Observation Versus Occlusion Therapy for Intermittent Exotropia

Intermittent exotropia (IXT) is the most common form of childhood-onset exotropia with an
incidence of 32.1 per 100,000 in children under 19 years of age. Intermittent exotropia is
characterized by an exotropia that is not constant and is mainly present in the distance but
may also be present at near. Many cases of IXT are treated using non-surgical interventions,
such as part-time occlusion, fusional vergence exercises, and over-minus lenses. The
rationale for such interventions is that they may improve the ability to control the IXT and
preserve stereoacuity, thereby potentially addressing both visual function and social
concerns, and may delay or eliminate the need for surgical correction of IXT. Nevertheless,
the natural history of IXT is unknown and in many cases it is not known whether withholding
treatment may in fact allow for spontaneous resolution or improvement in IXT, making
non-surgical or surgical intervention unnecessary. Moreover, although non-surgical treatments
for IXT are commonly prescribed, such treatments have not been subjected to rigorous study
and their efficacy in improving visual function or social concerns remains unclear.

One aim of the present study is to better understand the natural history of IXT. Available
reports on the natural history of IXT disagree on the progression of the disease. A 1966
study by von Noorden (cited in von Noorden and Campos) found that over an average of 3.5
years of follow-up, 75% of 51 patients showed signs of IXT progression, 9% showed no change,
and 16% improved without therapy. A 1968 retrospective study by Hiles et al found that after
a minimum of 6 years follow up with observation and nonsurgical treatment, 81% of 48 patients
showed no change in angle of deviation. The results of more recent retrospective studies show
some reporting that the majority of cases improve over time, others reporting that most cases
remain stable, and still others reporting that most cases deteriorate. It is therefore
unclear what proportion of patients, if left untreated, is likely to deteriorate, improve, or
remain stable over time. Natural history data acquired during this study will help determine
not only what proportion of patients change over time, but whether there are associated
prognostic indicators of deterioration or improvement. Such data will not only enable better
identification of those patients with IXT likely to benefit from treatment and those for whom
treatment is likely to be unnecessary, but will also improve the quality of medical advice to
parents regarding the likely progression of the disease, thus alleviating anxiety.

The aim of most forms of non-surgical treatments for IXT is to improve the strength and/or
quality of binocular single vision by either eliminating suppression, increasing awareness of
diplopia, and/or increasing positive fusional amplitudes. Commonly used non-surgical
treatment methods include: occlusion, fusional vergence exercises (sometimes known as vision
therapy or orthoptics), and over-minus lenses. When surveyed in 1990, members of the American
Association for Pediatric Ophthalmology and Strabismus reported that occlusion was the most
commonly used form of non-surgical treatment. More recently (2008), a poll of our
investigator group revealed again that occlusion was the most widely prescribed non-surgical
treatment for children affected by IXT.

Occlusion is thought to work by interrupting the development of or eliminating already
present suppression, an adaptation to avoid diplopia in IXT. Persistent or entrenched
suppression prevents normal binocular vision and may lead to permanent loss of stereoacuity.
If successful, occlusion may then result in improved binocular sensory fusion.

As reported in recent reviews of treatment for IXT, previous studies of occlusion vary
regarding the recommended occlusion dose (from 3 hours a day to full time), the optimum
duration of occlusion treatment (from 6 weeks to 42 months), and which eye should be occluded
(preferred/dominant eye or alternate eyes). For the majority of studies, part-time occlusion,
rather than full-time occlusion was preferred. In the three occlusion studies conducted
prospectively, the recommended dose was either 3 hours a day, 3 to 6 hours a day, or 4 to 6
hours a day, and the duration of occlusion ranged from 3 months to 6 months to up to 42 (mean
15) months. Nevertheless, these previous studies of occlusion for the treatment of IXT used a
variety of outcome measures at a variety of non-standardized time points; therefore, no
definite conclusions can be drawn from the existing literature.

Although occlusion treatment for IXT treatment is widely used, there have been no randomized
clinical trials evaluating its effectiveness. Understanding the degree of effectiveness of
occlusion treatment for IXT and the natural history of IXT has important public health
implications. Successful restoration of binocular alignment and normal binocular function
with occlusion therapy, or spontaneous improvement, will reduce the proportion of children
undergoing surgery. Defining the rate of success with either occlusion or observation is
therefore important in planning treatment for children with IXT. Alternatively, evidence of
low treatment effectiveness with occlusion will help avoid unnecessary treatment.

The present study is being conducted to assess the natural history of IXT and to establish
the effectiveness of occlusion in its treatment.

Inclusion Criteria:

- Age 12 months to < 11 years

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

- Intermittent exotropia at distance OR constant exotropia at distance and either
intermittent exotropia or exophoria at near

- Exodeviation at least 15PD at distance OR near measured by prism and alternate
cover test (PACT)

- Exodeviation at least 10PD at distance measured by PACT

- No previous surgical or non-surgical treatment for IXT (other than refractive
correction)

- Visual acuity in the worse eye at least 0.3 logMAR (20/40 on ATS HOTV or 70 letters on
E-ETDRS) for children ≥ 3 years of age

- No interocular difference of visual acuity more than 0.2 logMAR (2 lines on ATS HOTV
or 10 letters on E-ETDRS) for children ≥ 3 years of age

- No hyperopia greater than +3.50 D spherical equivalent in either eye

- No myopia greater than -6.00 D spherical equivalent in either eye

- No prior strabismus, intraocular, or refractive surgery

- No abnormality of the cornea, lens, or central retina

- Investigator willing to observe the IXT untreated for 3 years unless specific criteria
for deterioration are met

Exclusion Criteria:

- Pure phoria at both distance and near

- Prior non-surgical treatment for IXT other than refractive correction (e.g., vergence
therapy, occlusion, vision therapy/orthoptics, or deliberate over-minus with
spectacles more than 0.50D)

- Previous amblyopia treatment other than refractive correction within 1 year

- Vision therapy/orthoptics for any reason within the last year

- Interocular visual acuity difference more than 0.2 logMAR (2 lines on ATS HOTV for
patients 3 to < 7 years old or 10 letters on E-ETDRS for patients ≥ 7 years old)
(patients ≥ 3 years only) and/or investigator plans to initiate amblyopia treatment at
this time.

- Limitation of ocular rotations due to restrictive or paretic strabismus

- Craniofacial malformations affecting the orbits

- Ocular disorders which would reduce visual acuity (except refractive error)

- Prior strabismus surgery or botulinum injection, intraocular surgery, or refractive
surgery

- Strabismus surgery planned

- Known skin reactions to patch or bandage adhesives

- Significant neurological impairment such as cerebral palsy. Patients with mild speech
delays or common reading and/or learning disabilities are not excluded.

- Investigator planning to change refractive correction at this time (if the patient is
otherwise eligible, the investigator should consider prescribing refractive correction
and bringing the patient back at a later time for enrollment)