Intravitreal Triamcinolone Acetonide Versus Laser for Diabetic Macular Edema (IVT)

A Randomized Trial Comparing Intravitreal Triamcinolone Acetonide and Laser Photocoagulation for Diabetic Macular Edema

The study involves the enrollment of patients over 18 years of age with diabetic macular edema(DME). Patients with one study eye will be randomly assigned (stratified by visual acuity and prior laser) with equal probability to one of the three treatment groups:

1. Laser photocoagulation
2. 1mg intravitreal triamcinolone acetonide injection
3. 4mg intravitreal triamcinolone acetonide injection

For patients with two study eyes (both eyes eligible at the time of randomization), the right eye (stratified by visual acuity and prior laser) will be randomly assigned with equal probabilities to one of the three treatment groups listed above. The left eye will be assigned to the alternative treatment (laser or triamcinolone). If the left eye is assigned to triamcinolone, then the dose (1mg or 4 mg) will be randomly assigned to the left eye with equal probability (stratified by visual acuity and prior laser).

The study drug, triamcinolone acetonide, has been manufactured as a sterile intravitreal injectable by Allergan. Study eyes assigned to an intravitreal triamcinolone injection will receive a dose of either 1mg or 4mg. There is no indication of which treatment regimen will be better.

Patients enrolled into the study will be followed for three years and will have study visits every 4 months after receiving their assigned study treatment. In addition, standard of care post-treatment visits will be performed at 4 weeks after each intravitreal injection.

Study Overview

• Status: Completed
• Conditions: Diabetic Macular Edema
• Intervention / Treatment: Procedure: Standard of Care Group; Drug: 1mg triamcinolone acetonide; Drug: 4mg triamcinolone acetonide

Detailed Description

Diabetic retinopathy is a major cause of visual impairment in the United States. Diabetic macular edema (DME) is a manifestation of diabetic retinopathy that produces loss of central vision. Data from the Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR) estimate that after 15 years of known diabetes, the prevalence of diabetic macular edema is approximately 20% in patients with type 1 diabetes mellitus (DM), 25% in patients with type 2 DM who are taking insulin, and 14% in patients with type 2 DM who do not take insulin.

In a review of three early studies concerning the natural history of diabetic macular edema, Ferris and Patz found that 53% of 135 eyes with diabetic macular edema, presumably all involving the center of the macula, lost two or more lines of visual acuity over a two year period. In the Early Treatment Diabetic Retinopathy Study (ETDRS), 33% of 221 untreated eyes available for follow-up at the 3-year visit, all with edema involving the center of the macula at baseline, had experienced a 15 or more letter decrease in visual acuity score (equivalent to a doubling of the visual angle, e.g., 20/25 to 20/50, and termed "moderate visual acuity loss").

In the ETDRS, focal/grid photocoagulation of eyes with clinically significant macular edema (CSME) reduced the risk of moderate visual loss by approximately 50% (from 24% to 12%, three years after initiation of treatment). Therefore, 12% of treated eyes developed moderate visual loss in spite of treatment. Furthermore, approximately 40% of treated eyes that had retinal thickening involving the center of the macula at baseline still had thickening involving the center at 12 months, as did 25% of treated eyes at 36 months.

Although several treatment modalities are currently under investigation, the only demonstrated means to reduce the risk of vision loss from diabetic macular edema are laser photocoagulation, as demonstrated by the ETDRS, and intensive glycemic control, as demonstrated by the Diabetes Control and Complications Trial (DCCT) and the United Kingdom Prospective Diabetes Study (UKPDS). In the DCCT, intensive glucose control reduced the risk of onset of diabetic macular edema by 23% compared with conventional treatment. Long-term follow-up of patients in the DCCT show a sustained effect of intensive glucose control, with a 58% risk reduction in the development of diabetic macular edema for the DCCT patients followed in the Epidemiology of Diabetes Interventions and Complications Study.

The frequency of an unsatisfactory outcome following laser photocoagulation in some eyes with diabetic macular edema has prompted interest in other treatment modalities. One such treatment is pars plana vitrectomy. These studies suggest that vitreomacular traction, or the vitreous itself, may play a role in increased retinal vascular permeability. Removal of the vitreous or relief of mechanical traction with vitrectomy and membrane stripping may be followed by substantial resolution of macular edema and corresponding improvement in visual acuity. However, this treatment may be applicable only to a specific subset of eyes with diabetic macular edema. It also requires a complex surgical intervention with its inherent risks, recovery time, and expense. Other treatment modalities such as pharmacologic therapy with oral protein kinase C inhibitors and antibodies targeted at vascular endothelial growth factor (VEGF) are under investigation. The use of intravitreal corticosteroids is another treatment modality that has generated recent interest.

The optimal dose of corticosteroid to maximize efficacy with minimum side effects is not known. A 4mg dose of Kenalog is principally being used in clinical practice. However, this dose has been used based on feasibility rather than scientific principles.

There is also experience using Kenalog doses of 1mg and 2mg. These doses anecdotally have been reported to reduce the macular edema. There is a rationale for using a dose lower than 4mg. Glucocorticoids bind to glucocorticoid receptors in the cell cytoplasm, and the steroid-receptor complex moves to the nucleus where it regulates gene expression. The steroid-receptor binding occurs with high affinity (low dissociation constant (Kd) which is on the order of 5 to 9 nanomolar). Complete saturation of all the receptors occurs about 20-fold higher levels, i.e., about 100-200 nanomolar. A 4mg dose of triamcinolone yields a final concentration of 7.5 millimolar, or nearly 10,000-fold more than the saturation dose. Thus, the effect of a 1mg dose may be equivalent to that of a 4mg dose, because compared to the 10,000-fold saturation, a 4-fold difference in dose is inconsequential. It is also possible that higher doses of corticosteroid could be less effective than lower doses due to down-regulation of the receptor. The steroid implant studies provide additional justification for evaluating a lower dose, a 0.5mg device which delivers only 0.5 micrograms per day has been observed to have a rapid effect in reducing macular edema.

There has been limited experience using doses greater than 4mg. Jonas' case series reported results using a 25mg dose. However, others have not been able to replicate this dose using the preparation procedure described by Jonas.

In the trial, 4mg and 1mg doses will be evaluated. The former will be used because it is the dose that is currently most commonly used in clinical practice and the latter because there is reasonable evidence for efficacy and the potential for lower risk. Although there is good reason to believe that a 1mg dose will reduce the macular edema, it is possible that the retreatment rate will be higher with this dose compared with 4mg since the latter will remain active in the eye for a longer duration than the former. Insufficient data are available to warrant evaluating a dose higher than 4mg at this time.

• Study Type: Interventional
• Enrollment (Actual): 840
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72205-7199
      • Jones Eye Institute/University of Arkansas for Medical Sciences
  • California
    • Baldwin Park, California, United States, 91706
      • SCPMG Regional Offices - Kaiser Permanente
    • 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
    • Los Angeles, California, United States, 90033
      • Doheny Eye Institute
    • Los Angeles, California, United States, 90095
      • Jules Stein Eye Institute
    • Palm Springs, California, United States, 92262
      • Southern California Desert Retina Consultants, MC
    • San Francisco, California, United States, 94107
      • West Coast Retina Medical Group, Inc.
    • Santa Ana, California, United States, 92705
      • Orange County Retina Medical Group
    • Santa Barbara, California, United States, 93103
      • California Retina Consultants
    • Walnut Creek, California, United States, 94598
      • Bay Area Retina Associates
  • Colorado
    • Denver, Colorado, United States, 80204
      • Denver Health Medical Center
    • Louisville, Colorado, United States, 80027
      • Eldorado Retina Associates, P.C.
  • Connecticut
    • New Haven, Connecticut, United States, 06519-1600
      • Connecticut Retina Consultants
    • New Haven, Connecticut, United States, 06519
      • Connecticut Retina Consultants
  • Florida
    • Fort Myers, Florida, United States, 33912
      • National Ophthalmic Research Institute
    • Ft. Lauderdale, Florida, United States, 33334
      • Retina Group of Florida
    • Lakeland, Florida, United States, 33805
      • Central Florida Retina Institute
    • Lakeland, Florida, United States, 33805
      • Florida Retina Consultants
    • Sarasota, Florida, United States, 34239
      • Sarasota Retina Institute
    • Tampa, Florida, United States, 33603
      • International Eye Center
  • Georgia
    • Augusta, Georgia, United States, 30909
      • Southeast Retina Center, P.C.
  • Hawaii
    • Aiea, Hawaii, United States, 96701
      • Retina Consultants of Hawaii, Inc.
    • Honolulu, Hawaii, United States, 96813
      • Retina Associates of Hawaii, Inc.
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center
    • Chicago, Illinois, United States, 60611
      • Northwestern Medical Faculty Foundation
    • Joliet, Illinois, United States, 60435
      • Illinois Retina Associates
  • Indiana
    • Indianapolis, Indiana, United States, 46290
      • Raj K. Maturi, M.D., P.C.
    • New Albany, Indiana, United States, 47150
      • John-Kenyon American Eye Institute
  • Kentucky
    • Lexington, Kentucky, United States, 40509-1802
      • Retina and Vitreous Associates of Kentucky
    • Paducah, Kentucky, United States, 42001
      • Paducah Retinal Center
  • Maine
    • Bangor, Maine, United States, 04401
      • Maine Vitreoretinal Consultants
  • Maryland
    • Baltimore, Maryland, United States, 21237
      • Elman Retina Group, P.A.
    • Baltimore, Maryland, United States, 21287-9277
      • Wilmer Ophthalmological Institute at Johns Hopkins
    • Greenbelt, Maryland, United States, 20770-3502
      • The Retina Group of Washington
    • 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
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health System, Dept of Ophthalmology and Eye Care Services
    • Detroit, Michigan, United States, 48201-1423
      • Kresge Eye Institute
    • Grand Rapids, Michigan, United States, 49546
      • Associated Retinal Consultants
    • Royal Oak, Michigan, United States, 48073
      • Vision Research Foundation
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota
    • Minneapolis, Minnesota, United States, 55404
      • Retina Center, PA
  • Missouri
    • St. Louis, Missouri, United States, 63110
      • Barnes Retina Institute
    • St. Louis, Missouri, United States, 63104
      • St. Louis University Eye Institute
  • New Jersey
    • Lawrenceville, New Jersey, United States, 08648
      • Delaware Valley Retina Associates
  • New York
    • New York, New York, United States, 10003
      • The New York Eye and Ear Infirmary/Faculty Eye Practice
    • Rochester, New York, United States, 14642
      • University of Rochester
    • Slingerlands, New York, United States, 12159
      • Retina Consultants, PLLC
    • Syracuse, New York, United States, 13224
      • Retina-Vitreous Surgeons of Central New York, PC
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina, Dept. of Ophthalmology
    • Charlotte, North Carolina, United States, 28210
      • Charlotte Eye Ear Nose and Throat Assoc, PA
    • Charlotte, North Carolina, United States, 28211
      • Horizon Eye Care, 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
    • Dublin, Ohio, United States, 43017
      • OSU Eye Physicians and Surgeons, LLC.
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Dean A. McGee Eye Institute
  • 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
  • South Dakota
    • Rapid City, South Dakota, United States, 57701
      • Black Hills Regional Eye Institute
  • Tennessee
    • Knoxville, Tennessee, United States, 37909
      • Southeastern Retina Associates, P.C.
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center
  • Texas
    • Abilene, Texas, United States, 79605
      • West Texas Retina Consultants P.A.
    • Arlington, Texas, United States, 76012
      • Texas Retina Associates
    • Austin, Texas, United States, 78705
      • Retina Research Center
    • Dallas, Texas, United States, 75231
      • Texas Retina Associates
    • Galveston, Texas, United States, 77555-1106
      • University of Texas Medical Branch, Dept of Ophthalmology and Visual Sciences
    • Houston, Texas, United States, 77030
      • Retina Consultants of Houston, PA
    • Houston, Texas, United States, 77025
      • Retina and Vitreous of Texas
    • Houston, Texas, United States, 77002
      • Charles A. Garcia, PA & Associates
    • Lubbock, Texas, United States, 79424
      • Texas Retina Associates
    • McAllen, Texas, United States, 78503
      • Valley Retina Institute
  • Utah
    • Salt Lake City, Utah, United States, 84107
      • Rocky Mountain Retina Consultants
  • Washington
    • Seattle, Washington, United States, 98195
      • University of Washington Medical Center
  • Wisconsin
    • Madison, Wisconsin, United States, 53705
      • University of Wisconsin-Madison, Dept. of Ophthalmology
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wiconsin

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

To be eligible, the following inclusion criteria must be met:

1. Age ≥18 years
2. Diagnosis of diabetes mellitus (type 1 or type 2)
3. Able and willing to provide informed consent.
4. Patient understands that (1) if both eyes are eligible at the time of randomization, one eye will receive intravitreal triamcinolone acetonide and one eye will receive laser, and (2) if only one eye is eligible at the time of randomization and the fellow eye develops DME later, then the fellow eye will not receive intravitreal triamcinolone acetonide if the study eye received intravitreal triamcinolone acetonide (however, if the study eye was assigned to the laser group, then the fellow eye may be treated with the 4mg dose of the study intravitreal triamcinolone acetonide formulation, provided the eye assigned to laser has not received an intravitreal injection; such an eye will not be a "study eye" but since it is receiving study drug, it will be followed for adverse effects).

Exclusion Criteria

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

7. History of chronic renal failure requiring dialysis or kidney transplant.

8. A condition that, in the opinion of the investigator, would preclude participation in the study (e.g., unstable medical status including blood pressure and glycemic control). Note: Patients in poor glycemic control who, within the last 4 months, initiated intensive insulin treatment (a pump or multiple daily injections) or plan to do so in the next 4 months should not be enrolled.

9. Participation in an investigational trial within 30 days of study entry that involved treatment with any drug that has not received regulatory approval at the time of study entry.

10. Known allergy to any corticosteroid or any component of the delivery vehicle.

11. History of systemic (e.g., oral, IV, IM, epidural, bursal) corticosteroids within 4 months prior to randomization or topical, rectal, or inhaled corticosteroids in current use more than 2 times per week.

12. Patient is expecting to move out of the area of the clinical center to an area not covered by another clinical center during the 3 years of the study.

13. Blood pressure > 180/110 (systolic above 180 OR diastolic above 110). Note: If blood pressure is brought below 180/110 by anti-hypertensive treatment, patient can become eligible.

Study Eye Eligibility

Inclusion

1. Best corrected Electronic-Early Treatment Diabetic Retinopathy Study (e-ETDRS) visual acuity score of ≥ 24 letters (i.e., 20/320 or better) and ≤73 letters (i.e., 20/40 or worse).
2. Definite retinal thickening due to diabetic macular edema based on clinical exam involving the center of the macula.
3. Mean retinal thickness on two Optical Coherence Tomography (OCT) measurements ≥250 microns in the central subfield.

4. Media clarity, pupillary dilation, and patient cooperation sufficient for adequate fundus photographs.

   Exclusion

5. Macular edema is considered to be due to a cause other than diabetic macular edema.
6. An ocular condition is present such that, in the opinion of the investigator, visual acuity would not improve from resolution of macular edema (e.g., foveal atrophy, pigmentary changes, dense subfoveal hard exudates, nonretinal condition).
7. 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, Irvine-Gass Syndrome, etc.)
8. 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).
9. History of prior treatment with intravitreal corticosteroids.
10. History of peribulbar steroid injection within 6 months prior to randomization.
11. History of focal/grid macular photocoagulation within 15 weeks (3.5 months) prior to randomization.Note: Patients are not required to have had prior macular photocoagulation to be enrolled. If prior macular photocoagulation has been performed, the investigator should believe that the patient may possibly benefit from additional photocoagulation.
12. History of panretinal scatter photocoagulation (PRP) within 4 months prior to randomization.
13. Anticipated need for PRP in the 4 months following randomization.
14. History of prior pars plana vitrectomy.
15. History of major ocular surgery (including cataract extraction, scleral buckle, any intraocular surgery, etc.) within prior 6 months or anticipated within the next 6 months following randomization.
16. History of YAG capsulotomy performed within 2 months prior to randomization.
17. Intraocular pressure ≥25 mmHg.
18. History of open-angle glaucoma (either primary open-angle glaucoma or other cause of open-angle glaucoma.) Note: Angle-closure glaucoma is not an exclusion. A history of ocular hypertension is not an exclusion as long as (1) intraocular pressure (IOP) is <25 mm Hg, (2) the patient is using no more than one topical glaucoma medication, (3) the most recent visual field, performed within the last 12 months, is normal (if abnormalities are present on the visual field they must be attributable to the patient's diabetic retinopathy), and (4) the optic disc does not appear glaucomatous. If the intraocular pressure is 22 to <25 mm Hg, then the above criteria for ocular hypertension eligibility must be met.
19. History of steroid-induced intraocular pressure elevation that required IOP-lowering treatment.
20. History of prior herpetic ocular infection.
21. Exam evidence of ocular toxoplasmosis.
22. Aphakia.
23. Exam evidence of pseudoexfoliation.
24. Exam evidence of external ocular infection, including conjunctivitis, chalazion, or significant blepharitis.

In patients with only one eye meeting criteria to be a study eye at the time of randomization, the fellow eye must meet the following criteria:

1. Best corrected e-ETDRS visual acuity score ≥19 letters (i.e., 20/400 or better).
2. No prior treatment with intravitreal corticosteroids.
3. Intraocular pressure < 25 mmHg.
4. No history of open-angle glaucoma (either primary open-angle glaucoma or other cause of open-angle glaucoma.)Note: Angle-closure glaucoma is not an exclusion. A history of ocular hypertension is not an exclusion as long as (1) intraocular pressure is <25 mmHg, (2) the patient is using no more than one topical glaucoma medication, (3) the most recent visual field, performed within the last 12 months, is normal (if abnormalities are present on the visual field they must be attributable to the patient's diabetic retinopathy), and (4) the optic disc does not appear glaucomatous. If the intraocular pressure is 22 to <25 mmHg, then the above criteria for ocular hypertension eligibility must be met.
5. No history of steroid-induced intraocular pressure elevation that required IOP-lowering treatment.
6. No exam evidence of pseudoexfoliation.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 1; Standard of care group: conventional treatment consisting of focal/grid photocoagulation.	Procedure: Standard of Care Group; Standard of care group: conventional treatment consisting of focal/grid photocoagulation.; Other Names: soc with laser; modified ETDRS photocoagulation
Experimental: 2; Intravitreal injection of 1mg of triamcinolone acetonide	Drug: 1mg triamcinolone acetonide; Intravitreal injection of 1mg of triamcinolone acetonide at baseline. At each 4-month interval visit, the investigator will assess whether persistent or recurrent DME is present that warrants retreatment with the randomization assigned treatment. Retreatment, when indicated, will be performed within four weeks after the follow-up visit. Retreatment should not be performed sooner than 3.5 months from the time of the last treatment.; Other Names: corticosteroid
Experimental: 3; Intravitreal injection of 4mg of triamcinolone acetonide	Drug: 4mg triamcinolone acetonide; 4mg intravitreal triamcinolone acetonide injection at baseline. At each 4-month interval visit, the investigator will assess whether persistent or recurrent DME is present that warrants retreatment with the randomization assigned treatment. Retreatment, when indicated, will be performed within four weeks after the follow-up visit. Retreatment should not be performed sooner than 3.5 months from the time of the last treatment.; Other Names: corticosteroid

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change In Visual Acuity [Measured With Electronic-Early Treatment Diabetic Retinopathy Study (E-ETDRS)]Baseline to 2 Years.	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.	Baseline to 2 Years
Median Change in Visual Acuity Baseline to 2 Years	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.	Baseline to 2 Years
Distribution of Change in Visual Acuity Baseline to 2 Years	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.	baseline to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Central Subfield Thickness at 2 Years	Median central subfield thickness at two-years. Optical coherence Tomography (OCT) images were obtained by a certified operator using the Zeiss Stratus OCT machine. If the automated thickness measurements were judged by the reading center to be inaccurate, center point thickness was measured manually, and this value was used to impute a value for the central subfield.	2 Years
Mean Change in Central Subfield Thickness Baseline to 2 Years	Overall central subfield change from baseline. Optical coherence Tomography (OCT) images were obtained by a certified operator using the Zeiss Stratus OCT machine. The average of 2 baseline central subfield thickness measurements was used for analysis.If the automated thickness measurements were judged by the reading center to be inaccurate, center point thickness was measured manually, and this value was used to impute a value for the central subfield. Negative change denotes and improvement.	Baseline to 2 years
Median Change in Central Subfield Thickness Baseline to 2 Years	Overall central subfield change from baseline. Optical coherence Tomography (OCT) images were obtained by a certified operator using the Zeiss Stratus OCT machine. The average of 2 baseline central subfield thickness measurements was used for analysis.If the automated thickness measurements were judged by the reading center to be inaccurate, center point thickness was measured manually, and this value was used to impute a value for the central subfield. Negative change denotes an improvement.	Baseline to 2 Years
Overall Central Subfield Thickening Decreased by >=50% Baseline to 2 Years	Overall central subfield change from baseline. Optical coherence Tomography (OCT) images were obtained by a certified operator using the Zeiss Stratus OCT machine. If the automated thickness measurements were judged by the reading center to be inaccurate, center point thickness was measured manually, and this value was used to impute a value for the central subfield.	Baseline to 2 Years
Central Subfield Thickness < 250 Microns at 2 Years	Overall central subfield change from baseline. Optical coherence Tomography (OCT) images were obtained by a certified operator using the Zeiss Stratus OCT machine. If the automated thickness measurements were judged by the reading center to be inaccurate, center point thickness was measured manually, and this value was used to impute a value for the central subfield.	2 Years
Change in Visual Acuity From Baseline to 3 Years	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.	Baseline to 3 year
Change in Visual Acuity From Baseline to 3 Years	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 Value=0	Baseline to 3 year
Distribution of Visual Acuity Change Baseline to 3 Years	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	Baseline to 3 years
Central Subfield Thickness on Optical Coherence Tomography (OCT) at Three Years	Overall central subfield change from baseline. Optical coherence Tomography (OCT) images were obtained by a certified operator using the Zeiss Stratus OCT machine. If the automated thickness measurements were judged by the reading center to be inaccurate, center point thickness was measured manually, and this value was used to impute a value for the central subfield.	3 years
Change in Central Subfield Thickness on OCT Baseline to 3 Years	Overall central subfield change from baseline. Optical coherence Tomography (OCT) images were obtained by a certified operator using the Zeiss Stratus OCT machine. The average of 2 baseline central subfield thickness measurements was used for analysis.If the automated thickness measurements were judged by the reading center to be inaccurate, center point thickness was measured manually, and this value was used to impute a value for the central subfield. Negative change denotes an improvement.	Baseline to 3 years
Percentage of Eyes With a Change in Central Subfield Thickness on OCT <250 Microns From Baseline to 3 Years	Overall central subfield change from baseline. Optical coherence Tomography (OCT) images were obtained by a certified operator using the Zeiss Stratus OCT machine. The average of 2 baseline central subfield thickness measurements was used for analysis.If the automated thickness measurements were judged by the reading center to be inaccurate, center point thickness was measured manually, and this value was used to impute a value for the central subfield. Negative change denotes an improvement.	Baseline to 3 years

Collaborators and Investigators

• Sponsor: Jaeb Center for Health Research
• Collaborators: National Eye Institute (NEI); Allergan
• Investigators: Study Chair: Michael Ip, M.D., University of Wisconsin Medical School

Publications and helpful links

General Publications

• 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.
• Rittiphairoj T, Mir TA, Li T, Virgili G. Intravitreal steroids for macular edema in diabetes. Cochrane Database Syst Rev. 2020 Nov 17;11(11):CD005656. doi: 10.1002/14651858.CD005656.pub3.
• Bhavsar AR, Ip MS, Glassman AR; DRCRnet and the SCORE Study Groups. The risk of endophthalmitis following intravitreal triamcinolone injection in the DRCRnet and SCORE clinical trials. Am J Ophthalmol. 2007 Sep;144(3):454-6. doi: 10.1016/j.ajo.2007.04.011.
• Ip MS, Bressler SB, Antoszyk AN, Flaxel CJ, Kim JE, Friedman SM, Qin H; Diabetic Retinopathy Clinical Research Network. A randomized trial comparing intravitreal triamcinolone and focal/grid photocoagulation for diabetic macular edema: baseline features. Retina. 2008 Jul-Aug;28(7):919-30. doi: 10.1097/IAE.0b013e31818144a7.
• Diabetic Retinopathy Clinical Research Network. A randomized trial comparing intravitreal triamcinolone acetonide and focal/grid photocoagulation for diabetic macular edema. Ophthalmology. 2008 Sep;115(9):1447-9, 1449.e1-10. doi: 10.1016/j.ophtha.2008.06.015. Epub 2008 Jul 26.
• Diabetic Retinopathy Clinical Research Network (DRCR.net); Beck RW, Edwards AR, Aiello LP, Bressler NM, Ferris F, Glassman AR, Hartnett E, Ip MS, Kim JE, Kollman C. Three-year follow-up of a randomized trial comparing focal/grid photocoagulation and intravitreal triamcinolone for diabetic macular edema. Arch Ophthalmol. 2009 Mar;127(3):245-51. doi: 10.1001/archophthalmol.2008.610.
• Aiello LP, Edwards AR, Beck RW, Bressler NM, Davis MD, Ferris F, Glassman AR, Ip MS, Miller KM; Diabetic Retinopathy Clinical Research Network. Factors associated with improvement and worsening of visual acuity 2 years after focal/grid photocoagulation for diabetic macular edema. Ophthalmology. 2010 May;117(5):946-53. doi: 10.1016/j.ophtha.2009.10.002. Epub 2010 Feb 1.
• Bressler NM, Edwards AR, Beck RW, Flaxel CJ, Glassman AR, Ip MS, Kollman C, Kuppermann BD, Stone TW; Diabetic Retinopathy Clinical Research Network. Exploratory analysis of diabetic retinopathy progression through 3 years in a randomized clinical trial that compares intravitreal triamcinolone acetonide with focal/grid photocoagulation. Arch Ophthalmol. 2009 Dec;127(12):1566-71. doi: 10.1001/archophthalmol.2009.308.

Study record dates

Study Major Dates

• Study Start: July 1, 2004
• Primary Completion (Actual): May 1, 2008
• Study Completion (Actual): October 1, 2008

Study Registration Dates

• First Submitted: August 3, 2006
• First Submitted That Met QC Criteria: August 18, 2006
• First Posted (Estimate): August 22, 2006

Study Record Updates

• Last Update Posted (Estimate): August 26, 2016
• Last Update Submitted That Met QC Criteria: August 25, 2016
• Last Verified: August 1, 2016

More Information

Terms related to this study

• Keywords: intravitreal; triamcinolone; edema; laser; photocoagulation; macular; DME; diabetic
• Additional Relevant MeSH Terms: Eye Diseases; Retinal Degeneration; Retinal Diseases; Macular Degeneration; Macular Edema; Edema; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Anti-Inflammatory Agents; Immunosuppressive Agents; Immunologic Factors; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Triamcinolone; Triamcinolone Acetonide; Triamcinolone hexacetonide; Triamcinolone diacetate
• Other Study ID Numbers: NEI-105; U10EY018817-03 (U.S. NIH Grant/Contract); U10EY014231-09 (U.S. NIH Grant/Contract); U10EY014229-07 (U.S. NIH Grant/Contract)