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

Intravitreal Ranibizumab or Triamcinolone Acetonide in Combination With Laser Photocoagulation for Diabetic Macular Edema

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.

Study Overview

• Status: Completed
• Conditions: Diabetic Retinopathy; Diabetic Macular Edema
• Intervention / Treatment: Drug: Ranibizumab + laser; Drug: Ranibizumab + deferred laser; Drug: Triamcinolone Acetonide + laser; Drug: Sham injection + laser

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 Type: Interventional
• Enrollment (Actual): 691
• Phase: Phase 3

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Change in Visual Acuity (Letters) From Baseline to 1 Year Adjusted for Baseline Visual Acuity	Change in best correct visual acuity letter score from baseline to one year as measured by a certified tester using an electronic visual acuity testing machine based on the Early Treatment Diabetic Retinopathy Study (ETDRS) method. A positive change denotes an improvement. Best value on the scale 97, worst 0.	from baseline to 1 Year
Distribution of Change in Visual Acuity (Letters) From Baseline to 1 Year	Change in best correct visual acuity letter score as measured by a certified tester using an electronic visual acuity testing machine based on the Early Treatment Diabetic Retinopathy Study (ETDRS) method.	from baseline to 1 Year
Change in Visual Acuity From Baseline to 1 Year Among Eyes That Were Pseudophakic at Baseline		from baseline to 1 Year
Change in Visual Acuity From Baseline to 1 Year Among Eyes That Had Prior Treatment for Diabetic Macular Edema		from baseline to 1 Year
Change in Visual Acuity From Baseline to 1 Year Grouped by Baseline Visual Acuity Letter Score	Change in best correct visual acuity letter score as measured by a certified tester using an electronic visual acuity testing machine based on the Early Treatment Diabetic Retinopathy Study (ETDRS) method. A positive change denotes an improvement. Best value on the scale 97, worst 0.	from baseline to 1 Year
Change in Visual Acuity From Baseline to 1 Year Grouped by Optical Coherence Tomography Central Subfield Thickness	Change in best correct visual acuity letter score from baseline to one year as measured by a certified tester using an electronic visual acuity testing machine based on the Early Treatment Diabetic Retinopathy Study (ETDRS) method. A positive change denotes an improvement. Best value on the scale 97, worst 0.	from baseline to 1 Year
Change in Visual Acuity From Baseline to 1 Year Grouped by Diabetic Retinopathy Severity	Change in best correct visual acuity letter score from baseline to one year as measured by a certified tester using an electronic visual acuity testing machine based on the Early Treatment Diabetic Retinopathy Study (ETDRS) method. A positive change denotes an improvement. Best value on the scale 97, worst 0.	from baseline to 1 Year
Change in Visual Acuity From Baseline to 1 Year Grouped by Diffuse vs. Focal Edema as Characterized by the Investigator	Change in best correct visual acuity letter score from baseline to one year as measured by a certified tester using an electronic visual acuity testing machine based on the Early Treatment Diabetic Retinopathy Study (ETDRS) method. A positive change denotes an improvement. Best value on the scale 97, worst 0.	from baseline to 1 Year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Retinal Thickening of Central Subfield on Optical Coherence Tomography From Baseline to 1 Year	Negative change denotes an improvement.	from baseline to 1 year
Number of Injections in First Year	Maximum possible number of injections for each of the following groups: sham+prompt laser=13 sham injections;ranibizumab+prompt laser=13 ranibizumab injections; ranibizumab+deferred laser=13 ranibizumab injections; triamcinolone+prompt laser=4 triamcinolone injections and 9 sham injections.	from baseline to 1 year
Number of Laser Treatments Received Prior to the 1 Year Visit	One eye in the sham+prompt laser group did not receive laser until post 1-year due to an adverse event unrelated to study treatment. One eye in the triamcinolone+prompt laser did not receive laser until after 1-year due to missing 2 consecutive visits at the time of required laser treatment.	1 Year
Percentage of Eyes Receiving Laser at the 48 Week Visit (%)		1 Year
Mean Optical Coherence Tomography Retinal Volume at 1 Year		1 Year
Mean Change in Optical Coherence Tomography Retinal Volume From Baseline to 1 Year		from baseline to 1 Year

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Central Subfield Thickness < 250 With at Least a 25 Micron Decrease From Baseline to 1 Year		1 Year
Distribution of Logarithmic Transformation of Optical Coherence Tomography (LogOCT) Improvement and Worsening	Logarithmic transformation of optical coherence tomography central subfield thickness is calculated by taking the log base 10 of the ratio of the central subfield thickness divided by 200 and rounding to the nearest hundredth. The change is the change in the log values.	1 Year
Eyes With Alternative Treatments Prior to the 1-year Visit	Each combination of treatment only counted once.	1 Year
Change From Moderately Severe Non-proliferative Diabetic Retinopathy or Better From Baseline to 1-year	113 eyes had missing or ungradable photos at 1 year. Criteria are based on the ETDRS fundus photographic risk factors for the progression of diabetic retinopathy. ETDRS report no. 12. Ophthalmology 1991; 98:823-833	from baseline to 1 Year
Change From Severe Non-proliferative Diabetic Retinopathy or Worse From Baseline to 1-year	Criteria are based on the ETDRS fundus photographic risk factors for the progression of diabetic retinopathy. ETDRS report no. 12. Ophthalmology 1991; 98:823-833, ETDRS Severity Scale = Diabetic retinopathy absent, minimal non-proliferative diabetic retinopathy (PDR), mild to moderately severe non-PDR, severe non-PDR, scars of full pr partial panretinal photocoagulation present PDR absent, mild to moderate PDR, high risk PDR, cannot grade, missing.	from baseline to 1 Year
Cardiovascular Events According to Antiplatelet Trialists' Collaboration Through 1 Year	Antiplatelet Trialists' Collaboration is a collaborative overview of randomised trials of antiplatelet therapy - I: Prevention of death, myocardial infarction, and stroke by prolonged antiplatelet therapy in various categories of patients. Antiplatelet Trialists' Collaboration. MBJ 1994; 308:81-106. Nonfatal cerebrovascular accident includes ischemic or hemorrhagic or unknown events. Vascular death includes death from any potential vascular or unknown cause.	1 Year
Major Ocular Adverse Events During First Year of Follow-Up		1 Year

Collaborators and Investigators

• Sponsor: Jaeb Center for Health Research
• Collaborators: National Eye Institute (NEI); Genentech, Inc.; Allergan
• Investigators: Study Chair: Michael J. Elman, M.D., Elman Retina Group, PA

Publications and helpful links

General Publications

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

Helpful Links

• DRCR Retina Network

Study record dates

Study Major Dates

• Study Start: March 1, 2007
• Primary Completion (Actual): December 1, 2009
• Study Completion (Actual): February 1, 2014

Study Registration Dates

• First Submitted: March 6, 2007
• First Submitted That Met QC Criteria: March 6, 2007
• First Posted (Estimate): March 8, 2007

Study Record Updates

• Last Update Posted (Actual): October 7, 2019
• Last Update Submitted That Met QC Criteria: September 20, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Keywords: Ranibizumab; Triamcinolone; Lucentis; Diabetic Macular Edema; Combination Therapy; Diabetic Retinopathy; Laser photocoagulation
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Eye Diseases; Endocrine System Diseases; Diabetic Angiopathies; Diabetes Complications; Diabetes Mellitus; Retinal Degeneration; Macular Degeneration; Retinal Diseases; Diabetic Retinopathy; Macular Edema; Edema; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Anti-Inflammatory Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Ranibizumab; Triamcinolone; Triamcinolone Acetonide; Triamcinolone hexacetonide; Triamcinolone diacetate
• Other Study ID Numbers: NEI-133; U10EY018817-03 (U.S. NIH Grant/Contract); U10EY014231-09 (U.S. NIH Grant/Contract); U10EY014229-07 (U.S. NIH Grant/Contract)