Trial of Overminus Spectacle Therapy for Intermittent Exotropia

Intermittent Exotropia Clinical Trial

— IXT5  

Official title:

A Randomized Clinical Trial of Overminus Spectacle Therapy for Intermittent Exotropia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02807350
• Other study ID #: IXT5
• Secondary ID: 2U10EY011751
• Status: Completed
• Phase: N/A
• Start date: January 16, 2017
• Est. completion date: February 15, 2022

Study information

• Verified date: May 2022
• Source: Jaeb Center for Health Research
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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 information / eligibility

• Status: Completed
• Enrollment: 386
• Est. completion date: February 15, 2022
• Est. primary completion date: November 30, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 3 Years to 10 Years

Eligibility

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)]

Related Conditions & MeSH terms

• Exotropia
• Intermittent Exotropia

Intervention

Device:
• Overminus treatment
spectacles with full cycloplegic refraction plus 2.50 D overminus added to the sphere
• Non-overminus treatment
spectacles with full cycloplegic refraction without overminus

Locations

Country	Name	City	State
Canada	Alberta Children's Hospital	Calgary	Alberta
Canada	CHU - Sainte-Justine	Montreal	Quebec
United States	Akron Children's Hospital	Akron	Ohio
United States	University Eye Center at Ketchum Health	Anaheim	California
United States	The Emory Eye Center	Atlanta	Georgia
United States	Greater Baltimore Medical Center	Baltimore	Maryland
United States	Wilmer Eye Institute	Baltimore	Maryland
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Indiana University School Of Optometry	Bloomington	Indiana
United States	St Luke's Hospital	Boise	Idaho
United States	Boston Medical Center	Boston	Massachusetts
United States	Tufts Medical Center	Boston	Massachusetts
United States	Medical University of South Carolina, Storm Eye Institute	Charleston	South Carolina
United States	Pediatric Eye Specialists	Chattanooga	Tennessee
United States	Ann & Robert H. Lurie Children's Hospital of Chicago	Chicago	Illinois
United States	Illinois College of Optometry	Chicago	Illinois
United States	The Eye Specialists Center, LLC	Chicago Ridge	Illinois
United States	Cincinnati Children's Hospital	Cincinnati	Ohio
United States	The Ohio State University College of Optometry	Columbus	Ohio
United States	Concord Ophthalmologic Associates	Concord	New Hampshire
United States	Midwestern U Chicago College of Optometry	Downers Grove	Illinois
United States	Duke University Eye Center	Durham	North Carolina
United States	Nova Southeastern University College of Optometry, The Eye Institute	Fort Lauderdale	Florida
United States	Marshall B. Ketchum University	Fullerton	California
United States	University of Florida Shands Hospital	Gainesville	Florida
United States	Midwestern University Eye Institute	Glendale	Arizona
United States	Helen DeVos Children's Hospital Pediatric Ophthalmology	Grand Rapids	Michigan
United States	Pediatric Ophthalmology, P.C.	Grand Rapids	Michigan
United States	Texas Children's Hospital - Dept. Of Ophthalmology	Houston	Texas
United States	University of Houston College of Optometry	Houston	Texas
United States	Riley Hospital for Children	Indianapolis	Indiana
United States	Nemours Children's Clinic	Jacksonville	Florida
United States	Children's Mercy Hospitals and Clinics	Kansas City	Missouri
United States	Gundersen Health System	La Crosse	Wisconsin
United States	Conestoga Eye	Lancaster	Pennsylvania
United States	University of Kentucky Department of Neurology	Lexington	Kentucky
United States	Arkansas Childrens	Little Rock	Arkansas
United States	Loma Linda University Health Care, Dept. of Ophthalmology	Loma Linda	California
United States	Texas Tech University Health Science Center	Lubbock	Texas
United States	Southern College of Optometry	Memphis	Tennessee
United States	University of Minnesota	Minneapolis	Minnesota
United States	Saddleback Eye Medical Associates	Mission Viejo	California
United States	The Eye Specialist Center, LLC	Munster	Indiana
United States	State University of New York, College of Optometry	New York	New York
United States	Virginia Pediatric Eye Center	Norfolk	Virginia
United States	Dean A. McGee Eye Institute, University of Oklahoma	Oklahoma City	Oklahoma
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	Stanford University	Palo Alto	California
United States	Salus University/Pennsylvania College of Optometry	Philadelphia	Pennsylvania
United States	UPMC Children's Eye Center of Children's Hospital of Pittsburgh	Pittsburgh	Pennsylvania
United States	Eye Care Associates, Inc.	Poland	Ohio
United States	Western University College of Optometry	Pomona	California
United States	Casey Eye Institute	Portland	Oregon
United States	Pacific University College of Optometry	Portland	Oregon
United States	Mayo Clinic Department of Ophthalmology	Rochester	Minnesota
United States	U of MO St. Louis College of Optometry	Saint Louis	Missouri
United States	University of California San Francisco Department of Ophthalmology	San Francisco	California
United States	Houston Eye Associates	The Woodlands	Texas
United States	Children's Eye Care PC	West Bloomfield	Michigan
United States	Wolfe Eye Clinic	West Des Moines	Iowa
United States	Pediatric Eye Associates	Wilmette	Illinois

Sponsors (3)

Lead Sponsor	Collaborator
Jaeb Center for Health Research	National Eye Institute (NEI), Pediatric Eye Disease Investigator Group

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (1)

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 Ey — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mean Distance Control at 12-Months (On-Treatment Visit)	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).	12 months
Primary	Mean Distance Control at 18-Months (Off-Treatment Visit)	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).	18 months
Secondary	Number of Participants With No Spontaneous Tropia	The number of subjects with no spontaneous tropia at 12 months and at 18 months will be compared between treatment groups.	12 months
Secondary	No Spontaneous Tropia	The proportion of subjects with no spontaneous tropia at 12 months and at 18 months will be compared between treatment groups.	At 18 months
Secondary	Change in Distance Control	The proportion of subjects with =1 point improvement in distance control between baseline and 12 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).	12 months
Secondary	Change in Distance Control	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).	18 months
Secondary	Deterioration as Assessed by Motor Alignment and Stereoacuity at Near (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.	12 months
Secondary	Deterioration as Assessed by Motor Alignment and Stereoacuity at Near (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.	18 months
Secondary	Near Control (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).	12 months
Secondary	Near Control (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).	18 months
Secondary	Change in Near Control (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).	12 months
Secondary	Change in Near Control (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).	18 months
Secondary	Angle Magnitude (12 Months)	The magnitude of the deviation by Prism Alternate Cover Test (PACT) will be compared between treatment groups.	12 months
Secondary	Angle Magnitude (18 Months)	The magnitude of the deviation by Prism Alternate Cover Test (PACT) will be compared between treatment groups.	18 months
Secondary	Stereoacuity at 12 Months	A comparison of near stereoacuity will be assessed using the Randot Preschool stereotest at near (performed at 40 cm) between treatment groups.	12 months
Secondary	Stereoacuity at 18 Months	A comparison of near stereoacuity will be assessed using the Randot Preschool stereotest at near (performed at 40 cm) between treatment groups.	18 months
Secondary	Compliance With Spectacle Wear (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.	12 months
Secondary	Compliance With Spectacle Wear (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.	18 months
Secondary	Parent Symptom Survey [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.	At 12 months
Secondary	Parent Symptom Survey [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.	At 18 months

External Links

•   PEDIG public website