Laser-Ranibizumab-Triamcinolone for Proliferative Diabetic Retinopathy
- Conditions
- Diabetic Macular EdemaProliferative Diabetic Retinopathy
- Interventions
- Registration Number
- NCT00445003
- Lead Sponsor
- Jaeb Center for Health Research
- Brief Summary
The purpose of the study is to find out if treatment with an intravitreal injection of triamcinolone or an intravitreal injection of ranibizumab can prevent loss of vision caused by panretinal photocoagulation treatment. At the present time, it is not known whether intravitreal steroid or anti-vascular endothelial growth factor (anti-VEGF) injections are beneficial in preventing vision loss after panretinal photocoagulation (PRP) treatment. It is possible that one or both of the types of injections will prevent vision loss after PRP treatment. However, it is not known whether the benefits of the injections will outweigh the risks. It is possible that because of side effects, the injections may not be as good as laser alone in treating the diabetic retinopathy.
- Detailed Description
Proliferative diabetic retinopathy (PDR) is manifested in retinal neovascularization at the disc (NVD) or elsewhere (NVE). Vitreous hemorrhage or tractional detachment from PDR is a leading cause of severe visual loss and new onset blindness. Without intervention, 60 percent of individuals with diabetic retinopathy will eventually develop PDR, resulting in significant visual loss in nearly fifty percent.
Proliferative diabetic retinopathy is currently treated with panretinal photocoagulation (PRP) which destroys areas of the retina but preserves central vision. PRP is most effectively seen in a regression of new vessels, stabilization of the neovascularization, and reduced risk of visual loss. However, the treatment is associated with unavoidable side effects including macular edema with transient or permanent central vision loss, diminished vision loss, and night vision loss. The treatment applies laser burns to the peripheral retinal tissue, destroying outer photoreceptors and retinal pigment epithelium of the retina, and is thought to exert its effect by increasing oxygen delivery to the inner retina and decreasing viable hypoxic cells which are producing growth factors such as VEGF. Studies have implicated vascular endothelial growth factor (VEGF) as the substance leading to neovascularization and/or increased vascular permeability. Thus, it is reasonable to expect that inhibition of VEGF could reduce both PDR and transient vision loss from macular edema. There are several anti-VEGF drugs. Ranibizumab is the drug to be evaluated in this trial. In one trial of ranibizumab on DME, ten patients with chronic DME received a series of 0.5 mg intraocular injections. The treatments were well tolerated with no ocular or systemic adverse events. Since intraocular injections of ranibizumab significantly reduced foveal thickness and improved visual acuity in all ten patients, there is strong rationale to consider this drug as adjunctive therapy to PRP in a attempt to reduce the acute, transient edema that may occur with PRP.
Similarly, corticosteroids, a class of substances with anti-inflammatory properties, have demonstrated to inhibit the expression of VEGF. Triamcinolone acetonide is often used as a periocular injection for the treatment of cystoid macular edema (CME) secondary to uveitis. Clinically, triamcinolone acetonide is used in the treatment of proliferative vitreoretinopathy and choroidal neovascularization. Studies on patients with proliferative diabetic retinopathy randomly assigned to receive 4 mg triamcinolone 10 to 15 days prior to PRP treatment showed a reduction in central macular thickening, and fluorescein leakage was greater in the injection group than in the control group at 9 and 12 months follow up. Mean visual acuity improved by one line in the injection group and worsened by two lines in the control group.
In summary, there is strong rationale that using either intravitreal ranibizumab or intravitreal triamcinolone acetonide as an adjunct to PRP could reduce the magnitude of vision loss.
This study is being conducted to determine whether intravitreal injection of an anti-VEGF drug or an intravitreal injection of a corticosteroid can reduce the occurrence of macular edema and visual acuity impairment following PRP. Subjects will be randomly assigned with equal probability to one of the following three injection groups:
* Intravitreal injection of 0.5 mg ranibizumab (Lucentis™) at baseline and 4 weeks
* Intravitreal injection of 4 mg triamcinolone acetonide at baseline and sham injection at 4 weeks
* Sham injection at baseline and 4 weeks
The initial injection (or sham) is given on the day of randomization. Focal (macular) photocoagulation is given 7 to 10 days following the injection. Panretinal (scatter) photocoagulation can be initiated either on the same day as the focal photocoagulation (immediately following the focal photocoagulation) or on a subsequent day but must be initiated within 14 days of the baseline injection. Required follow-up visits occur at 4, 14, 34 and 56 weeks.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 333
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description 0.5mg Ranibizumab plus laser Focal/grid laser Intravitreal injections of 0.5mg Ranibizumab at baseline and at 4 weeks. Focal/grid laser for diabetic macular edema was performed 3 days to 10 days after the injection for all treatment groups. 4-mg Triamcinolone Acetonide plus Laser Focal/grid laser 4-mg Triamcinolone Acetonide at baseline and sham injection at 4 weeks. Focal/grid laser for diabetic macular edema was performed 3 days to 10 days after the injection for all treatment groups. Sham injection plus laser Sham injection Sham injection at baseline and 4 weeks. Focal/grid laser for diabetic macular edema was performed 3 days to 10 days after the injection for all treatment groups. Sham injection plus laser Focal/grid laser Sham injection at baseline and 4 weeks. Focal/grid laser for diabetic macular edema was performed 3 days to 10 days after the injection for all treatment groups. 0.5mg Ranibizumab plus laser Ranibizumab Intravitreal injections of 0.5mg Ranibizumab at baseline and at 4 weeks. Focal/grid laser for diabetic macular edema was performed 3 days to 10 days after the injection for all treatment groups. 4-mg Triamcinolone Acetonide plus Laser Triamcinolone Acetonide 4-mg Triamcinolone Acetonide at baseline and sham injection at 4 weeks. Focal/grid laser for diabetic macular edema was performed 3 days to 10 days after the injection for all treatment groups.
- Primary Outcome Measures
Name Time Method Change in Electronic Early Treatment Diabetic Retinopathy Study Visual Acuity Letter Score From Baseline to 14 Weeks baseline to 14 weeks Visual Acuity was measured with the Electronic Early Treatment Study (E-ETDRS) visual acuity test. Unit of measure is based on the E-ETDRS letter score scale, 0-97, where 0 = worst and 97 = best.
- Secondary Outcome Measures
Name Time Method Additional Treatments for Diabetic Macular Edema 14 weeks to 56-weeks Each combination of treatment is only counted once per treatment eye. Participants could have 2 study eyes, with random assignments to different treatments.
Total Optical Coherence Tomography Retinal Volume Baseline to 14-weeks Missing/ungradable as follows: Sham = 49, Ranibizumab = 37, Triamcinolone = 39. Visits occured between 70 days and 153 days from randomization adjusted for baseline optical coherence tomography (OCT) retinal volume, OCT retinal thickness and visual acuity, number of planned panretinal photocoagulation sittings, and correlation between 2 study eyes. Confidence intervals are adjusted for multiple comparisons.
Number of Eyes With Additional Number of Treatments for Diabetic Macular Edema 14 weeks to 56-weeks Treatments include any type or combination of treatment for diabetic macular edema. Eyes were only counted once, when receiving a combination of treatments.
Eyes With Anti-vascular Endothelial Growth Factor Treatment for Diabetic Macular Edema 14 weeks to 56-weeks Change in Optical Coherence Tomography Central Subfield Thickness Baseline to 14 weeks Change in Visual Acuity From Baseline baseline to 56-weeks Visual Acuity was measured with the Electronic Early Treatment Study (E-ETDRS) visual acuity test. Unit of measure is based on the E-ETDRS letter score scale, 0-97, where 0 = worst and 97 = best.
Change in Optical Coherence Tomography Retinal Volume Baseline to 14 weeks Missing or un-gradable data as follows for the sham plus focal/grid/panretinal photocoagulation laser, triamcinolone plus focal/grid panretinal photocoagulation laser, and Ranibizumab groups were 49, 37, and 39, respectively
Trial Locations
- Locations (54)
University of Illinois at Chicago Medical Center
🇺🇸Chicago, Illinois, United States
Bay Area Retina Associates
🇺🇸Walnut Creek, California, United States
Southeast Retina Center, P.C.
🇺🇸Augusta, Georgia, United States
Medical Associates Clinic, P.C.
🇺🇸Dubuque, Iowa, United States
Eyesight Ophthalmic Services, PA
🇺🇸Portsmouth, New Hampshire, United States
Southeastern Retina Associates, P.C.
🇺🇸Knoxville, Tennessee, United States
The New York Eye and Ear Infirmary/Faculty Eye Practice
🇺🇸New York, New York, United States
University of Pennsylvania Scheie Eye Institute
🇺🇸Philadelphia, Pennsylvania, United States
Texas Retina Associates
🇺🇸Lubbock, Texas, United States
University of California, Irvine
🇺🇸Irvine, California, United States
Charlotte Eye, Ear, Nose and Throat Assoc., PA
🇺🇸Charlotte, North Carolina, United States
Loma Linda University Health Care, Dept. of Ophthalmology
🇺🇸Loma Linda, California, United States
John-Kenyon American Eye Institute
🇺🇸New Albany, Indiana, United States
Horizon Eye Care, PA
🇺🇸Charlotte, North Carolina, United States
Retina-Vitreous Surgeons of Central New York, PC
🇺🇸Syracuse, New York, United States
Paducah Retinal Center
🇺🇸Paducah, Kentucky, United States
OSU Eye Physicians and Surgeons, LLC.
🇺🇸Dublin, Ohio, United States
Retina Consultants
🇺🇸Providence, Rhode Island, United States
Eldorado Retina Associates, P.C.
🇺🇸Louisville, Colorado, United States
Retina Center, PA
🇺🇸Minneapolis, Minnesota, United States
University of Minnesota
🇺🇸Minneapolis, Minnesota, United States
Raj K. Maturi, M.D., P.C.
🇺🇸Indianapolis, Indiana, United States
Ophthalmic Consultants of Boston
🇺🇸Boston, Massachusetts, United States
Joslin Diabetes Center
🇺🇸Boston, Massachusetts, United States
Case Western Reserve University
🇺🇸Cleveland, Ohio, United States
Casey Eye Institute
🇺🇸Portland, Oregon, United States
Retina and Vitreous of Texas
🇺🇸Houston, Texas, United States
Vitreoretinal Consultants
🇺🇸Houston, Texas, United States
Retinal Consultants of San Antonio
🇺🇸San Antonio, Texas, United States
University of Washington Medical Center
🇺🇸Seattle, Washington, United States
Sall Research Medical Center
🇺🇸Artesia, California, United States
Retina-Vitreous Associates Medical Group
🇺🇸Beverly Hills, California, United States
Southern California Desert Retina Consultants, MC
🇺🇸Palm Springs, California, United States
California Retina Consultants
🇺🇸Santa Barbara, California, United States
Retina Northwest, PC
🇺🇸Portland, Oregon, United States
Penn State College of Medicine
🇺🇸Hershey, Pennsylvania, United States
Palmetto Retina Center
🇺🇸Columbia, South Carolina, United States
West Texas Retina Consultants P.A.
🇺🇸Abilene, Texas, United States
Maine Vitreoretinal Consultants
🇺🇸Bangor, Maine, United States
Carolina Retina Center
🇺🇸Columbia, South Carolina, United States
Elman Retina Group, P.A.
🇺🇸Baltimore, Maryland, United States
Valley Retina Institute
🇺🇸McAllen, Texas, United States
University of Wisconsin-Madison, Dept of Ophthalmology/Retina Service
🇺🇸Madison, Wisconsin, United States
Illinois Retina Associates
🇺🇸Joliet, Illinois, United States
Retina Consultants of Delmarva, P.A.
🇺🇸Salisbury, Maryland, United States
Retina Consultants of Southwest Florida
🇺🇸Fort Myers, Florida, United States
Retina Vitreous Consultants
🇺🇸Ft. Lauderdale, Florida, United States
Central Florida Retina Institute
🇺🇸Lakeland, Florida, United States
Wilmer Ophthalmological Institute at Johns Hopkins
🇺🇸Baltimore, Maryland, United States
Southeastern Retina Associates, PC
🇺🇸Kingsport, Tennessee, United States
University of North Carolina, Dept of Ophthalmology
🇺🇸Chapel Hill, North Carolina, United States
Wake Forest University Eye Center
🇺🇸Winston-Salem, North Carolina, United States
Retina Research Center
🇺🇸Austin, Texas, United States
Virginia Retina Center
🇺🇸Leesburg, Virginia, United States