Trial of Overminus Spectacle Therapy for Intermittent Exotropia

The main objectives of this randomized trial comparing overminus lens treatment to
non-overminus (spectacles without overminus or spectacles with plano lenses) are to
determine:

- The long-term on-treatment effect of overminus treatment on distance IXT control score.

- The off-treatment effect of overminus treatment on distance IXT control score (following
weaning and 3 months off treatment).

The recently completed IXT3 pilot study (NCT02223650) addressed the question of whether
overminus lens therapy has an initial short-term therapeutic effect for IXT while wearing
overminus spectacles. There have been no rigorous studies that address the following
important questions related to overminus lens therapy:

- Does overminus lens therapy have a long-term therapeutic effect for IXT while wearing
overminus spectacles (over many months or years)?

- Does overminus lens therapy have a long-term therapeutic effect for IXT when overminus
spectacles are discontinued?

Inclusion Criteria:

- Age 3 years to < 11 years

- Intermittent exotropia (manifest deviation) meeting all of the following criteria:

- At distance: intermittent exotropia or constant exotropia

o Mean distance control score of 2 points or more (mean of 3 assessments over the
exam)

- At near: intermittent exotropia, exophoria, or orthophoria

o Subject cannot have a score of 5 points on all 3 near assessments of control

- Exodeviation at least 15∆ at distance measured by PACT

- Near deviation does not exceed distance deviation by more than 10∆ by PACT
(convergence insufficiency type IXT excluded)

- Distance visual acuity (any optotype method) in each eye of 0.4 logMAR (20/50) or
better if age 3 years and 0.3 logMAR (20/40) or better if 4 years or older.

- Interocular difference of distance visual acuity ≤0.2 logMAR (2 lines on a logMAR
chart)

- Refractive error between -6.00 diopters (D) standard error (SE) and +1.00D SE
(inclusive) in the most myopic / least hyperopic eye based on a cycloplegic refraction
performed within the past 2 months or at the end of the enrollment exam.

- If refractive error (based on cycloplegic refraction performed within past 2 months or
at the end of the enrollment exam) meets any of the following criteria, then pre-study
spectacles are required and must have been worn for at least 1 week prior to
enrollment:

- SE anisometropia ≥1.00D

- Astigmatism ≥1.50D in either eye

- SE myopia ≥-1.00D in either eye

Pre-study refractive correction, if worn, must meet the following criteria relative to the
cycloplegic refraction performed within past 2 months or at the end of the enrollment exam:

- SE anisometropia must be corrected within <1.00D of the SE anisometropic difference

- Astigmatism must be corrected within <1.00D of full magnitude; axis must be within 10
degrees.

- The SE of the spectacles must not meet the definition of substantial overminus (see
exclusion criteria below)

- Gestational age ≥ 32 weeks

- Birth weight > 1500 grams

- Parent understands the protocol and is willing to accept randomization to overminus
spectacles or non-overminus spectacles

- Parent has home phone (or access to phone) and is willing to be contacted by Jaeb
Center staff and Investigator's site staff

- Relocation outside of area of an active PEDIG site within next 18 months is not
anticipated

Exclusion Criteria:

- Treatment for IXT or amblyopia (other than refractive correction) within the past 4
weeks, including vision therapy, patching, atropine, or other penalization.

- Current contact lens wear

- Substantial deliberate overminus treatment within the past 6 months, defined as
spectacles overminused by more than 1.00D SE than the cycloplegic refractive error
(within 2 months or at the end of the enrollment exam)

- Prior strabismus, intraocular, or refractive surgery (including BOTOX injection)

- Abnormality of the cornea, lens, or central retina

- Down syndrome or cerebral palsy

- Severe developmental delay which would interfere with treatment or evaluation (in the
opinion of the investigator). Subjects with mild speech delays or reading and/or
learning disabilities are not excluded.

- Any disease known to affect accommodation, vergence, and ocular motility such as
multiple sclerosis, Graves orbitopathy, dysautonomia, myasthenia gravis, or current
use of atropine for amblyopia

- Anti-seizure medications [e.g., carbamazepine (Tegretol, Carbatrol, Epitol, or
Equetro), diazepam (Valium or Diastat), clobazam (Frisium or Onfri), clonazepam
(Klonopin), lorazepam (Ativan), ethosuximide (Zarontin), felbamate (Felbatol),
lacosamide (VIMPAT), gabapentin (Neurontin), oxcarbazepine (Oxtellar XR or Trileptal),
phenobarbital, phenytoin (Dilantin or Phenytek), pregabalin (Lyrica), tiagabine
(Gabitril), topiramate (Topamax), valproate (Depakote), or zonisamide (Zonegran),
vigabatrin (Sabril)]