Clinical trial NCT02807350: Trial of Overminus Spectacle Therapy for Intermittent Exotropia
Official title: A Randomized Clinical Trial of Overminus Spectacle Therapy for Intermittent Exotropia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Intermittent Exotropia
Keywords: Intermittent Exotropia
IXT
overminus
Lead sponsor: Jaeb Center for Health Research
Sponsor class: OTHER
Collaborators: name: Pediatric Eye Disease Investigator Group
name: National Eye Institute (NEI)
First posted: 2016-06-21
Enrollment: 386
Sex: ALL
Minimum age (years): 3
Maximum age (years): 10
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Mean Distance Control at 12-Months (On-Treatment Visit)
timeFrame: 12 months
measure: Mean Distance Control at 18-Months (Off-Treatment Visit)
timeFrame: 18 months
Secondary outcomes:
measure: Number of Participants With No Spontaneous Tropia
timeFrame: 12 months
measure: No Spontaneous Tropia
timeFrame: At 18 months
measure: Change in Distance Control
timeFrame: 12 months
measure: Change in Distance Control
timeFrame: 18 months
measure: Deterioration as Assessed by Motor Alignment and Stereoacuity at Near (12 Months)
timeFrame: 12 months
measure: Deterioration as Assessed by Motor Alignment and Stereoacuity at Near (18 Months)
timeFrame: 18 months
measure: Near Control (12 Months)
timeFrame: 12 months
measure: Near Control (18 Months)
timeFrame: 18 months
measure: Change in Near Control (12 Months)
timeFrame: 12 months
measure: Change in Near Control (18 Months)
timeFrame: 18 months
measure: Angle Magnitude (12 Months)
timeFrame: 12 months
measure: Angle Magnitude (18 Months)
timeFrame: 18 months
measure: Stereoacuity at 12 Months
timeFrame: 12 months
measure: Stereoacuity at 18 Months
timeFrame: 18 months
measure: Compliance With Spectacle Wear (12 Months)
timeFrame: 12 months
measure: Compliance With Spectacle Wear (18 Months)
timeFrame: 18 months
measure: Parent Symptom Survey [12 Months]
timeFrame: At 12 months
measure: Parent Symptom Survey [18 Months]
timeFrame: At 18 months
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Glendale
country: United States
facility: Midwestern University Eye Institute
state: Arizona
city: Little Rock
country: United States
facility: Arkansas Childrens
state: Arkansas
city: Anaheim
country: United States
facility: University Eye Center at Ketchum Health
state: California
city: Fullerton
country: United States
facility: Marshall B. Ketchum University
state: California
city: Loma Linda
country: United States
facility: Loma Linda University Health Care, Dept. of Ophthalmology
state: California
city: Mission Viejo
country: United States
facility: Saddleback Eye Medical Associates
state: California
city: Palo Alto
country: United States
facility: Stanford University
state: California
city: Pomona
country: United States
facility: Western University College of Optometry
state: California
city: San Francisco
country: United States
facility: University of California San Francisco Department of Ophthalmology
state: California
city: Fort Lauderdale
country: United States
facility: Nova Southeastern University College of Optometry, The Eye Institute
state: Florida
city: Gainesville
country: United States
facility: University of Florida Shands Hospital
state: Florida
city: Jacksonville
country: United States
facility: Nemours Children's Clinic
state: Florida
city: Atlanta
country: United States
facility: The Emory Eye Center
state: Georgia
city: Boise
country: United States
facility: St Luke's Hospital
state: Idaho
city: Chicago Ridge
country: United States
facility: The Eye Specialists Center, LLC
state: Illinois
city: Chicago
country: United States
facility: Ann & Robert H. Lurie Children's Hospital of Chicago
state: Illinois
city: Chicago
country: United States
facility: Illinois College of Optometry
state: Illinois
city: Downers Grove
country: United States
facility: Midwestern U Chicago College of Optometry
state: Illinois
city: Wilmette
country: United States
facility: Pediatric Eye Associates
state: Illinois
city: Bloomington
country: United States
facility: Indiana University School Of Optometry
state: Indiana
city: Indianapolis
country: United States
facility: Riley Hospital for Children
state: Indiana
city: Munster
country: United States
facility: The Eye Specialist Center, LLC
state: Indiana
city: West Des Moines
country: United States
facility: Wolfe Eye Clinic
state: Iowa
city: Lexington
country: United States
facility: University of Kentucky Department of Neurology
state: Kentucky
city: Baltimore
country: United States
facility: Greater Baltimore Medical Center
state: Maryland
city: Baltimore
country: United States
facility: Wilmer Eye Institute
state: Maryland
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Boston Medical Center
state: Massachusetts
city: Grand Rapids
country: United States
facility: Helen DeVos Children's Hospital Pediatric Ophthalmology
state: Michigan
city: Grand Rapids
country: United States
facility: Pediatric Ophthalmology, P.C.
state: Michigan
city: West Bloomfield
country: United States
facility: Children's Eye Care PC
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic Department of Ophthalmology
state: Minnesota
city: Kansas City
country: United States
facility: Children's Mercy Hospitals and Clinics
state: Missouri
city: Saint Louis
country: United States
facility: U of MO St. Louis College of Optometry
state: Missouri
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Concord
country: United States
facility: Concord Ophthalmologic Associates
state: New Hampshire
city: New York
country: United States
facility: State University of New York, College of Optometry
state: New York
city: Durham
country: United States
facility: Duke University Eye Center
state: North Carolina
city: Akron
country: United States
facility: Akron Children's Hospital
state: Ohio
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University College of Optometry
state: Ohio
city: Poland
country: United States
facility: Eye Care Associates, Inc.
state: Ohio
city: Oklahoma City
country: United States
facility: Dean A. McGee Eye Institute, University of Oklahoma
state: Oklahoma
city: Portland
country: United States
facility: Pacific University College of Optometry
state: Oregon
city: Portland
country: United States
facility: Casey Eye Institute
state: Oregon
city: Lancaster
country: United States
facility: Conestoga Eye
state: Pennsylvania
city: Philadelphia
country: United States
facility: Salus University/Pennsylvania College of Optometry
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Children's Eye Center of Children's Hospital of Pittsburgh
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina, Storm Eye Institute
state: South Carolina
city: Chattanooga
country: United States
facility: Pediatric Eye Specialists
state: Tennessee
city: Memphis
country: United States
facility: Southern College of Optometry
state: Tennessee
city: Houston
country: United States
facility: Texas Children's Hospital - Dept. Of Ophthalmology
state: Texas
city: Houston
country: United States
facility: University of Houston College of Optometry
state: Texas
city: Lubbock
country: United States
facility: Texas Tech University Health Science Center
state: Texas
city: The Woodlands
country: United States
facility: Houston Eye Associates
state: Texas
city: Norfolk
country: United States
facility: Virginia Pediatric Eye Center
state: Virginia
city: La Crosse
country: United States
facility: Gundersen Health System
state: Wisconsin
city: Calgary
country: Canada
facility: Alberta Children's Hospital
state: Alberta
city: Montreal
country: Canada
facility: CHU - Sainte-Justine
state: Quebec
Study officials:
affiliation: Marshall B. Ketchum University
name: Angela M Chen, OD, MS
role: STUDY_CHAIR
affiliation: Eye Care Associates, Inc.
name: S. Ayse Erzurum, MD
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.