National Cohort on Congenital Defects of the Eye

Study Overview
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Brief Summary
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Congenital malformations of the eye comprise various developmental defects including microphthalmia, anophthalmia, aniridia, and anterior segment anomalies (such as Peters and Axenfeld-Rieger anomalies). These malformations are frequently associated with extra-ocular features and intellectual disability. However, little is known about visual outcome, frequency and consequences of extra-ocular features in patients. The originality of the project will be to include a spectrum of malformation thought to be a phenotypic continuum (anophthalmia, microphthalmia, aniridia, anterior segment dysgnesis). In addition, we aim to conduct a 10 year follow-up of these children, thus allowing determining ocular and neurological outcomes as any other medical event. We should also be able to determine phenotypic factors that would be associated with good or poor visual and neurologic outcomes

Detailed Description
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Congenital malformations of the eye include several developmental abnormalities including microphtalmia, aniridia, and anterior segment abnormalities. Microphtalmia is a malformation of the eye that manifests as an eye smaller than normal. In the total absence of visible eyeball is called anophthalmitis. Malformation may concern one or both eyes. Aniridia is characterized by a partial or total absence of the iris. Anterior segment abnormalities include a broad spectrum of malformations affecting the cornea and iris. These are essentially the syndromes of Peters, Rieger and Axenfeld that drive glaucoma or cataract. These abnormalities are rare and often associated with extra-ocular malformations. Thus, a delay acquisitions may be present, secondary to sensory impairment, or directly related to a brain damage during development, leading to intellectual disability. The visual consequences of these malformations, as well as the frequency of extra-ocular and abnormalities of psychomotor development are still poorly known. Thus, predict the evolution the visual and neurological abilities of a child diagnosed with a congenital the eye will have been made during pregnancy or at birth and propose to these children a protocol well-defined care is proving very difficult at the moment. The aim of this study is to improve knowledge of these diseases by describing the course of visual and neuro-developmental functions. The study should also: Identify prognostic factors for the visual and neurological evolution of these diseases Assess the impact of these eye defects on the quality of life of patients and their family Search for correlations between the presence of certain genetic mutations and the appearanceocular or neuro-developmental abnormalities. All these observations should improve the management of these diseases. The patients involved are children and adults with congenital eye defects. This will be a retrospective and prospective observational study. Any patient responding to criteria for inclusion and not satisfying the criteria for exclusion, duly informed and having given its consent, may be included in the study by his doctor.

Official Title
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National Cohort on Congenital Defects of the Eye: Natural History, Genetic Determinisms and Improved Ocular and Extra-ocular Outcome Prediction for Better Patient Management

Conditions
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Anophthalmia, Microphthalmia, Aniridia, Anterior Segment Dysgenesis 6, Peters Anomaly Subtype, Anterior Segment Dysgenesis 3, Rieger Subtype

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Newborns and/or children from birth to 7 years old, Children from 8 years old affected with the following ocular defects: anophthalmia, microphthalmia, aniridia or anterior segment dysgnesis.whose parents will have properly evaluated risks and benefits of the study and will be given an informed consent to participate the protocol. Patients affiliated to the Régime National d'Assurance Maladie. Inclusion of foreign patients will be possible through the French inclusion centers when they agreed to be charged for all medical fees. Adults affected with the following ocular defects: anophthalmia, microphthalmia, aniridia or anterior segment dysgenesis Adult patients under guardianship whose guardians will have properly evaluated risks and benefits of the study and will be given an informed consent to participate the protocol. Indeed, intellectual disability may be associated with the ocular defects and we will need to include these patients in order to evaluate incidence of this event. Adult patients able to properly evaluate risks and benefits of the study and to give their informed consent to participate to the protocol. Adult parents of an affected child participating to the study and willing to participate to the inheritance study (results of DNA analysis). Inclusion of foreign patients will be possible through the French inclusion centres when they agreed to be charged for all medical fees. Pregnant women can be included in the study Exclusion Criteria: No exclusion criteria
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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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Visual acuity including distance and near vision, completed if necessary by a low vision evaluation with ETDRS scale, will be conducted with refraction under cycloplegia. |  | Up to 3 visits for patients < 6 years / Up to 2 visits for patients ≥ 6 years and < 8 years / 1 visit for patiens ≥ 8 years | 
| An accurate description of the binocular vision by orthoptists |  | Up to 3 visits for patients < 6 years / Up to 2 visits for patients ≥ 6 years and < 8 years / 1 visit for patiens ≥ 8 years | 
| Slit lamp examination and fundus with imaging will be useful to specify the disease. |  | Up to 3 visits for patients < 6 years / Up to 2 visits for patients ≥ 6 years and < 8 years / 1 visit for patiens ≥ 8 years | 
| An ultrasound measurement will evaluate axial length of eyeball. |  | Up to 3 visits for patients < 6 years / Up to 2 visits for patients ≥ 6 years and < 8 years / 1 visit for patiens ≥ 8 years | 
| Some imaging ocular techniques as videotopography (Pentacam) |  | Up to 3 visits for patients < 6 years / Up to 2 visits for patients ≥ 6 years and < 8 years / 1 visit for patiens ≥ 8 years | 
| Some imaging ocular techniques as ultrabiomicroscopy to evaluate anterior segment |  | Up to 3 visits for patients < 6 years / Up to 2 visits for patients ≥ 6 years and < 8 years / 1 visit for patiens ≥ 8 years | 
| Some imaging ocular techniques as macular OCT (spectral-domain optical coherence tomography) |  | Up to 3 visits for patients < 6 years / Up to 2 visits for patients ≥ 6 years and < 8 years / 1 visit for patiens ≥ 8 years | 
| Imaging techniques to evaluate retina and optic nerve will be completed as appropriate due to the condition of the patient (low vision, nystagmus…). |  | Up to 3 visits for patients < 6 years / Up to 2 visits for patients ≥ 6 years and < 8 years / 1 visit for patiens ≥ 8 years | 
| Neurological examination will be based on standard procedures (WISC at age 6 and WISCIV at age 10) |  | Up to 3 visits for patients < 6 years / Up to 2 visits for patients ≥ 6 years and < 8 years / 1 visit for patiens ≥ 8 years | 
| Procedures adapted to visually impaired children when necessary |  | Up to 3 visits for patients < 6 years / Up to 2 visits for patients ≥ 6 years and < 8 years / 1 visit for patiens ≥ 8 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ocular defects, unilateral or bilateral involvement |  | Up to 3 visits for patients < 6 years / Up to 2 visits for patients ≥ 6 years and < 8 years / 1 visit for patiens ≥ 8 years | 
| Extraocular malformations |  | Up to 3 visits for patients < 6 years / Up to 2 visits for patients ≥ 6 years and < 8 years / 1 visit for patiens ≥ 8 years | 
| Quality of life questionnaires | Short-Form Health Survey (SF-36) or equivalent adapted for children (SF-10) | Up to 3 visits for patients < 6 years / Up to 2 visits for patients ≥ 6 years and < 8 years / 1 visit for patiens ≥ 8 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Anophthalmia-Microphthalmia-Aniridia, anterior segment dysgenesis, Peters anomaly, Axenfeld-Rieger anomaly, Congenital malformations of the eye, Neuropsychological evaluation