Levodopa for the Treatment of Residual Amblyopia
Condition: Amblyopia
MeSH terms: Amblyopia
Intervention: Levodopa/Carbidopa; Placebo; Patching
Intervention description: Oral levodopa 0.76 mg/kg tid with carbidopa 0.17 mg/kg tid; Oral placebo tid; Two hours of daily patching
Intervention MeSH terms: Levodopa; Carbidopa
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 139.0
Sex: All
Minimum age: 7 Years
Maximum age: 12 Years
Healthy volunteers: No
Keywords: amblyopia, levodopa

Summary:

      The purpose of this study is to evaluate the efficacy and safety of oral levodopa and
      patching versus oral placebo and patching as treatment for residual amblyopia in children 7
      to <13 years old with visual acuity of 20/50 to 20/400 in the amblyopic eye.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Age 7 to 12

          2. Amblyopia associated with strabismus, anisometropia, or both

               -  Criteria for strabismus: One of the following criteria must be met: Heterotropia
                  at distance and/or near fixation on examination (with or without spectacles);
                  History of strabismus surgery; Documented history of strabismus which is no
                  longer present (which in the judgment of the investigator could have caused
                  amblyopia)

               -  Criteria for anisometropia: One of the following criteria must be met: ≥0.50 D
                  difference between eyes in spherical equivalent; ≥1.50 D difference between eyes
                  in astigmatism in any meridian

          3. Visual acuity, measured in each eye (amblyopic eye without cycloplegia) within 7 days
             prior to enrollment using the E-ETDRS protocol by a study certified visual acuity
             tester as follows:

               -  Visual acuity in the amblyopic eye 18 to 67 letters inclusive (20/50 to 20/400)

               -  Visual acuity in the fellow eye ≥78 letters (20/25 or better)

          4. Current amblyopia treatment (other than spectacles)

               -  12 weeks of at least 2 hours of occlusion per day prescribed for the fellow eye
                  during the immediate pre-enrollment period.

               -  While on current treatment, visual acuity has not improved one line (5 letters)
                  or more since a non-study visit at least 6 weeks ago. Both acuity measurements to
                  define no improvement must have been done using the same testing method.

               -  Treatment with atropine at any time during this pre-enrollment period is not
                  allowed.

               -  Any treatment prior to the current patching episode with stable acuity is
                  acceptable.

          5. Spectacle correction (if applicable) for measurement of enrollment visual acuity must
             meet the following criteria and be based on a cycloplegic refraction that is no more
             than 6 months old:

               1. Requirements for spectacle correction:

                    -  Spherical equivalent must be within 0.50 D of fully correcting the
                       anisometropia.

                    -  Hypermetropia of 3.00D or more must be corrected.

                    -  Hypermetropia must not be under corrected by more than 1.50 D spherical
                       equivalent, and reduction in plus sphere must be symmetric in the two eyes.

                    -  Cylinder power in both eyes must be within 0.50 D of fully correcting the
                       astigmatism.

                    -  Cylinder axis in both eyes is within 6 degrees of the axis in the spectacles
                       when cylinder power is ≥1.00 D.

                    -  Myopia of amblyopic eye greater than 0.50 D by spherical equivalent must be
                       corrected, and the glasses must not under correct the myopia by more than
                       0.25 D or overcorrect it by more than 0.50 D.

               2. Spectacles meeting above criteria must be worn :until visual acuity in amblyopic
                  eye is stable (defined as 2 consecutive visual acuity measurements by the same
                  testing method at least 4 weeks apart with no improvement of one line (5 letters)
                  or more.

          6. Eye examination within 6 months prior to enrollment

          7. Parent available for at least one year of follow-up, has access to phone), and willing
             to be contacted by clinical site and Jaeb Center staff

          8. In the investigator's judgment, the subject is likely to comply with prescribed
             treatment (e.g., no history of poor compliance with patching treatment) and unlikely
             to continue to improve by using 2 hours of patching per day alone.

        Exclusion Criteria:

          1. Myopia more than -6.00 D (spherical equivalent) in either eye.

          2. Current vision therapy or orthoptics

          3. Ocular cause for reduced visual acuity

               -  nystagmus per se does not exclude the subject if the above visual acuity criteria
                  are met

          4. Prior intraocular or refractive surgery

          5. History of narrow-angle glaucoma

          6. Bronchial asthma or severe pulmonary disease

          7. Strabismus surgery planned within 26 weeks

          8. Known allergy to levodopa or carbidopa

          9. History of dystonic reactions

         10. Current use of oral iron supplements including multivitamins containing iron during
             treatment with levodopa-carbidopa

         11. Current use of antihypertensive, anti-depressant medications, phenothiazines,
             butyrophenones, risperidone and isoniazid, non-specific monoamine oxidase inhibitors,
             or medication for the treatment of attention deficit hyperactivity disorder

         12. Known liver disease

         13. History of melanoma

         14. Known psychological problems

         15. Known skin reactions to patch or bandage adhesives

         16. Prior levodopa treatment

         17. Treatment with topical ophthalmic atropine within the past 12 weeks

         18. A physician-prescribed diet high in protein

         19. Females who are pregnant, lactating, or intend to become pregnant within the next 34
             weeks.

               -  A negative urine pregnancy test will be required for all females who have
                  experienced menarche.

               -  Requirements regarding pregnancy testing prior to enrollment may be further
                  defined by each individual Institutional Review Board.