A Pilot Study of Peribulbar Triamcinolone Acetonide for Diabetic Macular Edema
Condition: Diabetic Macular Edema
MeSH terms: Macular Edema; Edema
Intervention: Focal laser photocoagulation; 40mg triamcinolone; 20mg triamcinolone; 40mg triamcinolone + laser; 20mg triamcinolone + laser
Intervention description: Focal laser photocoagulation (modified Early Treatment Diabetic Retinopathy Study technique); Posterior peribulbar injection of 40 mg triamcinolone (Kenalog); Anterior peribulbar injection of 20 mg triamcinolone; Posterior peribulbar injection of 40 mg triamcinolone followed after one month by laser; Anterior peribulbar injection of 20 mg triamcinolone followed after one month by laser
Intervention MeSH terms: Triamcinolone; Triamcinolone Acetonide; Triamcinolone hexacetonide; Triamcinolone diacetate
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Participant)
Enrollment: 113.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: diabetic; macular; edema; peribulbar; triamcinolone; acetonide; laser; photocoagulation; intraocular; DME

Summary:

      The study involves the enrollment of patients over 18 years of age with diabetic macular
      edema involving the center of the macula who have not already been given maximal laser
      treatment.

      Patients with one study eye will be randomly assigned (stratified by prior laser) with equal
      probability to one of five treatment groups:

        1. Focal laser photocoagulation (modified ETDRS technique)

        2. Posterior peribulbar injection of 40 mg triamcinolone (Kenalog)

        3. Anterior peribulbar injection of 20 mg triamcinolone

        4. Posterior peribulbar injection of 40 mg triamcinolone followed after one month by laser

        5. Anterior peribulbar injection of 20 mg triamcinolone followed after one month by laser

      For patients with two study eyes (both eyes eligible at the time of randomization), the right
      eye (stratified by prior laser) will be randomly assigned with equal probabilities to one of
      the five treatment groups listed above. If the right eye was assigned to laser only, then the
      left eye will be assigned to one of the four triamcinolone groups above with equal
      probability (stratified by prior laser). If the right eye was assigned to receive
      triamcinolone, then the left eye will receive laser only.

      Triamcinolone acetonide will be the corticosteroid utilized in this study. The triamcinolone
      acetonide preparation to be used is Kenalog. Kenalog is manufactured by Bristol Myers Squibb
      and is approved by the Food and Drug Administration for intramuscular use for a variety of
      indications. Peribulbar injections of Kenalog have been used for a wide variety of ocular
      conditions, particularly uveitis and post-cataract extraction cystoid macular edema, for many
      years.

      Two different triamcinolone regimens will be assessed in the study: 40 mg injected
      posteriorly and 20 mg injected anteriorly. There is no indication of which treatment regimen
      will be better. Although the injection behind the eye is more common than the injection near
      the front of the eye, the injection near the front of the eye has less risk of injuring the
      eye. However, it is possible that the injection near the front of the eye may increase eye
      pressure more frequently. Little is known about which of the two injections decreases macular
      edema and improves vision more often.

      Patients enrolled into the study will be followed for three years and will have study visits
      1 month, 2 months, 4 months, 8 months and annually after receiving their assigned study
      treatment. For the first 8 months of the study, patients should only be retreated with their
      randomized treatment. However, if the patient's visual acuity has decreased by 15 letters or
      more, then any treatment may be given at the investigator's discretion. After completion of
      the 8-month visit, treatment is at investigator discretion.

      The primary objective of this study is to obtain estimates of efficacy and safety outcomes
      for each of the treatment groups. These estimates will provide a basis for the sample size
      estimation and hypothesis generation in a phase III trial.
    

Eligibility criteria:

        Subject Level Criteria Inclusion

        To be eligible, the following inclusion criteria (1-4) must be met:

          1. Age ≥18 years

          2. Diagnosis of diabetes mellitus (type 1 or type 2)

          3. At least one eye meets the study eye criteria

          4. Able and willing to provide informed consent.

             Study Level Exclusion Criteria

             A patient is not eligible if any of the following exclusion criteria (5-13) are
             present:

          5. History of chronic renal failure requiring dialysis or kidney transplant.

          6. 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). 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.

          7. 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.

          8. Known allergy to any corticosteroid or any component of the delivery vehicle.

          9. 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.

         10. History of steroid-induced intraocular pressure elevation that required IOP-lowering
             treatment in either eye.

         11. Warfarin (coumadin) currently being used.

         12. Blood pressure > 180/110 (systolic above 180 OR diastolic above 110). If blood
             pressure is brought below 180/110 by anti-hypertensive treatment, patient can become
             eligible.

         13. Patient is expecting to move out of the area of the clinical center to an area not
             covered by another clinical center during the next 8 months.

             The patient must have at least one eye meeting all of the inclusion criteria (a-e) and
             none of the exclusion criteria (f-t) listed below:

             Study Eye Inclusion Criteria

               1. Best corrected electronic Early Treatment Diabetic Retinopathy Study (E-ETDRS)
                  visual acuity score of ≥69 letters (i.e., 20/40 or better).

               2. Definite retinal thickening due to diabetic macular edema based on clinical exam.

               3. Retinal thickness in the Optical Coherence Tomography (OCT) central subfield
                  measuring 250 microns or more.

               4. Maximal laser has not already been given and investigator believes that either
                  peribulbar steroids or laser may benefit the eye (note: subjects may be enrolled
                  without having received prior macular laser).

               5. Media clarity, pupillary dilation, and patient cooperation sufficient for
                  adequate fundus photographs and OCT.

                  Study Eye Exclusion Criteria

               6. Macular edema is considered to be due to a cause other than diabetic macular
                  edema.

               7. 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).

               8. 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.).

               9. History of prior treatment with intravitreal, peribulbar, or retrobulbar
                  corticosteroids for DME.

              10. 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.

              11. History of panretinal scatter photocoagulation (PRP) within 4 months prior to
                  randomization or anticipated need for PRP in the 4 months following
                  randomization.

             m. History of prior vitrectomy.

             n. 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.

             o. History of YAG capsulotomy performed within 2 months prior to randomization.

             p. Intraocular pressure ≥25 mmHg.

             q. 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
             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.
             Note: if the intraocular pressure is 22 to <25 mm Hg, then the above criteria for
             ocular hypertension eligibility must be met.

             r. History of prior herpetic ocular infection.

             s. Exam evidence of ocular toxoplasmosis.

             t. Exam evidence of pseudoexfoliation.

             A patient may have two "study eyes" only if both are eligible at the time of
             randomization.