Clinical trial NCT01032330: Observation Versus Occlusion Therapy for Intermittent Exotropia
Official title: A Randomized Clinical Trial of Observation Versus Occlusion Therapy for Intermittent Exotropia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Exotropia
Keywords: intermittent exotropia
IXT
natural history
occlusion therapy
occlusion
patching
strabismus
strabismus treatment
stereoacuity
motor alignment
Lead sponsor: Jaeb Center for Health Research
Sponsor class: OTHER
Collaborators: name: Pediatric Eye Disease Investigator Group
name: National Eye Institute (NEI)
First posted: 2009-12-15
Enrollment: 611
Sex: ALL
Minimum age (years): 12
Maximum age (years): 10
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The present study is being conducted to assess the natural history of intermittent exotropia and to establish the effectiveness of occlusion in its treatment.

Study Objectives:

* To determine the effectiveness of occlusion for the treatment of intermittent exotropia among patients aged 3 to \< 11 years who have baseline near stereoacuity of 400 arcsec or better by Preschool Randot stereotest
* To determine the natural history of intermittent exotropia among patients aged 3 to \< 11 years who have baseline near stereoacuity of 400 arcsec or better by Preschool Randot stereotest

Detailed description: 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.

Eligibility criteria: 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)

Primary outcomes:
measure: Deterioration by 6 Months - Older Cohort
timeFrame: 6 months
measure: Deterioration by 3 Years - Older Cohort
timeFrame: 3 years
measure: Deterioration by 6 Months - Younger Cohort
timeFrame: 6 months
measure: Deterioration by 3 Years - Younger Cohort
timeFrame: 3 years
Secondary outcomes:
measure: Distance Stereoacuity - 3 Years
timeFrame: Between baseline and 3 years
measure: Near Stereoacuity - 6 Months
timeFrame: 6 months
measure: Near Stereoacuity - 3 Years
timeFrame: between baseline and 3 years
measure: Exotropia Control at Distance - 6 Months
timeFrame: 6 months
measure: Exotropia Control at Distance - 3 Years
timeFrame: 3 years
measure: Exotropia Control at Near - 6 Months
timeFrame: 6 months
measure: Exotropia Control at Near - 3 Years
timeFrame: 3 years
measure: PACT Exodeviation at Distance - 6 Months
timeFrame: 6 months
measure: PACT at Distance - 3 Years
timeFrame: 3 years
measure: PACT at Near - 6 Months
timeFrame: 6 months
measure: PACT at Near - 3 Years
timeFrame: 3 years
Other outcomes:
Locations:
city: Fullerton
country: United States
facility: Southern California College of Optometry
state: California
city: Rochester
country: United States
facility: Mayo Clinic Department of Ophthalmology
state: Minnesota
Study officials:
affiliation: Southern California College of Optometry, Fullerton, CA
name: Susan A Cotter, O.D., M.S.
role: STUDY_CHAIR
affiliation: Department of Ophthalmology, Mayo Clinic, Rochester, MN
name: Brian G Mohney, M.D.
role: STUDY_CHAIR
References:
citation: Pediatric Eye Disease Investigator Group; Cotter SA, Mohney BG, Chandler DL, Holmes JM, Repka MX, Melia M, Wallace DK, Beck RW, Birch EE, Kraker RT, Tamkins SM, Miller AM, Sala NA, Glaser SR. A randomized trial comparing part-time patching with observation for children 3 to 10 years of age with intermittent exotropia. Ophthalmology. 2014 Dec;121(12):2299-310. doi: 10.1016/j.ophtha.2014.07.021. Epub 2014 Sep 16.
citation: Pediatric Eye Disease Investigator Group; Mohney BG, Cotter SA, Chandler DL, Holmes JM, Chen AM, Melia M, Donahue SP, Wallace DK, Kraker RT, Christian ML, Suh DW. A Randomized Trial Comparing Part-time Patching with Observation for Intermittent Exotropia in Children 12 to 35 Months of Age. Ophthalmology. 2015 Aug;122(8):1718-25. doi: 10.1016/j.ophtha.2015.04.025. Epub 2015 Jun 11.
citation: Pediatric Eye Disease Investigator Group; Writing Committee; Mohney BG, Cotter SA, Chandler DL, Holmes JM, Wallace DK, Yamada T, Petersen DB, Kraker RT, Morse CL, Melia BM, Wu R. Three-Year Observation of Children 3 to 10 Years of Age with Untreated Intermittent Exotropia. Ophthalmology. 2019 Sep;126(9):1249-1260. doi: 10.1016/j.ophtha.2019.01.015. Epub 2019 Jan 26.
citation: Cotter SA, Mohney BG, Chandler DL, Holmes JM, Wallace DK, Melia BM, Wu R, Kraker RT, Superstein R, Crouch ER, Paysse EA; Pediatric Eye Disease Investigator Group. Three-year observation of children 12 to 35 months old with untreated intermittent exotropia. Ophthalmic Physiol Opt. 2020 Mar;40(2):202-215. doi: 10.1111/opo.12668.
citation: Pang Y, Gnanaraj L, Gayleard J, Han G, Hatt SR. Interventions for intermittent exotropia. Cochrane Database Syst Rev. 2021 Sep 13;9(9):CD003737. doi: 10.1002/14651858.CD003737.pub4.
citation: Holmes JM, Hercinovic A, Melia BM, Leske DA, Hatt SR, Chandler DL, Dean TW, Kraker RT, Enyedi LB, Wallace DK, Mohney BG, Cotter SA; Pediatric Eye Disease Investigator Group. Health-related quality of life in children with untreated intermittent exotropia and their parents. J AAPOS. 2021 Apr;25(2):80.e1-80.e4. doi: 10.1016/j.jaapos.2020.10.011. Epub 2021 Mar 8.