Trial of Overminus Spectacle Therapy for Intermittent Exotropia

Not Applicable

Completed

Conditions: Intermittent Exotropia

Registration Number: NCT02807350

Lead Sponsor: Jaeb Center for Health Research

Brief Summary: 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 intermittent exotropia (IXT) control score.

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

Detailed Description: 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?

In November 2019, a protocol amendment discontinued overminus lens treatment and extended the study for an additional 18 months after the 18-month randomized trial has ended. The objective of the extension study is to compare long-term refractive error between subjects originally treated with either overminus spectacles or non-overminus spectacles as part of the 18-month randomized trial; treatment is at investigator discretion.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 386

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)]

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Mean Distance Control at 18-Months (Off-Treatment Visit)	18 months	A comparison of mean control of the distance exodeviation (average of 3 measurements over the exam) between the 2.50D overminus group and the non-overminus group (spectacles without overminus or no spectacles) at 18 months (after treatment discontinuation). The Office Control Score provides a rating of exodeviation control on a 0 to 5 scale, in subjects with intermittent exotropia. Scores 3 to 5 reflect the proportion of time a spontaneous manifest exotropia is present during 30 seconds of observation (\<50% score 3; \>50% score 4; 100% score 5). If no spontaneous manifest exotropia is observed, scores 0 to 2 reflect the longest time to regain fusion after three, 10-second dissociations (\>5 seconds score 2; 1-5 seconds score 1; \<1 second score 0).
Mean Distance Control at 12-Months (On-Treatment Visit)	12 months	A comparison of mean control of the distance exodeviation (average of 3 measurements over the exam) between the 2.50 diopters (D) overminus group and the non-overminus group (spectacles without overminus or no spectacles) at 12 months. The Office Control Score provides a rating of exodeviation control on a 0 to 5 scale, in subjects with intermittent exotropia. Scores 3 to 5 reflect the proportion of time a spontaneous manifest exotropia is present during 30 seconds of observation (\<50% score 3; \>50% score 4; 100% score 5). If no spontaneous manifest exotropia is observed, scores 0 to 2 reflect the longest time to regain fusion after three, 10-second dissociations (\>5 seconds score 2; 1-5 seconds score 1; \<1 second score 0).

Secondary Outcome Measures

Name	Time	Method
Change in Distance Control	18 months	The proportion of subjects with ≥1 point improvement in distance control between baseline and 18 months will be compared between treatment groups. The proportion of subjects with ≥2 points improvement in distance control will be similarly compared between treatment groups. The Office Control Score provides a rating of exodeviation control on a 0 to 5 scale, in subjects with intermittent exotropia. Scores 3 to 5 reflect the proportion of time a spontaneous manifest exotropia is present during 30 seconds of observation (\<50% score 3; \>50% score 4; 100% score 5). If no spontaneous manifest exotropia is observed, scores 0 to 2 reflect the longest time to regain fusion after three, 10-second dissociations (\>5 seconds score 2; 1-5 seconds score 1; \<1 second score 0).
Number of Participants With No Spontaneous Tropia	12 months	The number of subjects with no spontaneous tropia at 12 months and at 18 months will be compared between treatment groups.
No Spontaneous Tropia	At 18 months	The proportion of subjects with no spontaneous tropia at 12 months and at 18 months will be compared between treatment groups.
Deterioration as Assessed by Motor Alignment and Stereoacuity at Near (12 Months)	12 months	The cumulative proportion of subjects who meet deterioration criteria by the time point will be estimated for each treatment group. Participants who meet either of the following at any visit by a specific timepoint (e.g., 12 months, 18 months) will be considered to have met deterioration criteria by that timepoint. * Motor deterioration: Control of the exodeviation measures 5 (constant exotropia) on all three assessments at distance and near. The exodeviation does not need to be constant throughout the entire exam provided that it is constant during all three assessments of control. * Stereoacuity deterioration: Drop in near stereoacuity of at least 2 octaves from enrollment stereoacuity, or to nil, confirmed by a retest by a Masked Examiner on a subsequent day. Note: participants with nil stereoacuity at enrollment will not be able to deteriorate with respect to a drop in near stereoacuity.
Deterioration as Assessed by Motor Alignment and Stereoacuity at Near (18 Months)	18 months	The cumulative proportion of subjects who meet deterioration criteria by the time point will be estimated for each treatment group. Participants who meet either of the following at any visit by a specific timepoint (e.g., 12 months, 18 months) will be considered to have met deterioration criteria by that timepoint. * Motor deterioration: Control of the exodeviation measures 5 (constant exotropia) on all three assessments at distance and near. The exodeviation does not need to be constant throughout the entire exam provided that it is constant during all three assessments of control. * Stereoacuity deterioration: Drop in near stereoacuity of at least 2 octaves from enrollment stereoacuity, or to nil, confirmed by a retest by a Masked Examiner on a subsequent day. Note: participants with nil stereoacuity at enrollment will not be able to deteriorate with respect to a drop in near stereoacuity.
Change in Near Control (12 Months)	12 months	For each timepoint, the change in near control since baseline will be reported. The Office Control Score provides a rating of exodeviation control on a 0 to 5 scale, in subjects with intermittent exotropia. Scores 3 to 5 reflect the proportion of time a spontaneous manifest exotropia is present during 30 seconds of observation (\<50% score 3; \>50% score 4; 100% score 5). If no spontaneous manifest exotropia is observed, scores 0 to 2 reflect the longest time to regain fusion after three, 10-second dissociations (\>5 seconds score 2; 1-5 seconds score 1; \<1 second score 0).
Near Control (18 Months)	18 months	Mean control of the near exodeviation (average of 3 measurements over the exam). The Office Control Score provides a rating of exodeviation control on a 0 to 5 scale, in subjects with intermittent exotropia. Scores 3 to 5 reflect the proportion of time a spontaneous manifest exotropia is present during 30 seconds of observation (\<50% score 3; \>50% score 4; 100% score 5). If no spontaneous manifest exotropia is observed, scores 0 to 2 reflect the longest time to regain fusion after three, 10-second dissociations (\>5 seconds score 2; 1-5 seconds score 1; \<1 second score 0).
Change in Near Control (18 Months)	18 months	For each timepoint, the change in near control since baseline will be reported. The Office Control Score provides a rating of exodeviation control on a 0 to 5 scale, in subjects with intermittent exotropia. Scores 3 to 5 reflect the proportion of time a spontaneous manifest exotropia is present during 30 seconds of observation (\<50% score 3; \>50% score 4; 100% score 5). If no spontaneous manifest exotropia is observed, scores 0 to 2 reflect the longest time to regain fusion after three, 10-second dissociations (\>5 seconds score 2; 1-5 seconds score 1; \<1 second score 0).
Angle Magnitude (12 Months)	12 months	The magnitude of the deviation by Prism Alternate Cover Test (PACT) will be compared between treatment groups.
Angle Magnitude (18 Months)	18 months	The magnitude of the deviation by Prism Alternate Cover Test (PACT) will be compared between treatment groups.
Stereoacuity at 12 Months	12 months	A comparison of near stereoacuity will be assessed using the Randot Preschool stereotest at near (performed at 40 cm) between treatment groups.
Near Control (12 Months)	12 months	Mean control of the near exodeviation (average of 3 measurements over the exam). The Office Control Score provides a rating of exodeviation control on a 0 to 5 scale, in subjects with intermittent exotropia. Scores 3 to 5 reflect the proportion of time a spontaneous manifest exotropia is present during 30 seconds of observation (\<50% score 3; \>50% score 4; 100% score 5). If no spontaneous manifest exotropia is observed, scores 0 to 2 reflect the longest time to regain fusion after three, 10-second dissociations (\>5 seconds score 2; 1-5 seconds score 1; \<1 second score 0).
Stereoacuity at 18 Months	18 months	A comparison of near stereoacuity will be assessed using the Randot Preschool stereotest at near (performed at 40 cm) between treatment groups.
Compliance With Spectacle Wear (12 Months)	12 months	Compliance with spectacle wear will be assessed at the 12-month and 18-month outcome exam. Parents will give an estimate of the proportion of the time their children wore their spectacles. Proportion of time worn will be described as excellent (76% to 100%), good (51% to 75%), fair (26% to 50%), or poor (≤ 25%). The distribution of compliance will be assessed for each treatment group at the outcome exam.
Parent Symptom Survey [12 Months]	At 12 months	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.
Parent Symptom Survey [18 Months]	At 18 months	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.
Compliance With Spectacle Wear (18 Months)	18 months	Compliance with spectacle wear will be assessed at the 12-month and 18-month outcome exam. Parents will give an estimate of the proportion of the time their children wore their spectacles. Proportion of time worn will be described as excellent (76% to 100%), good (51% to 75%), fair (26% to 50%), or poor (≤ 25%). The distribution of compliance will be assessed for each treatment group at the outcome exam.

Trial Locations

Locations (61): University of Alabama at Birmingham
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Birmingham, Alabama, United States
Midwestern University Eye Institute
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Glendale, Arizona, United States
Arkansas Childrens
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Little Rock, Arkansas, United States
University Eye Center at Ketchum Health
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Anaheim, California, United States
Marshall B. Ketchum University
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Fullerton, California, United States
Loma Linda University Health Care, Dept. of Ophthalmology
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Loma Linda, California, United States
Saddleback Eye Medical Associates
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Mission Viejo, California, United States
Stanford University
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Palo Alto, California, United States
Western University College of Optometry
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Pomona, California, United States
University of California San Francisco Department of Ophthalmology
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San Francisco, California, United States
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University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States