Intravitreal Triamcinolone Acetonide Versus Laser for Diabetic Macular Edema
Condition: Diabetic Macular Edema
MeSH terms: Macular Edema; Edema
Intervention: Standard of Care Group; 1mg triamcinolone acetonide; 4mg triamcinolone acetonide
Intervention description: Standard of care group: conventional treatment consisting of focal/grid photocoagulation.; 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.; 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.
Intervention MeSH terms: Triamcinolone; Triamcinolone Acetonide; Triamcinolone hexacetonide; Triamcinolone diacetate
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 840.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: diabetic; macular; edema; intravitreal; triamcinolone; laser; photocoagulation; DME

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.
    

Eligibility criteria:

        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.