Laser-Ranibizumab-Triamcinolone for Proliferative Diabetic Retinopathy
Condition: Proliferative Diabetic Retinopathy; Diabetic Macular Edema
MeSH terms: Macular Edema; Retinal Diseases; Diabetic Retinopathy
Intervention: Ranibizumab; Triamcinolone Acetonide; Sham injection; Focal/grid laser
Intervention description: Intravitreal injection of 0.5 mg ranibizumab 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; Focal/grid laser for diabetic macular edema was performed 3 days to 10 days after the injection for all treatment groups.
Intervention MeSH terms: Triamcinolone; Triamcinolone Acetonide; Triamcinolone hexacetonide; Ranibizumab; Triamcinolone diacetate
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Outcomes Assessor)
Enrollment: 333.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Diabetic Retinopathy; Diabetic Macular Edema; Lucentis; Ranibizumab; Triamcinolone; Panretinal Photocoagulation; Combination Therapy; pdr

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.
    

Eligibility criteria:

        General Inclusion Criteria

          -  Age >= 18 years

          -  Diagnosis of diabetes mellitus (type 1 or type 2)

          -  Fellow eye (if not a study eye) meets criteria.

          -  Able and willing to provide informed consent. Study Eye Inclusion Criteria Subjects
             may have one or two study eyes. Subjects with two study eyes will be randomly assigned
             to receive sham injection at baseline and 4 weeks in one eye and either ranibizumab or
             triamcinolone in the other eye.

          -  Presence of severe nonproliferative or proliferative diabetic retinopathy for which
             investigator intends to complete panretinal photocoagulation within 49 days after
             randomization.

          -  Diabetic macular edema(DME) present on clinical exam and central subfield thickness on
             Optical Coherence Tomography (OCT) >250 microns, within 8 days of randomization.

          -  Best corrected Electronic-Early Treatment Diabetic Retinopathy Study visual acuity
             letter score >=24 (i.e., 20/320 or better), within 8 days of randomization.

          -  Media clarity, pupillary dilation, and subject cooperation sufficient to administer
             panretinal photocoagulation and obtain adequate fundus photographs and OCT.

          -  If prior macular photocoagulation has been performed, the investigator believes that
             the study eye may possibly benefit from additional focal photocoagulation.

        General Exclusion Criteria

          -  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 drugs.

          -  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 endothelial growth factor(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 12 months of the study.

        Study Eye Exclusion Criteria, Study eye only:

          -  Prior panretinal photocoagulation that was sufficiently extensive that the
             investigator does not believe that at least 1200 additional burns are needed or
             possible within 49 days after randomization.

          -  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,
             preventing visual acuity loss would not improve from resolution of macular edema
             (e.g., foveal atrophy, pigment abnormalities, dense subfoveal hard exudates,
             non-retinal 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., retinal vein or artery 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 DME 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 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 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: angle-closure glaucoma is not an exclusion criterion).

          -  History of steroid-induced intraocular pressure elevation that required intraocular
             pressure-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.

        Fellow Eye Criteria

          -  Intraocular pressure < 25 mmHg.

          -  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 criterion).

          -  No history of steroid-induced intraocular pressure elevation that required intraocular
             pressure-lowering treatment.

          -  No exam evidence of pseudoexfoliation.