Intravitreal Triamcinolone Acetonide Versus Laser for Diabetic Macular Edema
- Conditions
- Diabetic Macular Edema
- Interventions
- Registration Number
- NCT00367133
- Lead Sponsor
- Jaeb Center for Health Research
- Brief Summary
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.
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 840
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description 1 Standard of Care Group Standard of care group: conventional treatment consisting of focal/grid photocoagulation. 2 1mg triamcinolone acetonide Intravitreal injection of 1mg of triamcinolone acetonide 3 4mg triamcinolone acetonide Intravitreal injection of 4mg of triamcinolone acetonide
- Primary Outcome Measures
Name Time Method Change In Visual Acuity [Measured With Electronic-Early Treatment Diabetic Retinopathy Study (E-ETDRS)]Baseline to 2 Years. 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.
Median Change in Visual Acuity Baseline to 2 Years 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.
Distribution of Change in Visual Acuity Baseline to 2 Years 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.
- Secondary Outcome Measures
Name Time Method Mean Change in Central Subfield Thickness Baseline to 2 Years 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.
Median Change in Central Subfield Thickness Baseline to 2 Years 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.
Central Subfield Thickness at 2 Years 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.
Change in Visual Acuity From Baseline to 3 Years Baseline to 3 year Change in best correct visual acuity letter score as measured by a certified tester using an electronic visual acuity testing machine based on the Early Treatment Diabetic Retinopathy Study (ETDRS) method. A positive change denotes an improvement. Best Value on the scale=97, Worst Value=0
Distribution of Visual Acuity Change Baseline to 3 Years 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
Central Subfield Thickness on Optical Coherence Tomography (OCT) at Three Years 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. 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.
Change in Central Subfield Thickness on OCT Baseline to 3 Years 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.
Overall Central Subfield Thickening Decreased by >=50% Baseline to 2 Years 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.
Central Subfield Thickness < 250 Microns at 2 Years 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.
Percentage of Eyes With a Change in Central Subfield Thickness on OCT <250 Microns From Baseline to 3 Years 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.
Trial Locations
- Locations (81)
National Ophthalmic Research Institute
🇺🇸Fort Myers, Florida, United States
St. Louis University Eye Institute
🇺🇸St. Louis, Missouri, United States
Retina-Vitreous Surgeons of Central New York, PC
🇺🇸Syracuse, New York, United States
Penn State College of Medicine
🇺🇸Hershey, Pennsylvania, United States
Southeastern Retina Associates, P.C.
🇺🇸Knoxville, Tennessee, United States
Doheny Eye Institute
🇺🇸Los Angeles, California, United States
Jules Stein Eye Institute
🇺🇸Los Angeles, California, United States
Elman Retina Group, P.A.
🇺🇸Baltimore, Maryland, United States
Wilmer Ophthalmological Institute at Johns Hopkins
🇺🇸Baltimore, Maryland, United States
Retina and Vitreous Associates of Kentucky
🇺🇸Lexington, Kentucky, United States
Northwestern Medical Faculty Foundation
🇺🇸Chicago, Illinois, United States
Retina Group of Florida
🇺🇸Ft. Lauderdale, Florida, United States
Orange County Retina Medical Group
🇺🇸Santa Ana, California, United States
Carolina Retina Center
🇺🇸Columbia, South Carolina, United States
Southern California Desert Retina Consultants, MC
🇺🇸Palm Springs, California, United States
Illinois Retina Associates
🇺🇸Joliet, Illinois, United States
Sarasota Retina Institute
🇺🇸Sarasota, Florida, United States
Retina Consultants of Hawaii, Inc.
🇺🇸Aiea, Hawaii, United States
University of Rochester
🇺🇸Rochester, New York, United States
Associated Retinal Consultants
🇺🇸Grand Rapids, Michigan, United States
Texas Retina Associates
🇺🇸Lubbock, Texas, United States
Maine Vitreoretinal Consultants
🇺🇸Bangor, Maine, United States
Vision Research Foundation
🇺🇸Royal Oak, Michigan, United States
Horizon Eye Care, PA
🇺🇸Charlotte, North Carolina, United States
OSU Eye Physicians and Surgeons, LLC.
🇺🇸Dublin, Ohio, United States
West Texas Retina Consultants P.A.
🇺🇸Abilene, Texas, United States
Central Florida Retina Institute
🇺🇸Lakeland, Florida, United States
Delaware Valley Retina Associates
🇺🇸Lawrenceville, New Jersey, United States
Retina Associates of Cleveland, Inc.
🇺🇸Beachwood, Ohio, United States
Palmetto Retina Center
🇺🇸Columbia, South Carolina, United States
University of Texas Medical Branch, Dept of Ophthalmology and Visual Sciences
🇺🇸Galveston, Texas, United States
The New York Eye and Ear Infirmary/Faculty Eye Practice
🇺🇸New York, New York, United States
Case Western Reserve University
🇺🇸Cleveland, Ohio, United States
Retina Consultants
🇺🇸Providence, Rhode Island, United States
Rush University Medical Center
🇺🇸Chicago, Illinois, United States
Ophthalmic Consultants of Boston
🇺🇸Boston, Massachusetts, United States
Joslin Diabetes Center
🇺🇸Boston, Massachusetts, United States
University of Washington Medical Center
🇺🇸Seattle, Washington, United States
Charles A. Garcia, PA & Associates
🇺🇸Houston, Texas, United States
Raj K. Maturi, M.D., P.C.
🇺🇸Indianapolis, Indiana, United States
Retina and Vitreous of Texas
🇺🇸Houston, Texas, United States
Retina Consultants of Houston, PA
🇺🇸Houston, Texas, United States
Henry Ford Health System, Dept of Ophthalmology and Eye Care Services
🇺🇸Detroit, Michigan, United States
West Coast Retina Medical Group, Inc.
🇺🇸San Francisco, California, United States
Denver Health Medical Center
🇺🇸Denver, Colorado, United States
Dean A. McGee Eye Institute
🇺🇸Oklahoma City, Oklahoma, United States
Retina Northwest, PC
🇺🇸Portland, Oregon, United States
Casey Eye Institute
🇺🇸Portland, Oregon, United States
Retina Center, PA
🇺🇸Minneapolis, Minnesota, United States
Vanderbilt University Medical Center
🇺🇸Nashville, Tennessee, United States
Rocky Mountain Retina Consultants
🇺🇸Salt Lake City, Utah, United States
Kresge Eye Institute
🇺🇸Detroit, Michigan, United States
University of Minnesota
🇺🇸Minneapolis, Minnesota, United States
Valley Retina Institute
🇺🇸McAllen, Texas, United States
International Eye Center
🇺🇸Tampa, Florida, United States
Medical College of Wiconsin
🇺🇸Milwaukee, Wisconsin, United States
Eldorado Retina Associates, P.C.
🇺🇸Louisville, Colorado, United States
Loma Linda University Health Care, Dept. of Ophthalmology
🇺🇸Loma Linda, California, United States
Retina-Vitreous Associates Medical Group
🇺🇸Beverly Hills, California, United States
SCPMG Regional Offices - Kaiser Permanente
🇺🇸Baldwin Park, California, United States
Jones Eye Institute/University of Arkansas for Medical Sciences
🇺🇸Little Rock, Arkansas, United States
Florida Retina Consultants
🇺🇸Lakeland, Florida, United States
Southeast Retina Center, P.C.
🇺🇸Augusta, Georgia, United States
The Retina Group of Washington
🇺🇸Greenbelt, Maryland, United States
Paducah Retinal Center
🇺🇸Paducah, Kentucky, United States
Retina Consultants of Delmarva, P.A.
🇺🇸Salisbury, Maryland, United States
Retina Consultants, PLLC
🇺🇸Slingerlands, New York, United States
Charlotte Eye Ear Nose and Throat Assoc, PA
🇺🇸Charlotte, North Carolina, United States
Black Hills Regional Eye Institute
🇺🇸Rapid City, South Dakota, United States
University of Pennsylvania Scheie Eye Institute
🇺🇸Philadelphia, Pennsylvania, United States
University of Wisconsin-Madison, Dept. of Ophthalmology
🇺🇸Madison, Wisconsin, United States
California Retina Consultants
🇺🇸Santa Barbara, California, United States
University of California, Irvine
🇺🇸Irvine, California, United States
Bay Area Retina Associates
🇺🇸Walnut Creek, California, United States
John-Kenyon American Eye Institute
🇺🇸New Albany, Indiana, United States
Barnes Retina Institute
🇺🇸St. Louis, Missouri, United States
Connecticut Retina Consultants
🇺🇸New Haven, Connecticut, United States
University of North Carolina, Dept. of Ophthalmology
🇺🇸Chapel Hill, North Carolina, United States
Retina Associates of Hawaii, Inc.
🇺🇸Honolulu, Hawaii, United States
Wake Forest University Eye Center
🇺🇸Winston-Salem, North Carolina, United States
Retina Research Center
🇺🇸Austin, Texas, United States