Hyperopia Treatment Study 1 (HTS1) - Glasses vs Observation

Study Overview
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Brief Summary
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The purpose of this study is to compare visual acuity outcomes and development of strabismus after a 3-year follow-up period in children age 12 to <72 months with moderate hyperopia (spherical equivalent +3.00D to +6.00D) who are prescribed glasses either immediately or only after confirmation of pre-specified deterioration criteria.

Detailed Description
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Moderate and high hyperopia are associated with the development of strabismus and amblyopia. The primary aims of treatment for asymptomatic moderate and high hyperopia in preschool children are to facilitate the development of normal visual acuity and to prevent the development of esotropia and amblyopia. Treatment consists of optical correction, typically using glasses. For children with high hyperopia (>+5.00D) and without strabismus or amblyopia, there is general consensus that a correction should be prescribed. Nevertheless, for children with moderate hyperopia (+3.00D to +5.00D) without strabismus or amblyopia, there is less consensus among pediatric eye care professionals. A survey by Lyons et al found that for a 2-year-old child with hyperopia greater than +3.00D, 65% of optometrists would prescribe glasses compared to 25% of ophthalmologists; for a 4-year old with hyperopia greater than +3.00D, 67% of optometrists would prescribe compared with 42% of ophthalmologists. The American Association for Pediatric Ophthalmology and Strabismus (AAPOS) recommends correcting +4.00D or more in 2 to 7 year olds and the American Academy of Ophthalmology recommends a threshold of +4.50D for correction in 2-to 3-year olds. Unlike ophthalmology, optometry does not provide specific recommendations based on age and level of refractive error. Such variation in practice highlights the lack of rigorously collected scientific evidence for the management of this condition. Across all levels of hyperopia, most ophthalmologists and optometrists usually prescribe less than the full cycloplegic refraction (71% in the Lyons survey) when no strabismus or amblyopia is present. The rationale for proactively correcting moderate hyperopia in an asymptomatic child is the prevention of esotropia, amblyopia, or asthenopia. The argument against correcting moderate hyperopia in an asymptomatic child is the expense and inconvenience of glasses that might be unnecessary and the potential disruption of emmetropization in infants and toddlers. At present, it remains uncertain whether correction of moderate hyperopia is beneficial in terms of visual acuity outcomes or strabismus development. There is some evidence that using partial correction of hyperopia allows emmetropization to take place. If refractive correction of moderate hyperopia does not reduce the incidence of amblyopia and/or esotropia compared to no refractive correction, then glasses can be avoided. However, if correcting moderate hyperopia does reduce the development of amblyopia and/or esotropia, then the benefits of preemptive refractive correction will have been identified.

Official Title
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Glasses Versus Observation for Moderate Hyperopia in Young Children (HTS1)

Conditions
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Hyperopia

Intervention / Treatment
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* Procedure: Glasses


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 12 to < 72 months Refractive error between +3.00D and +6.00D SE (by cycloplegic refraction) in either eye Astigmatism < 1.50D in both eyes Spherical equivalent anisometropia ≤ +1.50D For children 36 to <72 months of age: No evidence of subnormal visual acuity - Uncorrected monocular visual acuity in both eyes of 20/50 or better for age 36 to <48 months,20/40 or better for age 48 to <60 months, and 20/32 or better for ages 60 to <72 months measured without cycloplegia using the ATS-HOTV© visual acuity testing protocol Zero (0) or 1 logMAR line interocular difference (IOD) in uncorrected visual acuity measured without cycloplegia using the ATS-HOTV© visual acuity testing protocol Age-normal stereoacuity on the Randot Preschool Stereotest (see Table 2 of protocol) Gestational age >32 weeks Investigator is willing to prescribe glasses per protocol or observe the hyperopia untreated for 3 years unless specific criteria for deterioration outlined in section 3.3.3 are confirmed. Parent understands the protocol and is willing to accept randomization to either glasses or no glasses initially, and is willing to wear glasses as prescribed or accept that glasses will not be prescribed by the investigator unless specific deterioration criteria outlined in section 3.3.3 are confirmed. Parent has phone (or access to phone) and is willing to be contacted by Jaeb Center staff. Relocation outside of area of an active PEDIG site for this study within the next 36 months is not anticipated. Exclusion Criteria: A patient is excluded for any of the following reasons: Any measurable heterotropia at distance (3 meters) or at near (1/3 meter) by cover/uncover testing. Note that patients with heterophoria are eligible. Previous documented strabismus (parental report must be confirmed by investigator) Manifest or latent nystagmus evident clinically Previous treatment of refractive error with glasses or contacts unless duration of glasses or contacts wear was one week or less and occurred more than 2 months prior to enrollment. Previous intraocular, refractive, or extraocular muscle surgery Previous amblyopia treatment Previous vergence/accommodative therapy Parental concerns over learning or development Ocular co-morbidity that may reduce visual acuity Symptoms of blur or asthenopia Developmental delay diagnosed by pediatrician or Individualized Education Program (IEP) Known neurological anomalies (e.g. cerebral palsy, Down syndrome) Inability to perform visual acuity ATS-HOTV testing if ≥ 36 months of age

Ages Eligible for Study
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Minimum Age: 12 Months
Maximum Age: 71 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Glasses<br>Glasses are prescribed at enrollment and worn per protocol throughout the duration of the study. | Procedure: Glasses<br>* Glasses will be prescribed at enrollment with the sphere cut symmetrically by 1.00D and full cylinder correction.<br>|
| Placebo Comparator: Observation<br>Glasses will not be prescribed unless the patient has confirmation of one or more deterioration criteria as described in the protocol. | Procedure: Glasses<br>* Glasses will be prescribed at enrollment with the sphere cut symmetrically by 1.00D and full cylinder correction.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Confirmation of Failure Criteria | At the 36-month visit, each subject's condition will be classified as either failure or not a failure. The primary analytic approach will be a treatment group comparison of the proportion meeting failure criteria at 36-months using the Fisher's exact test. The participant met failure criteria if ANY of the following criteria (except strabismus surgery prior to the 3-year outcome exam) were met during testing at the 3-year examination both with and without trial frames (without prism or bifocal), and the criteria was confirmed by a retest Any measurable manifest strabismus in primary gaze at distance or at near not correctable with distance refractive correction alone Strabismus surgery prior to the 36-month exam Distance VA below age norms in either eye ≥2 logMAR lines of IOD if VA is 20/25 or worse in the better-seeing eye ≥3 logMAR lines of IOD if VA is 20/20 or better in the better-seeing eye Stereoacuity measured at near below age normal values | 36 months after randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Subgroup Analysis - Race | Treatment effect in subgroups based on baseline factors will be assessed. Outcome failure status at 36 months will be tabulated by subgroup and reviewed for consistency. Total number of patients who experienced failure at 3 years are shown. | 36 months after randomization | 
| Subgroup Analysis - Gender | Treatment effect in subgroups based on baseline factors will be assessed. Outcome failure status at 36 months will be tabulated by subgroup and reviewed for consistency. Total number of patients who experienced failure at 3 years are shown. | 36 months | 
| Subgroup Analysis - Family History of Amblyopia | Treatment effect in subgroups based on baseline factors will be assessed. Outcome failure status at 36 months will be tabulated by subgroup and reviewed for consistency. Total number of patients who experienced failure at 3 years are shown. | 36 months | 
| Subgroup Analysis - Family History of Strabismus | Treatment effect in subgroups based on baseline factors will be assessed. Outcome failure status at 36 months will be tabulated by subgroup and reviewed for consistency. Total number of patients who experienced failure at 3 years are shown. | 36 months | 
| Subgroup Analysis - SE Anisometropia | Treatment effect in subgroups based on baseline factors will be assessed. Outcome failure status at 36 months will be tabulated by subgroup and reviewed for consistency. Total number of patients who experienced failure at 3 years are shown. | 36 months | 
| Subgroup Analysis - Mean Refractive Error at Enrollment (Diopters) | Treatment effect in subgroups based on baseline factors will be assessed. Outcome failure status at 36 months will be tabulated by subgroup and reviewed for consistency. Total number of patients who experienced failure at 3 years are shown. | 36 months | 
| Deterioration Criteria Met (Prior to 3 Years) | Estimate of Cumulative Deterioration Rate. Proportion of subjects who deteriorated during the course of the study were evaluated. Reasons for deterioration included stereoacuity, strabismus, treatment due to parental concern, and treatment that was prescribed against protocol. | Enrollment to <36 months | 
| Mean Change in Spherical Equivalent (SE) Refractive Error (Diopters) | Refractive error is the measurement of the power of the lenses needed to focus light on the retina. This is measured in diopters (D). Spherical Equivalent is a pair of numbers, one for each eye, that gives an estimate of the refractive error in the eyes. Hyperopia is farsightedness, or a type of refractive error in which things are seen more clearly at a distance than at near. Myopia is nearsightedness, or refractive error in which things are seen more clearly at near. Mean change in SE refractive error is from baseline to 3 years, measured in diopters. Negative values indicate a shift in the myopic direction. | Enrollment to 3 years | 
| Percentage of Participants With Hyperopia Reduction | Percentage of Participants (%) in which hyperopia reduced by 1.00D (diopters) or more over 3 years | Enrollment to 3 years | 
| Best Visual Acuity | A treatment group comparison of the mean maximum visual acuity per subject at the masked 36-month visit (best visual acuity on any test with and without correction) will be performed using a t-test. Evaluated the best of the values reported with and without trial frames, during initial assessment and retest. Snellen visual acuity (VA) equivalents were converted to logarithm of minimum angle of resolution (logMAR) equivalents (in parentheses) as follows: 20/16 (-0.1), 20/20 (0), 20/25 (0.1), 20/32 (0.2), 20/40 (0.3), 20/50 (0.4) A logMAR value of less than 0 is associated with better than 20/20 vision, while a logMAR value greater than 0 is associated with worse than 20/20 vision. | 36 months after randomization | 
| Failure to Meet Age-Normal VA at Distance | Proportion who failed to meet age-normal VA at distance at 3 years. Participants were classified as failing to meet age-normal visual acuity if, for either eye, distance visual acuity was below age-normal values both with and without trial frames, during initial assessment and re-test. | 36 months | 
| Proportion With Amblyopia (at Distance) | A treatment group comparison of the proportion of subjects who developed amblyopia at distance during the course of the study will be performed using the Barnard's exact test. Participants were classified as having amblyopia if any of the following criteria were met: 1) the interocular difference was ≥2 logMAR lines of IOD if VA is 20/25 or worse in the better-seeing eye, or 2) the interocular differences was ≥3 logMAR lines of IOD if VA is 20/20 or better in the better-seeing eye. 3) VA less than age normal in each eye (presumed bilateral amblyopia) | 36 months after randomization | 
| Binocular Near Visual Acuity | A treatment group comparison of the mean binocular near visual acuity (logarithm of minimum angle of resolution, or logMAR) at the 36-month outcome exam will be performed. Assessment completed in randomized correction. Snellen visual acuity (VA) equivalents were converted to logarithm of minimum angle of resolution (logMAR) equivalents (in parentheses) as follows: 20/16 (-0.1), 20/20 (0), 20/25 (0.1), 20/32 (0.2), 20/40 (0.3), 20/50 (0.4) A logMAR value of less than 0 is associated with better than 20/20 vision, while a logMAR value greater than 0 is associated with worse than 20/20 vision. | 36 months after randomization | 
| Number of Participants With Strabismus at 3 Years | The number of participants who developed measurable heterotropia was estimated for each treatment group and the proportions were compared using Barnard's exact test. | 36 months after randomization | 
| Mean Stereoacuity | Mean stereoacuity at 3 years was measured in log seconds of arc (log arcsec) (see explanation below). Evaluated the best of the values reported with and without trial frames, during initial assessment and retest. Stereoacuity scores (seconds of arc) were calculated based on the Randot Preschool stereoacuity test (scores: 800, 400, 200, 100, 60 and 40). Seconds of arc refers to the visual angle that is being measured in order to determine depth perception. Lower scores indicate better stereoacuity. A logarithm base 10 transformation was used to convert stereoacuity scores to the log scale to calculate descriptive statistics (reported as seconds of arc, or arcsec). Seconds of arc were converted to logarithm of seconds of arc, or log arcsec (in parentheses) as follows: 40 (1.60), 60(1.78), 100 (2.00), 200 (2.30), 400 (2.60), 800 (2.90), Nil (3.20) | 36 months | 
| Failure to Meet Age-Normal Stereoacuity at 3 Years | Proportion who failed to meet age-normal stereoacuity. Participants were classified as failing to meet age-normal stereoacuity if near stereoacuity was below age-normal values both with and without trial frames, during initial assessment and re-test. | 36 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hyperopia, Glasses