Amblyopia Clinical Trials

⁃ Age 8-17 years

⁃ 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

⁃ 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.

⁃ 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

⁃ 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

⁃ Eye examination within 6 months prior to enrollment

⁃ 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

⁃ 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 Exclusions

⁃ Myopia \> -6.00 D spherical equivalent

⁃ Presence of associated findings that could cause reduced visual acuity

⁃ • Nystagmus does not exclude the subject if the above visual acuity criteria are met

⁃ Previous intraocular or refractive surgery

⁃ Strabismus surgery planned within 16 weeks

⁃ Current vision therapy or orthoptics

⁃ Known past or present liver or kidney disease

⁃ Known past or present mitochondrial/metabolic disorder

⁃ Known past or present psychological problems

⁃ Known allergies or contraindications to the use of valproate or anti-epileptic medication

‣ 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.

‣ Prior valproate use

‣ Known skin reaction to patch or bandage adhesives

‣ Treatment with topical atropine within the past 12 weeks

‣ 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