Valproate to Help Residual Amblyopia in Kids 8-17

Inclusion Criteria:

1. Age 8-17 years
2. Amblyopia associated with strabismus and/or anisometropia

   * Criteria for strabismus: must meet at least one of the following:

     * Heterotropia at distance and/or near with or without spectacle correction
     * History of strabismus surgery
     * Documented history of strabismus that is no longer present and felt by the investigator could have caused the amblyopia
   * Criteria for anisometropia: must meet at least one of the following:

     * ≥ 0.50 D difference in spherical equivalent between eyes
     * ≥ 1.50 D difference in astigmatism in any meridian between the eyes
3. Visual acuity measured in each eye within 7 days prior to enrollment using ETDRS protocol on a study certified visual acuity tester as follows:

   * Amblyopic eye visual acuity of 20/40 - 20/400
   * Sound eye acuity of ≥ 20/25.
4. Current amblyopia treatment (other than spectacle correction)

   * Subjects actively patching at the time of enrollment screening should continue patching through enrollment
   * Visual acuity in amblyopic eye has not improved ≥ 1 line (5 letters) by the same testing method from a previous visit ≥ 8 weeks earlier while on treatment

     * Since this determination is a pre-study examination, the method of visual acuity testing is not mandated
   * Atropine treatment at any time during this pre-enrollment period is not allowed
   * Any treatment prior to the current patching episode with stable acuity is allowed
5. Spectacle correction for measurement of enrollment visual acuity must meet the following criteria and be based on a cycloplegic refraction \< 6 months old:

   • Requirement for spectacle correction:
   * Spherical equivalent must be within 0.50 D of fully correcting anisometropia
   * Hyperopia ≥ 3.00 D must be corrected
   * Hyperopia may not be undercorrected by \> 1.50 D spherical equivalent and must be symmetrically reduced in each eye
   * Cylinder power must be within 0.50 D of fully correcting the astigmatism
   * Cylinder axis must be within 6 degrees of the axis in the spectacles when the cylinder power is ≥ 1.00 D
   * Myopia of the amblyopic eye \> 0.50 D spherical equivalent must be corrected

     ◊ Myopia may not be undercorrected by \> 0.25 D or overcorrected by \> 0.50D

     • Spectacles meeting the above criteria must be worn:
   * Until visual acuity in amblyopic eye has not improved ≥ 1 line (5 letters) by the same testing method during 2 consecutive visual acuity measurements at least 4 weeks apart (i.e. minimum of 8 weeks spectacle correction) ◊ Since this determination is a pre-study examination, the method of visual acuity testing is not mandated
6. Eye examination within 6 months prior to enrollment
7. Subject must be available for at least 6 months of follow-up, have access to a phone, and be willing to be contacted by clinical staff
8. By investigator judgment, the subject is likely to comply with prescribed treatment (i.e. no prior history of poor compliance with patching) and unlikely to continue to improve with 2 hours of daily patching alone

2.2.2 Exclusions

1. Myopia \> -6.00 D spherical equivalent
2. Presence of associated findings that could cause reduced visual acuity

   • Nystagmus does not exclude the subject if the above visual acuity criteria are met
3. Previous intraocular or refractive surgery
4. Strabismus surgery planned within 16 weeks
5. Current vision therapy or orthoptics
6. Known past or present liver or kidney disease
7. Known past or present mitochondrial/metabolic disorder
8. Known past or present psychological problems
9. Known allergies or contraindications to the use of valproate or anti-epileptic medication
10. Current use of medication for the treatment of seizures, bipolar disorder, or migraine, or any medication on the appended list of medications that interact with valproate/valproate acid and its derivatives which can be found here.
11. Prior valproate use
12. Known skin reaction to patch or bandage adhesives
13. Treatment with topical atropine within the past 12 weeks
14. Individuals capable of pregnancy who are pregnant, lactating, or may become pregnant within the next 6 months

    * A negative urine pregnancy test will be required for all participants who have experienced menarche at the time of enrollment
    * Individuals capable of pregnancy must convey an active suitable plan to avoid pregnancy that includes at least one of the following:
    * Hormonal Contraceptives:

      * Combined oral contraceptives (the pill)
      * Contraceptive patch
      * Vaginal contraceptive ring
      * Progestin-only pills
      * Hormonal injections (e.g., Depo-Provera)
      * Hormonal implants (e.g., Nexplanon)
    * Intrauterine Devices (IUDs):

      * Copper IUD (e.g., ParaGard)
      * Hormonal IUDs (e.g., Mirena, Skyla, Liletta)
    * Barrier Methods with Spermicide (less commonly used alone but may be used in combination with other methods for added protection):

      * Male condoms
      * Female condoms
      * Diaphragms with spermicide
      * Cervical caps with spermicide
    * Sterilization:

      * Tubal ligation (for females)
      * Vasectomy (Having a partner who has undergone a vasectomy, confirmed by semen analysis)
    * Abstinence or True Sexual Abstinence:

      o Refraining from heterosexual intercourse
    * Requirements regarding the establishment of pregnancy status and monitoring for pregnancy over the course of the study may be further defined by the IRB