Trial of Overminus Spectacle Therapy for Intermittent Exotropia

NCT ID: NCT02807350

Last Updated: 2022-06-03

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

386 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-01-16

Study Completion Date

2022-02-15

Brief Summary

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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

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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.

Conditions

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Intermittent Exotropia

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Outcome Assessors

Study Groups

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Overminus Treatment

spectacles with full cycloplegic refraction plus 2.50 D overminus added to the sphere

Group Type EXPERIMENTAL

Overminus treatment

Intervention Type DEVICE

spectacles with full cycloplegic refraction plus 2.50 D overminus added to the sphere

Non-overminus Treatment

spectacles with full cycloplegic refraction without overminus

Group Type ACTIVE_COMPARATOR

Non-overminus treatment

Intervention Type DEVICE

spectacles with full cycloplegic refraction without overminus

Interventions

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Overminus treatment

spectacles with full cycloplegic refraction plus 2.50 D overminus added to the sphere

Intervention Type DEVICE

Non-overminus treatment

spectacles with full cycloplegic refraction without overminus

Intervention Type DEVICE

Other Intervention Names

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Overminus spectacles Overminus glasses Overminus therapy

Eligibility Criteria

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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.

Exclusion Criteria

* 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


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

3 Years

Maximum Eligible Age

10 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Pediatric Eye Disease Investigator Group

NETWORK

Sponsor Role collaborator

National Eye Institute (NEI)

NIH

Sponsor Role collaborator

Jaeb Center for Health Research

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Angela M Chen, OD, MS

Role: STUDY_CHAIR

Marshall B. Ketchum University

S. Ayse Erzurum, MD

Role: STUDY_CHAIR

Eye Care Associates, Inc.

Locations

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University of Alabama at Birmingham

Birmingham, Alabama, United States

Site Status

Midwestern University Eye Institute

Glendale, Arizona, United States

Site Status

Arkansas Childrens

Little Rock, Arkansas, United States

Site Status

University Eye Center at Ketchum Health

Anaheim, California, United States

Site Status

Marshall B. Ketchum University

Fullerton, California, United States

Site Status

Loma Linda University Health Care, Dept. of Ophthalmology

Loma Linda, California, United States

Site Status

Saddleback Eye Medical Associates

Mission Viejo, California, United States

Site Status

Stanford University

Palo Alto, California, United States

Site Status

Western University College of Optometry

Pomona, California, United States

Site Status

University of California San Francisco Department of Ophthalmology

San Francisco, California, United States

Site Status

Nova Southeastern University College of Optometry, The Eye Institute

Fort Lauderdale, Florida, United States

Site Status

University of Florida Shands Hospital

Gainesville, Florida, United States

Site Status

Nemours Children's Clinic

Jacksonville, Florida, United States

Site Status

The Emory Eye Center

Atlanta, Georgia, United States

Site Status

St Luke's Hospital

Boise, Idaho, United States

Site Status

Ann & Robert H. Lurie Children's Hospital of Chicago

Chicago, Illinois, United States

Site Status

Illinois College of Optometry

Chicago, Illinois, United States

Site Status

The Eye Specialists Center, LLC

Chicago Ridge, Illinois, United States

Site Status

Midwestern U Chicago College of Optometry

Downers Grove, Illinois, United States

Site Status

Pediatric Eye Associates

Wilmette, Illinois, United States

Site Status

Indiana University School Of Optometry

Bloomington, Indiana, United States

Site Status

Riley Hospital for Children

Indianapolis, Indiana, United States

Site Status

The Eye Specialist Center, LLC

Munster, Indiana, United States

Site Status

Wolfe Eye Clinic

West Des Moines, Iowa, United States

Site Status

University of Kentucky Department of Neurology

Lexington, Kentucky, United States

Site Status

Greater Baltimore Medical Center

Baltimore, Maryland, United States

Site Status

Wilmer Eye Institute

Baltimore, Maryland, United States

Site Status

Tufts Medical Center

Boston, Massachusetts, United States

Site Status

Boston Medical Center

Boston, Massachusetts, United States

Site Status

Helen DeVos Children's Hospital Pediatric Ophthalmology

Grand Rapids, Michigan, United States

Site Status

Pediatric Ophthalmology, P.C.

Grand Rapids, Michigan, United States

Site Status

Children's Eye Care PC

West Bloomfield, Michigan, United States

Site Status

University of Minnesota

Minneapolis, Minnesota, United States

Site Status

Mayo Clinic Department of Ophthalmology

Rochester, Minnesota, United States

Site Status

Children's Mercy Hospitals and Clinics

Kansas City, Missouri, United States

Site Status

U of MO St. Louis College of Optometry

St Louis, Missouri, United States

Site Status

University of Nebraska Medical Center

Omaha, Nebraska, United States

Site Status

Concord Ophthalmologic Associates

Concord, New Hampshire, United States

Site Status

State University of New York, College of Optometry

New York, New York, United States

Site Status

Duke University Eye Center

Durham, North Carolina, United States

Site Status

Akron Children's Hospital

Akron, Ohio, United States

Site Status

Cincinnati Children's Hospital

Cincinnati, Ohio, United States

Site Status

The Ohio State University College of Optometry

Columbus, Ohio, United States

Site Status

Eye Care Associates, Inc.

Poland, Ohio, United States

Site Status

Dean A. McGee Eye Institute, University of Oklahoma

Oklahoma City, Oklahoma, United States

Site Status

Pacific University College of Optometry

Portland, Oregon, United States

Site Status

Casey Eye Institute

Portland, Oregon, United States

Site Status

Conestoga Eye

Lancaster, Pennsylvania, United States

Site Status

Salus University/Pennsylvania College of Optometry

Philadelphia, Pennsylvania, United States

Site Status

UPMC Children's Eye Center of Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, United States

Site Status

Medical University of South Carolina, Storm Eye Institute

Charleston, South Carolina, United States

Site Status

Pediatric Eye Specialists

Chattanooga, Tennessee, United States

Site Status

Southern College of Optometry

Memphis, Tennessee, United States

Site Status

Texas Children's Hospital - Dept. Of Ophthalmology

Houston, Texas, United States

Site Status

University of Houston College of Optometry

Houston, Texas, United States

Site Status

Texas Tech University Health Science Center

Lubbock, Texas, United States

Site Status

Houston Eye Associates

The Woodlands, Texas, United States

Site Status

Virginia Pediatric Eye Center

Norfolk, Virginia, United States

Site Status

Gundersen Health System

La Crosse, Wisconsin, United States

Site Status

Alberta Children's Hospital

Calgary, Alberta, Canada

Site Status

CHU - Sainte-Justine

Montreal, Quebec, Canada

Site Status

Countries

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United States Canada

References

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Chen AM, Erzurum SA, Chandler DL, Hercinovic A, Melia BM, Bhatt AR, Suh DW, Vricella M, Erickson JW, Miller AM, Marsh JD, Bodack MI, Martinson SR, Titelbaum JR, Gray ME, Holtorf HL, Kong L, Kraker RT, Rahmani B, Shah BK, Holmes JM, Cotter SA; Pediatric Eye Disease Investigator Group. Overminus Lens Therapy for Children 3 to 10 Years of Age With Intermittent Exotropia: A Randomized Clinical Trial. JAMA Ophthalmol. 2021 Apr 1;139(4):464-476. doi: 10.1001/jamaophthalmol.2021.0082.

Reference Type RESULT
PMID: 33662112 (View on PubMed)

Writing Committee for the Pediatric Eye Disease Investigator Group; Pediatric Eye Disease Investigator Group; Chen AM, Erzurum SA, Chandler DL, Hercinovic A, Wu R, Vricella M, Waters AL, Ticho BH, Erickson JW, Han S, McDowell PS, Li Z, Kraker RT, Holmes JM, Cotter SA. Refractive Error Change and Overminus Lens Therapy for Childhood Intermittent Exotropia. JAMA Ophthalmol. 2024 May 1;142(5):417-428. doi: 10.1001/jamaophthalmol.2024.0276.

Reference Type DERIVED
PMID: 38536764 (View on PubMed)

Holmes JM, Leske DA, Hercinovic A, Hatt SR, Chandler DL, Li Z, Melia BM, Chen AM, Erzurum SA, Crouch ER, Jenewein EC, Kraker RT, Cotter SA; Pediatric Eye Disease Investigator Group. Rasch-calibrated Intermittent Exotropia Symptom Questionnaire for Children. Optom Vis Sci. 2022 Jun 1;99(6):513-520. doi: 10.1097/OPX.0000000000001901. Epub 2022 Apr 12.

Reference Type DERIVED
PMID: 35412528 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Related Links

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http://pedig.jaeb.org/

PEDIG public website

Other Identifiers

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2U10EY011751

Identifier Type: NIH

Identifier Source: secondary_id

View Link

IXT5

Identifier Type: -

Identifier Source: org_study_id

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