Birdshot Chorioretinopathy : Prospective Follow-up and Immunogenetic Studies(CO-BIRD)

Study Overview
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Brief Summary
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The purpose of this study is twofold: To analyze the clinical features of a cohort of patients with birdshot chorioretinopathy (BCR), an inflammatory bilateral ocular disease, affecting the choroid and the retina. Various imaging techniques will be used to assess the effect of the disease on the retina and the choroid. A standardized assessment of the visual function will be performed with visual acuity, visual field and color vision testing. The quality of life of the patients will be evaluated with the VFQ-25 questionnaire. These analyses will help delineating different forms of the disease among its heterogeneous presentations. To identify predisposing factors for the disease. The condition is unique from the immunogenetic standpoint by its association with the HLA-A29 allele, which is the strongest link between an HLA class I antigen and a disease. To date, however, the mechanisms leading to birdshot chorioretinopathy remain unknown. GWAS (Genome Wide association Study) based on DNA of the cohort patients will be performed with the aim to identify other susceptibility genes associated with BCR.

Detailed Description
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Birdshot chorioretinopathy is a bilateral chronic posterior uveitis that has been named in 1980. The birdshot lesions are the hallmark of the disease. In their most typical aspect these lesions are ovoid shaped hypopigmented spots at the level of the choroid. One of the main difficulties of the diagnosis lies in the spectrum of presentations of the disease. The typical birdshot lesions are ovoid with their main axis oriented toward the optic disc. However, some are round and the can be clearly seen on fundus examination while others can be limited to subtle depigmentations. Typical lesions are one-quarter to one-half disc diameters, but confluent lesions may yield larger areas of depigmentation that are difficult to recognize. Although the typical lesions are depigmented, their presentation may change over time and pigment or atrophy may replace the initial cream-colored spots. The typical location, or the most easily seen location of the spots, is nasal to the optic disc. However, involvement of the posterior pole inside the temporal arcade is also possible. The spots usually predominate in the mid-periphery, but may also extend to the equator. A standardized classification of the birdshot lesions according to their size, their number, their pigmentation and their localization has been suggested to help in the categorization of the various disease presentations and for the longitudinal follow-up of affected patients. Spots clearly visible at the time of the diagnosis may disappear later. Hence, if the diagnosis of the birdshot chorioretinopathy is not made when spots are clearly visible, later presentations may not meet the definition commonly used for the disease. The disappearance of birdshot spots after treatment has been documented, but the effect of treatment on spots has not yet been assessed in large cohorts of patients. Indocyanine green angiography has been suggested as a reliable method to detect spots. However, it remains to be validated by a randomized assessment comparing indocyanine green angiography to color photographs for the detection of birdshot lesions. Fluorescein angiography is useful in patients with birdshot chorioretinopathy to assess disease activity. In active disease, angiographic findings include leakage of the retinal veins, macular edema and optic disk hyperfluorescence. These findings are not disease specific, but they require a careful examination of the fundus seeking subtle spots when birdshot lesions are not obvious. Given the above, the first goal of our prospective cohort study is to assess the heterogeneity of the disease, its spectrum of presentation and its evolution over time. One of the characteristics of birdshot chorioretinopathy is its association with the HLA-A29 allele, which constitutes the strongest link between a disease and class I HLA allele. The mechanism by which HLA-A29 confers a risk for birdshot chorioretinopathy is a key question that remains unanswered. As with other associations between HLA class I antigens and diseases (HLA-B27 with spondylarthropathies and HLA B51 with Behçet's disease), the physiopathogeny of these links have not been elucidated. Other factors playing a role in the physiopathogeny of the disease and not linked to the major histocompatibility complex are researched. A few families of patients with birdshot chorioretinopathy have been reported, which could point to additional genetic factors for disease susceptibility but does not rule out an environmental effect. Hence, the complex physiopathology of birdshot chorioretinopathy could involve the HLA-A29 allele, other unknown genetic factors, as well as environmental factors. Given the above, we are planning a GWAS (Genome Wide association Study) based on DNA of the cohort patients, which will be performed with the aim to identify other susceptibility genes associated with BCR.

Official Title
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Longitudinal Cohort Study of Patients With Birdshot Chorioretinopathy.

Conditions
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Birdshot Chorioretinopathy, Posterior Uveitis

Intervention / Treatment
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* Other: Observational study


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Bilateral disease Presence of at least three peripapillary birdshot lesions inferior or nasal to the optic disk in one eye Low-grade anterior segment intraocular inflammation (defined as ≤ 1+cells in the anterior chamber) Low grade vitreous inflammatory reaction (defined as ≤ 2+ vitreous haze‡) Supportive findings 1. HLA-A29 positivity 2. Retinal vasculitis 3. Cystoid macular edema Exclusion Criteria: Keratic precipitates Posterior synechiae Presence of infectious, neoplastic, or other inflammatory diseases that can cause multifocal choroidal lesions

Ages Eligible for Study
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Minimum Age: 18 Years

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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Birdshot chorioretinopathy<br>Patients with a diagnosis of birdshot chorioretinopathy, with confirmed HLA-A29 positivity. | Other: Observational study<br>* The goal of the study is purely observational. Treatment decisions will be made by physicians according to the grading of the intraocular inflammation related to birdshot chorioretinopathy and to their consequences on visual function. These treatment decisions will be independent from the observational study.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Best Corrected Visual Acuity (BCVA) | Standard decimal clarity for distance visual acuity. It is expressed from 0 which is minimum & worse value, corresponding to no light perception; to 1.0 (20/20) which is maximum & best value | Through study completion, an average of 1 year | 
| Visual field testing | Humphrey 30-2 automated threshold perimetry with foveal sensitivity. It is expressed in Mean Deviation from -25 decibels or unachievable which is minimum & worse value, to 0 decibel, which is maximum & best value. | Through study completion, an average of 1 year | 
| Color vision | Assessed with Desaturated Lanthony 15-Hue Test: an objective technic evaluating sensitivity to color & colour vision deficiency. Test result is categorized as Abnormal for minimum & worse evaluation; and Normal for maximum & best evaluation. | Through study completion, an average of 1 year | 
| National Eye Institute 25-Item Visual Function Questionnaire | Using a scale from 0 for minimum & worse, to 100 for maximum & best result; this questionnaire measures influence of visual impairment on various dimensions of quality of life such as emotional well-being and social functioning | Through study completion, an average of 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of birdshot spot size | It describes appearance of the birdshot spots as small for minimum or large for maximum. | Through study completion, an average of 1 year | 
| Assessment of birdshot spot number | Spots are counted and categorized as <10 for minimum value & >50 for maximum | Through study completion, an average of 1 year | 
| Assessment of birdshot spot localization | Spots are categorized as Juxtapapillary, Equator & Diffuse. | Through study completion, an average of 1 year | 
| Assessment of birdshot spot pigmentation | Spot pigmentation is analysed and categorized as No pigmentation for minimum & Sever for maximum. | Through study completion, an average of 1 year | 
| Assessment of edema | Papillary & macular edema are analysed by Optical Coherence Tomography, using a scale from 0 to 4 respectively for minimum & best, to maximum & worse value. | Through study completion, an average of 1 year | 
| Assessment of retinal vasculitis | Arterial & venous vasculitis are analysed by Fluorescein Angiography, using a scale from 0 to 4 respectively for minimum & best, to maximum & worse value. | Through study completion, an average of 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Prospective follow-up, birdshot chorioretinopathy.