Laser-Ranibizumab-Triamcinolone for Diabetic Macular Edema

Diabetic Retinopathy Clinical Trial

— LRT for DME  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00444600
• Other study ID #: NEI-133
• Secondary ID: U10EY018817-03U1
• Status: Completed
• Phase: Phase 3
• Start date: March 2007
• Est. completion date: February 2014

Study information

• Verified date: September 2019
• Source: Jaeb Center for Health Research
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 691
• Est. completion date: February 2014
• Est. primary completion date: December 2009
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Diabetic Macular Edema
• Diabetic Retinopathy
• Edema
• Macular Edema
• Retinal Diseases

Intervention

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.
• 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.
• 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.
• 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.

Locations

Country	Name	City	State
United States	West Texas Retina Consultants P.A.	Abilene	Texas
United States	Sall Research Medical Center	Artesia	California
United States	Southeast Retina Center, P.C.	Augusta	Georgia
United States	Retina Research Center	Austin	Texas
United States	Elman Retina Group, P.A.	Baltimore	Maryland
United States	Wilmer Eye Institute at Johns Hopkins	Baltimore	Maryland
United States	Retina Associates of Cleveland, Inc.	Beachwood	Ohio
United States	Retina-Vitreous Associates Medical Group	Beverly Hills	California
United States	Joslin Diabetes Center	Boston	Massachusetts
United States	Ophthalmic Consultants of Boston	Boston	Massachusetts
United States	University of North Carolina, Dept of Ophthalmology	Chapel Hill	North Carolina
United States	Charlotte Eye, Ear, Nose and Throat Assoc., PA	Charlotte	North Carolina
United States	Case Western Reserve University	Cleveland	Ohio
United States	Carolina Retina Center	Columbia	South Carolina
United States	Palmetto Retina Center	Columbia	South Carolina
United States	Texas Retina Associates	Dallas	Texas
United States	Medical Associates Clinic, P.C.	Dubuque	Iowa
United States	Retina Vitreous Consultants	Fort Lauderdale	Florida
United States	Retina Consultants of Southwest Florida	Fort Myers	Florida
United States	Penn State College of Medicine	Hershey	Pennsylvania
United States	Retina and Vitreous of Texas	Houston	Texas
United States	Vitreoretinal Consultants	Houston	Texas
United States	Raj K. Maturi, M.D., P.C.	Indianapolis	Indiana
United States	University of California, Irvine	Irvine	California
United States	University of Florida College of Med., Department of Ophthalmology	Jacksonville	Florida
United States	Illinois Retina Associates	Joliet	Illinois
United States	Southeastern Retina Associates, PC	Kingsport	Tennessee
United States	Southeastern Retina Associates, P.C.	Knoxville	Tennessee
United States	Central Florida Retina Institute	Lakeland	Florida
United States	Retina and Vitreous Associates of Kentucky	Lexington	Kentucky
United States	Loma Linda University Health Care, Dept. of Ophthalmology	Loma Linda	California
United States	Texas Retina Associates	Lubbock	Texas
United States	University of Wisconsin-Madison, Dept of Ophthalmology/Retina Service	Madison	Wisconsin
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Retina Center, PA	Minneapolis	Minnesota
United States	John-Kenyon American Eye Institute	New Albany	Indiana
United States	The New York Eye and Ear Infirmary/Faculty Eye Practice	New York	New York
United States	Paducah Retinal Center	Paducah	Kentucky
United States	Southern California Desert Retina Consultants, MC	Palm Springs	California
United States	University of Pennsylvania Scheie Eye Institute	Philadelphia	Pennsylvania
United States	Casey Eye Institute	Portland	Oregon
United States	Retina Northwest, PC	Portland	Oregon
United States	Eyesight Ophthalmic Services, PA	Portsmouth	New Hampshire
United States	Retina Consultants	Providence	Rhode Island
United States	Retina Consultants of Delmarva, P.A.	Salisbury	Maryland
United States	California Retina Consultants	Santa Barbara	California
United States	University of Washington Medical Center	Seattle	Washington
United States	Retina-Vitreous Surgeons of Central New York, PC	Syracuse	New York
United States	Bay Area Retina Associates	Walnut Creek	California
United States	Wake Forest University Eye Center	Winston-Salem	North Carolina

Sponsors (4)

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

Country where clinical trial is conducted

United States, 

References & Publications (14)

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. — View Citation

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. — View Citation

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. — View Citation

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 Triamci — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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 — View Citation

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 r — View Citation

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. — View Citation

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 tri — View Citation

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. — View Citation

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. — View Citation

* Note: There are 14 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Central Subfield Thickness < 250 With at Least a 25 Micron Decrease From Baseline to 1 Year		1 Year
Other	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
Other	Eyes With Alternative Treatments Prior to the 1-year Visit	Each combination of treatment only counted once.	1 Year
Other	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
Other	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
Other	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
Other	Major Ocular Adverse Events During First Year of Follow-Up		1 Year
Primary	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
Primary	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
Primary	Change in Visual Acuity From Baseline to 1 Year Among Eyes That Were Pseudophakic at Baseline		from baseline to 1 Year
Primary	Change in Visual Acuity From Baseline to 1 Year Among Eyes That Had Prior Treatment for Diabetic Macular Edema		from baseline to 1 Year
Primary	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
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	Percentage of Eyes Receiving Laser at the 48 Week Visit (%)		1 Year
Secondary	Mean Optical Coherence Tomography Retinal Volume at 1 Year		1 Year
Secondary	Mean Change in Optical Coherence Tomography Retinal Volume From Baseline to 1 Year		from baseline to 1 Year

External Links

•   DRCR Retina Network