Bilateral Refractive Amblyopia Treatment Study (ATS7)

The purpose of this study will be to:

• Determine the amount of visual acuity improvement with treatment of presumed bilateral refractive amblyopia
• Determine the time course of visual acuity improvement with treatment

There is a paucity of literature on bilateral amblyopia that is due to a substantial amount of refractive error (hypermetropia or astigmatism), and it is limited principally to review articles and case reports. The incidence is not known, but in one study, 4 of 830 (0.5%) children examined at the time of entry into school had bilateral amblyopia. Schoenleber et al performed a retrospective review of office records and identified 184 children with > +4.00 diopters of hypermetropia in both eyes, 12 of whom (6.5%) had bilateral amblyopia of 20/50 or worse. Ten of the 12 children (83%) improved to 20/40 or better in both eyes over a mean follow-up time of 22 months. Werner and Scott reported 6 cases of bilateral hypermetropic amblyopia with a spherical equivalent of at least +5.00 D and an initial visual acuity of 20/40 or worse in both eyes. All 5 patients with follow up improved with glasses alone, and 2 of these 5 had a most recent visual acuity worse than 20/40 in one eye with follow-up less than one year. Cavazos et al identified 218 eyes with hyperopia > +5.00 D or astigmatism >+2.00 D. Of these, 82 (38%) of the dominant eyes had an initial corrected visual acuity less than 20/25. Most improved to > 20/25, but many patients were lost to follow-up. In ongoing studies, bilateral refractive amblyopia is being evaluated in Native Americans.

1. Patients will be enrolled who have bilateral refractive error with hyperopia >+4.00 D and/or astigmatism >2.00 D and have visual acuity in each eye, measured using best correction derived from cycloplegic refraction, meeting the following criteria:

   • Using E-ETDRS testing for patients age 7 to <11 years: visual acuity 20 to 70 letters (20/40 to 20/400)
   • Using ATS HOTV testing for patients age 3 to <7 years visual acuity 20/50 to 20/400
2. Enrolled patients will be prescribed spectacles, which will be paid for by the study.

3. The patient will return for a Spectacle Baseline visit within 30 days, at which time the spectacles will be placed on the patient for the first time and binocular and monocular visual acuities will be measured.

   • Patients whose monocular acuity at the Spectacle Baseline Visit is 20/25 or better in both eyes will end the study
   • Patients whose monocular acuity at the Spectacle Baseline Visit is worse than 20/25 in at least one eye will begin a one-year period of study follow up

4. Follow-up visits are required at 5±:1 week, 13±:2 weeks, 26±:4 weeks, and 52±:4 weeks.

   • If at any follow-up visit a patient's monocular acuity is 20/25 or better in both eyes, the patient should return for the 52-week visit only and may skip the interim follow-up visits.

Sample size: The study plans to enroll 100 patients. At least 50 patients will be enrolled who have an interocular difference of less than 3 lines by ATS HOTV or less than 15 letters by E-ETDRS at the Spectacle Baseline visit.

Community sample

Inclusion Criteria:

• Age 3 to <11 years
• Able to perform single-surrounded single optotype visual acuity using the ATS HOTV protocol for children 3 to <7 years old and using the E-ETDRS protocol for children 7 to <11 years old
• Monocular visual acuity in each eye, measured using trial frames or phoropter with best correction derived from cycloplegic refraction, meeting the following criteria:
• Using E-ETDRS testing for patients age 7 to <11 years: visual acuity 20 to 70 letters (20/40 to 20/400)
• Using ATS HOTV testing for patients age 3 to <7 years acuity 20/50 to 20/400
• Refractive error that meets at least one of the following criteria in each eye:
• Spherical equivalent >+4.00 D
• Astigmatism >2.00 D
• Investigator believes that the patient's reduced visual acuity is due to bilateral, refractive amblyopia
• Investigator not planning to prescribe occlusion, patching or any other amblyopia treatment other than spectacles at this time
• Cycloplegic refraction and ocular examination within 2 months prior to enrollment

Exclusion Criteria:

• Myopia greater than -6.00 D of spherical power in plus cylinder form
• Ocular cause for decreased acuity in either eye; nystagmus per se will not exclude a patient from the study
• Refractive correction (spectacles or contact lenses) in past three months and no more than one month of refractive correction ever
• Prior treatment for amblyopia (other than the refractive correction permitted in previous exclusion criteria)
• Prior intraocular or refractive surgery
• Use of contact lenses during the study