Amblyopia
Conditions
Keywords
Amblyopia, Atropine, Patching
Brief summary
This study is designed to evaluate the effectiveness of treatment of residual amblyopia in children ages 3 to \< 10 years with visual acuity of 20/32 to 20/63 in the amblyopic eye. The study is a randomized clinical trial comparing intensive treatment (42 hours per week of patching plus daily atropine) with a control group that will have rapid weaning of existing treatment followed by spectacle correction only (if needed). The primary objective is to determine if this intensive treatment will improve visual acuity in patients with residual amblyopia. The primary outcome assessment is amblyopic eye visual acuity at 10 weeks. The primary analytic approach for the amblyopic eye acuity will be a treatment group comparison of the proportion of patients with at least two lines of visual acuity improvement.
Detailed description
Amblyopia is the most common cause of monocular visual impairment in both children and young and middle-aged adults. Both patching and atropine are accepted treatment modalities for the management of moderate amblyopia in children. Despite best efforts with conventional treatment, some patients fail to achieve normal visual acuity in the amblyopic eye. In a randomized trial conducted by PEDIG comparing atropine versus patching in 3 to 6 year olds with moderate amblyopia (ATS1), 261 of 402 patients (65%) had amblyopic eye visual acuity of 20/32 or worse after 6 months of treatment with patching or atropine. Beyond 6 months, treatment was at investigator discretion, and two years after randomization, 181 of 363 children (50%) still had amblyopic eye visual acuity of 20/32 or worse. In a randomized trial conducted by PEDIG comparing patching regimens, 129 of 181 patients with moderate amblyopia (71%) and 145 of 157 patients with severe amblyopia (92%) had amblyopic eye visual acuity of 20/32 or worse after 4 months of occlusion therapy. Many patients receive treatment beyond 6 months but still fail to achieve normal visual acuity in the amblyopic eye. It is unknown whether an intensive final push of combined treatment with daily patching and atropine will improve visual acuity in these patients. Although some clinicians prescribe simultaneous patching and atropine for selected patients, there are no published reports of its effectiveness. Also, we are not aware of reports of response to treatment of residual amblyopia. The study has been designed as a simple trial that, other than the type of amblyopia therapy being determined through the randomization process, approximates standard clinical practice. Patients will be randomized to one of two treatment regimens: * Intensive treatment: 42 hours per week of patching combined with daily atropine (1%) * Control group: Weaning of the current treatment (two hours of daily patching for patients currently using patching and once weekly atropine for patients currently using atropine) for 4 weeks, then no treatment other than spectacles (if needed).
Interventions
DEVICEPatching
42 hours per week of patching
DRUGAtropine
daily atropine (1%)
Sponsors
National Eye Institute (NEI)
Jaeb Center for Health Research
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
3 Years to 9 Years
Healthy volunteers
No
Inclusion criteria
* Age 3 to \< 10 years * Amblyopia associated with strabismus, anisometropia, or both * Visual acuity in the amblyopic eye between 20/32 and 20/63 inclusive * Visual acuity in the sound eye 20/32 or better and inter-eye acuity difference \>= 2 logMAR lines * Current/previous treatment with patching and/or atropine subject to the following stipulations: * No simultaneous treatment with patching and atropine in the past 6 months * No prior use of atropine in combination with the sound eye spectacle lens reduced by more than 1.50 D * Maximum level of any previous treatment: * Patching: up to 42 hours per week (averaging 6 hours daily) * Atropine: up to once daily * Current treatment with 42 hours per week patching or daily atropine * No improvement in best-corrected amblyopic eye visual acuity between two consecutive visits at least 6 weeks apart using the same testing method and optimal spectacle correction (if needed), with no improvement defined as follows: * No lines of improvement * For patients tested using E-ETDRS, letter score that is no more than 4 letters improved * Wearing spectacles with optimal correction (if applicable) * Investigator ready to wean or stop treatment
Exclusion criteria
* Current vision therapy or orthoptics * Ocular cause for reduced visual acuity * Prior intraocular or refractive surgery * Strabismus surgery planned within 10 weeks * Known allergy to atropine or other cycloplegic drugs * Known skin reactions to patch or bandage adhesives * Down Syndrome present
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Distribution of Amblyopic Eye Visual Acuity at 10 Weeks | 10 Weeks | Visual acuity was measured in each eye using the Amblyopia Treatment Study (ATS) visual acuity testing protocol resulting in a Snellen acuity score that can range from 20/16 to 20/800 for ages 3 to \<7; or with the electronic early treatment diabetic retinopathy study (E-ETDRS) method for 7 to \<10 year olds which resulted in a letter score that could range from 0 to 97 letters, with 0 being the worst and 97 being the best. Scores were converted to log of minimum angle of resolution (logMAR) equivalents for analyses (lower logMAR value is better than higher logMAR). |
| Mean (SD) Distribution of Visual Acuity at 10 Weeks | 10 Weeks | Visual acuity was measured in each eye using the Amblyopia Treatment Study (ATS) visual acuity testing protocol resulting in a Snellen acuity score that can range from 20/16 to 20/800 for ages 3 to \<7; or with the electronic early treatment diabetic retinopathy study (E-ETDRS) method for 7 to \<10 year olds which resulted in a letter score that could range from 0 to 97 letters, with 0 being the worst and 97 being the best. Scores were converted to log of minimum angle of resolution (logMAR) equivalents for analyses (lower logMAR value is better than higher logMAR). |
| Distribution of Amblyopic Eye Visual Acuity Change From Baseline to 10 Weeks | baseline to 10 Weeks | Change in logMAR from baseline to 10 weeks was calculated, with positive difference indicating improvement. Note one logMAR line = 5 letters or one Snellen line equivalent. |
| Mean (SD) Change in Visual Acuity in the Amblyopic Eye at the 10 Week Primary Outcome Exam | baseline to 10 Weeks | Change in logMAR from baseline to 10 weeks was calculated, with positive difference indicating improvement. Note one logMAR line = 5 letters or one Snellen line equivalent. |
Countries
United States
Participant flow
Recruitment details
Between October 2007 and March 2009, 27 subjects were randomized to the intensive group and 28 randomized to the weaning group.
Pre-assignment details
Eligible subjects were aged 3-\<10 with strabismic and/or anisometropic amblyopia, best-corrected amblyopic eye acuity of 20/32 to 20/63, interocular acuity difference greater than or equal to 2 lines, and no improvement in amblyopic eye acuity between 2 consecutive visits at least 6 weeks apart.
Participants by arm
| Arm | Count |
|---|---|
| Intensive 6 hours daily patching combined with daily atropine | 27 |
| Weaning For patients currently patching, a reduction of current treatment for 4 weeks with 2 hours daily patching or once weekly atropine followed by spectacles alone if needed. | 28 |
| Total | 55 |
Baseline characteristics
| Characteristic | Intensive | Total | Weaning |
|---|---|---|---|
| Age, Continuous | 6.9 years STANDARD_DEVIATION 1.1 | 6.9 years STANDARD_DEVIATION 1.2 | 6.9 years STANDARD_DEVIATION 1.3 |
| Age, Customized 3 to < 7 years | 15 participants | 28 participants | 13 participants |
| Age, Customized 7 to < 10 years | 12 participants | 27 participants | 15 participants |
| Cause of Amblyopia Anisometropia | 6 participants | 9 participants | 3 participants |
| Cause of Amblyopia Strabismus | 10 participants | 26 participants | 16 participants |
| Cause of Amblyopia Strabismus and Anisometropia | 11 participants | 20 participants | 9 participants |
| Current Treatment for Amblyopia at Enrollment Atropine | 9 participants | 16 participants | 7 participants |
| Current Treatment for Amblyopia at Enrollment Patching | 18 participants | 39 participants | 21 participants |
| Distance Visual Acuity in Amblyopic Eye 20/32 (0.24 to 0.16 logMAR) | 4 Participants | 8 Participants | 4 Participants |
| Distance Visual Acuity in Amblyopic Eye 20/40 (0.34 to 0.26 logMAR) | 7 Participants | 17 Participants | 10 Participants |
| Distance Visual Acuity in Amblyopic Eye 20/50 (0.44 to 0.36 logMAR) | 13 Participants | 25 Participants | 12 Participants |
| Distance Visual Acuity in Amblyopic Eye 20/63 (0.54 to 0.46 logMAR) | 3 Participants | 5 Participants | 2 Participants |
| Distance Visual Acuity in Fellow Eye 20/16 (-0.06 to -0.14 logMAR) | 7 Participants | 13 Participants | 6 Participants |
| Distance Visual Acuity in Fellow Eye 20/20 (0.04 to -0.04 logMAR) | 8 Participants | 19 Participants | 11 Participants |
| Distance Visual Acuity in Fellow Eye 20/25 (0.14 to 0.06 logMAR) | 10 Participants | 17 Participants | 7 Participants |
| Distance Visual Acuity in Fellow Eye 20/32 (0.24 to 0.16 logMAR) | 2 Participants | 6 Participants | 4 Participants |
| Mean (SD) Distance Visual Acuity in Amblyopic Eye | 0.35 logMAR STANDARD_DEVIATION 0.09 | 0.35 logMAR STANDARD_DEVIATION 0.09 | 0.34 logMAR STANDARD_DEVIATION 0.08 |
| Mean (SD) Distance Visual Acuity in Fellow Eye | 0.02 logMAR STANDARD_DEVIATION 0.09 | 0.03 logMAR STANDARD_DEVIATION 0.09 | 0.03 logMAR STANDARD_DEVIATION 0.1 |
| Mean (SD) Intereye Acuity Difference | 0.33 logMAR STANDARD_DEVIATION 0.11 | 0.32 logMAR STANDARD_DEVIATION 0.11 | 0.31 logMAR STANDARD_DEVIATION 0.1 |
| Mean (SD) Spherical Equivalent Refractive Error in Amblyopic Eye | 5.39 diopters STANDARD_DEVIATION 2.33 | 4.81 diopters STANDARD_DEVIATION 2.29 | 4.24 diopters STANDARD_DEVIATION 2.15 |
| Mean (SD) Spherical Equivalent Refractive Error in Fellow Eye | 3.46 diopters STANDARD_DEVIATION 2.38 | 3.37 diopters STANDARD_DEVIATION 2.13 | 3.29 diopters STANDARD_DEVIATION 1.9 |
| Race/Ethnicity, Customized African American | 0 participants | 0 participants | 0 participants |
| Race/Ethnicity, Customized Asian | 0 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized Hispanic or Latino | 7 participants | 11 participants | 4 participants |
| Race/Ethnicity, Customized More than one race | 2 participants | 3 participants | 1 participants |
| Race/Ethnicity, Customized Unknown or Not Reported | 0 participants | 0 participants | 0 participants |
| Race/Ethnicity, Customized White | 18 participants | 40 participants | 22 participants |
| Refractive Error in Amblyopic Eye (spherical equivalent/diopters) < 0.00D | 0 participants | 3 participants | 3 participants |
| Refractive Error in Amblyopic Eye (spherical equivalent/diopters) 0 to < +1.00 D | 1 participants | 1 participants | 0 participants |
| Refractive Error in Amblyopic Eye (spherical equivalent/diopters) +1.00 to < +2.00D | 3 participants | 4 participants | 1 participants |
| Refractive Error in Amblyopic Eye (spherical equivalent/diopters) +2.00 to < +3.00D | 0 participants | 2 participants | 2 participants |
| Refractive Error in Amblyopic Eye (spherical equivalent/diopters) +3.00 to < +4.00D | 1 participants | 6 participants | 5 participants |
| Refractive Error in Amblyopic Eye (spherical equivalent/diopters) greater than or equal to +4.00D | 22 participants | 39 participants | 17 participants |
| Refractive Error in Fellow Eye < 0.00D | 1 participants | 1 participants | 0 participants |
| Refractive Error in Fellow Eye 0 to < +1.00D | 2 participants | 4 participants | 2 participants |
| Refractive Error in Fellow Eye +1.00 to < +2.00D | 5 participants | 10 participants | 5 participants |
| Refractive Error in Fellow Eye +2.00 to < +3.00D | 4 participants | 8 participants | 4 participants |
| Refractive Error in Fellow Eye +3.00 to < +4.00D | 6 participants | 13 participants | 7 participants |
| Refractive Error in Fellow Eye greater than or equal to +4.00D | 9 participants | 19 participants | 10 participants |
| Region of Enrollment United States | 27 participants | 55 participants | 28 participants |
| Sex: Female, Male Female | 14 Participants | 25 Participants | 11 Participants |
| Sex: Female, Male Male | 13 Participants | 30 Participants | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 6 / 27 | 0 / 28 |
| serious Total, serious adverse events | 0 / 27 | 0 / 28 |
Outcome results
Primary
Distribution of Amblyopic Eye Visual Acuity at 10 Weeks
Visual acuity was measured in each eye using the Amblyopia Treatment Study (ATS) visual acuity testing protocol resulting in a Snellen acuity score that can range from 20/16 to 20/800 for ages 3 to \<7; or with the electronic early treatment diabetic retinopathy study (E-ETDRS) method for 7 to \<10 year olds which resulted in a letter score that could range from 0 to 97 letters, with 0 being the worst and 97 being the best. Scores were converted to log of minimum angle of resolution (logMAR) equivalents for analyses (lower logMAR value is better than higher logMAR).
Time frame: 10 Weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Intensive | Distribution of Amblyopic Eye Visual Acuity at 10 Weeks | 20/125 (0.84 to 0.76 logMAR) | 0 participants |
| Intensive | Distribution of Amblyopic Eye Visual Acuity at 10 Weeks | 20/100 (0.74 to 0.66 logMAR) | 0 participants |
| Intensive | Distribution of Amblyopic Eye Visual Acuity at 10 Weeks | 20/80 (0.64 to 0.56 logMAR) | 1 participants |
| Intensive | Distribution of Amblyopic Eye Visual Acuity at 10 Weeks | 20/63 (0.54 to 0.46 logMAR) | 1 participants |
| Intensive | Distribution of Amblyopic Eye Visual Acuity at 10 Weeks | 20/50 (0.44 to 0.36 logMAR) | 4 participants |
| Intensive | Distribution of Amblyopic Eye Visual Acuity at 10 Weeks | 20/40 (0.34 to 0.26 logMAR) | 13 participants |
| Intensive | Distribution of Amblyopic Eye Visual Acuity at 10 Weeks | 20/32 (0.24 to 0.16 logMAR) | 7 participants |
| Intensive | Distribution of Amblyopic Eye Visual Acuity at 10 Weeks | 20/25 (0.14 to 0.06 logMAR) | 1 participants |
| Intensive | Distribution of Amblyopic Eye Visual Acuity at 10 Weeks | 20/20 (0.04 to -0.04 logMAR) | 0 participants |
| Intensive | Distribution of Amblyopic Eye Visual Acuity at 10 Weeks | 20/16 (-0.16 to -0.24 logMAR) | 0 participants |
| Weaning | Distribution of Amblyopic Eye Visual Acuity at 10 Weeks | 20/25 (0.14 to 0.06 logMAR) | 3 participants |
| Weaning | Distribution of Amblyopic Eye Visual Acuity at 10 Weeks | 20/125 (0.84 to 0.76 logMAR) | 1 participants |
| Weaning | Distribution of Amblyopic Eye Visual Acuity at 10 Weeks | 20/40 (0.34 to 0.26 logMAR) | 9 participants |
| Weaning | Distribution of Amblyopic Eye Visual Acuity at 10 Weeks | 20/100 (0.74 to 0.66 logMAR) | 0 participants |
| Weaning | Distribution of Amblyopic Eye Visual Acuity at 10 Weeks | 20/16 (-0.16 to -0.24 logMAR) | 0 participants |
| Weaning | Distribution of Amblyopic Eye Visual Acuity at 10 Weeks | 20/80 (0.64 to 0.56 logMAR) | 1 participants |
| Weaning | Distribution of Amblyopic Eye Visual Acuity at 10 Weeks | 20/32 (0.24 to 0.16 logMAR) | 7 participants |
| Weaning | Distribution of Amblyopic Eye Visual Acuity at 10 Weeks | 20/63 (0.54 to 0.46 logMAR) | 4 participants |
| Weaning | Distribution of Amblyopic Eye Visual Acuity at 10 Weeks | 20/20 (0.04 to -0.04 logMAR) | 2 participants |
| Weaning | Distribution of Amblyopic Eye Visual Acuity at 10 Weeks | 20/50 (0.44 to 0.36 logMAR) | 0 participants |
p-value: 0.3ANCOVA
Primary
Distribution of Amblyopic Eye Visual Acuity Change From Baseline to 10 Weeks
Change in logMAR from baseline to 10 weeks was calculated, with positive difference indicating improvement. Note one logMAR line = 5 letters or one Snellen line equivalent.
Time frame: baseline to 10 Weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Intensive | Distribution of Amblyopic Eye Visual Acuity Change From Baseline to 10 Weeks | greater than or equal to 3 lines | 0 Participants |
| Intensive | Distribution of Amblyopic Eye Visual Acuity Change From Baseline to 10 Weeks | 2 to < 3 lines worse | 1 Participants |
| Intensive | Distribution of Amblyopic Eye Visual Acuity Change From Baseline to 10 Weeks | 1 to < 2 lines worse | 2 Participants |
| Intensive | Distribution of Amblyopic Eye Visual Acuity Change From Baseline to 10 Weeks | Within 1 logMAR line | 12 Participants |
| Intensive | Distribution of Amblyopic Eye Visual Acuity Change From Baseline to 10 Weeks | 1 to < 2 lines better | 9 Participants |
| Intensive | Distribution of Amblyopic Eye Visual Acuity Change From Baseline to 10 Weeks | 2 to < 3 lines better | 3 Participants |
| Intensive | Distribution of Amblyopic Eye Visual Acuity Change From Baseline to 10 Weeks | greater than or equal to 3 lines better | 0 Participants |
| Weaning | Distribution of Amblyopic Eye Visual Acuity Change From Baseline to 10 Weeks | Within 1 logMAR line | 8 Participants |
| Weaning | Distribution of Amblyopic Eye Visual Acuity Change From Baseline to 10 Weeks | greater than or equal to 3 lines | 1 Participants |
| Weaning | Distribution of Amblyopic Eye Visual Acuity Change From Baseline to 10 Weeks | 1 to < 2 lines better | 8 Participants |
| Weaning | Distribution of Amblyopic Eye Visual Acuity Change From Baseline to 10 Weeks | 2 to < 3 lines worse | 0 Participants |
| Weaning | Distribution of Amblyopic Eye Visual Acuity Change From Baseline to 10 Weeks | greater than or equal to 3 lines better | 1 Participants |
| Weaning | Distribution of Amblyopic Eye Visual Acuity Change From Baseline to 10 Weeks | 1 to < 2 lines worse | 4 Participants |
| Weaning | Distribution of Amblyopic Eye Visual Acuity Change From Baseline to 10 Weeks | 2 to < 3 lines better | 5 Participants |
p-value: 0.3ANCOVA
Primary
Mean (SD) Change in Visual Acuity in the Amblyopic Eye at the 10 Week Primary Outcome Exam
Change in logMAR from baseline to 10 weeks was calculated, with positive difference indicating improvement. Note one logMAR line = 5 letters or one Snellen line equivalent.
Time frame: baseline to 10 Weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intensive | Mean (SD) Change in Visual Acuity in the Amblyopic Eye at the 10 Week Primary Outcome Exam | 0.056 logMAR | Standard Deviation 0.096 |
| Weaning | Mean (SD) Change in Visual Acuity in the Amblyopic Eye at the 10 Week Primary Outcome Exam | 0.053 logMAR | Standard Deviation 0.15 |
Primary
Mean (SD) Distribution of Visual Acuity at 10 Weeks
Visual acuity was measured in each eye using the Amblyopia Treatment Study (ATS) visual acuity testing protocol resulting in a Snellen acuity score that can range from 20/16 to 20/800 for ages 3 to \<7; or with the electronic early treatment diabetic retinopathy study (E-ETDRS) method for 7 to \<10 year olds which resulted in a letter score that could range from 0 to 97 letters, with 0 being the worst and 97 being the best. Scores were converted to log of minimum angle of resolution (logMAR) equivalents for analyses (lower logMAR value is better than higher logMAR).
Time frame: 10 Weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intensive | Mean (SD) Distribution of Visual Acuity at 10 Weeks | 0.30 logMAR | Standard Deviation 0.1 |
| Weaning | Mean (SD) Distribution of Visual Acuity at 10 Weeks | 0.29 logMAR | Standard Deviation 0.18 |
p-value: 0.3ANCOVA