Regimens of Intermittent Occlusion Therapy for Amblyopia in Children

• Sponsor: Salus University (Other)
• Overall Status: Terminated
• CT.gov ID: NCT02767856
• Collaborator: (none)
• Enrollment: 32
• Location: 1
• Arms: 2
• Actual Duration (Months): 56.9
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

This study is designed to answer the question: What if the Intermittent Occlusion (IO-therapy) glasses were prescribed all day (12-hours) in which the total time of treatment only took 4 weeks instead of the current treatment time (4 hours) in which it takes 12 weeks?

Children aged 3- to 8-years with untreated moderate unilateral amblyopia will be enrolled and randomized into 2 groups: 1) Intense 12-hour IO-therapy Group for 4 weeks treatment; or 2) Standard 4-hour IO-therapy glasses Group for 12 weeks treatment.

Condition or Disease	Intervention/Treatment	Phase
Amblyopia	Device: IO-therapy Glasses	N/A

Study Design

• Study Type: Interventional
• Actual Enrollment: 32 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Intense vs Standard Regimens of Intermittent Occlusion Therapy for Unilateral Moderate Amblyopia in Children
• Actual Study Start Date: Sep 1, 2016
• Actual Primary Completion Date: May 30, 2021
• Actual Study Completion Date: May 30, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Intense 12-hour IO-therapy Group Participants wear 12-hour daily IO-therapy glasses for 4 weeks	Device: IO-therapy Glasses
Active Comparator: Standard 4-hour IO-therapy Group Participants wear 4-hour daily IO-therapy glasses for 12 weeks	Device: IO-therapy Glasses

Outcome Measures

Primary Outcome Measures

1. Visual Acuity Improvement [4 weeks for the Intense Group and 12 weeks for the Standard Group]

   visual acuity difference between the primary outcome measure and baseline in the amblyopic eye; visual acuity was measured with ATS- HOTV method

Secondary Outcome Measures

1. Stereoacuity Test [4 weeks for the Intense Group and 12 weeks for the Standard Group]

   Stereoacuity in arcsec was converted to log scale. so log10(stereo) will be reported. The higher value indicates a poorer binocular visual function.

2. Objective Total Treatment Hours [4 weeks for the Intense Group and 12 weeks for the Standard Group]

   Objective total treatment hours at the primary outcome visit measured with a microsensor

3. Objective Adherence [4 weeks for the Intense Group and 12 weeks for the Standard Group]

   objective adherence measured with a microsensor to the treatment regimen

Eligibility Criteria

Criteria

• Ages Eligible for Study: 3 Years to 8 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

The following criteria must be met for the patient to be enrolled in the study:

1. Age 3 to < 8 years

2. Unilateral amblyopia associated with strabismus (comitant or incomitant), anisometropia, or both

Criteria for strabismus: At least one of the following criteria must be met:

• Heterotropia at distance and/or near fixation on examination (with or without spectacles)

• History of strabismus surgery

• Documented history of strabismus which is no longer present (which in the judgment of the investigator could have caused amblyopia)

Criteria for anisometropia: At least one of the following criteria must be met:

• 0.50 D difference between eyes in spherical equivalent

• 0.50 D difference between eyes in astigmatism in any meridian

1. Amblyopic eye has no myopia (> -0.25 D spherical equivalent).

2. Visual acuity, measured in each eye without cycloplegia within 7 days prior to enrollment using the ATS single-surround HOTV letter protocol as follows:

• Visual acuity in the amblyopic eye between 20/40 and 20/80 inclusive

• Visual acuity in the sound eye 20/32 or better

• Inter-eye acuity difference ≥ 2 logMAR lines (i.e., amblyopic eye acuity at least 2 lines worse than sound eye acuity)

1. No previous amblyopia treatment within 6 months.

2. Spectacle correction (if applicable) for measurement of enrollment visual acuity must meet the following criteria and be based on a cycloplegic refraction within 6 months:

• Requirements for spectacle correction:

• For patients meeting criteria for only strabismus

• Hypermetropia if corrected must not be undercorrected by more than +1.50 D spherical equivalent, and the reduction in plus sphere must be symmetric in the two eyes. Otherwise, spectacle correction is at investigator discretion.

• For patients meeting criteria for anisometropia or combined-mechanism

• Spherical equivalent must be within 0.50 D of fully correcting the anisometropia

• Hypermetropia must not be undercorrected by more than +1.50 D spherical equivalent, and reduction in plus must be symmetric in the two eyes

• Cylinder power in both eyes must be within 0.50 D of fully correcting the astigmatism

• Cylinder axis in the spectacle lenses in both eyes must be within 6 degrees of the axis of the cycloplegic refraction

Spectacles meeting above criteria must be worn either:

• for 4 weeks immediately prior to enrollment, or

• until visual acuity in amblyopic eye is stable (defined as two consecutive visual acuity measurements at least 4 weeks apart with no improvement of one line or more)

• An acuity measurement done any of the following ways may be considered the first of two consecutive measurements:

• in current glasses,

• in trial frames with full correction of hypermetropia with cycloplegia, or

• in new glasses.

1. Wearing optimal spectacle correction for a minimum of 4 weeks at the time of enrollment.

2. Ocular examination within 6 months prior to enrollment.

3. Gestational age > 34 weeks and birth weight > 1500 grams

4. Parent willing to accept randomization

5. Parent willing to be contacted and has access to phone

6. Parent does not anticipate relocation outside area within study period.

Exclusion Criteria:

1. Amblyopic eye has myopia worse than -3.00 D spherical equivalent.

2. Prior intraocular or refractive surgery

3. Ocular pathologies that impact vision

4. Cognitive impairment that prohibits accurate data collection

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Salus University	Elkins Park	Pennsylvania	United States

Sponsors and Collaborators

• Salus University

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol, Statistical Analysis Plan, and Informed Consent Form - Apr 9, 2019

More Information

Publications

None provided.

• Responsible Party: Salus University
• ClinicalTrials.gov Identifier: NCT02767856
• Other Study ID Numbers: HJW1604
• First Posted: May 10, 2016
• Last Update Posted: Jul 25, 2022
• Last Verified: May 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Additional relevant MeSH terms: Amblyopia

Study Results

Participant Flow

Arm/Group Title	Intense 12-hour IO-therapy Group	Standard 4-hour IO-therapy Group
Arm/Group Description	Participants wear 12-hour daily IO-therapy glasses for 4 weeks IO-therapy Glasses	Participants wear 4-hour daily IO-therapy glasses for 12 weeks IO-therapy Glasses
Period Title: Overall Study
STARTED	18	14
COMPLETED	7	12
NOT COMPLETED	11	2

Baseline Characteristics

Arm/Group Title	Intense 12-hour IO-therapy Group	Standard 4-hour IO-therapy Group	Total
Arm/Group Description	Participants wear 12-hour daily IO-therapy glasses for 4 weeks IO-therapy Glasses	Participants wear 4-hour daily IO-therapy glasses for 12 weeks IO-therapy Glasses	Total of all reporting groups
Overall Participants	18	14	32
Age (Count of Participants)
<=18 years	18 100%	14 100%	32 100%
Between 18 and 65 years	0 0%	0 0%	0 0%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	5.7 (1.4)	6.0 (1.5)	5.8 (1.4)
Sex: Female, Male (Count of Participants)
Female	11 61.1%	6 42.9%	17 53.1%
Male	7 38.9%	8 57.1%	15 46.9%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 11.1%	5 35.7%	7 21.9%
Not Hispanic or Latino	14 77.8%	8 57.1%	22 68.8%
Unknown or Not Reported	2 11.1%	1 7.1%	3 9.4%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	1 5.6%	1 7.1%	2 6.3%
Native Hawaiian or Other Pacific Islander	0 0%	1 7.1%	1 3.1%
Black or African American	3 16.7%	2 14.3%	5 15.6%
White	14 77.8%	10 71.4%	24 75%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Visual acuity at baseline (logMAR) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [logMAR]	0.38 (0.11)	0.385 (0.11)	0.38 (0.11)

Outcome Measures

1. Primary Outcome

Title	Visual Acuity Improvement
Description	visual acuity difference between the primary outcome measure and baseline in the amblyopic eye; visual acuity was measured with ATS- HOTV method
Time Frame	4 weeks for the Intense Group and 12 weeks for the Standard Group

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Intense 12-hour IO-therapy Group	Standard 4-hour IO-therapy Group
Arm/Group Description	Participants wear 12-hour daily IO-therapy glasses for 4 weeks IO-therapy Glasses	Participants wear 4-hour daily IO-therapy glasses for 12 weeks IO-therapy Glasses
Measure Participants	7	12
Mean (Standard Deviation) [logMAR]	0.17 (0.11)	0.13 (0.12)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Intense 12-hour IO-therapy Group, Standard 4-hour IO-therapy Group
	Comments	Baseline and primary visit outcome
	Type of Statistical Test	Equivalence
	Comments	The study did not enroll enough samples. The stats here are only for reference.
Statistical Test of Hypothesis	p-Value	0.48
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.04
	Confidence Interval	(2-Sided) 95%; -0.08 to 0.16
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Stereoacuity Test
Description	Stereoacuity in arcsec was converted to log scale. so log10(stereo) will be reported. The higher value indicates a poorer binocular visual function.
Time Frame	4 weeks for the Intense Group and 12 weeks for the Standard Group

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Intense 12-hour IO-therapy Group	Standard 4-hour IO-therapy Group
Arm/Group Description	Participants wear 12-hour daily IO-therapy glasses for 4 weeks IO-therapy Glasses	Participants wear 4-hour daily IO-therapy glasses for 12 weeks IO-therapy Glasses
Measure Participants	7	11
Mean (Standard Deviation) [log(arcsec)]	3.04 (0.78)	3.16 (0.93)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Intense 12-hour IO-therapy Group, Standard 4-hour IO-therapy Group
	Comments
	Type of Statistical Test	Equivalence
	Comments	The study did not reach the target sample size. the stats are for reference.
Statistical Test of Hypothesis	p-Value	0.26
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.12
	Confidence Interval	(2-Sided) 95%; -0.75 to 0.99
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Objective Total Treatment Hours
Description	Objective total treatment hours at the primary outcome visit measured with a microsensor
Time Frame	4 weeks for the Intense Group and 12 weeks for the Standard Group

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Intense 12-hour IO-therapy Group	Standard 4-hour IO-therapy Group
Arm/Group Description	Participants wear 12-hour daily IO-therapy glasses for 4 weeks IO-therapy Glasses	Participants wear 4-hour daily IO-therapy glasses for 12 weeks IO-therapy Glasses
Measure Participants	6	10
Mean (Standard Deviation) [hour]	135.5 (30.5)	109.2 (58.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Intense 12-hour IO-therapy Group, Standard 4-hour IO-therapy Group
	Comments
	Type of Statistical Test	Equivalence
	Comments	The study did not reach the target sample size. The stats are for reference.
Statistical Test of Hypothesis	p-Value	0.26
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	26.3
	Confidence Interval	(2-Sided) 95%; -21.75 to 74.20
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Objective Adherence
Description	objective adherence measured with a microsensor to the treatment regimen
Time Frame	4 weeks for the Intense Group and 12 weeks for the Standard Group

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Intense 12-hour IO-therapy Group	Standard 4-hour IO-therapy Group
Arm/Group Description	Participants wear 12-hour daily IO-therapy glasses for 4 weeks IO-therapy Glasses	Participants wear 4-hour daily IO-therapy glasses for 12 weeks IO-therapy Glasses
Measure Participants	6	10
Mean (Standard Deviation) [percent]	43.0 (12.7)	54.1 (40.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Intense 12-hour IO-therapy Group, Standard 4-hour IO-therapy Group
	Comments
	Type of Statistical Test	Equivalence
	Comments	The study did not reach the target sample size. The stats are for reference.
Statistical Test of Hypothesis	p-Value	0.44
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	11.1
	Confidence Interval	(2-Sided) 95%; -41.3 to 19.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	From enrollment until the primary outcome visit and the follow-up visits. For the Intense Group, the primary outcome visit is at 4 weeks, and they also follow up at 12 weeks; for the Standard group, the primary outcome visit is at 12 weeks, if improved, they follow up at 24 weeks.
Adverse Event Reporting Description	Reverse amblyopia: defined as two or more logMAR lines worse in the fellow non-amblyopic eye at the primary visit; significant changes in ocular alignment: defined as deviation changes of ≥10Δ; any injury associated with IO-therapy glasses or the microsensor.
Arm/Group Title	Intense 12-hour IO-therapy Group		Standard 4-hour IO-therapy Group
Arm/Group Description	Participants wear 12-hour daily IO-therapy glasses for 4 weeks IO-therapy Glasses		Participants wear 4-hour daily IO-therapy glasses for 12 weeks IO-therapy Glasses
All Cause Mortality
	Intense 12-hour IO-therapy Group		Standard 4-hour IO-therapy Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/7 (0%)		0/12 (0%)
Serious Adverse Events
	Intense 12-hour IO-therapy Group		Standard 4-hour IO-therapy Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/7 (0%)		0/12 (0%)
Other (Not Including Serious) Adverse Events
	Intense 12-hour IO-therapy Group		Standard 4-hour IO-therapy Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/7 (0%)		0/12 (0%)

Limitations/Caveats

Termination leads to small numbers of subjects analyzed. Several participants lost follow-up. One patient withdrew from the study due to a dislike of the device.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.