.1%) 4/105 (3.8%) 2/145 (1.4%) 0/0 (NaN) 0/0 (NaN) 0/0 (NaN)
    General disorders
    Influenza10/139 (7.2%) 6/97 (6.2%) 6/105 (5.7%) 11/145 (7.6%) 0/0 (NaN) 0/0 (NaN) 0/0 (NaN)
    Nasopharyngitis10/139 (7.2%) 10/97 (10.3%) 10/105 (9.5%) 14/145 (9.7%) 0/0 (NaN) 0/0 (NaN) 0/0 (NaN)
    Respiratory, thoracic and mediastinal disorders
    Upper respiratory tract infection8/139 (5.8%) 12/97 (12.4%) 7/105 (6.7%) 6/145 (4.1%) 0/0 (NaN) 0/0 (NaN) 0/0 (NaN)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

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

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/TitleAdam R. Glassman, Director DRCR.net Coordinating Center
    OrganizationJaeb Center for Health Research
    Phone813-975-8690
    Emaildrcrnet@jaeb.org
    Responsible Party:
    Jaeb Center for Health Research
    ClinicalTrials.gov Identifier:
    NCT00444600
    Other Study ID Numbers:
    • NEI-133
    • U10EY018817-03
    • U10EY014229-07
    • U10EY014231-09
    First Posted:
    Mar 8, 2007
    Last Update Posted:
    Oct 7, 2019
    Last Verified:
    Sep 1, 2019