New Visual Acuity and Crowding Tests for Better Detection of Amblyopia

Study Overview
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Brief Summary
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Amblyopia, or 'lazy eye', is the reduction in vision usually in one eye, due to abnormal visual development without organic cause. It is a preventable and leading cause of monocular vision loss (prevalence of around 3%) and increases lifetime risk of bilateral visual impairment from 10% in the general population, to 18% in amblyopes. In the UK, vision screening in children aims to detect amblyopia and other undiagnosed visual conditions. Laboratory research suggest that amblyopia could be better detected by modifying standard clinical vision tests to enhance and quantify crowding. Crowding is the negative effect that surrounding features have on the visibility of a target. Crowding distance and crowding magnitude are considerably greater in amblyopic eyes than in normal healthy eyes. Modifications that should lead to improved amblyopia detection are 1) place letters closer together on a vision chart, 2) define letters by contrast, rather than luminance, and 3) use a new thinner font in the form of numbers, to allow crowding distance in central vision to be measured. In this project, these modifications will be tested in amblyopic children for the first time. Amblyopic children aged 3 to 11 years (n=32) will be recruited from ACPOS (Addenbrooke's Community Paediatric Ophthalmology Service) at ARU. They will have their vision measured with the three modified tests as well as an uncrowded test. The child will view letters and numbers on a computer screen and respond (verbally or by indicating their choice on a matching card). Testing is fun and game-like with breaks for rewards. Results will be compared to standard vision measurement (SLT: Sonksen LogMAR Test) from the child's ACPOS visit. Amblyopic data will be compared to control data from normal healthy children aged 3 to 11 years (n=200), and age-matched children with normal vision (n=16) from ACPOS (false referrals from school screening).

Detailed Description
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In the UK, a national vision screening is employed to detect amblyopia and other undiagnosed visual conditions in school-aged children, so that they can be managed effectively. Better detection of amblyopia could be achieved by modifying current visual acuity tests, which measure the spatial resolution limit (or capacity for clarity and sharpness) of vision and by measuring crowding distance; previously unmeasured in a clinical setting. By strengthening crowding magnitude, and better quantifying its spatial distance in paediatric populations, it is hoped that the ability to detect amblyopia, and monitor its improvement with treatment will be significantly enhanced. Three recent suggestions regarding modifications to current visual acuity tests may lead to improved detection of crowding-sensitive conditions, such as amblyopia. First, closer placement of surrounding letters to the target letter should increase the magnitude of crowding in the amblyopic eye in particular, leading to increased visual acuity differences between eyes. Second, contrast modulated stimuli should enhance crowding in amblyopic eyes. Third, a new thinner font will allow clinical measures of foveal crowding distance. In this project, these three modifications will be tested for the first time in the target clinical population. Several studies reported that optotypes (letters or symbols) on a vision chart should be placed closer together than they currently are on commercially-available charts, which use 2.5 to 5 stroke-widths separation between target and neighbouring letters. Closer placement disrupts target optotype identification in normal peripheral vision and in central vision of amblyopic eyes due to crowding. In one vision test in the proposed study, a laterally-reversible target letter (e.g., H, O, T or V) will be surrounded by four other letters (U, A, L, C). This arrangement, in which letters were separated by 0.5 optotype widths (or 2.5 stroke widths) was first formally used in the Cambridge Crowding Test. In the proposed experiments, the surrounding letters will be placed 1 stroke-width away from the target letter, the optimal position recommended by recent studies. Visual acuities for target letters will be measured for both amblyopic and non-amblyopic eyes of child participants, in a clinical environment. These results will be compared with visual acuities acquired during the clinical appointment using the Sonksen logMAR Test (SLT), which is the standard visual acuity test used in Cambridge University Hospital, Addenbrooke's Orthoptic Department In the Sonksen logMAR Test (SLT), a single line of 4 letters separated from each other by 5 stroke-widths (or 1 optotype width), is contained within a box, separated from the letters also by 5 stroke-widths. Recognition of target optotypes created by contrast-differences (second-order stimuli) is prone to greater crowding effects than is recognition of optotypes created by luminance-differences (first-order stimuli). This effect is present in normal vision, however even greater visual losses for contrast-defined targets, as well as stronger crowding effects, have been reported in amblyopia. By presenting a contrast-modulated (CM) target letter (H, O, T or V) surrounded by four other letters (U, A, L, C) placed 1 stroke-width away (in the modified Cambridge Crowding Test arrangement), this research aims to examine whether this second-order vision test will exaggerate differences between the eyes of amblyopic children, when compared to those measured in visually 'normal' children. The results will again be compared to those obtained with the Sonksen logMAR test (SLT), a first-order vision test, to compare their sensitivities to amblyopia detection. Finally, crowding distance, the spatial distance over which crowding occurs, in normal foveal (central) vision is small (2-4 arcmin) and cannot be measured with current standard clinical optotypes due to their large size (5 arcmin for 0.0 logMAR acuity). To get around this difficulty, a new vision test was recently created to quantify the crowding distance or critical spacing of crowding . It uses a new Pelli font, which is much thinner horizontally than standard clinical fonts, allowing the optotypes to get closer to each other in physical space. This 'Crowding Distance Test' permits quantification of the critical spacing of crowding for the first time in a clinical population. The new Pelli font, each optotype appearing like tall skinny numbers, has already been trialled on 'visually normal' school-aged children, but not yet examined on children with greater sensitivity to visual crowding, i.e., amblyopes. The third vision test in the proposed research, will investigate whether or not crowding distance measures made in each eye, results in greater inter-ocular differences, leading to better detection of anisometropic and strabismic amblyopia than does the current clinical standard visual acuity test, the Sonksen logMAR test (SLT). By using closer first-order target optotypes, second-order target optotypes, and quantifying crowding distance in paediatric populations, the ability to detect amblyopia and monitor amblyopia treatment, could be significantly improved for the first time since the 1960s. At that time crowding was first quantified in a clinical population of adult amblyopes and was subsequently incorporated into commercially available tests as best practice.

Official Title
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Examination of New Visual Acuity and Clinical Crowding Tests for Better Detection of Amblyopia

Conditions
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Amblyopia

Intervention / Treatment
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* Diagnostic Test: Visual acuity tests


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Test participants; Male and female 3 to 11-year-old children diagnosed by ACPOS clinicians as likely having amblyopia (strabismic or anisometropic). They will be tested following 6 weeks (or more) of refractive adaption. Control Participants; Male and female 3 to 11-year-old children who have been falsely referred into the Hospital Eye Service (ACPOS) by the visual screening service, but have satisfactory visual functions, as per the national screening guidelines. All participants must be able to complete the Sonsken logMAR Test (SLT) either verbally or via use of a matching card. Exclusion Criteria: Uncorrected refractive error. The presence of any other vision limiting medical condition, not listed in the inclusion criteria. Any prior or existing medical history of epilepsy or seizures.

Ages Eligible for Study
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Minimum Age: 3 Years
Maximum Age: 11 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Control<br>Visual acuity tests on control participants | Diagnostic Test: Visual acuity tests<br>* Participants to have visual acuity tested with the three modified vision tests.<br>* Other names: Enhanced Cambridge Crowding test;|
| Experimental: Amblyopic<br>Visual acuity tests on amblyopic participants. | Diagnostic Test: Visual acuity tests<br>* Participants to have visual acuity tested with the three modified vision tests.<br>* Other names: Enhanced Cambridge Crowding test;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Visual Acuity | LogMAR | Vision measured at the time of testing. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Amblyopia, Visual Acuity, Crowding