A Pilot Clinical Trial of Overminus Spectacle Therapy for Intermittent Exotropia

Study Overview
=================
Brief Summary
-----------------
The objective of this short-term, pilot randomized trial comparing 2.50 diopters (D) overminus lens treatment vs. non-overminus (spectacles without overminus or no spectacles) in children with intermittent exotropia (IXT) 3 to <7 years of age is to determine whether to proceed to a full-scale, longer-term randomized trial.

Detailed Description
-----------------
The objective of this short-term, pilot randomized trial comparing 2.50D overminus lens treatment vs. non-overminus (spectacles without overminus or no spectacles) is to determine whether to proceed to a full-scale, longer-term randomized trial. This decision will be based primarily on assessing the initial (8-week) response to overminus by comparing treatment groups on the following outcomes: Mean distance IXT control score (each patient's score is the mean of 3 control scores) (primary outcome) The proportion of subjects with treatment response, defined as 1 or more points improvement in mean of 3 distance IXT control scores (secondary outcome) Adverse effects, near visual acuity outcomes, and spectacle wear compliance

Official Title
-----------------
A Pilot Randomized Clinical Trial of Overminus Spectacle Therapy for Intermittent Exotropia

Conditions
-----------------
Intermittent Exotropia

Intervention / Treatment
-----------------
* Device: Overminus treatment
* Device: Non-overminus treatment


Participation Criteria
=================
Eligibility Criteria
-----------------
The following criteria must be met for the child to be enrolled in the study: Age 3 years to < 7 years Intermittent exotropia (manifest deviation) meeting all of the following criteria: Intermittent exotropia or constant exotropia at distance Mean distance control score of 2 points or more (mean of 3 assessments over the exam) Intermittent exotropia, exophoria, or orthophoria at near 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) No previous non-surgical treatment for IXT (other than refractive correction), including vision therapy for IXT, within the past 6 months. No previous substantial overminus treatment, defined as wearing spectacles that are overminused by 1.00D SE or more (treatment with lenses overminused by less than 1.00D SE is allowed at any time prior to enrollment). No vision therapy, patching, atropine, or other penalization for amblyopia during the last 2 weeks No prior strabismus, intraocular, or refractive surgery (including BOTOX injection) Cycloplegic refraction within 7 months, but NOT on the day of enrollment Spherical equivalent (SE) in both eyes between -6.00D and +1.00D inclusive Distance visual acuity 0.3 logMAR (20/40) or better (by ATS-HOTV) in both eyes No interocular difference of distance visual acuity more than 0.2 logMAR (2 lines) Child must be wearing refractive correction (pre-study spectacles) for at least 1 week if refractive error (based on cycloplegic refraction performed within 7 months) meets any of the following: SE anisometropia ≥1.00 D Astigmatism ≥1.00 D in either eye SE myopia ≥-0.50 D in either eye Refractive correction must meet the following criteria relative to the cycloplegic refraction: SE anisometropia must be within <1.0D of the SE anisometropic difference Astigmatism must be within <1.00D of full magnitude; axis must be within 10 degrees if ≤1.00D, and within 5 degrees if >1.00D. The SE of the spectacles must be within <1.00D of the full cycloplegic refraction SE. A correction that yields at least 1.00 D more minus SE than the cycloplegic refraction SE is considered previous substantial overminus lens treatment and the patient is not eligible. No current contact lens wear No abnormality of the cornea, lens, or central retina Gestational age ≥ 32 weeks Birth weight > 1500 grams No Down syndrome or cerebral palsy No 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. No disease known to affect accommodation, vergence, and ocular motility such as multiple sclerosis, Graves orbitopathy, myasthenia gravis, diabetes mellitus, or Parkinson disease No current use of any ocular or systemic medication known to affect accommodation or vergence, such as anti-anxiety agents (e.g., Librium or Valium), anti-arrhythmic agents (e.g., Cifenline, Cibenzoline), anti-cholinergics (e.g., motion sickness patch (scopolamine)), bladder spasmolytic drugs (e.g., Propiverine), hydroxychloroquine, chloroquine, phenothiazines (e.g., Compazine, Mellaril, Thorazine), tricyclic antidepressants (e.g., Elavil, Nortriptyline, Tofranil) Parent understands the protocol and is willing to accept randomization to overminus spectacles or non-overminus status 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 8 weeks is not anticipated

Ages Eligible for Study
-----------------
Minimum Age: 3 Years
Maximum Age: 6 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Overminus Treatment<br>2.50D overminus spectacles | Device: Overminus treatment<br>* 2.50D overminus spectacles<br>* Other names: Overminus therapy;|
| Active Comparator: Non-overminus Treatment<br>spectacles without overminus or no spectacles | Device: Non-overminus treatment<br>* spectacles without overminus or no spectacles<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Distance Exotropia Control Score | At each visit, control of the exodeviation was measured at distance (6 meters) and at near (1/3 meters) using the Office Control Score* which ranges from 0 (phoria, best control) to 5 (constant exotropia, worst control). Due to the variability of single measures of control, we used a triple control score, which is a mean of 3 measures obtained at specific time-points during a 20- to 40-minute office examination. The primary analysis was an intention-to-treat treatment group comparison of mean 8-week distance control using an analysis of covariance (ANCOVA) model which adjusted for baseline distance control. *Mohney BG, Holmes JM. An office-based scale for assessing control in intermittent exotropia. Strabismus 2006;14(3):147-50. | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Near Exotropia Control Score | At each visit, control of the exodeviation was measured at near (1/3 meters) using the Office Control Score which ranges from 0 (phoria, best control) to 5 (constant exotropia, worst control). Due to the variability of single measures of control, we used a triple control score, which is a mean of 3 measures obtained at specific time-points during a 20- to 40-minute office examination. The secondary analysis was an intention-to-treat treatment group comparison of mean 8-week near control using an analysis of covariance (ANCOVA) model which adjusted for baseline near control. | 8 weeks | 
| Distribution of Distance Control Score at 8-week Outcome | Control of exodeviation will be assessed in the habitual correction at distance (6 meters) and near (1/3 meter) using a standardized IXT control scale. | 8 weeks | 
| Distribution of Near Control Score at 8-week Outcome | Control of exodeviation will be assessed in the habitual correction at distance (6 meters) and near (1/3 meter) using a standardized IXT control scale. | 8 weeks | 
| Proportion of Subjects With Distance Control Treatment Response | A comparison of the proportion of subjects showing a treatment response, defined as an improvement of at least 1 point in distance control (mean of the 3 assessments over the exam) between enrollment and 8 weeks. | 8 weeks | 
| Symptom Survey Response to Question: Has Child Looked Over His/Her Spectacles Since Enrollment? | A brief survey of symptoms that may be associated with overminus such as headaches, eye strain, and problems with spectacle wear will be administered to the parents of the subjects. Parents are asked to respond to the survey questions based on their observations of their child in the past 2 weeks. Response options are based on frequency of observations; never, rarely, sometimes, often, always, and not applicable. Survey items were derived based on expert opinion of pediatric ophthalmologists and optometrists on the study planning committee. The response options were a 5-point Likert-type scale based on frequency of observations: never = score of 0, almost never = 1, sometimes = 2, often = 3, and always = 4. | 8 weeks | 
| Stereoacuity | Stereoacuity will be assessed with habitual correction using the Randot Preschool stereotest at near (performed at 40 cm). A specific level of stereoacuity is not required for eligibility. | 8 weeks | 
| Distance Visual Acuity | Monocular distance visual acuity testing with the habitual correction and without cycloplegia was measured using the Amblyopia Treatment Study HOTV testing protocol on any certified visual acuity system. The treatment groups were not different with respect to 8-week control PACT at distance | 8 weeks | 
| Binocular Near Visual Acuity | Binocular near visual acuity was tested in habitual correction using the ATS4 near visual acuity test. The treatment groups were not different with respect to 8-week control at near. | 8 weeks | 
| Symptom Survey Response to Question: Has Your Child Had Eyestrain (Tired, Sore, or Uncomfortable Eyes)? | A brief survey of symptoms that may be associated with overminus such as headaches, eye strain, and problems with spectacle wear will be administered to the parents of the subjects. Parents are asked to respond to the survey questions based on their observations of their child in the past 2 weeks. Response options are based on frequency of observations; never, rarely, sometimes, often, always, and not applicable. Survey items were derived based on expert opinion of pediatric ophthalmologists and optometrists on the study planning committee. The response options were a 5-point Likert-type scale based on frequency of observations: never = score of 0, almost never = 1, sometimes = 2, often = 3, and always = 4. | 8 weeks | 
| Symptom Survey Response to Question: Since Enrollment Has Your Child Avoided Reading or Doing Things up Close? | A brief survey of symptoms that may be associated with overminus such as headaches, eye strain, and problems with spectacle wear will be administered to the parents of the subjects. Parents are asked to respond to the survey questions based on their observations of their child in the past 2 weeks. Response options are based on frequency of observations; never, rarely, sometimes, often, always, and not applicable. Survey items were derived based on expert opinion of pediatric ophthalmologists and optometrists on the study planning committee. The response options were a 5-point Likert-type scale based on frequency of observations: never = score of 0, almost never = 1, sometimes = 2, often = 3, and always = 4. | 8 weeks | 
| Symptom Survey Response to Question: Has Your Child Reported Blurry Vision? | A brief survey of symptoms that may be associated with overminus such as headaches, eye strain, and problems with spectacle wear will be administered to the parents of the subjects. Parents are asked to respond to the survey questions based on their observations of their child in the past 2 weeks. Response options are based on frequency of observations; never, rarely, sometimes, often, always, and not applicable. Survey items were derived based on expert opinion of pediatric ophthalmologists and optometrists on the study planning committee. The response options were a 5-point Likert-type scale based on frequency of observations: never = score of 0, almost never = 1, sometimes = 2, often = 3, and always = 4. | 8 weeks | 
| Proportion of Subjects With Near Control Treatment Response | A comparison of the proportion of subjects showing a treatment response, defined as an improvement of at least 1 point in near control (mean of the 3 assessments over the exam) between enrollment and 8 weeks. | 8 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
IXT, Intermittent Exotropia, overminus